WELLNESS-2008

Neurological-Restless Leg Syndrome

noreply@blogger.com (Kishen) — Fri, 22 Feb 2008 02:05:00 +0000

Fighting the Urge

A disorder of the central nervous system, restless leg syndrome (RLS) is characterized by the irresistible urge to move the legs. This urge usually occurs during sleep or periods of inactivity and is frequently accompanied, or caused by, uncomfortable and unpleasant sensations that are partially or completely relieved by movement. Some of the words patients with RLS use to describe the feeling include “creepy-crawly,” “burning,” “tingling,” “twitching,” and “painful.”

The symptoms of the condition tend to occur at exactly the wrong time—when people are trying to relax or sleep. As quality and quantity of sleep become an issue, daytime fatigue and exhaustion follow, affecting work and mental performance (National Institutes of Health 2005).

Although the cause of RLS is unknown, researchers believe that it results from abnormal functioning of the central nervous system. RLS produces excitability in a region of the brain known as the subcortical area. This excitability is caused by a dysfunction in a nerve-signaling chemical called dopamine (Allen RP et al 2001b; Odin P et al 2002). Dopamine is a central neurotransmitter that is particularly important in the regulation of movement.

The exact prevalence of RLS is undetermined. It may be more common than is currently thought because people may not report it to their physicians, and some physicians may wrongly attribute the symptoms to nervousness, insomnia, stress, arthritis, muscle cramps, or aging (National Institutes of Health 2005). RLS is associated with diabetes and smoking. Studies show that it affects between 1 percent and 5 percent of younger adults and up to 20 percent of adults older than 60 years (Kasper DL et al 2005). There is also a clear familial connection; about one third of patients with RLS have multiple family members who are also affected by the condition (Kasper DL et al 2005). The prevalence of RLS closely correlates to race. It is rare among Asians (0.1 percent to 5 percent) (Chaudhuri KR 2003) and most common among people of northern European descent.

Up to 90 percent of patients with RLS experience a more common condition known as periodic limb movement disorder (PLMD), which is especially common in patients who are undergoing dialysis (Rijsman RM et al 2004). PLMD is characterized by involuntary leg twitching or jerking movements during sleep that typically occur every 10 to 60 seconds, sometimes throughout the night. The symptoms cause repeated awakening and severely disrupted sleep. Unlike RLS, the movements caused by PLMD are involuntary. Although many patients with RLS also develop PLMD, most people with PLMD do not experience RLS (National Institutes of Health 2005).
Although the exact cause of RLS is unknown, a number of conditions are associated with it including:

1)Iron deficiency

2)Low dopamine levels

3)Lesions within the spinal cord or peripheral nerves

4)Pregnancy-related deficiencies in iron, folate, and magnesium (Lee KA et al 2001;

5)Manconi M et al 2004)

6)Kidney disease, particularly end-stage kidney disease

7)Medications, such as tricyclic antidepressants, selective serotonin reuptake inhibitors, lithium, and caffeine (National Heart, Lung, and Blood Institute 2000)

RLS is classified into primary and secondary forms. Primary RLS occurs in the absence of other conditions. It tends to onset earlier and is associated with a single genetic defect (Desautels A et al 2001). Secondary RLS is linked to iron deficiency and other conditions such as pregnancy, anemia, kidney disease, and brain dysfunction (Bonati MT et al 2003; Rye DB 2004; Stiasny-Kolster K et al 2004). RLS is also associated with hyperalgesia (increased pain sensation), which is most likely connected to dopamine activity.

Iron and Dopamine Abnormalities

The brains of patients with RLS exhibit abnormalities in the relationship between iron and dopamine. An enzyme involved in dopamine synthesis—tyrosine hydroxylase—requires iron for proper function. In animal studies, iron insufficiency appears to cause abnormal dopamine function (Allen RP et al 2001a). It is believed that patients with RLS may have impaired iron absorption in the brain (Connor JR et al 2003). The iron deficiencies are pronounced in certain parts of the brain that help control body movement. In autopsies of people with RLS, iron levels have been particularly low in a region of the brain called the substantia nigra (Connor JR et al 2003).

Further evidence of the relationship between iron deficiency and RLS is found in the three major secondary causes of RLS—end-stage renal disease, pregnancy, and iron deficiency, which all involve low levels of iron (Allen RP et al 2001b).

Diagnosis and Conventional Treatment

The diagnosis of RLS begins by excluding other conditions, such as anemia, diabetes, kidney disease, and iron deficiency. Electromyography and nerve conduction studies are sometimes recommended to measure electrical activity in muscles and nerves; Doppler ultrasonography can be used to evaluate muscle activity in the legs.

Such tests can document any damage or disease in nerves and nerve roots (such as peripheral neuropathy and radiculopathy) or other leg-related movement disorders.

In some cases, sleep studies such as polysomnography (a test that records the patient's brain waves, heartbeat, and breathing for an entire night) are undertaken to identify the presence of PLMD (National Institutes of Health 2005). Actigraphy, a sleep test in which a wristwatch-like device is applied to the wrist or ankles to record and measure muscle movements during sleep, may also be recommended.

Once RLS is diagnosed, it can be treated with medications (Rye DB 2004 Dec). Some of the more common conventional medications used to treat RLS include:

Levodopa—Levodopa (L-dopa) is a form of dihydroxyphenylalanine, the immediate precursor to dopamine. However, unlike dopamine, it can be taken orally and cross the blood-brain barrier. Once inside brain cells, the medication converts to dopamine. L-dopa is usually given with other medications that inhibit its effect outside of the central nervous system (Odin P et al 2002). The disadvantages of L-dopa are its short-term effects (1 to 2 hours) and a side effect known as augmentation, whereby RLS symptoms appear earlier in the day and with increasing severity (Odin P et al 2002). L-dopa can also cause nausea.

Dopamine agonists—Alternatives to L-dopa including dopamine agonists such as cabergoline, ropinirole, and pramipexole. In general, dopamine agonists have milder augmentation symptoms compared to L-dopa and are considered the treatment of choice (Kasper DL et al 2005). They have had success in relieving symptoms in more than 70 percent of patients (National Institutes of Health 2005). L-dopa and dopamine agonists can significantly reduce the number of limb movements per hour and improve the subjective quality of sleep.

Sleep agents—Minor tranquilizers such as benzodiazepines (Kasper DL et al 2005).

Anticonvulsant medications—Medications that slow convulsions (Kasper DL et al 2005).

Some medications that induce or worsen RLS include atypical neuroleptic drugs, caffeine, classical neuroleptic drugs (such as D2 receptor antagonists), H2-blocking agents, lithium, metoclopramide, and mianserin (Odin P et al 2002).

Nutrients to Help Resist the Urge
Because RLS has been associated with specific nutrient deficiencies, researchers have studied the effects of supplementation in patients who have RLS. The results have been promising.

Iron
A deficiency in iron can trigger RLS. Not only can iron levels be low in people with RLS, but iron storage in the body appears to be abnormal due to a low level of a protein called ferritin and a high level of the transporter protein transferrin. Transferrin transports iron in cerebrospinal fluid and in plasma. Fewer symptoms of RLS are apparent in people with ferritin levels greater than 50 micrograms per liter (mcg/L) (Sun ER et al 1998). A ferritin deficiency can arise from low iron intake, inadequate absorption, or excessive blood loss.

Symptoms of RLS can improve or be resolved completely through oral or intravenous iron supplementation. Studies showed relief from symptoms of RLS after supplementation with 200 milligrams (mg) of intravenous iron administered over a few days (Allen RP et al 2001a,b; Nordlander NB 1953; O'Keeffe ST et al 1994).

The absorption of iron from food and supplements can vary based on the form of iron used. Intestinal uptake can vary based on biological need. Heme (deep red, ferrous component of hemoglobin) sources of iron, such as red meat, are utilized the most effectively by the body. Other chelated forms of iron, such as iron protein succinylate or iron bis-glycinate are also excellent. These forms of iron can reverse anemia more quickly and with less constipation than the typical iron salts most doctors prescribe (Hertrampf E et al 2004).

Other nutrients can enhance the activity of iron in the body. Adequate vitamin A is essential, as it helps to mobilize iron from storage sites. Adding zinc to iron supplements may increase hemoglobin levels more than taking iron supplements alone. In the same way, taking 250 to 500 mg of vitamin C can raise the absorption of iron, although it may also increase its side effects. Iron absorption will increase if it is ingested on an empty stomach (Allen RP et al 2001a).

Folic acid

Folic acid is the synthetic form of folate, the water-soluble B vitamin that helps produce and maintain new cells in part through the creation of DNA and RNA. Folate can even protect cells from changes to DNA (Mattson MP et al 2003). Also, folate is needed to make red blood cells and prevent anemia (National Kidney and Urologic Diseases Information Clearinghouse 2005).

RLS is related to folate deficiency, particularly in the form of RLS that is associated with familial inheritance and with pregnancy. Patients with this type of RLS have benefited from intake of between 5 and 10 mg of folic acid per day, or from taking folinic acid (Botez MI 1976; Botez MI et al 1977). People taking folic acid should ensure that they receive at least 500 to 1000 mcg of vitamin B12 each day to make sure the folic acid isn’t masking a vitamin B12 deficiency.

Some people do not have the enzyme 5-methyltetrahydrofolate reductase, which converts folate into its bioactive form. These individuals often present with high levels of homocysteine and associated health concerns such as heart disease and depression; folinic acid (5-formyltetrahydrofolate) is the only option. It is a metabolically active form of folate, capable of boosting levels of the coenzyme forms of the vitamin in circumstances where folic acid has little to no effect (Kelly GS 1998).

Magnesium

Magnesium has also been shown to partly relieve RLS. Particularly for people with nighttime RLS, 250 mg of magnesium citrate taken before bed may decrease symptoms and aid sleep. Therapeutic dosages range from 250 to 800 mg of elemental magnesium a day (Rijsman RM et al 1999).

Life Extension Foundation Recommendations

Eating a well-balanced diet and getting adequate amounts of iron, folate, magnesium, and vitamin E may help avert or reduce symptoms of RLS. It is also recommended that patients not smoke (Mountifield JA 1985) and reduce their intake of (or avoid entirely) caffeine, sugar, and alcohol (Lutz EG 1978).

To help monitor healthy blood levels of nutrients, patients with RLS might consider having the following blood tests:

1)Complete blood cell (CBC) count and chemistry panel

2)Serum ferritin

3)Red blood cell (RBC) count

4)Magnesium

5)Vitamin B12

The Life Extension Foundation suggests the following nutrients may be helpful in managing RLS:

Folic acid—400 to 800 mcg daily. Take with 500 to 1000 mcg of

vitamin B12 daily in the form of methylcobalamin.

Magnesium citrate—100 to 250 mg before bed, depending on the severity of the symptoms.

Iron—Dosing is based on individual needs. Better forms are iron protein succinylate or iron bis-glycinate. Take with 250 to 500 mg of vitamin C to help the body absorb the iron.

Restless Leg Safety Caveats

An aggressive program of dietary supplementation should not be launched without the supervision of a qualified physician. Several of the nutrients suggested in this protocol may have adverse effects. These include:

Folic acid

1)Consult your doctor before taking folic acid if you have a vitamin B12 deficiency.

2)Daily doses of more than 1 milligram of folic acid can precipitate or exacerbate the neurological damage caused by a vitamin B12 deficiency.

Iron

Do not take iron if you have hemochromatosis or hemosiderosis.
Consult your doctor before taking iron supplements if you have an elevated serum ferritin level, alcoholic cirrhosis, a pancreatic insufficiency, or a history of chronic liver failure, chronic alcoholism, gastritis, peptic ulcer disease, or gastrointestinal bleeding.

Magnesium

1)Do not take magnesium if you have kidney failure or myasthenia gravis.

Vitamin B12 (cyanocobalamin)

1)Do not take cyanocobalamin if you have Leber's optic atrophy.

RESPIRATORY-ASTHMA

noreply@blogger.com (Kishen) — Thu, 21 Feb 2008 05:38:00 +0000

Asthma is the most common chronic pulmonary disorder in the United States. The condition is characterized by hypersensitivity and inflammation of the lung’s airway (bronchial) tissue, and asthma attacks can leave a person gasping for breath. While most cases are mild, more than 5000 deaths are attributed to asthma attacks each year, according to the American Academy of Allergy, Asthma and Immunology (AAAAI 2006).

The incidence of asthma cases has surged in recent years, although researchers aren’t sure exactly why. According to some studies, up to 5 percent of the US population is affected by asthma, with half of these cases developing before age 10 (Kasper DL et al 2005). Asthma attacks can be triggered by allergies and environmental irritants. Scientists have also discovered links between asthma and other diseases and conditions, including gastroesophageal reflux disease (GERD) and obesity (Flaherman V et al 2006).

People with asthma usually rely on medications to control their condition. During severe asthma attacks, patients need “rescue medications,” which are designed to restore airflow. When attacks aren’t occurring, many asthmatics take “maintenance medications,” or medications that have been shown to reduce the risk of acute asthma attacks. Both classes of medications have side effects, but because of the more severe side effects (such as high blood pressure) associated with rescue medications, the goal of conventional therapy is to prevent attacks with the right dosages of maintenance drugs.

Life Extension takes this philosophy one step further. Under the best circumstances, asthmatics could control their condition without the use of any medications, completely avoiding the side effects associated with prescription drugs. In recent years, researchers have learned a great deal about asthma and natural methods to inhibit the underlying inflammatory cascade that causes so much misery. Life Extension has also uncovered evidence that a common herbal extract, butterbur, is a highly effective asthma therapy. Finally, oxidative stress, which can wreak havoc with cells, has been linked to asthma, thus antioxidants have a definite role in therapy.

Lifestyle changes can also affect the frequency of asthma attacks and their severity. People who smoke are strongly encouraged to quit. Numerous smoking-cessation strategies are available, from nicotine replacement to group therapy. It may also help to reduce exposure to second-hand smoke and air pollution whenever possible. There is an increased risk of asthma among people who live in heavily populated urban areas. Finally, seeking treatment for diseases such as GERD and obesity may help reduce the severity of asthma.

Understanding Asthma: Inflammation and Oxidative Stress

Asthma is primarily a disorder of the bronchial tubes, the airways that connect the windpipe (trachea) and the lungs. The bronchial tubes are surrounded by smooth muscle. The tubes themselves are lined with mucus glands and contain inflammatory immune-system cells called mast cells, lymphocytes, and eosinophils. When activated, these cells produce inflammatory mediators such as histamine and leukotrienes, which bind with receptors on cells within the bronchial tubes.

During as asthma attack, a cascade of events is launched that results in the production of histamine and leukotrienes. Leukotrienes are derived from the inflammatory arachidonic acid. These inflammatory mediators cause a host of changes in bronchial tissue: they trigger a dramatic increase in mucus secretion and a simultaneous rapid constriction of the bronchial smooth muscle, which narrows the bronchial tubes and reduces the amount of air that can pass through them. Over the course of the subsequent few hours, inflammatory cells move into the area, capillaries begin to leak fluid, and direct tissue damage occurs, triggering further inflammation and swelling. The net result is wheezing and coughing and eventual trapping of air in the alveoli (a tiny, thin-walled, capillary-rich sac in the lungs, or air sac) and smaller airways. This air trapping is most dangerous to the asthmatic because it progressively limits the amount of air that can be exchanged between the lungs and the blood stream, eventually causing rising carbon dioxide levels and falling oxygen levels. The increased muscular effort required to move air increases oxygen demand, tissue metabolism, and acid production, eventually resulting in exhaustion and, in extreme cases, respiratory collapse and arrest.

Why the bronchial tubes become so sensitive in asthmatics is not fully understood, but research suggests that immune-system cells known as T cells play a central role. Some T cells induce inflammation to fight off a foreign threat, while others reduce inflammation once the threat has subsided. Conditions such as asthma, in which the body overreacts to threats, may be related to an imbalance or malfunction of these and other immune-system components (Tosca MA et al 2003; Howard TD et al 2002; Ray A et al 2000).

The idea behind nutritional supplementation is to disrupt this inflammatory cascade whenever possible. For example, omega-3 fatty acids have been shown to inhibit the production of arachidonic acid, which reduces the concentration of inflammatory leukotrienes (Wong KW 2005). Other nutrients, such as curcumin, interfere with other causative factors in the inflammatory cascade, such as inhibiting nuclear factor kappa beta and an enzyme that converts arachidonic acid to leukotriene B4.

It is very important that asthmatics take whatever steps are necessary to control their condition. Unchecked, asthma can cause permanent damage to the bronchial tubes, a situation known as airway remodeling. Under constant inflammatory stress, the bronchial tubes undergo structural change. The bronchial tubes thicken; the surrounding smooth muscle increases; the epithelium (the fragile layer of cells lining the bronchial tubes) sloughs off into the passageways; and mucus production increases. These changes can permanently reduce lung function and increase the frequency of asthma attacks (Larj MJ et al 2004; Nakagawa T et al 2004).

Scientists are also beginning to better understand the interaction between allergies, asthma, and oxidative stress. Oxidative stress occurs when highly reactive molecules, known as free radicals, interact with molecules within the body, especially DNA and mitochondrial membranes. Experimental evidence suggests that some pollutants, such as vehicle exhaust, may produce oxidative stress in the bronchial tubes (Gilmour MI et al 2006). Studies suggest that dietary supplementation with precursors of glutathione (an internal antioxidant), such as cysteine and alpha-lipoic acid, can enhance the pulmonary defenses, thus countering oxidative stress (Bridgeman MM et al 1991).

Interestingly, asthma and GERD seem to be strongly associated. GERD is a chronic condition in which partially digested stomach contents, including acid, flow backward into the esophagus. Heartburn and other symptoms usually result. Although the relationship between asthma and GERD is unclear, there is evidence for two related mechanisms. The irritation by acid of nerve receptors in the esophagus may produce a reflex irritability in the vagus nerve, producing increased sensitivity to cough-inducing stimuli in the lungs. Alternatively (or in addition), microscopic food particles and acid may be aspirated into the lungs from the refluxed material, triggering the initial round of inflammation that sets off the attack (Jiang SP et al 2005). Both mechanisms involve an initial inflammatory stimulus from the irritating stomach contents.

Good nutrition and eating habits are important in the prevention of GERD. For more information on how to treat GERD, see the chapter Gastroesophageal Reflux Disease.

Diagnosis and Medications Used to Treat Asthma
There is no single means of diagnosing asthma. A patient’s medical history, including any existing or former breathing difficulties, allergies, or skin conditions, such as eczema, are important clues. Family medical history is also important because asthma tends to run in families. Very often, patients have a history of chronic or recurrent cough for months or years before the diagnosis of asthma is finally made.

Physicians may perform pulmonary function tests to determine various parameters of lung function, such as total volume of air and the rate and force of expiration (breathing out). They may also perform a “bronchoprovocation” test, which involves the induction of a minor asthma attack by the use of histamine or some other substance.

Medication to treat asthma can be categorized as short-acting rescue medication or as maintenance medication. Rescue medications are designed to provide immediate relief from the symptoms of an asthma attack. Long-acting control medications reduce inflammation and prevent asthma attacks from occurring. Asthma experts agree that the major goal of medication is to optimize long-term control medications so that rescue medications, with their many side effects, can be minimized or eliminated (Simons FE 1999).

Bronchodilators are usually used as rescue medications (except when combined with steroids for long-term maintenance). They work by relaxing the bronchial muscles. These medications can be inhaled, injected, or taken orally. Bronchodilators are of three types:

Beta-2 agonists (e.g., albuterol). Short-acting beta-2 agonists are meant only for immediate relief of symptoms and may be given in conjunction with a maintenance medication. Long-acting beta-2 agonists are sometimes prescribed as stand-alone maintenance medications. Numerous brands of beta agonists are on the market.

Anticholinergics. These medications block the action of acetylcholine, a neurotransmitter. They produce effects similar to those of the beta-2 agonists, with a similar side effect profile.

Theophylline. Chemically similar to caffeine, this drug is not a first-line treatment because it is not as effective as other medications. Theophylline use has been associated with vitamin B6 deficiency (Shimizu T et al 1996).

Although effective for short periods of time, bronchodilators can be stressful for the body. These medications mimic the action of adrenaline, which is released during the “fight or flight” response and causes dilation of the bronchial tubes. Side effects include rapid heart rate, increased blood pressure, increased blood sugar levels, irregular heart rhythms, and a variety of other responses (Nizet TA et al 2004; Wraight JM et al 2004; Rodrigo GJ et al 2002).

In general, however, the goal of asthma therapy is to reduce the need for rescue medications by keeping patients stable on maintenance medications. Maintenance medications include the following:

Corticosteroids. These medications reduce inflammation by down-regulating production of inflammatory cytokines. Corticosteroids usually require several hours to onset, with peak effects not seen for one to three days. These medications can be inhaled or administered via nasal spray but also may be taken orally or injected.

Commonly used inhaled medications include Beclovent® (beclomethasone), Pulmicort® (budenoside), and AeroBid® (triamcinolone). Nasally administered medications include Beconase® (beclomethasone), Rhinocort® (budesonide), Flonase® (fluticasone), and Nasonex® (mometasone).

Long-term use of systemic (oral or injected) corticosteroids is associated with cataracts and glaucoma, osteoporosis, muscle weakness, chemical-induced diabetes, hypertension, adrenal gland dysfunction, and edema. Corticosteroids also deplete the body of calcium, magnesium, potassium, and zinc and may lead to osteoporosis. Some of these nutrients should be supplemented during long-term corticosteroid therapy (Banov CH 2004). Inhaled corticosteroid medications produce far fewer side effects because of the low doses of steroids involved. These drugs are associated with local side effects, however, such as thinning of the oral or nasal mucus membranes and yeast infections.

Leukotriene modifiers. These make up a relatively new class of drug that prevents or reduces inflammation by inhibiting the production or activity of leukotrienes. Leukotrienes are synthesized from arachidonic acid by lipoxygenase enzymes. Commonly used leukotriene modifiers include Singulair® (montelukast), Accolate® (zafirlukast), and Zyflo® (zileuton).

Mast cell stabilizers. These medications prevent mast cells (a type of immune cell) from releasing histamines, which can lead to an allergic reaction or an asthma attack. Mast cell stabilizers are less effective than other medications and are not frequently prescribed. They are usually reserved for individuals who cannot tolerate the side effects of other asthma medications.

A new type of treatment targets a class of immunoglobulins called immunoglobulin E, which activates mast cells and other inflammatory cells that trigger asthma attacks. Several trials have demonstrated the promise of this product in allergic asthma activity and as a therapy that may help patients reduce or avoid corticosteroids (Boushey HA Jr 2001). It is designed for use in moderate to severe asthma only. Side effects, which may be serious, include allergic reactions, hypotension (low blood pressure), arthritis, and kidney failure.

Butterbur: An Herbal Approach to Asthma
Butterbur (Petasites hybridus) is a perennial shrub that has been used since ancient times to treat a variety of conditions. As far back as the 17th century, butterbur was used to treat cough, asthma, and skin wounds (MMWR 2001). Today, researchers have uncovered the mechanism of action that makes butterbur effective.

Scientists have identified and isolated the compounds in butterbur that help reduce symptoms in asthma. Called petasins, these chemicals inhibit leukotrienes and histamines, which are responsible for symptom aggravation in asthma (Thomet OA et al 2002).

So far, a few research teams have examined butterbur’s effectiveness in asthmatics, with encouraging results. In one open trial of 64 adults and 16 children and adolescents, asthma patients were treated for two months with butterbur extract, followed by an optional two-month open trial. They were measured throughout the study for the severity and frequency of asthma attacks. According to researchers, all the measured symptoms improved throughout the study, and 40 percent of patients were able to reduce their intake of traditional asthma medications (Danesch UC 2004).

Another study examined butterbur in conjunction with inhaled corticosteroid therapy. In this trial, 16 asthmatics were given butterbur or placebo while they continued their constant dose of inhaled steroid medications. Butterbur therapy, at 50 mg daily, was shown to reduce several measures of symptoms, leading researchers to conclude that butterbur is an effective adjunct therapy to corticosteroids. They called for further study of butterbur as a stand-alone therapy for mild asthmatics, who might be able to forgo their prescription medications (Lee DK et al 2004).

Antioxidant Therapy
Researchers are also finding that antioxidants have the unique power to reduce lung and bronchial damage in people with asthma. The lungs are at particular risk for oxidative damage because their primary function is the exchange of oxygen and waste gases. Antioxidants protect the body’s tissues by scavenging oxidant molecules and rendering them less harmful. Antioxidants can be ingested, as in the case of vitamin C, or produced internally, as in the case of glutathione.

Nutritional approaches, although often slow to act in advanced disease, can enhance the effect of medical therapy by interfering with the inflammatory process and reducing oxidation, thereby potentially reducing the need for higher doses of medication. However, patients should always consult a physician before changing their diet or medication therapy.

Antioxidants (vitamins C, E, and A). A number of studies have suggested that consuming antioxidants such as vitamins C, E, beta-carotene, flavonoids, selenium, and other nutrients reduces the risk of bronchoconstriction associated with asthma.

For instance, studies have shown that vitamin C and possibly vitamin E supplementation can alleviate the severity of asthma symptoms (Ford ES et al 2004; Rubin RN et al 2004; Wijnhoven HA et al 2003; Trenga CA et al 2001; Fogarty A et al 2000; Hijazi N et al 2000; Seaton A et al 2000). Dietary supplementation with vitamin C and vitamin A (the substances that give fruits and vegetables their color) has also been associated with reduced susceptibility to asthma attacks. Other studies have demonstrated that vitamin C or E supplementation may be a valuable addition to the treatment of patients with allergic rhinitis (otherwise known as hay fever) and asthma.

Dietary supplementation of vitamin C has also been found to help a specific form of asthma called exercise-induced asthma (EIA). People with EIA are usually symptom free when not exercising. Studies have found that 1 or 2 g vitamin C daily diminished episodes of EIA. (Jaber R 2002).

Flavonoids. Flavonoids are the brightly colored pigments found in most fruits and vegetables. In plants, they assist with photosynthesis, but when consumed, they have antioxidant properties and have been associated with improved lung function. One study (Knekt P 2002) demonstrated that a high dietary intake of the flavonoids quercetin (found in wine, tea, and onions), naringenin (found in oranges and grapefruit), and hesperetin (found in oranges and lemons) was associated with a lower prevalence of asthma. It is interesting to note that quercetin has a chemical structure similar to cromolyn, a mast cell stabilizer sometimes used to treat asthma (Braunwald E et al 2001).

Other bioflavonoids are reported effective in the treatment of asthma. Researchers recently looked at the effects of lycopene (the red pigment found in tomatoes and some fruits) on patients with EIA. More than half of patients (55 percent) showed improvement in the amount of air they could exhale (Neuman I et al 2000). Other studies found that pycnogenol (an extract of French maritime pine bark) appeared to reduce asthmatic symptoms (Rohdewald P 2002).

Ginkgo biloba. Ginkgo biloba, a flavonoid-rich extract of leaves of the Ginkgo biloba tree, may be an effective asthma therapy, according to the results of several studies (Mahmoud F 2000; Li MH et al 1997).

Vitamin B6. Only a limited number of studies have been conducted on vitamin B6 as it pertains to asthma (Sur S et al 1993). Although the results did not show a clear improvement in all asthma cases, researchers found that the asthma drug theophylline appeared to lower the blood level of vitamin B6. Theophylline is rarely prescribed in the United States. In cases when it is prescribed, a patient’s vitamin B6 levels should be checked periodically to determine if supplementation is needed.

RESPIRATORY-ASTHMA

noreply@blogger.com (Kishen) — Thu, 21 Feb 2008 05:27:00 +0000

Minerals and Fatty Acids to Relieve Asthma Suffering

Selenium. Studies have shown that individuals with chronic asthma may suffer from a selenium deficiency, increased oxidative stress, and decreased glutathione activity (Allam MF et al 2004; Fogarty A et al 2000). Selenium is an essential dietary mineral that plays a vital role in activating glutathione. In a recent study, women with relatively low blood selenium levels during pregnancy gave birth to infants with a higher incidence of asthma (Shaheen SO et al 2004). These results suggest that dietary supplementation with selenium may diminish the susceptibility to asthma.

Magnesium. Several studies have indicated that patients with asthma have lower levels of magnesium within the cells lining the airways. When daily magnesium supplementation was given to children with mild to moderate asthma, a significant decrease in the use of rescue beta-agonist inhalers was demonstrated (Bede O et al 2003). These results suggest that intracellular magnesium levels are associated with the severity of asthma and the frequency of asthma attacks. Maintaining normal magnesium levels appears to be an important component of asthma therapy.

Zinc. Zinc appears to affect apoptosis, or “programmed cell death.” All cells contain genetic code that determines when they should die. A defect may cause cells to die prematurely, leading to inflammation, which can trigger an asthma attack. Zinc may have a role in preventing premature cell death in the asthmatic lung, which might have a protective effect (Truong-Tran AQ et al 2003). However, more research is necessary to determine the role zinc might play in the lungs generally and asthma specifically (Richter M et al 2003).

Calcium and vitamin D. Steroid use, particularly oral or systemic, is associated with the development of osteopenia (reduced bone density) and eventual osteoporosis (a condition in which bones lose mass and density) (Braunwald E et al 2001; Gennari C 2001). When asthma patients are on long-term oral steroid therapy, supplemental calcium and phosphate are recommended to prevent osteopenia. Calcium citrate contains the highest available elemental calcium in capsule form (Gennari C 2001). Periodic bone densitometry evaluation is recommended for assessing the development of osteoporosis (Mortensen L et al 1998).

Preventing osteopenia involves the oral intake of 1200 mg elemental calcium along with supplemental vitamin D (1000 IU) daily. In the event that osteoporosis develops, a bisphosphonate is usually added to the therapy (Gennari C 2001).

Omega-3 and other polyunsaturated fatty acids. Omega-3 fatty acids, also known as fish oils, may play a role in the prevention of asthma by reducing the tendency toward inflammation. A study of the immune status of neonates showed that the neonatal production of inflammatory cells associated with asthma was significantly decreased in infants of supplemented mothers (Dunstan JA et al 2003).

The current literature is supportive of dietary omega-3 polyunsaturated fatty acid use as a means of modifying asthma susceptibility and severity. However, fish oil supplementation has been associated with a worsening of asthma in aspirin-sensitive asthmatics (Jaber R 2002). Therefore, it should not be used by this subpopulation of asthmatics. If asthma patients are unsure about their sensitivity to aspirin, they should check with their doctor before taking fish oil supplements.

Borage oil. Borage oil, an herbal extract, contains a high percentage of a substance called gamma-linolenic acid (GLA). GLA is a type of fat that has been shown to regulate leukotrienes, biochemicals that can trigger asthma attacks. An asthma medication called zileuton works in much the same way.

Although more research must be done, borage oil, which contains GLA, may prove to be an attractive alternative as a dietary leukotriene-modifying therapy. Researchers found that daily supplementation of GLA had an impact on leukotrienes and warranted further study (Ziboh VA et al 2004).

Curcumin. Curcumin inhibits nuclear factor kappa beta, a major component for translating inflammatory stimuli into actions such as production of cytokines and changes in inflammatory cell function. Curcumin has been found to reduce the inflammatory responses of lymphocytes in human asthmatics, and in a laboratory animal model of asthma, treatment with curcumin reduced airway hyperresponsiveness (Kobayashi T et al 1997).

Life Extension Foundation Recommendations

Asthma is closely related to environmental health and allergies. People who suffer from allergies should obtain a high-quality high-efficiency particulate air filter in the home and avoid potential allergens whenever possible. Exercise may help improve lung function, but asthma patients should be aware that exercising in cold or polluted air (such as a winter morning run) can aggravate their condition.

Some asthma patients are given corticosteroids to reduce inflammation. Because these drugs can cause osteoporosis, people taking any form of corticosteroid should also supplement with calcium and vitamin D to support strong bones. The following dosages are suggested:

1)Calcium—1200 milligrams (mg) daily

2)Vitamin D—1000 international units (IU) daily

Similarly, although theophylline is rare in the United States, it is sometimes prescribed for asthma. This drug has been shown to reduce levels of vitamin B6. For people taking theophylline, the following dosage of vitamin B6 is suggested:

3)Vitamin B6—150 mg daily

Finally, all patients with asthma may be able to reduce their symptoms or reduce their medications by taking the following supplements that combat inflammation and target free radicals:

4)Butterbur—50 to 150 mg daily

5)Vitamin C—2000 to 3000 mg daily

6)Vitamin E—400 IU daily, with at least 200 mg gamma tocopherols

7)Vitamin A—5000 IU daily

8)Selenium—200 micrograms (mcg) daily

9)Quercetin—500 to 1000 mg daily (use only water-soluble quercetin)

10)Ginkgo biloba—120 mg daily

11)Lycopene—15 mg daily

12)Magnesium—340 to 1000 mg daily

13)Zinc—30 mg daily

14)EPA/DHA—1400 mg EPA and 1000 mg DHA daily

15)GLA—900 to 1800 mg daily

16)Curcumin—800 to 1600 mg daily

Product Availability
All the nutrients and supplements discussed in this section are available through the Life Extension Foundation Buyers Club, Inc.
The blood tests discussed in this section are available through Life Extension National Diagnostics, Inc.

Asthma Safety Caveats
An aggressive program of dietary supplementation should not be launched without the supervision of a qualified physician. Several of the nutrients suggested in this protocol may have adverse effects. These include:

Curcumin

1)Do not take curcumin if you have a bile duct obstruction or a history of gallstones. Taking curcumin can stimulate bile production.

2)Consult your doctor before taking curcumin if you have gastroesophageal reflux disease (GERD) or a history of peptic ulcer disease.

3)Consult your doctor before taking curcumin if you take warfarin or antiplatelet drugs. Curcumin can have antithrombotic activity.

4)Always take curcumin with food. Curcumin may cause gastric irritation, ulceration, gastritis, and peptic ulcer disease if taken on an empty stomach.

5)Curcumin can cause gastrointestinal symptoms such as nausea and diarrhea.

EPA/DHA

1)Consult your doctor before taking EPA/DHA if you take warfarin (Coumadin). Taking EPA/DHA with warfarin may increase the risk of bleeding.

2)Discontinue using EPA/DHA 2 weeks before any surgical procedure.

Ginkgo biloba

1)Individuals with a known risk factor for intracranial hemorrhage, systematic arterial hypertension, diabetes, or seizures should avoid ginkgo.

2)Do not use prior to or after surgery.

3)Avoid concomitant use of ginkgo with NSAIDS, blood thinners, diuretics, or SSRI’s.
Gastrointestinal symptoms (nausea and diarrhea) may occur.

4)Allergic skin reactions may occur.

5)Elevations in blood pressure may occur.

GLA

1)Consult your doctor before taking GLA if you take warfarin (Coumadin). Taking GLA with warfarin may increase the risk of bleeding.

2)Discontinue using GLA 2 weeks before any surgical procedure.

3)GLA can cause gastrointestinal symptoms such as nausea and diarrhea.
Magnesium

Do not take magnesium if you have kidney failure or myasthenia gravis.
Quercetin

Quercetin can cause headache, mild tingling of the extremities, and gastrointestinal symptoms such as nausea.

Selenium

1)High doses of selenium (1000 micrograms or more daily) for prolonged periods may cause adverse reactions.

2)High doses of selenium taken for prolonged periods may cause chronic selenium poisoning. Symptoms include loss of hair and nails or brittle hair and nails.
Selenium can cause rash, breath that smells like garlic, fatigue, irritability, and nausea and vomiting.

Vitamin A

1)Do not take vitamin A if you have hypervitaminosis A.

2)Do not take vitamin A if you take retinoids or retinoid analogues (such as acitretin, all-trans-retinoic acid, bexarotene, etretinate, and isotretinoin). Vitamin A can add to the toxicity of these drugs.

3)Do not take large amounts of vitamin A. Taking large amounts of vitamin A may cause acute or chronic toxicity. Early signs and symptoms of chronic toxicity include dry, rough skin; cracked lips; sparse, coarse hair; and loss of hair from the eyebrows. Later signs and symptoms of toxicity include irritability, headache, pseudotumor cerebri (benign intracranial hypertension), elevated serum liver enzymes, reversible noncirrhotic portal high blood pressure, fibrosis and cirrhosis of the liver, and death from liver failure.

Vitamin C

1)Do not take vitamin C if you have a history of kidney stones or of kidney insufficiency (defined as having a serum creatine level greater than 2 milligrams per deciliter and/or a creatinine clearance less than 30 milliliters per minute.

2)Consult your doctor before taking large amounts of vitamin C if you have hemochromatosis, thalassemia, sideroblastic anemia, sickle cell anemia, or erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency. You can experience iron overload if you have one of these conditions and use large amounts of vitamin C.

Vitamin E

1)Consult your doctor before taking vitamin E if you take warfarin (Coumadin).

2)Consult your doctor before taking high doses of vitamin E if you have a vitamin K deficiency or a history of liver failure.

3)Consult your doctor before taking vitamin E if you have a history of any bleeding disorder such as peptic ulcers, hemorrhagic stroke, or hemophilia.

4)Discontinue using vitamin E 1 month before any surgical procedure.

Zinc

1)High doses of zinc (above 30 milligrams daily) can cause adverse reactions.

2)Zinc can cause a metallic taste, headache, drowsiness, and gastrointestinal symptoms such as nausea and diarrhea.

3)High doses of zinc can lead to copper deficiency and hypochromic microcytic anemia secondary to zinc-induced copper deficiency.

4)High doses of zinc may suppress the immune system.

RESPIRATORY-BRONCHITIS (Acute)

noreply@blogger.com (Kishen) — Thu, 21 Feb 2008 03:11:00 +0000

Acute bronchitis is one of the most common reasons people in the United States seek medical care. It is important to distinguish episodes of acute bronchitis from the chronic bronchitis that is associated with chronic obstructive pulmonary disease (COPD), which is discussed elsewhere in this book.

During an episode of acute bronchitis, the tissue lining the bronchi becomes irritated and inflamed, causing increased secretion of mucus and a narrowing of the airways. This produces the characteristic cough (Treanor JJ et al 2000). For many people, the cough itself becomes an aggravating factor and worsens their condition.

Up to 95 percent of cases of acute bronchitis are caused by viral infection, with most of the rest caused by environmental irritants. The most common viral causes are influenza, parainfluenza, and the common cold viruses. Unfortunately, in many cases (up to 70 percent), antibiotics are prescribed for acute viral bronchitis, making it one of the leading situations in which antibiotics are misused. Accordingly, the American College of Physicians and the U.S. Centers for Disease Control have issued guidelines aimed at stopping physicians from automatically prescribing antibiotics to patients with acute bronchitis. According to these two organizations, the only form of bronchitis that should be treated with antibiotics is pertussis (whooping cough). However, because of the risk that acute bronchitis can also be caused by certain bacteria, some physicians will also prescribe antibiotics to certain patients to prevent further infection.

Unfortunately, there is little that can be done to stop an episode of acute bronchitis once it begins. The most common recommendation for treatment is to wait for the inflammation to subside naturally, which will relieve the coughing and other symptoms. In very severe cases, a physician might recommend medications that limit coughing, reduce mucus production, and open airways. However, many of these medications have unpleasant side effects.

Life Extension’s approach to acute bronchitis is based on two simple ideas:

1)The best defense is a good offense. Since acute bronchitis is usually caused by viral infection, every effort should be made to prevent exposure to these viruses from progressing to a full-blown infection. Life Extension has developed an aggressive program to help people avoid infections by these common viruses. To read about this program in detail, please see the chapters Influenza and Common Cold or refer to the section at the end of this chapter. It is important that people act quickly if they suspect they are coming down with a viral infection.

2)Although no medication or dietary supplement has been shown to specifically inhibit acute bronchitis, it may be possible to reduce symptoms by attacking the underlying cause of the condition, namely inflammation and its associated free radical damage and mucus production. Many nutrients have been shown to possess powerful anti-inflammatory and antioxidant capabilities.

Diagnosing and Treating Acute Bronchitis

The diagnosis of acute bronchitis can be somewhat complicated because of the many conditions it resembles. Patients with acute bronchitis typically show up at the physician’s office with a productive cough and signs of bronchial obstruction, including wheezing and breathlessness. Other symptoms may include chest pain and hoarseness. Fever is rarely associated with acute bronchitis, so if a fever is present in addition to a cough, the diagnosis is likely to be influenza or pneumonia. Other conditions that may be accompanied by a chronic cough and are sometimes mistaken for acute bronchitis include postnasal drip syndrome, asthma, and gastroesophageal reflux disease (GERD).

It is important to note that in nonsmokers, acute bronchitis should generally not be treated with antibiotics. These drugs are ineffective against the viruses that typically cause acute bronchitis, and their overuse leads to antibiotic-resistant pathogens. If therapy is warranted, physicians will likely suggest medications that control symptoms of acute bronchitis, such as coughing and mucus production. Pain relievers such as aspirin or nonsteroidal anti-inflammatories may be used, along with over-the-counter nasal decongestants. Cough suppression is not considered a primary treatment goal; the cough will resolve as the inflammation subsides and the bronchi heal.

People with acute bronchitis are also advised to drink plenty of fluids to help thin the mucus and hydrate the body. Expectorants, or medications that thin mucus, may also be recommended. The only antiviral drugs of value are those that specifically treat influenza virus in patients whose bronchitis is caused by this virus. There is some evidence that anti-influenza drugs can reduce the unnecessary use of antibiotics. Bronchodilators, which open airways, are rarely prescribed except to adults who are wheezing and have evidence of restrictive airway disease (Smucny J et al 2004).

Whether it is treated or not, acute bronchitis will typically resolve on its own as the inflammation of the bronchi gradually subsides and the airways open again. Nevertheless, the condition is aggravating and painful while it persists, so early intervention—at the first sign of symptoms of viral infection—is important to prevent acute bronchitis. More information on Life Extension’s aggressive early intervention programs for the common cold and influenza can be found elsewhere in this book. Life Extension also advocates that people practice good “viral hygiene” by washing their hands as frequently as possible and avoiding coming into close contact with infected people.

Antioxidant Therapy

Antioxidants, which combat free radicals and reduce oxidative stress, are important weapons in the fight against respiratory infections. During an infection, the immune system is activated into producing inflammatory cytokines and increasing free radical production (Biesalski HK et al 1995). The oxidative stress caused by increased free radical production enhances the inflammation already present, leading to a self-reinforcing cycle of inflammation and free radical production.

Vitamin C. Although few clinical trials have addressed antioxidants and acute bronchitis, it is logical that people suffering from inflammation of the bronchi and elevated free radical damage would benefit from a strong antioxidant defense. There is also good evidence that large doses of vitamin C can interfere with viral infections at the first sign of symptoms (Gorton HC et al 1999), thus reducing one’s risk of developing acute bronchitis.

a)In one study, investigators examined cold and flu symptoms in two groups of students. Individuals in the control group were given conventional pain relievers and decongestants, whereas those in the test group were treated with hourly doses of 1000 mg vitamin C for the first six hours and then three times a day thereafter. Flu and cold symptoms in the test group decreased 85 percent compared with the control group (Gorton HC et al 1999).

b)In a randomized, double-blind study, older patients hospitalized with acute respiratory infections (bronchitis and bronchopneumonia) were given 200 mg vitamin C daily. On evaluation two and four weeks after admission, significant increases in vitamin C concentration in plasma and white cells were noted, even in the presence of acute respiratory infection. Patients were further evaluated by a clinical scoring system based on primary symptoms of their respiratory illness. Those receiving vitamin C fared significantly better than those who received placebo (Hunt C et al 1994).

Vitamin E. Evidence from animal and human studies also shows that vitamin E, a powerful antioxidant, plays an important role in the maintenance of the immune system. Even marginal deficiencies in vitamin E may predispose individuals to viral infections by reducing the immune response. Therefore, supplying the body with additional antioxidants could reduce oxidative stress and enhance immune function (Beharka A et al 1997). A recent review has proposed that supplementation with antioxidants may improve or exert a protective effect on lung health (Romieu I 2005).

N-acetylcysteine. N-acetylcysteine (NAC) is a precursor of glutathione, an important internal antioxidant. NAC has been in clinical use for more than 30 years as a mucolytic drug. NAC is routinely used to boost antioxidant levels and dissolve mucus in people suffering from respiratory ailments (Kupczyk M et al 2002).

In a randomized study of 24 bronchitis patients with an average age of 66, the addition of 600 mg NAC twice daily to standard therapy improved symptoms and quality of life (Reichenberger F et al 2002). Other investigators have shown that administration of NAC reduces episodes of influenza and influenza-like illnesses, especially in older high-risk individuals (De Flora A et al 1997).

Inflammation and Additional Nutrient Support

Omega-3 fatty acids. The defining feature of acute bronchitis is inflammation that produces symptoms. Fortunately, many nutrients have been shown to reduce inflammation by interfering with the cascade of chemical reactions that causes inflammation. Among the best known are the omega-3 fatty acids. These essential fatty acids have been shown to decrease the production of bronchorestrictive leukotrienes by reducing the production of arachidonic acid. Some researchers believe that this effect explains why Eskimos, who eat a lot of these fatty acids in a diet rich in cold-water fish, experience less lung disease than other populations (Schwartz J 2000).

Curcumin. Curcumin, which is derived from the common spice turmeric, is also a natural anti-inflammatory. This supplement is a natural inhibitor of nuclear factor kappa beta, which mediates most inflammatory processes in the body. Curcumin has shown promise in protecting lung tissue against inflammation induced by chemical and infectious agents in the laboratory (Venkatesan N 2000). Although there are no human trials examining curcumin in acute bronchitis, its antioxidant and anti-inflammatory properties make it a logical therapy.

Bromelain. Bromelain, an extract of the pineapple plant, has also demonstrated anti-inflammatory and mucolytic properties (Maurer HR 2001). Bromelain is a collective term for enzymes found in pineapple fruit, stem, and leaves. These enzymes are proteolytic, meaning they break down protein into its constituent peptides and amino acids. Bromelain has been found to be a mucolytic, or a compound that breaks down mucus (Bernkop-Schnurch A et al 2000). A recent review also noted that bromelain may offer therapeutic benefits to individuals who have bronchitis and sinusitis (Maurer HR 2001).

Life Extension’s Flu and Common Cold Program

Because acute bronchitis is so often caused by the flu virus and the common cold, a summary of Life Extension’s flu and common cold prevention program is presented here. For a more complete description, please see the appropriate chapters. At the first sign of infection, consider taking the following supplements. This program is not meant for long-term consumption because of the high doses. Follow these recommendations for only a few days.

Vitamin C. Megadoses of vitamin C (1000 mg every hour for the first 6 hours and three times daily thereafter) administered during or after influenza infection decreased influenza symptoms in a large group of students (Gorton HC et al 1999).

Vitamin E. Both human and animal studies have shown that vitamin E can help fight influenza infection by boosting the immune system (Hara M et al 2005; Gay R et al 2004). Animal studies have shown that vitamin E, in conjunction with other antioxidants, can help protect against the flu by reducing the oxidative damage associated with the virus:

After being infected with the influenza virus, aged mice fed a diet supplemented with vitamin E had significantly lower pulmonary viral levels and maintained their body weight, unlike control mice or mice fed with other antioxidants. Levels of pro-inflammatory cytokines, including interleukin-6 and tumor necrosis factor-alpha, were lowest in the group supplemented with vitamin E (Han SN et al 2000).
Vitamin E was shown to reduce the viral activity in the lungs of middle-aged mice after exposure to influenza (Meydani M 1999).
Supplementation with vitamin E before infection helped protect the lungs of the mice against lipid peroxidation (Mileva M et al 2002).

Selenium and zinc. A combination supplement containing selenium and zinc can reduce the severity of flu infection.

1)In one study, seniors who received an experimental formula of zinc, selenium, fermentable oligosaccharides (a kind of sugar that enhances beneficial bacteria), and structured triacylglycerides for 183 days showed signs of enhanced immune function and had fewer days of upper respiratory symptoms (Langkamp-Henken B et al 2004).

2)A two-year supplementation program of vitamins and micronutrients showed that selenium and zinc significantly reduced infections in elderly residents of nursing homes (Girodon F et al 1997) and enhanced the residents’ immune response to influenza vaccination (Girodon F et al 1999).
Mice that are deficient in selenium are more susceptible to influenza infection (Beck MA 2001). In selenium-deficient mice, the pro-inflammatory response is stronger and the immune response is weaker than in mice that have an adequate level of selenium (Beck MA et al 2003). Moreover, the genome of viruses in selenium-deficient mice shifts toward more virulent, resistant strains (Beck MA et al 2004).

Zinc has also been studied extensively for its ability to inhibit the viruses (such as the rhinovirus) that cause the common cold (Hulisz D 2004; Prasad AS et al 2000; Marshall S 1998; Mossad SB et al 1996).

Lactoferrin. Lactoferrin is a subfraction of whey and has antiviral, antimicrobial, anticancer, and immune-enhancing effects. Lactoferrin is concentrated in the saliva, where it comes into direct contact with pathogens and kills or suppresses them through a variety of mechanisms (Kawasaki Y et al 1993; Schoen P et al 1997). Lactoferrin may stimulate macrophages, which in turn may help induce cell-mediated immunity (Zimecki M et al 2002). Lactoferrin is present naturally in many mucous membrane secretions, suggesting an innate antimicrobial function (Zimecki M et al 2002; Nishiya K et al 1982). A recent study showed that lactoferrin inhibits viral infection by interfering with the ability of certain viruses to bind to cell receptor sites (Waarts BL et al 2005).

Elderberry extract. Studies show that a black elderberry extract (Sambucol) has antiviral properties against 10 strains of influenza virus. In a double-blind, placebo-controlled, randomized study, elderberry extract reduced the duration of influenza symptoms by one to two days (Barak V et al 2001; Zakay-Rones Z et al 1995).

Tea. Green tea has been shown to inhibit bacteria and viruses and stimulate the immune system. Black tea and extracted components, such as catechin and saponins (Hayashi K et al 2000), inhibit influenza virus growth, infectivity, and symptoms (Iwata M et al 1997a,b). In a cell culture study, the active ingredients in green tea were found to be powerful inhibitors of all varieties of influenza virus (Song JM et al 2005).

Garlic.

Garlic has been valued for centuries for its medicinal properties. Garlic, and its active component, allicin, have a wide spectrum of antifungal, antibacterial, and antiviral action. It benefits the immune system by increasing the number of natural killer cells and the killer activities of spleen cells (Harris JC et al 2001; Kyo E et al 2001). One recent study tested an allicin-containing garlic supplement on a group of 146 volunteers for four months. Half the group took one garlic capsule daily while the other half received a placebo. The placebo group had 63 percent more infections than the group that took the garlic capsule. Even more significant, those who took garlic capsules and who did catch a cold experienced symptoms for an average of only 1.52 days, compared with 5.01 days for the placebo group (Josling P 2001). Aged garlic has also been shown to have antiviral properties, particularly against influenza B (Tsai Y et al 1985) and to have immunomodulatory effects (Kyo E et al 2001).

Dehydroepiandrosterone and melatonin. In addition, the hormones dehydroepiandrosterone (DHEA) and melatonin have been shown to bolster the body’s immune response (Maestroni GJ 1993, 1999; Padgett DA et al 1997, 2000). Taking higher-than-usual doses (200 to 400 mg) of DHEA in the morning and higher-than-usual doses (10 to 50 mg) of melatonin before bedtime would appear to be logical approaches to battling a viral infection.

Cimetidine. The antiviral drug cimetidine (Tagamet®) is an over-the-counter drug used to treat heartburn. It also has potent immune system-boosting effects that can drastically reduce the duration of certain viral infections. Because cimetidine is safe for most people to take, 800 to 1000 mg taken at night (or 200 mg three times a day and 400 mg at night) can help boost the immune system in the event of exposure to influenza. Cimetidine in 200-mg tablets can be purchased over the counter. The directions in over-the-counter package inserts indicate that it is safe to take as much as 800 mg cimetidine a day. Some published studies state that up to 1000 mg cimetidine daily is safe (Choi YS et al 1993).

Life Extension Foundation Recommendations

By staying healthy and avoiding viral infection and environmental pollutants whenever possible, your chances of contracting acute bronchitis will be greatly reduced. Acute bronchitis is more common during the winter months, the flu and cold season, than at other times. Common-sense strategies to prevent acute bronchitis include ensuring appropriate and thorough hand washing to avoid exposure to viruses and reducing exposure to such irritants as air pollution, tobacco, and smoke (Hueston WJ et al 1998).

If exposure to a potential virus has already occurred, Life Extension’s aggressive anticold and antiflu program may help reduce the risk of infection. At the first sign of infection, the following supplements may help ward off more serious illness:

1)Cimetidine—800 to 1000 milligrams (mg) daily

2)Pure Gar brand garlic—9000 mg once or twice daily (consume food after ingesting this amount of garlic to reduce esophageal burning)

3)Kyolic aged garlic extract—3600 mg daily

4)DHEA—200 to 400 mg daily in the morning

5)Lactoferrin—1200 mg daily

6)Zinc—two 24-mg lozenges every two hours while awake. This is a very high dosage of zinc and is toxic if taken for long periods. Take this much zinc only for a few days.

7)Melatonin—10 to 50 mg at bedtime

8)Vitamin C—6000 mg daily (1000 mg every hour for the first six hours), then 3000 mg daily (1000 mg several hours apart).

9)Vitamin E—400 international units (IU) daily

10)Green tea—725 mg daily. A decaffeinated form is available for people who are sensitive to caffeine.

11)Selenium—200 micrograms (mcg) daily

12)Elderberry extract—30 mg, three times daily

Once acute bronchitis has developed, the following nutrients might help reduce inflammation and provide your body with valuable antioxidant support:

13)Vitamin C—2000 to 3000 mg daily

14)Vitamin E—400 IU daily, with at least 200 mg gamma tocopherol

15)NAC—600 to 1800 mg daily

16)EPA/DHA—1400 mg EPA and 1000 mg DHA daily

17)GLA—900 to 1800 mg daily

18)Curcumin—800 to 1600 mg daily

19)Bromelain—500 mg daily, with food

Product Availability
All the nutrients and supplements discussed in this section are available through the Life Extension Foundation Buyers Club, Inc.

The blood tests discussed in this section are available through Life Extension National Diagnostics, Inc.

Bronchitis Safety Caveats
An aggressive program of dietary supplementation should not be launched without the supervision of a qualified physician. Several of the nutrients suggested in this protocol may have adverse effects. These include:

Bromelain

1)Consult your doctor before taking bromelain if you are taking anticoagulants or antithrombotic agents. Bromelain can thin the blood.

2)Bromelain can cause gastrointestinal symptoms such as nausea and diarrhea.

3)Bromelain can cause bleeding from the uterus between menstrual periods (metrorrhagia) and excessive uterine bleeding during menstruation (menorrhagia).

Curcumin

1)Do not take curcumin if you have a bile duct obstruction or a history of gallstones. Taking curcumin can stimulate bile production.

2)Consult your doctor before taking curcumin if you have gastroesophageal reflux disease (GERD) or a history of peptic ulcer disease.

3)Consult your doctor before taking curcumin if you take warfarin or antiplatelet drugs. Curcumin can have antithrombotic activity.

4)Always take curcumin with food. Curcumin may cause gastric irritation, ulceration, gastritis, and peptic ulcer disease if taken on an empty stomach.

5)Curcumin can cause gastrointestinal symptoms such as nausea and diarrhea.

DHEA

1)Do not take DHEA if you could be pregnant, are breastfeeding, or could have prostate, breast, uterine, or ovarian cancer.

2)DHEA can cause androgenic effects in woman such as acne, deepening of the voice, facial hair growth and hair loss.

EPA/DHA

1)Consult your doctor before taking EPA/DHA if you take warfarin (Coumadin). Taking EPA/DHA with warfarin may increase the risk of bleeding.

2)Discontinue using EPA/DHA 2 weeks before any surgical procedure.

Garlic

1)Garlic has blood-thinning, anticlotting properties.

2)Discontinue using garlic before any surgical procedure.

3)Garlic can cause headache, muscle pain, fatigue, vertigo, watery eyes, asthma, and gastrointestinal symptoms such as nausea and diarrhea.

4)Ingesting large amounts of garlic can cause bad breath and body odor.

GLA

1)Consult your doctor before taking GLA if you take warfarin (Coumadin). Taking GLA with warfarin may increase the risk of bleeding.

2)Discontinue using GLA 2 weeks before any surgical procedure.
GLA can cause gastrointestinal symptoms such as nausea and diarrhea.

Green Tea

1)Consult your doctor before taking green tea extract if you take aspirin or warfarin (Coumadin). Taking green tea extract and aspirin or warfarin can increase the risk of bleeding.

2)Discontinue using green tea extract 2 weeks before any surgical procedure. Green tea extract may decrease platelet aggregation.

3)Green tea extract contains caffeine, which may produce a variety of symptoms including restlessness, nausea, headache, muscle tension, sleep disturbances, and rapid heartbeat.

Melatonin

1)Do not take melatonin if you are depressed.

2)Do not take high doses of melatonin if you are trying to conceive. High doses of melatonin have been shown to inhibit ovulation.

3)Melatonin can cause morning grogginess, a feeling of having a hangover or a “heavy head,” or gastrointestinal symptoms such as nausea and diarrhea.

NAC

1)NAC clearance is reduced in people who have chronic liver disease.

2)Do not take NAC if you have a history of kidney stones (particularly cystine stones).

3)NAC can produce a false-positive result in the nitroprusside test for ketone bodies used to detect diabetes.

4)Consult your doctor before taking NAC if you have a history of peptic ulcer disease. Mucolytic agents may disrupt the gastric mucosal barrier.

5)NAC can cause headache (especially when used along with nitrates) and gastrointestinal symptoms such as nausea and diarrhea.

Selenium

1)High doses of selenium (1000 micrograms or more daily) for prolonged periods may cause adverse reactions.

2)High doses of selenium taken for prolonged periods may cause chronic selenium poisoning. Symptoms include loss of hair and nails or brittle hair and nails.

3)Selenium can cause rash, breath that smells like garlic, fatigue, irritability, and nausea and vomiting.

Vitamin C

1)Do not take vitamin C if you have a history of kidney stones or of kidney insufficiency (defined as having a serum creatine level greater than 2 milligrams per deciliter and/or a creatinine clearance less than 30 milliliters per minute.

2)Consult your doctor before taking large amounts of vitamin C if you have hemochromatosis, thalassemia, sideroblastic anemia, sickle cell anemia, or erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency. You can experience iron overload if you have one of these conditions and use large amounts of vitamin C.

Vitamin E

1)Consult your doctor before taking vitamin E if you take warfarin (Coumadin).

2)Consult your doctor before taking high doses of vitamin E if you have a vitamin K deficiency or a history of liver failure.

3)Consult your doctor before taking vitamin E if you have a history of any bleeding disorder such as peptic ulcers, hemorrhagic stroke, or hemophilia.

4)Discontinue using vitamin E 1 month before any surgical procedure.

Zinc

1)High doses of zinc (above 30 milligrams daily) can cause adverse reactions.

2)Zinc can cause a metallic taste, headache, drowsiness, and gastrointestinal symptoms such as nausea and diarrhea.

3)High doses of zinc can lead to copper deficiency and hypochromic microcytic anemia secondary to zinc-induced copper deficiency.

4)High doses of zinc may suppress the immune system.

RESPIRATORY-CHRONIC OBSTRUCTIVE PULMONARyY DISEASE

noreply@blogger.com (Kishen) — Thu, 21 Feb 2008 02:19:00 +0000

Emphysema and Chronic Bronchitis

Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating lung disease. The disease is characterized by irreversible airflow limitation in the lungs. The umbrella of COPD encompasses the following conditions:

1)Emphysema, in which the alveoli in the lungs, the tiny sacs where oxygen transfer takes place, are destroyed and enlarged

2)Chronic bronchitis, or the permanent inflammation of airways, accompanied by a chronic cough
COPD exacts a tremendous toll on society. It affects more than 16 million people in the United States, and by 2020 it is expected to rise from the sixth- to the third-most-common cause of death in the world (Kasper DL et al 2005). Unfortunately, there is no single safe and effective treatment. However, because COPD is an inflammatory disease in which sufferers are subjected to high levels of oxidative stress, high doses of antioxidants and natural anti-inflammatories may be able to slow the disease’s progression and reduce the amount of prescription medication needed.

Inflammation and Airway Restriction

The major cause of COPD in the United States is cigarette smoking, although it has also been linked to other factors, such as hyperresponsive airways, respiratory infections, and exposure to dust and environmental pollutants. The longer and more heavily people smoke, the more likely they are to develop COPD.

COPD is usually a progressive disease that develops slowly, often over the course of decades. In a typical case, a cigarette smoker would experience declining lung function for many years before being diagnosed with COPD and receiving therapy. During those years, while the disease is developing, the lungs are undergoing several changes characteristic of the disease.

The bulk of lung tissue is composed of alveoli, or tiny sacs, where the exchange of oxygen and carbon dioxide takes place. One of the primary factors in COPD is emphysema, which occurs when alveoli enlarge and cluster. This process destroys the very sensitive areas where gases are exchanged across thin walls. Emphysema occurs in stages. First, chronic exposure to an irritant, such as cigarette smoke, causes inflammatory cells (such as macrophages and neutrophils) to gather in the airspaces of the lung. These inflammatory cells release chemicals that damage the extracellular matrix of the lung, that is, the proteins that are responsible for providing structure to the lungs. Finally, the ability of the lung to repair the extracellular matrix is compromised, resulting in the coalescence of alveoli into larger, less efficient air chambers.

People with emphysema also suffer from airway obstruction, especially in airways less than 2 mm in diameter. A number of changes occur in these airways that aggravate the disease, including hypertrophy of smooth muscle cells, the formation of scar tissue in the airway walls (fibrosis), and the infiltration of inflammatory cells.

Underlying all this damage is an inflammatory response mounted by the immune system. In a typical case, cigarette smoke in the lungs would come into contact with macrophages (immune system cells) that normally patrol the airspace. In response to the toxins in the smoke, the macrophages release inflammatory chemicals and begin to recruit more immune-system cells, which in turn release more inflammatory chemicals, as well as enzymes that degrade the extracellular matrix.

These changes in the lung are detectable but incremental. Symptoms appear gradually and may actually have been present for many years before a patient seeks medical treatment. Coughing, sputum production, and breathlessness are the characteristic symptoms associated with COPD. Early in the disease, the patient’s physical examination may even be normal. Later in the disease, however, patients sometimes develop the classic “barrel chest” associated with COPD. It occurs because residual air is trapped in the lungs, leading to their hyperinflation. In addition, the increased effort required to exhale can produce wheezing, while pursed lips or grunting respirations may signal the patient’s efforts to keep the airways open by increasing pressure at the beginning of expiration (Lim TK 1996).

COPD is a variable condition, with some patients having more symptoms of emphysema, such as breathlessness and “air hunger,” while others manifest more symptoms of chronic bronchitis or asthma, such as wheezing and air trapping (Kasper DL et al 2005). The manifestations of COPD are not limited to the lungs. COPD also puts patients at increased risk of atherosclerosis and osteoporosis. Poor lung function and poor nutrition may cause muscle weakness, abnormalities in fluid and electrolyte balance, and depression.

Genetic Causes of COPD

Although cigarette smoking is the major risk factor for COPD, in recent years researchers have uncovered genetic abnormalities that may make people more susceptible to the disease. Hereditary deficiency of an enzyme called alpha-1 antitrypsin confers significant increased risk (Kasper DL et al 2005). Unlike other forms of COPD, lung damage in alpha-1 antitrypsin deficiency appears relatively early in life (Lee P et al 2002). Patients with alpha-1 antitrypsin deficiency also may have liver disease and other organ system damage, and they are more vulnerable to the damaging effects of cigarette smoke (US National Library of Medicine 2005).

Variations in other genes may explain some of the variability in severity and age at onset of COPD, and researchers hope to identify markers of these genes that will permit early identification of people at the greatest risk (US National Library of Medicine 2005; Meyers DA et al 2004).

Diagnosis and Conventional Treatment

COPD should be considered in any individual with a chronic cough, sputum production, shortness of breath, or risk factors such as tobacco use, alpha-1 antitrypsin deficiency, or occupational exposure to dust and chemicals. Diagnostic testing should include pulmonary function tests (PFTs). PFTs determine lung volume and capacity and take dynamic measurements, such as the amount of air the patient can force out of the lungs during a given time interval. The results of PFTs are used to determine the severity of COPD, which in turn can establish the likely prognosis and may help guide treatment (Pierson DJ 2006). Other tests, such as x-rays, computed tomography, and magnetic resonance imaging, may be performed if complications such as pneumonia are suspected.

COPD cannot be cured, in part because it usually is the result of years of development. According to the Global Initiative for Chronic Obstructive Lung Disease, effective COPD management has the following goals (Global Strategy 2004):

1)Preventing disease progression

2)Relieving symptoms

3)Improving exercise tolerance and health status

4)Preventing and treating complications and exacerbations

5)Reducing mortality

Among the most important steps for smokers is to quit smoking immediately. Studies have shown that if smoking is ceased early in the disease, the rate of lung decline might be slowed to that of a normal nonsmoker (Kasper DL et al 2005).

Bronchodilators are first-line therapy for COPD (Sutherland ER 2004). This large group of drugs includes the following (Weder MM 2005):

1)Beta agonists, or agents derived from adrenaline (such as albuterol)

2)Anticholinergics, or agents related to atropine (such as ipratropium)

3)Methylxanthines, or agents related to caffeine (such as theophylline)

All three categories have some effectiveness, but all three also produce significant side effects, such as increased heart rate and blood pressure, trembling, and cardiac arrhythmias. The anticholinergics, particularly some of the more recent long-acting agents such as tiotropium, may provide the best combination of tolerability and duration of action (Koumis T 2005). Side effects of these drugs include chest pain, blurred vision, and more. Theophylline has fallen out of use in the industrialized world because of better alternatives, but its low cost and wide availability make it a still-useful agent in less-developed countries (Weder MM 2005).

Patients who cannot be maintained on bronchodilators may need to start an inhaled steroid medication. At low doses, these medications are safe, and they have been shown to contribute to an improvement in quality of life for patients suffering from COPD (Calverley PM 2004).

When COPD patients experience an exacerbation of their disease, more aggressive medical therapy may be required. The most commonly used medications in this situation are the short-acting bronchodilators, which are sometimes used on an as-needed basis to relieve acute symptoms (Chorostowska-Wynimko J 2005; Urbano FL 2005). Inhaled and occasionally oral steroid medications may be added as well. If the acute exacerbation is caused by a bacterial infection, antibiotics may be prescribed.

The most severe exacerbations of COPD require hospitalization, often with mechanical ventilation in an intensive care unit. Unfortunately, ventilatory management of COPD patients is complex and has many pitfalls. This has led to increased use of home, noninvasive, positive-pressure ventilation systems that may stave off the need for more-aggressive treatment (Brochard L 2003; Wijkstra PJ 2003).

New drugs. About 70 therapeutic drugs are in development for related COPD needs. The newest class of drugs is phosphodiesterase-4 inhibitors; two of these, roflumilast and cilomilast, may be available in the near future (Business Wire 2004). Phosphodiesterase-4 inhibitors produce bronchial smooth muscle relaxation by taking away the intracellular stimulus that maintains contraction. This effect is similar to that of the other bronchodilators, though it is produced by a different and more targeted mechanism and produces fewer side effects. These drugs have been shown to reduce inflammation, improve lung function, decrease exacerbations, and improve quality of life (Vignola AM 2004).

Researchers are also reporting amazing results with retinoic acid, a biologically active form of vitamin A. In a mouse model of emphysema, retinoic acid was able to completely restore lung architecture and alveolar function (Hind M et al 2004; Maden M et al 2004). Human studies have been similarly encouraging. In one randomized, double-blind, placebo-controlled study, all-trans-retinoic acid was administered in low doses to 20 patients with severe emphysema. The drug was well tolerated, with few side effects, and the researchers called for longer studies with higher doses (Mao JT et al 2002). The same group of investigators also found that retinoic acid restores the balance of important enzymes called matrix metalloproteinases that are thought to contribute to alveolar breakdown (Mao JT et al 2003).

Flu vaccines. Flu vaccines can reduce COPD exacerbations, serious illness, and death by 50 percent. They are given in the fall or twice a year, in fall and winter. Vaccines that prevent infection with the bacterial organism pneumococcus can reduce complications such as pneumonia and may reduce the rate of exacerbations of the disease. (Alfageme I et al 2006; Ansaldi F et al 2005).

Nutritional Therapy

Medications and surgery can be effective in treating symptoms, but they do little to prevent disease progression. Mortality rates from COPD are still high, and quality of life is often severely impaired.

Nutritional supplementation aimed at increasing antioxidant capacity and reducing inflammation may offer significant added value (Schols A 2003; Romieu I et al 2001). In addition, people with COPD have increased energy requirements because it is harder for them to breathe. Difficulty breathing may affect eating, potentially resulting in malnutrition. Proper nutrition through a balanced diet and appropriate supplementation is important in COPD management.

Because of the role of oxidant stress in causing and perpetuating COPD (Drost EM et al 2005) and the low levels of natural antioxidants in patients’ tissues (Kluchova Z et al 2006; Rahman I et al 2006; Nadeem A et al 2005), antioxidant supplementation may be helpful (Kelly FJ 2005; Spurzem JR et al 2005; Romieu I et al 2001).

Vitamins A, C, and E. Levels of vitamins A and E are significantly lower during exacerbations of COPD than they are in stable COPD, suggesting that antioxidants should be used during exacerbations (Tug T et al 2005). Although vitamins A, C, and E are beneficial, vitamin A may be most important because it catalyzes removal of the most reactive form of oxygen radical (Tug T et al 2005). Serum levels of vitamin A are lower in those with moderate or severe COPD. Vitamin A supplements for 30 days improved performance on PFTs in one small study (Paiva SA et al 1996).

Vitamin E levels are low in smokers, increasing their susceptibility to injury from free radicals. Vitamin E supplementation can reduce the risk of COPD in smokers (Daga MK et al 2003). Serum vitamin C levels are also frequently reduced in COPD (Tug T et al 2005). High-dose vitamin C may prevent oxidant-mediated lung injury during inflammation. Vitamin C also reactivates vitamin E that has been depleted by oxidant molecules.

Coenzyme Q10. When coenzyme Q10 (CoQ10) was given to eight COPD patients with low levels of the nutrient, they experienced improved oxygenation of blood without a change in lung function. Oxygen pressure significantly improves, and heart rate decreases. Exercise performance increases. CoQ10 affects muscular energy metabolism in chronic lung diseases (Fujimoto S et al 1993).

N-acetylcysteine. N-acetylcysteine (NAC) is a powerful antioxidant that protects against toxins, including acrolein, found in cigarette smoke. NAC is a selective immune-system enhancer, improving symptoms by breaking down mucus and preventing recurrence of lung illness such as chronic bronchitis. Supplementation with NAC reduces exacerbation and improves chronic bronchitis (Stey C et al 2000).

L-carnitine. Respiratory infections increase the frequency and severity of exacerbations. L-carnitine may boost immune function, enhance fatty acid and glucose energy metabolism, and prevent wasting syndrome. In one very recent human trial, carnitine improved exercise tolerance and the strength of respiratory muscles in COPD patients; levels of the metabolic by-product lactate, which causes fatigue, were also reduced (Borghi-Silva A et al 2006).

Bromelain. Bromelain, which is present in the pineapple fruit, can benefit stable COPD patients and decrease exacerbations by reducing mucus production (Bernkop-Schnurch A et al 2000). Individuals allergic to pineapple may be sensitive to bromelain. Gastritis can be aggravated by bromelain (Jaber R et al 2002).

Essential Fatty Acids
Essential fatty acids are those that cannot be produced by the body and must come from dietary or supplemental sources. Omega-3 fatty acids are essential in modulating toxic inflammatory responses. Omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) protect against damaging inflammatory reactions and, with vitamin E, build healthy cell membranes and repair tissues (Ergas D et al 2002; Fernandes G et al 1996).

The destructive effects of chronic inflammation on cellular structures can be reduced by supplementing with EPA and DHA, which repair both cell and mitochondrial membranes (Chapkin RS et al 2002). Mitochondrial membranes, because of their involvement in energy production, are especially susceptible to oxidant damage.

Supplementing with omega-3 fatty acids improves oxygen transfer in adult respiratory distress syndrome, a condition in which oxidant damage and inflammation cause impaired lung function. Omega-3 supplements have been shown to be beneficial in patients with COPD. One study showed a significant improvement in dyspnea and pulse oximetry levels and a decrease in inflammatory markers in serum and sputum in a group of patients receiving supplementation, compared with controls (Matsuyama W et al 2005). Higher dietary levels of omega-3 fatty acids may protect smokers against COPD (Shahar E et al 1994).

Nondrug Strategies

Smoking cessation and patient education. The major cause of COPD is cigarette smoking. Comprehensive smoking cessation programs include counseling, organized “quit” plans, and when necessary, nicotine replacement therapy (such as gum, inhalers, skin patches, and other methods). Drugs such as bupropion (Wellbutrin®) are also effective when taken under a doctor’s care (Cornuz J 2006). Both hypnosis and acupuncture may be helpful in quitting smoking (Zwick H 2005). The National Network of Tobacco Cessation Quitlines at 1-800-QUITNOW (1-800-784-8669) can provide information on finding a quitline in any geographical area in the United States.

Exercise programs. Because air passage is obstructed in COPD, the lungs and heart work harder to carry oxygen throughout the body. Exercise programs strengthen chest muscles and facilitate breathing. Multidisciplinary pulmonary rehabilitation programs provide well-monitored exercise programs.

Breathing exercises. Breathing exercises induce relaxation and make breathing easier. Pursed-lip breathing stimulates relaxation, increasing oxygen intake and preventing shortness of breath. It has been shown to increase exercise tolerance and shorten recovery times (Garrod R et al 2005). Breathing exercise regimens are an important part of a COPD rehabilitation program. Respiratory therapists working closely with physicians can specify the best regimen for each individual (Beckerman M et al 2005).

Oxygen. Oxygen therapy alleviates a lack of oxygen but increases oxidative stress, potentially increasing damage to airways. Patients with COPD are known to have reduced antioxidant capacity (Kluchova Z et al 2006; Rahman I et al 2006), which may be further diminished by oxygen therapy (Nadeem A et al 2005). A recent study, however, demonstrated that supplemental oxygen actually reduced levels of oxidant molecules and inflammatory cytokines in exercising patients with COPD, presumably by supporting normal metabolism and preventing stress-induced oxidant species from being produced (van Helvoort HA et al 2006).

Surgery. Surgical interventions are becoming more important in COPD as techniques improve (Kasper DL et al 2005). When alveoli coalesce in emphysema, they can form large blebs, or bullae; surgical removal of these bullae can help restore lung volume and allow remaining healthy parts of the lung to function better. Similarly, lung volume reduction surgery has been used successfully to improve lung function and quality of life. Lung transplantation is also a consideration for COPD sufferers.

Life Extension Foundation Recommendations
Any patients with COPD, emphysema, or bronchitis are urged to stop smoking and to limit their exposure to environmental toxins whenever practical. Additionally, exercise, breathing exercises, and oxygen therapy may be helpful, as well as the use of steam and hot-mist vaporizers. If the breathing difficulty results in trouble eating, a strong multivitamin that includes magnesium is recommended to prevent malnutrition and restore energy to damaged cells.

Studies have shown that retinoic acid has a remarkable ability to restore alveolar architecture. Retinoic acid is available as Vesanoid (tretinoin) for the treatment of leukemia, but it can be prescribed for COPD.

In addition, the following nutrients have been shown to restore antioxidant capacity and help reduce inflammation:

1)Vitamin A—25,000 international units (IU) daily

2)Vitamin C—3000 milligrams (mg) daily

3)Vitamin E—400 IU daily (with at least 200 mg gamma tocopherol)

4)NAC—600 mg, three times daily

5)CoQ10—200 to 400 mg daily

6)Omega-3 fatty acids—1000 mg DHA and 1400 mg EPA daily

7)Gamma-linolenic acid—900 to 1800 mg daily

8)Acetyl-L-carnitine—2000 to 3000 mg daily

9)Bromelain—500 mg at the beginning of each meal

Product Availability
All the nutrients and supplements discussed in this section are available through the Life Extension Foundation Buyers Club, Inc.

The blood tests discussed in this section are available through Life Extension National Diagnostics, Inc. ORDER ON LINE
COPD Safety Caveats

An aggressive program of dietary supplementation should not be launched without the supervision of a qualified physician. Several of the nutrients suggested in this protocol may have adverse effects. These include:

Acetyl-L-Carnitine

1)Acetyl-L-carnitine can cause gastrointestinal symptoms such as nausea and diarrhea.

Bromelain

1)Consult your doctor before taking bromelain if you are taking anticoagulants or antithrombotic agents. Bromelain can thin the blood.

2)Bromelain can cause gastrointestinal symptoms such as nausea and diarrhea.

3)Bromelain can cause bleeding from the uterus between menstrual periods (metrorrhagia) and excessive uterine bleeding during menstruation (menorrhagia).

Coenzyme Q10

1)See your doctor and monitor your blood glucose level frequently if you take CoQ10 and have diabetes. Several clinical reports suggest that taking CoQ10 may improve glycemic control and the function of beta cells in people who have type 2 diabetes.

2)Statin drugs (such as lovastatin, simvastatin, and pravastatin) are known to decrease CoQ10 level.

EPA/DHA

1)Consult your doctor before taking EPA/DHA if you take warfarin (Coumadin). Taking
2)EPA/DHA with warfarin may increase the risk of bleeding.

3)Discontinue using EPA/DHA 2 weeks before any surgical procedure.

GLA

1)Consult your doctor before taking GLA if you take warfarin (Coumadin). Taking GLA with warfarin may increase the risk of bleeding.

2)Discontinue using GLA 2 weeks before any surgical procedure.

3)GLA can cause gastrointestinal symptoms such as nausea and diarrhea.

NAC

1)NAC clearance is reduced in people who have chronic liver disease.

2)Do not take NAC if you have a history of kidney stones (particularly cystine stones).

3)NAC can produce a false-positive result in the nitroprusside test for ketone bodies used to detect diabetes.

4)Consult your doctor before taking NAC if you have a history of peptic ulcer disease. Mucolytic agents may disrupt the gastric mucosal barrier.

5)NAC can cause headache (especially when used along with nitrates) and gastrointestinal symptoms such as nausea and diarrhea.

Vitamin A

1)Do not take vitamin A if you have hypervitaminosis A.

2)Do not take vitamin A if you take retinoids or retinoid analogues (such as acitretin, all-trans-retinoic acid, bexarotene, etretinate, and isotretinoin). Vitamin A can add to the toxicity of these drugs.

3)Do not take large amounts of vitamin A. Taking large amounts of vitamin A may cause acute or chronic toxicity. Early signs and symptoms of chronic toxicity include dry, rough skin; cracked lips; sparse, coarse hair; and loss of hair from the eyebrows. Later signs and symptoms of toxicity include irritability, headache, pseudotumor cerebri (benign intracranial hypertension), elevated serum liver enzymes, reversible noncirrhotic portal high blood pressure, fibrosis and cirrhosis of the liver, and death from liver failure.

Vitamin C

1)Do not take vitamin C if you have a history of kidney stones or of kidney insufficiency (defined as having a serum creatine level greater than 2 milligrams per deciliter and/or a creatinine clearance less than 30 milliliters per minute.

2)Consult your doctor before taking large amounts of vitamin C if you have hemochromatosis, thalassemia, sideroblastic anemia, sickle cell anemia, or erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency. You can experience iron overload if you have one of these conditions and use large amounts of vitamin C.

Vitamin E

1)Consult your doctor before taking vitamin E if you take warfarin (Coumadin).

2)Consult your doctor before taking high doses of vitamin E if you have a vitamin K deficiency or a history of liver failure.

3)Consult your doctor before taking vitamin E if you have a history of any bleeding disorder such as peptic ulcers, hemorrhagic stroke, or hemophilia.

4)Discontinue using vitamin E 1 month before any surgical procedure.

RESPIRATORY-SINUSITIS

noreply@blogger.com (Kishen) — Thu, 21 Feb 2008 01:59:00 +0000

Sinusitis

The sinuses are air-filled sacs in the facial bones of the head. They have several functions, including warming incoming air and helping to form certain sounds. When the sinuses become infected and inflamed, the condition is known as sinusitis. Sinusitis ranges from a minor annoyance to a serious condition that might require surgery.

The four pairs of sinuses are listed below, in order from highest frequency of infection to least:

1)Maxillary sinuses, located in the cheekbone, right below the eye sockets

2)Ethmoid sinuses, located behind the bridge of the nose

3)Frontal sinuses, located in the lower forehead, in the middle of the head just above the eye sockets

4)Sphenoid sinuses, located behind the eyes

The sinuses are lined with cells covered with small, hair-like projections called cilia, which help clear mucus from the chambers and keep them bacteria free (Rubin BK et al 2004). When the ability to clear the passageways is blocked, however, the sinuses may become infected. Sinusitis is classified by duration of illness (acute or chronic), by cause (infectious or other), and by the type of infectious agent involved (bacterial, fungal, or viral). According to the National Institutes for Health, approximately 37 million Americans are affected by sinusitis every year. Health care providers report nearly 32 million cases of chronic sinusitis every year (National Institute of Allergy and Infectious Diseases 2005).

Even if it is not considered serious, sinusitis can have a major impact on quality of life (Bhattacharyya N 2003; Chester AC 2003; Linder JA et al 2003). In rare cases, sinusitis can cause infections of the brain and other complications (National Institute of Allergy and Infectious Diseases 2005).

Researchers in Japan have found a link between chronic sinusitis in older people and cognitive impairment (Matsui T et al 2003). A study of an older population found significant differences in Mini-Mental Status Examination. Examination scores between people with chronic sinusitis and those without (Matsui T et al 2003) underscore the importance of treating sinusitis infections appropriately in this age group.

Causes and Risk Factors for Sinusitis
Acute sinusitis is almost always caused by bacteria, fungi, or viruses. Bacteria that cause sinusitis include streptococcal and staphylococcal strains, which also cause the common cold. Fungi are known to cause sinusitis, but mainly in immunocompromised people (such as those with HIV/AIDS) or people who are sensitive to fungi (Shin SH et al 2004; Parikh SL et al 2004). People at highest risk for sinusitis are those with allergies, asthma, or an increased immune response to fungi; smokers; or those with compromised immune systems (Kasper DL et al 2005).

Noninfectious risk factors for sinusitis include rapid changes in air pressure (e.g., when diving, flying, or high-altitude hiking) and exposure to chemical irritants (Rubin BK et al 2004; American Academy of Family Physicians 2005). Additional risk factors for sinusitis are conditions that cause sinus obstruction, such as tumors, and conditions that alter mucus clearance, such as cystic fibrosis (Rubin BK et al 2004).

Diagnosis of Sinusitis

No single test confirms a diagnosis of sinusitis. In most cases, the diagnosis will be made on the basis of symptoms, which depend on which sinus or sinuses are affected. Common symptoms include:

Headache

1)Pain in the forehead, over the area where the frontal sinuses are located

2)Upper jaw pain

3)Toothache

4)Pain in the eyes

5)Swelling of the eyelids or areas around the eyes

6)Earache

7)Neck pain

8)Tenderness on the sides of the nose

9)Loss of smell

10)Thick or colored nasal discharge

Conventional Treatment of Sinusitis

Decongestants. The major decongestants used in over-the-counter medications are phenylephrine and pseudoephedrine. Decongestants are usually coupled with a pain reliever, such as acetaminophen, ibuprofen, or aspirin. Over-the-counter medications are used to (1) reopen the nasal passages by reducing the volume of mucus, (2) reduce nasal congestion, (3) relieve pain and pressure, and (4) reduce the potential for complications.

Antibiotics. Antibiotics are used to treat bacterial sinusitis (Rubin BK et al 2004). In very serious cases, intravenous antibiotics may be recommended (Rubin BK et al 2004). They are ineffective in viral sinusitis.

Pain relievers. Pain relievers are often used in conjunction with decongestants. Acetaminophen, ibuprofen, and aspirin are all commonly used in sinusitis.

Corticosteroids. Steroids are used to suppress inflammation. They may be used in topical nasal sprays.

Nonpharmacological therapies. Sinusitis sufferers sometimes use the following therapies, sometimes in combination with pharmaceuticals.

1)Steam treatment

a)A warm, moist towel to the face

b)A humidifier

2)Nasal saline wash

a)If symptoms are mild to moderate, some healthcare providers will delay treatment with medications in favor of nasal saline solution. However, if symptoms continue for seven days or longer, more aggressive treatment is implemented.

3)Surgery

a)Surgical treatment to debride abscesses or to remove impacted mucus is used for very serious cases of sinusitis.

Nutrient and Supplemental Therapy
Because most cases of sinusitis are caused by bacterial or viral infection, such infections should be treated aggressively—at the first sign of infection—to prevent them from spreading into the sinuses. In addition to getting plenty of rest and drinking a lot of fluid, sufferers may take the following supplements, which have been shown to inhibit infection with viral or bacterial agents that cause the common cold and influenza:

Dehydroepiandrosterone (DHEA). Aging humans gradually lose youthful levels of DHEA, an adrenal hormone and precursor to other important hormones in the body (Shealy CN 1995). Numerous studies have shown that DHEA causes powerful immune-enhancing and antiviral effects (Ben-Yehuda A et al 1998; Corsini E et al 2002; Danenberg HD et al 1995, 1997; Degelau J et al 1997; Padgett DA et al 1997, 2000). The administration of 50 mg DHEA daily to older men resulted in the following immune enhancements compared to placebo :

1)35 percent increase in the number of monocyte immune cells

2)29 percent increase in the number of B immune cells

3)62 percent increase in B cell activity

4)40 percent increase in T cell activity

5)50 percent increase in interleukin (IL)-2

6)22 percent to 37 percent increase in natural killer (NK) cell number

7)45 percent increase in NK cell activity

One reason influenza can be so lethal to older people is that their immune systems are weak. A deficiency in DHEA appears to be partially responsible for the age-related decline in immune function (Fulop T Jr et al 1999; Khorram O et al 1997). One study showed that a metabolite of DHEA augmented activation of helper T cells and protected mice from a lethal influenza virus infection (Padgett DA et al 1997).

Lactoferrin. Lactoferrin has well-documented antiviral, antimicrobial, anticancer, and immune enhancing effects. Lactoferrin secretion is increased during sinusitis, leading researchers to conclude that it is a potent part of the body's natural defense mechanism against sinusitis.

Lactoferrin has been found to directly and indirectly inhibit viruses such as respiratory syncytial virus, human HIV, cytomegalovirus, and herpes simplex type I infection (Puddu P et al 1998; Superti F et al 1997; Harmsen MC et al 1995; Swart PJ et al 1996, 1998; Sano H et al 2003). Specifically, lactoferrin has been shown to increase NK cells (Yamauchi K et al 1998; Swart PJ et al 1998; Waarts BL et al 2005).

Lactoferrin may stimulate macrophages, which in turn may help to induce cell-mediated immunity. Although many of the studies of lactoferrin's functioning have involved animals, lactoferrin is naturally present in many mucous membrane secretions in people, suggesting an innate human antimicrobial function (Nishiya K et al 1982; Zimecki M et al 2002).

A recent study showed that human lactoferrin interferes with the ability of certain viruses to bind to cell receptor sites (Waarts BL et al 2005).

Melatonin. Melatonin, a hormone produced by the pineal gland, has immunity-enhancing benefits in addition to its well-known role as a sleep aid. Melatonin enhances the production of key immune system components, such as NK cells, IL-2, IL-4, IL-10, and gamma interferon (Lissoni P et al 1989, 1994, 1995; Maestroni GJ 1999; Bubenik GA et al 1998). Melatonin has been specifically shown to decrease viral load and prevent death in mice infected with certain viruses. One study of melatonin concluded, “The immunomodulatory, antioxidant, and neuroprotective effects of melatonin suggest that this indole must be considered as an additional therapeutic alternative to fight viral diseases” (Maestroni GJ 1999).

Another study reviewed animal research that examined the immune function benefits of melatonin and found that melatonin activated IL-2 and gamma interferon, the body's natural hormone-like agents that facilitate helper T cell production (Bonilla E et al 2004).

Garlic. With all the high-tech advances occurring in medicine, garlic might be expected to be a relic of the past. Yet the scientific literature documents that garlic has powerful effects against certain viruses.

For instance, one study tested one capsule daily of an allicin-containing garlic supplement (like Pure Gar) on a group of 146 volunteers (Josling P 2001). Over several months half the group received the garlic while the other half got a placebo. The placebo group had 63 percent more common cold infections than the garlic group. Even more significant, those in the garlic group who did catch a cold had symptoms for an average of only 1.52 days, compared with 5.01 days for the placebo group. The doctors who conducted this garlic study concluded, “An allicin-containing supplement can prevent attack by the common cold virus.”

Ribavirin is a prescription drug that has potent antiviral effects (Cattral MS et al 1996; Christie JM et al 1999; da Silva LC et al 2002; de Ledinghen V et al 2002; Di Bisceglie AM et al 1995; Fried MW et al 2002; Galban GE et al 2000; Kumada H 2002; Murphy ME et al 2000; Reichard O et al 1998; Schalm SW et al 1997a,b,1999; Schvarcz R et al 1995). Yet, a Chinese study has found that (at least in the test tube) garlic is more effective than ribavirin in inhibiting viruses that attack the intestinal tract (Luo R et al 2001). Since 1983 the Life Extension Foundation has recommended ribavirin to treat various viral infections, but in this particular study, garlic was shown to be superior.

A number of published studies indicate that both high-allicin garlic (such as Pure Gar) and aged garlic (such as Kyolic aged garlic) support healthy immune function while exerting antiviral effects (Guo NL et al 1993; Josling P 2001; Kyo E et al 2001; Liu ZF et al 2004; Moon DG et al 2000; Tsai Y et al 1985; Weber ND et al 1992). Garlic may be nature's most powerful weapon against certain viruses.

Essential fatty acids. Maintaining the proper ratio of omega-3 to omega-6 fatty acids can maximize the production of anti-inflammatory prostaglandins E1 and E3 while suppressing proinflammatory prostaglandin E2 and leukotriene B4. Most people consume too much omega-6 relative to omega-3 fatty acids. The main omega-3 fatty acids are docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). DHA and EPA exert anti-inflammatory and antithrombotic effects, partly by competing with pro-inflammatory chemicals (Calder PC 2005; Conner WE 2001). Studies suggest that fish oils reduce the production of pro-inflammatory cytokines such as interleukin-1 beta and tumor necrosis factor. Additionally, they can suppress B- and T-lymphocyte synthesis (Kelley DS et al 2000; Endres S et al 1993; Burns EA et al 2004).

Green tea. Green tea, which is rich in antioxidants, has demonstrated the ability to inhibit bacteria (Sakanaka S et al 2000; Stapleton PD et al 2004) and viruses (Song JM et al 2005) and has also been shown to have a protective effect on immune function (Yamamoto Y et al 2004).

Vitamin C. Vitamin C is a potent free radical scavenger and antioxidant derived from citrus fruits and green vegetables. It protects tissues from oxidative stress and enables the actions of vitamin E. Vitamin C in high doses may reduce symptoms associated with viruses and respiratory infections such as colds and flu, which are associated with sinusitis (Gorton HC et al 1999; Hemila H 2004). Multiple studies have found that high doses of vitamin C alleviate common cold and flu symptoms, indicating that the vitamin does indeed have physiologic effects on colds (Hemila H 1997, 2004; Gorton HC et al 1999). In a five-year clinical trial of 50 mg versus 500 mg vitamin C daily, the high-dose group reported fewer colds than the low-dose group (Sasazuki S et al 2005). From a meta-analysis of four double-blind, placebo-controlled trials, Linus Pauling found a 45 percent decrease in the incidence of colds when 1000 mg ascorbic acid (vitamin C) was used daily (Pauling L 1971). Some studies, however, show that vitamin C does not affect the frequency or duration of a common cold.

Zinc. Zinc supports the actions of antiseptic agents and kills microbes directly (Zeelie JJ et al 1998; Sheng J et al 2005). Zinc deficiency is closely associated with susceptibility to infection (Bogden 2004). A number of published studies show that, if zinc lozenges are taken within 24 hours of the onset of common cold symptoms, the severity and duration of cold miseries are significantly diminished (Hulisz D 2004; Prasad AS et al 2000; Marshall S 1998; Mossad SB et al 1996).

Rhinoviruses attach to specific cell receptor sites in sinus and throat tissues, become lodged in the nose and throat, and then replicate out of control. By binding to the same cell receptor sites as do cold viruses, zinc inhibits the ability of rhinoviruses to take hold in the body (Gwaltney JM 2002).

A meta-analysis of all the published literature on zinc lozenges was conducted in 2004 and concluded, “Clinical trial data support the value of zinc in reducing the duration and severity of symptoms of the common cold when administered within 24 hours of the onset of common cold symptoms. Additional clinical and laboratory evaluations are warranted to further define the role of ionic zinc for the prevention and treatment of the common cold and to elucidate the biochemical mechanisms through which zinc exerts its symptom-relieving effects” (Hulisz D 2004).

Patients seeking to relieve cold symptoms by means of zinc should suck on two 24-mg zinc lozenges at the very first symptom of a cold and take two more lozenges every two hours while awake. Once rhinoviruses bind to their receptor sites in the nasal tissues and begin replicating, zinc lozenges lose their efficacy. Considering how inexpensive zinc lozenges are, it makes sense to keep them on hand so that they are available immediately if cold symptoms appear.

One caveat is that chronic use of zinc in doses of more than 100 mg daily may suppress immune function (Chandra RK 1984). If someone takes two zinc lozenges every two hours over the course of a day, the total zinc intake could easily exceed 300 mg daily. This does not appear to be a problem in the short term. If your cold symptoms do not subside after a few days of taking zinc lozenges, it would be best to stop taking them. Remember that less than 100 mg zinc daily can improve immune function, but taking more than 100 mg daily concerns some doctors.

Propolis. Before the discovery of antibiotics, honey was used in the fight against bacteria. The antibacterial effects of this folk remedy have since been confirmed by scientific study ( Lusby PE et al 2005). In addition, in vitro and in vivo studies have shown that bee propolis has antiviral and anti-inflammatory properties and an inhibitory effect on the growth and adherence of streptococci bacteria (Cohen HA et al 2004; Duarte S et al 2003; Mirzoeva OK et al 1996; Serkedjieva J et al 1992; Szmeja Z et al 1989). One study demonstrated that propolis decreased the duration of the common cold to just a few days. This study showed that cold symptoms in the propolis treatment group improved 2.5 times faster than in the placebo group (Szmeja Z et al 1989).

Warning: Raw honey should NEVER be given to a child under one year of age because it presents a significant risk of potentially fatal botulism. This risk vanishes in older children and adults.

Beta-carotene and vitamin E. Beta-carotene has been shown to have a powerful effect in boosting NK cell activity in older men. In a controlled, double-blind study, the effects of 10 to 12 years of beta-carotene supplementation on NK cell activity were evaluated. Although no significant difference was seen in NK cell activity in the middle-aged groups, older men supplemented with beta-carotene had significantly greater NK cell activity than the control group of men of comparable age (Santos et al 1996).

The best-publicized study of the use of vitamin E to boost immune function appeared in 1997 (Meydani et al 1997). The double-blind, placebo-controlled study looked at healthy humans at least 65 years of age. Supplementation with vitamin E for four months improved certain clinically relevant indices of cell-mediated immunity. These results show that a level of vitamin greater than that currently recommended by the Food and Drug Administration enhances certain clinically relevant in vivo indices of T-cell-mediated immune function in healthy older persons.

N-acetylcysteine. N-acetylcysteine (NAC) is an acetylated ester of the amino acid L-cysteine. NAC raises levels of glutathione, a potent internal antioxidant (Roes EM et al 2002). For many years, NAC has been used to treat bronchitis and other lung conditions as an expectorant or mucus thinner as well as an anti-inflammatory.

Rosmarinic acid. Rosmarinic acid is a plant polyphenol found in plants of the Lamiaceae genus, which includes basil, sage, mint, rosemary, and perilla leaf (al Sereiti MR et al 1999). Oral supplementation with extracts of rosmarinic acid has been shown to suppress allergic reactions in mice and, more recently, in humans (Makino T et al 2001; Takano H et al 2004). Rosmarinic acid relieves allergy symptoms by preventing the activation of immune responder cells and by inducing apoptosis, or cellular suicide, in already activated immune responder cells (Hur YG et al 2004). Natural flavonoids like rosmarinic acid kill only excess allergy-activated immune cells while leaving the vast bulk of responder cells to fight off bacteria and other foreign invaders, thus possibly preventing the progression to allergic sinusitis.

Life Extension Foundation Recommendations

People with sinusitis often benefit from steam treatments and nasal saline wash. In addition, the following supplements are suggested to prevent infection:

1)DHEA —15 to 75 milligrams (mg) for three to six weeks, followed by blood testing to make sure optimal levels of this hormone are maintained. If symptoms of an infection are just beginning, 200 to 400 mg may be taken as soon as possible.

2)Lactoferrin —900 mg daily with meals, or 1200 mg at the first sign of infection

3)Melatonin —3 to 10 mg prior to bedtime, or up to 50 mg at the first sign of infection

4)Pure Garlic —9000 mg once or twice daily (eat other food immediately after ingesting the garlic to minimize stomach or esophageal burning.)

5)Kyolic aged garlic extract—3600 mg daily

6)Essential fatty acids —700 to 1400 mg of EPA and 500 to 1000 mg of DHA daily with food

7)Zinc—Suck on two 24-mg lozenges every two hours while awake, beginning at the first sign of symptoms. This should be continued for only a few days to avoid toxic side effects. Continue with 30 mg of orally ingested zinc daily.

8)Beta-carotene— 25,000 international units (IU) daily

9)Vitamin C—2.5 to 6 grams (g) daily

10)Vitamin E —400 IU of alpha-tocopherol and 200 mg or more of gamma-tocopherol daily

11)NAC— 600 mg twice daily with vitamin C
Propolis —500 to 1500 mg daily

12)Green tea —725 mg green tea powder extract. Use a decaffeinated formula if you are sensitive to caffeine.

13)Rosmarinic acid—100 mg daily

Sinusitis Safety Caveats

An aggressive program of dietary supplementation should not be launched without the supervision of a qualified physician. Several of the nutrients suggested in this protocol may have adverse effects. These include:

Beta-Carotene

1)Do not take beta-carotene if you smoke. Daily intake of 20 milligrams or more has been associated with a higher incidence of lung cancer in smokers.

2)Taking 30 milligrams or more daily for prolonged periods can cause carotenoderma, a yellowish skin discoloration (carotenoderma can be distinguished from jaundice because the whites of the eyes are not discolored in carotenoderma).
DHEA

3)Do not take DHEA if you could be pregnant, are breastfeeding, or could have prostate, breast, uterine, or ovarian cancer.

4)DHEA can cause androgenic effects in woman such as acne, deepening of the voice, facial hair growth and hair loss.

EPA/DHA

1)Consult your doctor before taking EPA/DHA if you take warfarin (Coumadin). Taking EPA/DHA with warfarin may increase the risk of bleeding.

2)Discontinue using EPA/DHA 2 weeks before any surgical procedure.

Garlic

1)Garlic has blood-thinning, anticlotting properties.

2)Discontinue using garlic before any surgical procedure.

3)Garlic can cause headache, muscle pain, fatigue, vertigo, watery eyes, asthma, and gastrointestinal symptoms such as nausea and diarrhea.

4)Ingesting large amounts of garlic can cause bad breath and body odor.

Green Tea

1)Consult your doctor before taking green tea extract if you take aspirin or warfarin (Coumadin). Taking green tea extract and aspirin or warfarin can increase the risk of bleeding.

2)Discontinue using green tea extract 2 weeks before any surgical procedure. Green tea extract may decrease platelet aggregation.

3)Green tea extract contains caffeine, which may produce a variety of symptoms including restlessness, nausea, headache, muscle tension, sleep disturbances, and rapid heartbeat.

Melatonin

1)Do not take melatonin if you are depressed.

2)Do not take high doses of melatonin if you are trying to conceive. High doses of melatonin have been shown to inhibit ovulation.

3)Melatonin can cause morning grogginess, a feeling of having a hangover or a “heavy head,” or gastrointestinal symptoms such as nausea and diarrhea.

NAC

1)NAC clearance is reduced in people who have chronic liver disease.

2)Do not take NAC if you have a history of kidney stones (particularly cystine stones).

3)NAC can produce a false-positive result in the nitroprusside test for ketone bodies used to detect diabetes.

4)Consult your doctor before taking NAC if you have a history of peptic ulcer disease. Mucolytic agents may disrupt the gastric mucosal barrier.

5)NAC can cause headache (especially when used along with nitrates) and gastrointestinal symptoms such as nausea and diarrhea.

Propolis

1)Propolis, when ingested, can cause hypersensitivity reactions such as rhinitis, conjunctivitis, rash, and bronchospasm.

Vitamin C

1)Do not take vitamin C if you have a history of kidney stones or of kidney insufficiency (defined as having a serum creatine level greater than 2 milligrams per deciliter and/or a creatinine clearance less than 30 milliliters per minute.

2)Consult your doctor before taking large amounts of vitamin C if you have hemochromatosis, thalassemia, sideroblastic anemia, sickle cell anemia, or erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency. You can experience iron overload if you have one of these conditions and use large amounts of vitamin C.

Vitamin E

1)Consult your doctor before taking vitamin E if you take warfarin (Coumadin).

2)Consult your doctor before taking high doses of vitamin E if you have a vitamin K deficiency or a history of liver failure.

3)Consult your doctor before taking vitamin E if you have a history of any bleeding disorder such as peptic ulcers, hemorrhagic stroke, or hemophilia.

4)Discontinue using vitamin E 1 month before any surgical procedure.

Kidney Disease-1

noreply@blogger.com (Kishen) — Thu, 21 Feb 2008 01:53:00 +0000

1)Kidney Function

2)Kidney Disorders

3)Factors Affecting Function

4)Autosomal Dominant Polycystic Kidney Disease

5)Treatment

6)Summary

For many years, the Centers for Disease Control (CDC) has listed kidney disease as one of the top 10 causes of death by disease in the United States. Kidney disease also plays a significant role in hypertension and diabetes, two other diseases that are also included on the CDC's list of top ten causes of death each year. End-stage renal (kidney) disease (ESRD) is growing at a rate of 4-8% each year in the United States. Someone with advanced ESRD may require either therapeutic or regular dialysis, or both, and may eventually require a kidney transplant to save his or her life. When kidney function is reduced to 10-15% or less, dialysis is started in ESRD patients. Sometimes ESRD patients are placed on a waiting list for a kidney transplant.

According to statistics compiled by the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)(2001), kidney conditions such as inflammation, kidney stones, and cancer affected some 2.553 million persons; ESRD affected 424,179 people; polycystic kidney diseases affected 600,000 people; and other urinary conditions such as kidney infections, bladder infections, and cystitis affected millions more, costing billions of dollars of medical care funded by the public and by private individuals (NCHS 1999; Grantham et al. 2000; USRDS 2001).

Due to the limited scope of this protocol, we will briefly describe some of the more common kidney disorders and treatments. However, two conditions will be described in greater detail: autosomal dominant polycystic kidney disease (ADPKD) and kidney stones. ADKPD is a common human genetic disease, resulting in many cases of ESRD and eventually the need for kidney transplantation. Kidney stones affect approximately 10% of the U.S. population at some point in their lives (LaPorte et al. 1990). Unfortunately, about 60% of persons who have a kidney stone will develop another stone. In statistics reported by the NIDDK, urinary stones accounted for 1.325 million visits to physicians in 1997 (NIDDK 2001b).

Attention to overall kidney health is essential. If you have healthy kidneys, take care of them. Educate yourself about how to do this. We will provide information in the paragraphs that follow to assist you in being proactive in maintaining healthy kidneys. If you have a health condition such as diabetes or hypertension that poses a threat to your kidneys, seek a qualified medical professional to treat and control these conditions. Then carefully follow monitoring and treatment advice. Information will also be provided to assist you in supporting kidneys that have already sustained damage.

KIDNEY FUNCTION
The kidneys are bean-shaped organs that act as sophisticated filters to remove organic waste products from the blood and then excrete these waste products, along with excess salt and water, from the body through the urine. We are normally born with two kidneys located on either side of the lower back just below the rib cage. The kidneys are such incredibly well-functioning organs that only one normal, healthy kidney is required for good health. Each kidney is 4-5 inches long, weighs about 6 ounces, and contains about 1 million nephrons. Nephrons are the working units of the kidney that are responsible for waste removal (NIDDK 1998). As part of our normal aging process, kidney function diminishes as the number of functional nephrons is reduced.

The kidneys play a role in controlling the acid-base balance in the body as well as helping to control blood pressure. Another function of the kidneys is to produce hormones such as erythropoietin, which regulates the production and release of red blood cells from the bone marrow.

Each day, the kidneys filter approximately 200 quarts of blood, producing about 2 quarts of waste products and water (NIDDK 1998). These waste products and excess water pass from the kidneys through the ureters (tubes that connect the kidneys to the bladder) and into the bladder where they are briefly stored before being eliminated as liquid waste via the urine. Filtered waste products include the normal organic material from the breakdown of cells, proteins, excess food by-products, and various minerals, as well as the individual waste excretions from cells of the body. Alcohol, drugs, excess protein, minerals, and ingested toxins are also filtered by the kidneys. These toxic agents can have a dramatic, destructive effect on the health and function of the kidneys.

The rate of blood flow through the kidneys is about 20% of the total blood pumped by the heart each minute. (Anatomical Chart Company 2002®, Lippincott Williams & Wilkins)

Kidney function is often measured by using routine blood and urine tests to indicate gross problems. These tests measure creatine levels, possible blood in the urine, blood urea nitrogen (BUN), proteinuria (protein in the urine), and mineral content, including calcium, magnesium, phosphorus, sodium, potassium, oxalic acid, and other elements. If blood or urine tests indicate improper kidney function, additional testing is indicated using conventional x-rays, needle biopsy, ultrasound, a computed tomography scan (CT scan), or magnetic resonance imaging (MRI) (NORD 2002).

KIDNEY DISORDERS

1)Kidney Stones

2)Medical Intervention

3)Prevention

Kidney disease is any disorder that affects how the kidneys function. A list of all of the diseases and conditions that can affect kidney function and the possible causes are beyond the scope of this protocol. However, some of these disorders include analgesic nephropathy, chronic nephritis, diabetes, ESRD, hypertension, infection, injury, stones, lupus erythematosus, and ADPKD (NORD 2002).

Symptoms of renal disease can include frequent headaches and urination, itching, poor appetite, fatigue, burning bladder, anemia, baggy eyes, nausea and vomiting, swollen or numb hands or feet, poor concentration, darkened skin, and muscle cramps (NORD 2002).

Kidney Stones (Calculi)
Kidney stones (or calculi) are a common condition and also an incredibly painful one. It is estimated that in the United States, 10% of us will pass a kidney stone at some time in our lives. Men have more kidney stones than women, and white people are more prone to kidney stone formation than black people. The incidence of kidney stones is higher in the summer. This may be because we perspire more in the summer and our urine becomes more concentrated.

A kidney stone is a solid, rock-like type of material that has formed or is present in the kidneys, ureters, or bladder. A kidney stone is formed from mineral substances that precipitate from the urine. Kidney stones can stay in the kidney or travel down the urinary tract. Small stones are sometimes passed from the body with either a small or large degree of pain. Larger stones may lodge in the ureter, bladder, or urethra, blocking urine flow and causing extreme pain (NIDDK 1998).

Most kidney stones contain calcium combined with either oxalate or phosphate. Calcium stones are formed when extra calcium is not eliminated in the urine. Another type of kidney stone is a struvite stone. A struvite stone can form following a urinary infection. Uric acid stones form when there is too much acid in the urine. A rare type of kidney stone is made up of cystine. Evidence shows that cystine-based stones tend to run in families (the result of a genetic disease) (NIDDK 1998).

Kidney stones vary widely in size: from a grain of sand, to the size of a pearl, or to the size of a golf ball. However, most kidney stones are quite small. Kidney stones can grow to a size that is life threatening or that requires surgical removal. Some large kidney stones cannot be surgically removed because of the age of the patient or because of the danger of associated trauma to a vital organ.

Kidney stones are usually yellow or brown in color. Their structure and texture can be smooth or jagged. Another common visual characteristic is a crystalline appearance with different mineral striations appearing throughout the structure of the stone. Examination and testing of a kidney stone by a specialist in urology can determine significant information about the possible cause of the kidney stone and perhaps suggest a remedy for people who have the potential to form additional kidney stones (NIDDK 1998).

As noted earlier, kidney stones tend to run in families. They can also be associated with geographic factors as well. Therefore, people who live in tropical climates may be at greater risk for kidney stone formation because of the way the body manages water in a tropical setting. As a percentage, perspiration often becomes the prevalent method of how the body excretes water in tropical or very hot conditions, and urination may decline slightly because urine is stored longer in the urinary tract. Although it seems obvious, the fact is that most people do not drink enough water every day, and in tropical areas this is even more significant. Excessive perspiration becomes even more significant when performing hard physical labor or engaging in strenuous sports activities in very hot conditions. The body loses large amounts of water during excessive perspiration. For example, a NFL lineman can lose as much as a gallon of water or as much as 10 lbs of water weight during a 4-hour game. Therefore, sufficient water intake is both a preventive and a therapeutic measure.

The symptoms of a kidney stone attack include sudden extreme pain in the lower back, side, or groin; blood in the urine; fever and chills; vomiting; a bad odor or cloudy appearance to the urine; and a burning sensation during urination. Any of these symptoms require evaluation by a physician. Pain in the lower back, side, or groin can also be indicative that a kidney stone is moving or that there is a serious urinary tract blockage that requires immediate medical intervention. Kidney stone episodes frequently include urinary tract infections (UTIs). Recurrent, untreated UTIs can eventually cause permanent kidney damage and reduced kidney function.

Passing a kidney stone can be as simple as drinking large amounts of liquid and running up and down stairs or jumping up and down vigorously to dislodge the stone! This practice uses the basic physics of gravity to get the stone moving so that it can be passed normally. If you know you are passing a kidney stone, try to catch it in a strainer or retrieve it so it can be examined by a nephrologist or urologist (NIDDK 1998).

Medical Intervention for Kidney Stones
Many kidney stones pass from the body on their own with no medical help. However, more complex procedures are required to assist stones that cannot be passed or to remove stones that are growing larger (NIDDK 1998). Either lithotripsy or surgical removal of the stone is used when a kidney stone is firmly lodged in the ureters, bladder, or urethra. In the past, problem kidney stones represented a significant health concern because the only way to remove them was invasive surgery with a high risk of postoperative infection. It is now possible for urologists to avoid surgery except as a last resort or when there is no other alternative. Newer methods to remove kidney stones include using ureteroscopy, tunnel surgery, extracorporeal shock wave lithotripsy (ESWL), and percutaneous lithotripsy. All of these methods break the stone into smaller pieces so that the stone can be removed or passed through the urinary tract (NIDDK 1998).

Preventing Kidney Stones
Research into the prevention of recurrent kidney stones has produced many helpful dietary guidelines, nutritional protocols, and lifestyle changes that can reduce or eliminate the potential for future kidney stones. Using these effective protocols can significantly reduce the chance of recurring kidney stones after a first episode. They may also help pass a recurrent stone faster and with less difficulty.

In 1997, a research division of a healthcare provider conducted a double-blind study with a group of 64 patients who had a history of renal calculi to determine if potassium/magnesium citrate would prevent the recurrent formation of calcium oxalate kidney stones (Ettinger et al. 1997). The patients were given 42 mEq (milliequivalent) potassium, 21 mEq magnesium, and 63 mEq citrate or a placebo daily for 3 years. New renal calculi formed in 63.6% of patients receiving the placebo. However, patients receiving the potassium/magnesium citrate protocol presented with 12.9% recurrent renal calculi. Ettinger et al. (1997) concluded that "potassium/magnesium citrate effectively prevents recurrent calcium oxalate stones, and this treatment given for up to 3 years reduces risk of recurrence by 85%."

Contrary to what was considered to be "common sense" thinking in the past, two major studies have shown that calcium should not be reduced for patients with a history of kidney stones (Takei 1998; Williams 2001). It was originally postulated that patients with a history of renal calculi should limit their intake of calcium. In fact, current recommendations from the National Institutes of Health published on their Web site continue to call for calcium-restricted diets. Such dietary changes also affect the alkali and pH of the body by calling for the restriction of foods such as apples, beets, parsley, broccoli, spinach, and pineapples. However, newer findings contradict these dietary restrictions and offer scientific evidence that uncombined intestinal oxalic acid is the real culprit for calcium oxalate kidney stones (Ohgitani 2000).

Harvard researchers studied nearly 92,000 nurses over a period of 12 years to determine the relationship between calcium intake and the occurrence of renal calculi (the well-known Harvard Nurses' Health Study). The conclusion of this massive study was that those nurses who consumed diets that were higher in calcium were at lower risk for kidney stones!

The reason that this type of dietary modification reduced the chance of kidney stones was relatively simple. A high percentage of kidney stones are comprised of calcium and oxalic acid which form calcium oxalate inside the kidneys. Oxalic acid is able to pass through the intestinal wall into the blood and enter the kidneys where it has a chance to combine with calcium. Calcium oxalate, when normally combined inside the digestive tract, does not pass through the intestinal wall and into the blood, but is eliminated with other waste products. Therefore, when oxalic acid combines with dietary calcium or supplemental calcium inside the intestinal tract, oxalic acid will never reach the kidneys and therefore calcium oxalate kidney stones cannot be formed.

The Harvard Nurses' Health Study presented the following important findings: dietary calcium intake from food or supplements reduced the risk for renal calculi; calcium supplementation must be taken with food and in small dosages (< 400 mg); plant foods high in calcium, fiber, vitamins, minerals, antioxidants, and some protein were an excellent source for dietary phytochemicals.

Another study conducted in South Africa found that "mineral water containing calcium and magnesium deserves to be considered as a possible therapeutic or prophylactic agent in calcium oxalate kidney stone disease" (Rodgers 1997). A French mineral water containing calcium (202 ppm) and magnesium (36 ppm) was selected as the delivery method. Twenty subjects of each sex who had previously formed calcium oxalate renal calculi and 20 healthy volunteers of each sex participated in the study. Each subject provided 24-hour urine collection samples each day during the study. The mineral water was ingested over a 3-day period. Then the participants switched to tap water. The cycle was repeated at least twice by each subject. The male stone formers received the most benefit, showing nine risk factors that were favorably affected by the mineral water containing calcium and magnesium (Rogers 1997).

Recommendations from the National Kidney and Urologic Diseases Information Clearinghouse (1998) include a few simple things to do to avoid kidney stones:

1)Drink more water. Try to drink at least 12 full glasses of water each day. Drinking extra water helps to flush substances that form stones from the kidneys.

2)It is not necessary to eliminate coffee, tea, and colas from your diet, but limit caffeine because it can increase fluid loss. Consider drinking ginger ale, lemon-lime soda, and fruit juices.

3)Follow your physician's recommendations about dietary limitations. If you form uric acid stones, your physician will probably ask you to eat less meat because meat breaks down to form uric acid.

4)Follow your physician's recommendations about taking medicines to prevent stone formation.

Kidney Disease-2

noreply@blogger.com (Kishen) — Thu, 21 Feb 2008 01:46:00 +0000

FACTORS AFFECTING KIDNEY FUNCTION

1)Analgesics

2)Autoimmune

3)Congenital and Genetic

4)Drug Reactions

5)Homocysteine

6)Hypertension

7)Impaired Blood Supply

8)Infection

9)Inflammatory Cytokines

10)Metabolic

11)Tumors

12)Other

Adults lose renal function and capacity with normal aging. A number of factors, including drug reactions and degenerative disease not endemic to the kidneys, may bring added stress.

Analgesics
An analgesic is any medicine that is intended to kill pain. Analgesics that contain narcotics are for more severe pain and require a prescription from a physician. However, many analgesics can be purchased as over-the-counter (OTC) products (aspirin, ibuprofen, acetaminophen, and naproxen). OTC products require no prescription from a physician. OTC analgesics rarely present a problem for most people if they are taken according to the recommended dosage. However, some conditions such as chronic kidney disease or taking OTC analgesics for a long time or in combination with other analgesics make OTC analgesics dangerous. According to the NIDDK (1998), analgesics such as aspirin, ibuprofen, acetaminophen, and naproxen have been attributed to incidence of acute kidney failure in persons with lupus erythematosus or chronic renal conditions; persons of advanced age; or persons who have had a recent binge of alcohol consumption.

Some cases involved a single dose or no more than 10 days of analgesic use. Painkillers that combine two or more analgesics (e.g., aspirin and acetaminophen together) with caffeine or codeine are more likely to cause kidney damage. These mixtures are often sold in powder form. Single analgesics (e.g., aspirin alone) have been found to be less likely to cause kidney damage (NIDDK 1998). According to Fored et al. (2001), more research is required to determine whether the use of aspirin or acetaminophen contributes to kidney failure or whether people who have ailments that predispose them to kidney failure are more likely to use painkillers. Fored et al. (2001) recommended that each patient be considered individually with respect to their risk of kidney failure, length of time the painkiller will be taken, and other existing illnesses, particularly in the elderly and persons with chronic conditions. If possible, avoid acetaminophen-based analgesics, as these may be most toxic to the kidneys.

Autoimmune
Glomeruli, the tiny blood vessels in the nephrons where blood is filtered in the kidneys, can become inflamed by autoimmune disorders. When an autoimmune disorder occurs, the body attacks itself with its own immune system. Examples of an autoimmune disorder are Goodpasture syndrome and lupus erythematosus. In the kidneys, this type of inflammation is called glomerulonephritis (Glanze 1996; NIDDK 1999). While glomerulonephritis is usually caused by an autoimmune disorder, it can also be caused by infection (e.g., by streptococcal bacterial).

Congenital and Genetic
Congenital abnormalities of the kidneys are not uncommon. Sometimes the two kidneys are joined together at their base. Some people are born with only one kidney, both kidneys on the same side of the body, or with underdeveloped kidneys that are barely functional. Polycystic kidney disease is a genetic condition that may manifest at birth, but often appears in young adulthood or even middle age.

Drug Reactions
Acute kidney damage can result from an allergic reaction to a drug; taking large quantities of a drug for a long period of time; taking out-dated tetracyclines; taking long-term or large amounts of pain killers; taking potent antibiotics; accidental ingestion of poisons; toluene inhalation (e.g., industrial exposure and glue sniffing); or combining prescription drugs, over-the-counter drugs (aspirin, acetaminophen, ibuprofen, naproxen sodium), and alcohol (NIDDK 1998). Regular blood tests to assess kidney function are recommended for anyone who takes medicine known to damage the kidneys or who has a condition that puts them at risk for developing kidney disease.

Homocysteine
Discovered in 1932, homocysteine is a sulfur-containing amino acid normally found in small amounts in the blood of healthy persons. Homocysteine is derived from dietary protein (meat, milk, eggs) and is metabolized in the liver using vitamins B6 and B12. High levels of homocysteine can result from genetic disease (homocystinuria); kidney disease; hyperthyroidism; psoriasis; systemic lupus erythemotosus; drug treatment for chronic diseases; and dietary vitamin deficiencies (folic acid, B6, B12) (Welch et al. 1998).

Homocysteine levels tend to increase with age and are higher in men than in women. High levels of homocysteine can be very damaging to the kidneys and the vascular system (Dierkes et al. 1999; Marangon et al. 1999; Levin et al. 2002). Accumulation of toxic homocysteine has been associated with the development of cardiovascular disease (artherosclerosis, stroke, heart attack); pulmonary embolism and deep venous thrombosis; dementias (Alzheimer's disease, multi-infarct dementia); and kidney disease ESRD (Joosten et al. 1997; McCaddon et al. 1998; Welch et al. 1998; Dierkes et al. 1999; Levin et al. 2002; Seshadri et al. 2002). Cardiovascular disease (CVD) is common in patients with chronic kidney disease (CKD) and is responsible for the majority of morbidity and mortality in patients (Levin et al. 2002).

As early as 1969, researchers began to make clinical observations linking elevated homocysteine to vascular diseases (McCully 1969). Subsequent investigations confirmed these observations (Clarke et al. 1991; Ueland et al. 1992; Stampfer et al. 1992; 1995; Selhub et al. 1995; Welch et al. 1998). In CVD, there is evidence that elevated levels of homocysteine are related to arterial wall damage, but the mechanism is unclear (Welch et al. 1998). It may be that homocysteine has a toxic effect on the endothelial (cellular) lining of blood vessels. Data from a study on healthy U.S. physicians (14,916) with no prior history of heart disease demonstrated that highly elevated homocysteine levels are associated with a more than threefold increase in the risk of heart attack over a 5-year period. This finding was published in 1992 in the Journal of the American Medical Association (JAMA) as part of the Physicians' Health Study (Stampfer et al. 1992). The Framingham Heart Study (1041 elderly subjects) (Selhub et al. 1995) and other studies have also confirmed that elevated homocysteine is an independent risk factor for heart disease (Chaveau et al. 1993; van Guldener et al. 2000; Hoffer et al. 2001; Suliman et al. 2001).

In kidney disease, homocysteine levels in the blood increase because the kidneys do not properly filter homocysteine. Elevated levels of homocysteine are commonly seen in renal patients, sometimes three or four times higher than normal levels (van Guldener et al. 2000; Friedman et al. 2001; Herrmann et al. 2001; Suliman et al. 2001). Homocysteine is consistently elevated to very high levels in patients who require dialysis (Levin et al. 2002). Plasma homocysteine concentrations often decrease after dialysis (Welch et al. 1998). Therefore, to further help lower homocysteine levels, dialysis patients often require high levels of nutrients, including folic acid, vitamin B12, TMG (also known as betaine or trimethylglycine), and vitamin B6 (Bostom et al. 1996; Chauveau et al. 1996; Robinson et al. 1996; Sadava et al. 1996; Tucker et al. 1996; Welch et al. 1998; van Guldener et al. 2000; Herrmann et al. 2001; Levin et al. 2002).

Folic acid was used in a study conducted in 82 patients undergoing dialysis 3 times a week for 4 weeks (hemodialysis, 70 patients; peritoneal dialysis, 12 patients) (Dierkes et al. 1999). The results demonstrated that in both groups, homocysteine concentration was reduced by 35% after taking 2.5-5 mg of folic acid after each dialysis treatment.

As noted earlier, although dialysis has the effect of lowering homocysteine levels, folic acid further reduced homocysteine levels and, more importantly, had long-term effects even after supplementation was withdrawn (Dierkes et al. 1999).

Although the relationship between CVD and CKD is convincing, therapeutic strategies appear to be underused in the care of patients with kidney disease. CVD and CKD have similar traditional risk factors (diabetes, hypertension, dyslipidemia, obesity) as well as nontraditional risk factors (hyperhomocysteinemia, anemia, disturbed mineral metabolism, parathyroid excess). Because these risk factors are also specific to kidney disease and are modifiable, they should be identified and treated in persons with CKD (Levin et al. 2002). Patients with mild hyperhomocysteinemia have no clinical signs and are typically asymptomatic until the third or fourth decade of life (Welch et al. 1998).

For some time, physicians have recognized the danger of homocysteine and they recommend use of vitamin supplements to lower homocysteine levels (Tucker et al. 1996; Welch et al. 1998). The "normal range" used by commercial laboratories is 5-15 micromoles/L of blood. However, epidemiological data reveal that homocysteine levels above 6.3 result in a steep, progressive risk of heart attack, with each three-unit increase equaling a 35% increase in risk for heart attack (Verhoef et al. 1996; Robinson et al. 1996). There may be no safe "normal range" for homocysteine. A survey in Cardiologia reported that the average American's level of homocysteine is 10 (Andreotti et al. 1999).

For many persons, daily intake of TMG (500 mg), folic acid (800 mcg), vitamin B12 (1000 mcg), vitamin B6 (100 mg), choline (250 mg), inositol (250 mg), and zinc (30 mg) will keep homocysteine levels in a safe range. Unfortunately, without a homocysteine blood test, it is impossible to know if the proper amounts of nutrients are being taken. Therefore, the only way to be certain is to have a blood test to ascertain that your homocysteine level is below 7. Sometimes treatment must be individualized for complicated conditions. High levels of homocysteine can require up to 6 grams of TMG or vitamin B6 (in cystathione-B synthase deficiencies).

Hypertension
High blood pressure (or hypertension) creates a significant risk factor for kidney failure. This risk factor is amplified for persons who have ADPKD. Li Kam Wa et al. (1997) investigated the 24-hour blood pressure profile of ambulatory patients, particularly to measure nocturnal fall of blood pressure. The researchers found that in ADPKD patients, the reduction in nocturnal blood pressure was attenuated (lessened), indicating increased risk for kidney damage. Further studies are needed to evaluate the contribution that nocturnal hypertension makes on the overall progression of renal failure. However, in another related study of untreated children, it was found that nocturnal hypertension was a major risk factor for renal deterioration (Ligens et al. 1997).

Impaired Blood Supply
Any condition that impairs blood flow to the kidneys can damage or cause obstruction in the small blood vessels in the kidneys (e.g., diabetes mellitus, hemolytic uremic syndrome, physiological shock, lupus erythematosus).

InfectionA kidney may become infected when the flow of urine is restricted in the urinary tract (NIDDK 1998). An obstruction may lead to stagnation of urine in the kidney that allows infection to spread into the bladder. Possible causes of an obstruction are a congenital defect, a kidney stone, a bladder tumor, or enlargement of the prostate gland. Tuberculosis of the kidney occurs when infection is carried by the blood to the kidney from somewhere else in the body (usually the lungs).

Inflammatory Cytokines
Destructive cell-signaling chemicals called inflammatory cytokines contribute to degenerative, inflammatory, and autoimmune diseases (Van der Meide et al. 1996; Licinio et al. 1999). Degenerative diseases appear to be factors in or possible underlying causes of kidney failure and disease (congestive heart failure, anemia, rheumatoid arthritis, fibrinogen formation, fibrosis, diabetes, asthma, lupus, psoriasis). People who have multiple degenerative disorders often exhibit excess levels of pro-inflammatory markers in their blood. Therefore, seemingly unrelated inflammatory or autoimmune diseases can have a common link to kidney disease: inflammatory cytokines. In kidney failure, inflammatory cytokines restrict circulation and damage nephrons (the filtering units of the kidneys).

For those who have degenerative diseases, particularly multiple ones, cytokine profile and C-reactive protein blood tests are highly recommended (available through your own physician or Life Extension Foundation). If your cytokine test reveals excess levels of cytokines--tumor necrosis factor-alpha (TNF-alpha), interleukin-1b (IL-1b)--nutritional supplementation, dietary modifications, and low-cost prescription medications (pentoxifylline or PTX) are advised (see the Inflammation: Chronic protocol for a discussion of systemic inflammation and recommendations for reducing inflammatory conditions).

Metabolic
Kidney stones are more common in middle age and are usually caused by excessive concentrations of substances such as calcium, uric acid, or cystine in the urine (NIDDK 1998). Hyperparathyroidism, cystinuria, and hyperoxaluria are rare, inherited metabolic disorders that can cause kidney stones. In cystinuria, too much of the amino acid cystine can lead to the formation of stones made of cystine. In patients with hyperoxaluria, the body produces too much of the salt oxalate. Excessive oxalate in the urine cannot be dissolved, crystals settle out, and stones form. Absorptive hypercalciuria occurs when the body absorbs too much calcium from food. The extra calcium ends up in the urine and the high levels cause calcium oxalate or calcium phosphate crystals to form in the kidneys or urinary tract. Other causes are hyperuricosuria (a disorder of uric acid metabolism), gout, excess intake of vitamin D, and blockage of the urinary tract. Certain diuretics ("water" pills) or calcium-based antacids can increase the risk of kidney stone formation by increasing the amount of calcium in the urine (NIDDK 1998).

Tumors
Tumors in the kidneys, either benign or malignant, are rare. When malignant, the most common type is renal cell carcinoma, particularly in adults over 40.

Other
Urinary tract infections (UTIs) are frequently occurring health conditions that are caused by various urinary systemic infections, sexual contact, bacteria entering the kidneys via the bloodstream or the urethra, kidney stone blockages, and kidney damage (Glanze 1996). Infection can lead to impaired kidney function. Therefore, a kidney infection should be treated immediately to prevent more serious disease. A direct blow to the kidneys can also cause extensive damage (e.g., a car accident, industrial accident, sports injury, or accidental fall) (NORD 2002).

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

ADPKD is one of the most common genetic diseases in humans. It is a systemic disease that is caused by at least three different genes: PKD1, PKD2, and PKD3. However, most of the mutations are found in the PKD1 gene (Merta et al. 1997; Sessa et al. 1997). ADPKD is a very serious disease. Worldwide, it is responsible for 8-10% of all cases of ESRD. Patients with ADPKD develop cysts in both kidneys. These cysts continue to grow over the lifetime of the patient and ultimately lead to hypertension, reduced kidney function, and eventually renal failure. Poor kidney function in ADPKD patients accounts for many kidney transplants each year. According to the PKD Foundation (Kansas City, www.pkdcure.org), 60% of individuals with ADPKD develop kidney failure or ESRD. The only treatment is dialysis or transplant. Interestingly, because ADPKD is genetic in origin, persons who receive kidney transplants do not reacquire their genetic mutation with transplanted kidneys. Common symptoms are frequent infections, blood in the urine, and back pain.

Kidney Disease-3

noreply@blogger.com (Kishen) — Thu, 21 Feb 2008 01:39:00 +0000

Polycystic kidney disease may occur at birth, during childhood, or in adults. Congenital polycystic disease can be detected at birth and may affect all or only small parts of one or both kidneys. Childhood polycystic kidney disease can cause death after a few years because of liver and kidney failure. In some adults, the disease may actually be present at birth, but not manifest any symptoms until young adulthood or middle age. In adults, it can affect either one or both kidneys (Glanze 1996). Polycystic kidney disease is characterized by autonomous cellular proliferation, pockets of fluid accumulation within the cysts, and intraparenchymal fibrosis of the kidney. Other clinical observations include renal failure, liver cysts, and cardiac valve abnormalities (Bacallao et al. 1997).

The traditional method of detecting ADPKD has been by using ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) of the kidneys to look for the presence of renal cysts. However, the challenge is to detect ADPKD in people who carry the defective gene, but who may not have any symptoms or show any developed cysts and therefore be undiagnosed as having ADPKD. Newer methods of DNA testing can now identify individuals who carry the defective gene, but are not symptomatic. For example, every member of four Chinese families with a known history of ADPKD showed unique DNA patterns (Yuan 1997). DNA diagnostic testing methods have value for patients with existing ADPKD as well as for presymptomatic patients.

ADPKD progresses to end-stage renal insufficiency before the age of 73 in about 50% of affected patients (Grantham 1997). Some patients are affected by numerous cysts that form inside the proximal and distal tubules, while other patients are spared. Why this is the case remains a mystery. The formation of cysts begins in early childhood, affecting less than 1% of tubules as a consequence of mutated DNA. The risk factors associated with polycystic kidney disease include gender (males progress more quickly than females), race (black patients progress more rapidly than whites), and other contributing factors such as hypertension and proteinuria. These factors can aggravate and accelerate polycystic kidney disease through to end term (Grantham 1997).

Because hypertension is a common and serious factor of ADPKD that usually occurs early in the disease before renal function begins to decrease, Doppler ultrasonography has been used to assess renal vascular resistance (RVR) by measuring resistive and pulsatility indices. In a study of 42 patients with ADPKD and 65 control subjects, Brkljacic et al. (1997) found that Doppler indices do reflect increased RVR in those patients with ADPKD and that renal function disturbance did manifest systemic arterial hypertension. The abnormality of the kidneys in these patients was easily observed using ultrasound. However, this method did not show ADPKD potential for patients if renal cysts were not present. DNA testing is required to determine whether a patient carries the PDK1 and PDK2 chromosomes.

The occurrence of cardiovascular complications is a very common cause of death for persons with ADPKD. Chapman et al. (1997) examined the relationship of known cardiovascular risk factors, hypertension, and ADPKD. According to the researchers, left ventricular hypertrophy (LVH) is an important risk factor for premature cardiovascular death in persons with essential hypertension. Hypertension occurs frequently and early in ADPKD patients. In 116 adult ADPKD patients and 77 healthy controls, Chapman et al. (1997) found a higher frequency of LVH in ADPKD men (46% versus 20%) and women (37% versus 12%) compared to the control subjects. LVH in ADKPD patients was associated with higher systolic and diastolic blood pressure. According to the researchers, the role of blood pressure as a contributing factor to LVH in ADPKD patients may be partly due to early onset and inadequate treatment.

The possibility is being explored that ADPKD may have an emerging infectious disease component as well. Research has shown fungal DNA in kidney tissue and cyst fluids of ADPKD patients, but not in healthy kidneys of persons without ADPKD (Miller-Hjelle et al. 1997). In a differential activation protocol assay, the researchers showed bacterial endotoxin and fungal beta-D-glucans in cyst fluids from human kidneys with PKD. Tissue and cyst fluids were examined for fungal components, and the serological tests showed Fusarium, Aspergillus, and Candida antigens. Miller-Hjelle et al. (1977) concluded that "endotoxin and fungal components, sphingolipid biology in PKD, the structure of PKD gene products, infection, and integrity of gut function [will establish a mechanism] for microbial provocation of human cystic disease."

TREATMENT FOR KIDNEY DISEASES

1)Conventional

2)Natural and Adjuvant

Treatment of kidney disease is a complex issue and depends on the type of disease, the underlying cause, and the duration of the disease. Treatment usually starts with addressing the original cause such as inflammation. Inflammation from infection is treated with antibiotics. Inflammation caused by an immune reaction is more difficult to treat. In this case, immunosuppressant drugs (corticosteroids) are used in an attempt to control the immune reaction.

In the case of acute kidney failure, treating the underlying cause may return the kidneys to normal function. Sometimes dietary restrictions (less salt and protein) are required until the kidneys are better able to handle these substances. Diuretic medicines help the body to excrete more water and salt. However, with chronic kidney failure, medicines are used to stop progression of the disease so it does not reach ESRD.

When kidney disease does not respond to treatment with dietary restrictions and medicines, dialysis or kidney transplantation are the next treatments to consider (Glanze 1996). Dialysis is a technique used to remove waste products from the blood and excess fluid from the body in the case of renal failure. Kidney transplantation is a surgical procedure in which the diseased kidney (sometimes both kidneys) is removed and replaced with a healthy kidney from a donor (NIDDK 1999).

Conventional Medical Treatment

1)Medicine and Drugs

2)Kidney Dialysis

3)Transplantation

Medicine and Drugs

In the United States, 4% of the population is at risk for kidney disease. As part of an annual physical checkup, we should have three important tests: blood levels of creatinine, blood urea nitrogen, and urine levels of protein. Small elevations of creatinine can be an early sign of kidney disease. According to the National Kidney Foundation (2001a), 11 million Americans have elevated blood levels of creatinine. Healthy kidneys remove creatinine, but when kidney function diminishes, creatinine levels in the blood go up. Early detection leads to early treatment, which can occur at a stage when treatment can help prevent kidney disease from advancing to a more serious stage. Diabetes is the leading cause of chronic kidney disease, followed by hypertension. See your physician regularly and follow prescribed dietary and drug treatment to control blood sugar levels and blood pressure (National Kidney Foundation 2001a). Treatments for conditions which can lead to kidney disease include numerous prescription drugs and treatment protocols. (See the Life Extension protocols on Diabetes, Immune Enhancement, Cardiovascular Disease [sections on Homocysteine and Hypertension], Thyroid Deficiency, and Urinary Tract Infection for additional information on specific conditions and treatment.)

Kidney Dialysis

Kidney dialysis is a medical treatment used to filter out waste products from the blood. Dialysis has been proven to be an effective technique for removing wastes and extra fluid from the body. According to the annual report of the U.S. Renal Data System (2001), over 243,000 persons in the United States were using dialysis treatment in 1999. Dialysis treatment permits these people to live relatively normal lives within the limitations of their disease.

There are two types of dialysis methods: hemodialysis and peritoneal dialysis. The most common technique is hemodialysis, accounting for slightly over 85% of dialysis treatment. The remaining 15% of patients use peritoneal dialysis (NIDDK 2001b). Neither hemodialysis nor peritoneal dialysis is uncomfortable and both are equally effective in removing wastes and extra fluids from the body. The choice is usually one of preference or level of convenience desired by the patient in consultation with appropriate medical professionals.

Even for patients who use dialysis, kidney failure can cause other health-related problems over time, including high blood pressure (including a latent nocturnal factor), bone disease, anemia, and nerve damage. As kidney function declines past the minimum threshold, kidney transplant becomes the only hope for patients with advanced ESRD.

Studies on human dialysis patients indicate that a high number of free radicals are formed in response to dialysis and that antioxidant dietary supplements can protect against this damage (Saionji 1999; Wratten 1999; Clermont et al. 2000).

Transplantation
Statistical surveys are made of medical facilities yearly. The most recent statistics available indicate that kidney transplantation accounted for 13,483 transplant operations in 1999 (NIDDK 2001b). In the United States, many people live with a functioning kidney as a result of transplantation. However, it is very difficult to obtain accurate statistics on the number of persons who live with a functioning kidney transplant at any given time. Unfortunately, each year patients die while awaiting a matching donor kidney. According to the NIDDK (2001b), as of November 2, 2001, there were 50,305 people waiting for kidney transplants. To be a potential candidate for kidney transplantation, a person must have kidney function estimated to be below 15% and must not be positive for certain diseases, such as unstable coronary artery disease, infection, or glomerulonephritis. (Glomerulonephritis is inflammation of the tiny blood vessels in the nephrons where blood is filtered in the kidneys. It is usually caused by an autoimmune disease, but can also be caused by infection.)

Can Renal Replacement Be Deferred? A study was conducted to determine if a very low-protein diet could defer renal replacement therapy (RRT) in patients with chronic renal failure. High protein intake is known to be stressful for the kidneys and over time can be a contributing factor to a slow, pervasive decline in kidney function. Two groups of patients (23 and 53 patients, respectively) were put on a very low-protein diet (0.3 g/kg) combined with supplemental amino acids. The patients in these groups were well-motivated RRT candidates who were closely monitored for nearly 1 year. During the course of the study, indications of malnutrition did not occur, and the patients were able to maintain acceptable kidney function (glomerular filtration rate or GFR < 10 mL/min or < 15/mL/min for diabetic patients) (Walser 1999).

Note: Since 1973, Medicare has picked up 80% of ESRD treatment costs, including the costs of dialysis and transplantation and of some medications. To qualify for benefits, a patient must be insured or eligible for benefits under Social Security or be a spouse or child of an eligible American. Private insurance and state Medicaid programs often cover the remaining 20% of treatment costs.

Natural and Adjuvant Treatment

1)Dietary Management

2)Inflammation

3)Dietary Supplements

Dietary Management
In the early stages of kidney disease, careful dietary management may slow down the process of kidney disease. A diet low in sodium, potassium, and phosphorus, three substances regulated by the kidneys, is essential in managing kidney disease. Other dietary restrictions, such as reducing protein, may also be required. Your physician might suggest that you consult a renal dietitian who has special training in diets for persons with kidney disease. Persons who are vegetarians naturally have diets high in potassium and phosphorus and therefore need good nutritional advice. If you have to limit phosphorus, sodium, or protein, remember the following:

1)Phosphorus is especially high in dairy products (milk, cheese, ice cream); dried beans and peas; nuts and peanut butter; some salt substitutes; and cocoa, beer and cola soft drinks.

2)Sodium is especially high in table salt, canned soup, processed cheese, snack foods, prepared and "fast foods," pickles, olives, sauerkraut, and smoked and cured food (ham, bacon, luncheon meat).

3)Protein is found in large amounts in food from animal sources (poultry, meat, seafood, eggs, dairy products). Protein is found in smaller amounts in food from plant sources (bread, cereal, grain, vegetables, fruit).
However, a certain amount of phosphorus, sodium, and protein is necessary for good health. To keep yourself healthy, it is important to learn to read labels and make better choices. For example, non-dairy creamers and milk substitutes are a good way to lower dietary phosphorus.

Avoid losing too much weight. It is important to maintain a good level of calories because calories give you energy. If you are limiting protein, you will need to get more calories from other foods. Good ways to increase calories are to:

1)Increase unsaturated fats from vegetable oils (corn, cottonseed, safflower, soybean, sunflower), olive oil, and mayonnaise salad dressings.

2)Use sugar from gum drops, jelly beans, marshmallows, honey, jam, and jelly.

3)Use canned or frozen fruits in heavy syrup.

Note: The recommendations for using sugar may not be appropriate for diabetics or overweight individuals. If you are diabetic, consult your physician or dietitian for alternative recommendations.

Protecting Kidneys Against Inflammatory Attack

Pentoxifylline (PTX) is a prescription drug approved by the FDA to treat peripheral vascular disease. The standard dose is 1200 mg a day to improve circulation. To suppress proinflammatory cytokines often involved in age-related renal impairment, a lower dose of 400 mg twice a day can be used. (Refer to pentoxifylline precautions in the summary section before using this drug.)

A controlled study on human diabetics with advanced renal failure showed that 400 mg a day of PTX reduced tumor necrosis factor-alpha (TNF-alpha) levels by approximately 35%. In the pentoxiphylline group, a measurement of kidney impairment was reduced 59%. There were no changes in those given placebo. The researchers noted that inflammatory cytokines such as TNF-alpha have long been implicated in the development and progression of diabetic kidney failure (Navarro et al. 1999a). Organ failure induced by TNF-alpha has been confirmed by other studies (Boldt et al. 2001).

In advanced kidney failure, anemia can be induced by an inflammatory cytokine attack on erythropoietin, the major natural hormone responsible for red blood cell (RBC) production. In a group of 7 anemic patients with advanced renal failure, PTX suppressed TNF-alpha and reversed the anemic state (Navarro et al. 1999b).

Dietary Supplements

Dietary supplements are often recommended by physicians and renal dietitians (National Kidney Foundation 2001e). Their recommendations are guided by the results of blood tests that you will be required to take regularly as part of monitoring your condition and treatment results. Always speak with your physician or renal dietitian before using or adding any supplements or herbal products.

Multivitamins. In addition to eating a diet that contains appropriate nutrients and levels of protein, a comprehensive multivitamin is often required to replace vitamins that are lost during dialysis treatments (National Kidney Foundation 2001e).

Vitamin B. Vitamins B6, B12, and folate (folic acid) are members of the B vitamin group. The B vitamins are known for having many beneficial qualities, including promoting growth; improving heart function; lowering homocysteine; protecting against atherosclerosis caused by excess homocysteine; helping with the formation and regeneration of red blood cells and preventing anemia; and increasing energy and endurance (McGregor et al. 2000).

Kidney Disease-4

noreply@blogger.com (Kishen) — Thu, 21 Feb 2008 01:36:00 +0000

Vitamin C. Vitamin C is an antioxidant that helps keep many different types of tissues healthy. Vitamin C helps wounds and bruises heal faster and may aid in preventing infection (2001e).

Vitamin D. Additional vitamin D, which promotes the absorption of calcium, along with calcium supplements, may also be recommended. Some physicians prescribe vitamin D in a pill form called vitamin D3 (National Kidney Foundation 2001e).

Vitamin E. Supplementation with vitamin E may protect the kidneys from free-radical damage, a major factor in renal health. In experiments in rats, Sadava et al. (1996) found that a dietary deficiency of vitamin E caused progressive and pronounced renal damage. Vitamin E has been shown to restore tubular flow to rats with severe kidney disease by suppressing the free radicals that cause tubulointerstitial damage (Hahn 1998).

Calcium. Calcium along with vitamin D helps keep your bones healthy. Calcium is also used to bind to phosphorus from dietary food. Your physician will advise you about taking calcium (National Kidney Foundation 2001e).

Phosphorus. The proper amount of phosphorus is needed for healthy bones. As noted earlier, when the kidneys do not work properly, blood levels of phosphorus can get too high, causing calcium to be taken from the bones. Calcium taken from the bones will make them weak. It is important to keep phosphorus and calcium balanced to maintain strong bones (National Kidney Foundation 2001c).

Potassium. Another function of the kidneys is to maintain the right amount of potassium. Potassium plays an essential role in keeping your heartbeat regular and your other muscles working properly, but high blood levels of potassium are to be avoided. You can help control your potassium level by avoiding foods that are high in potassium (National Kidney Foundation 2001d).

Iron. A low level of red blood cells is known as anemia. Because red blood cells carry oxygen to all the tissues and organs throughout the body, low levels of oxygen may result in reduced performance of vital organs including the kidneys. Anemia is common in people who have kidney disease. Healthy kidneys produce a hormone called erythropoietin (EPO). EPO stimulates the bone marrow to produce red blood cells. However, diseased kidneys often do not make enough EPO and therefore the bone marrow makes fewer red blood cells. Other common causes of anemia are from loss of blood during hemodialysis and low levels of iron and folic acid. Anemia often starts in the early stages of kidney disease and tends to worsen as the disease progresses. According to the NIDDK (2001a), nearly everyone with end-stage kidney failure has anemia.

A CBC (complete blood count) determines the hematocrit (Hct) or the percentage of the blood that consists of red blood cells. It also measures the amount of hemoglobin (Hgb) in the blood. If at least half of normal kidney function (serum creatinine is greater than 2 mg/dL) has been lost and Hct is low, the most likely cause of anemia is decreased EPO production. The National Kidney Foundation's Dialysis Outcomes Quality Initiative (DOQI) recommends that a detailed evaluation of anemia in men and postmenopausal women on dialysis should begin when the Hct value falls below 37%. For women of childbearing age, evaluation should begin when the Hct falls below 33%.

If no other cause for EPO deficiency is found, the deficiency can be treated with a genetically engineered form of the hormone (usually injected under the skin 2 or 3 times a week). Hemodialysis patients who cannot tolerate EPO injections in their skin can receive EPO intravenously during dialysis treatment. However, intravenous dosing requires a larger, more expensive dose and it may not be as effective.

Many people who need EPO treatment also need iron supplementation because EPO alone will not relieve the effects of anemia if iron levels are too low. Sometimes iron can be taken in a pill form, but according to the NIDDK, iron pills often do not work as well in people with kidney failure as iron given intravenously. Iron supplements should only be taken if prescribed by a physician based on blood analysis (National Kidney Foundation 2001e).

In addition to EPO and iron, some people also need vitamin B12 and folic acid supplements. Supplementation with EPO, iron, and appropriate B vitamins helps raise hemoglobin levels and most patients with kidney disease feel better, have more energy, and live longer (NIDDK 2001a).

L-Carnitine. For patients who are in a predialysis stage, are undergoing dialysis, or are post-transplant, nutritional supplementation with L-carnitine that has been lost during dialysis may reduce the side effects of common renal problems, such as cardiomyopathy and blood platelet aggregation, and may also help improve the patient's perception of their overall quality of life. L-carnitine is an amino acid that has shown effectiveness in providing cellular energy in both healthy individuals and those with chronic diseases.

General muscle weakness is a common complaint among patients undergoing hemodialysis. One study that measured the serum amount of L-carnitine found that hemodialysis lowered L-carnitine levels and posed new problems for patients (Wanic-Kossowska et al. 1998). This study measured muscle atrophy via nerve conduction and velocity testing and found indications of "neurogenic atrophy of the muscles." This well-known type of muscle weakness was further studied by doctors in Japan who reported that low dosages of L-carnitine (500 mg daily) showed improvement in two-thirds of 30 patients who were studied for 12 weeks. The patients reported less muscle weakness, general fatigue, and cramps and aches. This study concluded that low doses of L-carnitine could improve muscle weakness and should be considered as a prolonged adjuvant therapy for dialysis patients (Sakurauchi et al. 1998).

ESRD affects every aspect of a patient's life. Therefore, improved quality of life is very important for dialysis patients, potentially affecting compliance with medical, nursing, and nutritional prescriptions. In one study, patients were given the Medical Outcomes Study Short Form to assess quality of life from their perspective before taking L-carnitine and at 1.5-month intervals for the duration of the study (Sloan et al. 1998). This double-blind study was conducted on 101 patients who received L-carnitine or placebo just before and immediately after dialysis. After 3 months of supplementation (1 gram of L-carnitine before and after every hemodialysis treatment), patients reported an "improved vitality and general health." It was noted that serum albumin concentration was directly correlated with the patients' feelings of well being.

A study of L-carnitine therapy on erythropoiesis and blood platelet aggregation was conducted in patients with chronic renal failure, and it was found that L-carnitine caused a "significant rise in collagen-induced platelet aggregation." The 22-month study divided the patients into three groups. Group I received erythropoietin; Group II received erythropoietin and L-carnitine; and Group III received L-carnitine. Iron concentration and platelet count measured in urea concentration were relatively unchanged. The rise of collagen was observed after only 2 months of L-carnitine therapy (Kalinowski et al. 1999).

Curcumin. A potent antioxidant extract from the spice turmeric (Curcuma longa), curcumin has a wide range of health benefits: antiviral, anti-inflammatory, anticancer, and cholesterol-lowering. An interesting study in rats investigated the effect of curcumin on nephrosis caused by adriamycin. Adriamycin is a drug commonly used in chemotherapy (Venkatesan et al. 2000). The results indicated that curcumin "remarkably" prevented kidney injury caused by adriamycin. Venkatesan et al. (2000) stated that their data demonstrated that curcumin offered protection "by suppressing oxidative stress and increasing kidney glutathione content and glutathione peroxidase activity." They suggest that administration of curcumin offers promise in the treatment of nephrosis that is caused by adriamycin.

Another group (Suresh Babu et al. 1998) studied the effect of curcumin on streptozotocin-induced diabetes. Streptozotocin is also a commonly used chemotherapy drug. According to Suresh et al. (1998), their data "suggested that dietary curcumin brought about significant beneficial modulation of the progression of renal lesion in diabetes." This benefit of dietary curcumin on diabetic nephropathy may be mediated by its ability to lower blood cholesterol levels.

Ginkgo Biloba. Already known for its antioxidant effects, ginkgo biloba may also protect small blood vessels against loss of tone, prevent capillary fragility, inhibit atherosclerosis, and treat diabetic vascular disease. Naidu et al. (2000) studied gentamicin-induced nephrotoxicity in rats. Gentamicin is an antibiotic used to treat serious infections. Unfortunately, it has the undesirable side effects of causing kidney damage and irreversible hearing loss. Naidu et al. (2000) found that gentamicin treatment increased levels of blood urea and serum creatinine. However, they also found that ginkgo biloba extract (GBE) protected the rats from gentamicin-induced nephrotoxicity by preventing changes in blood urea, serum creatine, and creatine clearance.

Also in a study in rats, Umegaki et al. (2000) examined the effects of GBE extract on the development of hypertension, platelet activation, and renal dysfunction in deoxycorticosterone acetate-salt hypertensive rats. After 20 days, the rats fed a 2% GBE diet had attenuated development of hypertension.

In another interesting study in rats by Fukaya et al. (1999), encouraging results of co-administration of cisplatin and GBE were reported. Cisplatin is an effective antineoplastic agent (cancer killing) used for treating solid tumors. However, cisplatin also has the undesirable side effects of causing hearing loss and nephrotoxicity. Fukaya et al. (1999) concluded that co-administration of cisplatin with GBE was beneficial to ameliorate cisplatin-induced toxicity without attenuating the antitumor activity of cisplatin.

Grape Seed Extract. Known for its powerful antioxidant qualities, grape seed extract also acts as a smooth muscle relaxant in blood vessels to combat hypertension. Ray et al. (2000) studied the protective effects of grape seed extract against biological, pharmacological, and toxicological effects of certain drugs to the kidneys, lungs, and heart in mice (acetaminophen, amiodarone, and doxorubicin). Ray et al. (2000) found that "grape seed extract preexposure prior to acetaminophen, amiodarone, and doxorubicin provided near complete protection in terms of serum chemistry changes and significantly reduced DNA fragmentation." Moderate to massive tissue damage occurred by all three drugs in the absence of grape seed extract. Bagchi et al. (2000) also found that grape seed extract "demonstrated excellent protection against acetaminophen overdose-induced liver and kidney damage."

Green Tea. Yokozawa et al. (1999) studied the effects of green tea tannin to ameliorate cisplatin-induced renal injury in rats. They found that green tea tannin suppressed the cytotoxicity of cisplatin, "the suppressive effect increasing with the dose of green tea tannin." Additional testing showed rats given green tea tannin had decreased blood levels of urea nitrogen and creatinine and decreased urinary levels of protein and glucose, indicating less kidney damage. Yokozawa et al. (1999) concluded that "based on the evidence available, it appeared that green tea tannin eliminated oxidative stress and was beneficial to renal function." Earlier, researchers (Wardle 1999; Yokozawa et al. 1996) reported that green tea tannin was found to be beneficial for the kidney under oxidative stress. In 1991, Mukoyama et al. found that green tea had antiviral activity, inhibiting rotaviruses and enteroviruses in rhesus monkeys.

Soy. There is evidence that dietary phytoestrogens have a beneficial role in chronic renal disease (Velasquez et al. 2001; Ranich et al. 2001). Nutritional intervention studies demonstrated that consuming soy-based protein and flaxseed reduced proteinuria and attenuated renal functional or structural damage in both animals and humans. To date the studies have been of relatively short durations and involved small numbers of subjects. However, the results are encouraging and further investigations are needed. Three groups of researchers (Tomobe et al. 1998; Aukema et al. 1999; Ogborn et al. 2000) investigated the effects of a soy protein diet on polycystic kidney disease. Although the studies were conducted in rats and mice, the research teams suggested that dietary soy protein-based diets had beneficial effects in polycystic kidney disease: soy diet prevented significant elevation in serum creatinine in diseased vs. normal animals (Ogborn et al. 2000); soy protein is effective in retarding cyst development and this beneficial effect may be unrelated to genistein (an isoflavonoid present in soy protein) content (Tomobe et al. 1998); dietary protein level and source significantly affect polycystic kidney disease, with the effects being most pronounced in female animals fed low protein diets and soy protein-based diets (Aukema et al. 1999).

Taurine. Taurine is abundant in the brain, heart, gallbladder, and kidneys and plays an important role in health and disease in these organs. Taurine is an amino acid that has been shown to protect against experimentally induced lipid peroxidation of the renal glomerular and tubular cells and may alleviate tubular disorders such as glomerular impairment (Trachtman et al. 1996). It is also thought to lower blood pressure by balancing the ratio of sodium to potassium in the blood. Taurine may also regulate the increased nervous system activity that can contribute to high blood pressure. According to Franconi et al. (1995), some people with Type I diabetes appear to be deficient in the amino acid taurine.

Trimethylglycine (Betaine). Trimethylglycine (TMG) plays a role in the manufacture of carnitine and serves to protect the kidneys from damage (Chambers 1995). TMG has been reported to play a role in reducing blood levels of homocysteine, a toxic breakdown product of amino acid metabolism that is believed to promote atherosclerosis. The main nutrients involved in controlling homocysteine levels are folic acid, vitamin B6 and vitamin B12, but TMG has been reported to be helpful in some individuals whose elevated homocysteine levels did not improve with these other nutrients. TMG has also shown to be helpful in certain rare genetic disorders involving cysteine metabolism (Wilken et al. 1983; Wendel et al. 1984; Gahl et al. 1988; Barak et al. 1996; Selhub 1999; van Guldener et al. 1999). Its primary use as a nutritional supplement is in supporting proper liver function and possibly reducing the risk of urinary tract infections.

SUMMARY

The kidneys are remarkably resilient organs and can sometimes recover normal function from acute trauma as a result of injury, overdose of drugs, or poisoning, with prompt medical attention. However, there are forms of kidney disease that include conditions that can rapidly reduce kidney function or slowly reduce kidney function over several years, producing few or no symptoms. Damage from these conditions is not reversible. When kidney function is reduced to less than 10-15%, dialysis is required. When dialysis is no longer able to support kidney function, kidney transplantation is the only recourse.

If you have healthy kidneys, protect them. Start with a healthy diet; drink lots of water; give careful attention to the over-the-counter medicines you take, particularly when combined with prescription medicines or other over-the-counter products; consume alcohol responsibly (remember, over-the-counter or prescription drugs can be very damaging to the kidneys when combined with alcohol); protect your kidneys from injury if you engage in sporting activities; and consider taking protective supplements and nutrients to support overall kidney health.

As part of an annual physical checkup, request tests for blood levels of creatinine and blood urea nitrogen and urine levels of protein. Small elevations of creatinine can be an early sign of kidney disease. Early detection leads to early treatment which can occur at a stage when there is treatment to help prevent kidney disease from advancing to a more serious stage.

Because diabetes is the leading cause of chronic kidney disease, followed by hypertension, see your physician regularly and follow prescribed dietary and drug treatment to control blood sugar levels and hypertension (National Kidney Foundation 2001a) (refer to the Life Extension protocols on Diabetes and Hypertension for additional information).

Prevent damage to the kidneys from kidney stones by increasing water intake to 12 full glasses of water every day; limiting coffee, tea, and colas because caffeine increases fluid loss; increasing calcium intake using dietary factors; and including appropriate calcium/magnesium supplementation (taken only with food).

Research into gene therapy holds great hope for genetic kidney diseases. Of particular interest is research on the PKD1 gene, which is responsible for 85% or more of all ADPKD disease. ADKPD often progresses to kidney failure in young adulthood or middle age and accounts for the need for kidney transplantation for many persons.

If you have early stage kidney disease or chronic kidney disease, follow the dietary recommendations of your physician or a renal dietitian. For example, a diet low in sodium, potassium, and phosphorus, three substances regulated by the kidneys, is essential in managing kidney disease. Other dietary restrictions, such as reducing protein, may be required depending on the cause of kidney failure and the type of treatment being used (e.g., such as dialysis). Patients with chronic kidney failure may also need to limit their fluid intake.

Kidney Disease-5

noreply@blogger.com (Kishen) — Thu, 21 Feb 2008 01:28:00 +0000

Also follow your physician's recommendations concerning the addition of daily dietary supplements. Multivitamins, minerals, and other supplements may be prescribed or recommended to help replace essential nutrients lost during dialysis treatments. Consult medical professionals who are experienced in treating kidney disorders and follow their recommendations for treatment carefully. Establish good dietary habits that are appropriate for your situation. The following supplements are supportive of overall kidney health. The recommendations are for healthy individuals. If you have any form of kidney disease, consult your physician before adding or changing any supplements that you may currently be taking.

Supplements

1)Take a multivitamin to replace vitamins and minerals that are lost during dialysis or are deficient in your diet. Life Extension Mix is an excellent source of specific nutrients to defend the body against degenerative diseases. Life Extension Mix is available in several forms. Three tablets of Life Extension Mix Caps taken 3 times daily with meals are suggested.

2)Complete B-Complex contains safe and effective levels of all B-complex vitamins. Three capsules taken daily with meals are suggested.

3)Vitamin C has been shown to improve immune function, accelerate healing, and maintain healthy blood vessels. Vitamin C can come from dietary sources or from supplements: 2.5-6 grams daily from all sources are recommended. Each capsule of Vitamin C Caps provides 1000 mg of vitamin C (1 gram).

4)Vitamin D is necessary for proper utilization of calcium and phosphorus. Take one 1000-IU capsule of Vitamin D3 with fat-containing, low-fiber meals.

5)Vitamin E is known for its healing, cardiovascular, and immune-boosting benefits. Take one 400-IU capsule of Vitamin E succinate daily with fat-containing, low-fiber meals.

6)Calcium is vital for maintaining strong, healthy bones. It is suggested that postmenopausal women take 6 Bone Assure capsules daily. Four capsules are suggested for men. Bone Assure is most effective if taken at night with low-fiber meals.

7)Iron supplementation is often required for people who have anemia and need EPO treatment as a result of kidney disease and hemodialysis. If iron levels are too low, EPO alone will not relieve the effects of anemia. xSometimes iron can be taken in a pill form. However, iron may be more effective if given intravenously.
Only take iron pills if your physician prescribes them for you.

8)l-carnitine has beneficial qualities for conditions associated with low cellular energy, immune dysfunction, and diabetic complications. One to four 500-mg capsules of l-carnitine capsules taken in divided doses on an empty stomach with juice or water are suggested.

9)Curcumin is a potent antioxidant with antiviral, anti-inflammatory, anticancer, and cholesterol-lowering benefits. One 900-mg capsule of curcumin taken with meals is recommended.

10)Ginkgo biloba has been used for its protective qualities in vascular disease. Super Gingko Extract provides more of the active ingredients, but eliminates most of the ginkgolic acid part of the gingko leaf. Take one 120-mg capsule of Super Ginkgo Extract daily.

11)Grape seed extract has powerful, natural free radical scavengers. It can act as a relaxant for blood vessels to combat hypertension. One to two 100-mg capsules of grape seed extract daily are suggested.

12)Green tea has demonstrated many protective qualities, including its antioxidant benefits (neutralizing cancer-causing agents and protecting against free-radical damage); reducing cholesterol, blood glucose, and blood pressure levels; and inhibiting viruses and bacteria. Take one 350-mg capsule of Super Green Tea Extract (95%) with meals daily for prevention purposes. For those who are sensitive to caffeine or do not want to consume it, Super Green Tea (95% decaf) is available in a decaffeinated form. Consult your physician when taking larger quantities for disease treatment purposes.

13)Soy has protective qualities for kidney function in addition to its well-known anticancer, cholesterol lowering, and post-menopausal symptom alleviating benefits. Consider taking one 135-mg Mega Soy Extract capsule twice daily for general disease prevention purposes.

14)Taurine has potential benefits for the kidneys. By helping to lower blood pressure, it also regulates the increased nervous system activity that can contribute to high blood pressure. People with Type I diabetes may be deficient in taurine. One to four 1000-mg capsules of Taurine Capsules taken daily either with meals or on an empty stomach are suggested.

15)TMG (betaine) is possibly one of the most important nutrients with preventative benefits for heart disease, stroke, liver disease, and to slow aging. Consider taking one to five 500-mg tablets of TMG tablets daily.

16)The docosahexaenoic acid (DHA) fraction of fish oil may be the most effective non-prescription supplement to suppress pro-inflammatory cytokines. Super GLA/DHA provides 920 mg of GLA, 1000 mg of DHA, and 400 mg of EPA in 6 capsules taken daily.

17)DHEA, a hormone that decreases with age, has been shown to suppress IL-6, an inflammatory cytokine that often increases with age. Typical doses of DHEA are 25-50 mg daily (although some people take 100 mg daily). Refer to the DHEA protocol for suggested blood tests to safely and optimally use DHEA.

18)Consider taking nettle leaf (1000 mg daily) to suppress the pro-inflammatory cytokine TNF-alpha.

19)Vitamin E and N-acetyl-cysteine (NAC) are protective antioxidants with anti-inflammatory properties. Take 1-2 capsules daily of Gamma E Tocopherols/Tocotrienols. NAC is an amino acid with antiviral and liver protectant properties. One 600-mg capsule daily is recommended.

20)Vitamin K helps reduce levels of IL-6, an inflammatory cytokine. One 10-mg capsule daily is recommended for prevention purposes.

21)Magnesium deficiency leads to increase of urine alkalinity, often resulting in the formation of calcium phosphate stones. Magnesium (500 mg daily) reduces calcium absorption.

Overlooked Prescription Drug

Kidneys are especially vulnerable to attack by proinflammatory cytokines. Pentoxifylline (PTX) is a drug that has been shown to protect against this type of kidney damage. The suggested dose is 400 mg twice a day of PTX.

PTX should not be used in patients with bleeding disorders such as those with recent cerebral or retinal hemorrhage. Patients taking Coumadin should have more frequently monitored of prothrombin time. Those suffering from other types of bleeding should receive frequent physician examinations. Furthermore, we would consider evaluating the individual patient's coagulation status to see what effect PTX has on the template bleeding time. This is an inexpensive test that relates the biological effect of PTX or other agents like aspirin (nonsteroidal anti-inflammatory agents) on the function of platelets. All of these agents affect platelet aggregation and this effect can be manifested in a prolonged template bleeding time. According to two studies, PTX should be avoided by Parkinson's patients. It is important to note that the body does use TNF-alpha to acutely fight infections. If patients are showing any sign of infectious disease, drugs like Enbrel that inhibit the effects of TNF-alpha are temporarily discontinued. A new FDA advisory states that patients should be tested and treated for inactive, or latent, tuberculosis prior to therapy with another TNF-alpha inhibiting therapy (e.g., infliximab). Since PTX, fish oil, and nettle directly suppress TNF-alpha, perhaps these agents should be temporarily discontinued during the time when one has an active infection.

FOR MORE INFORMATION
Contact the National Kidney Foundation, (800) 622-9010 or http://www.kidney.org; the American Foundation for Urologic Disease, (800) 242-2383 or www.access.digex.net/~afud; and the National Kidney and Urologic Diseases Information Clearinghouse, (301) 654-4415 or e-mail nkudic@info.niddk.nih.gov ; (website) www.niddk.nih.gov , for more information.

Product availability

Life Extension Mix, Complete B-Complex, vitamin D3, vitamin E succinate, vitamin C, Iron Protein Plus, DHEA, NAC, Gamma E Tocopherol/Tocotrienols, vitamin K, Bone Assure, L-carnitine Capsules, Curcumin, Super Ginkgo Extract, grape skin extract, Super Green Tea Extract (95%), Super Green Tea (95% decaf), Mega Soy Extract, Optizinc, Taurine Capsules, TMG Tablets, Folic Acid + B12, L-Methionine Powder, calcium, and magnesium are available by ordering online.

Urinary Tract Infection

noreply@blogger.com (Kishen) — Thu, 21 Feb 2008 01:16:00 +0000

1)Bacterial Utis And Interstitial Cystitis

2)Causes

3)Prevention

4)Alternative Treatments

5)Summary

According to the Journal of the American Medical Association (JAMA), urinary tract infections (UTIs) account for more than 11 million physician visits annually in the United States (Howell et al. 2002). UTIs may be caused by bacteria, viruses (herpes simplex Type 2), fungi (Candida), and a variety of parasites (worms, protozoa). Unfortunately, UTIs have become increasingly resistant to first-line antibiotic therapy. There are two types of UTIs: lower and upper.

Lower UTIs occur in the urethra or bladder and are more common in women than in men (because the female urethra is much shorter and provides less of a barrier to bacterial invasion), with as many as one third of all women experiencing a UTI in their lifetime (Valiquette 2001). Urine that is in the bladder should be sterile. In healthy adults, however, the large bowel is not sterile and bacteria coming from normal intestinal flora can pass into the bladder. When large-bowel bacteria colonize the bladder, the result is cystitis or a bladder infection.

Cystitis or infection of the bladder are common examples of a lower UTI. Although rare in young men, cystitis can occur in men as a result of urethral obstruction from a prior infection of a sexually transmitted disease or from a congenital defect of the urethra requiring surgical correction.

Upper UTIs are infections that involve kidneys (pyelonephritis), ureters (ureteritis), or both. Upper UTIs can occur in both men and women as a complication of a lower UTI. Upper UTIs can also arise without lower urinary tract involvement. The latter may occur in younger women or men as a result of an obstruction somewhere in the urinary tract. Examples are a kidney stone or abdominal tumor which obstructs the ureter. Symptoms of an upper UTI include fever, chills, lower back pain, nausea, and vomiting. The most common organism causing the infection is a bacteria named Escherichia coli.

Although men are not generally prone to lower UTIs, they can develop upper UTIs as they become older because they cannot fully empty their bladders as a result of prostatic enlargement. Urine cannot remain sterile when it stays in the bladder for long periods of time. In elderly men, this evolves into full-blown urinary retention, a condition in which a liter or more of urine may have to be drained via a catheter. Urinary retention is potentially very serious and can result in urosepsis, a condition in which overwhelming disseminated infection invades the bloodstream. Urosepsis can be fatal.

One of the more common predisposing factors for UTIs is diabetes mellitus: spillage of glucose into the urine as well as other factors provide a good culture medium for bacteria (Patterson et al. 1997). Other causes include improper bladder emptying from neurological diseases such as paraplegia; valve leakage between the ureter and the bladder; and indwelling urinary catheters that are left unchanged for too long a period of time. The underlying cause of any UTI must be properly diagnosed and promptly treated.

Bacterial UTIs and Interstitial CystitIS

1)Bacterial UTIs

2)Interstitial Cystitis

Bacterial UTIs
In women of reproductive age, bacterial infections are the most common type of infection occurring in the bladder. Often this is the result of a bruised urethra resulting from intercourse, although the exact mechanism is not entirely clear. However, we now know that condoms may be a contributing factor to the high incidence of UTIs in reproductive age groups. In a study in Epidemiology, researchers at the University of California-Berkeley conducted a nested case control study among a cohort of 519 women aged 15-29 years and found that male condom use was associated with increased UTI risk, with the largest risk being associated with exclusive condom use and use of Nonoxynol-9-coated condoms (Handley et al. 2002). Symptoms of cystitis include a frequent, urgent desire to urinate, burning pain with urination, and often pain above the pelvic bone and in the lower back. Urine may be cloudy and contain visible blood. What is most significant is that many women have recurrent bouts of cystitis, but no underlying cause, including sexual intercourse (recurrent cystitis is found in nuns), can be found. The infection is clearly caused by bacteria, but the reason for recurrence remains unclear.

Interstitial Cystitis
As noted earlier, cystitis is caused by an infectious organism. This distinguishes cystitis from another disease called interstitial cystitis. Interstitial cystitis is also more common in women than in men. A person who has interstitial cystitis can usually tell you the exact moment the symptoms began. Often interstitial cystitis is characterized by severe superpubic pain which is relieved by urinating. However, time after time, when patients go to a physician, bacteria do not grow in a culture of their urine.

Unfortunately, interstitial cystitis is not widely recognized by many primary care physicians. As a result, the average time until diagnosis is 7 years! The pain associated with interstitial cystitis is said to rival that of cancer. Eventually, the diagnosis is made when a urologist finally decides to perform cystoscopy and look in the bladder. The appearance of the bladder may be totally normal. However, when the urologist attempts to fill the bladder with water, he finds that the bladder capacity is markedly diminished. Additionally, when the water is released, the bladder wall oozes blood in a manner causing a characteristic appearance called glomeration. If a biopsy is taken, mast cells, not normally present in the bladder, are seen. Mast cells are a diagnostic finding.

In a worst-case scenario, the condition progresses with ever-increasing replacement of normal bladder tissue with fibrosis or scar tissue. The bladder capacity lessens. Persons with interstitial cystitis can go few places and cannot maintain employment because they must urinate constantly. They cannot sleep at night because they must continually get up to urinate. Some patients require replacement of the bladder dome with part of their own colon to increase bladder capacity. Other patients require removal of the bladder and creation of a urinary diversion to an exterior bag (urostomy).

Interstitial cystitis has no known cure. Treatment has consisted of bladder installations of DMSO (di-methylsulfoxide) and other agents; hydrostatic dilatation of the bladder under pressure; and use of a drug called Elmiron which is effective in 30% of cases. Changes in diet may also be helpful. Relief of symptoms is variable. Presently, there are some who think there is an agent responsible for interstitial cystitis that has not yet been identified. Research trials, including trials with antibiotics, are presently being conducted.

What Causes a UTI?

Escherichia coli (E. coli), a bacterium normally found in the digestive tract and present on the skin around the rectal area, is the organism most often responsible for UTIs. Other bacteria can also be involved, but E. coli is by far the most prevalent cause of UTIs (over 80%).

Structure of the female anatomy predisposes women to infection because the urethral opening is located very close to the anus, which is a common source of bacteria. Therefore, bacteria can easily migrate across the perineum (the narrow band of flesh between the anus and the vagina) to the urethra. Bacterial invasion can result in acute cystitis, the most common type of UTI. A more rare condition is urethritis, a condition in which only the urethra is inflamed. When bacteria from the bladder ascend to the kidneys via the ureters, they can cause a more serious infection called pyelonephritis. Although men do get UTIs, the structure of their physical anatomy makes infection less likely. The male urethra is much longer, and secretions from the prostate gland provide a better barrier against this type of infection.

URINARY TRACT INFECTION PREVENTION

Because UTIs can be the result of more serious medical conditions, it is important to seek prompt medical advice for proper diagnosis and treatment. Most UTIs are painful and bothersome, but usually they can be successfully treated with antibiotics. A list of the antibiotics that are specific for treating UTIs would be lengthy. Just a few of the commonly used drugs are Bactrim, Ceclor, Ceftin, Cipro, Keflex, Macrodantin, and Septra. All drugs for UTIs require a prescription from a physician. Besides the use of prescription drugs, there are certain steps that persons with chronic UTIs can take to lower the likelihood of recurrence:

1)Avoid caffeine, alcohol, and spicy foods that can further irritate the bladder.

2)Use several capsules of a probiotic (Lactobacillus acidophilus) regularly.

3)Drink 8-10 glasses of water or other fluids each day to dilute bacteria in the urine.

4)Eat plain yogurt to help control development of a yeast infection after taking antibiotics for a UTI.

5)Cleanse well with soap and water before and after sexual activity. Your partner should do the same.

6)Take showers instead of baths.

7)Wear cotton underwear and loose-fitting clothes.

8)For women: if using a diaphragm, clean thoroughly, rinse, and carefully dry the diaphragm after each use. After using the toilet, always wipe from front to back.

ALTERNATIVE TREATMENTS FOR RECURRENT URINARY TRACT INFECTIONS

1)Cranberry Juice

2)Cranberries Under the Microscope

3)Probiotics

4)Acupuncture

Cranberry Juice

Cranberry juice can be an effective deterrent to the recurrence of simple UTIs (Schmidt et al. 1988). Cranberry juice has developed into a popular nondrug means to reduce or treat UTIs. Studies document that drinking eight 8-ounce glasses of cranberry juice twice a day (or a total of 16 glasses daily), may eradicate most simple UTIs. As long as cranberry juice consumption is continued the infections are not likely to return. One way that cranberry juice works is to prevent bacteria from adhering to the linings of the urinary tract. Studies suggest that bacterial infections (bacteriuria) and the associated influx of white blood cells into the urine (pyuria) can be reduced by nearly 50% in elderly women who drink 300 mL of cranberry juice cocktail each day (Fleet 1994).

In a study in JAMA, researchers at Rutgers University and the University of Michigan assessed whether the consumption of cranberry juice cocktail prevented adhesion of antibiotic-resistant pathogenic E. coli to the uroepithelium in 39 women aged 18-39 years with confirmed UTIs (Howell et al. 2002). According to the researchers, after cranberry juice cocktail consumption, the urine prevented adhesion of 31 (80%) of the 39 isolates and 19 (79%) of the 24 antibiotic-resistant isolates in all bioassays, while preconsumption urine failed to prevent adhesion in any of the samples.

According to the study, the anti-adhesion activity was evident in the urine within 2 hours and persisted for up to 10 hours following ingestion of cranberry juice cocktail. In addition, the extracted cranberry juice pro-anthocyanidins inhibited adhesion of all isolates at concentrations ranging from 6-375 mcg/mL, demonstrating potent in vitro anti-adhesion activity against antibiotic-resistant strains. According to the researchers, these data suggest that consumption of cranberry juice cocktail may offer protection against both sensitive and resistant strains of P-fimbriated E. coli (the initial step in development of UTIs) and support previous findings which have found cranberry juice to be an effective alternative option in the treatment of UTIs (Howell et al. 2002).

In urostomy patients (surgical diversion of urine away from a diseased or defective bladder and through the skin to the outside of the body), problem urinary wall skin conditions are common and may stem from alkaline urine. Cranberry juice appears to acidify urine and have bacteriostatic properties. Thus, cranberry juice is widely recommended for the reduction of UTIs. A study showed that drinking cranberry juice could help to prevent and improve skin complications for urostomy patients. The study also showed that in patients with severe urinary wall disease, cranberry juice resulted in improvements of skin conditions and a reduction in skin complications (Tsukada et al. 1994).

Most people will find it difficult to drink sixteen 8-ounce glasses of cranberry juice a day. Fortunately, there are dietary supplements that will provide the equivalent of eight to sixteen 8-ounce glasses of cranberry juice in just one capsule. A major advantage of using cranberry juice concentrate supplements is that cranberry juice is high in sugar. If a person were to consume 8-16 glasses of cranberry juice each day, the high fructose intake would induce weight gain and possibly create other serious health problems. (Refer to the Obesity protocol for information about the dangers of chronic consumption of large amounts of sugars.)

Cranberries Under the Microscope
In work undertaken separately and in parallel in both the United States and Israel, studies have now established that:

1)Adherence of bacteria to the walls of the urinary tract is an important prerequisite for the colonization of E. coli. Bacteria adhere to the cells of the urinary tract using hair-like fimbriae (or pili) that protrude from the surfaces of the bacteria. These fimbriae attach to specific monosaccharide or oligosaccharide receptors on urothelial cells. The fimbriae are designated either Type I (mannose sensitive) or Type P (mannose resistant).

2)By adhering to urinary tract cells, E. coli can withstand normal body-cleaning mechanisms and overcome nutrient deprivation, leading to infection and toxicity.

3)The cranberry factor (juice or supplements) contains a potent factor that affects and disables the cell structure of E. coli, thus inhibiting the ability of bacteria to adhere to the wall of the urinary tract.

4)The cranberry factor is composed of certain condensed tannins (or proanthocyanidins) which collectively prevent E. coli from colonizing in the urinary tract.

In 1994, a landmark study demonstrated that regular use of cranberry juice significantly reduced bacterial growth in the urinary tract, as well as the body's response to infection in the form of white blood cells. This study added impetus to the familiar lore about cranberries and their benefits against UTIs (Avorn et al. 1994).

Self-medication with cranberry juice cocktail is often a common approach to dealing with a UTI, and cranberry juice has frequently been recommended by physicians as an adjunct to antibiotic treatments, but this recommendation could certainly be termed old-fashioned.

It is important to remember that cranberry juice cocktail contains only 27% cranberry juice (the remainder is sweetened water). While cranberry juice cocktail may be somewhat effective against UTIs, drinking large amounts of this super-sweetened product has many drawbacks for a health-conscious society: too much sugar and too many calories. Even pure cranberry juice contains high amounts of body-fat-inducing fructose. This is not a preference of most people. For diabetics, using cranberry juice is an impossible recommendation.

An excellent alternative is using a cranberry supplement. These highly concentrated cranberry capsules have shown efficacy in preventing and facilitating treatment in persons with UTIs.

The ultimate way of treating UTIs is to prevent adherence of bacteria to the urinary wall. The development of a low-cost cranberry extract supplement provides an ideal supplement for persons who are at risk for developing a UTI. The recommended dose of this cranberry extract supplement is just one capsule a day.

Probiotics
Probiotics are various strains of "good" bacteria (Lactobacillus, bifidus, etc.) that naturally inhabit the colon and vagina. Research shows that the presence and dominance of Lactobacillus in the gut and vagina are associated with a reduced risk of UTIs and bacterial vaginosis. Apparently a higher level of "friendly" bacteria in the vagina and the intestines inhibits the colonization of unwanted pathogenic bacteria. Additionally, friendly bacteria such as acidophilus and bifidus aid the immune system, aid digestion, and synthesize vitamins in the intestine.

The significance of the function of friendly bacteria in UTIs has been reported in several studies (Asahara et al. 2001; Reid 2001, 2002; Reid et al. 2001, 2002; Strus et al. 2002). When several different strains of Lactobacillus were used orally and introduced vaginally, there was a reduced risk of UTIs and improvement of normal vaginal flora. It is believed that the mechanism of friendly bacteria is similar to that of cranberries in that it involves antiadhesion factors and it also creates by-products that are lethal to pathogens, possibly modulating immune signaling effects. Lactobacillus strains taken from normal vaginal flora have been shown to contain antagonistic activity against a variety of bacteria known to cause infections of the urinary tract and vagina. In mouse model studies of UTIs, researchers introduced specific strains of Lactobacillus intraurethrally and found that Lactobacillus worked as an effective treatment and preventive of UTIs (Asahara et al. 2001).

Acupuncture
In a study from Norway, researchers conducted a 6-month clinical trial to evaluate the effect of acupuncture on 67 women with recurrent cystitis. The trial was divided into three groups: the acupuncture group, a sham-acupuncture group, and an untreated control group. In the 6-month trial period, 85% of subjects in the acupuncture group were free of cystitis, compared with 58% in the sham group and 36% in the control group. The results of the study suggest that acupuncture treatment might be a viable alternative in the prevention of chronic cystitis (Aune et al. 1998).

SUMMARY

To Treat Recurrent UTIs:

1)Obtain a thorough evaluation by a nephrologist or urologist.

2)Take 1 Cran-Max (500-mg) cranberry juice concentrate capsule daily.

3)Use 4-6 capsules of a probiotic containing acidophilus, taken orally. Use 1-2 capsules, inserted vaginally.

4)Take 1-2 capsules of proanthocyanidins (grape seed extract).

5)Consider taking magnesium (100 mg), or calcium (1000 mg) 3 or 4 times daily.

To Treat Interstitial Cystitis:

1)Obtain a thorough evaluation by a nephrologist or urologist with experience in interstitial cystitis.

2)For pain management, consider using buprinorphine--a 1-5 mg sublingual troche every 6-8 hours. (See the protocol on Pain for additional information).

3)Consider using intravenous vitamin C, 50 grams, administered 3 times a week by a knowledgeable physician.

4)Consider using intravenous DMSO.

DMSO should not be used during pregnancy.

For a physician familiar with orthomolecular medicine, contact the American College for Advancement in Medicine: (800)532-3688.

For more information

Contact the Bladder Health Council, 300 West Pratt Street, Suite 401, Baltimore, MD 21201. For more information about interstitial cystitis, contact the Interstitial Cystitis Association of America, P.O. Box 1553, Madison Square Station, New York, NY 10159.

Product availability

Cran-Max, Life-Flora (Lactobacillus acidophilus and bifidus), calcium, magnesium, and grapeseed extract may be ordered by calling (800) 544-4440 or by ordering online. Buprinorphine is available as a sublingual troche at Medical Center Pharmacy, (800) 723-PILL.

Cancer Radiation Therapy-1

noreply@blogger.com (Kishen) — Thu, 21 Feb 2008 00:57:00 +0000

Along with surgery and chemotherapy, radiation therapy (radiotherapy) is one of the most important methods of cancer treatment. At least 50 percent of all cancer patients will receive radiotherapy at some stage during the course of their illness. It is currently used to treat localized solid tumors, such as cancers of the skin, brain, breast, or cervix, and can also be used to treat leukemia and lymphoma (Tobias JS 1992).

Most types of radiation do not attack cancer cells specifically, and therefore cause injury to normal tissues surrounding the tumor. The adverse effects are a major factor limiting the success of radiation treatment. However, proton therapy and CyberKnife® therapy are technologically advanced forms of radiotherapy that cause little damage to normal tissue because they focus intensely on the tumor.

The effectiveness of radiation therapy can be enhanced by both radiosensitizers, such as genistein, curcumin, green tea, and hyperthermia, and radioprotectors, such as ginseng, glutathione, whey protein, and shark liver oil. Overall, the use of specific nutritional supplements, drugs, and other strategies may prevent and help to alleviate and treat the side effects caused by radiation, and thereby improve the effectiveness of radiotherapy.

Principles of Radiation Therapy (Radiotherapy)
Radiation therapy is the treatment of cancer with ionizing radiation. Radiation works by damaging the DNA (genetic material) within the tumor cells, making them unable to divide and grow. Radiation is often given with the intent of destroying the tumor and curing the disease (curative treatment). However, although radiation is directed at the tumor, it is inevitable that the normal, non-cancerous tissues surrounding the tumor will also be affected by the radiation and therefore damaged (Burnet NG et al. 1996). The goal of radiation therapy is to maximize the dose to tumor cells while minimizing exposure to normal, healthy cells (Emami B et al. 1991).

Because no single therapy can provide complete treatment for a patient with a solid tumor, radiotherapy is often used in combination with surgery or chemotherapy to improve the chances of a successful treatment outcome. Sometimes radiation is used to relieve symptoms, such as pain or seizures; this is called palliative treatment (Hoskin PJ et al. 1992).

What Is Ionizing Radiation?

Radiation used for cancer treatment is called ionizing radiation because it forms ions as it passes through a tissue. Ions are atoms that have acquired an electric charge through the gain or loss of an electron (Dunne-Daly CF 1999). Ions can cause cell death or genetic change either directly or indirectly. The direct effect causes a change in the molecular structure of biologically important molecules, most likely DNA. The indirect action of radiation occurs when it interacts with water molecules in the cells, resulting in the production of highly reactive and unstable free radicals or reactive oxygen species, which immediately react with any biomolecules in the surrounding area, producing cellular damage (Fang YZ et al. 2002).

This damage can lead to cell death by two mechanisms (Ross GM 1999). The first process, known as apoptosis, results in cell death within a few hours of radiation (Kerr JF et al. 1994). The second mechanism is radiation-induced failure of cell division and the inhibition of cellular proliferation, which in turn leads to cell death. Several enzymatic and nonenzymatic antioxidant defense mechanisms exist in cells and prevent excessive damage through the scavenging and inactivation of these reactive oxygen species (Mates JM et al. 2000).

Types of Radiation Therapy

External beam radiation therapy (EBRT). EBRT creates a radiation beam and aims it at the tumor. The radiation adequately covers the tumor but minimizes the dose to the non-tumor normal tissues. Radiation is given in fractions rather than as a single dose, and the use of this fractionated radiotherapy allows normal cells time to repair between each radiation session, protecting them from injury.

Conventional fractionation in the United States is 1.8 to 2 Gray (Gy) per day, administered five days a week for five to seven weeks, depending on the particular clinical situation. (Gray is a unit of measure of absorbed radiation dose.) While this schedule is strictly for the convenience of physicians trying to maintain a normal workweek, the relatively long intervals between doses of radiation may allow cancer cells (as well as normal cells) to recover and regrow.

A number of different radiotherapy schedules have been suggested to overcome this problem (Shah N et al. 2000). These include hyperfractionation, in which the time between fractions is reduced from 24 hours to 6 to 8 hours to enhance the toxic effects on tumor cells (Fu KK et al. 2000) while still preserving an adequate time interval for the recovery of normal cells. Continuous hyperfractionated accelerated radiation therapy (CHART) is an intense schedule of treatment, in which multiple daily fractions are administered within a short period of time. Clinical studies have shown benefits of altered fractionation over conventional treatment for several cancers, including head and neck cancer (Goodchild K et al. 1999) and non-operable lung cancer (Ghosh S et al. 2003).

Proton beam radiation therapy. This is one of the most precise and sophisticated forms of external beam radiation therapy available. The advantage of proton radiation therapy over x-rays is its ability to deliver higher doses of shaped beams of radiation directly into the tumor while minimizing the dose to normal tissues. This leads to reduced side effects and improved survival rates (Suit HD 2003). As of 2002, more than 32,000 patients around the world had received part or all of their radiation treatment by proton beams.

There are approximately 19 proton treatment centers worldwide. Two major hospital-based facilities in the United States that regularly treat patients with proton beams (often fractionated) are Loma Linda University Medical Center in southern California (LLUMC Proton Treatment Center) and the Northeast Proton Treatment Center at Massachusetts General Hospital in Boston. The Midwest Proton Radiotherapy Institute in Bloomington, Indiana (http://www.mpri.org/) treats children and adults with certain brain tumors, as well as those with tumors that are close to vital organs and therefore cannot be treated successfully using traditional methods.

The efficacy of proton beam radiation therapy has been clinically proven (Shipley WU et al. 1995) in prostate (Slater JD et al. 1999; Zietman AL et al. 2005), lung (Bush DA et al. 1999), hepatocellular (Matsuzaki Y et al. 1995), and uveal melanoma (Courdi A et al. 1999; Munzenrider JE 1999; Spatola C et al. 2003), sarcomas of the skull base and cervical spine (Munzenrider JE et al. 1999), optic pathway gliomas (Fuss M et al. 1999), astrocytomas (Habrand JL et al. 1999), benign meningioma (Gudjonsson O et al. 1999), non-resectable rectal, esophageal (Koyama S et al. 2003), and liver cancers (Ask A et al. 2005b), head and neck cancers, including thyroid cancer (Ask A et al. 2005a; Sugahara S et al. 2005), and more.

Intensity modulated radiation therapy (IMRT). IMRT creates a shaped radiation beam, delivering high doses of radiation to the tumor and significantly smaller doses of radiation to the surrounding normal tissues (Hurkmans CW et al. 2002; Nutting C et al. 2000). This may result in a higher cancer-control rate and a lower rate of side effects (Garden AS et al. 2004; Welsh JS et al. 2005).

IMRT has been used successfully in the treatment of several types of cancer, including prostate (De Meerleer G et al. 2004), cervical (Ahmed RS et al. 2004), nasopharyngeal (Kwong DL et al. 2004), and pediatric cancers (Penagaricano JA et al. 2004).

Brachytherapy. Brachytherapy can be used for many types of cancers, but it is most commonly used to treat prostate cancer (Woolsey J et al. 2003) and gynecologic cancers, such as cervical or uterine cancer (Nakano T et al. 2005). Brachytherapy usually involves the insertion of devices around or within the tumor to hold radioactive sources or seeds. Radioactive isotopes, such as cesium, are then inserted into the delivery device, either temporarily or permanently, allowing for the slow delivery of a high dose of radiation to the interior of the tumor (Fieler VK 1997).

Radioimmunotherapy (RIT). Radioimmunotherapy, one of the newest developments in the treatment of non-Hodgkin's lymphoma (Harris M 2004), has achieved a high tumor response rate (up to 80 percent) in several clinical trials (Witzig TE et al. 2002). Radioimmunotherapy uses drugs called monoclonal antibodies, which have a radioactive isotope attached to them. This is targeted to the surface of a cancer cell, destroying it. Radioimmunotherapy can be used (in a targeted fashion) to treat single cells that have spread around the body (Riley MB et al. 2004). Because the radiation does not concentrate in any one area of the body, radioimmunotherapy does not cause side effects commonly seen with external beam radiation therapy. The most significant side effect associated with radioimmunotherapy may be a temporary drop in white blood cell or platelet count (Witzig TE et al. 2003).

Stereotactic body radiation therapy (SBRT). SBRT is a standard form of treatment for primary and metastatic brain cancer (Phillips MH et al. 1994). It is delivered using a machine called a gamma knife, which uses converging beams of gamma radiation that meet at a central point within the tumor, where they add up to a very high, precisely focused dose of radiation in a single fraction. Due to this precision, the cancer can be located in an area of the brain or spinal cord that might normally be considered inoperable (Song DY et al. 2004).

CyberKnife®. CyberKnife® is a non-invasive, precise radiation technique that can deliver concentrated and accurate beams of radiation to any site in the body. This system combines robotics and advanced image guidance cameras to locate the tumor’s position in the body and deliver highly focused beams of radiation that converge at the tumor, avoiding normal tissue. It is a successful method used to treat spinal tumors (Gerszten PC et al. 2004b) or tumors at other critical locations that are not amenable to open surgery or radiation, as well as to treat medically inoperable patients (Gerszten PC et al. 2004a). It can also be used to treat benign tumors and lesions in a previously irradiated site, or to boost standard radiotherapy (Bhatnagar AK et al. 2005; Degen JW et al. 2005).

Three-dimensional conformal radiation therapy (3D-CRT). 3D-CRT is a technique that uses imaging computers to precisely map the location of a tumor (Symonds RP 2001). The patient is fitted with a plastic mold or cast to keep the body part still so that the radiation can be aimed more accurately from several directions. By aiming the radiation more precisely at the tumor, it is possible to reduce radiation damage to normal tissues surrounding the tumor by up to 50 percent (Perez CA et al. 2002).

Radiation Therapy versus Medical X-rays (Diagnostic Imaging)

Although diagnostic x-rays provide great benefits, including the earlier detection of cancers and the possibility of early treatment, their use is associated with small increases in cancer risk (Ron E 2003). One study estimated that cancer risk due to diagnostic x-rays varied from 0.6 percent to 3 percent in the 15 developed countries studied (Berrington de Gonzalez A et al. 2004).

Therefore, it is prudent to avoid unnecessary x-ray procedures. Up to 30 percent of chest x-rays may not be necessary (McCreath GT et al. 1999). Unnecessary computed tomography (CT) examinations may result in increased radiation exposure (Fleszler F et al. 2003; Frush DP 2004). The cumulative risk of cancer mortality from CT examinations in the United States is about 800 radiation-induced cancer deaths per 1 million examinations in children under the age of 15 (Brenner D et al. 2001).

Mammography (chest x-ray) uses low-dose x-rays to create a detailed image of the breasts. Although there is some controversy regarding mammography’s effectiveness in reducing breast cancer mortality, successful treatment is linked to early diagnosis, as mammography can often show changes in the breast before they can be detected by manual examination (Olsen O et al. 2001).

The effective radiation dose from a mammogram is about the same as the average person receives from background radiation over a three-month period (Sabel M et al. 2001).

At present, the consensus view is that the benefits of screening women over 50 years of age with yearly or twice-yearly mammograms substantially outweighs the associated risks due to radiation exposure (Beckett JR et al. 2003). However, there appears to be no significant benefit for women under the age of 40, and there may be harm for women under 30 due to the danger of cancer developing after exposure to radiation (Brenner DJ et al. 2002). Therefore, the main area of controversy concerns women between the ages of 40 and 49

Radiation: A Cause of Cancer?

The link between radiation and cancer was first recognized by studying atomic bomb survivors in Japan (Wakeford R 2004). Some cases of leukemia are related to radiation exposure and usually develop within a few years of exposure, peaking at five to nine years after exposure, then slowly declining (Ron E 2003; Wakeford R 2004). The development of other types of cancer after radiation exposure can take much longer to occur. Most cancers do not occur until 10 years after radiation exposure and some are diagnosed 15 or more years later (Hall EJ et al. 2003).

What You Have Learned So Far

1)Radiation therapy is one of the primary methods currently used to treat cancer.

2)It involves targeting the tumor with a beam of ionizing radiation, leading to the death of tumor cells through either the production of reactive oxygen species or from direct DNA damage.

3)Radiation cannot selectively target the tumor; therefore, normal cells within the radiation field suffer damage, leading to potentially serious side effects (Porock D 2002).

4)Ionizing radiation is used in many diagnostic techniques, such as mammography and computed tomography (CT) scans.

5)Radiation is a potent carcinogen that can give rise to a second radiation-induced cancer.

6)Exposure to diagnostic x-rays should be kept to a minimum, and women under the age of 49 should not undergo yearly mammograms.

Strategies to Optimize Radiotherapy Response

Tumor gene analysis. An examination of the genetic material of tumor cells often reveals differences between the cells that can be manipulated therapeutically. For example, the tumor suppressor gene p53 is the most frequently mutated gene in human tumors (Cuddihy AR et al. 2004), and tumors containing wild type p53 (p53 that is not mutated) are associated with a significantly better prognosis when treated with radiation (Alsner J et al. 2001; Ma L et al. 1998). However, this is not a universal finding (Saunders M et al. 1999).

Results of the largest known biomarker study of prostate cancer patients treated with radiation therapy indicate that the presence of a protein biomarker called Ki-67 is a significant predictor of outcome in men treated with both radiation and hormones (Li R et al. 2004). When a tumor cell tests positive for Ki-67, the tumor is actively growing, and the greater the proportion of prostate tumor cells with Ki-67, the more aggressive the cancer (Wilson GD et al. 1996). Ki-67 can be measured by a test offered by Genzyme Genetics (www.GenzymeGenetics.com).

Guarding against anemia. Anemia is one of the most common blood abnormalities of cancer. In patients with solid tumors, the incidence of anemia has been reported to vary between 45 percent in those with colon cancer up to 90 percent in patients with small-cell lung cancer (Knight K et al. 2004). An association between hemoglobin level and controlling tumor growth and survival has been identified for a large number of cancers, including breast (Henke M et al. 2004), cervical (Winter WE3 et al. 2004), and head and neck cancers (Daly T et al. 2003).

Cancer patients with low hemoglobin levels do not respond as well to radiotherapy as non-anemic patients (Ludwig H et al. 2001), due to impairment of oxygen transport to tumor cells (Dunst J 2004). Hemoglobin values measured during treatment are believed to be predictive of outcome (Tarnawski R et al. 1997).

Treatment outcome might be improved by correcting anemia (low hemoglobin levels) (Grogan M et al. 1999). Nutritional supplements that may help correct anemia include melatonin, folic acid, and vitamin B12; for more information, refer to the Blood Disorders chapter. The use of erythropoietin (sold under the drug brand name Procrit®) with minimal iron supplementation (Olijhoek G et al. 2001) or blood transfusions (Bokemeyer C et al. 2004) may be required in some cases. Erythropoietin is a growth factor that produces a steady, sustained increase in hemoglobin levels (Cheer SM et al. 2004; Stuben G et al. 2003).

Measurement of tumor oxygen levels. Low tumor oxygen levels (hypoxia) and anemia in the patient are associated with increased risk of spread (metastasis) and recurrence (Harrison L et al. 2004; Vaupel P 2004), especially for cervical cancers, head and neck cancers, and soft tissue sarcomas (Brizel DM et al. 1996; Nordsmark M et al. 2004). Hypoxia presents a problem for radiotherapy because radiation’s ability to kill cancer cells (i.e., radiosensitivity) rapidly decreases in areas of oxygen depletion, as free radicals cannot be produced due to limited oxygen supply (Fridovich I 1999).

Tumor oxygen levels are usually measured by the use of electrodes inserted directly into the tumor (Coleman CN 2003; Vaupel P et al. 2001). If a tumor is found to be hypoxic, strategies to improve oxygen levels could be employed to improve radiotherapy (Overgaard J et al. 2005) or, alternatively, radiotherapy may be reconsidered.

Tumor hypoxia has been exploited in cancer treatment (Brown JM 2000). A number of chemical agents, such as misonidazole, that preferentially sensitize hypoxic cells to radiation have been developed and tested in the clinic, particularly for the treatment of head and neck cancers (Brown JM et al. 2004). However, some have poor clinical effectiveness (Brown JM 1995). A number of approaches (e.g., carbogen and nicotinamide (ARCON)) have been introduced and are now in clinical trials (Kaanders JH et al. 2004).

Hypoxia is also implicated in the activation of angiogenic cytokines—especially vascular endothelial growth factor (VEGF)—that are necessary for the growth of new tumor blood vessels (Shweiki D et al. 1992; Vaupel P 2004) and thus tumor growth. Angiogenic inhibitors seek to interrupt the process of angiogenesis (the creation of new blood vessels) to prevent new tumor blood vessel formation, whereas vascular (blood vessel)-disrupting agents aim to cause direct damage to the existing tumor blood supply (Tozer GM et al. 2004). Lead agents of both categories (e.g., Combretastatin A-4) have now advanced into clinical trials (Thorpe PE 2004).

Silymarin/silibinin inhibits VEGF secretion in a range of human cancer cell lines, in concentrations that should be clinically feasible (Yang SH et al. 2003). Other naturally derived agents that impede cancer-induced angiogenesis include green tea polyphenols, fish oil, selenium, copper restriction, and curcumin (Gururaj AE et al. 2002).

Cancer Radiation Therapy-2

noreply@blogger.com (Kishen) — Thu, 21 Feb 2008 00:49:00 +0000

Hyperbaric oxygen treatment (HBOT). Following the identification of hypoxia as a possible source of radiation resistance, a major effort was made to solve the problem through the use of hyperbaric oxygen. Hyperbaric oxygen is a mode of therapy in which the patient breathes pure, 100-percent oxygen at pressures two to three times greater than normal atmospheric pressure (Feldmeier JJ 2004). The concentration of oxygen normally dissolved in the bloodstream is thus raised many times above normal (up to 2000 percent).

This hyperoxygenation provides immediate support to poorly perfused tumor tissue in areas of compromised blood flow (Plafki C et al. 1998). These include radiation-damaged tissue that has lost blood supply and is oxygen deprived due to scarring and narrowing of the blood vessels within the area treated (Anderson DW 2003). Healing is dependent on oxygen delivery to the injured tissues, and hyperbaric oxygen therapy provides a better healing environment, leads to the growth of new blood vessels, and also helps to eradicate anaerobic bacteria that may cause infection via toxin inhibition and inactivation (Anderson DW 2003; Marx RE et al. 1990).

Hyperbaric oxygen has been used to treat normal tissue injury caused by radiation therapy in several sites, including the head and neck (Feldmeier JJ et al. 2002), pelvis (Corman JM et al. 2003), breast (Carl UM et al. 2001), prostate (Mayer R et al. 2001), and brain (Kohshi K et al. 2003), with few serious side effects.

In a study of 45 patients with radiation-induced late side effects, the majority showed improvement in their condition after either hyperbaric oxygen therapy alone or hyperbaric oxygen therapy followed by other surgical or medical procedures (Bui QC et al. 2004). In particular, osteoradionecrosis (necrosis, or death of the bone following radiotherapy) appeared to be highly responsive to hyperbaric oxygen therapy (Mounsey RA et al. 1993). This condition usually involves the lower jaw in a minority (8 percent) of head and neck cancer patients treated with radiation therapy, is difficult to treat, leads to intense pain and fracture, and makes oral feeding impossible (Reuther T et al. 2003).

However, the use of hyperbaric oxygen therapy is not widespread, partly because it is cumbersome and difficult in practice and partly because many of the studies to date have involved small numbers of patients (Gothard L et al. 2004; Haffty BG et al. 1999). Larger trials are needed to investigate the true efficacy of hyperbaric oxygen therapy.

Breathing oxygen during radiotherapy. The inhalation of oxygen during radiotherapy may increase the radiation kill effect on the tumor by counteracting areas of hypoxia-based radioresistance, and thus improve overall survival. Stage II cervical cancer patients, with squamous cell carcinoma, who received oxygen (normobaric) during all radiotherapy sessions had significantly improved loco-regional cancer control (Sundfor K et al. 1999).

Patients with Stage III (7 percent) and Stage IV (93 percent) advanced squamous cell carcinomas of the head and neck who breathed pure, normobaric oxygen for 15 to 20 minutes during irradiation had improved mean survival time (15.8 versus 11.8 months) and three-year survival (19 percent versus 2 percent), respectively (p < 0.05). Thus, breathing normobaric oxygen before and during radiation therapy could increase the effectiveness of conventional radiotherapy for advanced squamous cell carcinomas of the head and neck (Zajusz A et al. 1995).

Radioprotectors/radiosensitizers. Researchers are investigating two types of drugs that may increase the effectiveness of radiation therapy (Yuhas JM et al. 1977). Radiosensitizers make tumor cells more susceptible to radiation damage, while radioprotectors protect normal tissues from the damaging effects of radiation, allowing a higher dose of radiation to be directed at the tumor.

Radiosensitizers are chemicals that increase the damaging effects of radiation if administered simultaneously. Two types of radiosensitizers have been used in conjunction with radiation therapy:

1)Halogenated pyrimidines, such as bromodeoxyuridine, which depend on the amount of drug incorporated in the cell (Jackson D et al. 1987). As tumor cells divide more rapidly than the surrounding normal cells, they take up more of the radiosensitizer.

2) Hypoxic cell sensitizers, which increase the radiosensitivity of only those cells located in areas of low oxygen (Brown JM 1989). As many tumors contain large regions of hypoxic cells compared to normal tissues, these drugs are able to produce a differential effect, that is, they are toxic to hypoxic cells only.

Amifostine (Ethyol®) has been approved by the FDA specifically for use as a radioprotector. It is approved for the prevention of xerostomia (dry mouth) in head and neck cancer patients treated with radiation therapy (Hensley ML et al. 1999). Adequate hydration is critical before amifostine administration (given intravenously once daily as a 3-minute infusion starting 15 to 30 minutes before standard fraction radiation therapy).

The two major side effects of amifostine that cause treatment discontinuation are vomiting and transient low blood pressure (hypotension) (Capizzi RL et al. 2000), and these adverse effects limit its wide acceptance.

Ginseng. Ginseng has several beneficial effects on blood vessels (Yun TK 2001). In experimental studies, ginseng was shown to be a promising radioprotector (Kim SR et al. 2003), that is, it may protect normal healthy tissue from damage during radiation therapy (Kim TH et al. 1996; Lee TK et al. 2004). In a clinical study, ginseng polysaccharide injection improved immune function in nasopharyngeal carcinoma patients during radiotherapy (Xie FY et al. 2001).

Glutathione is a natural antioxidant synthesized from the amino acids glutamine, cysteine, and glycine (Walzem RL et al. 2002). A severe reduction in glutathione content can predispose cells to oxidative damage. When tumor cells are irradiated, either lethal damage can occur and the cells die, or the damage can be modified via DNA repair and not lead to permanent cell death.

Cancer cells have higher glutathione levels than the surrounding normal healthy cells. Therefore, selective tumor depletion of glutathione presents a promising strategy in cancer management. Dietary glutamine supplementation lowers glutathione levels in tumor cells (Kennedy RS et al. 1995; Todorova VK et al. 2004), but increases production in normal tissues. Furthermore, glutamine supplementation decreases the toxicity of radiation therapy (Klimberg VS et al. 1992; Rouse K et al. 1995).

Whey protein is an effective and safe cysteine donor for glutathione replenishment (Kennedy RS et al. 1995; See D et al. 2002). Radiation therapy is known to cause immunosuppression (Wara WM et al. 1979). Cysteine is the critical limiting amino acid for intracellular glutathione synthesis (Bounous G 2000). The amino acid precursors to glutathione present in whey might increase glutathione concentration in relevant tissues, stimulate immunity, and detoxify potential carcinogens (Bounous G 2000). Glutathione stimulation is thought to be whey’s primary immune-modulating mechanism (Marshall K 2004).

Alkylglycerols are active ingredients of shark liver oil. They have been widely used for the treatment of cancer in Scandinavian countries (Krotkiewski M et al. 2003), and research suggests their use may result in a lower incidence of normal tissue radiation damage (Hasle H et al. 1991). Although their protective mechanism is not fully understood (Hichami A et al. 1997), they cause increased tumor cell death (apoptosis) and have many beneficial effects on the immune system, including the stimulation of neutrophils and macrophages (Tchorzewski H et al. 2002). Doses of shark liver oil up to 100 mg three times a day can be taken with no unfavorable side effects (Pugliese PT et al. 1998).

Hyperthermia with radiotherapy. Hyperthermia is the artificial elevation of the temperature of a tissue. Tumor cells can be selectively killed by temperatures between 40° and 44° centigrade (C) as compared with normal cells (van der Zee J 2002) because of improved tissue oxygenation and a consequent temporary increase in radiosensitivity (Song CW et al. 1997).

Numerous studies have shown that the combination of hyperthermia and radiation therapy improves clinical outcomes, particularly in breast cancer, melanoma, head and neck tumors, cervical cancer, and glioblastoma (van der Zee J et al. 2003).

Normal tissue toxicity with hyperthermia only results if the tissue temperature exceeds 44° C for more than one hour (Fajardo LF 1984). The toxicity from superficial hyperthermia is usually a skin burn; for deep-seated tumors, a subcutaneous fat or muscle burn may occur, which heals spontaneously (van der Zee J 2002).

Phytochemicals. Phytochemicals such as epigallocatechin-3 gallate (EGCG) found in green tea, curcumin, and genistein have been shown to enhance the radiation-induced death of cancer cells in addition to restraining tumor growth in animal models (Dorai T et al. 2004; Sarkar FH et al. 2004). They also have antioxidant properties and can therefore neutralize the detrimental effects of reactive oxygen species on normal cells (Katiyar SK et al. 2001).

EGCG (mainly derived from green tea) may increase the efficacy of radiation therapy by decreasing the activity of vascular endothelial growth factor (VEGF) (Lee YK et al. 2004). VEGF acts as a crucial survival factor for tumor cells (Ferrara N 2005).

Soy isoflavones, including genistein, daidzein, and glycitin (mainly derived from soybean), have been found to slow cancer growth in experimental animal studies (Sarkar FH et al. 2004). Genistein significantly enhances the radiation effect (that is, acts as a radiosensitizer) for cervical cancer cells (Yashar CM et al. 2005).

Curcumin, a natural anti-proliferative compound for many types of tumor, is extracted from the spice turmeric (Sikora E et al. 1997). Curcumin blocks the nuclear factor-kappa beta (NF-?B) activation process (Singh S et al. 1995). The maintenance of appropriate levels of NF-?B activity is crucial for normal cell division, and NF-?B activation is involved in the enhanced growth properties observed in several cancers (Bharti AC et al. 2002). Curcumin can sensitize squamous cell carcinoma cells to the ionizing effects of radiation (Khafif A et al. 2005). In prostate cancer cell lines, curcumin is a potent radiosensitizer and acts by overcoming the effects of radiation-induced prosurvival gene (bcl-2) expression (Chendil D et al. 2004).

Preventing and Counteracting Adverse Effects of Radiotherapy

Antioxidant use and radiation therapy

A survey of cancer patients found that 63 percent use vitamins and herbs (including antioxidants), and the majority combine them with conventional therapies (Richardson MA et al. 2000). Critics argue that excessive nutrient-derived antioxidant use during radiation therapy could, in theory, protect cancer cells against the damaging effects of reactive oxygen species or oxidants, which are formed by radiation. This could occur by the antioxidants directly scavenging reactive oxygen species or repairing cellular damage in tumor cells (Salganik RI 2001). However, this theory has never been confirmed by clinical studies, and antioxidants can have protective effects that have nothing to do with oxidation (Block KI 2004).

Furthermore, there is no controversy surrounding physician-prescribed antioxidants such as amifostine (Ethyol®), an FDA-approved orphan drug for the prevention of xerostomia (dry mouth) in head and neck cancer patients undergoing radiation treatment. Amifostine has been clearly shown to reduce the incidence of side effects (xerostomia and mucositis) in patients receiving head and neck irradiation (Schuchter LM et al. 2002). It has also been used in combination with radiation therapy in the treatment of lung, prostate, breast, cervical, and esophageal cancer patients, with much success. The problem with amifostine is that it causes intolerable nausea, vomiting, diarrhea, and abdominal cramping, which limits its use.

The use of supplemental antioxidants is further supported in that they may help protect normal cells from the increased damage and side effects caused by radiation therapy (Lamson DW et al. 1999). Moreover, it has been shown that levels of antioxidants are decreased in cancer patients in response to radiation therapy (Sabitha KE et al. 1999). Thus, supplementation with dietary antioxidants (such as vitamins C and E) may improve the efficacy of radiation therapy by increasing tumor response and decreasing some of its toxicity on normal cells (Prasad KN et al. 2002).

Dietary antioxidants (including vitamin E, vitamin C, and selenium) as well as antioxidant enzymes found within cells (e.g., superoxide dismutase and glutathione peroxidase) can help maintain an appropriate balance between the desirable and undesirable effects of reactive oxygen species formed by radiation therapy (Seifried HE et al. 2003).

In several clinical radiotherapy studies, supplementation with the antioxidants vitamin E, selenium, and melatonin during treatment was shown to improve the efficacy of radiation therapy by decreasing radiation toxicity in normal cells and enhancing the immune response (Kiremidjian-Schumacher L et al. 2000; Malmberg KJ et al. 2002; Prasad KN et al. 2002).

Many clinical studies (detailed herein) have shown that antioxidant supplementation (with vitamins C and E, N-acetylcysteine, glutamine, and glutathione) both before and during radiotherapy prevents normal tissue complications (De Maria D et al. 1992; Ersin S et al. 2000; Huang EY et al. 2000; Kaya E et al. 1999; Kim JA et al. 1983; Klimberg VS et al. 1990; Mills EE 1988; Wagdi P et al. 1996), thus improving radiotherapy outcomes.

Overall, the data suggest that careful, sensible use of the antioxidants outlined herein may be helpful in improving the outcome of radiation therapy. Natural antioxidants (such as tocopherols, ascorbic acid, squalene, and lecithin) are present in most plant-based foods (Foley DJ et al. 2002) and in fruit, fish, herbs, and cereals (Shahidi F 2000).

Vitamin A. Radiation therapy effectiveness is increased when combined with vitamin A, which is thought to be due to an increased immune response against the tumor (Tannock IF et al. 1972). Vitamin A (8000 IU taken orally twice daily for seven weeks) appeared to be very effective in the treatment of radiation-induced anorectal damage in a patient with human immunodeficiency virus (HIV) infection (Levitsky J et al. 2003).

In a randomized, double-blind trial comparing retinol palmitate (vitamin A, 10,000 IU taken orally for 90 days) to placebo, oral retinol palmitate significantly reduced the rectal symptoms of radiation proctopathy in 19 patients six months after pelvic radiotherapy (Ehrenpreis ED et al. 2005).

Vitamin C. Experimental studies show that radiation treatment reduces the level of vitamin C in the body (Beliaev IK 1991). Conversely, studies of mice have shown that supplementing vitamin C at high doses preferentially radiosensitizes tumors while offering some protection to normal tissues (Tewfik FA et al. 1982).

Vitamin E. Vitamin E has been recognized as one of the most important antioxidants. Tocopheryl succinate (dry powder vitamin E) enhanced radiation damage to ovarian and cervical cancer cells in culture, while protecting healthy cells (Kumar B et al. 2002).

Vitamin E and selenium have been reported to have an increased beneficial effect when used in combination (Weiss JF et al. 2000). A study of rats showed that pre-treatment with both selenium and vitamin E for four weeks before radiation gave some protection against radiation-induced intestinal injury.

Selenium. A large number of selenium derivatives have been studied for their radioprotective effects (Weiss JF et al. 2003). Selenium is a very efficient scavenger of reactive oxygen species and a radiosensitizer, with a very low toxicity profile (Schueller P et al. 2004).

Supplementation with 200 mcg daily of sodium selenite for eight weeks, beginning on the first day of standard treatment (surgery and/or radiation) for squamous cell carcinoma of the head and neck, resulted in a significantly enhanced immune response during and after therapy (Kiremidjian-Schumacher L et al. 2000).

Coenzyme Q10. Coenzyme Q10 (CoQ10), a mitochondrial enzyme, has been shown to have a therapeutic benefit in cancer patients at doses of 90 to 390 mg daily. A decrease in distant metastasis (Lockwood K et al. 1994) and increase in long-term survival (Lockwood K et al. 1995) have been noted in breast cancer patients. However, a study of mice indicated that CoQ10 reduced the effect of radiation therapy when used at a dose equivalent to 700 mg in humans; therefore, as a precaution, a dose of 100 to 400 mg a day should not be exceeded (Lund EL et al. 1998).

Melatonin.Melatonin is the chief secretory hormone of the pineal gland. Melatonin reduces oxidative damage from the production of free radicals (Reiter RJ 2004). Several studies indicate that melatonin functions as a radioprotector (Karbownik M et al. 2000), reducing the toxic effects of radiation on mammalian cells (Vijayalaxmi et al. 2004). In experiments and animal models, administration of melatonin has inhibited the growth and division of several types of cancer cells, particularly breast cancer and melanoma cells (Blask DE et al. 1986; Subramanian A et al. 1991).

Several reports indicate that melatonin administration improves quality of life for many cancer patients (Conti A et al. 1995). Patients with glioblastoma generally experience a poor survival rate, which is typically less than six months. A radio-neuroendocrine approach utilizing radiotherapy with melatonin supplementation (20 mg daily) in patients with untreatable glioblastoma showed that the likelihood of survival at one year was significantly higher in those who received melatonin with radiotherapy (6 of 14 patients alive) versus radiotherapy alone (1 of 16 patients alive) (Lissoni P et al. 1996a). A reduction in radiation-induced toxicity was also observed in the melatonin-treated group.

Melatonin reduces gamma radiation-induced primary DNA damage in human white blood cells (lymphocytes) (Vijayalaxmi 1998). It has been suggested that supplementing with an adjuvant therapy of melatonin may benefit cancer patients who are suffering from toxic therapeutic regimens such as radiotherapy and/or chemotherapy, and may alleviate symptoms caused by radiation-induced organ injuries (Karslioglu I et al. 2005).

Preventing Normal Tissue Complications

The goal of radiation therapy is to deliver a precisely measured dose of ionizing radiation to a defined tumor area, with as little damage as possible to surrounding healthy, non-cancerous tissue (Burnet NG et al. 1996). However, a number of patients undergoing radiation therapy will experience a range of side effects, which may lead to an interruption of treatment or limiting the dose of radiation (Fowler JF et al. 1992).

Radiation’s effects on normal tissues are commonly divided into two categories: “early” and “late” reactions. Early, or acute, effects occur within a few days or weeks of irradiation (Herskind C et al. 1998). Late effects appear after a period of months or years and occur predominantly in slowly growing tissues such as the lungs, kidneys, heart, liver, and central nervous system.

The size of the radiation treatment field, the dose per fraction, and the total dose of radiation received are important factors associated with these effects (Emami B et al. 1991).

Heart damage.
The use of 3D-CRT reduces the dose and volume of radiation exposure to the heart (Hurkmans CW et al. 2002). However, significant risks remain, and cardiovascular abnormalities may result following radiation therapy (Lipshultz SE et al. 1993). Hodgkin's disease survivors treated with chest radiation therapy are at increased risk of death as a result of cardiovascular disease (Lee CK et al. 2000). Women treated with radiation therapy following mastectomy for left-sided breast cancer, which involves exposure of the heart, have been shown to have an increased frequency of cardiovascular disease (Gyenes G et al. 1998).

In a small trial of a mixture of antioxidants—including vitamin E (600 mg), vitamin C (1 gram), and N-acetylcysteine (200 mg)—taken during treatment, researchers sought to determine the mixture’s ability to prevent heart damage during chemotherapy and radiation therapy. No patient taking the antioxidant mixture had a decrease in ejection fraction (the amount of blood pumped out of the heart during each heartbeat) of greater than 10 percent. By contrast, in the control group, in which four of six patients were treated with radiation therapy and two of seven patients underwent chemotherapy, the ejection fraction reduction was greater than 10 percent, indicative of a weakened heart (Wagdi P et al. 1996).

Gastrointestinal mucositis (inflammation of the gut lining).
More than 70 percent of patients treated for cancer of the prostate, bladder, and other malignancies in the pelvic region develop acute inflammatory small intestinal changes (Resbeut M et al. 1997). Acute enteritis or proctitis (inflammation of the intestine or rectum, respectively) is characterized by diarrhea, abdominal pain, and tenesmus (fecal urgency with cramp-like rectal pain) that usually starts during the second week of radiation therapy and resolves within two weeks of completing treatment (Ajlouni M 1999). In 5 percent to 10 percent of patients, serious gastrointestinal problems may occur, including bowel obstructions and bleeding (Denton AS et al. 2000).

Both glutamine (Hall JC et al. 1996) and arginine (Gurbuz AT et al. 1998) are amino acids that have an important role in maintaining mucosal growth and function. Supplementation with these amino acids before or after abdominal irradiation appears to decrease the likelihood of both acute and chronic effects on the lower intestine (Ersin S et al. 2000; Kaya E et al. 1999; Klimberg VS et al. 1990), but not all studies have shown benefits (Hwang JM et al. 2003; Kozelsky TF et al. 2003). Oral glutamine supplementation may enhance radiation therapy by protecting normal tissues from (and sensitizing tumor cells to) radiation damage (Savarese DM et al. 2003). In one study, oral glutamine supplementation (30 grams per day) reduced gut permeability and protected lymphocytes in patients with esophageal cancer during radiochemotherapy (Yoshida S et al. 1998).

Patients receiving 1200 mg of intravenous glutathione (diluted in normal saline solution) 15 minutes before pelvic irradiation suffered less post-therapy diarrhea (28 percent, compared to 52 percent for controls) and were more likely to complete their treatment without interruption than a control group (71 percent, compared to 52 percent) (De Maria D et al. 1992).

Several studies have reported a positive effect of hyperbaric oxygen therapy in patients with chronic radiation cystitis or proctitis (inflammation of the bladder or rectum, respectively) (Ennis RD 2002). Radiation-induced hemorrhagic cystitis can be treated successfully with hyperbaric oxygen therapy; it is well tolerated even in patients debilitated by advanced cancer and blood loss. Long-term remission is possible in most patients, and re-treatment effectively manages recurrent bleeding (Chong KT et al. 2005; Neheman A et al. 2005).

Short-chain fatty acids and butyrate are derived from the bacterial fermentation of unabsorbed carbohydrates within the colon (Cook SI et al. 1998). They are readily absorbed in the large bowel and are beneficial in treating colitis (inflammation of the bowel) (Kim YI 1998). A small study of seven patients who had received previous radiation therapy (for an average of 23 months before the study) examined the use of short-chain fatty acid enemas (administered twice daily for four weeks) for the treatment of proctitis (inflammation of the rectum) and found a significant decrease in rectal bleeding (al-Sabbagh R et al. 1996). This was confirmed in another study of 20 patients who presented with proctitis within three weeks of completing radiation therapy. Half were treated daily with one 80-ml sodium butyrate enema (80 mmol/L) and half with a sodium chloride placebo over a three-week period (Vernia P et al. 2000). All patients treated with butyrate reported a significant improvement in their symptoms compared to only three patients in the placebo group who reported a slight improvement.

Cancer Radiation Therapy-3

noreply@blogger.com (Kishen) — Wed, 20 Feb 2008 15:35:00 +0000

Hair loss. Radiation therapy can cause hair loss (alopecia), but only in the area being treated (Irvine L et al. 1999). Hair loss is usually temporary and re-growth is evident within a few weeks after completion of therapy.

Melatonin has been reported to have a beneficial effect on hair growth in animals (Oxenkrug G et al. 2001). Furthermore, a study of 40 women suffering from alopecia sought to determine whether topically applied melatonin influences hair growth. A melatonin solution (0.1 percent) or placebo was applied to the scalp daily for six months. Positive results were obtained in the melatonin-treated group (Fischer TW et al. 2004).

Liver damage. Hepatocellular carcinoma is a common malignancy, and 3D-conformal radiation therapy is increasingly used in treatment as part of multimodal therapy (Cheng JC et al. 2000). However, one of the most frequently encountered complications following such treatment is radiation-induced liver disease, occurring in approximately 18 percent of patients (Cheng JC et al. 2002b). Patients present with fatigue, rapid weight gain, and, in rare cases, jaundice, approximately four to eight weeks after treatment (Lawrence TS et al. 1995). Radiation-induced liver disease leads to the deterioration of liver function, and up to half of radiation-induced liver disease patients may die from this complication (Cheng JC et al. 2002a).

Silymarin, a flavonoid complex found in the herb milk thistle, is frequently used in the treatment of liver disease (Levy C et al. 2004; Saller R et al. 2001). It functions as an antioxidant (Feher J et al. 1987), maintains cellular glutathione content (Soto C et al. 2003), and has a low toxicity profile (Ladas EJ et al. 2003). A study of rats found that an intravenous injection of silymarin (50 mg/kg) 30 minutes before a single dose of radiation protected against radiation-induced liver disease (Ramadan LA et al. 2002). Silymarin is well tolerated and produces a small increase in glutathione and a decrease in lipid peroxidation in peripheral blood cells in certain patients (Lucena MI et al. 2002).Treatment with silymarin (600 mg/day) was found to reduce the lipoperoxidation of cell membranes and insulin resistance (Velussi M et al. 1997).

Hypersensitivity reactions: skin/fibrosis. Acute radiation dermatitis (inflammation of the skin) is a common side effect of radiotherapy. Dermatitis includes redness (erythema) and dry or moist peeling skin (desquamation). It has been estimated that 87 percent of all women undergoing radiation therapy for breast cancer will develop some degree of radiation dermatitis (Fisher J et al. 2000). Severe radiation dermatitis can be painful, may lead to infections, and can cause permanent scarring.

No standard treatment has been recommended for the prevention of radiation-induced dermatitis, though several therapies have been suggested (Westbury C et al. 2000; Wickline MM 2004). Several dressing types used to treat radiation dermatitis can provide a moist healing environment that is optimal for cell migration across the wound, thereby shortening healing time (Margolin SG et al. 1990).

Topical agents such as corticosteroid creams and other products, including aloe vera gel or trolamine (Biafine®), are commonly prescribed at the onset of radiation dermatitis or at the beginning of radiotherapy (Bostrom A et al. 2001; Schmuth M et al. 2002). Biafine® is a water-based emulsion that has been used in France since 1973 to alleviate symptoms of radiation dermatitis (Fenig E et al. 2001; Fisher J et al. 2000).

Calendula, derived from the marigold flower, has purported anti-inflammatory properties and is often used for wound healing. A recent trial found that calendula was significantly better than Biafine® in preventing mild-to-severe acute radiation dermatitis in breast cancer patients, as well as in providing pain relief (Pommier P et al. 2004). Patients applied the preparation to the irradiated skin at least twice a day at the onset of radiation therapy and continued this until completion of treatment.

In clinical trials, the application of aloe vera gel was no better than placebo or aqueous cream in reducing radiation-induced dermatitis (Heggie S et al. 2002; Williams MS et al. 1996). However, aloe vera gel added to soap has a protective effect for patients who received higher cumulative radiation doses, prolonging the time to detectable skin damage from three to five weeks (Olsen DL et al. 2001).

Dexpanthenol (vitamin B5) creams have been shown to improve acute radiotherapy skin reactions in some (Roper B et al. 2004) but not all studies (Lokkevik E et al. 1996).

N-acetylcysteine is capable of stimulating radio-protective cytokines (Baier JE et al. 1996). The application of gauze soaked in 10 percent N-acetylcysteine for 15 minutes before radiation therapy was associated with more rapid healing of skin reactions and less use of pain relievers compared to an untreated control group (Kim JA et al. 1983).

Unsaturated essential fatty acids (EFAs) are necessary for the production of prostaglandins (PGEs) (inflammatory modulators) and play an important role in maintaining cell membrane structure by regulating membrane fluidity (Horrobin DF 1992). The ability of EFAs containing both gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA) to modify radiation-induced skin reactions was studied in pigs (Hopewell JW et al. 1994). Oral administration of 3 ml of oil daily for four weeks before and up to 16 weeks after irradiation significantly reduced both acute and late radiation skin damage. Prospective studies suggest that prostaglandins have great potential in minimizing the adverse effects of radiotherapy on normal tissue. The potential use of misoprostol, a PGE(1) analogue, before irradiation may be considered in the prevention of radiation-induced side effects (Lee TK et al. 2002).

Radiation-induced fibrosis, a serious late effect of radiotherapy, is mainly characterized by changes in the connective tissue involving excessive extracellular matrix deposition and hyperactive fibroblasts (Burger A et al. 1998). A combination of pentoxifylline (Trental®), a methylxanthine derivative structurally related to theophylline and caffeine, and vitamin E (alpha tocopherol) may be effective in treating radiation-induced fibrosis (Delanian S et al. 1999). Pentoxifylline promotes healing and relieves pain following radiation damage (Futran ND et al. 1997), and vitamin E was used for its ability to scavenge reactive oxygen species (Rudolph R et al. 1988). Twenty-two patients who developed radiation-induced fibrosis following radiotherapy for breast cancer were treated with 800 mg/day of pentoxifylline and 1000 IU/day of vitamin E. The area of radiation-induced fibrosis was significantly reduced when these patients were examined after six months, with no adverse effects reported (Delanian S et al. 2003). For more information, see the later section of this chapter on Pulmonary Toxicity.

Lymphedema. Lymphedema is an accumulation of protein-rich fluid that results in swelling of the underlying skin. It may occur in the arm following radiotherapy for breast cancer, due to interruption of axillary (armpit) lymphatic drainage or because of axillary lymph node dissection or axillary radiation, or both. It results in pain, decreased stretching ability of tissue around the joints, and increased weight of the extremity (Allegra C et al. 2002). The reported incidence of lymphedema varies, with rates of 2 percent to 24 percent reported in a review of breast cancer patients (Petrek JA et al. 1998), and of 22 percent to 56 percent for the head and neck region (Dietz A et al. 1998).

Several non-pharmacological options are available for managing lymphedema (Harris SR et al. 2001), including the use of graded compression garments (Collins CD et al. 1995) and pneumatic compression pumps (Dini D et al. 1998).

Arm exercises may also help to control the symptoms caused by lymphedema, by strengthening the muscle-pumping action and consequently increasing lymph flow. Many clinicians encourage patients to continue exercising two or three times a day for six months, then daily for life (Granda C 1994). Scrupulous skin care should be followed and maintenance of an ideal body weight should be encouraged, as obesity is a contributing factor for the development of lymphedema (Johansson K et al. 2002).

Clinical studies have shown a beneficial effect of selenium in treating lymphedema at different locations (Bruns F et al. 2004; Kasseroller RG et al. 2000). Forty-eight patients were evaluated either 10 months (upper-limb) or 4 months (head and neck) after the end of radiotherapy. Patients received 500 mcg of sodium selenite per day over four to six weeks. Approximately 80 percent of patients showed a significant improvement in their lymphedema and quality of life (Micke O et al. 2003).

Other investigators concluded that sodium selenite represents a suitable adjuvant treatment of secondary lymphedema. Treatment with sodium selenite (1000 mcg daily for three weeks) can be instituted immediately after treatment and before wound healing when manual lymphatic decongestion therapy cannot be applied (Zimmermann T et al. 2005).

The Importance of Exercise
Fatigue is a major determinant of quality of life and is present in as many as 50 percent to 70 percent of patients with cancer at diagnosis (Irvine D et al. 1994). Several studies have investigated fatigue during radiation therapy for both breast (Geinitz H et al. 2001) and prostate cancer (Janda M et al. 2000). The initiation of radiation therapy is accompanied by significant increases in fatigue (Kurzrock R 2001). However, levels of fatigue tend to return to pre-treatment levels within several weeks of completing treatment (Jacobsen PB et al. 2003).

A number of studies have examined the therapeutic value of exercise during cancer treatment (Brown JK et al. 2003; Courneya KS 2003). A trial was performed to determine whether aerobic exercise would reduce the incidence of fatigue and prevent deteriorating physical function during radiotherapy for localized prostate carcinoma (Windsor PM et al. 2004). Those men who followed advice to rest if they became fatigued demonstrated a slight deterioration in physical function and a significant increase in fatigue at the time of radiotherapy. By contrast, a home-based, moderate-intensity walking program produced a significant improvement in physical function, with no significant increase in fatigue.

An exercise program of walking (self-paced walks of 20 to 30 minutes, 4 to 5 days per week) was evaluated in participants who were to receive radiation therapy after surgery for breast cancer (Mock V et al. 1997). Before radiation therapy, patients were assigned to either the exercise intervention group or a control group. Those who underwent the walking program experienced significantly less fatigue on the completion of radiation therapy than those in the control group.

Kidney toxicity (nephrotoxicity). The kidney is one of the most radiosensitive organs at risk of developing damage after abdominal irradiation. Radiation nephropathy takes various forms, the most common of which, acute radiation nephritis, presents as azotemia (dangerously high levels of nitrogen waste products in the bloodstream), hypertension, and anemia, starting at 6 to12 months following treatment (Cohen EP et al. 2003). If left untreated, this can lead to renal failure, and survival on chronic dialysis is poor (Cohen EP et al. 1998).

Dietary protein restriction is effective in treating various chronic kidney diseases (Levey AS et al. 1999) though care must be taken to maintain adequate nutrition (Youngman LD 1993).

All-trans retinoic acid (a vitamin A-like drug) exacerbates radiation nephropathy, possibly by inhibiting renal nitric oxide production, and its use should be restricted during renal irradiation (Moulder JE et al. 2002).

Nerve toxicity (neurotoxicity). The nervous system is particularly sensitive to radiation therapy, and radiation-induced neurotoxicity can involve the central nervous system and peripheral nervous system (Liang BC 1999).

Radiation therapy for skull-base, orbital, and sinus tumors invariably involves the irradiation of brain tissue (Chong VF et al. 2002). Following brain irradiation, acute toxicity may cause headaches, dizziness, fatigue, and problems with speech (Young DF et al. 1974). Corticosteroids are useful in relieving a number of these acute complications, but should be used only as long as medically necessary, as they may have side effects. Early physical therapy can prevent lymphedema, frozen shoulder, and atrophy (muscle wasting). For more information, see the Peripheral Neuropathy chapter.

Radiation necrosis. Radiation necrosis (tissue ulceration) and cognitive dysfunction are the main late complications of brain irradiation. Radiation necrosis may occur from six months to two years following treatment (Keime-Guibert F et al. 1998), and is caused primarily by blood vessel damage (Lyubimova N et al. 2004). Up to 20 percent of patients receiving stereotactic radiosurgery and 80 percent undergoing interstitial brachytherapy will develop symptoms of radiation necrosis (Wen PY et al. 1994).

This is a serious condition with symptoms that vary from fatigue to dementia, and may require surgical intervention (Strohl RA 1998). Non-surgical treatments that have been clinically investigated include steroids, heparin, low-iron diets with iron chelators, pentoxifylline, and hyperbaric oxygen therapy (Chuba PJ et al. 1997; Hornsey S et al. 1990). Hyperbaric oxygen therapy is important in the treatment and healing of soft tissue radiation necrosis, particularly of the brain (Dion MW et al. 1990; Hart GB et al. 1976; Kohshi K et al. 2003).

The use of pentoxifylline is deemed safe and effective in preventing radiation necrosis, particularly in the prevention of radiation-induced lung toxicity (Ozturk B et al. 2004). At an oral dose of 400 mg three times daily, pentoxifylline has a protective effect against radiation necrosis complications, possibly by reducing platelet aggregation and preventing tumor necrosis factor-mediated inflammation (Aygenc E et al. 2004; Hong JH et al. 1995).

Osteoradionecrosis (see the earlier section of this chapter on Hyperbaric Oxygen Treatment) is a late adverse effect of radiation therapy that does not resolve spontaneously. In a preliminary study, a combination of pentoxifylline (800 mg daily), tocopherol (vitamin E, 1000 IU daily), and clodronate (1600 mg daily, Bonefos®) was of clinical benefit, with more than 50 percent regression of progressive osteoradionecrosis observed at six months in 12 patients (Delanian S et al. 2002b; Futran ND et al. 1997). In another study, this same regimen completely reversed severe progressive osteoradionecrosis when administered daily for three years (Delanian S et al. 2002a).

Oral complications. Between 60 percent and 90 percent of head and neck cancer patients receiving standard radiation therapy will develop inflammation of the lining of the mouth (mucositis) (Sutherland SE et al. 2001), which usually improves within a few weeks after completing treatment (Sonis ST et al. 2001).

One of the most important factors that predisposes someone to oral mucositis is preexisting oral or dental disease (Dodd MJ et al. 1996). Oral mucositis can lead to secondary complications, including infection, poor nutritional intake, and xerostomia (dry mouth). Several treatment interventions have been suggested for preventing and treating oral mucositis, though no effective treatment currently exists (Clarkson JE et al. 2003; Worthington HV et al. 2004).

Maintaining good oral hygiene is important in preventing mucositis, and it is particularly important to instigate this at least a week before starting radiation therapy (Shieh SH et al. 1997). Patients should brush twice daily with a soft-bristled tooth brush, floss daily, and rinse the mouth once daily with normal saline (1/2 teaspoon of salt in eight ounces of water) or sodium bicarbonate (baking soda or Alka-Seltzer®) (Dodd MJ et al. 2000).

A trial of head and neck cancer patients indicated that oral glutamine (16 grams in 240 ml of normal saline, four times daily during radiation) may significantly reduce the duration and severity of oral mucositis during radiotherapy (Huang EY et al. 2000).

Honey reduces the symptoms of mucositis. Forty patients diagnosed with head and neck cancer were divided into two groups. One group was advised to take 20 ml of pure honey 15 minutes before, 15 minutes after, and 6 hours after radiotherapy. In the honey-treated group, symptomatic mucositis was reduced significantly, and there was either no change in weight or positive weight gain compared to the control group (Biswal BM et al. 2003).

Antibiotics supplied either as a topical pastille or paste may be beneficial in preventing mucositis (Donnelly JP et al. 2003; Okuno SH et al. 1997). The overgrowth of certain yeast and bacteria, which occurs following radiation therapy, may be important in the progression of this condition (Spijkervet FK et al. 1991). Head and neck cancer patients who were given a pastille containing amphotericin, polymixin, and tobramycin to suck four times daily were significantly less likely to develop the most serious form of mucositis than those who received a placebo (Symonds RP et al. 1996). However, this beneficial finding has not been seen in all studies using antibiotics (Stokman MA et al. 2003; Wijers OB et al. 2001).

Alternatively, the flower Matricharia camomile may be beneficial in reducing mucositis during radiotherapy (Henriksson R et al. 1999), due to its antibacterial properties (Carl W et al. 1991). In a study in which Kamillosan® (a camomile preparation) oral rinse was given to patients receiving radiation therapy and chemotherapy, mucositis was less severe than expected (Carl W et al. 1991).

Hydrolytic enzymes have anti-inflammatory properties and are effective in reducing normal tissue reactions such as oral (Kaul R et al. 1999) and gastrointestinal mucositis (Dale PS et al. 2001). They function by reducing cytokine levels (Lehmann PV 1996). In one clinical study, 53 patients were given three tablets, three times a day, containing papain (100 mg), trypsin (40 mg), and chymotrypsin (40 mg). The treatment was started three days before radiation therapy and continued until five days after completion of treatment (Gujral MS et al. 2001). Both mucositis and skin reactions were significantly reduced in the enzyme-treated group compared to controls.

Beta-carotene (75 mg daily) during radiation therapy for advanced squamous cell carcinoma of the mouth markedly reduced the incidence of severe mucositis without causing noticeable side effects (Mills EE 1988).

Damage to the salivary glands is another common adverse effect of radiotherapy. Reduced saliva production can cause chronic dry mouth. This is a significant problem for cancer patients, with a reported prevalence of between 29 percent and 77 percent (Maltoni M et al. 1995). Xerostomia can greatly impair a patient's ability to speak, chew, swallow, and taste, and therefore is often accompanied by a loss of appetite and weight, leading to adverse effects on quality of life (Brown CG et al. 2004).

To manage this condition, some patients use artificial saliva substitutes, but most patients find them inadequate (van der Reijden WA et al. 1996). Salivary gland dysfunction after therapeutic radiation is a difficult, if not impossible, condition to reverse, though some evidence suggests that patients with this condition should be considered for hyperbaric oxygen therapy (Bui QC et al. 2004). The use of non-cinnamon or mint-based sugar-free drops, chewing gum, fresh pineapple chunks, or frequent sips of water to maintain adequate hydration has been suggested to stimulate salivary flow (Krishnasamy M 1995).

Poor appetite and cachexia. Patients undergoing radiotherapy for cancer of the head and neck or gastrointestinal tract are at higher risk of developing malnutrition (van Bokhorst-de van der S et al. 1999). Malnutrition increases the risk of infections and treatment toxicities, and decreases the response to treatment (Nitenberg G et al. 2000).

Cachexia is treated by attempting to increase nutritional intake and inhibit muscle and fat wasting. This is done by manipulating the metabolism with various pharmacological agents and by treating the causes of reduced food intake, such as nausea and vomiting (Davis MP et al. 2004) (for more information, see the chapter on Catabolic Wasting). Diets that include the omega-3 fatty acids EPA and DHA (Wigmore SJ et al. 2000), melatonin (Lissoni P et al. 1996b), and vitamin supplements (alpha-lipoic acid, 300 mg/day; carbocysteine lysine salt, 2.7 grams/day; vitamin E, 400 mg/day; vitamin A, 30,000 IU/day; vitamin C, 500 mg/day) (Mantovani G et al. 2004) have shown promise in some, but not all (Bruera E et al. 2003), studies undertaken.

Pulmonary toxicity. The lung is among the most radiosensitive organs, and therefore the risk of severe side effects seriously compromises treatment outcome. Radiation pneumonitis (inflammation of the lung) is a common acute side effect occurring in 5 percent to 30 percent of patients treated for lung cancer between one month and six months after radiotherapy (Tsujino K et al. 2003). Radiation therapy-induced fibrosis is associated with scarring of the lung and typically occurs months to years after radiotherapy.

The amino acids taurine and L-arginine may protect against radiation-induced lung fibrosis by reducing production of collagen, a protein implicated in the fibrotic process (Song L et al. 1998).

The drug pentoxifylline down-regulates the production of proinflammatory cytokines, particularly tumor necrosis factor-alpha (TNF-alpha), and may therefore protect against radiation-induced, cytokine-mediated damage (Rube CE et al. 2002). In a clinical trial, 64 patients with non-small cell lung cancer were randomly divided into a pentoxifylline (400 mg, three times a day) plus radiotherapy group or a radiotherapy-only group (Kwon HC et al. 2000). Following treatment, patients in the pentoxifylline plus radiotherapy group had significantly longer survival and time to relapse.

A potentially important determinant of lung toxicity risk may be vitamin A nutritional status. Human studies have linked low vitamin A intake and/or reduced serum retinol levels with an increased risk of lung dysfunction (Chytil F 1992). Low levels of vitamin A have been found in human lung tissues obtained from patients undergoing lung resection (Redlich CA et al. 1996). Retinoids may exert their effects by modulating inflammatory cytokines and growth factors (Zitnik RJ et al. 1994). Experimental animal studies suggest that supplemental vitamin A may reduce lung inflammation after thoracic radiation and may be an important radioprotective agent in the lung (Redlich CA et al. 1998).

Radiation-induced nausea and vomiting typically occur within 24 hours of treatment, and over 80 percent of patients undergoing radiation of the upper body will develop symptoms of nausea and vomiting (Anonymous 1999; Goldsmith B 2004). If untreated, nausea and vomiting can cause physiological changes, including dehydration, electrolyte imbalance, malnutrition, and cachexia (Henriksson R et al. 1992).

The use of 5-hydroxytryptamine (5-HT3)-receptor antagonists, such as granisetron (Kytril®), is the current “gold standard” in treating nausea and vomiting resulting from radiation therapy (Goldsmith B 2004).

Hypnosis effectively treated anticipatory nausea in pediatric (Zeltzer LK et al. 1991) and adult cancer patients (Morrow GR et al. 1982). Clinical research found acupuncture to be effective for nausea in cancer patients, whether it be postoperative nausea or chemotherapy-induced nausea (Dundee JW et al. 1989a; Dundee JW et al. 1989b; Mayer DJ 2000). Acupuncture may also reduce radiation-induced symptoms (Johnstone PA et al. 2002; Lu W 2005; Samuels N 2003).

Cancer Radiation Therapy-4

noreply@blogger.com (Kishen) — Wed, 20 Feb 2008 12:32:00 +0000

Second cancers. Although long-term survival following treatment for primary cancer has increased significantly in recent years, one of the most serious side effects of cancer treatment is the induction of a new tumor (Fossa SD 2004). Second cancers account for up to 10 percent of all cancer diagnoses (Bhatia N et al. 2001). A study of patients with primary cancer in adulthood showed a 1.3-fold increased risk of developing a second cancer from radiation therapy (Curtis RE et al. 1985).

The increased risk of second malignancy usually, though not exclusively, occurs in the radiation field. The risk is dose dependent and appears to be higher when radiation exposure occurs at a younger age. The latency period is long; for example, secondary leukemia usually develops 1 to 10 years after radiotherapy, whereas an interval of more than 6 years and often decades is usual for solid tumors (Somerville HM 2003).

A large number of studies have evaluated the risk of solid tumors following radiotherapy for Hodgkin's disease (Bhatia S et al. 2002; Ng AK et al. 2002). Survivors of Hodgkin's disease appear to face a 2 percent to 4 percent greater risk of second malignancy per person per year (Somerville HM 2003).

Overall, it should be noted that the risk of second cancers is generally low, and the benefit of radiation therapy for patient survival outweighs the risk of developing a second tumor (Travis LB 2002).

Sexual dysfunction. Erectile dysfunction occurs in 7 percent to 84 percent of prostate cancer patients treated with radiation, even with the development of advanced radiation techniques such as proton beam therapy and 3D-CRT, which spare more normal tissue (Incrocci L et al. 2002).

Sixty patients presenting with erectile dysfunction 39 months after radiation treatment for prostate cancer were enrolled in a 12-week study to determine the efficacy of sildenafil citrate (Viagra®). Patients reported a significant increase in erectile function, with only mild side effects, at a dose of 100 mg taken one hour before sexual activity (Incrocci L et al. 2003).

Vaginal stenosis (narrowing) occurs in up to 88 percent of women undergoing brachytherapy for gynecological cancers (Hartman P et al. 1972). The time of onset of stenosis varies widely, from six weeks to several years after treatment (Lancaster L 2004). Stenosis leads to thinning of the vaginal mucosa, scarring, and eventually scar tissue (Abitbol MM et al. 1974). This results in shortening and narrowing of the vagina, leading to dyspareunia (pain during intercourse) and sexual dysfunction (Bergmark K et al. 1999).

Several treatment options have been suggested to manage radiation injuries of the vulva and vagina (Fraunholz IB et al. 1998). Proper personal hygiene is crucially important in managing acute vulva skin reactions (Grigsby PW et al. 1995). Dilatation of the vagina either through the use of vaginal dilators or regular sexual intercourse should be performed to help prevent stenosis. Use of dilators should start before or immediately on completion of treatment and continue indefinitely (Lancaster L 2004).

A Cancer “cure” that may be lethal:

Radiation Therapy Increases stroke risk
Although head and neck cancer is the fifth most common cancer, most people are not familiar with this type of cancer (Vermorken JB 2005). The mortality rate for those diagnosed with head and neck cancer (which does not include brain tumors) is high (Fortin A et al. 2001).

Radiation therapy is an important part of treating many different head and neck tumors, and is often used after surgery (Hunter SE et al. 2003). Lethal radiation necrosis to the brain is one potential side effect (Eisbruch A et al. 1999).

Another danger of radiation therapy to the head is increased risk of stroke (Abayomi OK 2004). A study of head and neck cancer patients who received radiation therapy found that stroke rates were five times greater than expected (Dorresteijn LD et al. 2002) This elevated stroke risk was found many years after administration of radiation. The average time between radiation treatment and stroke was 10.9 years, but the increased risk of stroke persisted for 15 years after radiation therapy.

For cancer patients treated with radiation therapy who later die from a stroke, the official cause of death is stroke, even though the cancer radiation therapy probably caused the stroke. This is an example of how cancer cure statistics are misleading. The government contends that radiation therapy is curing cancer patients, yet long-term radiation side effects cause many deaths that are not attributed to cancer.

The government claims that more cancer victims are living beyond five years, but ignores the fact that the toxic therapies often used to eradicate cancer can themselves cause premature death (Lassen UN et al. 1999).

(The authors of this study do not recommend that head and neck cancer patients refuse radiation therapy, as it often adds years to their lives. Patients who have received radiation therapy to the head or neck should take extra precautions to reduce their risk of stroke.)

Importance of Diet During Treatment
Radiation therapy can change nutritional needs and alter the body's absorption and use of food (Brown JK et al. 2003). Common cancer symptoms and toxic effects of radiation treatment include fatigue, anorexia, weight change, nausea, vomiting, pain, and changes in taste and bowel habits (Brown JK et al. 2003).

Some researchers have suggested a low-fat (10 percent of calories from fat) and high-fiber (25 to 30 grams from vegetables and fruits) diet be consumed during and after cancer treatment (Boyd NF et al. 1997). Such a diet can interfere with tumor growth by reducing tumor-stimulating signals (Rao CV et al. 1993). Lifestyle changes that should be encouraged include quitting smoking, reducing consumption of caffeine and alcoholic beverages, exercising daily, and reducing stress levels (Prasad KN et al. 1999).

Nutritional Intervention During Radiotherapy
Dietary changes such as the use of low-residue and elemental diets are suggested for those patients undergoing pelvic radiotherapy, as they place less strain on the digestive system than do conventional diets (McGough C et al. 2004). Several studies have investigated dietary interventions in those undergoing pelvic radiotherapy (McGough C et al. 2004):

Dietary fat regimens, using 20 to 40 grams of fat per day, significantly reduced diarrhea and the frequency of bowel motions (Bye A et al. 1992). There was no difference in stool frequency or use of anti-diarrhea medication through dietary lactose restriction (Stryker JA et al. 1986).

Probiotics. The use of probiotics has a positive effect on gastrointestinal toxicity (Delia P et al. 2002). Probiotics refer to "friendly" bacteria that contribute to the health of the gastrointestinal tract. Twenty-four female patients suffering from gynecological malignancies all received dietary counseling recommending a low-fat, low-residue diet during their radiotherapy. Half the patients also received 150 ml of a fermented milk product supplying at least 2x109 Lactobacillus acidophilus bacteria daily and 6.5 percent lactulose as substrate for the bacteria. The results indicated significantly reduced diarrhea in the group receiving probiotics, though with increased flatulence (Salminen E et al. 1988).

Elemental diets are liquid diets consisting of essential amino acids, glucose, vitamins, and necessary minerals (Bounous G 1983). Nutrients are usually in digested form so they do not stress the digestive system. The use of an elemental diet during radiotherapy (Brown MS et al. 1980) resulted in a statistically significant decrease in the incidence and severity of acute diarrhea (Craighead PS et al. 1998; McArdle AH et al. 1986). In one favorable study, the elemental diet began three days before radiation therapy and was continued until completion. Patients were also placed on a modified diet that recommended low fiber, moderate fat intake, and adequate proteins and carbohydrates (Craighead PS et al. 1998).

Micronutrient supplementation in patients with proctitis (inflammation of the rectum) has been previously outlined (Levitsky J et al. 2003). A study of 19 patients treated with pelvic radiotherapy for more than six months examined whether vitamin A could reduce the resulting radiation-induced proctitis (Ehrenpreis ED et al. 2005). Ten patients received 10,000 IU of oral vitamin A for 90 days, after which seven reported a significant improvement in symptoms, compared to only two of nine placebo-treated patients who reported improvement.

In a pilot study, 20 patients with chronic radiation proctitis due to previous pelvic irradiation took vitamin E (400 IU, three times daily) and vitamin C (500 mg, three times daily) supplements for up to one year. Significant improvements were reported in the side effects of bleeding and diarrhea, but not pain (Kennedy M et al. 2001). However, in another study in which the same doses were administered, all symptoms subsided following 6 to 12 weeks of treatment (El Younis C et al. 2003).

For More Information
The complications related to radiation can be acute (such as low blood cell counts) and chronic (gastrointestinal, pulmonary, neuropathic, and cardiac). For more information on some of the topics outlined in this chapter, please consult the following chapters:

1)Blood Disorders

2)Catabolic Wasting

3)Complementary Adjuvant Cancer Therapies

4)Erectile Dysfunction

5)Neuropathy.

For general information on all aspects of radiation therapy, please visit: http://www.cancerlinksusa.com/radiation.htm.

Proton Therapy Centers in North America

The Loma Linda University Medical Center (LLUMC), California. LLUMC sponsors Prolit, a proton therapy literature database.

Northeast Proton Therapy Center at Massachusetts General Hospital in Boston.

Particle Therapy Co-operative Group (PTCOG) and the PTCOG publication Particles.

Midwest Proton Radiotherapy Institute, Bloomington, Indiana.

Proton Radiation Therapy at TRIUMF Vancouver, Canada. Pion Therapy is also available.

UC-Davis, California. The Berkeley Eye Program.

Life Extension Foundation Recommendations

For optimal results, the majority of these supplements or dietary changes should be introduced before starting radiation treatment. Refer to the text for a more detailed explanation of the dose and duration of the specific supplements.

1)R-lipoic acid—300 milligrams (mg) daily

2)Beta-carotene—25,000 international units (IU) or 75 mg daily

3)Coenzyme Q10—100 to 400 mg daily

4)Curcumin—up to 3.2 grams daily

5)Panax ginseng (Siberian)—200 to 1000 mg daily

6)Green tea extract—725 mg three times daily

7)Hydrolytic enzymes— papain (100 mg), trypsin (40 mg), and chymotrypsin (40 mg): three days before radiation therapy and continuing until five days after completion of treatment

8)Kamillosan—10 drops in 1 ounce of water, three times daily (http://www.smallflower.com/).

9)L-arginine—900 mg daily

10)L-glutamine—20 to 40 grams administered before starting radiation therapy

11)Melatonin—up to 20 mg daily

12)Multivitamin/multimineral supplement (without copper)

13)N-acetylcysteine—200 to 600 mg daily

14)Omega-3 fatty acids—1 to 2 grams (g) daily

15)Probiotics—2x109 Lactobacillus acidophilus daily

16)Pure honey—20 milliliters (ml), 15 minutes before, 15 minutes after, and 6 hours after radiotherapy

17)Selenium—200 to 1000 micrograms (mcg) daily

18)Silymarin—150 to 600 mg daily

19)Soy extract containing 50 mg of isoflavones—twice daily

20)Taurine—1000 mg daily

21)Vitamin A— 8000 to 30,000 IU daily

22)Vitamin C— 500 mg three times daily

23)Vitamin E—400 to 1200 IU daily

24)Whey protein isolate—20 grams daily.

Cancer Radiation Therapy Safety Caveats

An aggressive program of dietary supplementation should not be launched without the supervision of a qualified physician. Several of the nutrients suggested in this protocol may have adverse effects. These include:

All-trans retinoic acid (ATRA)

a)All-trans retinoic acid (ATRA) has been shown to exacerbate radiation nephropathy.

Beta-Carotene

1)Do not take beta-carotene if you smoke. Daily intake of 20 milligrams or more has been associated with a higher incidence of lung cancer in smokers.

2)Taking 30 milligrams or more daily for prolonged periods can cause carotenoderma, a yellowish skin discoloration (carotenoderma can be distinguished from jaundice because the whites of the eyes are not discolored in carotenoderma).

Coenzyme Q10

1)See your doctor and monitor your blood glucose level frequently if you take CoQ10 and have diabetes. Several clinical reports suggest that taking CoQ10 may improve glycemic control and the function of beta cells in people who have type 2 diabetes.

2)Statin drugs (such as lovastatin, simvastatin, and pravastatin) are known to decrease CoQ10 levels.

Curcumin

1)Do not take curcumin if you have a bile duct obstruction or a history of gallstones. Taking curcumin can stimulate bile production.

2)Consult your doctor before taking curcumin if you have gastroesophageal reflux disease (GERD) or a history of peptic ulcer disease.

3)Consult your doctor before taking curcumin if you take warfarin or antiplatelet drugs. Curcumin can have antithrombotic activity.

4)Always take curcumin with food. Curcumin may cause gastric irritation, ulceration, gastritis, and peptic ulcer disease if taken on an empty stomach.
Curcumin can cause gastrointestinal symptoms such as nausea and diarrhea.

EPA/DHA

1)Consult your doctor before taking EPA/DHA if you take warfarin (Coumadin). Taking
2)EPA/DHA with warfarin may increase the risk of bleeding.

3)Discontinue using EPA/DHA 2 weeks before any surgical procedure.

Ginseng

1)Consult your doctor before taking ginseng if you have high blood pressure. Overuse of ginseng can increase blood pressure.

2)Consult your doctor before taking ginseng if you take nonsteroidal anti-inflammatory drugs (NSAIDs) and/or warfarin (Coumadin). Taking NSAIDs or warfarin with ginseng can increase the risk of bleeding.

3)Consult your doctor before taking ginseng if you have diabetes. Taking ginseng can cause an extreme drop in your blood glucose level.

4)Ginseng can cause breast pain, vaginal bleeding after menopause, insomnia, headaches, and nosebleeds.

Green Tea

1)Consult your doctor before taking green tea extract if you take aspirin or warfarin (Coumadin). Taking green tea extract and aspirin or warfarin can increase the risk of bleeding.

2)Discontinue using green tea extract 2 weeks before any surgical procedure. Green tea extract may decrease platelet aggregation.

3)Green tea extract contains caffeine, which may produce a variety of symptoms including restlessness, nausea, headache, muscle tension, sleep disturbances, and rapid heartbeat.

L-Arginine

1)Do not take L-arginine if you have the rare genetic disorder argininemia.
Consult your doctor before taking L-arginine if you have cancer. L-arginine can stimulate growth hormone.

2)Consult your doctor before taking L-arginine if you have kidney failure or liver failure.

3)Consult your doctor before taking L-arginine if you have herpes simplex. L-arginine may increase the possibility of recurrence.

L-Glutamine

1)Consult your doctor before taking L-glutamine if you have kidney failure or liver failure.

2)L-glutamine can cause gastrointestinal symptoms such as nausea and diarrhea.

NOTE: Glutamine and Arginine

Many clinical trials utilizing glutamine and arginine resulted in beneficial outcomes for cancer patients, and four clinical trials are ongoing. However, some doctors are concerned that supplemental arginine and glutamine may promote tumor cell proliferation in patients, though this has not been clinically observed and is based solely on laboratory studies.

Lipoic Acid

Consult your doctor before taking lipoic acid if you have diabetes and glucose intolerance. Monitor your blood glucose level frequently. Lipoic acid may lower blood glucose levels.

Melatonin

1)Do not take melatonin if you are depressed.

2)Do not take high doses of melatonin if you are trying to conceive. High doses of melatonin have been shown to inhibit ovulation.

3)Melatonin can cause morning grogginess, a feeling of having a hangover or a “heavy head,” or gastrointestinal symptoms such as nausea and diarrhea.

Milk Thistle

1)Consult your doctor before taking milk thistle with tranquilizers such as Haldol, Serentil, Stelazine, and Thorazine. Milk thistle combats the effect of tranquilizers.

2)Do not combine milk thistle with the blood pressure medication Regitine. Milk thistle combats the effect of Regitine.

NAC

1)NAC clearance is reduced in people who have chronic liver disease.

2)Do not take NAC if you have a history of kidney stones (particularly cystine stones).

3)NAC can produce a false-positive result in the nitroprusside test for ketone bodies used to detect diabetes.

4)Consult your doctor before taking NAC if you have a history of peptic ulcer disease. Mucolytic agents may disrupt the gastric mucosal barrier.

5)NAC can cause headache (especially when used along with nitrates) and gastrointestinal symptoms such as nausea and diarrhea.

Selenium

1)High doses of selenium (1000 micrograms or more daily) for prolonged periods may cause adverse reactions.

2)High doses of selenium taken for prolonged periods may cause chronic selenium poisoning. Symptoms include loss of hair and nails or brittle hair and nails.

3)Selenium can cause rash, breath that smells like garlic, fatigue, irritability, and nausea and vomiting.

Soy

1)Do not take soy if you have an estrogen receptor-positive tumor.

2)Soy has been associated with hypothyroidism.

Vitamin A

1)Do not take vitamin A if you have hypervitaminosis A.

2)Do not take vitamin A if you take retinoids or retinoid analogues (such as acitretin, all-trans-retinoic acid, bexarotene, etretinate, and isotretinoin). Vitamin A can add to the toxicity of these drugs.

3)Do not take large amounts of vitamin A. Taking large amounts of vitamin A may cause acute or chronic toxicity. Early signs and symptoms of chronic toxicity include dry, rough skin; cracked lips; sparse, coarse hair; and loss of hair from the eyebrows. Later signs and symptoms of toxicity include irritability, headache, pseudotumor cerebri (benign intracranial hypertension), elevated serum liver enzymes, reversible noncirrhotic portal high blood pressure, fibrosis and cirrhosis of the liver, and death from liver failure.

Vitamin C

1)Do not take vitamin C if you have a history of kidney stones or of kidney insufficiency (defined as having a serum creatine level greater than 2 milligrams per deciliter and/or a creatinine clearance less than 30 milliliters per minute.

2)Consult your doctor before taking large amounts of vitamin C if you have hemochromatosis, thalassemia, sideroblastic anemia, sickle cell anemia, or erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency. You can experience iron overload if you have one of these conditions and use large amounts of vitamin C.

Vitamin E

1)Consult your doctor before taking vitamin E if you take warfarin (Coumadin).

2)Consult your doctor before taking high doses of vitamin E if you have a vitamin K deficiency or a history of liver failure.

3)Consult your doctor before taking vitamin E if you have a history of any bleeding disorder such as peptic ulcers, hemorrhagic stroke, or hemophilia.

4)Discontinue using vitamin E 1 month before any surgical procedure.

For more information see the Safety Appendix

Blood Test Availability
Cancer cell markers (tumor antigen profile) can be determined via Genzyme Genetics (http://www.genzymeimpath.com/lymphoma_leukemia.html) and may be ordered by a physician by telephoning 1-800-966-4440.

Tests for angiogenesis markers (e.g., VEGF) are available at UCLA’s Jonsson Comprehensive Cancer Center (http://www.cancer.mednet.ucla.edu/).

Hemoglobin levels (part of a Chemistry Panel/Complete Blood Count) may be tested via Life Extension/National Diagnostics, Inc. and may be ordered on line

Cancer Surgery

noreply@blogger.com (Kishen) — Wed, 20 Feb 2008 12:26:00 +0000

a)How Tumors Grow

b)Removing One Tumor May Stimulate the Growth of Many More

c)How to Enter Clinical Trials

d)The First Anti-angiogenesis Drug Is Approved

e)Protecting Against Surgery-Induced Immune Suppression

f)Avoid Analgesic Drugs That Promote Metastasis

g)Summary

Surgery poses many risks to a cancer patient. The known side effects associated with the surgical removal of tumors include anesthesia complications, infections, and immune suppression.

A surgery side effect of concern to cancer patients is that the removal of the primary tumor may directly stimulate cancer spread (the propagation of metastatic lesions). Metastatic tumors require the formation of new tumor blood vessels (called angiogenesis) to grow.

Once the primary tumor has been surgically removed, the amount of endostatin and angiostatin to control new tumor blood vessel growth is drastically reduced, and metastasized lesions begin proliferating out of control. If the immune depression that surgery induces is factored in, the failure of surgery to meaningfully prolong the life of cancer patients becomes quite understandable. Surgery reduces growth control factors (endostatin and angiostatin) while simultaneously weakening the immune surveillance that might be keeping metastatic lesions under some degree of control (Oliver et al. 1996).

Cancer has long baffled medical science. Until recently, scientists did not fully understand why the disease so often begins rapidly spreading throughout the body after surgery. This protocol identifies previously unknown factors involved in the long-term failure of cancer surgeries. The educated patient now has access to drugs to facilitate systemic control of cancer rather than to promote metastasis.

Even more exciting is the news that drugs such as endostatin and angiostatin are in clinical trials. If the FDA approves these drugs, the surgical removal of a large primary tumor might actually "cure" many more cancer patients. In the meantime, there are other anti - angiogenesis drugs that may help prevent the rapid growth of metastatic lesions after the primary tumor is removed.

How Tumors Grow

Almost every tissue in the body derives blood from the thinner-than-a-hair capillaries that lace our tissues. Through capillaries, nutrients, oxygen, and various signaling molecules diffuse into cells. These mechanisms maintain health, fight disease, and allow the body to flourish and grow.

Tumors start out without a vascular circulation. In the early stages of tumor development, they are limited to nutrients that can diffuse from the nearest capillaries. Then, tumors begin to stimulate healthy tissue to make thousands of new blood vessels to supply the cancerous growth--a process called angiogenesis. Without this ability to nourish itself and grow, a tumor cannot enlarge. If the blood supply can be reduced or cut off, the tumor will shrink or die.

Removing One Tumor May Stimulate the Growth of Many More

Recurrence is the point when cancer cells from the primary tumor are detected following the primary treatment for the cancer.

Ipsilateral breast tumor recurrence following conservative surgery and radiation for early stage invasive cancer occurs in approximately 15% of all patients at 10 years and is reduced with surgical excisions which achieve negative margins (Fowble 1999). Local recurrence continues to be a major problem following surgical treatment for rectal cancer, because of the frequency with which it occurs (varying from 4% to 51%), its impact on quality of life, the fact that treatment is rarely successful (McLeod 1997), and the proposed ways of reducing this remain controversial ( McCall et al. 1995).

All patients undergoing laparoscopic surgery for malignancies should have careful follow-up with special attention to the port sites, as port-site metastasis after laparoscopic lymphadenectomy is a phenomenon that occurs following this type of cancer surgery ( Tjalma et al. 2001).

Several drugs--including interferons, steroids, and certain hormonal agents--have been developed to stop or slow angiogenesis. In fact, at least 11 anti-angiogenic drugs are in clinical trials, and three have proved effective enough to make it to the final phase.

Some of the drugs, like endostatin, are derived from natural proteins, while others are based on smaller molecules. Ironically, one promising drug in clinical trials is thalidomide, which once was sold as a sedative that caused notorious birth defects.

Another drug, 2-methoxyestradiol (2-ME), is a natural estrogen metabolite believed to be an inhibitor of angiogenesis and also an anti - tumor agent.

In addition, researchers are investigating a drug called Col-3 and are negotiating with several biotechnology companies to examine other anticancer compounds.

Of all the anti - angiogenic drugs, endostatin and angiostatin appear to hold the greatest potential for saving lives. These drugs are nontoxic and have shown efficacy against every type of cancer tested. These drugs suppressed metastatic tumor growth rates by 90% (Hajitou et al. 2002). Another study showed primary tumors regressing to become dormant microscopic lesions (O'Reilly et al. 1997).

Based on this new information, angiostatin and endostatin may greatly increase the number of cancer patients who become disease-free after surgery.

How to Enter Clinical Trials

Endostatin was the first endogenous angiogenesis inhibitor to enter into clinical trials. Endostatin given to 21 advanced solid tumor patients daily as a 1-hour intravenous infusion (for 28 days) was well - tolerated (Thomas et al 2003).

The safety and efficacy of recombinant human Angiostatin protein administered in combination with chemotherapy (paclitaxel and carboplatin) to patients with non-small-cell lung cancer is currently being investigated in a clinical trial: http://clinicaltrials.gov/ct/search?term=angiostatin

For more information about cancer clinical trials call the Cancer Information Service, (800) 4-CANCER.

Physicians may request information about trials from the PDQ Search Service by calling (800) 345-3300, faxing (800) 380-1575, or e-mailing pdqsearch@icicc.nci.nih.gov.

There are many anti - angiogenesis drugs in clinical studies. In some cases, the FDA may allow an unapproved drug to be released before it is officially approved. Here are some of the anti - angiogenesis drugs being tested and the sponsoring companies:

The First anti-angiogenesis drug is approved

Cancer Treatment: The Critical Factors-1

noreply@blogger.com (Kishen) — Wed, 20 Feb 2008 11:27:00 +0000

Step One: Evaluating Tumor Cell Population
Step Two: Determine Sensitivity or Resistance to Chemotherapy
Step Three: Protecting Against Anemia
Step Four: Inhibiting the Cyclooxygenase-2 (COX-2) Enzyme
Step Five: Suppressing ras Oncogene Expression
Step Six: Correcting Coagulation Abnormalities
Step Seven: Maintaining Bone Integrity
Step Eight: Inhibiting Angiogenesis

Summary
Determining the best way of treating cancer remains highly controversial, even among mainstream oncologists. What may surprise the reader is the large number of documented therapies that have been overlooked by establishment medicine.

The fundamental objective of this book is to encourage the expedient transfer of published scientific findings from the research bench to the clinical setting where the patient may benefit. This is the concept of translational medicine, which means translating knowledge from the laboratory side of medicine to the front lines of patient care.

Physicians who practice translational medicine react uniquely when informed about a novel therapy. Their curiosity first motivates them to evaluate the new approach in order to reaffirm safety and efficacy in the context of treatment that is appropriate to the patient's condition. The dedicated translational physician uses novel therapeutics based on:

a)That which has been established to be effective,

b)That which has a good chance of being effective, and

c)That which will do no harm or, in the context of the patient's condition, that which is worth taking an appropriate risk.

Once satisfied that a novel therapy has merit, enlightened physicians then integrate this new finding into individual treatment regimens. These physicians, in essence, are translating the results from promising studies directly into life-saving treatments.

As simple as this approach may seem, few physicians practice translational medicine. For instance, the scientific literature documents that if a cancer patient is anemic, the odds of survival are greatly reduced. Regrettably, few oncologists are aggressive in their evaluation and treatment of anemia in everyday practice even though anemia directly correlates with increased mortality.

Oncologists learn about new discoveries at scientific conferences, in medical journals, and on the Internet. Only a fraction of these doctors, however, translate this knowledge into enhanced treatments that would benefit their patients. In fact, many of the outstanding established medical advances are not utilized routinely by large numbers of physicians treating cancer patients.

The lay public is often surprised to learn how seldom breakthrough discoveries are used to save human lives. The facts are that managed care and bureaucratic overregulation have relegated most oncologists to the practice of assembly line medicine. Sadly, in the most advanced medical system in the world today, we have seen a move away from translational medicine and into "fast-food medicine" or, as some would call it, "McMedicine. " In this book, we emphasize the need for physicians to return to real medicine and apply what they have learned, making translational medicine a cornerstone of their treatment philosophy so that medical care can evolve.

It is difficult for most cancer patients to locate an oncologist who routinely translates new findings into clinical practice. This protocol reveals overlooked conventional research findings in order to provide the patient and their oncologist with the latest scientific information.

Cancer patients should become educated about the treatment options discussed in this protocol, so they can better discuss them with their oncologist. The objective is to include as many different therapies as is practical and affordable. Cancer is an extremely difficult disease to treat, and a multimodality therapy is therefore highly recommended.

Once you understand how many therapy options already exist in the conventional setting, you should feel more confident of a positive long-term outcome.

In this protocol, we discuss the following eight critical steps that may significantly improve a successful outcome when considered in the treatment of most cancers:

1)Evaluating the molecular biology of the tumor cell population

2)Analyzing the patient's living tumor cells to determine sensitivity or resistance to chemotherapy

3)Protecting against anemia

4)Inhibiting the cyclooxygenase-2 (COX-2) enzyme

5)Suppressing r R as oncogene expression

6)Correcting coagulation abnormalities

7)Maintaining bone integrity

8)Inhibiting angiogenesis

Step One: Evaluating the Molecular Biology of the Tumor Cell Population

How To Implement Step One
Throughout this protocol, you will see terminology relating to the molecular aspects of the cancer cell. When we use the term molecular , we are referring to specific characteristics of cancer cells such as

Tumor-promoting genes (oncogenes)
Tumor suppressor genes
Receptors or docking sites on the cell membrane where communication with proteins occur
Cellular differentiation, that is, the degree of maturity, and probability of response of the cancer cell to certain therapies
These individual variations--the unique biology of the cancer cell--help to explain why a particular therapy may be highly effective for some cancer patients but fail others.

People typically think of their disease based on the organ it affects (i.e., adenocarcinoma of the lung, colon cancer, etc.). The problem is that not all adenocarcinomas of the lung are the same. With the advent of advanced molecular diagnostic profiling, it is possible to identify the specific strengths and vulnerabilities of each patient's cancer cell line in order to design a comprehensive, yet tailored, treatment program. We will describe the most important molecular cancer cell tests, along with potentially effective therapies to consider. Most of the suggested therapies will require that your physician be involved in this process.

It is critical to obtain a description of the type of cells that populate your tumor. Not only does this assist the oncologist in recommending the most effective conventional therapy, but it also helps determine what adjuvant nutritional and off-label drug therapies to consider. The human eye alone can serve to provide the most basic information about a cancer cell through the microscopic examination of the cell's morphology or general characteristics. Taking this one step further is evaluation by an immunohistochemistry test. This test detects markers of diagnostic value on and within the cell surface, through the application of colored dye or stains. In order to perform this and other tests, it is necessary for a sample of your tumor to be sent to a specialized laboratory. The contact information for one of these laboratories (GENZYNE, Inc.) is listed at the end of this section.

GENZYNE provides a comprehensive range of customized analyses to help cancer specialists correctly diagnose difficult tumors, establish prognosis in many cancers (including breast, prostate, and colon), and determine optimal treatment. By providing this information, GENZYNE starts treatment on the right course and helps avoid unnecessary therapies. The findings from an GENZYNE tumor cell test enable patients to benefit from both more effective and more cost-effective cancer management. A typical GENZYNE analysis provides information that can prevent ineffective and potentially debilitating treatments costing many thousands of dollars. GENZYNE performs more specialized analyses for cancer than any other laboratory in the world. Through their review of over 960,000 patient profiles to date, GENZYNE has developed one of the world's largest, most comprehensive cancer databases.

GENZYNE serves more than 8300 physicians, over 2000 hospitals, and over 570 oncology practices. Their expert medical consultation and advanced technologies (immunohistochemistry, flow cytometry and image analysis, cytogenics, molecular pathology, and chemotherapeutic resistance testing) allow community hospitals and small practices to provide the same sophisticated services as major academic medical centers.

When a patient might have cancer, physicians confront a chain of pressing questions. What type of cancer is it? Where did it originate? Where has it spread? Which treatments are most likely to work? Finding the answers quickly and accurately is vital. GENZYNE helps clinicians pose the right questions and get the answers they need.

As far as simple diagnosis is concerned, 15-20% of all cancers defy classification by visual examination. In fact, the diagnosis of "metastatic cancer of unknown primary site" is the eighth most common cancer diagnosis. In a majority of these difficult cases, GENZYNE's medical expertise and advanced technologies lead to an accurate diagnosis.

Visual examination of tumors provides very little information about their growth rate or the type of treatment to which they will respond. GENZYNE's prognostic expertise can accurately establish whether the cancer has spread, evaluate its aggressiveness, and predict the effects of therapy. The results are greater predictability of outcome, increased survival, and decreased overall costs.

Difficult cancers have traditionally been treated as follows: if one therapy proves ineffective, then try another until a successful therapy is found or all options are exhausted. GENZYNE eliminates the need for this trial-and-error method by providing individualized information to determine the optimal therapy before initiating treatment.

GENZYNE provides highly sensitive patient monitoring for the follow-up care of many cancers. For example, GENZYNE can determine whether certain types of lymphomas have recurred before they can be detected by any other method. The earlier tumor recurrence is detected, the greater the likelihood of therapeutic success.

GENZYNE not only offers a full range of diagnostic and prognostic cancer analyses, but also emphasizes client service. Typically within 48 hours after receiving a specimen, GENZYNE returns the stained slides along with a thorough and detailed case report to a physician. If your oncologist wants to consult with a member of the GENZYNE staff, telephone lines are open. In Appendix A at the end of this protocol are examples of typical GENZYNE laboratory reports that your oncologist receives.

Contact information for GENZYNE is as follows:

New York
521 West 57th Street, Sixth Floor
New York, NY 10019

Los Angeles
5300 McConnell Avenue
Los Angeles, CA 90066

Phoenix
810 East Hammond Lane
Phoenix, AZ 85034
Telephone: (800) 447-5816
Website: www.genzyme.com

How to implement step ONE

Make certain your surgeon sends a specimen of your tumor to GENZYME for immunohistochemistry testing, using the contact information just provided. You may have to pay out of pocket for this test because not all insurance plans reimburse for it. Please note that this test may not be of benefit to all cancer patients. While it provides a basis for improved treatment, not all cancers are effectively treatable with today's technologies.

Step Two: Analyzing the Patient's Living Tumor Cells to Determine Sensitivity or Resistance to CHEMOTHERAPY

How to Implement Step Two
If chemotherapy is being considered, it is desirable to know which of the chemotherapy drugs will have a high probability of being effective against your particular cancer before any toxic agents are administered into your body. It is equally as important, if not more important, to know if your particular cancer cells exhibit extreme drug resistance (EDR) to specific chemotherapy drugs. EDR implies a probability of 95% that the chemotherapy drugs exhibiting EDR will be ineffective in killing the cancer cells. A company called Rational Therapeutics, Inc. performs chemo-sensitivity tests on the living specimens of your cancer cells to determine the optimal combination of chemotherapy drugs, as well as determining EDR.

Rational Therapeutics, Inc., was founded in 1993 by Dr. Robert Nagourney, a prominent hematologist and oncologist. Rational Therapeutics pioneers cancer therapies that are specifically tailored for each individual patient and is a leader in individualized cancer strategies. With no financial ties to outside healthcare organizations, recommendations are made without financial or scientific prejudice.

Rational Therapeutics develops and provides cancer therapy recommendations which have been designed scientifically for each patient. Following the collection of living cancer cells obtained at the time of biopsy or surgery, Rational Therapeutics performs an Ex-Vivo Apoptotic (EVA) assay on your tumor sample to measure drug activity (sensitivity and resistance). Ex-vivo apoptotic means that your tumor cells are grown outside of your body for the purpose of determining which drug or drug combination most effectively induces cell death (apoptosis) in the laboratory. Each patient is highly individualized with regard to his or her sensitivity to chemotherapy drugs. Your responsiveness to chemotherapy is as unique as your fingerprints. Therefore, this test will help to exactly determine which drug(s) will be most effective for you. Dr. Nagourney will then make a treatment recommendation based on these findings.

The treatment program developed through this approach is known as assay-directed therapy . In 1999, there were more than 1.2 million newly diagnosed cases of cancer in the United States, with 563,000 deaths attributed to this disease. Unfortunately, 50% of newly diagnosed cancer patients have advanced disease that is beyond the hope of a surgical or radiation cure. Patients with advanced disease and those with recurrent disease are candidates for systemic therapy, which is administered usually in the form of chemotherapy. Despite the enormity of the cancer problem, in the last 45 years, there has been virtually no major change in the outcome for the common advanced solid tumors such as those of the lung, prostate, colon, and breast. While there have been improvements in treating lymphomas, certain types of leukemia, and some earlier-stage cancers, the grim facts indicate more aggressive tumor diagnostic tests are needed to provide the medical oncologist with better prognostic information about your individual tumor.

At present, cancer chemotherapies are prescribed by medical oncologists, according to fixed schedules. These schedules are standardized drug regimens that correspond to specific cancers by type or diagnosis. These schedules, developed over years of clinical trials, assign patients to the drugs for which they have the greatest statistical probability of response.

Patients with cancers that exhibit multidrug resistance are on the wrong side of the probability curve, that is, they will likely receive treatments that are wrong for them. A failed attempt at chemotherapy is detrimental to the physical and emotional well-being of patients, is financially burdensome, and may preclude further effective therapies.

Rational Therapeutics provides custom-tailored, assay-directed therapy based on your tumor response in the laboratory. This eliminates much of the guess work prior to your undergoing the potentially toxic side effects of chemotherapy regimens that could prove to be of little value against your cancer. In Appendix B at the end of this protocol are typical laboratory reports your oncologist receives from Rational Therapeutics.

Here is the contact information for Rational Therapeutics:

Rational Therapeutics, Inc.
750 East 29th Street
Long Beach, CA 90806
Telephone: (562) 989-6455 ; Fax: (562) 989-8160
Email: www.rationaltherapeutics.com

How to implement step TWO

Get in touch with Rational Therapeutics using the contact information provided so that your surgeon can follow the precise instructions required to send a living specimen of your tumor for chemo sensitivity testing. It is important that your surgeon carefully coordinate with Rational Therapeutics in order to ensure your cells arrive in a viable condition. You may have to pay for this test yourself because your insurance may not reimburse for it. Please note that this test may not be of benefit to all cancer patients. While it provides a basis for improved treatment, not all cancers are effectively treatable with today's technologies.

Cancer Treatment: The Critical Factors-2

noreply@blogger.com (Kishen) — Wed, 20 Feb 2008 11:22:00 +0000

Step Three: Protecting Against AnemIA

How To Implement Step Three
Anemia diminishes the chances that a cancer patient will survive. Since red blood cells carry oxygen, fewer numbers of red blood cells result in less oxygen transport. When normal cells are oxygen deprived, they lack the vigor to overcome cancer. Cancer cells, on the other hand, thrive in a low oxygen environment. The journal Cancer reported that anemia increased the risk of mortality in cancer patients by about 65% (Caro et al. 2001).

Anemia is defined functionally as lack of sufficient red blood cells to maintain tissue oxygenation. Anemia develops when the demand for new red blood cells exceeds the capacity of the bone marrow to produce them. This may be due to inadequate red blood cell production, as occurs when cancer or cancer therapies inhibit the production of erythropoietin, a glycoprotein hormone secreted by the kidney, which acts on stem cells of the bone marrow to stimulate red blood cell production (Spivak 1994).

Cancer-related anemia also results from activation of the immune and inflammatory systems (responses orchestrated by the tumor), leading to an increased release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1). Such cytokines circumvent the ability of the bone marrow to respond to available circulating erythropoietin, resulting in lesser numbers of oxygen-carrying red blood cells being produced (Cazzola 2000). In addition, the lifespan of red blood cells (normally 120 days in men and about 110 days in women) is shortened in cancer-related anemia; thus, production cannot compensate sufficiently for the shorter survival time. The energy-depleting cycle of abnormal metabolism (leading to malnutrition and wasting disease) also is a contributing factor to the progression of anemia.

Weakness, fatigue or faintness, shortness of breath and increased heart rate, headaches, confusion, dementia, depression, cold extremities, dizziness, pallor, and sore mouth are complaints of anemia that complicate recovery. Severe anemia may also result in heart failure.

Too many oncologists wait for anemia to develop before prescribing drugs like Procrit® and Aranesp® to boost red blood cell production. Other oncologists have prescribed high doses of drugs like Procrit® in an attempt to push levels of hemoglobin (the protein in blood that binds with oxygen) to the upper end of the normal reference range. This was done based on research indicating benefits to cancer patients with higher hemoglobin measurements.

Based on new research findings, the FDA is mandating a black box warning on drugs like Procrit®, AranespI® and Epogen® that warns oncologists to not over-dose these drugs for the purpose of pushing hemoglobin up beyond 12 g/dL (grams per deciliter of blood). The reason for this new black box warning are increased risks of death reported in certain cancer patients who were prescribed higher doses of these red blood cell stimulating drugs.

Based on the conflicting findings that exist today, cancer patients should continue to aggressively protect against anemia, but should not take higher-than-recommended doses of Procrit and other red blood cell boosting drugs.

One problem that cancer patients encounter is that some insurance companies will not pay for expensive drugs like Procrit unless severe anemia is demonstrated. Patients should advocate for immediate access to these red blood cell boosting drugs if indications of anemia manifest, such as low hemoglobin. Anemia appears to contribute to angiogenesis--the vascular network supplying life to the tumor. Vascular endothelial growth factor (VEGF) is an endothelial cell specific mitogen, an agent that induces cell division. The expression of VEGF appears to be an indicator of the angiogenic potential and correlates with the biological aggressiveness of a tumor.

How to implement step THREE

If your hemoglobin or hematocrit levels indicate you are anemic or that you are not in optimal ranges, ask your physician to prescribe an individualized dose of Procrit.
In order for Procrit to effectively boost red blood cell production, it is essential that your body have adequate iron stores. Even if you have adequate iron stores prior to Procrit therapy, the rapid production of red blood cells induced by Procrit may eventually deplete total body iron stores. Therefore, it is important to obtain baseline studies to exclude the presence of iron deficiency.
Note: Iron deficiency is best diagnosed by checking the serum ferritin to see if the values are low. Many physicians obtain a serum iron and serum iron binding capacity and divide the former by the latter to obtain the transferrin saturation. If this result is < 10%, there is a probability of iron deficiency anemia (IDA). A more modern approach to a diagnosis of iron deficiency anemia, however, is to check the serum ferritin; if it is greater than 220, IDA is essentially ruled out. However, if the serum ferritin level is lower than 220, a blood test called the soluble transferrin receptor (sTfR) assay should be obtained. This measures the receptors for transferrin--receptors that bind to the available iron. If this value is 28 or higher, there is a significant chance of IDA. Regular blood tests to assess ferritin and, when indicated, sTfR will assist your doctor in determining whether or not you need iron supplementation.
Dietary supplements that can help protect against anemia include folic acid (800 mcg/day), vitamin B12 (500 mcg/day), and melatonin (3-10 mg/day, taken at night) (Vaziri et al. 1996; Herrera et al. 2001).

Step Four: Inhibiting the Cyclooxygenase-2 (COX-2) ENZYME

How To Implement Step Four
Our diet, the amount of saturated and polyunsaturated fat we eat, and the unfavorable fats that we create in our bodies play a crucial role in the development and progression of malignancy. A critical pathway that represents a "Rosetta Stone" to all aspects of our health is that involving the metabolism of omega-6 fatty acids leading to either di-homo gamma-linolenic acid (DGLA) or to arachidonic acid.

These "roads" are called the eicosanoid pathways. The metabolism of DGLA leads to the production of fats that are actually beneficial to our health, that is, good eicosanoids. Unfortunately, in today's world, this is the "road less traveled" for most people. The metabolism of arachidonic acid, the bad eicosanoid pathway, leads to most of the health maladies currently faced by our society. A key enzyme in the bad eicosanoid pathway is cyclooxygenase (cyclooxygenase or COX). It is the COX-2 enzyme that results in the production of prostaglandin E2 or PGE2.

Initially, scientists believed COX-2 was merely an inducible response to inflammation. It is now speculated that COX-2 performs biological functions in the body, particularly in the brain and kidneys as well as the immune system. COX-2 becomes troublesome when up - regulated (sometimes 10- to 80-fold) by pro - inflammatory stimuli (interleukin-1, growth factors, tumor necrosis factor, and endotoxin). When over - expressed, COX-2 participates in various pathways that could promote cancer, that is, angiogenesis, cell proliferation, and the production of inflammatory prostaglandins (Sears 1995; Newmark et al. 2000).

A number of researchers have established the COX-2 cancer connection:

The Wall Street Journal (September 7, 1999) reported the results of a trial involving a group of rats given a potent carcinogen along with a COX-2 inhibitor. Rats treated with the COX-2 inhibitor experienced a 90% reduction in cancer compared to a group of rats not given a COX-2 inhibitor. Also, the tumors that appeared were 80% smaller and less numerous than in the control group.
An article in the journal Cancer Research showed that COX-2 levels in pancreatic cancer cells are 60 times greater than in adjacent normal tissue (Tucker et al. 1999).
Solid tumors contain oxygen-deficient or hypoxic areas, that is, a reduction of oxygen supply to a tissue below physiological levels. Cells low in oxygen cloud prognosis, promoting up - regulation of COX-2 and angiogenesis, as well as establishing a resistance to ionizing radiation (Gately 2000).
Greater microvessel density was observed in cancers over - expressing COX-2, compared to those with less COX-2 activity (Uefuji et al. 2000).
Within the nonsteroidal anti-inflammatory drug (NSAIDs) class (NSAIDs) is a subclass referred to as COX-2 inhibitors (cyclooxygenase inhibitors). COX-2 inhibitors are popularly prescribed to relieve pain but now have found a place in oncology. It began when scientists recognized that people who regularly take NSAIDs lowered their risk of colon cancer by as much as 50% (Reddy et al. 2000).

COX-2 inhibitors also significantly reduced colon polyps (considered precursors to cancer) in individuals with a propensity to polyp formation. Laboratory animals showed a similar benefit, that is, about 52% fewer polyps among mice treated with COX-2 inhibitors (Nakatsugi et al. 1997; Moran 2002). JAMA reported that a 9.4-year epidemiological study showed that COX-2 upregulation was related to more advanced tumor stage, tumor size, and lymph node metastasis as well as diminished survival rates among colorectal cancer patients (Sheehan et al. 1999). With more regular use of aspirin (a COX-2 inhibitor), the risk of dying from the disease decreased (Brody 1991; Knorr 2000). The journal Gastroenterology reported additional encouragement, showing that three different colon cell lines underwent apoptosis (cell death) when deprived of COX-2; when lovastatin was added to the COX-2 inhibitor, the kill rate increased another fivefold (Agarwal et al. 1999). The benefits, however, observed with COX-2 inhibitors extend beyond colon protection (Tsujii et al. 1998).

The COX-2 enzyme is increased in neoplastic epithelium in a number of other types of cancers (breast, bladder, lung, prostate, and head and neck cancers) as well as the blood vessel network surrounding the cancerous mass. Tumors expressing COX-2 are considered more treacherous than tumors that lack COX-2 (in part) because of the angiogenic (blood vessel-promoting) nature of cyclooxygenase. It appears cancer cells use COX-2 as a biological mechanism to fuel rapid cell division, growing larger tumor cells than those that lack COX-2 stimulation (Tsujii et al. 1998).

The Life Extension Foundation predicts that COX-2 inhibitors will eventually be approved to treat cancer. Progressive oncologists already have COX-2 inhibitors in their anticancer protocols, but the numbers are few. Unfortunately, the risks associated with traditional NSAIDs include gastrointestinal perforation, ulceration and bleeding and less frequently, renal and liver disease.

Blood tests to assess liver and kidney function are essential, along with serum tumor markers and imagery testing to determine gains or losses during COX-2 inhibiting therapy.

While there are potential side effects to COX-2 inhibiting drugs, some cancer patients accept this small risk in exchange for the anticancer benefit. Since the COX-2 enzyme appears an excellent target for pharmacological intervention, a number of natural COX-2 inhibitors, safe and with diverse anticancer properties, are detailed in the protocol entitled Cancer Adjuvant Therapy .

How to implement step FOUR

Ask your physician to prescribe one of the following COX-2 inhibiting drugs:

a)Lodine XL, 1000 mg once daily, or

b)Celebrex, 100-200 mg every 12 hours

Step Five: Suppressing ras Oncogene ExpressiON

How To Implement Step Five
The family of proteins known as Ras plays a central role in the regulation of cell growth. It fulfills this fundamental role by integrating the regulatory signals that govern the cell cycle and proliferation.

Defects in the Ras-Raf pathway can result in cancerous growth. Mutant Ras genes were among the first oncogenes identified for their ability to transform cells to a cancerous phenotype, that is, a cell observably altered because of distorted gene expression. Mutations in one of three genes (H, N, or K-Ras) encoding Ras proteins are associated with upregulated cell proliferation and are found in an estimated 30-40% of all human cancers. The highest incidences of Ras mutations are found in cancers of the pancreas (80%), colon (50%), thyroid (50%), lung (40%), liver (30%), melanoma (30%), and myeloid leukemia (30%) ( Duursma et al. 2003; Minamoto et al. 2000 ; Vachtenheim 1997; Bartram 1988 ; Bos 1989; Minamoto et al. 2000 ).

According to information in Scientific American , the differences between oncogenes and normal genes are slight. The mutant protein that an oncogene ultimately creates may differ from the healthy version by only a single amino acid, but this subtle variation can radically alter the protein's functionality.

The Ras-Raf pathway is used by human cells to transmit signals from the cell surface to the nucleus. Such signals direct cells to divide, differentiate, or even undergo programmed cell death (apoptosis).

A Ras protein gene usually behaves as a relay switch within the signal pathway that tells the cell to divide. In response to stimuli transmitted to the cell from outside, cell-signaling pathways are activated; in the absence of stimulus, the Ras protein remains in the "off” position. A mutated Ras protein gene behaves like a switch stuck on the "on" position, continuously misinforming the cell, instructing it to divide when the cycle should be turned off (Gibbs et al. 1996; Oliff et al. 1996). Researchers have known for some time that injecting anti-Ras antibodies, specific for amino acid 12, cause a reversal of excessive proliferation and a transient alteration of the mutated cell to one of a normal phenotype (Feramisco et al. 1985).

To establish new methods for diagnosing pancreatic cancer, K-Ras mutations were examined in the pancreatic juice of pancreatic cancer patients. Pancreatic juice was positive for K-Ras in 87.8% (36/41) of patients. When combined with p53 mutations in the stool and CA 19-9 (a blood marker for pancreatic cancer), it may be possible to identify the disease in its earliest stage. Thus, a program can be implemented that includes addressing mutant K-Ras and p53 to achieve a more favorable outcome (Lu et al. 2001).

Greater understanding regarding the activity of mutant Ras genes opens exciting avenues of treatment. Researchers found that newly formed r R as molecules are functionally immature. Precursor Ras genes must undergo several biochemical modifications to become mature, active versions. After such maturation, the Ras proteins attach to the inner surface of the cells outer membrane where they can interact with other cellular proteins and stimulate cell growth.

The events resulting in mature Ras genes take place in three steps, the most critical being the first, referred to as the farnesylation step. A specific enzyme, farnesyl-protein transferase (FPTase), speeds up the reaction. One strategy for blocking Ras protein activity has been to inhibit FPTase. Inhibitors of this enzyme block the maturation of Ras protein and reverse the cancerous transformation induced by mutant Ras genes (Oliff et al. 1996).

A number of natural substances impact the activity of Ras oncogenes. For example, a historic body of literature indicates individuals consuming large quantities of citrus products have a lower incidence of cancer. One of the essential oils within citrus products is limonene, a monoterpene that has been shown to act as a farnesyl transferase inhibitor. Administering high doses of limonene to cancer-bearing animals blocks the farnesylation of Ras, thus inhibiting cell replication (Bland 2001; Asamoto et al. 2002). A study conducted at Mercy Hospital of Pittsburgh also showed that diallyl disulfide, a naturally occurring organosulfide from garlic, inhibits p21 H-Ras oncogenes, displaying a significant restraining effect on tumor growth (Singh et al. 2000).

Cancer Treatment: The Critical Factors-3

noreply@blogger.com (Kishen) — Wed, 20 Feb 2008 11:15:00 +0000

Researchers at Rutgers University investigated the ability of different green and black tea polyphenols to inhibit H-Ras oncogenes. The Rutgers team found that all the major polyphenols contained in green and black tea except epicatechin showed strong inhibition of cell growth (Chung et al. 1999). Texas A&M University also found that fish oil decreased colonic Ras membrane localization and reduced tumor formation in rats. In view of the central role of oncogenic Ras in the development of colon cancer, the finding that omega-3 fatty acids modulate Ras activation likely explains why dietary fish oil protects against colon cancer (Collett et al. 2001).

Statins are a class of popular cholesterol-lowering drugs. Mevacor (lovastatin), Zocor (simvastatin), and Pravachol (pravastatin) are statin drugs shown to inhibit the activity of Ras oncogenes (Wang et al. 2000). Statin drugs block the hydroxymethylglutaryl - coenzyme A (HMG-COA) reductase enzyme, which depletes cells of farnesyl pyrophosphate. Levels of total Ras do not decrease but rather shifts in when Ras protein occurs, that is, farnesylated Ras decreases and unmodified, non un farnesylated Ras increases (Hohl et al. 1995).

Illustrative of the potential of statin therapy, patients with primary liver cancer were treated with either the chemotherapeutic drug 5-FU or a combination of 5-FU and 40 mg/day of pravastatin. Median survival increased from 9 months, among patients treated with only 5-FU, to 18 months when using 5-FU combined with the statin drug pravastatin (Pravachol®). Increased survival was attributed to decreased cellular proliferation and incidence of metastasis (Wang et al. 2000).

If a statin drug is planned to be co - administered with chemotherapy, some patients are medicated cyclically, that is, 3 weeks of a statin drug such as lovastatin (80 mg/day) followed by a 2-week break before restarting the statin. Other regimens involve using the statin drug for 6 continuous months or until signs of toxicity develop.

Note: Some cancer patients may benefit from coenzyme Q10 supplementation when taking statin therapy. For a detailed explanation, please consult the Coenzyme Q10 section in the Cancer Adjuvant Therapy protocol.

Individuals with cancer should consider an immunohistochemistry test of their cancer tissue for mutated ras genes at GENZYME Laboratories ( see the beginning of this protocol ), a recommendation the Life Extension Foundation first made in 1997. The Life Extension Foundation strongly believes all cancer patients should undergo immunohistochemical testing to determine p53 and Ras status. As mentioned previously, the following laboratory can perform the test:

GENZYME Laboratories,
Telephone: (800) 447-5816

How to implement step fiVE

Ask your physician to prescribe one of the following statin drugs to inhibit the activity of Ras oncogenes:

Mevacor (lovastatin), 40 mg twice each day, or
Zocor (simvastatin), 40 mg twice each day, or
Pravachol (pravastatin), 40 mg once a day
Note: These statin drugs can produce toxic effects in patients. Physician oversight and careful surveillance with monthly blood tests (at least initially) to evaluate liver function, muscle enzymes, and lipid levels are suggested.

In addition to statin drug therapy, consider supplementing with the following nutrients to further suppress the expression of Ras oncogenes:

Fish Oil Capsules: 2100 mg of EPA and 1500 mg of DHA day (Six Super Omega-3 fish oil capsules provide this potency)
Green Tea Extract: 1400 mg of tea polyphenols a day (Two Mega Green Tea Extract Caps provide this potency)
Aged Garlic Extract: 2400 mg (Four Kyolic® Reserve capsules provides this potency)

Step Six: Correcting Coagulation AbnormalitiES

How to Implement Step Six

Both experimental and clinical data have shown that coagulation disorders are common in patients with cancer, although clinical symptoms occur less often. Many cancer patients reportedly have a hypercoagulable state, with recurrent thrombosis due to the impact of cancer cells and chemotherapy on the coagulation cascade (Samuels et al. 1975). Pulmonary embolism is a particular problem for patients with pancreatic and gastric cancer, cancer of the large bowel, and women with ovarian cancer (Cafagna et al. 1997). Thus, momentum is building for anticoagulant therapy through reports, the vast majority of which are derived from secondary analyses of clinical trials on the treatment of thromboembolism.

Research on low-molecular-weight heparin (LMWH), an anticoagulant, shows promise in regard to increasing cancer survival rates. Data comparing unfractionated heparin to LMWH indicate that LMWH is equally beneficial if not more beneficial to cancer patients in terms of survival. The improved life expectancy gathered from anticoagulant therapy is not solely a result of the reduced complications from thromboembolism, but also from enzyme interactions, cellular growth modifications, and anti - angiogenic factors (Cosgrove et al. 2002). It appears heparin inhibits the formation of cancer's vascular network by binding to angiogenic promoters, that is, basic fibroblast growth factor and VEGF (Mousa 2002).

Another important aspect of anticoagulant therapy involves breaking down fibrin, a coagulation protein found in blood. Fibrin has various strategies it employs to accommodate the tumor. For example, fibrin covers maverick cells with a protective coat, hindering recognition by the immune system. In addition, fibrin relays a signal to the cancer cell to start angiogenesis, the growth of new blood vessels. As fibrin encourages a healthy vascular network and tumor growth increases, it sets the stage for metastasis.

German scientists evaluated whether cancer fatalities in women with previously untreated breast cancer were reduced using LMWH therapy. The study showed that breast cancer patients receiving LMWH, compared to women receiving unfractionated heparin, had a lower rate of mortality during the first 650 days following surgery. The survival advantage was evidenced after even a short course of therapy (von Tempelhoff et al. 2000). In another study of 300 breast cancer patients, none of the trial participants developed metastasis while receiving anticoagulant therapy although 37 (12.3%) died from the disease (Wellness Directory of Minnesota 2002).

Similar advantages were evidenced among small cell lung cancer patients undergoing anticoagulant therapy in union with conventional treatments. When anticoagulants were a part of the program, subjects enjoyed a better prognosis, that is, greater numbers of complete responses, longer median survival, as well as better survival rates at 1, 2, and 3 years compared to patients denied treatment (Lebeau et al. 1994 ; ). See the following references, however ( however, see also Zacharski et al. 1984, 1987; Chahinian et al. 1989).

How to Implement Step Six

Ascertain if you are in a hypercoagulable state by having your blood tested for prothrombin time (PT), partial thromboplastin time (PTT), and D-dimers. A hypercoagulable state is suggested if the shortening of the PT and PTT are seen in conjunction with elevation of D-dimers ( see table on laboratory tests for hypercoagulability ).

If there is any evidence of a hypercoagulable (prethrombotic) state, ask your physician to prescribe the appropriate individualized dose of low-molecular-weight heparin (LMWH). Repeat the prothrombin blood test every 2 weeks to guard against overcoagulation. If you cannot afford LMWH, ask that lower-cost Coumadin be prescribed instead.

Step Seven: Maintaining Bone Integrity

How to Implement Step Seven
Some types of cancer (breast and prostate) have a proclivity to metastasize to the bone (Hohl et al. 1995; Wang et al. 2000). The result may be bone pain, which also may be associated with weakening of the bone and an increased risk of fractures (Spivak 1994; Caro et al. 2001).

Patients with prostate cancer have been found to have a very high incidence of osteoporosis or osteopenia even before the use of therapies that lower the male hormone testosterone (Cazzola 2000). In settings such as prostate cancer, when excessive bone loss is occurring, there is a release of bone-derived growth factors, such as TGF-beta - 1, which stimulate the prostate cancer cells to grow further (Samuels et al. 1975; Dunst et al. 1999). In turn, prostate cancer cells elaborate substances such as interleukin-6 (IL-6), which has as one of its main effects the further breakdown of bone (Cafagna et al. 1997; Mousa 2002). Thus, a vicious cycle results: bone breakdown, the stimulation of prostate cancer cell growth, and the production of interleukin IL -6 and other cell products, which leads to further bone breakdown ( see Figure 3 ).

The intravenous (IV) or oral administration of any of the drugs called bisphosphonates, such as Aredia (IV), Zometa (IV), and Fosamax or Actonel (oral), can be used to stop this vicious cycle. Such agents stop excessive bone breakdown (resorption) and favor bone formation (Zacharski et al. 1984; Zacharski 1987; Chahinian et al. 1989; von Templehoff et al. 2000). Administration of bisphosphonates should be accompanied by an adequate intake of a bone supplement that supplies all raw materials to make healthy bone. These include calcium, magnesium, boron, silica, and vitamin D.

The problem that prostate and breast cancer patients face is that bisphosphonate therapy is approved for treatment only after cancer cells have metastasized to the bone and become clinically apparent by a nuclear medicine bone scan. If bisphosphonates were administered to those with certain types of cancers, the risk of bone metastasis could be significantly reduced (Zurborn et al. 1982; Kohli et al. 2002). The Life Extension Foundation recommended bisphosphonate drugs (similar to those mentioned above) for certain types of cancer patients more than a decade ago. For many cancer patients, it would be ideal to continue bisphosphonate drug therapy a year or longer. Insurance companies, however, do not pay for bisphosphonates until after the cancer has metastasized to the bone.

Maintaining bone integrity may inhibit the growth of a wide range of cancers. Even when bone is broken down as a result of normal aging, the release of growth factors, such as interleukin IL -6 and transforming growth factor, can fuel tumor cell propagation.

Bisphosphonate class drugs, along with the appropriate mineral supplements and exercise to stimulate bone formation, can help to maintain bone integrity and, thus, save the lives of cancer patients.

The Life Extension Foundation strongly advises that the status of bone integrity should be evaluated periodically by means of a quantitative computerized tomography bone mineral density study called QCT. At the very least, this should be done annually. We prefer to use the QCT scan over the D E XA since the QCT is not falsely affected by arthritis or calcifications in blood vessels that are commonly seen in men and women in their 50s and over. It is fairly common to see patients with a normal D E XA scan and yet the QCT will be blatantly abnormal.

QCT sites possibly near you can be found via Mindways, Inc. at (877) 646-3929 or Image Analysis at (800) 548-4849.

Tests that assess bone breakdown are inexpensive and involve a random urine collection obtained in the morning at the time of the second voided specimen. One such highly accurate test of bone resorption is called DPD (deoxypyridinoline). This test provides information on excessive bone breakdown (resorption).

The deoxypyridinoline (DPD) cross links urine test can be ordered through the Life Extension Foundation by calling 1-800-208-3444.

How to implement step SEVEN

• If you have a type of cancer with a proclivity to metastasize to the bone (breast or prostate), ask your physician for a bisphosphonate drug before evidence of bone metastasis occurs. An oral bisphosphonate drug to consider is Actonel in the high dose of 30 mg twice a week. Alternatively, Fosamax can be used at a dose of 70 mg once a week. These agents should be taken on an empty stomach at least 1 hour and optimally 2 hours before breakfast. Some people experience gastroesophageal side effects from oral bisphosphonate drug therapy and prefer administration directly into the vein. An IV-administered bisphosphonate drug such as Aredia may be administered monthly beginning at 30 mg the first month, 60 mg the second month, and working up to 90 mg for subsequent months. Alternatively, Zometa can be given at a dose of 4 mg intravenously over 15 minutes every 3-4 weeks. When taking a bisphosphonate drug, it is important to take a wide array of bone-protecting supplements such as calcium, magnesium, zinc, manganese, and vitamin D3. Six capsules a day of a product called Bone Assure provides optimal potencies of bone-protecting nutrients.

• Because excessive bone breakdown releases growth factors into the bloodstream that can fuel cancer cell growth, the DPD urine test should be done every 60-90 days to detect bone loss. A QCT bone density scan should be done annually. If either of these tests reveals bone loss, ask your physician to initiate bisphosphonate drug therapy. Every cancer patient should take a bone-protecting supplement such as Bone Assure to protect against excess bone deterioration.

Cancer Treatment: The Critical Factors-4

noreply@blogger.com (Kishen) — Wed, 20 Feb 2008 10:54:00 +0000

Step Eight: Inhibiting Angiogenesis

How To Implement Step Eight
Angiogenesis, the growth of new vessels from preexisting blood vessels, is critical during fetal development but occurs minimally in healthy adults. Exceptions occur during wound healing, in inflammation, following a myocardial infarction, in female reproductive organs, and in pathologic conditions such as cancer (Shammas et al. 1993; Suh 2000).

Angiogenesis is a strictly controlled process in the healthy, adult human body, a process regulated by endogenous angiogenic promoters and inhibitors. Dr. Judah Folkman, the father of the angiogenesis theory of cancer, explains: "Blood vessel growth is controlled by a balancing of opposing factors. A tilt in favor of stimulators over inhibitors might be what trips the lever and begins the process of tumor angiogenesis."

According to the National Cancer Institute, solid tumors cannot grow beyond the size of a pinhead, that is, 1-2 cubic mm, without inducing the formation of new blood vessels to supply the nutritional needs of the tumor. Since rapid vascularization and tumor growth appear to occur concurrently, interrupting the vascular growth cycle is paramount to overcoming the malignancy.

Tumor angiogenesis results from a cascade of molecular and cellular events, usually initiated by the release of angiogenic growth factors. At a critical phase in the growth of a tumor, the tumor sends out signals to nearby endothelial cells to activate new blood vessel growth. The pro - angiogenic growth factors diffuse in the direction of preexisting blood vessels, encouraging development (Folkman 1992 b ; Folkman et al. 1992 a ).

Various agents are known to activate endothelial cell growth, including angiogenin, estrogen, interleukin-8, fibroblast growth factors (both acidic and basic), prostaglandin E2, tumor necrosis factor, granulocyte colony-stimulating factor, and VEGF. VEGF and basic fibroblast growth factors are expressed by many tumors and appear particularly important to tumor development and angiogenesis (NIH/NCI 1998)

A number of substances from orthodox and natural pharmacology (angiostatin, endostatin, interferons, interleukin-2, curcumin, green tea, lactoferrin, N-acetyl-cysteine (NAC), resveratrol, grape seed-skin extract, retinoic acid (vitamin A), and vitamin D) are anti - angiogenic in nature ( to read more about natural products with an anti - angiogenesis profile, please turn to the Cancer Adjuvant Therapy protocol). Endostatin, a fragment of collagen XVIII, and angiostatin, a fragment of plasminogen involved in the coagulation process, have produced remarkable results in animal models.

Anti-angiogenesis drugs approved by the FDA to consider include Avastatin® and thalidomide.

How to implement step Eight

There are clinical trials using other anti-angiogenesis agents. Call (800) 422-6237 or log on to www.cancer.gov/clinicaltrials to find out if you are eligible to participate.
In the Cancer Adjuvant Therapy protocol of this book, there are nutrients that have demonstrated potential antiangiogenesis effects such as green tea extract and curcumin. Refer to the Cancer Adjuvant Therapy protocol for information and dosing recommendations.

SUMMARY

1)Step One

2)Step Two

3)Step Three

4)Step Four

5)Step Five

6)Step Six

7)Step Seven

8)Step Eight

Implementing The Eight Steps
This protocol has described therapies that a leading-edge oncologist can prescribe to improve the odds of long-term survival and possible cure.

The fundamental message is to have your oncologist thoroughly assess the individual characteristics of your tumor, your blood system, and available treatments. Based on this evaluation, patients can interact with their oncologists to determine what therapies may work synergistically with standard conventional treatments.

The objective of this multimodality approach is to attack tumor cells where they are most vulnerable. The primary determining factor in choosing the specific drugs is finding the various tumor cell and blood tests recommended in this protocol, along with historical statistical data that can help ascertain how your tumor will respond to specific therapies.

The following summary is a succinct reiteration of the eight approaches discussed in this protocol:

Step One: Evaluating the Molecular Biology of the Tumor Cell Population

How to implement: Make certain your surgeon sends a specimen of your tumor to IMPATH (Telephone: (800) 447-5816, website: www.impath.com ) for immunohistochemistry testing, using the contact information just provided. You may have to pay out-of-pocket for this test.

Step Two: Analyzing the Patient's Living Tumor Cells to

Determine Sensitivity or Resistance to Chemotherapy

How to implement: Get in touch with Rational Therapeutics (Telephone: (562) 989-6455, website: www.rationaltherapeutics.com) using the contact information provided so that your surgeon can follow the precise instructions required to send a living specimen of your tumor for chemosensitivity testing. It is important that your surgeon carefully coordinate with Rational Therapeutics in order to ensure your cells arrive in a viable condition. You may have to pay for this test yourself because insurance may not reimburse you for it.

Step Three: Protecting Against Anemia

How to implement: If your hemoglobin or hematocrit levels are not in the optimal ranges, ask your physician to prescribe an individualized dose of Procrit.

In order for Procrit to effectively boost red blood cell production, it is essential that your body have adequate iron stores. Even if you have adequate iron stores prior to Procrit therapy, the rapid production of red blood cells induced by Procrit may deplete iron stores. Anyone using Procrit should have periodic assessment of their iron stores by means of a serum ferritin level. If less than 200, a soluble transferrin receptor (sTfR) level should be obtained. If evidence of iron deficiency is found, your physician will consider iron supplementation after ruling out excessive blood loss due to a variety of causes.

Dietary supplements that can help protect against anemia due to other causes include folic acid (800 mcg/day), vitamin B12 (500 mcg/day), and melatonin (3-10 mg/day, at night) (Vaziri et al. 1996; Herrera et al 2001).

Step Four: Inhibiting the COX-2 Enzyme

How to implement: Ask your physician to prescribe one of the following COX-2 inhibiting drugs:

Lodine XL, 1000 mg once daily, or
Celebrex, 100-200 mg every 12 hours, or

Step Five: Suppressing Ras Oncogene Expression

How to implement: Ask your physician to prescribe one of the following statin drugs to inhibit the activity of Ras oncogenes:

Lovastatin, 40 mg twice daily, or
Zocor, 40 mg twice daily, or
Pravachol, 40 mg once daily
Note: These statin drugs can produce toxic effects in a minority of patients. Physician oversight and monthly blood tests to evaluate liver function are suggested.

In addition to statin drug therapy, consider supplementing with the following nutrients to further suppress the expression of Ras oncogenes:

Fish Oil Capsules: 8-12 capsules of Mega EPA/DHA w/Sesame Lignans per day.
Green Tea Extract: two-three 725 mg capsules daily.
Garlic Extract: 3 tablets daily with meals.

Step Six: Correcting Coagulation Abnormalities

How to implement: Ascertain if you are in a hypercoagulable (prethrombotic) state by having your blood tested for prothrombin (PT), partial thromboplastin time (PTT), and D-dimers. A prethrombotic state is indicated by a shortening of PT and/or PTT and an increase in D-dimers.

If there is any evidence of a prethrombotic state, ask your physician to prescribe the appropriate individualized dose of LMWH. If you cannot afford LMWH, ask that lower-cost Coumadin be prescribed instead. Anticoagulation requires significant patient education and monitoring of laboratory tests to minimize the risks of hemorrhage due to overanticoagulation. As in all biological systems, a balance must be established if health is to be restored.

Step Seven: Maintaining Bone Integrity

How to implement: If you have a type of cancer with a proclivity to metastasize to the bone (breast or prostate), ask your physician for a bisphosphonate drug before evidence of bony metastasis occurs. An oral bisphosphonate drug to consider is Actonel at a dose of 30 mg twice a week or Fosamax at a dose of 70 mg once a week. Either drug must be taken at least 1 hour before breakfast and with water only. Some people experience gastroesophageal side effects from oral bisphosphonate drug therapy and prefer administration directly into the vein. An IV-administered bisphosphonate drug such as Aredia may be administered monthly beginning at 30 mg the first month, 60 mg the second month, and working up to 90 mg for subsequent months.

A newer, more potent IV bisphosphonate, Zometa, can be used at a starting dose of 1-2 mg for the first dose and then 4 mg every 3-4 weeks thereafter. Zometa is routinely given as a 15-minute infusion. When taking a bisphosphonate drug, it is important to take a wide array of bone-protecting supplements such as calcium, magnesium, zinc, manganese, and vitamin D3. Six capsules a day of a product called Bone Restore provide optimal potencies of bone protecting nutrients. Some physicians also prescribe a synthetic vitamin D such as Calcitriol (Rocaltrol) or Hectorol.

Since excessive bone breakdown releases growth factors into the bloodstream that can fuel cancer cell growth, the DPD urine test (which can be ordered through the Life Extension Foundation (800)-208-3444) should be done every 60-90 days to detect bone loss. A QCT bone density scan should be done annually. If either of these tests reveals bone loss, ask your physician to initiate bisphosphonate drug therapy. Every cancer patient should take a bone-protecting supplement like Bone Restoree to protect against excess bone deterioration.

Step Eight: Inhibiting Angiogenesis

How to implement: There are a number of clinical trials using anti - angiogenesis agents such as angiostatin. Call (800) 422-6237 or log on to www.cancer.gov/clinicaltrials to find out if you are eligible to participate. In the Cancer Adjuvant Therapy protocol of this book, there are nutrients that have demonstrated potential antiangiogenesis effects such as green tea extract and curcumin. Refer to the Cancer Adjuvant Therapy protocol for information and dosing recommendations. The drug Avastatin® is now approved, and may be considered as an anti-angiogenesis therapy against a variety of cancers.

Implementing the Eight Steps
As can be seen from the eight-step list, a patient might be prescribed several treatments in addition to standard therapy for the purposes of inhibiting the COX-2 enzyme, suppressing the r R as oncogene, protecting against anemia/hypercoagulation, inhibiting blood vessel growth in the tumor (angiogenesis), maintaining bone integrity, and so forth.

While these therapies are substantiated in the published scientific literature and most are part of mainstream medicine, few cancer patients are benefiting from this knowledge.

If you are determined to wage modern medicine against your tumor, some or all of these therapies should be considered, depending on your individual situation. The reader is advised to refer to the Cancer Adjuvant Therapy protocol for additional guidance. If standard therapies such as radiation or chemotherapy are being contemplated , please refer to the Cancer Surgery, Cancer Radiation and/or Cancer Chemotherapy protocols.

Product availability

Super EPA/DHA w/Sesame Lignans, Mega Green Tea Extract, Kyolic® Reserve Garlic Extract and melatonin, folic acid, vitamin B12, and Bone Restore are available by ordering on line

Staying Informed

The information published in this protocol is only as current as the day the manuscript was sent to the printer. This protocol raises many issues that are subject to change as new data emerge. Furthermore, cancer is still a disease with unacceptably high mortality rates, and none of our suggested regimens can guarantee a cure.

The Life Extension Foundation is constantly uncovering information to provide to cancer patients. A special website has been established for the purpose of updating patients on new findings that directly pertain to the published cancer protocols. Whenever Life Extension discovers information that may benefit cancer patients it will be posted on the website www.lefcancer.org.

Before utilizing the cancer protocols in this book, we suggest that you check www.lefcancer.org to see if any substantive changes have been made to the recommendations described in this protocol. Based on the sheer number of newly published findings, there could be significant alterations to the information you have just read.

Cancer Vaccines and Immunotherapy-1

noreply@blogger.com (Kishen) — Wed, 20 Feb 2008 10:43:00 +0000

Cancer immunotherapies, including cancer vaccines, are novel investigational cancer therapies. In contrast to chemotherapy and radiotherapy regimens that are often associated with severe side effects, cancer immunotherapy stimulates the body’s immune system and natural resistance to cancer, thus offering a gentler means of cancer treatment that is less damaging to the rest of the body. Surgery is generally (but not always) performed, prior to immunotherapy, to remove most of the tumor (Hanna MG, Jr. et al 2001; Jocham D et al 2004). Vaccination or immunotherapy prompts the immune system to kill residual cancer cells that persist after surgery and could result in the cancer recurring.

The status of the patient’s immune system is the key physiological factor affecting the outcome of cancer immunotherapy. However, each individual’s immune status is in turn affected by several factors (including age, tumor-induced and surgery-associated immunosuppression, and nutritional status) that need to be assessed, and some require continuous monitoring for the successful application of immunotherapeutic regimens. Immune cells play a central role in mediating the effects of immunotherapy, and specific nutritional supplements that enhance immune cell function can be effective in preparing patients for immunotherapy or vaccination (Malmberg KJ et al 2002).

Therapeutic cancer vaccines developed for melanoma, renal cell carcinoma, and colorectal cancer have shown benefits in phase III trials by extending the disease-free survival period (before relapse) and overall survival. In addition, several immunotherapy clinical trials have been performed for metastatic breast cancer and non-Hodgkin’s lymphoma.

The Immune System and Cancer
Evidence showing the role of the immune system in detecting and killing cancer cells has been available for some time (Richardson MA et al 1999; Wiemann B et al 1994; Hellstrom IE et al 1968; Oliver RT et al 1989; Penn I 1986, 1988; Vose BM et al 1985). This knowledge has been used in developing immunotherapies to bolster the immune system’s natural capacity to counteract cancer cells.

How Does the Immune System Detect Cancer Cells?
Cancer cells display abnormal proteins (antigens) on their surface, and the immune system can detect and destroy cancer cells because of these proteins (Knuth A et al 1991; Naftzger C et al 1991). (An antigen is a substance that causes the immune system to make a specific immune response.)

The immune system has an innate ability to resist cancer development; however, in most cases, the immune system fails due to a series of sophisticated strategies that tumor cells use to evade immune detection. These strategies range from methods designed to hide tumor cells, to active incapacitation of immune cells by tumor-produced agents that lower the immune system’s responses, which are known as immunosuppressive agents (Cordon-Cardo C et al 1991; Junker U et al 1996; Pantel K et al 1991; Ranges GE et al 1987; Sarris AH et al 1999; Staveley-O'Carroll K et al 1998). Therefore, a prerequisite to successful cancer immunotherapy is the implementation of strategies to boost the immune system’s natural resistance to cancer.

T cells and B cells (lymphocytes) are immune system cells responsible for what is known as specific immunity (Brodsky FM et al 1991; Janeway CA, Jr et al. 1994; Levine TP et al 1991). By contrast, other immune cells (for example, eosinophils, natural killer (NK) cells, and macrophages) generate non-specific responses to infections by bacteria and parasites (Klein E et al 1993; Mantovani A et al 1992). T cells and B cells respond only when they detect specific markers that identify infected cells (Brodsky FM et al 1991; Janeway CA, Jr et al. 1994; Levine TP et al 1991).

A Role for the Immune System in Cancer Control
The role of the immune system in counteracting the development of cancer was initially supported by individual clinical case reports. Groundbreaking work in the late 1800s by a New York surgeon, William Coley, noted that some cancer patients who were simultaneously suffering from bacterial infections had regression in their tumors (Richardson MA et al 1999; Wiemann B et al 1994). He concluded that, in trying to fight off the bacterial infection, the patients’ immune systems had become highly activated and that this had given them some resistance to the tumor. Coley later concocted a crude vaccine preparation, called “Coley’s toxins,” that was made up of killed bacteria. While some of Coley’s patients enjoyed complete tumor regression, the responses were somewhat varied and his work was initially regarded with skepticism (Richardson MA et al 1999; Wiemann B et al 1994).

However, more recent research has produced a considerable body of scientific evidence documenting the immune system’s role in controlling cancer growth. For example, cancer occurs more frequently in individuals with weakened immune systems (Oliver RT et al 1992; Penn I 1986, 1988). In addition, some types of cancer undergo spontaneous regression, again adding weight to the notion that the immune system is naturally able to fight cancer (Oliver RT et al 1989). Furthermore, cancer patients often have specific antibodies (proteins that bind to antigens) circulating in their blood, again demonstrating that the immune system can detect tumor cells and mount a specific response (Hellstrom IE et al 1968) that also involves specific T cells, or T lymphocytes (Itoh K et al 1988; Muul LM et al 1987; Vose BM et al 1985).

Why Do Tumors Escape Immune Detection?
Under normal circumstances, all cells display segments of their proteins on their surface. Upon infection with a viral or bacterial agent, cells display on their surface sample segments from these foreign proteins (Brodsky FM et al 1991; Janeway CA, Jr et al. 1994; Levine TP et al 1991). T cells and B cells patrolling the body for foreign invaders seek and destroy any cells that display these foreign proteins on their surface. These proteins are called antigens, substances that can stimulate a specific immune response or activity.

In cancer, the tumor cell also displays a sample of its abnormal proteins on its surface, which can signal the immune system that it is no longer a normal, healthy cell. These protein segments—either from proteins over-produced in the cancer cell or from viral or bacterial proteins that infected the cell and caused the cancer—act as red flags and attract the attention of T cells and B cells (Wang RF 1999). Tumor cells evade immune detection by failing to display protein segments (antigens) on their surface, thus, in effect, hiding from immune cells (Cordon-Cardo C et al 1991; Pantel K et al 1991).

In aggressive cases, tumor cells can also evade immune detection by producing agents that reduce immune cell activity (Junker U et al 1996; Ranges GE et al 1987; Sarris AH et al 1999; Staveley-O'Carroll K et al 1998). Alternatively, the immune system may not be able to cope with a tumor’s rapid growth if the initial immune response to the tumor is not sufficient to reject or control it completely. Despite the immune system’s natural ability to detect and kill cancer cells, in most circumstances the immune system fails to control tumor growth. The goal of immunotherapy is to specifically target tumor antigens as a means of killing cancer cells (Knuth A et al 1991; Naftzger C et al 1991). Table 1 shows some tumor antigens (substances that stimulate an immune response) that form the basis of cancer vaccines in clinical studies.

What You Have Learned So Far
The immune system has a natural ability to detect and kill cancer cells; however, tumors that develop in the presence of a competent immune system evolve complex immune-evasion strategies to avoid destruction and removal of the tumor.
Not all tumors are naturally programmed to alert the immune system and mount an immune response, due to loss or coverage of cell surface antigens.
The goal of immunotherapy is to produce anti-tumor effects through activation of the patient’s immune system or through patient supplementation with natural substances, and thus to ultimately destroy the cancer.
Therapeutic cancer vaccines are used to boost the immune system as a way to control established cancer. Preventive cancer vaccines are used to vaccinate people against infectious agents known to cause cancer.
Surgery is often performed to remove most of the tumor before cancer immunotherapy or vaccination, which should then eliminate any persisting tumor cells that would grow or spread.
For each individual, immune system status is the key factor that will affect the success of cancer vaccine therapy.
Cancer patients preparing to undergo immunotherapy should ensure optimal immune system function through adequate nutrition and the use of nutritional supplements.

Types of Immunotherapy
Monoclonal Antibody (mAb). Monoclonal antibodies target specific tumor antigens, such as tumor growth factors, and can enhance the immune response against cancer. Many monoclonal antibodies (for example, Herceptin®) have other anti-cancer activities such as biological response modification and signal transduction inhibition, which slow or prevent cancer growth signals. Monoclonal antibody therapies for various cancers are outlined in Table 1.

Herceptin®. Approximately 25 percent to 30 percent of breast cancer patients exhibit an excess of the protein HER-2/neu (a member of the human epidermal growth factor receptor family), which can be measured in the blood via its extracellular domain (Hayes DF et al 2001). HER2/neu-positive breast cancer cells are associated with aggressive disease and decreased overall survival.

Herceptin® (trastuzumab) is the first monoclonal antibody that "targets" the HER2/neu protein on human cancer cells. This drug is approved for the treatment of metastatic breast cancers that are HER2-positive (Luftner D et al 2005) and provides a median overall response rate of 23 percent (Vogel CL et al 2001). Herceptin® attaches to HER2 present on cancer cells, thus preventing cancer proliferation and inducing cancer cell death (apoptosis). Herceptin® is also a biological response modifier and a mediator of antibody-dependent cell-mediated cytotoxicity via natural killer cells and monocytes (Baselga J et al 2001). Because Herceptin® damages the heart, an echocardiogram and complete blood count are usually monitored.

Cytokine Therapy
Cytokines such as interleukin-2 and the interferons (alpha, beta, and gamma) have been used clinically in cancer patients.

Interleukin-2 (IL-2). Interleukin-2 (IL-2) is naturally produced in the body by T cells after activation by antigen, but it can also be given as a drug (immunotherapy). Clinical use of IL-2 counteracts the immunodeficiency state caused by the tumor and conventional treatments. IL-2 does not directly affect cancer cells; rather, its effects result from its ability to stimulate immune reactions in the body. Used as immunotherapy for metastatic melanoma (7 percent complete response) and kidney cancer (9 percent complete response), IL-2 can mediate durable regression (that is, prevent cancer recurrence) (Rosenberg SA 2001). However, a significant side effect of IL-2 therapy is vascular leak syndrome (Baluna R et al 1997).

Various interleukin-2 dosing schedules and combinations with interferon alpha (IFN-alpha) have been tested in patients with advanced melanoma. Response rates reported with IL-2 alone or in combination with IFN-alpha vary from 10 percent to 41 percent, with a small but significant proportion of durable responses (Keilholz U et al 2002a). High-dose interleukin-2 immunotherapy is useful in patients with metastatic renal cell carcinoma, and even in highly selected dialysis patients (Brusky JP et al 2006; McDermott DF et al 2005). IL-2 combined with thalidomide can produce durable, active responses in patients with metastatic renal cell carcinoma (Amato RJ et al 2006).

Treatment of skin and soft-tissue melanoma metastases by injection of IL-2 directly into the tumors resulted in complete response in 62.5 percent of patients (the longest remission lasting 38 months) and partial response in 21 percent of patients (Radny P et al 2003).

Preoperative immunotherapy with interleukin-2 in pancreatic cancer patients achieved a positive effect on postoperative complications and increased two-year survival (33 percent in the treated group compared to 10 percent in the control group) (Angelini C et al 2006).

Interferon. Interferons (IFNs) are produced naturally in the body in response to viral infections, but they can also be given as a drug (immunotherapy). Interferon alfa has immunomodulatory, anti-angiogenic, anti-proliferative, and anti-tumor properties (Iqbal Ahmed CM et al 2003) against leukemia (CLL, CML, and HCL) (Bonifazi F et al 2001; Guilhot F et al 2004) and lymphoma (Jonasch E et al 2001), and, in combination with other anti-cancer agents, against breast cancer (Nicolini A et al 2005). Adjuvant high-dose interferon alfa-2b is approved for all melanoma patients with intermediate- and high-risk disease, but it benefits only 20 percent to 30 percent of patients and its use is limited due to its toxicity (Tsao H et al 2004). A favorable outcome in patients with high-risk melanoma treated with adjuvant interferon alfa-2b appears to depend on the development of autoimmunity during or after treatment (Gogas H et al 2006). Adverse reactions to interferon therapy include flu-like symptoms of fever, chills, fatigue, and muscle aches.

Gene Therapy. Cancer gene therapy has provided preliminary results through phase I clinical trials. In advanced breast cancer or melanoma patients, gene therapy with MetXia-P450 (a novel recombinant retroviral vector that encodes the human cytochrome P450 type 2B6 gene) was safe, well tolerated, and produced an anti-tumor response, suggesting it merits further clinical assessment (Braybrooke JP et al 2005).

In mesothelioma patients, gene therapy with intrapleural adenoviral (Ad) vector encoding the herpes simplex virus thymidine kinase "suicide gene" (Ad.HSVtk/ganciclovir) was safe, well tolerated, and resulted in long-term durable responses in two patients, which may have been due to induction of anti-tumor immune responses. The researchers hypothesize that approaches aiming to enhance the immune effects of adenoviral gene transfer (that is, with the use of cytokines) may lead to increased numbers of therapeutic responses in otherwise untreatable pleural (lung) cancers (Sterman DH et al 2005).

Cancer Vaccines
In contrast to chemotherapy and radiotherapy, cancer vaccines are not associated with any serious side effects. Cancer vaccines and the immune system have the ability to mount and amplify antigen-specific anti-tumor responses (Sprent J et al 2001, 2002). These activities cannot be produced by chemotherapy or radiotherapy. Once the immune system generates T cells specific for a particular antigen, a group of “memory cells” that remember this antigen will remain in the body, and in the event of a second threat from that antigen, an immune response will be mounted much faster than the first one (Sprent J et al 2001, 2002).

Phase I clinical studies assessing the safety of cancer vaccines have shown them to be associated with no toxicities outside reports of mild flu-like symptoms, irritation at the vaccination site, and fatigue (Carr A et al 2003; Soiffer R et al 2003; Woodson EM et al 2004).

Preventive cancer vaccines are being developed as a means of preventing cancers caused by chronic viral, bacterial, and parasitic infections that are associated with up to 20 percent of all cancer cases, including cervical and liver cancers (Bhopale GM et al 2004; Herrera LA et al 2005).

Therapeutic cancer vaccines. Most cancer vaccines are therapeutic, in that they are intended to treat existing cancer rather than to prevent it (Dalgleish AG 2004; Hellstrom KE et al 2003). The cancer patient would initially undergo surgery to remove most of the tumor. Vaccination would then be undertaken to generate a specific immune response capable of clearing any residual cancer, thus preventing relapse (Hellstrom KE et al 2003; Hodge JW 1996; Reinartz S et al 2004) and extending the period of remission or survival in the patient.

The manner in which therapeutic cancer vaccines are used in the clinic is summarized in Table 3.

Stage 1
Cancer diagnosis

Stage 2
Surgery to remove accessible tumor

Stage 3
Vaccination

Stage 4
Patient monitoring

Cancer Vaccines and Immunotherapy-2

noreply@blogger.com (Kishen) — Wed, 20 Feb 2008 10:36:00 +0000

How Cancer Vaccines Work

The immune system is capable of both specific and non-specific responses against tumor cells. However, successful cancer vaccines must stimulate the immune system to act largely in a tumor-specific fashion.

A successful cancer vaccine would present tumor antigens to immune cells and activate CD4 (also known as helper T cells) and CD8 T cells (also known as cytotoxic or killer T cells). CD8 T cells become activated and directly kill the tumor cells (Janeway CA, Jr et al. 1994), while CD4 T cells are indirectly activated by dendritic cells and macrophages (Grohmann U et al 1998) to produce messengers (cytokines) that boost CD8 (killer) T-cell activity (Seder RA et al 1994).

B cells are immune cells that produce antibodies to human tumors (Disis ML et al 1994; Sorokine I et al 1991). Cancer immunotherapy that generates a good antibody response produces a better clinical outcome for the patient (Hoover HC, Jr et al. 1993; Mittelman A et al 1994).

The immune system also has a range of non-specific tools that can be stimulated into action by cancer vaccines, including natural killer cells and macrophages (Klein E et al 1993; Mantovani A et al 1992).

Types of Cancer Vaccines

Therapeutic cancer vaccines are classified into two main categories:

Whole cell vaccines: self (autologous), donor (allogenic), or dendritic cell
Synthetic protein antigens (soluble vaccines).
Whole cell vaccines use inactivated whole tumor cells as the vaccine given to the cancer patient. These inactivated tumor cells have a range of abnormal tumor proteins to which the patient’s immune cells respond by generating an anti-tumor immune response and attacking any cancer cells persisting after surgery. Using the whole tumor cell as a vaccine eliminates the problem of having to identify the various key antigens, most of which remain unknown.

Self Versus Donor (Autologous Versus Allogenic) Vaccines. The tumor cells used in whole cell vaccines can be derived from the patient’s own (self or autologous) tumor (Lahn M et al 1997) after it has been removed during surgery. Alternatively, these tumor cells can be obtained from a tumor sample removed from another individual (donor or allogenic) with the same cancer type (Chan AD et al 1998).

Dendritic Cell Vaccines. Dendritic cells are finger-like cells that pick up proteins from tumor cells (antigens) or invading organisms (bacteria, viruses, and parasites), and process and present them to young lymphocytes (Avigan D 1999; Hajek R et al 2000), which then initiate immune responses (Bodey B et al 2004; Vieweg J et al 2005).

Dendritic cell-based cancer vaccines, prepared from blood samples taken from the cancer patient (Hajek R et al 2000; Tjoa BA et al 2000), have been used to treat prostate cancer (Murphy G et al 1996), colorectal cancer (Chen W et al 2000), non-small cell lung cancer (Hirschowitz EA et al 2004), breast cancer (Allan CP et al 2004), and B-cell cancers (Adema GJ et al 2005; Ragde H et al 2004; Reichardt VL et al 2004). Dendritic cells pulsed with tumor cells (lysate) are partially efficient in triggering effective anti-melanoma immunity in stage IV patients (Escobar A et al 2005). Dendritic cell cancer vaccines are safe and well tolerated in humans.

Synthetic protein antigens are mass-produced synthetic versions of abnormal proteins displayed by tumors, and can generate immune responses capable of destroying cells in the body that display these antigens (Schulz M et al 1991). This type of vaccination is given to patients with immune system boosters (adjuvants) or other messengers to further enhance immune system activity (Schulz M et al 1991). Dendritic cells, which coordinate the function of immune cells, are often used as a vehicle to deliver these synthetic proteins to the immune system (Liu KJ et al 2004).

Clinical Studies Using Different Types of Cancer Vaccines

Melanoma. Melanoma is perhaps the cancer that has been the central focus of cancer vaccine research.

Synthetic Proteins. Proteins that have been identified as tumor antigens for melanoma include tyrosinase, MART-1 (also known as Melan A), gp100 (Jager E et al 1996), and products of the MAGE gene family (Gaugler B et al 1994; Van Der BP et al 1991). These proteins are not unique to melanoma cells, but are normal body proteins that are overproduced by melanoma cells and therefore called melanoma-associated antigens (Jager E et al 1996).

Vaccines made up of MART-1, tyrosinase, and gp100 synthetic proteins were successfully used to vaccinate melanoma patients and induced objective tumor regression in all patients (Jager E et al 1996). Other melanoma cancer vaccines have used synthetic MAGE proteins and have been noted to cause complete tumor regression in some patients (Marchand M et al 1999; Weber JS et al 1999).

Gangliosides (GM2, GM3, GD2, and GD3). Gangliosides are cell surface molecules that are abnormally displayed or overproduced by all tumors. They are linked to an increased ability of tumors to spread, or metastasize (Bitton RJ et al 2002; Fredman P et al 2003), and to poor clinical outcomes (Hakomori S 2001). Therefore, they represent targets for vaccine-generated immune responses. Indeed, vaccination with purified gangliosides, prepared from laboratory-grown melanoma cells, showed that they were capable of generating an immune response in melanoma patients (Tai T et al 1985).

Another clinical study has shown that vaccination of melanoma patients (after surgery to remove skin, lymph node, and other metastases) with a concoction containing GM3, GD3, GM2, and GD2 generated strong immune responses that were associated with increased disease-free survival (Portoukalian J et al 1991). The successful use of ganglioside cancer vaccines is supported by improved survival of stage III melanoma patients who where treated with a GM2 vaccine following surgery to remove most of the tumor (Livingston PO et al 1994).

Heat Shock Proteins (HSPs). Heat shock proteins are abundant cell proteins known as molecular chaperones because they guide the assembly and eventual loading of proteins, prepared within the cell, into the external structures on which they are displayed to immune cells guarding the body (Przepiorka D et al 1998; Ren W et al 2004). Heat shock proteins from tumor cells therefore contain the perfect sample of tumor antigens for that particular tumor type and have proved effective as a basis for cancer vaccines, particularly for melanoma and renal cell carcinoma (Hoos A et al 2003; Huang XF et al 2003; Oki Y et al 2004).

A Phase III trial was performed with 300 patients with stage IV melanoma using heat shock protein (gp96)-peptide complexes derived from the patients’ own tumors (given once weekly for the first four weeks and every other week thereafter). The patients with skin and lymph node disease survived an estimated median of 626 days compared to 383 days in the control group (Srivastava PK 2006).

Non-Hodgkin’s Lymphoma. Other vaccine approaches (for example, anti-idiotype) have demonstrated clinical benefit in the treatment of non-Hodgkin’s lymphoma (Bendandi M 2004; Caspar CB et al 1997; Rodriguez CM et al 2004) and are being assessed for multiple myeloma treatment (Titzer S et al 2000).

Pancreatic, Lung, Colorectal, Breast, and Ovarian Cancers. Carcinoembryonic antigen (CEA). CEA is a glycoprotein (a protein attached to sugar groups) that is normally produced by cells only during fetal development. However, it is grossly overproduced by almost 50 percent of all human cancers (Huang EH et al 2002; Marshall J 2003; Ullenhag GJ et al 2004), including colon, rectal, breast, ovarian, lung, pancreatic, and gastrointestinal tract cancers (Marshall J 2003; Morse MA et al 1999). Indeed, CEA can be detected in blood samples from cancer patients and is therefore used to monitor cancer therapy and progression (Marshall J 2003).

CEA loaded into dendritic cells and used as a cancer vaccine generated (CD4 and CD8) anti-tumor responses that were associated with disease stabilization (Berinstein NL 2002; Liu KJ et al 2004; Ueda Y et al 2004). CEA delivered to the cancer patient’s immune system (by a poxvirus) brought about disease stabilization in up to 37 percent of treated patients (Berinstein NL 2002). A CEA-based vaccine (ALVAC-CEA) developed using vaccinia virus has also been shown to be safe in humans and capable of generating specific anti-tumor immune responses (Marshall J 2003).

Breast and Ovarian Cancer. Sialyl-Tn (STn). Sialyl-Tn is a carbohydrate that is overproduced by several types of cancer cells, including breast, ovarian, colorectal, gastric, and pancreatic cancer cells (Holmberg LA et al 2004). As a result, this tumor-associated antigen is a good candidate for a therapeutic vaccine for these cancers.

A sialyl-Tn-based cancer vaccine called Theratope®, developed by a Canadian company (Biomira Inc.), is effective in the treatment of breast and ovarian cancer patients (Holmberg LA et al 2000, 2001). In a clinical setting, this vaccine was safe and was associated with reduced risk of relapse (longer remission period) or death (Holmberg LA et al 2000, 2001).

Enhancing Immunotherapy Responses

Boosters for the Immune System. Tumor cells used as vaccine are often manipulated to produce and secrete messengers such as interleukin-2 and granulocyte macrophage colony stimulating factor (GM-CSF), which directly activate immune cells (Dranoff G et al 1997; Osanto S et al 2000; Sallusto F et al 1994). In the clinical setting, vaccines are often administered with immune system boosters (adjuvants), such as bacillus Calmette-Guerin (BCG) and DETOX, to make the immune system more responsive to the presented antigens (Harris JE et al 2000; Knutson KL 2002; Sondak VK et al 2003).

Cancer Vaccines in Clinical Trials (Phase III)

A variety of candidate cancer vaccines showed promise in early (phase I and II) clinical studies (Murphy G et al 1996; Weber JS et al 1999). However, most failed to translate this success to the larger phase III studies that examine the impact of the vaccine-induced immune response on the period of remission (or disease stabilization) enjoyed by the patient, and on overall survival. The former is also referred to as disease-free survival or progression-free survival (Kaufman HL 2005). Consequently, when making a balanced assessment of cancer vaccines as a treatment option, it is important to focus on vaccines that have reached phase III studies. With the exception of lung cancer, therapeutic cancer vaccines have progressed to phase III clinical studies for all the major cancer types.

Renal Cell Carcinoma. A cancer vaccine for renal cell carcinoma has recently been tested in a phase III setting using autologous (self-donated) cancer cells and lysates (prepared by breaking down cancer cells) (Doehn C et al 2003; Jocham D et al 2004). This study involved 558 renal cell carcinoma patients who were vaccinated (six injections in the skin once a month) with the autologous tumor cell vaccine after surgery (Jocham D et al 2004). After 70 months of follow-up, the progression-free survival of vaccinated patients was 67.8 percent compared to 59.3 percent in non-vaccinated patients (Jocham D et al 2004). These results support the use of this renal cell carcinoma vaccine following surgery (removal of a kidney) in renal cell carcinoma cases not larger than 2.5 cm (Jocham D et al 2004).

Melanoma. Several types of cancer vaccines for melanoma have progressed to phase III clinical assessment, including ganglioside and whole cell (allogenic and autologous)-based vaccines (Hsueh EC et al 1998; Knutson KL 2002; Sondak VK et al 2003).

A whole cell melanoma vaccine (CancerVax/Canvaxin) has been tested in a phase III clinical trial by comparing the outcomes of 935 vaccinated patients (after surgery) and 667 non-vaccinated patients (Hsueh EC et al 1998; Morton DL et al 2002). The five-year overall survival of vaccinated patients was 49 percent compared to 37 percent in the non-vaccinated group of patients (Morton DL et al 2002).

Melacine, a melanoma cancer vaccine prepared from allogenic (donor) tumor cells, has also progressed to phase III clinical evaluation (Sondak VK et al 2003; Sosman JA et al 2003). This vaccine is given to patients with an immunological booster and has been shown to confer vaccinated patients with survival benefits (Sondak VK et al 2003).

A ganglioside-based vaccine, developed for melanoma treatment and administered with an adjuvant, was initially shown to induce antibodies that could clear melanoma cells (Knutson KL 2002). However, evaluation of this vaccine in phase III studies produced somewhat disappointing results, as a standard treatment of high-dose interferon therapy generated better results in relation to relapse-free survival and overall survival (Kirkwood JM et al 2001).

Colon Cancer. Cancer vaccines for colorectal cancer that have progressed to phase III clinical studies have focused on the use of CEA proteins and whole cell autologous (self) tumor cells (Hanna MG, Jr. et al 2001; Harris JE et al 2000; von MM 2005). An autologous tumor cell vaccine used in combination with BCG as an adjuvant (immune booster) has been tested in a study of 412 stage II and III colorectal cancer patients who had undergone surgery to remove most of the tumor (Harris JE et al 2000). Vaccinations were given four weeks after surgery and patients who received this treatment showed benefits in disease-free survival and overall survival (Harris JE et al 2000).

Breast Cancer. The vaccine Theratope® (manufactured by Biomira Inc.), based on the tumor-associated antigen sialyl-Tn, is currently being evaluated in a large phase III study of 1000 metastatic breast cancer patients (Holmberg LA et al 2004; Ibrahim NK et al 2003). Findings from this study have yet to be published.

Note: Biomira Inc., a pharmaceutical company, does not treat patients. However, Biomira provides vaccines to physicians at various cancer clinics in North America and Europe where government-approved clinical trials are ongoing. The vaccines are provided only to physicians who are currently involved in vaccine exploration and who have extensive experience with these agents. To speak to Biomira's Medical Information Assistant, call 1-877-234-0444, ext. 500.

Prostate Cancer. Provenge®, a dendritic cell-based vaccine for prostate cancer, is being evaluated in phase III clinical studies by the US company Dendreon (Rini BI 2002). This vaccine involves loading synthetic prostate cancer cell proteins (recombinant protein antigens) into the patient’s dendritic cells (grown in the laboratory) and administering them as vaccine. Clinical studies have shown that this vaccine has activity in patients with hormone-independent prostate cancer (Schellhammer PF et al 2005). More recent media reports (NewsRX.com) have indicated that this vaccine improved survival in men with advanced prostate cancer in phase III studies; however, these results have not yet been published in the scientific literature.

Blood (Hematological) Cancers. The National Cancer Institute is currently overseeing a large phase III clinical study using an idiotype-based vaccine given to patients with follicular lymphoma after they have undergone chemotherapy (Kwak LW 2003).

Factors Affecting Immune System Status

Age. While cancer is more common in the elderly (Holmes FF et al 1991), immune strength gradually declines with age and can pose a problem for the successful use of immunotherapy in the elderly (Ginaldi L et al 1999; Pawelec G et al 2002). Although age-related decline in immune status is a natural feature of the immune system, it is also aggravated by lifestyle factors such as diet (Lesourd B et al 1999). Therefore, nutritional supplements to boost immune function may have even more significance in elderly cancer patients than in young adults.

Tumor-Induced and Surgery-Associated Immunosuppression. Two types of immunosuppression affect the successful outcome of immunotherapy: immunosuppression from the tumor and that associated with surgery to remove the tumor. Tumor-induced immunosuppression, due to the production of immunosuppressive factors by cancer cells, is overcome by surgical removal of the tumor mass (Morton DL 1978) and thus creates an environment in which immune cells can better respond to immunotherapy. However, the process of surgery and the associated use of particular anesthetic and analgesic drugs also dampens immune cell function, again reducing the effectiveness of any immunotherapy used (Vallejo R et al 2003). It is recommended that anesthetic and analgesic drugs be carefully selected to minimize immunosuppression, and that patients prepare for surgery by optimizing nutritional and immune status (Vallejo A et al 2002).

Nutritional Status. The production of immune-suppressing (immunosuppressive) agents by cancer cells presents a significant obstacle to cancer immunotherapy (Junker U et al 1996; Sarris AH et al 1999). Excessive production of pro-inflammatory cytokines and reactive oxygen species may damage the immune system, resulting in adverse immunotherapy outcome and cancer progression.

Therefore, nutritional supplements that improve the function of key immune cells will affect the efficacy of immunotherapy and could also be used to prepare patients for immunotherapy (Malmberg KJ et al 2002).

The impact of nutrition on the function of immune cells that play a key role in the efficacy of cancer immunotherapy is well established (Calder PC et al 2002b; Chandra RK 1999). Studies of cancer patients demonstrate that nutritional supplements can play a role in restoring immune status depleted by cancer and surgery to normal levels that would be more responsive to immunotherapy treatment (Malmberg KJ et al 2002).

Nutritional Therapy
Although the direct effect of nutritional supplements on the effectiveness of cancer immunotherapy has yet to be clinically evaluated, the impact of nutrition, particularly micronutrients, on immune cell function (that is, immunonutrition) is central to the success of any cancer treatment (Calder PC et al 2002b; Chandra RK 1999). Several nutrients are able to modulate immune response and counteract inflammatory processes. Zinc, omega-3 fatty acids, and glutamine all act differently to modulate immune response, but all appear to have the potential to protect against cancer progression (Grimble RF 2001).

Immunonutrition has gained recognition as an adjuvant cancer therapy and should be an integral part of cancer immunotherapy, particularly against cancers associated with chronic inflammation (Philpott M et al 2004), as it has beneficial effects on patient outcomes, enhances the immune response, and improves the prognosis of cancer patients (Chermesh I et al 2004).

Cells of the immune system that are essential for the success of cancer vaccines include:

1)Dendritic cells

2)CD4 T cells (lymphocytes)

3)CD8 T cells (lymphocytes)

4)B cells (lymphocytes)

5)Natural killer (NK) cells

6)Macrophages

7)Neutrophils.

Micronutrients that have been established as being essential to the optimal function of these immune cells include zinc, vitamins C and E, folic acid, and glutamine (Calder PC et al 1999; Calder PC et al 2002b).

Zinc. Zinc supplements improve immune cell function (Ibs KH et al 2003; Prasad AS et al 2002). Indeed, diets lacking in zinc are linked to reduced CD4 and CD8 T-cell function (Chandra RK 1999). While deficiencies in zinc also compromise the function of natural killer cells, macrophages, and neutrophils (Ibs KH et al 2003), this impairment of the immune system can be reversed by dietary zinc supplements (Chandra RK 1999; Ibs KH et al 2003). Zinc supplements should, however, be carefully monitored, as excessive intake (over 100 mg per day) is counterproductive and reverses any benefits seen with the suggested doses of 20 to 50 mg per day (Calder PC et al 2002b; Hercberg S et al 1998; Kohn S et al 2000).

Zinc supplements of 50 mg a day improve the structure of Langerhans’ cells (a type of dendritic cell found in the skin epidermis) by endowing them with a more dendritic (or finger-like) structure that improves their mobility and thus their ability to pick up antigens and transport them to lymphocytes (Kohn S et al 2000).

Cancer Vaccines and Immunotherapy-3

noreply@blogger.com (Kishen) — Wed, 20 Feb 2008 10:22:00 +0000

Antioxidants (Vitamins C and E). Supplementing the diet of colorectal cancer patients with high doses of vitamin E (750 mg per day) for two weeks increased lymphocyte numbers and improved the lymphocytes’ ability to produce messengers (interleukin-2 and interferon gamma) that are associated with the type of immune response required to destroy cancer cells (Malmberg KJ et al 2002). Therefore, high-dose vitamin E supplements may be considered to support the use of cancer vaccines and immunotherapy. Long-term supplementation at lower doses of 100 to 200 mg a day has improved immune function (Calder PC et al 2002b; Pallast EG et al 1999).

Vitamin C supplements also improve immune function and protect lymphocytes against damage (Lenton KJ et al 2003; Schneider M et al 2001).

Folic Acid. Deficiencies in folic acid impair the immune system by reducing the ability of CD8 T cells to divide and increase in number (Courtemanche C et al 2004). In addition, low levels of folic acid lead to genetic instability in lymphocytes and increased cell death, or apoptosis (Courtemanche C et al 2004; Duthie SJ et al 1998). However, the impairment of lymphocyte function can be restored by folic acid supplements (Courtemanche C et al 2004).

Vitamin B12. Vitamin B12 plays a key role in immune function, as B12 deficiencies in humans lead to low numbers of CD8 T cells and impair the activity of natural killer cells (Tamura J et al 1999). These cells are essential for the cytotoxic arm of the immune system, which in turn is essential for destroying cancer cells. Supplementing with B12 restores CD8 T-cell numbers and natural killer cell activity (Tamura J et al 1999).

Vitamin B6. Deficiencies in vitamin B6 impair the immune system and are associated with a reduced ability of lymphocytes to produce messengers (cytokines) required for sustained immune activation (Doke S et al 1998).

Selenium. Selenium supplements (100 mcg a day) improve immune cell function by increasing the cells’ ability to produce messengers (cytokines) associated with the type of immune responses required to clear tumor cells (Broome CS et al 2004).

Glutamine. Glutamine supplements (30 grams a day) sustain immune cell function (Yoshida S et al 1998). Clinical studies have shown glutamine supplements to be particularly effective in counteracting immunosuppression associated with surgery (Calder PC et al 1999; O'Riordain MG et al 1996), and thus to be of benefit to patients undergoing an immunotherapy/vaccination regimen after surgical removal of the tumor.

Ginseng. The medicinal herb ginseng improves immune cell function (Larsen MW et al 2004). Of particular importance to the successful use of cancer vaccines is the recently reported ability of ginseng products to drive the development of dendritic cells that are essential for successful cancer vaccination (Takei M et al 2004).

Melatonin. Melatonin hormone supplements (20 mg a day, at bedtime) improve lymphocyte function and have been tested in clinical studies of blood cancers (El-Sokkary GH et al 2003; Lissoni P et al 2000).

Garlic. Garlic extracts boost the activity of natural killer cells against tumor cells (Hassan ZM et al 2003).

Mushroom Extracts (AHCC). Extracts from various mushrooms boost immune cell function (Kidd PM 2000). In particular, active hexose correlated compound (AHCC) improves the function of natural killer cells and confers benefits to liver cancer patients after surgical removal of the tumor (Matsui Y et al 2002).

Omega-3 Fatty Acids. The ratio of omega-3 and omega-6 polyunsaturated fatty acids (PUFA) modulates the inflammatory response. Inflammatory cells typically contain high levels of arachidonic acid and low levels of omega-3 PUFA (Calder PC 2002, 2002a). Increasing omega-3 fatty acid intake antagonizes arachidonic acid levels in inflammatory cell membranes, and decreases the amount of arachidonic acid that is available for production of pro-inflammatory arachidonic acid-derived mediators (Calder PC 2003).

Omega-3 PUFA may have indirect immunomodulatory activity mediated through tumor necrosis factor-alpha (TNF-a) and nuclear factor-kappa beta (NF-?B) production (Babcock TA et al 2002). Administration of omega-3 fatty acids before and after surgery (prior to immunotherapy) may have a favorable effect on outcome by lowering the magnitude of inflammatory response and preventing immune suppression (Weiss G et al 2002). Fatty fish such as salmon, mackerel, tuna, and herring are good sources of long-chain omega-3 PUFA.

Tracking Your Progress

Monthly Blood Tests. A range of blood tests and other diagnostic procedures can be used to monitor the effectiveness of cancer immunotherapy. Results from these tests provide information required to assess the effectiveness of this new treatment modality.

The following tests are essential for monitoring the effectiveness of immunotherapy.

Tumor antigen profile: determining the antigens (abnormal proteins) produced by each tumor is important in assessing the use of cancer vaccines or other forms of immunotherapy as a treatment choice. Tumor antigen profile should also be monitored during immunotherapy, as the tumor can develop variations that stop the display of these antigens as a means of escaping detection.

Immune cell function: the function of lymphocytes is monitored during cancer immunotherapy by a variety of techniques. These include proliferation assays to assess their ability to expand in response to activation, and cell-kill (cytotoxic) assays to assess the ability of CD8 lymphocytes to kill tumor cells (Clay TM et al 2001; Keilholz U et al 2002b; Lyerly HK 2003).

PSA: prostate-specific antigen can be detected in blood samples from prostate cancer patients and has been established as a reliable marker for disease progression or patient response to therapy (Coetzee LJ et al 1996; Kiper A et al 2005). Prostate cancer patients treated with cancer vaccines in clinical studies showed reductions in their PSA levels (Noguchi M et al 2004b; Noguchi M et al 2004a).

CEA: monitoring of serum levels of carcinoembryonic antigen is recommended for colorectal cancer patients as a marker for disease progression or response to treatment (Sunga AY et al 2005).

Angiogenesis markers: angiogenesis is the process of forming new blood vessels, which is essential for tumors to spread to other parts of the body. Increased levels of the angiogenic factor vascular endothelial growth factor (VEGF) in the blood of cancer patients serves as a robust indicator of disease progression and can be used to monitor response to treatment with cancer immunotherapy (Bonfanti A et al 2000; Brostjan C et al 2003; Poon RT et al 2001). Circulating endothelial cells, detectable in the blood of cancer patients, are increased and have also been established as another indicator of disease progression (Beerepoot LV et al 2004; Mancuso P et al 2003).

Growth factors: serum levels of the growth factors pleiotrophin (PTN) and fibroblast growth factor-2 (FGF-2) are increased in prostate cancer patients and can be used as a marker for disease progression or response to therapy (Aigner A et al 2003).

Immunosuppressive agents: levels of tumor-produced immunosuppressive agents (for example, interleukin-10 (IL-10) (Sarris AH et al 1999) and transforming growth factor-beta (TGF-ß) (Junker U et al 1996)) can be detected in patients’ serum and used to check for disease progression or response to treatment.

X-rays and scans: can be used to monitor the response or progression of disease during cancer immunotherapy.

Physical examination: regular physical examinations can detect changes in body mass and enlarged lymph nodes that may be signs of disease progression (Sunga AY et al 2005).
For More Information
Cancer immunotherapy patients may wish to read the following chapters and design a program that addresses the full range of their cancer problems:

a)Complementary Adjuvant Cancer Therapies

b)Cancer Surgery

c)Immune System Enhancement

d)Blood Disorders

e)Medical Testing.

The National Cancer Institute Clinical Trials Database lists and describes ongoing clinical trials at different locations throughout the US. This can be accessed at the website http://cancertrials.nci.nih.gov/ or by calling the Cancer Information Service at 1-800-4-CANCER.

The American Cancer Society, 1-800-ACS-2345.

Life Extension Foundation Recommendations

Patients should ask their physicians for assistance in obtaining information on ongoing cancer vaccine and other immunotherapy clinical studies, and the criteria for subject enrollment and participation. Immunotherapy patients should consult their physicians before starting to use any nutritional supplements while receiving treatment. In addition, if using nutritional supplements, they should ask their physicians for assistance in ensuring the implementation of blood tests and diagnostic procedures that are essential in monitoring the effectiveness of any adjuvant therapy for cancer.

Some guidelines for using nutritional supplements with immune-boosting cancer therapies include:

1)Zinc—20 to 50 milligrams (mg) daily (Hercberg S et al 1998; Kohn S et al 2000)

2)Vitamin C—120 mg daily (Hercberg S et al 1998)

3)Vitamin E—800 international units (IU) of d-alpha tocopheryl succinate daily for two weeks (Malmberg KJ et al 2002); 400 IU daily for long-term use (Calder PC et al 2002b; Pallast EG et al 1999)

4)Folic acid—800 micrograms (mcg) daily (Fenech M 2001)

5)Vitamin B12—7 mcg daily (Fenech M 2001)

6)Vitamin B6—2.1 to 2.7 mg (one B-complex capsule) daily (Kwak HK et al 2002)

7)Selenium—100 mcg daily (Broome CS et al 2004)

8)Glutamine—30 grams (g) daily (Yoshida S et al 1998)

9)Ginseng, panax—100 mg daily (Anderson GD et al 2003)

10)Melatonin—20 mg daily, at bedtime (Lissoni P et al 2000)

11)Garlic—250 mg daily (Dhawan V et al 2004)

12)Mushroom extract—active hexose correlated compound: 3 g daily (Matsui Y et al 2002)

13)Fish oil—containing EPA: 4.7 g daily (Kew S et al 2004).

Note that most cancer patients take higher doses of vitamin C (2000 to 20,000 mg/day), selenium (200 to 400 mcg/day), vitamin B6 (100 to 750 mg/day), and vitamin B12 (100 to 300 mcg/day). These doses are considerably higher than the doses used in the studies cited above.

Blood Test Availability

Tests for PSA, CEA, selenium, vitamin B12, and folate serum levels are available via Life Extension/National Diagnostics, Inc., and may be ordered on line.
Tumor antigen profile can be determined via Genzyme Genetics (http://www.genzymegenetics.com) and may be ordered by a physician by calling 1-800-966-4440.

Tests for immune cell function, serum growth factor levels, and immunosuppressive agents (IL-10) are available at UCLA’s Jonsson Comprehensive Cancer Center (http://www.cancer.mednet.ucla.edu/).

X-rays, scans, and physical examinations can be arranged through your physician.

Cancer Vaccines and Immunotherapies Safety Caveats

An aggressive program of dietary supplementation should not be launched without the supervision of a qualified physician. Several of the nutrients suggested in this protocol may have adverse effects. These include:

EPA/DHA

Consult your doctor before taking EPA/DHA if you take warfarin (Coumadin). Taking EPA/DHA with warfarin may increase the risk of bleeding.
Discontinue using EPA/DHA 2 weeks before any surgical procedure.

Folic acid

Consult your doctor before taking folic acid if you have a vitamin B12 deficiency.
Daily doses of more than 1 milligram of folic acid can precipitate or exacerbate the neurological damage caused by a vitamin B12 deficiency.

Garlic

Garlic has blood-thinning, anticlotting properties.
Discontinue using garlic before any surgical procedure.
Garlic can cause headache, muscle pain, fatigue, vertigo, watery eyes, asthma, and gastrointestinal symptoms such as nausea and diarrhea.
Ingesting large amounts of garlic can cause bad breath and body odor.

Ginseng

Consult your doctor before taking ginseng if you have high blood pressure. Overuse of ginseng can increase blood pressure.
Consult your doctor before taking ginseng if you take nonsteroidal anti-inflammatory drugs (NSAIDs) and/or warfarin (Coumadin). Taking NSAIDs or warfarin with ginseng can increase the risk of bleeding.
Consult your doctor before taking ginseng if you have diabetes. Taking ginseng can cause an extreme drop in your blood glucose level. Ginseng can cause breast pain, vaginal bleeding after menopause, insomnia, headaches, and nosebleeds.

L-Glutamine

Consult your doctor before taking L-glutamine if you have kidney failure or liver failure.
L-glutamine can cause gastrointestinal symptoms such as nausea and diarrhea.

Melatonin

Do not take melatonin if you are depressed.
Do not take high doses of melatonin if you are trying to conceive. High doses of melatonin have been shown to inhibit ovulation.
Melatonin can cause morning grogginess, a feeling of having a hangover or a “heavy head,” or gastrointestinal symptoms such as nausea and diarrhea.
Selenium

High doses of selenium (1000 micrograms or more daily) for prolonged periods may cause adverse reactions.
High doses of selenium taken for prolonged periods may cause chronic selenium poisoning. Symptoms include loss of hair and nails or brittle hair and nails.
Selenium can cause rash, breath that smells like garlic, fatigue, irritability, and nausea and vomiting.

Vitamin B6

Individuals who are being treated with levodopa without taking carbidopa at the same time should avoid doses of 5 milligrams or greater daily of vitamin B6.

Vitamin B12 (cyanocobalamin)

Do not take cyanocobalamin if you have Leber's optic atrophy.

Vitamin C

a)Do not take vitamin C if you have a history of kidney stones or of kidney insufficiency (defined as having a serum creatine level greater than 2 milligrams per deciliter and/or a creatinine clearance less than 30 milliliters per minute.

b)Consult your doctor before taking large amounts of vitamin C if you have hemochromatosis, thalassemia, sideroblastic anemia, sickle cell anemia, or erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency. You can experience iron overload if you have one of these conditions and use large amounts of vitamin C.

Vitamin E
a)Consult your doctor before taking vitamin E if you take warfarin (Coumadin).

b)Consult your doctor before taking high doses of vitamin E if you have a vitamin K deficiency or a history of liver failure.

c)Consult your doctor before taking vitamin E if you have a history of any bleeding disorder such as peptic ulcers, hemorrhagic stroke, or hemophilia.

e)Discontinue using vitamin E 1 month before any surgical procedure.

Zinc

a)High doses of zinc (above 30 milligrams daily) can cause adverse reactions.

b)Zinc can cause a metallic taste, headache, drowsiness, and gastrointestinal symptoms such as nausea and diarrhea.

c)High doses of zinc can lead to copper deficiency and hypochromic microcytic anemia secondary to zinc-induced copper deficiency.

d)High doses of zinc may suppress the immune system.

Cancer Chemotherapy-1

noreply@blogger.com (Kishen) — Wed, 20 Feb 2008 10:13:00 +0000

1)Choosing The Best Chemotherapy Drugs

2)Making Chemotherapy Drugs Work More Effectively

3)Going Beyond Chemotherapy

4)Mitigation Of Chemotherapy Side Effects

5)Anti-Nausea Drugs For Chemotherapy Patients

6)Natural Approaches To Enhancing Chemotherapy Efficancy

7)Summary

Cancer cells are everything we would like healthy cells to be: They quickly adapt to toxic environments, they readily alter themselves to assure their continued survival, and they utilize biologic mechanisms to promote cellular immortality. All of these factors make cancer an extremely difficult disease to treat.

Chemotherapy drugs have a high rate of failure because they usually kill only specific types of cancer cells within a tumor or the cancer cells mutate and become resistant to the chemotherapy. Cancer chemotherapy could save more lives if the latest scientific findings were incorporated into clinical medicine.

What concerns us is that respected cancer journals are publishing articles that identify safer and more effective treatment regimens, yet few oncologists are incorporating these synergistic methods into their clinical practice. Cancer patients often suffer through chemotherapy sessions that do not integrate the latest scientific findings. Our objective is to provide the patient with more options to discuss with their oncologist and to bring about multimodality approaches to improve the probability of a successful outcome.

It is impossible to design a single chemotherapy protocol that is effective against all types of cancer. The oncologist might need to administer several chemotherapy drugs at varying doses because tumor cells express survival factors with a wide degree of individual cell variability. This protocol conveys the findings from published scientific studies so that a cancer patient will have a logical basis to augment the effects of chemotherapy and also reduce the potential for side effects.

How Does Chemotherapy Work?

According to the National Cancer Institute, almost all normal cells grow and die in a controlled way through a process called apoptosis. Cancer cells, on the other hand, keep dividing and forming more cells without a control mechanism to induce normal apoptosis.

Anticancer drugs destroy cancer cells by stopping them from growing or dividing at one or more points in their growth cycle. Chemotherapy may consist of one or several cytotoxic drugs that kill cells by one or more mechanisms. The chemotherapy regimen chosen by most conventional oncologists is based on the type of cancer being treated. As you will read later in this protocol, there are factors other than the type of cancer that can be used to determine the ideal chemotherapy drugs that should be used to treat an individual patient.

The goal of chemotherapy is to shrink primary tumors, slow the tumor growth, and kill cancer cells that may have spread (metastasized) to other parts of the body from the original, primary tumor. However, chemotherapy kills both cancer cells and healthy normal cells. Oncologists try to minimize damage to normal cells and to enhance the cell killing (cytotoxic) effect on cancer cells. Too often, unfortunately, this delicate balance is not achieved.

Clinical studies show that for certain types of cancer chemotherapy prolongs survival and increases the percentage of patients achieving a remission. A partial remission is defined as 50% or greater reduction in the measurable parameters of tumor growth as may be found on physical examination, radiologic study, or by biomarker levels from a blood or urine test. A complete remission is defined as complete disappearance of all such manifestations of disease. The goal of all oncologists is to strive for a complete remission that lasts a long time--a durable complete remission, or CR. Unfortunately, the vast majority of remissions that are achieved are partial remissions. Too often, these are measured in weeks to months and not in years. Some types of cancer do not show any meaningful response to chemotherapy.

CHOOSING THE BEST CHEMOTHERAPY DRUGS TO KILL YOUR TUMOR

A)Protecting Against Anemia

B)Inhibiting the COX-2 Enzyme

C)Controlling Cancer Cell Growth

D)Combining a COX-2 Inhibitor with a Statin Drug and Chemotherapy

E)Should Antioxidants Be Taken at the Same Time as Chemotherapy

It is highly desirable to know what drugs are effective against your particular cancer cells before these toxic agents are systemically administered to your body. A company called Rational Therapeutics, Inc., performs chemosensitivity tests on living specimens of your cancer cells to determine the optimal combination of chemotherapy drugs.

Dr. Robert Nagourney, a prominent hematologist/oncologist, founded Rational Therapeutics, Inc., in 1993. Rational Therapeutics pioneers cancer therapies that are specifically tailored for each individual patient. They are a leader in individualized cancer strategies. With no economic ties to outside healthcare organizations, recommendations are made without financial or scientific prejudice.

Rational Therapeutics develops and provides cancer therapy recommendations that have been designed scientifically for each patient. Following the collection of living cancer cells obtained at the time of biopsy or surgery, Rational Therapeutics performs an Ex-Vivo Apoptotic (EVA) assay on your tumor sample to measure drug activity (sensitivity and resistance). This will determine exactly which drug(s) will be most effective for you. They then make a treatment recommendation. The treatment program developed through this approach is known as assay-directed therapy.

At present, medical oncologists, according to fixed schedules, prescribe chemotherapy. These schedules are standardized drug regimens that correspond to specific cancers by type or diagnosis. These schedules, developed over many years of clinical trials, assign patients to the drugs for which they have the greatest statistical probability of response.

Patients with cancers that exhibit multidrug resistance will likely receive treatments that are wrong for them. A failed attempt at chemotherapy is detrimental to the physical and emotional well being of patients, is financially burdensome, and may preclude further effective therapies.

Rational Therapeutics' EVA assay uses your living tumor cells to determine which drug or drug combination induces apoptosis in the laboratory. Each patient is highly individualized with regard to sensitivity to chemotherapy drugs. A patient's responsiveness to chemotherapy is as unique as their fingerprints.

Rational Therapeutics, leading the way in custom-tailored, assay-directed therapy, provides personal cancer strategies based on the tumor response in the laboratory. This eliminates much of the guesswork prior to the patient undergoing the potentially toxic side effects of chemotherapy regimens that could prove to be of little value against their cancer. Rational Therapeutics may be contacted at:

Rational Therapeutics, Inc.
750 East 29th Street
Long Beach, CA 90806
Telephone: (562) 989-6455; Fax: (562) 989-8160
Web site: www.rationaltherapeutics.com

In addition to the EVA chemosensitivity testing, we advocate immunohistochemistry testing of your tumor to provide additional data that will assist in making treatment decisions. The importance of the immunohistochemistry test is described in the Cancer Treatment: The Critical Factors protocol. The immunohistochemistry test can be done if your physician sends a specimen of your tumor to a specialty laboratory called Impath (www.impath.com). Impath can be reached by calling (800) 447-5816. Impath also performs chemosensitivity testing of living tumors (fresh specimens). Because many chemotherapy patients' primary tumors were previously removed or irradiated, Impath can perform the immunohistochemistry test with a frozen or parraffin-preserved tissue sample that is accessible through the pathology laboratory that examined your previous tumor(s).

Protecting Against Anemia
The importance of maintaining or enhancing the oxygen-carrying capacity of blood cannot be overemphasized. Blood oxygen-carrying capacity may be the single most important factor in determining whether chemotherapy is successful.

In response to a low-oxygen environment, cancer cells send out growth signals that result in increased angiogenesis (blood vessel growth into the tumor). Oxygen deprivation not only induces angiogenesis, but also causes cancer cells to express additional survival factors that make them highly resistant to the toxic effects of chemotherapy.

It is an established fact that a low-oxygen environment (hypoxia) promotes tumor growth. If nothing else in this protocol is followed, correcting a hypoxic state could vastly enhance the odds of long-term survival.

The first step in correcting hypoxia is to guard against anemia. Anemia is common in cancer patients, and the result is that less oxygen is delivered to the tumor, that is, hypoxia occurs. The importance of avoiding anemia is well established in scientific literature. A study was conducted to systematically review and obtain an estimate of the effect of anemia on the survival of cancer patients. This study found that the increased risk of mortality in cancer patients who were anemic was an astounding 65% (Caro et al. 2001)!

Chemotherapy often induces anemia that then exacerbates hypoxia in the tumor. The best way of evaluating blood oxygen-carrying capacity is to measure hematocrit and hemoglobin levels. These are standard components of the complete blood count (CBC) test that should be routinely performed in all cancer patients.

Since cancer cells thrive in a hypoxic environment, the cancer patient's hematocrit and hemoglobin should be maintained in the upper one-third of normal range prior to the initiation of chemotherapy. Table 1 describes the optimal ranges of hematocrit and hemoglobin for cancer patients.

Hypoxia (low oxygen) promotes tumor growth by inducing angiogenesis and causing cancer cells to express survival factors that interfere with the ability of chemotherapy to kill them. Chemotherapy drugs are supposed to promote apoptosis. In a hypoxic environment, however, cancer cells develop survival mechanisms that protect them against apoptosis.

There are nutrients that help improve anemic states, but any cancer patient who does not have his or her hematocrit and hemoglobin in the upper one-third of the normal range (as described in Table 1) should consider the drug Procrit (or Epogen) to achieve such levels. Procrit is a natural erythropoietin that stimulates the production of red blood cells. There is also a new long-acting erythropoietin agent approved by the FDA called Aranesp, which allows dosing every 2 weeks instead of weekly injections.

If an oncologist fails to address anemia, the patients should assume the role of advocate, demanding that attention be paid to the quality of his blood counts.

A problem that cancer patients will encounter is that oncologists normally view low blood counts as normal in cancer patients and are reluctant to prescribe Procrit unless anemia is demonstrated. Because Procrit is an expensive drug, most insurance companies refuse to pay for it unless a cancer patient is severely anemic (<10g/dL). Remember, anemia means hematocrit and hemoglobin are below the low-normal laboratory reference ranges. A cancer patient, on the other hand, should aim to have levels in the high upper-third range of normal for hematocrit and hemoglobin. Some insurance companies will not pay for Procrit until hematocrit levels are at least 20% below the lowest normal range. Is it any wonder that chemotherapy fails for so many cancer patients?

Since most insurance companies will not pay for Procrit for the purpose of boosting hematocrit and hemoglobin to the upper ranges of normal, patients may have to pay for this drug as an out-of-pocket expense. The first hurdle is convincing the oncologist to prescribe Procrit. The good news is that most cancer patients may only need Procrit for a few months, so the high cost does not have to be borne indefinitely.

The Life Extension Foundation has located pharmacies that will sell Procrit at lower prices. If your insurance company will not reimburse for this costly drug, call (800) 544-4440 for referrals to pharmacies that may charge less than conventional retail prices.

Inhibiting the COX-2 Enzyme
Some progressive oncologists are prescribing cyclooxygenase-2 (COX-2) inhibitor drugs along with chemotherapy to improve the odds of successful treatment. COX-2 is an enzyme that many types of cancers use in order to propagate. COX-2 and its byproducts such as prostaglandin E2 (PGE2) have been shown to help fuel the growth of cancers such as colon, pancreas, estrogen-negative breast, prostate, bladder, and lung cancer.

Drugs that inhibit the cyclooxygenase enzyme are known as COX-2 inhibitors. Celebrex and Vioxx are two popular COX-2 inhibitors. Both Celebrex and Vioxx are nonsteroidal anti-inflammatory drugs (NSAIDs) that are usually prescribed to treat the symptoms of rheumatoid arthritis and osteoarthritis. There appears to be more research about Celebrex in the treatment of cancer than Vioxx.

Since chemotherapy can cause gastrointestinal bleeding, careful physician monitoring is needed when using a COX-2 inhibiting drug such as Celebrex. Caution is urged for those with known kidney disease, poor heart-lung function, liver disease, or susceptibility to stress-induced ulcers. The protocol entitled Cancer Treatment: The Critical Factors has a detailed description of the connection between COX-2 and cancer and why inhibiting the COX-2 enzyme is so important in treating many cancers.

In 1996, Life Extension recommended that most cancer patients take a COX-2 inhibiting drug because of solid evidence that cancer cells use the COX-2 enzyme to sustain their rapid division. In 1996, Americans had to import a COX-2 inhibitor named nimesulid from other countries because this class of drug was not widely available in the United States.

Experiments in laboratory animals suggest that drugs such as Celebrex could help cure cancer, especially if combined with chemotherapy or radiation (Hsueh et al. 1999; Pyo et al. 2001; Swamy et al. 2002). There are 100 separate cancer studies involving COX-2 inhibitors going on worldwide at this time.

Doctors are predicting that COX-2 inhibiting drugs may become standard therapy in 5-10 years. There was adequate evidence in 1996, however, to recommend COX-2 inhibiting drugs available to cancer patients. There are three potent COX-2 inhibiting drugs on the American marketplace. You may ask your physician to prescribe one of the following COX-2 inhibitors:

Lodine XL, 1000 mg once a day or
Celebrex, 200-400 mg every 12 hours or