Get Herbs

Finding The Root Of All Evil

2013-04-13T16:21:00.000-04:00

It can be a difficult and extremely frustrating process finding the cause of your many, varied and seemingly unconnected symptoms. And it will take time, some curiosity, objectivity and some serious cash. Tests. Tests cost money, appointments cost money, data costs money, time off work costs money (opportunity cost at least for you economists). But without finding the reason you have become unable to adequately digest typical foods there is a good possibility of recurrence, in fact, a probability or certainty of recurrence.

Here's my quick list and I will update this as I come across more possible causes of digestive dysbiosis as I continue my research:

Gallbladder and liver congestion or other issues
Colon congestion
Hypochlorhydria (more likely a consequence rather than a cause)
Leaky Gut (for our purposes this can be a "cause" but it has its own causes we will explore)
Celiac disease
Hypothyroidism
Chronic diarrhea
Candidiasis (possibly a consequence rather than a cause)
Colitis (possibly a consequence rather than a cause)
Excessive and/or long term anti-biotic use
Diverticulitis (possibly a consequence)
Cancer
An episode of serious/extended digestive upset (dysentery, e coli, salmonella, giardiasis, etc)

Keep in mind I'm looking for cold, hard causes - not symptoms or consequences of dysbiosis. CAUSES. This is what your gastroenterologist is looking for when he innocently (or not so innocently) recommends for the millionth time that you get a colonoscopy/endoscopy (double). CAUSES. More often that not he doesn't find anything and then refers you to a nutritionist or dietitian since he claims he can no longer help you. OH how many times I've heard this sad, painful, frustrating story. How many deductibles have been wasted on endoscopies? Not to mention the prep will throw you off for a week and you'll have to take 1+ day off of work.

But that's the least of your worries. You need an enemy you can stare down and focus your ever-dwindling financial resources on destroying. Fortunately, all the causes I note above can be confirmed or denied with the following tests:

HIDC for gallbladder function
Endoscopy/colonoscopy for celiac, colitis and diverticulitis (also CT Scan for diverticulitis)
Genova Diagnostics GI Effects Microbial Ecology Profile for #5, #8, #11, #6
Genova Diagnostics Nutreval will help you find your deficiencies
Saliva analysis will be helpful in determining any adrenal insufficiencis or need for DHEA supplementation which is quite common in chronic fatigue-related health problems
Blood test for hypothyroidism

That's not that bad for finding the root cause(s) of your misery. The challenge will be creating a plan once you find the root cause of your digestive dysfunction. Most likely your plan will include multiple steps as you've probably screwed up multiple cycles in the process of living through months if not years of dysbiosis and malabsorption. For example, if you have hypochlorhydria that means you probably have SIBO, food intolerances, chronic diarrhea, insomnia, chronic fatigue, foggy thinking, memory issues, hypothyroidsim and even gallbladder issues and liver congestion issues. If you're walking you probably don't have acute liver issues since this is one of the most important organs in your body. Much to say, you'll have to attack each of those issues in a specific order until you can finally rid yourself of SIBO and your other symptoms by antibiotic or any effective means.

If I had to put ONE CAUSE at the top of the pyramid, well, I couldn't do it. But I could put TWO CAUSES at the top of the list: Thyroid/Adrenal Issues and Leaky Gut. If I could put THREE CAUSES all at the top of importance list it would be: Thyroid/Adrenal Issues, Episode of Extended Digestive Upset and Leaky Gut. If you take care of these, you will find that nearly all of your other symptoms will fall away (perhaps very slowly) by default. Until you take care of these three you will not heal. It is simply impossible to heal with these conditions lingering on in your body. In order: address your thyroid, address your adrenal issues, address your leaky gut. When you have done all these to your gut's satisfaction, your symptoms will either vanish or be 95% eliminated.

Let's address them one by one...

The liver and gallbladder are closely related. For our purposes, the liver produces bile and stores it in the gallbladder. The liver and gallbladder release the bile into the small intestine especially when fatty foods are eaten and this bile serves to enable digestion and absorption of nutrition as well as regulate bacteria and any sort of intruders such as parasites, viruses and pathogenic bacteria. For most of us, pathogenic bacteria are not the problem but bacteria are not well regulated when bile is not healthy or free-flowing and abundant. That's why typically the types of bacteria that overgrow are not pathogenic and therefore our body's immune response to that bacteria is confused at best. For example, Streptococcus and non-pathogenic E Coli. can overgrow and these strains are found in the nasal, oral, esophageal and intestinal tracts. So why would your immune system have an easy time regulating these strains when they are already typically present and have been all your life?

On an American diet which pays no attention to balance or food/liquid combinations and highly values fat, carbs and sugar the liver and gallbladder do not thrive. In fact, the American diet is just about the worst possible situation you can consistently throw your liver into. For some people, their liver finds a way and in the absence of any sort of upsetting event (giardia, dysentery, extended pathogenic infection, extended use of antibiotics, extended diarhhea, etc) things generally work out. I am not one of those people. I traveled abroad in high school and ended up with giardia on extended anti-biotics, never quite got better and continued to have daily diarhhea for 12 years before food intolerances and dysbiosis fully set in. That is exactly when I hit the books and dedicated most of my free time to uncovering the mysteries of a screwed up digestive system.

The liver/gallbladder needs to be flushed, cleaned and healed. See here for more info on how to do this. Initially this process takes about 2 months and after that just minimal maintenance is needed. Bile can coagulate and form soft or hard stones that get lodged in both your liver and gallbladder. If this coagulated bile stays there long enough it can start to become toxic and even get infected. When it gets toxic, you start releasing toxic bile into your small intestine which further irritates the lining of your gut, does not adequately do its job of aiding digestion or regulate bacteria and parasites. Can you see the many vicious cycles forming as we address more and more gut issues? Unless you flush and cleanse and heal your liver/gallbladder you will be continuing to release toxic bile into your intestines and further contributing to dysfunction and dysbiosis.

You'll soon see (if you haven't already) that there are no shortcuts with your body. Under the right conditions, given adequate time, your body will heal itself. Without the right conditions and the right amount of time, your body will not heal itself and will be driven further into dysfunction whether that process is slow or fast. If I could sum up this blog in one idea it would be the exploration of the details surrounding the conditions in which your body will heal itself. This is the central question. Why do all this? Life to the full. That's why.

The colon can build up residue and impacted fecal matter on its walls. This can also happen on the walls of the small intestine. This is a breeding ground for unwanted bacteria and parasites and since you do your absorbing of nutrition through the walls of the intestines, when they are blocked then obviously this inhibits absorption. This further contributes to dysfunction. Your colon will not cleanse itself to the extent that we're looking for and the liver doesn't have a chance if your colon is not cleansed first. See here for more info on how to go about this. This will only take about 10 days but requires 5 days of fasting which I was not able to do so I just did the colon cleanse during a liquid diet and separated my liquid food intake from the herbal cleanse intake by an hour or so and this seemed to work fine. This way, I still managed 1300 calories per day while colon cleansing. You may be surprised what comes out of you, or if you're not the sifting-through-your-own-feces type then you can simply trust that what you're doing is greatly aiding your cause.

Leaky gut is perhaps the most pernicious enemy in this whole ordeal. You've taken care of the colon. Wonderful. You're taken care of the liver/gallbladder combo. Great. Leaky gut may haunt the remainder of your recovery and will be the responsible party for setbacks, unexpected issues, random blow-ups. The problem with this entire digestive set-up is that you can't see any of the activity that is going on in your gut. The only thing you have to go on is other folks' experience, logic, a bit of science/nutrition and this inner intangible "feel good" barometer that, when properly calibrated, tells you when something is helping or hurting your healing process. Leaky gut refers to the propensity of your small intestine in particular to become perforated as the result of the dysbiosis, toxic bile, bacterial imbalance and parasites that find themselves deep-seated in your small intestine's ecosystem. When its perforated, your body responds with hypochlorhydria which further disables you from being able to digest your food fully. The perforations will also allow undigested food particles (cue gluten and other allergens) to enter your blood stream directly which tips off your immune system to react and label these allergens as intruders. Thus, you begin to react to things like wheat, gluten, onions, eggs, soy, lactose, anything really. Fortunately, these food intolerances are not allergies and can be dealt with simply by addressing the situation and creating conditions that allow the leaky gut to heal.

Again we focus on creating a situation in which your body can heal itself. The elements involved with healing the leaky gut include:

colon cleanse, liver cleanse, parasite cleanse
giving your system a rest by going on a liquids only diet for 1-2 weeks
eliminating ALL allergens while still nourishing your body adequately
listening to your gut and slowly only adding simple foods you can digest fully
incorporating fermented foods (veggies, yoghurt) into each meal
beef marrow bone broth with copious amounts of glutamine morning and evening
rest, stretching, breathing, general stress reduction (these attempt to enable general bodily healing)

Give your body enough time under these conditions and you will heal. If you don't, something else is still lingering at the root of your digestive dysfunction.

Your quest is a quest to feel as AMAZING as you possibly can. That makes it sound nice doesn't it? This quest may cost a lot of money, this quest may make you lose A LOT of weight, this quest may bring you to funny places where you are eating very funny things but this quest must be undertaken inasmuch as your body requires for your healing. In other words, you are not the decider of what it will take for your gut to heal. You are NOT in control of this. Sorry. Your gut is in the driver's seat. If it heals in a few months, wonderful. If it takes years then it takes years, but if you do not delve as deep as is required into the quest you will not be giving your body the conditions it needs to heal itself.

My quest has included a month of a liquid diet that cost me $12000+/year, multiple attempts and failures with various supplements, too many setbacks to count, extended periods of refusing to admit that my diet was not restrictive enough, months of worrying about my low weight and therefore hesitating to take the extreme measures required to cleanse my colon and liver. OH how I wish it was easier to heal my gut but it's just not. I had to say goodbye to eating at restaurants for 4 years straight. I had to say goodbye to scrambled eggs at one point. I had to say goodbye ANY kind of processed food for 4+ years. I had to say goodbye to "convenience" and "easy." Why? Because it's what my gut required in order to heal. Your gut does not lie to you. It needs what it needs. It won't negotiate, it is not open to discussion.

In summary, do everything you can to find the CAUSE of your chronic and recurring digestive issues because there is one...or ten...somewhere...hiding. Once you find the causes then create and constantly update and revise your plan for creating the conditions your body needs in order to heal itself.

The Grossest Thing I've Ever Done

2013-04-01T16:08:00.001-04:00

Fecal transplant. Yup, you guessed it! Someone else poops, you take it and immediately put it in your arse. There's a little more to it but that's the basic gist. I guess the only thing more disgusting would be to eat someone else's poo or snort someone else' poo (no joke) though hardy anyone recommends that. Though if you get dysentery in an area of the world that has camels, that link above will help you out in a crunch.

FMT (fecal microbial transplant) was a technique developed mainly to treat patients with C. difficile infection which is quite horrible and even deadly. The bacteria colonizes the human colon, kicks out almost all other bacterial strains and releases a toxin that destroys the lining of the colon which causes horrible and destructive symptoms. Anti-biotics have been known to not be able to cure C. diff, however if you empty out your gut as if you're preparing for a colonoscopy/endoscopy and then take on an enema of a healthy donor's fresh poop blended with saline solution then the C. diff will be taken care of. Fight fire with fire.

FMT has been expanding in popularity not only to folks with C. diff infections but also folks how have upset their bacterial balance at some point during theirs lives due to excessive or long term anti-biotic use or some other upset event such as giardia, parasites, dysentery drinking river water, etc. As long as you can find a healthy donor with no food allergies or sensitivities and they're willing to give you their fresh poo then you're good to go.

Some would say IBS can be boiled down to the presence of bacteria in the small intestine sufficient enough to produce noticeable gas and thus the patient reports symptoms. Therefore adding more bacteria to the small intestine is not going to help. However, adding a proper bacterial fingerprint to the large intestine without going through the small intestine seems more logical.

Does it work? It cures C diff., it makes many folks feel better but at this point I am not able to write that it is curative for the average IBS patient. The purpose here is to be helpful so PLEASE, by all means prove me wrong and point me in the direction of success stories where someone was lactose intolerant or gluten intolerant and then went through with an FMT and later was able to eat dairy and wheat without a problem. Or someone who had incurable diarrhea and after an FMT was cured. I'm all ears. Again, I've heard many stories about FMT making people feel better for even a few months but symptoms and issues seem to return. I've made it a point to focus this blog on CURATIVE means and methods and have tried to specifically stray from mere recommendations for feeling better or minor relief from symptoms.

Once again I have no interest in position taking so I'm all ears if a reader can point me to reports that FMT has been curative in anything other than C. diff cases or other harsh infectious cases. IBS is considered by many to be a non-pathogenic bacterial imbalance and/or overgrowth especially involving the small intestine which in healthy folks is mostly free of any type of bacterial presence in any appreciable amount.

However, I went through with an FMT and I will most likely try it again after I've done a few more months of liver flushing. The most comprehensive summary can be found here. Again we find a fairly intense protocol that is quite cheap! A $15 blender, a $5 enema bag, some water, some salt and a healthy donor's fresh poo (free).

Instructions are simple:

Have your donor lined up and on a whole foods, high fiber diet for two weeks before the planned FMT date. The goal is for the donor's poo schedule to be predictable and daily.
Empty your gut: Miralax and Dulcolax the day before.
Have your donor poo into plastic wrap over the toilet bowl.
Harvest about 1/4 cup of poo and put it directly into your blender which should already be filled with about 250 mL of purified water and 1/2 teaspoon of salt.
Blend for 30 seconds or until complete liquefied (any chunks will clog the enema bag).
Cinch the tubing with the plastic piece so the poo does just start flowing out of the line then pour into the enema bag, squeeze air out of enema bag and hang bag on towel rack a few feet higher than the floor.
Lay on the floor slightly on your left side and elevate your arse with a pillow. Take a deep breath, relax.
Insert the lubricated enema bag tip into your rectum.
Un-cinch the tubing and allow the poo to flow into your arse.
Take it slow and cinch the tube to slow things down if things seem to be progressing too fast.
Move onto your front side after 5 mintues of holding all the poo on your left side.
Move onto your right side after 5 minutes of being on your front.
Get to a toilet after 15 mintues (if you can last that long) and let loose. You may have to go a few times over the next hour or so.

Now you've done the grossest thing you've (probably) ever done! It might take a week or even months for you to feel "normal" again but the idea is that now you've given yourself a healthy, balanced bacterial fingerprint that will hopefully thrive in your colon and create a healthier environment and increase the functioning of what your colon is supposed to be doing for you.

MY ONE CAUTION is that to your body you have just completely swapped out your bacterial fingerprint that you've developed since birth and that is a BIG DEAL. Not many folks have reported many issues with FMT, however I would recommend eating a completely HYPOallergenic diet for a few weeks to a few months after performing an FMT to allow your body to adjust to this new bacterial balance. Some say immediately go high fiber after FMT but I would add just go easy on the allergens. I immediately noticed I was very sensitive to the same foods children are sensitive to: eggs, soy, etc. And I'm not talking "intolerance," I'm talking "allergy" just like children can have: all-out histamine reaction that can land you in the hospital.

Also, if you've done an FMT and have anything to report, please comment below. I'd love to hear more about this since it seems to be gaining popularity. I've done it myself but I can't say that it made a huge difference and I'd love to be proven wrong.

Bringing the Gall Bladder and Liver Back From the Dead

2013-04-01T11:27:00.001-04:00

There are numerous variables and factors that contribute to the miracle of digestion. As you probably have picked up by now, it's an extremely complex process that has evolved in the human species over millions of years and it has co-evolved with bacteria and the most consistently available food sources and types. Hint, hint: this is why diet is one of the most important contributors to health or unhealth.

Your body was literally built around fruit, vegetables, grains and animal meat. When you add chemicals, preservatives, excess fats or sugars, excess refined grains to stress your digestive organs and if stressed over a long period of time your organs will eventually crumble under the pressure and all sorts of problems emerge one after another in a cascade waterfall of terribly gut-wrenching (literally) proportions. However, your organs and internal cycles and systems are hardy and strong, built to last and can recover under the right circumstances. And that is where we find ourselves; at the foot of the staircase of recovery.

There are a few different undertakings described in detail on this blog but we are about to walk right into the middle of what I could call the MOST IMPORTANT undertaking: flushing and healing your liver and therefore your gallbladder.

There's not much to your gallbladder. It's a sac that holds bile and is meant to release the bile when you eat most anything but especially anything containing fat. Your liver makes bile (among many other tasks) and then both stores the bile in your gallbladder and sends off bile directly to your small intestine. However, it can't make bile fast enough to deal with a fatty meal such as scrambled eggs or a hamburger. This is why folks who have their gallbladder removed (as you can probably guess this is not recommended) avoid fatty foods but it's not just fatty foods they avoid. See here to see a list of what's to be avoided if you have your gallbladder removed. Pretty extensive. Also, I've talked to folks who have had their gallbladder removed and they are not better as a result. That's very frustrating to hear especially in light of the numerous success stories of those who have undertaken flushing and cleansing protocols to regain healthy and abundant bile flow.

Your doctor may give you a HIDA scan to measure exactly how much your gallbladder contracts after you're given a sufficient solution comprised of fat/oil. I've read numerous stories of folks who end up in the single digits: 4% functionality, 9% functionality, even 0% functionality. At this result your doctor declares your gallbladder defunct and schedules it to be removed. Over 800,000 gallbladders are removed every year in the good ol' USA and I wonder how many of those removals could have been avoided with a simple 2-month (cheap as dirt!) protocol. In fact, there's really no way for anyone but your local grocery store and pharmacy to make any money off this protocol which is great news.

So if step 1 is to control your symptoms with diet, an immediately close step 2 is to begin flushing your liver and gallbladder every 1 or 2 weeks for a total of 8-10 times or until you stop seeing (soft) gallstones in your toilet the day after the flush. If you flush every week this protocol should take 2 months but will monopolize every Friday night and Saturday morning for those 2 months. If you flush every other week you at least give yourself a Friday night and Saturday morning every other week which is nice.

Anyway, here's the flush protocol below. In addition to the flush, taking milk thistle, Taurine and high quality Vitamin E which will help heal your liver as well as dissolve any calcified gall stones. Calcified gallstones are generally not found in younger folks but can more typically found in those age 60 and above. What the average liver flusher is looking for is the soft gallstones and the sludge that will not show up on any scan your doctor will give you. In fact, your doctor may go so far as to tell you there aren't any soft gallstones or sludge in your gallbladder. But if you're going so far as to look up digestive health online then I would empirically disagree. Speaking of "empirical," we can see if you have soft gallstones by trying the flush below once and seeing what we find. Don't stray from doing exactly as the protocol says or you may compromise the success of the flush:

Buy a carton of Epsom Salts and a ripe grapefruit (the more absolutely delicious it smells the more ripe it is) and some extra virgin olive oil.
On the Friday, don't eat any fat and drink only water. Eat cereals, grains, veggies...pretend you're a vegetarian for the day. Also, don't eat ANYTHING after 2pm. You can drink water after 2PM as needed but don't overdo it.
Be home by 5:30pm. Mix 2.5 cups of water with the juice of 1/2 the grapefruit and dump in 4 tablespoons of Epsom Salts. Shake well and set aside. No need to refrigerate.
6PM - drink 1/3 of the solution you just made.
8PM - drink another 1/3 of the solution you just made.
Between 8PM and 9:30PM poop your guts out and get your "house in order." The Epsom Salts make every duct in your body dilate (get bigger) so this results in diarrhea. Get ready for bed, clean the kitchen, kiss your spouse goodnight, etc. At 10PM you will need to go immediately to bed and lay still for the rest of the evening. You should stop pooping around 9:30 which is nice!
9:50PM - go to the bathroom one last time then mix 1/2 cup of olive oil with the juice of the other half of the grapefruit and shake well. You should be prepared at this point to go immediately to bed after drinking the olive oil so make sure everything is in order and you are ready for this.
10PM - drink the olive oil solution you just made. Get it down quickly, rinse your mouth with water and get your arse right to bed. Elevate your head/upper body with a few pillows and lay still for the rest of the night. If at some point during the night you gotta go, then you gotta go but just lay still and sleep if possible. It's been said you can also take ornithine to help you sleep but I haven't tried it.
6AM - you will probably wake up naturally and have to poo. Take the last 1/3 of the Epsom Salt solution to keep all your ducts dilated. You may want to transfer from your bed to your couch at this point as you will be getting up regularly to poo for the next few hours.
6AM - 10AM - poop as needed. I usually go 4-6 times before I get all the gallstones out. You will notice small green or brown gooey balls of various sizes. I usually release a few hundred by the end of the day on Saturday but I'm ready to go out and enjoy the day by early afternoon which is nice.

You did it! Quite an adventure for sure, especially if you've never embarked on any sort of cleansing journey. So much for no gallstones, right?! The theory behind it is quite simple. Your liver stores bile in your gallbladder all day since you don't eat any fat and then you dilate your ducts with Epsom Salts to allow more space for gallstones to be pushed out. When all the sudden you pound a high concentration of oil, your gallbladder contracts and your liver bile floods out taking the gallstones with the bile. Without Epsom Salts it wouldn't happen and without steering clear of fat for the entire day it won't happen or won't work nearly as well. It's not very "fun" but if you can find it in you to pull through and do it 8+ times you might just find yourself in a new feel good zone you haven't experienced in years. Again, a healthy and abundant bile flow is the KEY to all this curing stuff we've been talking about.

You should be aware that there are a lot of naysayers out there who claim the so called "gallstones" are just coagulated olive oil mixed with bile and they are not in fact coming out of your liver/gallbladder.

There are two reasons why I disagree: First off if this were true then every time you flushed, even if you flushed every other day then you should come up with the same exact result which does not happen. You need to wait at least a week in between flushes for the soft gallstones to move into a position where they would be expelled by the high pressure bile after you drink the olive oil.

Second, most folks report that after 8-10 flushes they start to see much less or even no gallstones. Then they continue to flush every few months or twice a year and only see a few gallstones. This suggests that all this goo is in fact coming out of you and it's not just congealed olive oil and bile.

On top of this, SO MANY PEOPLE have reported feeling much, much better after flushing regularly and some have even reported a total loss of all digestive issues and symptoms. This makes sense since if you restore the flow of bile, you restore the cornerstone of your digestion.

If you try it, please comment below and let us all know how it goes. Cheers, to the re-birth of your liver!

Association Between Hypothyroidism and Small Intestinal Bacterial Overgrowth (SIBO)

2013-02-22T13:25:00.001-05:00

This is a very helpful paper discussing the connections between SIBO and Hypothyroidism taken from http://jcem.endojournals.org/content/92/11/4180.full.

Objectives: Small intestinal bacterial overgrowth is defined as an abnormally high bacterial population level in the small intestine. Intestinal motor dysfunction associated with hypothyroidism could predispose to bacterial overgrowth. Luminal bacteria could modulate gastrointestinal symptoms and interfere with levothyroxine absorption. The aims of the present study were to assess the prevalence and clinical pattern of bacterial overgrowth in patients with a history of overt hypothyroidism and the effects of bacterial overgrowth decontamination on thyroid hormone levels.

Methods: A total of 50 consecutive patients with a history of overt hypothyroidism due to autoimmune thyroiditis was enrolled. Diagnosis of bacterial overgrowth was based on positivity to a hydrogen glucose breath test. Bacterial overgrowth positive patients were treated with 1200 mg rifaximin each day for a week. A glucose breath test, gastrointestinal symptoms, and thyroid hormone plasma levels were reassessed 1 month after treatment.

Results: A total of 27 patients with a history of hypothyroidism demonstrated a positive result to the breath test (27 of 50, 54%), compared with two in the control group (two of 40, 5%). The difference was statistically significant (P < 0.001). Abdominal discomfort, flatulence, and bloating were significantly more prevalent in the bacterial overgrowth positive group. These symptoms significantly improved after antibiotic decontamination. Thyroid hormone plasma levels were not significantly affected by successful bacterial overgrowth decontamination.

Conclusions: The history of overt hypothyroidism is associated with bacterial overgrowth development. Excess bacteria could influence clinical gastrointestinal manifestations. Bacterial overgrowth decontamination is associated with improved gastrointestinal symptoms. However, fermenting carbohydrate luminal bacteria do not interfere with thyroid hormone levels.

SMALL INTESTINAL bacterial overgrowth (SIBO) is a clinical condition, caused by an increased level of microorganisms exceeding the presence of more than 10⁶ colony forming units/ml intestinal aspirate or colonic-type bacteria within the small intestine (1).

SIBO is considered a malabsorption syndrome because bacteria can adhere and damage small bowel absorptive surface, and can metabolize carbohydrates, lipids, and proteins normally absorbed in the small bowel (2). Although asymptomatic cases exist, SIBO is clinically characterized by signs and symptoms such as abdominal pain, bloating, flatulence, diarrhea, and weight loss (3).

Antibiotic therapy is the cornerstone of the treatment of SIBO. Several absorbable and nonabsorbable broad-spectrum antibiotics can be used. Rifaximin is a rifamycin derivative with antibacterial activity caused by the inhibition of bacterial synthesis of RNA (4). It is active against gram-positive and gram-negative bacteria, including both aerobes and anaerobes (5). Rifaximin 1200 mg/d is an effective treatment to achieve SIBO decontamination without increasing the incidence of side effects (6).

In the healthy subject, the main mechanisms restricting the bacterial colonization in the upper gut are the gastric acid barrier, mucosal and systemic immunity, and intestinal clearance. When these mechanisms fail, bacterial overgrowth develops. Failure of the gastric acid barrier can be caused by Helicobacter pylori-induced gastritis, drug-induced inhibition of acid secretion, autoimmune disease, malnutrition, and aging (7). Regarding local mucosal and systemic immunity, conditions such as HIV or immunoglobulin deficiencies (IgA deficit) can be linked to SIBO development.

Failure of intestinal clearance can be associated with anatomical abnormalities, such as gastrointestinal surgery, intestinal diverticula or fistula, or with conditions that impair intestinal peristalsis, such as myopathic, neuropathic, autoimmune, inflammatory, metabolic, and endocrine diseases (7).

With regard to endocrine disorders, it is known that thyroid hormones may influence gut motility modulating neurological and smooth muscle function (8, 9). Several studies have shown that hypothyroidism could be associated with decreased frequency of rhythmic colonic activity and slower oro-cecal transit time both in animal (10) and human subjects (11).

These neuromuscular disorders are responsible for diarrhea and constipation observed in patients affected by hyperthyroidism and hypothyroidism, respectively (12, 13).

Patients with hypothyroidism are supplemented with synthetic T₄ hormone (levothyroxine-LT4) in oral doses to achieve physiological thyroid hormone serum levels. Many causes of LT4 malabsorption are known and discussed in literature (14). Common causes are gastrointestinal diseases (15, 16, 17) and infections (18), pancreatic and liver diseases (19), gastrointestinal surgical procedures (20, 21), dietary interactions (22), drugs (23, 24), and pregnancy (25). However, causes of malabsorption are sometimes unknown, and increased doses of T₄ are needed for hypothyroidism treatment.

Aims of the present study are to assess: 1) whether a history of overt hypothyroidism is associated with SIBO development, 2) the clinical manifestation of SIBO and the effects of SIBO decontamination in patients with a history of overt hypothyroidism, and 3) whether the presence of SIBO affects thyroid hormone levels.

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Patients and Methods

The study was conducted between September 2005 and July 2006 on consecutive outpatients from the Gastroenterology, Endocrinology, and Internal Medicine Departments of the Gemelli Hospital, Catholic University of Rome.

Eligibility criteria

Patients with a history of overt hypothyroidism due to autoimmune thyroiditis were enrolled. The diagnosis was based on standard biochemical and instrumental criteria, which included a biochemical assay of venous blood for thyroid hormones, autoantibodies to thyroid antigens (thyroid peroxidase antibody, antithyroglobulin antibody), and thyroid ultrasound (26, 27). Serum thyroid hormones and thyroid autoantibodies were determined by commercial kits (Roche Elecsys 1010/2010 and Modular Analytics E170 analyzers; Roche Diagnostics, Indianapolis, IN). Free T₃, free T₄, and TSH were determined by immunochemiluminescence assay (normal range 2.3–4.2 pg/ml, 8.5–15.5 pg/ml, and 0.35–2.80 μUI/ml, respectively), and thyroid peroxidase antibody and antithyroglobulin antibody were determined by immunofluorescence assay (normal range < 20.0 U/ml and < 80.0 U/ml, respectively).

Diagnosis of overt hypothyroidism was based on serum TSH levels above 2.8 μUI/ml, and free T₃and T₄ decreased. Autoimmune origins of hypothyroidism were defined by the presence of thyroid autoantibodies and typical thyroid ultrasound signs, such as reduced echogenicity (26, 27).

All patients were supplemented with synthetic T₄ hormone in oral doses, and they achieved euthyroid condition in the 2–6 months before enrolment.

All patients included in the study gave written informed consent.

The exclusion criteria were: age younger than 18 yr; other causes of hypothyroidism; use of antimicrobial agents within the previous 3 months; hypersensitivity to the antibiotics; pregnancy or breast-feeding; clinical conditions predisposing to SIBO; and evidence of major concomitant diseases, including tumors and hepatic and/or renal insufficiency.

All patients were instructed to maintain their usual diet and oral dose of T₄, and to avoid prokinetics, other antibiotics, and drugs interfering with intestinal motility during the study period.

For each patient, age at hypothyroidism diagnosis, time from diagnosis, and median daily dose of T₄ were recorded.

The control group consisted of healthy subjects, without a history and clinical evidence of thyroid disease and without any well-known clinical conditions predisposing them to SIBO. They were enrolled among the medical staff of our hospital, and were of similar sex and age.

All participants in the study came from Rome and the surrounding area.

Breath hydrogen (H₂) testing

Glucose breath test (GBT) was performed under standard conditions. In the 30 d preceding the test, no patients received antibiotics or laxatives. To minimize basal H₂ excretion, subjects were asked to have a carbohydrate-restricted dinner on the day before the test and to fast for at least 12 h. On the day of testing, patients did a mouthwash with 20 ml chlorhexidine 0.05%. Smoking and physical exercise were not allowed for 30 min before and during the test. End-alveolar breath samples were collected immediately before glucose ingestion. A dose of 50 g glucose in the form of iso-osmotic solution was then administered, and samples were taken every 10 min for 2 h, respectively using a two-bag system. The two-bag system is a device consisting of a mouthpiece, a T valve, and two collapsible bags; the first one collects dead space air, and the second one collects alveolar air. From this bag the breath sample was aspirated into a 20-ml plastic syringe. Samples were analyzed immediately using a model Quintron Gas Chromatograph (Quintron Instrument Co., Milwaukee, WI).

The test was considered as indicative of the presence of SIBO when the peak, i.e. the increase over the baseline of H₂ levels, was more than 12 parts per million (28).

The reproducibility of GBTs in our laboratory in patient populations (n = 20) is good, with a κ-statistic of 0.88 and 95% agreement on tests performed 1 wk apart.

Antibiotic treatment

All patients affected by SIBO received rifaximin (Normix 200 mg tablets; Alfa-Wassermann, Woerden, The Netherlands) 1200 mg/d (two tablets three times a day) for 7 d.

A GBT was repeated 1 month after the end of therapy in all treated patients to assess SIBO eradication.

Laboratory parameters

The main hematochemical parameters (total blood cell count, glucose, blood urea nitrogen, creatinine, electrolytes, total protein, albumin, bilirubin, aspartate aminotransferase, alanine aminotransferase, c-glutamyl-transpeptidase, alkaline phosphate, and prothrombin time) were evaluated in all patients at enrolment and 3 d after the end of the antibiotic treatment in patients affected by SIBO.

Thyroid hormone levels were assessed in all patients at enrolment, and 1 month after the end of the antibiotic treatment in patients affected by SIBO and 1 month after the first evaluation in patients without SIBO.

Symptoms assessment

Each patient was asked to complete a questionnaire using a four-point Likert scale (0 = absence, 1 = mild, 2 = moderate, and 3 = severe), including classic gastrointestinal symptoms (abdominal discomfort/pain, bloating, flatulence, constipation, and diarrhea), at enrollment. All symptoms were reevaluated after antibiotic treatment.

“Adverse experiences” occurring during the treatment period were recorded on daily diary cards, with the following grades: 1, mild; 2, moderate; and 3, severe (13). Patient compliance was assessed by a pill count of the drugs boxes returned the day after the last day of therapy administration. Low compliance was defined as more than 20% of pills returned. Side effects were defined as the occurrence of: 1) abnormalities in the main hematochemical parameters considered; and 2) “adverse experiences,” considered as clinical findings or patient complaints that were not present in the 24 h immediately before enrollment in the trial.

Data analysis

To detect differences in SIBO prevalence, the χ² test was used. Differences according to age at hypothyroidism diagnosis, time from diagnosis, and median daily dose of T₄ between hypothyroid patients with or without SIBO were evaluated by the Levene test. To detect gastrointestinal symptoms, we used a four-point Likert scale (0 = absence, 1 = mild, 2 = moderate, and 3 = severe), but for the purpose of statistical analysis, the prevalence of gastrointestinal symptoms was considered as a binomial variable (1–3 = present/0 = absent). Differences were evaluated by the χ² or Fisher exact test, as appropriate. Differences in thyroid hormone levels before and after antibiotic treatment were evaluated by the Student’s t test. The statistical analysis was performed using Stata 6.0 (StataCorp, College Station, TX). A P value less than 0.05 was considered significant.

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Results

Patients characteristics

A total of 50 patients with hypothyroidism and 40 controls were enrolled. Characteristics of the study groups are summarized in Table 1⇓.

View this table:

TABLE 1.

Demographic and clinical characteristics of patients with a history of hypothyroidism and control group

GBT positivity in patients and controls

In the patients’ group, 27 subjects were found to be positive to GBT (27 of 50, 54%) compared with two in the control group (two of 40, 5%). The difference between groups was statistically significant (P < 0.001; odds ratio 22.3, 95% confidence interval 4.8–102.7; Fig. 1⇓).

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FIG. 1.

SIBO prevalence in patients with a history of hypothyroidism (group A) vs. control group (group B). *, P < 0.001.

Clinical parameters of hypothyroidism and SIBO

No significant association was found between the presence of SIBO and age at hypothyroidism diagnosis, time from diagnosis, and median T₄ daily dose (Table 2⇓).

View this table:

TABLE 2.

Age at hypothyroidism diagnosis, time from diagnosis, and median T₄ daily dose in patients with and without SIBO

Gastrointestinal symptoms in SIBO-positive and SIBO-negative patients

The prevalence of SIBO-related gastrointestinal symptoms in patients with a history of hypothyroidism are reported in Table 3⇓. Abdominal discomfort, bloating, and flatulence were significantly associated with SIBO (P < 0.01). There was no statistically significant correlation between SIBO positivity and bowel habit (constipation or diarrhea).

View this table:

TABLE 3.

Prevalence of gastrointestinal symptoms (%) in patients with a history of hypothyroidism affected by SIBO (group 1) vs. patients with history of hypothyroidism without SIBO (group 2)

Decontamination rate and side effects profile

The GBT decontamination rate in SIBO patients was 70.4% (19 of 27) after a 1-wk course with rifaximin 1200 mg/d. No dropouts were recorded.

No abnormalities in the tested laboratory parameters (total blood cell count, liver and kidney function) were observed at the control performed 3 d after the end of the treatment.

Compliance with rifaximin was excellent. More than 95% of patients in all groups took the prescribed number of tablets for the 7-d treatment. The prevalence of adverse events was very low: one patient complained of nausea and one of headache. The adverse events reported were both mild and disappeared rapidly after treatment.

Gastrointestinal symptoms and SIBO decontamination

A significant improvement in abdominal discomfort, bloating, and flatulence was observed in the group of patients decontaminated after rifaximin therapy (P < 0.01). No differences were found with regard to constipation and diarrhea after SIBO decontamination (Table 4⇓).

View this table:

TABLE 4.

Prevalence of gastrointestinal symptoms (%) in 19 patients with a history of hypothyroidism affected by SIBO and successfully decontaminated before and after antibiotic treatment

None of the recorded gastrointestinal symptoms significantly improved in the group of treated but nondecontaminated patients (data not shown).

Thyroid hormone levels and SIBO decontamination

Median T₄ daily dosage (μg/d; μg/kg) was similar between patients who responded and those who did not respond to the antibiotic treatment (96.54; 1.42 vs. 94.89; 1.34).

No statistically significant difference was observed regarding thyroid hormone levels in the 19 SIBO decontaminated patients before and after antibiotic treatment (Table 5⇓).

View this table:

TABLE 5.

Thyroid hormone plasma levels in patients with a history of hypothyroidism affected by SIBO, eradicated by rifaximin, before and after antibiotic treatment

Thyroid hormone levels were also reassessed in patients without SIBO showing values similar to those of the first evaluation (data not shown).

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Discussion

Interdigestive migrating motor complexes play a major role in the clearance of bacteria from the gut (29). In rats, bacterial overgrowth is induced by pharmacological disruption of migrating motor complexes, and restoration of intestinal motility reduces endoluminal bacterial density to normal values (30, 31, 32). Several diseases characterized by the disruption of normal motor events are often associated with SIBO: scleroderma (33), idiopathic intestinal pseudo-obstruction, autonomic neuropathy, and radiation enteropathy (34, 35, 36). Thyroid hormones may influence gut motility modulating neurological and smooth muscle function, and hypothyroidism could be associated with decreased frequency of rhythmic colonic activity and slower oro-cecal transit time (10, 11). Our study shows that a history of overt hypothyroidism is a risk factor for SIBO development. The pathogenic link could be that intestinal motor dysfunction associated with hypothyroidism reduces the ability of the small bowel to clear luminal bacteria. In our study all enrolled patients had a history of overt hypothyroidism. It could be very interesting to evaluate if differences exist between subclinical and overt hypothyroidism concerning association with SIBO. We can speculate that the prevalence of intestinal overgrowth could be related to the severity of hypothyroidism. On the other hand, intestinal motility could be more heavily altered in overt hypothyroid patients developing SIBO. Intestinal myoelectrical activity, oro-cecal transit time, and intestinal neurohormonal regulation should be studied in future trials to confirm this hypothesis, and elucidate pathophysiological mechanisms behind the association between hypothyroidism and SIBO.

In the present study, all patients were under levothyroxine therapy, achieving euthyroidism at enrollment. It is possible that once SIBO is established during the hypothyroid phase, it does not clear spontaneously, even if made euthyroid.

The prevalence of gastrointestinal symptoms such as abdominal discomfort, bloating, and flatulence is significantly higher in SIBO-positive patients compared with SIBO-negative, and decontamination therapy is associated with statistically significant levels of clinical improvement. These findings suggest that, in patients with hypothyroidism, the presence of gastrointestinal symptoms after reaching a euthyroid condition is related to SIBO persistence. It is well known that, in patients affected by chronic functional disorders, gastrointestinal symptoms respond to placebo in 20–50% of cases. However, two recent randomized double-blind placebo-controlled trials by Pimentel (37) and Sharara (38) et al. showed that rifaximin significantly improved gastrointestinal symptoms in patients with chronic functional disorders and that symptom improvement was associated with a reduction in H₂ breath excretion. In addition, in our study, rifaximin is administered only for a short time, with benefits tested after 1 month; the placebo effect could be minimal after this time.

SIBO-related bacteria excess can also interfere with the absorption of many substances, such as carbohydrates, proteins, and lipids (2). A direct mucosal injury resulting from bacterial adherence and increased production of enterotoxins could affect the activity of brush-border disaccharidases. On the other hand, bacteria can compete with the host for nutrient use (2). In our study the presence of SIBO is not associated with T₄ malabsorption, and SIBO decontamination does not modify thyroid hormone levels. Bacterial population contaminating the upper gut is extremely complex, and metabolic functions are very difficult to investigate (39). In the present study, SIBO diagnosis is based on the H₂ breath test. Its positivity suggests the presence of sugars fermenting bacteria (40), thus producing H₂ and other metabolites. It is possible that this test does not identify bacteria using proteins and amino acids such as T₄ as their prevalent energetic substrates. It could explain why SIBO does not interfere with thyroid hormone levels in our study. On the other hand, the high prevalence of symptoms such as bloating and flatulence could reflect a prevalent “fermentative bacteria” in our population.

In conclusion, a history of overt hypothyroidism is associated with SIBO development and persistence. Excessive bacteria could modulate neuromuscular function and influence clinical manifestations. SIBO decontamination is associated with gastrointestinal symptom improvement. Finally, carbohydrate fermenting bacteria do not interfere with thyroid hormone levels.

Further studies are needed to characterize the bacteria species involved in SIBO, and clarify their metabolic functions and their relationship with intestinal motility.

Welcome! Let the Healing Begin...

2013-02-19T20:28:00.001-05:00

Hi, I was privileged enough to live through the past 12+ years of hell and survive so I pulled together this blog to prevent others from continuing into that same hell. I started to slowly decline in my late teens after a trip to Central America where I apparently drank the wrong water. I've never been the same since.

It started with a bout of giardia and tropical sprue and it's as if I never kicked it. Slowly its affects left me with chronic diarrhea, increasing sensitivity to foods which led to all out food allergies (lactose, gluten, wheat, onions, soy, sulfates/sulfites, corn, and the list goes on and on to the point of nausea), uncontrollable weight loss, hypothyroidism, vitamin D deficiency (quite possibly the worst of all consequences listed), brain fog, forgetfulness, blood shot eyes, thinning hair, rotting teeth, chronic fatigue, joint muscle bone pain, heart palpitations, insomnia, total loss of appetite, weakness, depression, anxiety, panic attacks, all amounting to a complete and utter loss of motivation and hope...well, almost.

That is, until I started to leave denial in the dust of my feet and go on the offense and attack my demons. I got to the point where I was teetering on the edge of life and non-life; at a cross-roads with an eternally present decision to make based on one question: am I worth it? My wife, family, friends and community helped me to come to the reluctant decision that YES, my life does mean something and I am worth EFFORT.

I hit the books hard, I hit the health forums harder, I called doctors until they called me back, I spent A LOT of money and even more time trying to figure out what got me into this morbid pile of poo (pun intended). All because I am worth it and I'm convinced until you understand your value to god and your community you may not be able to take the leap necessary to turn your life as far as you need to in order to regain your health. Remember when you could eat normal food and not worry about it? Remember when you felt good?

I do, and I did just about everything I could to claw my way back to that kind of thriving. Jesus said he came so that humans could have life to the full and I decided one day with the help of my community that I would settle for nothing less no matter what it took.

I did just that and then I wrote this blog and then I kept going and even wrote a book and tried to make it as funny as possible.

But alas, where do I start? There's so much to say and there's so much I didn't know when I started and I don't want to skip anything so that my beloved readers can get AS MUCH AS POSSIBLE from my 12 years which were lost to the oblivion of chronic debilitating illness. I've organized the blog as much as I can but my best advice is to just start reading...

I Don't Feel Good

Denial

Okay, Something Is Seriously Wrong With Me

The Science Behind Why You Feel Like Total Sh!t

IBS - Finally a Diagnosis! Kind of...

SIBO - Small Intestine Bacterial Overgrowth

Is SIBO Just Another Word for IBS?

Parasites and False Negative Test Results

The Vicious Cycle(s)

Doctors, Colonoscopies and Endoscopies

The Specific Carbohydrate Diet and/or GAPS Diet

Beyond IBS to More Difficult Issues

The "Feel Good" Zone

Pursuing a Cure

Doing The Most Disgusting Thing I've Ever Done Before

The Recovery

Me and Jesus

Oh but wait, there's more...

The 10 Year Cleanse

The 30 Year Cleanse

The 60 Year Cleanse

Feel free to comment, contact me, contact other commentors, do whatever you need to do to GET BETTER.

Cheers,

Tim

Vitamin D, Osteomalacia and SIBO

2013-02-17T20:59:00.000-05:00

Vitamin D is a group of fat-soluble secosteroids responsible for intestinal absorption of calcium and phosphate. In humans, vitamin D is unique because it can be ingested as cholecalciferol (vitamin D₃) or ergocalciferol (vitamin D₂) and because the body can also synthesize it (from cholesterol) when sun exposure is adequate (hence its nickname, the "sunshine vitamin").

Although vitamin D is commonly called a vitamin, it is not actually an essential dietary vitamin in the strict sense, as it can be synthesized in adequate amounts by most mammals exposed to sunlight (cats and dogs cannot synthesize vitamin D and must receive it in their diet). An organic chemical compound (or related set of compounds) is only scientifically called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from their diet. However, as with other compounds commonly called vitamins, vitamin D was discovered in an effort to find the dietary substance that was lacking in a disease, namely, rickets, the childhood form of osteomalacia.^[1] Additionally, like other compounds called vitamins, in the developed world vitamin D is added to staple foods, such as milk, to avoid disease due to deficiency.

Measures of serum levels reflect endogenous synthesis from exposure to sunlight as well as intake from the diet, and it is believed that synthesis may contribute generally to the maintenance of adequate serum concentrations. The evidence indicates that the synthesis of vitamin D from sun exposure works in a feedback loop that prevents toxicity but, because of uncertainty about the cancer risk from sunlight, no recommendations are issued by theInstitute of Medicine, USA, for the amount of sun exposure required to meet vitamin D requirements. Accordingly, the Dietary Reference Intakes for vitamin D assume that no synthesis occurs and that all of a person's vitamin D is from their diet, although that will rarely occur in practice.

In the liver vitamin D is converted to calcidiol, which is also known as calcifediol (INN), 25-hydroxycholecalciferol, or 25-hydroxyvitamin D—abbreviated 25(OH)D; and which is the specific vitamin D metabolite that is measured in serum to determine a person's vitamin D status.^[2]^[3] Part of the calcidiol is converted by the kidneys to calcitriol, the biologically active form of vitamin D.^[4] Calcitriol circulates as a hormone in the blood, regulating the concentration of calcium and phosphate in the bloodstream and promoting the healthy growth and remodeling of bone. Calcidiol is also converted to calcitriol outside of the kidneys for other purposes, such as the proliferation, differentiation and apoptosis of cells; calcitriol also affects neuromuscular function and inflammation.^[5]

Beyond its use to prevent osteomalacia or rickets, the evidence for other health effects of vitamin D supplementation in the general population is inconsistent.^[6]^[7] The best evidence of benefit is for bone health^[8] and a decrease in mortality in elderly women.

Health effects of supplements

The effects of vitamin D supplementation on health are uncertain.^[7] A United States Institute of Medicine, (IOM) report states: "Outcomes related to cancer, cardiovascular disease andhypertension, diabetes and metabolic syndrome, falls and physical performance, immune functioning and autoimmune disorders, infections, neuropsychological functioning, and preeclampsiacould not be linked reliably with calcium or vitamin D intake and were often conflicting."^[8]^:5 Some researchers claim the IOM was too definitive in its recommendations and made a mathematical mistake when calculating the blood level of vitamin D associated with bone health.^[10] Members of the IOM panel maintain that they used a "standard procedure for dietary recommendations" and that the report is solidly based on the data. Research on vitamin D supplements, including large scale clinical trials, is continuing.^[10]

[edit]Mortality

Low blood levels of vitamin D are associated with increased mortality,^[11] and giving supplementary vitamin D₃ to elderly women in institutional care seems to decrease the risk of death.^[9] Vitamin D₂, alfacalcidol, and calcitriol do not appear to be effective.^[9] However, both an excess and a deficiency in vitamin D appear to cause abnormal functioning and premature aging.^[12]^[13]^[14] The relationship between serum calcidiol level and all-cause mortality is parabolic,^[8] Harm from vitamin D appears to occur at a lower vitamin D level in the black population than in the white population.^[8]^:435

[edit]Bone health

Vitamin D deficiency causes osteomalacia (called rickets when it occurs in children). Beyond that, low serum vitamin D levels have been associated with falls, and low bone mineral density.^[15]

In 2012, the U.S. Preventive Services Task Force issued a draft statement recommending that there is not enough evidence to indicate that healthy postmenopausal women should use supplemental doses of calcium or vitamin D to prevent fractures.^[16]

Some studies have shown that supplementation with vitamin D and calcium may improve bone mineral density slightly, as well as decreasing the risk of falls and fractures in certain groups of people, specifically those older than 65 years.^[15]^[17] This appears to apply more to people in institutions than those living independently.^[18] The quality of the evidence is, however, poor.^[19] And there does not appear to be a benefit to bone health from vitamin D without sufficient calcium.^[20]

[edit]Cardiovascular disease

Evidence for health effects from vitamin D supplementation for cardiovascular health is poor.^[6]^[21]^[22] Moderate to high doses may reduce cardiovascular disease risk but are of questionable clinical significance.^[6]^[23]

[edit]Multiple sclerosis

Low levels of vitamin D are associated with multiple sclerosis. Supplementation with vitamin D may have a protective effect but there are uncertainties and unanswered questions.^[24]^[25]^[26] "The reasons why vitamin D deficiency is thought to be a risk factor for MS are as follows: (1) MS frequency increases with increasing latitude, which is strongly inversely correlated with duration and intensity of UVB from sunlight and vitamin D concentrations; (2) prevalence of MS is lower than expected at high latitudes in populations with high consumption of vitamin-D-rich fatty fish; and (3) MS risk seems to decrease with migration from high to low latitudes."^[24] A clinical trial sponsored by Charite University in Berlin, Germany was begun in 2011, with the goal of examining the efficacy, safety and tolerability of vitamin D3 in the treatment of Multiple Sclerosis.^[27]^[28]

[edit]Cancer

Low vitamin D levels are associated with some cancers and with worse outcomes in other cancers, but taking supplements does not appear to help people with prostate cancer.^[29] Currently evidence is insufficient to support supplementation in those with cancer.^[29] Results for a protective or harmful effect of vitamin D supplementation in other types of cancer are inconclusive.^[7]^[30]

[edit]Pregnancy

Pregnant women who take an adequate amount of vitamin D during gestation, may experience positive immune effects.^[31] Pregnant women throughout the world do not take the recommended dose of vitamin D, which could negatively impact the health of the mother and her fetus.^[31] 4000 IU of vitamin D3 was considered a superior regimen for supplementing pregnant women.^[31]

[edit]Other

Vitamin D appears to have effects on immune function.^[32] It has been postulated to play a role in influenza with lack of vitamin D synthesis during the winter as one explanation for high rates of influenza infection during the winter.^[33] For viral infections, other implicated factors include low relative humidities produced by indoor heating and low temperatures that favor virus spread.^[34] Low levels of vitamin D appear to be a risk factor for tuberculosis,^[35] and historically it was used as a treatment.^[36] As of 2011, it is being investigated in controlled clinical trials.^[36] Vitamin D may also play a role in HIV.^[37] Although there are tentative data linking low levels of vitamin D to asthma, there is inconclusive evidence to support a beneficial effect from supplementation.^[38]Accordingly, supplementation is not currently recommended for treatment or prevention of asthma.^[39] Also, preliminary data is inconclusive for supplemental vitamin D in promotion of human hair growth.^[40]

[edit]Deficiency

Main article: Hypovitaminosis D

A diet deficient in vitamin D causes osteomalacia (called rickets when it occurs in children), which is a softening of the bones. In the developed world, this is a rare disease.^[41]^[42] Low blood calcidiol (25-hydroxy-vitamin D) can result from avoiding the sun.^[43] Deficiency results in impaired bone mineralization and leads to bone-softening diseases^[44] including:

Rickets, a childhood disease characterized by impeded growth and deformity of the long bones, can be caused by calcium or phosphorus deficiency as well as a lack of vitamin D; today it is largely found in low-income countries in Africa, Asia or the Middle East^[45] and in those with genetic disorders such as pseudovitamin D deficiency rickets.^[46] Rickets was first described in 1650 by Francis Glisson who said it had first appeared about 30 years previously in the counties of Dorset and Somerset.^[47] In 1857, John Snow suggested that rickets, then widespread in Britain, was being caused by the adulteration of bakers' bread with alum.^[48] The role of diet in the development of rickets^[49]^[50] was determined by Edward Mellanby between 1918–1920.^[51]Nutritional rickets exists in countries with intense year-round sunlight such as Nigeria and can occur without vitamin D deficiency.^[52]^[53] Although rickets and osteomalacia are now rare in Britain, there have been outbreaks in some immigrant communities in which osteomalacia sufferers included women with seemingly adequate daylight outdoor exposure wearing Western clothing.^[54] Having darker skin and reduced exposure to sunshine did not produce rickets unless the diet deviated from a Western omnivore pattern characterized by high intakes of meat, fish and eggs, and low intakes of high-extraction cereals.^[55]^[56]^[57] The dietary risk factors for rickets include abstaining from animal foods.^[54]^[58] Vitamin D deficiency remains the main cause of rickets among young infants in most countries, because breast milk is low in vitamin D and social customs and climatic conditions can prevent adequate UVB exposure. In sunny countries such as Nigeria, South Africa, and Bangladesh, where the disease occurs among older toddlers and children, it has been attributed to low dietary calcium intakes, which are characteristic of cereal-based diets with limited access to dairy products.^[57] Rickets was formerly a major public health problem among the US population; in Denver where ultraviolet rays are approximately 20% stronger than at sea level on the same latitude,^[59] almost two-thirds of 500 children had mild rickets in the late 1920s.^[60] An increase in the proportion of animal protein^[58]^[61] in the 20th century American diet coupled with increased consumption of milk ^[62]^[63] fortified with relatively small quantities of vitamin D coincided with a dramatic decline in the number of rickets cases.^[64]
Osteomalacia, a bone-thinning disorder that occurs exclusively in adults, is characterized by proximal muscle weakness and bone fragility. The effects of osteomalacia are thought to contribute to chronic musculoskeletal pain,^[65]^[66] There is no persuasive evidence of lower vitamin D levels in chronic pain sufferers.^[67]

The Director General of Research and Development and Chief Scientific Adviser for the UK Department of Health and NHS said that children aged six months to five years should be given vitamin D supplements, particularly during the winter. However, vitamin D supplements are not recommended for people who get enough vitamin D from their diets and from sunlight.^[68]

Some research shows that dark-skinned people living in temperate climates have lower vitamin D levels.^[69]^[70]^[70] It has been suggested that dark-skinned people are less efficient at making vitamin D because melanin in the skin hinders vitamin D synthesis; however, a recent study has found novel evidence that low vitamin D levels among Africans may be due to other reasons.^[71]Recent evidence implicates parathyroid hormone in adverse cardiovascular outcomes. Black women have an increase in serum PTH at a lower 25(OH)D level than white women.^[72] A large scale association study of the genetic determinants of vitamin D insufficiency in Caucasians found no links to pigmentation.^[73]^[74]

On the other hand, the uniform occurrence of low serum 25(OH)D in Indians living in India^[75] and Chinese in China,^[76] does not support the hypothesis that the low levels seen in the more pigmented are due to lack of synthesis from the sun at higher latitudes. The leader of the study has urged dark-skinned immigrants to take vitamin D supplements nonetheless, saying, "I see no risk, no downside, there's only a potential benefit.^[77]^[78] "

[edit]Toxicity

For more details on this topic, see hypervitaminosis D.

In healthy adults, sustained intake of more than 1250 micrograms/day (50,000 IU) can produce overt toxicity after several months;^[79] those with certain medical conditions such as primaryhyperparathyroidism^[80] are far more sensitive to vitamin D and develop hypercalcemia in response to any increase in vitamin D nutrition, while maternal hypercalcemia during pregnancy may increase fetal sensitivity to effects of vitamin D and lead to a syndrome of mental retardation and facial deformities.^[80]^[81] Pregnant or breastfeeding women should consult a doctor before taking a vitamin D supplement.The FDA advised manufacturers of liquid Vitamin D supplements that droppers accompanying these products should be clearly and accurately marked for 400 international units (IU). In addition, for products intended for infants, FDA recommends that the dropper hold no more than 400 IU.^[82] For infants (birth to 12 months), the tolerable upper limit (maximum amount that can be tolerated without harm) is set at 25 micrograms/day (1000 IU). One thousand micrograms (40,000 IU) per day in infants has produced toxicity within one month.^[79] After being commissioned by the Canadian and American governments, the Institute of Medicine (IOM) as of 30 November 2010, has increased the tolerable upper limit (UL) to 2500 IU per day for ages 1–3 years, 3000 IU per day for ages 4–8 years and 4000 IU per day for ages 9–71+ years (including pregnant or lactating women).^[83] Vitamin D overdose causes hypercalcemia, and the main symptoms of vitamin D overdose are those of hypercalcemia: anorexia, nausea, and vomiting can occur, frequently followed by polyuria, polydipsia, weakness, insomnia, nervousness, pruritus, and, ultimately, renal failure. Proteinuria, urinary casts, azotemia, and metastatic calcification (especially in the kidneys) may develop.^[79] Vitamin D toxicity is treated by discontinuing vitamin D supplementation and restricting calcium intake. Kidney damage may be irreversible. Exposure to sunlight for extended periods of time does not normally cause vitamin D toxicity.^[80] Within about 20 minutes of ultraviolet exposure in light-skinned individuals (3–6 times longer for pigmented skin), the concentrations of vitamin D precursors produced in the skin reach an equilibrium, and any further vitamin D that is produced is degraded.^[84]^[84]

Published cases of toxicity involving hypercalcemia in which the vitamin D dose and the 25-hydroxy-vitamin D levels are known all involve an intake of ≥40,000 IU (1000 μg) per day.^[80]Recommending supplementation, when those supposedly in need of it are labeled healthy, has proved contentious, and doubt exists concerning long term effects of attaining and maintaining high serum 25(OH)D by supplementation.^[85]

[edit]Forms

Name	Chemical composition	Structure
Vitamin D₁	molecular compound of ergocalciferol withlumisterol, 1:1
Vitamin D₂	ergocalciferol (made from ergosterol)
Vitamin D₃	cholecalciferol (made from 7-dehydrocholesterolin the skin).
Vitamin D₄	22-dihydroergocalciferol
Vitamin D₅	sitocalciferol (made from 7-dehydrositosterol)

Several forms (vitamers) of vitamin D exist (see table). The two major forms are vitamin D₂ or ergocalciferol, and vitamin D₃ or cholecalciferol; vitamin D without a subscript refers to either D₂ or D₃ or both. These are known collectively as calciferol.^[86] Vitamin D₂ was chemically characterized in 1932. In 1936, the chemical structure of vitamin D₃ was established and proven to result from the ultraviolet irradiation of 7-dehydrocholesterol.^[87]

Chemically, the various forms of vitamin D are secosteroids; i.e., steroids in which one of the bonds in the steroid rings is broken.^[88] The structural difference between vitamin D₂ and vitamin D₃ is in their side chains. The side chain of D₂ contains a double bond between carbons 22 and 23, and a methyl group on carbon 24.

Vitamin D₃ (cholecalciferol) is produced by ultraviolet irradiation (UV) of its precursor 7-dehydrocholesterol. This molecule occurs naturally in the skin of animals and in milk. Vitamin D₃ can be made by exposure of the skin to UV, or by exposing milk directly to UV (one commercial method).

Vitamin D₂ is a derivative of ergosterol, a membrane sterol named for the ergot fungus, which is produced by some kinds of phytoplankton, invertebrates, yeasts, and higher fungi such as mushrooms. The vitaminergocalciferol (D₂) is produced in all of these organisms from ergosterol, in response to UV irradiation. Like all forms of vitamin D, it cannot be produced without UV irradiation. D₂ is not produced by green land plants orvertebrates, because they lack the precursor ergosterol.^[89] The biological fate for producing 25(OH)D from vitamin D₂ is expected to be the same as for 25(OH)D₃,^[90] although some controversy exists over whether or not D₂ can fully substitute for vitamin D₃ in the human diet.^[91] ^[92]

[edit]Photosynthesis of vitamin D in primitive species.

Photosynthesis of vitamin D in the ocean by phytoplankton (such as coccolithophore and Emiliania huxleyi) has existed for more than 500 million years and continues to the present. Although primitive vertebrates in the ocean could absorb calcium from the ocean into their skeletons and eat plankton rich in vitamin D, land animals required another way to satisfy their vitamin D requirement for a calcified skeleton without relying on plants. Land vertebrates have been making their own vitamin D for more than 350 million years.^[93]

Vitamin D can be synthesized only via a photochemical process, so land vertebrates had to ingest foods that contained vitamin D or had to be exposed to sunlight to photosynthesize vitamin D in their skin to satisfy their body's vitamin D requirement.^[94]

[edit]Production in the skin

In the epidermal strata of the skin, production is greatest in the stratum basale (colored red in the illustration) and stratum spinosum (colored light brown).

Vitamin D₃ (cholecalciferol) is produced photochemically in the skin from 7-dehydrocholesterol. 7-Dehydrocholesterol is produced in relatively large quantities, 10,000 to 20,000 IU of vitamin D are produced in 30 minutes of whole-body exposure,^[95] in the skin of most vertebrate animals, including humans.^[96] 7-dehydrocholesterol reacts with ultraviolet light of UVB type at wavelengths between 270 and 300 nm, with peak synthesis occurring between 295 and 297 nm.^[97] These wavelengths are present in sunlight when the UV index is greater than three, as well as in the light emitted by the UV lamps in tanning beds (which produce ultraviolet primarily in the UVA spectrum, but typically produce 4% to 10% of the total UV emissions as UVB). At a UV index greater than three, which occurs daily within the tropics, daily during the spring and summer seasons in temperate regions, and almost never within the arctic circles, vitamin D₃ can be made in the skin.

Depending on the intensity of UVB rays and the minutes of exposure, an equilibrium can develop in the skin, and vitamin D degrades as fast as it is generated.^[84]

The skin consists of two primary layers: the inner layer called the dermis, composed largely of connective tissue, and the outer, thinner epidermis. Thick epidermis in the soles and palms consists of five strata; from outer to inner they are: the stratum corneum, stratum lucidum, stratum granulosum,stratum spinosum, and stratum basale. Vitamin D is produced in the two innermost strata, the stratum basale and stratum spinosum.

The naked mole rat appears to be naturally cholecalciferol deficient, as serum 25-OH vitamin D levels are undetectable.^[98] In some animals, the presence of fur or feathers blocks the UV rays from reaching the skin. In birds and fur-bearing mammals, vitamin D is generated from the oily secretions of the skin deposited onto the feathers or fur and is obtained orally during grooming.^[99]

[edit]Interactive metabolism and pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^[100]

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Vitamin D Synthesis Pathway edit

[edit]Sunscreen

Sunscreen absorbs ultraviolet light and prevents it from reaching the skin. It has been reported that sunscreen with a sun protection factor (SPF) of 8 based on the UVB spectrum can decrease vitamin D synthetic capacity by 95 percent, whereas sunscreen with an SPF of 15 can reduce synthetic capacity by 98 percent (Matsuoka et al., 1987).^[101]

[edit]Mechanism of action

Calcium regulation in the human body.^[102] The role of vitamin D is shown in orange.

Vitamin D is carried in the bloodstream to the liver, where it is converted into the prohormone calcidiol. Circulating calcidiol may then be converted intocalcitriol, the biologically active form of vitamin D, either in the kidneys or by monocyte-macrophages in the immune system. When synthesized by monocyte-macrophages, calcitriol acts locally as a cytokine, defending the body against microbial invaders.^[103] Following the final converting step in the kidney, calcitriol (the physiologically active form of vitamin D) is released into the circulation. By binding to vitamin D-binding protein (VDBP), a carrier protein in the plasma, calcitriol is transported to various target organs.^[88]

Calcitriol mediates its biological effects by binding to the vitamin D receptor (VDR), which is principally located in the nuclei of target cells.^[88] The binding of calcitriol to the VDR allows the VDR to act as a transcription factor that modulates the gene expression of transport proteins (such as TRPV6and calbindin), which are involved in calcium absorption in the intestine.^[104]

The vitamin D receptor belongs to the nuclear receptor superfamily of steroid/thyroid hormone receptors, and VDRs are expressed by cells in mostorgans, including the brain, heart, skin, gonads, prostate, and breast. VDR activation in the intestine, bone, kidney, and parathyroid gland cells leads to the maintenance of calcium and phosphorus levels in the blood (with the assistance of parathyroid hormone and calcitonin) and to the maintenance ofbone content.^[64]

Vitamin D increases expression of the tyrosine hydroxylase gene in adrenal medullary cells. It also is involved in the biosynthesis of neurotrophic factors, synthesis of nitric oxide synthase, and increased glutathione levels.^[105]

The VDR is known to be involved in cell proliferation and differentiation. Vitamin D also affects the immune system, and VDRs are expressed in severalwhite blood cells, including monocytes and activated T and B cells.^[106]

Apart from VDR activation, various alternative mechanisms of action are known. An important one of these is its role as a natural inhibitor of signal transduction by hedgehog (a hormone involved in morphogenesis).^[107]^[108]

One of the most important roles of vitamin D is to maintain skeletal calcium balance by promoting calcium absorption in the intestines, promoting bone resorption by increasing osteoclast number, maintaining calcium and phosphate levels for bone formation, and allowing proper functioning of parathyroid hormone to maintain serum calcium levels. Vitamin D deficiency can result in lowerbone mineral density and an increased risk of reduced bone density (osteoporosis) or bone fracture because a lack of vitamin D alters mineral metabolism in the body.^[109] Thus, although it may initially appear paradoxical, vitamin D is critical for proper bone formation despite its role as a potent stimulator of bone resorption.^[110]

[edit]Recommendations

[edit]Dietary reference intakes

Different institutions propose different recommendations concerning daily amounts of the vitamin.

Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited.^[111]

(Conversion : 1 µg = 40 IU and 0.025 µg = 1 IU)^[112]

[edit]Australia and New Zealand

About a third of Australians have vitamin D deficiency.^[113] Australia and New Zealand have established average intakes for vitamin D, as follows:^[114] children 5.0 μg /day; adults 19–50 yr 5.0 μg/day, 51–70 yr 10.0 μg/day, >70 yr 15.0 μg/day.

[edit]Canada

According to Health Canada^[115] the recommended dietary allowances (RDA) for vitamin D are:

Age group	RDA	Tolerable Upper Intake
Infants 0–6 months	400 IU*	1000 IU
Infants 7–12 months	400 IU*	1500 IU
Children 1–3 years	600 IU	2500 IU
Children 4–8 years	600 IU	3000 IU
Children and Adults 9–70 years	600 IU	4000 IU
Adults > 70 years	800 IU	4000 IU
Pregnancy & Lactation	600 IU	4000 IU

Note*: Adequate Intake rather than Recommended Dietary Allowance.

[edit]European Union

The recommended daily amount for vitamin D in the European Union is 5 µg.^[116]

The European Menopause and Andropause Society (EMAS) recommended 15 µg (600 IU) until age 70, and 20 µg (800 IU) in older than 71 years, in postmenopausal women. This dose should be increased up to 4,000 IU/day in some patients with very low vitamin D status or in case of co-morbid conditions.^[117]

According to the European Food Safety Authority the Tolerable Upper Intake Levels^[118] are:

0-12 months: 25 µg/day (1000 IU)
1-10 years: 50 µg/day (2000 IU)
11-17 years: 100 µg/day (4000 IU)
17+: 100 µg/day (4,000 IU)
Pregnant/lactating women: 100 µg/day (4,000 IU)

[edit]United States

According to the United States Institute of Medicine,^[8] the recommended dietary allowances of vitamin D are:

1–70 years of age: 600 IU/day (15 μg/day)
71+ years of age: 800 IU/day (20 μg/day)
Pregnant/lactating: 600 IU/day (15 μg/day)

[edit]Upper intake levels

The Tolerable Upper Intake Level is defined as "the highest average daily intake of a nutrient that is likely to pose no risk of adverse health effects for nearly all persons in the general population.^[8]^:403 " Although tolerable upper intake levels are believed to be safe, information on the long-term effects is incomplete and these levels of intake are not recommended:^[8]^:403^:433

0–6 months of age: 1,000 IU (25 µg/day)
6–12 months of age: 1,500 IU (37.5 µg/day)
1–3 years of age: 2,500 IU (62.5 µg/day)
4–8 years of age: 3,000 IU (75 µg/day)
9–71+ years of age: 4,000 IU (100 µg/day)
Pregnant/lactating: 4,000 IU^[8]^:5(100 µg/day)

[edit]Comment

The Dietary Reference Intake for vitamin D issued by the American (U.S.) Institute of Medicine (IOM) in 2010 superseded a previous recommendation which had Adequate Intake status. The recommendations were formed assuming the individual has no skin synthesis of vitamin D because of inadequate sun exposure. The reference intake for vitamin D refers to total intake from food, beverages and supplements, is intended for the North American population, and assumes that calcium requirements are being met.^[8]^:5

One school of thought contends that human physiology is fine tuned to an intake of 4000–12,000 IU/day from sun exposure with concomitant serum 25-hydroxyvitamin D levels of 40 to 80 ng/mL^[119] and that this is required for optimal health. Proponents of this view, who include some members of the panel that drafted a now superseded 1997 report on vitamin D from the Institute of Medicine, contend that the IOM's warning about serum concentrations above 50 ng/mL lacks biological plausibility. They suggest that for some people reducing the risk of preventable disease requires a higher level of vitamin D than that recommended by the IOM.^[120]^[119]

[edit]Serum 25-hydroxyvitamin D

US labs generally report 25(OH)D levels as ng/mL. Other countries often use nmol/L.

A U.S. Institute of Medicine committee concluded that a serum 25-hydroxyvitamin D level of 20 ng/mL (50 nmol/L) is desirable for bone and overall health. The Dietary Reference Intakes for vitamin D are chosen with a margin of safety and 'overshoot' the targeted serum value to ensure that the specified levels of intake achieve the desired serum 25-hydroxyvitamin D levels in almost all persons. It is assumed there are no contributions to serum 25-hydroxyvitamin D level from sun exposure and the recommendations are fully applicable to people with dark skin or negligible exposure to sunlight.^:1

The Institute found that serum 25-hydroxyvitamin D concentrations above 30 ng/mL (75 nmol/L) are "not consistently associated with increased benefit". Serum 25-hydroxyvitamin D levels above 50 ng/mL (125 nmol/L) may be cause for concern.^[8]

There is a lower risk of cardiovascular disease when vitamin D ranged from 20 to 60 nmol/L (8 to 24 ng/mL). There appears to be a "threshold effect" once 60 nmol/L (24 ng/mL) have been reached i.e., levels of vitamin D over 60 nmol/L did not show added benefit.^[121]

[edit]Allowable health claims

Apart from the above discussion on health effects or scientific evidence for lowering disease risk, governmental regulatory agencies stipulate for the food industry health claims allowable as statements on packaging.

European Food Safety Authority (EFSA)^[122]

normal function of the immune system
normal inflammatory response
normal muscle function
reduced risk of falling in people over age 60^[123]

US Food and Drug Administration (FDA)

may reduce the risk of osteoporosis^[124]

Health Canada

adequate calcium and regular exercise may help to achieve strong bones in children and adolescents and may reduce the risk of osteoporosis in older adults. An adequate intake of vitamin D is also necessary^[125]

Other possible agencies with claim guidance: Japan FOSHU^[126] and Australia-New Zealand.^[127]

[edit]Dietary sources

[edit]Vitamin D₂

Main article: Ergocalciferol

Fungus, from USDA nutrient database (per 100 g):^[128]

Mushrooms, portabella, exposed to ultraviolet light, raw: Vitamin D₂: 11.2 μg (446 IU)
Mushrooms, portabella, exposed to ultraviolet light, grilled: Vitamin D₂: 13.1 μg (524 IU)
Mushrooms, shiitake, dried: Vitamin D₂: 3.9 μg (154 IU)
Mushrooms, shiitake, raw: Vitamin D₂: 0.4 μg (18 IU)
Mushrooms, portabella, raw: Vitamin D₂: 0.3 μg (10 IU)
Mushroom powder, any species, illuminated with sunlight or artificial ultraviolet light sources

Vitamin D₂, or ergocalciferol found in fungi, is synthesized from viosterol, which in turn is activated when ultraviolet light stimulates ergosterol.^[129]

Human bioavailability of vitamin D₂ from vitamin D₂-enhanced button mushrooms via UV-B irradiation is effective in improving vitamin D status and not different from a vitamin D₂ supplement.^[130]from UV-irradiated yeast baked into bread is bioavailable.^[131] By visual assessment or using a chromometer, no significant discoloration of irradiated mushrooms, as measured by the degree of "whiteness", was observed.^[132] Claims have been made that a normal serving (approx. 3 oz or 1/2 cup, or 60 grams) of fresh mushrooms treated with ultraviolet light have increased vitamin D content to levels up to 80 micrograms,^[133] or 2700 IU if exposed to just 5 minutes of UV light after being harvested.^[134]

Plants

Alfalfa (Medicago sativa subsp. sativa), shoot: 4.8 μg (192 IU) vitamin D₂, 0.1 μg (4 IU) vitamin D₃ (per 100 g).^[135]

Lichen

Cladina arbuscula specimens grown under different natural conditions: The contents of vitamin D3 range from 0.67 to 2.04 μg g⁻¹ dry matter in the thalli of C. arbuscula specimens grown under different natural conditions, while provitamin D3 could not be detected. The ranges for provitamin D2 and vitamin D2 were 89-146 and 0.22-0.55 μg g⁻¹ dry matter, respectively, while the contents of provitamin D3 were below the detection limit (0.01 microg g(-1) dry matter).^[136]

[edit]Vitamin D₃

Main article: Cholecalciferol

In some countries, staple foods are artificially fortified with vitamin D.^[137]

Animal sources ^[5]
- Fish liver oils, such as cod liver oil, 1 Tbs. (15 ml) provides 1360 IU (90.6 IU/ml)
- Fatty fish species, such as:
  - Catfish (wild), 85 g (3 oz) provides 425 IU (5 IU/g)
  - Salmon, cooked, 100 g (3.5 oz) provides 360 IU (3.6 IU/g)
  - Mackerel, cooked, 100 g (3.5 oz), 345 IU (3.45 IU/g)
  - Sardines, canned in oil, drained, 50 g (1.75 oz), 250 IU (5 IU/g)
  - Tuna, canned in oil, 100 g (3.5 oz), 235 IU (2.35 IU/g)
  - Eel, cooked, 100 g (3.5 oz), 200 IU (2.00 IU/g)
- A whole egg provides 20 IU if egg weighs 60 g (0.333 IU/g)
- Beef liver, cooked, 100 g (3.5 oz), provides 15 IU (0.15 IU/g)

[edit]History

American researchers Elmer McCollum and Marguerite Davis in 1913 discovered a substance in cod liver oil which later was called "vitamin A". British doctor Edward Mellanby noticed dogs that were fed cod liver oil did not develop rickets and concluded vitamin A, or a closely associated factor, could prevent the disease. In 1921, Elmer McCollum tested modified cod liver oil in which the vitamin A had been destroyed. The modified oil cured the sick dogs, so McCollum concluded the factor in cod liver oil which cured rickets was distinct from vitamin A. He called it vitamin D because it was the fourth vitamin to be named.^[138]^[139]^[140] It was not initially realized that, unlike other vitamins, vitamin D can be synthesised by humans through exposure to UV light.

In 1923, it was established that when 7-dehydrocholesterol is irradiated with light, a form of a fat-soluble vitamin is produced (now known as D₃). Alfred Fabian Hess showed "light equals vitamin D."^[141] Adolf Windaus, at the University of Göttingen in Germany, received the Nobel Prize in Chemistry in 1928, for his work on the constitution of sterols and their connection with vitamins.^[142]In 1929 a group at NIMR in Hampstead, London, were working on the structure of vitamin D, which was still unknown, as well as the structure of steroids. A meeting took place with J.B.S. Haldane, J.D. Bernal and Dorothy Crowfoot to discuss possible structures, which contributed to bringing a team together. X-ray crystallography demonstrated that sterol molecules were flat, not as proposed by the German team led by Windaus. In 1932 Otto Rosenheim and Harold King published a paper putting forward structures for sterols and bile acids which found immediate acceptance.^[143] The informal academic collaboration between the team members Robert Benedict Bourdillon, Otto Rosenheim (mentioned above), Harold King (mentioned above) and Kenneth Callow was very productive and led to the isolation and characterization of vitamin D.^[144] At this time the policy of the Medical Research Council was not to patent discoveries, believing that results of medical research should be open to everybody. In the 1930s Windaus clarified further the chemical structure of vitamin D.^[145]

In 1923, American biochemist Harry Steenbock at the University of Wisconsin demonstrated that irradiation by ultraviolet light increased the vitamin D content of foods and other organic materials.^[146] After irradiating rodent food, Steenbock discovered the rodents were cured of rickets. A vitamin D deficiency is a known cause of rickets. Using $300 of his own money, Steenbock patented his invention. His irradiation technique was used for foodstuffs, most memorably for milk. By the expiration of his patent in 1945, rickets had been all but eliminated in the US.^[147]

In 1971-72 the further metabolism of vitamin D to active forms was discovered. In the liver vitamin D was found to be converted to calcidiol^[148]^[149] Part of the calcidiol is then converted by the kidneys to calcitriol, the biologically active form of vitamin D.^[4] Calcitriol circulates as a hormone in the blood, regulating the concentration of calcium and phosphate in the bloodstream and promoting the healthy growth and remodeling of bone. Both calcidiol and calcitriol were identified by a team led by Michael F. Holick.^[150]^[4]

[edit]Industrial production

Vitamin D₃ (cholecalciferol) is produced industrially by exposing 7-dehydrocholesterol to UVB light, followed by purification.^[151] The 7-dehydrocholesterol is a natural substance in wool grease (lanolin) from sheep or other woolly animals. Vitamin D₂ (ergocalciferol) is produced in a similar way using ergosterol from yeast or mushrooms as a starting material.^[151]

This article taken from Wikipedia (http://en.wikipedia.org/wiki/Vitamin_D)

iHerb.com Coupon Code

2012-08-31T15:07:00.001-04:00

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Get Herbs!

What To Know Before You Buy Herbal Supplements

2012-08-15T19:38:00.000-04:00

www.iherb.com

Echinacea to prevent colds. Ginkgo to improve memory. Flaxseed to lower cholesterol. The list of herbal remedies goes on and on.

Herbal supplements, sometimes called botanicals, aren't new. Plants have been used for medicinal purposes for thousands of years. However, herbal supplements haven't been subjected to the same scientific scrutiny and aren't as strictly regulated as medications. For example, makers of herbal supplements don't have to get approval from the Food and Drug Administration (FDA) before putting their products on the market.

Yet some herbal supplements — including products labeled as "natural" — have drug-like effects that can be dangerous. So it's important to do your homework and investigate potential benefits and side effects of herbal supplements before you buy. And be sure to talk with your doctor, especially if you take medications, have chronic health problems, or are pregnant or breast-feeding.

Are herbal supplements safe?

Herbal supplements are regulated by the FDA, but not as drugs or as foods. They fall under a category called dietary supplements. The rules for dietary supplements are as follows:

Manufacturers don't have to seek FDA approval before putting dietary supplements on the market. In addition, companies can claim that products address a nutrient deficiency, support health or are linked to body functions — if they have supporting research and they include a disclaimer that the FDA hasn't evaluated the claim.
Manufacturers must follow good manufacturing practices to ensure that supplements are processed consistently and meet quality standards. These regulations are intended to keep the wrong ingredients and contaminants, such as pesticides and lead, out of supplements, as well as make sure that the right ingredients are included in appropriate amounts.
Once a dietary supplement is on the market, the FDA is responsible for monitoring its safety. If the FDA finds a product to be unsafe, it can take action against the manufacturer or distributor or both, and may issue a warning or require that the product be removed from the market.

These regulations provide assurance that herbal supplements meet certain quality standards and that the FDA can intervene to remove dangerous products from the market.

The rules do not, however, guarantee that herbal supplements are safe for anyone to use. Because many supplements contain active ingredients that have strong effects in the body, these products can pose unexpected risks. For example, taking a combination of herbal supplements or using supplements together with prescribed medications could lead to harmful, even life-threatening results. For this reason, it's important to talk with your doctor before using herbal supplements.

How do you know what's in an herbal supplement?

The FDA requires that the following information be included on the labels of all herbal supplements:

The name of the herbal supplement
The name and address of manufacturer or distributor
A complete list of ingredients — either in the Supplement Facts panel or listed beneath it
Serving size, amount and active ingredient

If you don't understand something on an herbal supplement's label, ask your doctor or pharmacist for an explanation.

An easy way to compare ingredients in products is by using the Dietary Supplements Labels Database, which is available on the National Library of Medicine's website. The database has information on the ingredients for thousands of dietary supplements sold in the United States. You can look up products by brand name, uses, active ingredient or manufacturer.

How do you know if herbal supplements' claims are true?

Manufacturers of herbal supplements are responsible for ensuring that the claims they make about their products aren't false or misleading and that they're backed up by adequate evidence. However, they aren't required to submit this evidence to the FDA.

So be a smart consumer and do a little homework. Don't just rely on a product's marketing. Look for objective, research-based information to evaluate a product's claims. To get reliable information about a particular supplement:

Ask your doctor or pharmacist. Even if they don't know about a specific supplement, they may be able to point you to the latest medical guidance about its uses and risks.
Look for scientific research findings. Two good sources include the National Center for Complementary and Alternative Medicine (NCCAM) and the Office of Dietary Supplements. Both have websites that provide information to help consumers make informed choices about dietary supplements.
Contact the manufacturer. If you have questions about a specific product, call the manufacturer or distributor. Ask to talk with someone who can answer questions, such as what data the company has to substantiate its products' claims.

Who shouldn't use herbal supplements?

If you have health issues, it's essential that you talk with your doctor before trying herbal supplements. In fact, in some high-risk situations, your doctor will likely recommend that you avoid herbal supplements altogether.

It's especially important that you talk to your doctor before using herbal supplements if:

You're taking prescription or over-the-counter (OTC) medications. Some herbs can cause serious side effects when mixed with prescription and OTC drugs, such as aspirin, blood thinners or blood pressure medications. Talk to your doctor about possible interactions.
You're pregnant or breast-feeding. Medications that may be safe for you as an adult may be harmful to your fetus or your breast-feeding infant. As a general rule, don't take any medications — prescription, OTC or herbal — when you're pregnant or breast-feeding unless your doctor approves.
You're having surgery. Many herbal supplements can affect the success of surgery. Some may decrease the effectiveness of anesthetics or cause dangerous complications, such as bleeding or high blood pressure. Tell your doctor about any herbs you're taking or considering taking as soon as you know you need surgery.
You're younger than 18 or older than 65. Older adults may metabolize medications differently. And few herbal supplements have been tested on children or have established safe doses for children.

Safety tips for using herbal supplements

If you've done your homework and plan to try an herbal supplement, play it safe with these tips:

Follow supplement instructions. Don't exceed recommended dosages or take the herb for longer than recommended.
Keep track of what you take. Take only one supplement at a time to determine if it's effective. Make a note of what you take — and how much for how long — and how it affects you.
Be cautious about supplements manufactured outside the United States. Herbal products from some European countries are highly regulated and standardized. But toxic ingredients and prescription drugs have been found in supplements manufactured elsewhere, particularly China, India and Mexico.
Check alerts and advisories. The FDA and NCCAM maintain lists of supplements that are under regulatory review or that have been reported to cause adverse effects. Check their websites periodically for updates.

Click here to read this article written by the Mayo Clinic Staff

The History Of CoQ10 and Its Long List of Health Benefits

2012-08-06T20:11:00.003-04:00

Coenzyme Q₁₀, also known as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated at times to CoQ₁₀ /ˌkoʊ ˌkjuː ˈtɛn/, CoQ, or Q₁₀ is a1,4-benzoquinone, where Q refers to the quinone chemical group, and 10 refers to the number of isoprenyl chemical subunits in its tail.

This oil-soluble, vitamin-like substance is present in most eukaryotic cells, primarily in the mitochondria. It is a component of the electron transport chain and participates in aerobic cellular respiration, generating energy in the form of ATP. Ninety-five percent of the human body’s energy is generated this way.^[1]^[2] Therefore, those organs with the highest energy requirements—such as the heart, liver and kidney—have the highest CoQ₁₀concentrations.^[3]^[4]^[5] There are three redox states of coenzyme Q₁₀: fully oxidized (ubiquinone), semiquinone (ubisemiquinone), and fully reduced (ubiquinol). The capacity of this molecule to exist in a completely oxidized form and a completely reduced form enables it to perform its functions in the electron transport chain and as an antioxidant respectively.

Discovery and History

Coenzyme q10 was first discovered by Professor Fredrick L. Crane and colleagues at the University of Wisconsin-Madison Enzyme Institute in 1957. In 1958, its chemical structure was reported by Dr. Karl Folkers and coworkers at Merck; in 1968, Folkers became a professor in the Chemistry Department at the University of Texas at Austin. In 1961 Peter Mitchell proposed the electron transport chain (which includes the vital protonmotive role of CoQ10) and he received a Nobel price for the same in 1978. In 1972, Gian Paolo Littarru and Karl Folkers separately demonstrated a deficiency a CoQ10 in human heart disease. The 1980s witnessed a steep rise in the number of clinical trials due to the availability of large quantities of pure CoQ10 and methods to measure plasma and blood CoQ10 concentrations. The antioxidant role of the molecule as a free radical scavenger was widely studied by Lars Ernster. Numberous scientists around the globe started studies on this molecule since then in relations to various diseases including cardiovascular diseases and cancer.

[edit]Chemical properties

The oxidized structure of CoQ₁₀ is shown on the top-right. The various kinds of Coenzyme Q can be distinguished by the number of isoprenoid subunits in their side-chains. The most common Coenzyme Q in human mitochondria is CoQ₁₀. Q refers to the quinone head and 10 refers to the number of isoprene repeats in the tail. The image below has three isoprenoid units and would be called Q₃.

[edit]Biochemical role

CoQ₁₀ is found in the membranes of many organelles. Since its primary function in cells is in generating energy, the highest concentration is found on the inner membrane of the mitochondrion. Some other organelles that contain CoQ₁₀ include endoplasmic reticulum, peroxisomes, lysosomes, and vesicles.

[edit]CoQ₁₀ and electron transport chain

CoQ₁₀ is fat-soluble and is therefore mobile in cellular membranes; it plays a unique role in the electron transport chain (ETC). In the inner mitochondrial membrane, electrons from NADH and succinate pass through the ETC to the oxygen, which is then reduced to water. The transfer of electrons through ETC results in the pumping of H+ across the membrane creating a proton gradient across the membrane, which is used by ATP synthase (located on the membrane) to generate ATP. CoQ₁₀ functions as an electron carrier from enzyme complex I and enzyme complex II to complex III in this process. This is crucial in the process, since no other molecule can perform this function. Thus, CoQ₁₀ functions in every cell of the body to synthesize energy.

[edit]Antioxidant function of CoQ₁₀

The antioxidant nature of CoQ₁₀ derives from its energy carrier function. As an energy carrier, the CoQ₁₀ molecule is continually going through an oxidation-reduction cycle. As it accepts electrons, it becomes reduced. As it gives up electrons, it becomes oxidized. In its reduced form, the CoQ₁₀ molecule holds electrons rather loosely, so this CoQ molecule will quite easily give up one or both electrons and, thus, act as an antioxidant.^[9] CoQ₁₀ inhibits lipid peroxidation by preventing the production of lipid peroxyl radicals (LOO). Moreover, CoQH₂ reduces the initial perferryl radical and singlet oxygen, with concomitant formation of ubisemiquinone and H₂O₂. This quenching of the initiating perferryl radicals, which prevent propagation of lipid peroxidation, protects not only lipids, but also proteins from oxidation. In addition, the reduced form of CoQ effectively regenerates vitamin E from the a-tocopheroxyl radical, thereby interfering with the propagation step. Furthermore, during oxidative stress, interaction of H₂O₂ with metal ions bound to DNA generates hydroxyl radicals and CoQ efficiently prevents the oxidation of bases, in particular, in mitochondrial DNA.^[9] In contrast to other antioxidants, this compound inhibits both the initiation and the propagation of lipid and protein oxidation. It also regenerates other antioxidants such as vitamin E. The circulating CoQ₁₀ in LDL prevents oxidation of LDL, which may provide benefit in cardiovascular diseases.

[edit]Biosynthesis

Starting from acetyl-CoA, a multistep process of mevalonate pathway produces farnesyl-PP (FPP), the precursor for cholesterol, CoQ, dolichol, and isoprenylated proteins. An important enzyme in this pathway is HMG Co-A reductase, which is usually a target for intervention in cardiovascular complications. The "statin" family of cholesterol reducing medications block HMG Co-A reductase, so taking CoQ10 may alleviate a statin side effect of rhabdomyolysis. The long isoprenoid side-chain of CoQ is synthesized by trans-prenyltransferase, which condenses FPP with several molecules of isopentenyl-PP (IPP), all in the trans configuration.^[10] The next step involves condensation of this polyisoprenoid side-chain with 4-hydroxybenzoate, catalyzed by polyprenyl-4-hydroxy benzoate transferase. Hydroxybenzoate is synthesized from tyrosine or phenylalanine. In addition to their presence in mitochondria, these initial two reactions also occur in the endoplasmic reticulum and peroxisomes, indicating multiple sites of synthesis in animal cells.^[11] Increasing the endogenous biosynthesis of CoQ₁₀ has attained attention in the recent years as a strategy to fight CoQ₁₀ deficiency.

Genes involved include PDSS1, PDSS2, COQ2, and COQ8/CABC1.^[12]

[edit]Absorption and metabolism

[edit]Absorption

CoQ₁₀ is a crystalline powder that is insoluble in water. Absorption follows the same process as that of lipids and the uptake mechanism appears to be similar to that of vitamin E, another lipid-soluble nutrient.This process in the human body involves the secretion of pancreatic enzymes and bile into the small intestines that facilitate emulsification and micelle formation that is required for the absorption of lipophilic substances.^[13] Food intake (and the presence of lipids) stimulates bodily biliary excretion of bile acids and greatly enhances the absorption of CoQ₁₀. Exogenous CoQ₁₀ is absorbed from the small intestinal tract and is best absorbed if it is taken with a meal. Serum concentration of CoQ₁₀ in fed condition is higher than in fasting conditions.^[14]^[15]

[edit]Metabolism

Data on the metabolism of CoQ₁₀ in animals and humans are limited.^[16] A study with ¹⁴C-labeled CoQ₁₀ in rats showed most of the radioactivity in the liver 2 hours after oral administration when the peak plasma radioactivity was observed, but it should be noted that CoQ₉ is the predominant form of coenzyme Q in rats.^[17] It appears that CoQ₁₀ is metabolised in all tissues, while a major route for its elimination is biliary and fecal excretion. After the withdrawal of CoQ₁₀ supplementation, the levels return to normal within a few days, irrespective of the type of formulation used.^[18]

[edit]CoQ₁₀ deficiency and toxicity

There are two major factors that lead to deficiency of CoQ₁₀ in humans: reduced biosynthesis, and increased utilization by the body. Biosynthesis is the major source of CoQ₁₀. Biosynthesis requires at least 12 genes, and mutations in many of them cause CoQ deficiency. CoQ₁₀ levels can also be affected by other genetic defects (such as mutations of mitochondrial RNA, ETFDH, APTX and BRAF, genes that are not directly related to the CoQ₁₀ biosynthetic process) while the role of statins is controversial.^[19] Some chronic disease conditions (cancer, heart disease, etc.) are also thought to reduce the biosynthesis and increase the demand for CoQ₁₀ in the body, but there are no definite data to support these claims. Toxicity is not usually observed with high doses of CoQ₁₀. A daily dosage up to 3600 mg was found to be tolerated by healthy as well as unhealthy persons.^[20] However, some adverse effects, largely gastrointestinal, are reported with very high intakes. The observed safe level (OSL) risk assessment method indicated that the evidence of safety is strong at intakes up to 1200 mg/day, and this level is identified as the OSL.^[21]

[edit]Clinical assessment techniques

Although CoQ₁₀ can be measured in plasma, these measurements reflect dietary intake rather than tissue status. Currently, most clinical centers measure CoQ₁₀ levels in cultured skin fibroblasts, muscle biopsies, and in blood mononuclear cells.^[19] Culture fibroblasts can be used also to evaluate the rate of endogenous CoQ₁₀ biosynthesis, by measuring the uptake of 14C-labelled p-hydroxybenzoate.^[22]

[edit]Inhibition by statins and beta blockers

Coenzyme Q₁₀ shares a biosynthetic pathway with cholesterol. The synthesis of an intermediary precursor of coenzyme Q₁₀, mevalonate, is inhibited by some beta blockers, blood pressure-lowering medication,^[23] and statins, a class of cholesterol-lowering drugs.^[24] Statins can reduce serum levels of coenzyme Q₁₀ by up to 40%.^[25] Some research suggests the logical option of supplementation with coenzyme Q₁₀ as a routine adjunct to any treatment that may reduce endogenous production of coenzyme Q₁₀, based on a balance of likely benefit against very small risk.^[26]^[27] However, there are still no conclusive data that support the role of CoQ₁₀ deficiency in the pathogenesis of statin-related myopathy.

[edit]Pharmacokinetics

Some reports have been published on the pharmacokinetics of CoQ₁₀. The plasma peak can be observed 2–6 hours after oral administration, mainly depending on the design of the study. In some studies, a second plasma peak was also observed at about 24 hours after administration, probably due to both enterohepatic recycling and redistribution from the liver to circulation.^[13] Tomono et al. used deuterium-labelled crystalline CoQ₁₀ to investigate pharmacokinetics in human and determined an elimination half-time of 33 hours.^[28]

[edit]Improving the bioavailability of CoQ₁₀

The importance of how drugs are formulated for bioavailability is well known. In order to find a principle to boost the bioavailability of CoQ₁₀ after oral administration, several new approaches have been taken and different formulations, and forms have been developed and tested on animals or humans.^[16]

[edit]Reduction of particle size

An obvious strategy is reduction of the particle size to as low as the micro- and nano-scale. Nanoparticles have been explored as a delivery system for various drugs and an improvement of the oral bioavailability of drugs with poor absorption characteristics has been reported;^[29] the pathways of absorption and the efficiency were affected by reduction of particle size. This protocol has so far not proved to be very successful with CoQ₁₀, although reports have differed widely.^[30]^[31] The use of the aqueous suspension of finely powdered CoQ₁₀ in pure water has also revealed only a minor effect.^[18]

[edit]Soft-gel capsules with CoQ₁₀ in oil suspension

A successful approach was to use the emulsion system to facilitate absorption from the gastrointestinal tract and to improve bioavailability. Emulsions of soybean oil (lipid microspheres) could be stabilised very effectively by lecithin and were utilised in the preparation of soft gelatine capsules. In one of the first such attempts, Ozawa et al. performed a pharmacokinetic study on beagle dogs in which the emulsion of CoQ₁₀ in soybean oil was investigated; about two times higher plasma CoQ₁₀ level than that of the control tablet preparation was determined during administration of a lipid microsphere.^[18] Although an almost negligible improvement of bioavailability was observed by Kommuru et al. with oil-based soft-gel capsules in a later study on dogs,^[32] the significantly increased bioavailability of CoQ₁₀ was confirmed for several oil-based formulations in most other studies.^[33]

[edit]Novel forms of CoQ₁₀ with increased water-solubility

Facilitating drug absorption by increasing its solubility in water is a common pharmaceutical strategy and has also been shown to be successful for Coenzyme Q₁₀. Various approaches have been developed to achieve this goal, with many of them producing significantly better results over oil-based soft-gel capsules in spite of the many attempts to optimize their composition.^[16]Examples of such approaches are use of the aqueous dispersion of solid CoQ₁₀ with tyloxapol polymer,^[34] formulations based on various solubilising agents, i.e., hydrogenated lecithin,^[35] and complexation with cyclodextrins; among the latter, complex with β-cyclodextrin has been found to have highly increased bioavailability.^[36]^[37] and is also used in pharmaceutical and food industry for CoQ₁₀-fortification.^[16] Also some other novel carrier systems like liposomes, nanoparticles, dendrimers etc. can be used to increase the bioavailability of Coenzyme Q₁₀.

[edit]Supplementation benefits

Heart health

According to the Mayo Clinic, "CoQ₁₀ has been used, recommended, or studied for numerous conditions, but remains controversial as a treatment in many areas."^[38] Coenzyme Q₁₀, in its reduced form as solubilized ubiquinol, is approved for use as an orphan product in the treatment of Huntington's disease and pediatric congestive heart failure;^[39] other uses are still unproven, including in the treatment of high triglycerides levels and athletic performance.^[40]

[edit]

Coenzyme Q₁₀ helps to maintain a healthy cardiovascular system. There is evidence of CoQ₁₀ deficiency in heart failure. Recently, CoQ₁₀ plasma concentrations have been demonstrated as an independent predictor of mortality in chronic heart failure, CoQ₁₀ deficiency being detrimental to the long-term prognosis of chronic heart failure.^[41] CoQ₁₀ is available as medicine in several European countries, but is in these countries also available as a food supplement. Oxidation of the circulating LDL is thought to play a key role in the pathogenesis of atherosclerosis, which is the underlying disorder leading to heart attack and ischemic strokes^[42]^[43]^[44] and CHD. Studies in the last decade have demonstrated that the content of Ubiquinol in human LDL affords protection against the oxidative modifications of LDL themselves, thus lowering their atherogenic potency.^[45]^[46]

[edit]Migraine headaches

Supplementation of coenzyme Q₁₀ has been found to have a beneficial effect on the condition of some sufferers of migraine headaches. So far, three studies have been done, of which two were small, did not have a placebo group, were not randomized, and were open-label,^[47] and one was a double-blind, randomized, placebo-controlled trial, which found statistically significant results despite its small sample size of 42 patients.^[48] Dosages were 150 to 300 mg/day.

It has been used effectively in the prophylaxis of migraines, especially in combination with a daily supplement of magnesium citrate 500 mg and riboflavin (vitamin B2) 400 mg.

[edit]Cancer

CoQ₁₀ is also being investigated as a treatment for cancer, and as relief from cancer treatment side-effects.^[49]^[50]^[51]^[52]

[edit]Cardiac arrest

Another recent study shows a survival benefit after cardiac arrest if coenzyme Q₁₀ is administered in addition to commencing active cooling of the body to 90–93 degrees Fahrenheit (32–34 degrees Celsius).^[53]

[edit]Blood pressure

There are several reports concerning the effect of CoQ₁₀ on blood pressure in human studies.^[54]

A recent (2007) meta-analysis of the clinical trials of CoQ₁₀ for hypertension reviewed all published trials of coenzyme Q₁₀ for hypertension, and assessed overall efficacy, consistency of therapeutic action, and side-effect incidence. Meta-analysis was performed in 12 clinical trials (362 patients) comprising three randomized controlled trials, one crossover study, and eight open-label studies. The meta-analysis concluded that coenzyme Q₁₀ has the potential in hypertensive patients to lower systolic blood pressure by up to 17 mm Hg and diastolic blood pressure by up to 10 mm Hg without significant side-effects.^[55]

[edit]Periodontal disease

A review study has shown that there is no clinical benefit to the use of CoQ₁₀ in the treatment of periodontal disease.^[56] Most of the studies suggesting otherwise were outdated, focused on in-vitro tests,^[57]^[58]^[59] had too few test subjects and/or erroneous statistical methodology and trial set-up,^[60]^[61] or were sponsored by a manufacturer of the product.^[62]

Dr. Bruno Loos, head of the periodontology department at Academisch Centrum Tandheelkunde Amsterdam (ACTA), states that the Pharma Nord website links to scientific articles that should prove the effectiveness of Coenzyme Q₁₀ for periodontal disease, but all are of very poor quality.^[63] The Dutch Academy of Periodontics (NvvP) has issued numerous warnings against claims of any link between Coenzyme Q₁₀ and periodontal disease.^[64]^[65]

[edit]Lifespan

One study demonstrated that low dosages of coenzyme Q₁₀ reduce oxidation and DNA double-strand breaks, and a combination of a diet rich in polyunsaturated fatty acids and coenzyme Q₁₀supplementation leads to a longer lifespan in rats.^[66] Coles and Harris demonstrated an extension in the lifespan of rats when they were given coenzyme Q₁₀ supplementation.^[67] But multiple studies have since found no increase in lifespan or decrease in aging in mice and rats supplemented with coenzyme Q₁₀.^[68]^[69]^[70]^[71] Another study demonstrated that coenzyme Q₁₀ extends the lifespan of C. elegans (nematode).^[72]

[edit]Radiation injury

In 2002, a study reported that, in rat experiments, coenzyme Q₁₀ taken as dietary supplement reduced radiation damage to the animals' blood.^[73]

[edit]Parkinson's disease

A 2002 study in 80 Parkinson's disease patients found 1200 mg/day reduced the progression by 44%.^[74]^[75] A phase III trial of 1200 mg/d and 2400 mg/d ran until August 2011. This study was terminated and the summary concluded: "The investigational drug is unlikely to demonstrate efficacy over placebo for this indication. However, no safety issues were discovered."^[76]

[edit]Coenzyme Q₁₀ concentrations in foods and dietary intake

Detailed reviews on occurrence of CoQ₁₀ and dietary intake were published in 2010.^[77] Besides endogenous synthesis, CoQ₁₀ is also supplied to the organism by various foods. However, despite the scientific community’s great interest in this compound, a very limited number of studies have been performed to determine the contents of CoQ₁₀ in dietary components. The first reports on this issue were published in 1959, but the sensitivity and selectivity of the analytical methods at that time did not allow reliable analyses, especially for products with low concentrations.^[77]Developments in analytical chemistry have since enabled a more reliable determination of CoQ₁₀ concentrations in various foods (Table below).

CoQ₁₀ levels in selected foods^[77]
Food	Coenzyme Q₁₀ concentration [mg/kg]
Beef
heart	113
liver	39–50
muscle	26–40
Pork
heart	11.8–128.2
liver	22.7–54.0
muscle	13.8–45.0
Chicken
heart	116.2–132.2
Fish
sardine	5–64
mackerel
red flesh	43–67
white flesh	11–16
salmon	4–8
tuna	5
Oils
soybean	54–280
olive	4–160
grapeseed	64–73
sunflower	4–15
rice bran	/
coconut
Nuts
peanuts	27
walnuts	19
sesame seeds	18–23
pistachio nuts	20
hazelnuts	17
almond	5–14
Vegetables
parsley	8–26
broccoli	6–9
cauliflower	2–7
spinach	up to 10
grape	6–7
Chinese cabbage	2–5
Fruit
avocado	10
blackcurrant	3
strawberry	1
orange	1–2
grapefruit	1
apple	1

Meat and fish are the richest source of dietary CoQ₁₀ and levels over 50 mg/kg can be found in beef, pork and chicken heart, and chicken liver. Dairy products are much poorer sources of CoQ₁₀compared to animal tissues. Vegetable oils are also quite rich in CoQ₁₀. Within vegetables, parsley, and perilla are the richest CoQ₁₀ sources, but significant differences in their CoQ₁₀ levels can be found in the literature. Broccoli, grape, and cauliflower are modest sources of CoQ₁₀. Most fruit and berries represent a poor to very poor source of CoQ₁₀, with the exception of avocado, with a relatively high CoQ₁₀ content.^[77]

[edit]Intake

In the developed world, the estimated daily intake of CoQ₁₀ has been determined at 3–6 mg per day, derived primarily from meat.^[77]

[edit]Effect of heat and processing

Cooking by frying reduces CoQ₁₀ content by 14–32%.^[78]

Drugs vs Herbs

2012-07-31T20:24:00.000-04:00

Lets start with a brief history of herbal medicine. The first evidence we have of the use of herbal medicine is from Egypt in around 2000 B.C.

From there it spread both East, into spiritual medicines like Ayurveda, and West, where it is still gaining in popularity even now. It is estimated that 80% of world uses some form of herbal medicine today.

Herbal medicine has continuously grown since those times, but benefited particularly from the invention of the printing press in the 1400s. From this point on, recipes and remedies were easily available to more than just doctors. Famous herbalists included the Chinese author Chung Yun (who died in 1933 after supposedly using herbs to live 256 years!).

These days herbal medicine is marketed aggressively across the world, so it’s a good time to take a look at why this is, and what advantages herbal medicine can offer over prescription drugs.

In Favor of Herbal Remedies

The first point to make is that roughly half of today’s prescription and over-the-counter medicines are derived from plants. New drugs don’t just get created in the lab. Scientists trawl through jungles, rivers, wetlands and any other natural habitat they can find, looking for a new compound to test against all the sample viruses and bacteria they keep for this purpose.

In other words, natural medicine really is the basis for modern medical practice, just a few steps back along the line of development. The difference is that you are taking a 100% natural product, rather than one that has been processed in a lab and lost much of its goodness along the way.

Secondly, herbal medicine has gone through the most rigorous clinical trial imaginable! After thousands of years of regular use by a cross-section of the population, it’s safe to say that any side effects or interactions have been well documented and explored.

Compare this to a typical 10 week clinical trial, commissioned by a pharmaceutical company desperate to bring its new drug to market, that will often take no heed of longer term effects.

Lastly, remember that natural supplements often bring other benefits beyond what you strictly expect. For example, you might take feverfew to give relief from a migraine, then find that your stomach upset has also disappeared. These dual effects are what makes herbology so interesting.

Additionally, many herbs contain a variety of vitamins and minerals that your body desperately needs. Needless to say, it’s far better to get your Recommended Daily Amount from a natural plant or herb than from a manufactured supplement.

Against Herbal Remedies

The arguments against using herbal remedies are also worth looking at. It is true that they offer little statutory protection, because many are not regulated by the FDA like drugs are.

For this reason we would always recommend to check with your doctor before starting any herbal treatment. It is also important to read the label and see what precautions the manufacturer is recommending.

Secondly, one of the reasons that prescription drugs can be so strong and effective is that the pharmaceutical companies have isolated the active ingredients in the herb or plant. In other words you are getting exactly what you need and nothing more.

Herbalists would say that this misses the point, because it is the interaction of all the parts of the herb that results in its power as a remedy. Isolating the active ingredient eliminates vitamins, minerals and other substances that may work in support of the active ingredient. Why change something that has worked for thousands of years?

Click here to read the rest of the article...

(you can buy herbal supplements at iHerb.com and use coupon code OPU856 for $5 OFF)

Get Herbs

Finding The Root Of All Evil

The Grossest Thing I've Ever Done

Bringing the Gall Bladder and Liver Back From the Dead

Association Between Hypothyroidism and Small Intestinal Bacterial Overgrowth (SIBO)

Patients and Methods

Eligibility criteria

Breath hydrogen (H2) testing

Antibiotic treatment

Laboratory parameters

Symptoms assessment

Data analysis

Results

Patients characteristics

GBT positivity in patients and controls

Clinical parameters of hypothyroidism and SIBO

Gastrointestinal symptoms in SIBO-positive and SIBO-negative patients

Decontamination rate and side effects profile

Gastrointestinal symptoms and SIBO decontamination

Thyroid hormone levels and SIBO decontamination

Discussion

Welcome! Let the Healing Begin...

Vitamin D, Osteomalacia and SIBO

[edit]Mortality

[edit]Bone health

[edit]Cardiovascular disease

[edit]Multiple sclerosis

[edit]Cancer

[edit]Pregnancy

[edit]Other

[edit]Deficiency

[edit]Toxicity

[edit]Forms

[edit]Photosynthesis of vitamin D in primitive species.

[edit]Production in the skin

[edit]Interactive metabolism and pathway map

[edit]Sunscreen

[edit]Mechanism of action

[edit]Recommendations

[edit]Dietary reference intakes

[edit]Australia and New Zealand

[edit]Canada

[edit]European Union

[edit]United States

[edit]Upper intake levels

[edit]Comment

[edit]Serum 25-hydroxyvitamin D

[edit]Allowable health claims

[edit]Dietary sources

[edit]Vitamin D2

[edit]Vitamin D3

[edit]History

[edit]Industrial production

iHerb.com Coupon Code

What To Know Before You Buy Herbal Supplements

Are herbal supplements safe?

How do you know what's in an herbal supplement?

How do you know if herbal supplements' claims are true?

Who shouldn't use herbal supplements?

Safety tips for using herbal supplements

The History Of CoQ10 and Its Long List of Health Benefits

Discovery and History

[edit]Chemical properties

[edit]Biochemical role

[edit]CoQ10 and electron transport chain

[edit]Antioxidant function of CoQ10

[edit]Biosynthesis

[edit]Absorption and metabolism

[edit]Absorption

[edit]Metabolism

[edit]CoQ10 deficiency and toxicity

[edit]Clinical assessment techniques

[edit]Inhibition by statins and beta blockers

[edit]Pharmacokinetics

[edit]Improving the bioavailability of CoQ10

[edit]Reduction of particle size

[edit]Soft-gel capsules with CoQ10 in oil suspension

[edit]Novel forms of CoQ10 with increased water-solubility

[edit]Supplementation benefits

[edit]

Breath hydrogen (H₂) testing

[edit]Vitamin D₂

[edit]Vitamin D₃

[edit]CoQ₁₀ and electron transport chain

[edit]Antioxidant function of CoQ₁₀

[edit]CoQ₁₀ deficiency and toxicity

[edit]Improving the bioavailability of CoQ₁₀

[edit]Soft-gel capsules with CoQ₁₀ in oil suspension

[edit]Novel forms of CoQ₁₀ with increased water-solubility

[edit]Coenzyme Q₁₀ concentrations in foods and dietary intake