The Pillars of Health:The Prelude

About COVID-19 Booster Vaccinations

2021-12-31T13:18:00.001-05:00

By Dr. Dhia Aldoori December 31, 2021

To the question posed by ‘Anonymous’, whether I “believe” in booster vaccinations for COVID-19 my current stance is I have reservations on their administration. There are some people with special circumstances (older age, immune system compromised, absence of antibody response to initial vaccination) that may benefit from the booster. There also may be a slight temporary boost in immunity from having a booster shot as well. That said, we should focus our resources on vaccinating those who are not vaccinated in the world, and this will help overcome this virus (among other things decreasing the probability of new variants of SARS-Cov-2 arising).

My opinions have been expressed in words which I find hard to improve upon in the viewpoint published in Lancet in October 2021 which I pretty much agree with on almost everything they wrote [1]. What follows is from their writing and notations from me are in orange:

“A new wave of COVID-19 cases caused by the highly transmissible delta variant (and now the omicron variant) is exacerbating the worldwide public health crisis, and has led to consideration of the potential need for, and optimal timing of, booster doses for vaccinated populations.[2]

Although the idea of further reducing the number of COVID-19 cases by enhancing immunity in vaccinated people is appealing, any decision to do so should be evidence-based and consider the benefits and risks for individuals and society. COVID-19 vaccines continue to be effective against severe disease, including that caused by the delta variant. Most of the observational studies on which this conclusion is based are, however, preliminary, and difficult to interpret precisely due to potential confounding and selective reporting.

Even if boosting were eventually shown to decrease the medium-term risk of serious disease, current vaccine supplies could save more lives if used in previously unvaccinated populations than if used as boosters in vaccinated populations.

Boosting could be appropriate for some individuals in whom the primary vaccination, defined here as the original one-dose or two-dose series of each vaccine, might not have induced adequate protection—e.g., recipients of vaccines with low efficacy or those who are immunocompromised[3].

Although the benefits of primary COVID-19 vaccination clearly outweigh the risks, there could be risks if boosters are widely introduced too soon, or too frequently, especially with vaccines that can have immune-mediated side-effects (such as myocarditis, which is more common after the second dose of some mRNA vaccines,[4] or Guillain-Barre syndrome, which has been associated with
adenovirus-vectored COVID-19 vaccines[5]).

Current evidence does not, therefore, appear to show a need for boosting in the general population, in which efficacy against severe disease remains high. Even if humoral immunity appears to wane, reductions in neutralising antibody titre do not necessarily predict reductions in vaccine efficacy over time, and reductions in vaccine efficacy against mild disease do not necessarily predict reductions in the (typically higher) efficacy against severe disease. This effect could be because protection against severe disease is mediated not only by antibody responses, which might be relatively short lived for some vaccines, but also by memory responses and cell-mediated immunity, which are generally longer lived.

Of interest, reported effectiveness against severe disease in Israel was lower among people vaccinated either in January or April than in those vaccinated in February or March, exemplifying the difficulty of interpreting such data. A recent report on the experience in Israel during the first 3 weeks of August 2021, just after booster doses were approved and began to be deployed widely, has suggested efficacy of a third dose (relative to two doses). Mean follow-up was, however, only about 7 person-days (less than expected based on the apparent study design); perhaps more importantly, a very short-term protective effect would not necessarily imply worthwhile long-term benefit.[6]

…even in populations with fairly high vaccination rates the unvaccinated are still the major drivers of transmission and are themselves at the highest risk of serious disease.[7]

If boosters (whether expressing original or variant antigens) are ultimately to be used, there will be a need to identify specific circumstances in which the direct and indirect benefits of doing so are, on balance, clearly beneficial. any decisions about the need for boosting or timing of boosting should be based on careful analyses of adequately controlled clinical or epidemiological data, or both, indicating a persistent and meaningful reduction in severe disease, with a benefit–risk evaluation that considers the number of severe cases that boosting would be expected to prevent, along with evidence about whether a specific boosting regimen is likely to be safe and effective against currently circulating variants.

The vaccines that are currently available are (relatively) safe, effective, and save lives. The limited supply of these vaccines will save the most lives if made available to people who are at appreciable risk of serious disease and have not yet received any vaccine. Even if some gain can ultimately be obtained from boosting, it will not outweigh the benefits of providing initial protection to the unvaccinated."

Bibliography:

[1] P. R. Krause et al., “Considerations in boosting COVID-19 vaccine immune responses,” Lancet, vol. 398, no. 10308, pp. 1377–1380, Oct. 2021, doi: 10.1016/S0140-6736(21)02046-8/ATTACHMENT/99B4689E-FA37-476A-B30E-8D1E3B4E33BC/MMC1.PDF.

[2] E. Callaway, “COVID vaccine boosters: the most important questions,” Nature, vol. 596, no. 7871, pp. 178–180, Aug. 2021, doi: 10.1038/D41586-021-02158-6.

[3] N. Kamar, F. Abravanel, O. Marion, C. Couat, J. Izopet, and A. Del Bello, “Three Doses of an mRNA Covid-19 Vaccine in Solid-Organ Transplant Recipients,” N. Engl. J. Med., vol. 385, no. 7, pp. 661–662, Aug. 2021, doi: 10.1056/NEJMC2108861.

[4] J. W. Gargano et al., “Use of mRNA COVID-19 Vaccine After Reports of Myocarditis Among Vaccine Recipients: Update from the Advisory Committee on Immunization Practices — United States, June 2021,” MMWR. Morb. Mortal. Wkly. Rep., vol. 70, no. 27, pp. 977–982, Jul. 2021, doi: 10.15585/MMWR.MM7027E2.

[5] “Statement of the WHO Global Advisory Committee on Vaccine Safety (GACVS) COVID-19 subcommittee on reports of Guillain-Barré Syndrome (GBS) following adenovirus vector COVID-19 vaccines.” [Online]. Available: https://www.who.int/news/item/26-07-2021-statement-of-the-who-gacvs-covid-19-subcommittee-on-gbs. [Accessed: 31-Dec-2021].

[6] Y. M. Bar-On et al., “Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel,” N. Engl. J. Med., vol. 385, no. 15, pp. 1393–1400, Oct. 2021, doi: 10.1056/NEJMOA2114255.

[7] J. B. Griffin et al., “SARS-CoV-2 Infections and Hospitalizations Among Persons Aged ≥16 Years, by Vaccination Status - Los Angeles County, California, May 1-July 25, 2021,” MMWR. Morb. Mortal. Wkly. Rep., vol. 70, no. 34, pp. 1170–1176, 2021, doi: 10.15585/MMWR.MM7034E5.

Ivermectin and Covid-19

2021-11-22T11:19:00.000-05:00

By Dhia Aldoori November 22, 2021

I have updated my knowledge and stance on ivermectin use in humans for treating the SARS-CoV-2 viral infection to where I consider it to have potential benefit in treating severe cases of COVID 19. I may endorse (not yet though) its regular use in severe cases after randomized controlled trials are carried out on it.[1]–[6][7],[8]

Bibliography:

[1] S. Ahmed et al., “A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness,” Int. J. Infect. Dis., vol. 103, no. 0, pp. 214–216, Feb. 2021, doi: 10.1016/j.ijid.2020.11.191.

[2] N. Okumuş et al., “Evaluation of the effectiveness and safety of adding ivermectin to treatment in severe COVID-19 patients,” BMC Infect. Dis., vol. 21, no. 1, 2021, doi: 10.1186/s12879-021-06104-9.

[3] S. Lehrer and P. H. Rheinstein, “Ivermectin docks to the SARS-CoV-2 spike receptor-binding domain attached to ACE2,” In Vivo (Brooklyn)., vol. 34, no. 5, 2020, doi: 10.21873/invivo.12134.

[4] J. C. Rajter, M. S. Sherman, N. Fatteh, F. Vogel, J. Sacks, and J.-J. Rajter, “Use of Ivermectin Is Associated With Lower Mortality in Hospitalized Patients With Coronavirus Disease 2019,” Chest, vol. 159, no. 1, pp. 85–92, Jan. 2021, doi: 10.1016/j.chest.2020.10.009.

[5] F. Heidary and R. Gharebaghi, “Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen,” Journal of Antibiotics, vol. 73, no. 9. 2020, doi: 10.1038/s41429-020-0336-z.

[6] L. Caly, J. D. Druce, M. G. Catton, D. A. Jans, and K. M. Wagstaff, “The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro,” Antiviral Res., vol. 178, 2020, doi: 10.1016/j.antiviral.2020.104787.

[7] G. Momekov and D. Momekova, “Ivermectin as a potential COVID-19 treatment from the pharmacokinetic point of view: antiviral levels are not likely attainable with known dosing regimens,” Biotechnol. Biotechnol. Equip., vol. 34, no. 1, pp. 469–474, Jan. 2020, doi: 10.1080/13102818.2020.1775118.

[8] “Ivermectin | COVID-19 Treatment Guidelines.” [Online]. Available: https://www.covid19treatmentguidelines.nih.gov/therapies/antiviral-therapy/ivermectin/. [Accessed: 22-Nov-2021].

Notes about Vaccinating With the Covid-19 Janssen/Biotech Vaccine Given the Recent CVST Pause

2021-04-17T08:17:00.002-04:00

By Dr. Dhia Aldoori April 16, 2021

As of today I am aware of 6 patients with the diagnosis of cerebral venous sinus thrombosis (CVST) who have received the Johnson & Johnson (Janssen/Biotech Vaccine) within three weeks of manifestations emanating from CVST.¹ One sadly passed away, one currently in hospital and all are female.

Pending further analysis of the safety of administering this vaccination, a ‘pause’ has been advised by the CDC (Centers for Disease Control) and Food and Drug Administration (FDA). A pause doesn’t mean stopping this vaccine and a caregiver may discuss administration of it with her/his patient and go ahead and advise its receipt.¹

A limited literature search revealed there has been the association of cerebral venous sinus thrombosis (CVST) with prior medical conditions. Examples are thrombophilias (blood platelet abnormalities), inflammatory bowel disease, transient situations (e.g., pregnancy, dehydration, and infection), some medications (e.g., oral contraceptives), substance abuse, and unpredictable events (e.g., head trauma).²

Considering above and pending clarification of the situation I would say you should avoid getting the Janssen Biotech, Inc. (a pharmaceutical company of Johnson & Johnson) vaccine if you have any of the above conditions mentioned in paragraph 3 above.

Furthermore I would not critique those who do not have a possible predisposing condition and wish to avoid this vaccine until the dust is settled. Bear in mind this is a vaccine that is not fully vetted study/safety wise (like the Pfizer and Moderna vaccines), and hence being administered by virtue of the Emergency Use Authorization (EUA) pathway.

Bibliography

1. Joint Media Call: FDA & CDC to Discuss Janssen COVID-19 Vaccine - 4/13/2021 - YouTube. Accessed April 16, 2021. https://www.youtube.com/watch?v=_ELXnGYgsJY

2. Saposnik G, Barinagarrementeria F, Brown RD, et al. Diagnosis and management of cerebral venous thrombosis: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42(4):1158-1192. doi:10.1161/STR.0b013e31820a8364

Notes about Vaccinating against COVID-19 (Pfizer/BioNtech, Moderna and Janssen/Biotech vaccines)

2021-03-31T15:22:00.003-04:00

By Dr. Dhia Aldoori March/2021

(Orange font text targets other caregivers or indicates that that text is my conclusion.)

When the vaccines looked like they were going to hit the stage somewhere in December 2020, I started looking for the data related to its testing. I was looking at efficacy, safety, how many people were vaccinated, how many controls (individuals given sham vaccinations to compare) were employed, mechanism of action, etc.

The numbers we were hearing were the stellar efficacy of 95% and 94.5% for the Pfizer/BioNtek and Moderna vaccines, respectively.

Starting with ingredients:

The Pfizer-BioNTech COVID-19 Vaccine includes the following ingredients: mRNA (messenger ribonucleic acid), lipids ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 2 [(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 1,2-Distearoyl-sn-glycero-3- phosphocholine, and cholesterol), potassium chloride, monobasic potassium phosphate, sodium chloride, dibasic sodium phosphate dihydrate, and sucrose.[1]

The Moderna COVID-19 Vaccine contains the following ingredients: messenger ribonucleic acid (mRNA), lipids (SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG], cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC]), tromethamine, tromethamine hydrochloride, acetic acid, sodium acetate, and sucrose.[2]

Both Pfizer/BioNtech and Moderna vaccines do NOT contain live virus and therefore can NOT cause infection in recipients. They also do NOT interact with our own DNA in any way, but rather use mRNA (messenger ribonucleic acid). How it works: the ‘instructions’ (mRNA) enter immune cells, who ‘listen’ to the instructions and make the spike protein piece. After the protein piece is made, the cell breaks down the instructions and gets rid of them. Next, the cell displays the protein (spike) piece on its surface which trigger an immune response with cytokines and ultimate antibody production which can defend against severe disease caused by SARS-CoV-2. (I do not know yet to what extent it prevents against actual infection – science pending).

The next thing here I want to look at is, what do they mean by ‘efficacy’?

The Moderna vaccine phase 3 trial had 30,351 participants. The primary efficacy end point relied on manifestation of symptoms suggestive of COVID-19 with a positive SARS-CoV-2 by RT-PCR. In those aged 65 and older the efficacy was 100% (meaning no symptoms), and in ages 18 to under 65 the efficacy was 93.4% with an overall participant average efficacy of 94.5%. None vaccinated had severe illness or were admitted to a hospital. [3]

The Pfizer/BioNtech vaccine phase 3 trial had 44,000+ participants. Here also the primary efficacy end point relied on manifestation of symptoms suggestive of COVID-19 with a positive SARS-CoV-2 by RT-PCR or in some cases a local nucleic acid amplification test (NAAT) result. There was 1 severe COVID-19 occurrence from 14 days after Dose 2 out of 18,175 vaccinated. In the placebo group of 18,261 there were 3 severe cases.[4] (I thought there would be more in the placebo group.) The other efficacy endpoint I looked at was based on the first COVID-19 occurrence based on CDC defined symptoms from 7 days after dose 2. See table 22 in reference [4]. The number of vaccinated participants was 19,965 and the placebo group was 20,172. The number of cases in the vaccinated group was 9, and the number of cases in the placebo group was 172 ending with a vaccine efficacy of 94.7%. (I am assuming the different numbers of vaccinated and placebo seen, results from the different times at which data was extracted for analysis, or because of their status regarding whether or not they were infected previously. I could not tell which.)

Given that both methods relied on reporting symptoms, I surmise an unknown number of participants must have gotten COVID-19 without being detected, as they were symptom free subjectively. (I wish all the participants would have had periodic, e.g. weekly testing for the virus, which would have given us more accurate numbers overall.)

The safety issues: (I have relied on the CDC - Centers for Disease Control - which I do trust at this time for safety information.) COVID-19 vaccines appear relatively safe to date (March 28, 2021) after millions of people in the United States have received COVID-19 vaccines, and these vaccines will continue to undergo safety monitoring. Some people have no side effects. Others have reported common side effects after COVID-19 vaccination like swelling, redness and pain at injection site, fever, headache, tiredness, muscle pain, chills, and nausea. A small number of people have had a severe allergic reaction (called “anaphylaxis”) after vaccination, but this is extremely rare.[5] That said, the word ‘rare’ takes on a different meaning when you know that the actual reports of death through March 22, 2021 have been 2,216. That’s a very unfortunate loss of life representing 0.0018% of 126 million doses of COVID-19 vaccines administered in the United States from December 14, 2020.[6] So I recommend getting the vaccine in a venue that has the capacity to deal with a possible severe allergic reaction. Also stay for 15–30 minutes after your injection for observation, which becomes even more important if you are an allergy prone person.

The third vaccine I would like to talk about is the vaccine from Janssen Biotech, Inc. (a pharmaceutical company of Johnson & Johnson). The related Emergency Use Authorization (EUA) application is dated February 26, 2021 and since has been granted by the Food and Drug Administration (FDA). This vaccine is administered in 1 shot with similar side effects to the two dose vaccines (Pfizer/BioNtech, Moderna).

The Janssen COVID-19 Vaccine includes the following ingredients: recombinant, replication-incompetent (i.e. can NOT cause infections) adenovirus type 26 expressing the SARS-CoV-2 spike protein, citric acid monohydrate, trisodium citrate dihydrate, ethanol, 2-hydroxypropyl-β-cyclodextrin (HBCD), polysorbate-80, sodium chloride.[7]

How it works: after administration of Ad26.COV2.S, binding of the Ad26 vector to cellular receptors is mediated by fibers on the Ad26 capsid. After transduction of the cell, episomal vector DNA drives cellular production of the transgene encoded S protein. The S protein is then expressed on the cell membrane where it is sensed by the host immune system, resulting in humoral and cellular immune responses directed against the SARS-CoV-2 S protein.[8]

The J&J/Janssen vaccine was 66.3% effective in clinical trials (efficacy) at preventing laboratory-confirmed COVID-19 illness in people who had no evidence of prior infection 2 weeks after receiving the vaccine. The vaccine had high efficacy at preventing hospitalization and death in people who did get sick. No one who got COVID-19 at least 4 weeks after receiving the J&J/Janssen vaccine had to be hospitalized.[9]

The efficacy numbers will change as more people are vaccinated.

So, what is the actual benefit from these vaccines? They help prevent serious illness and death from SARS-CoV-2. Also, of vital import is it will help end the pandemic by increasing herd immunity (assuming enough individuals get it) and by virtue of lessening manifestations of COVID-19 which spread the virus such as coughing and resultant aerosolization of virus particles.

To get or not to get: GET. The risk/benefit ratio is very convincing to me in favor of getting one of the vaccines above. I personally received my first Moderna shot December 29, 2020 and the second one January 26, 2021. (The second shot laid me out in bed the next day with significant achiness, headache, and chills – so allegedly my immune system is still intact J.)

Bibliography

[1] Pfizer, “PFIZER-BIONTECH COVID-19 VACCINE.” https://www.fda.gov/media/144414/download (accessed Mar. 29, 2021).

[2] Moderna TX and Inc, “FACT SHEET FOR RECIPIENTS AND CAREGIVERS EMERGENCY USE AUTHORIZATION (EUA) OF.” Accessed: Mar. 29, 2021. [Online]. Available: www.modernatx.com/covid19vaccine-eua.

[3] FDA and Cber, “Vaccines and Related Biological Products Advisory Committee December 17, 2020 Meeting Briefing Document - FDA,” 2020.

[4] Pfizer, “Vaccines and Related Biological Products Advisory Committee December 10, 2020 Meeting Briefing Document- Sponsor,” 2020.

[5] CDC, “Safety of COVID-19 Vaccines | CDC.” https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/safety-of-vaccines.html (accessed Mar. 28, 2021).

[6] CDC, “Selected Adverse Events Reported after COVID-19 Vaccination | CDC.” https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/adverse-events.html (accessed Mar. 28, 2021).

[7] D. Administration, “FACT SHEET FOR RECIPIENTS AND CAREGIVERS EMERGENCY USE AUTHORIZATION (EUA) OF.” Accessed: Mar. 29, 2021. [Online]. Available: www.janssencovid19vaccine.com.

[8] JANSSEN BIOTECH, “Vaccines and Related Biological Products Advisory Committee February 26, 2021 Meeting Briefing Document- Sponsor,” 2021. Accessed: Mar. 29, 2021. [Online]. Available: https://www.fda.gov/media/146219/download.

[9] “Information About Johnson & Johnson’s Janssen COVID-19 Vaccine | CDC.” https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/janssen.html (accessed Mar. 29, 2021).

COVID-19: The Jury is OUT again on Hydroxychloroquine

2020-06-12T15:33:00.000-04:00

The jury is out again on hydroxychloroquine (HCQ) and chloroquine (CQ) as a result of refusal of Surgisphere Corporation (the analyzing agency of the database elements presented in the paper) to divulge the full dataset, client contracts, and the full ISO audit report to peer review for analysis. The claim was that such transfer would violate client agreements and confidentiality requirements.
This retraction is appropriate in my view as the full scientific evaluation wasn't completed.
In spite of the retraction, the information and data didn't appear flawed to me and therefore I would hesitate in endorsing use of HCQ and CQ pending further elucidation of this quandary.

Frustrating stuff.

D. Aldoori

[Retraction—Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet]
[COVID-19 Running Notes]

COVID-19: The Jury is Back on Hydroxychloroquine

2020-05-23T18:40:00.000-04:00

At this time, I recommend against using chloroquine or hydroxychloroquine to prevent or treat COVID-19 infection. This recommendation is mostly based on the study published in the Lancet online, May 22, 2020.[1]

Included in this study were 96,032 hospitalized patients from 671 hospitals who were diagnosed with COVID-19 between Dec 20, 2019, and April 14, 2020 and met the inclusion criteria for said study. It was convincingly a large multinational real-world analysis.

The authors (who I agree with), did not observe any benefit of hydroxychloroquine or chloroquine (when used alone or in combination with a macrolide) on in-hospital outcomes, when initiated early after diagnosis of COVID-19. Each of the drug regimens of chloroquine or hydroxychloroquine alone or in combination with a macrolide was associated with an increased hazard for clinically significant occurrence of ventricular arrhythmias and increased risk of in-hospital death with COVID-19.[1]

[1] M. R. Mehra, S. S. Desai, F. Ruschitzka, and A. N. Patel, “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis,” Lancet, vol. 0, no. 0, 2020. Link to study.

Can the Surgical N95 Respirator Mask Halt the SARS-CoV-2 Virus?

2020-04-24T16:24:00.000-04:00

How does the surgical N95 respirator mask by 3M stop the SARS-CoV-2 virus from accessing the airway passages of the wearer?

Coronavirus virions are spherical with diameters of approximately 125 nm. Where an ‘nm’, indicates a nanometer which is a billionth of a meter.

The indicated mask is documented to have a filter efficiency level of at least 95% against particulate aerosols free of oil and was tested against a 0.3 micron (0.0000003 meter) particle (mass median aerodynamic diameter). Where a micron is one millionth of a meter.

Given above facts where the virion (0.000000125 meter) is 2.4 times smaller than the mask’s preventive ‘entry’ capacity of 0.0000003 meter, one may wonder is it not going to go through?

Answer: viruses do not fly through the air all by themselves, rather they are carried in the aerosol particles expelled from the infected with or carrier person of the virus. This originates from the coughing or sneezing process. And since aerosols seem to average at 1.25 microns (0.00000125 meter), which is larger than the 0.3 micron above, therefore the virus conveying aerosol should be stopped by the mask.

Notably here, the aerosols with its virions lodge in the outside of the mask and therefore the wearer should avoid touching the outward surface of the mask.

COVID-19: Should I wear a protective mask? Masks for general public?

2020-04-09T18:17:00.000-04:00

Question (TK): Hi there, what are your thoughts on the general public buying masks online to wear when shopping or going outside? I know there is a shortage of masks in hospitals, but it seems like there’s a surplus online, so I assume hospitals aren’t buying the ones I am finding. An example:

Amazon Link

Answer (Dhia Aldoori): I think it is a good idea for all to wear masks in public at this time, particularly when you are going to be in a place which may force too close person proximity, and always if you are sick with the possibility people may come near you (especially important in a closed environment).

That said, let us (health professionals) have first dibs on the really useful kind, the NIOSH N95 version by 3M which I couldn’t find on Amazon.

The ones in the link are apparently abundant and will help prevent aerosol projection from a cougher and sneezer, and prevent a person from unconsciously hand-face touching. It won’t protect against incoming viruses. The other kind does, and isn’t currently very available to many caregivers.

Running Notes COVID-19

COVID-19: Using Anti-inflammatory Medications

2020-04-09T09:48:00.000-04:00

At this time I am of the opinion that avoidance of NSAIDs for flu like symptoms is the way to go [non steroidal anti-inflammatory drugs are like ibuprofen (Advil, Motrin), naproxen (Aleve), diclofenac (Voltaren), meloxicam (Mobic), etc.]. Of course, that is if you even feel inclined to band-aid your symptoms. Barring an allergy or medical condition where it is contraindicated, I would go with acetaminophen (Tylenol). Covid-19: ibuprofen should not be used for managing symptoms, say doctors and scientists.
The theory behind this is that NSAIDs may hinder the natural inflammation cascade of events otherwise needed to fight against viral infections. That said, even acetaminophen, has an antipyretic action which I am not sure I want to impede during this process. I change my stance if there is excessive fever making the patient uncomfortable or symptomatic (e.g. delirious).
I am more a fan of rest, hydrate, good nutrition (beef barley soup rocks) and stay warm. After you do the preceding, hydrate some more. 🙂

COVID-19: Running Notes (quick link above or click on my picture above)

2020-03-24T09:45:00.000-04:00

Clicking on the quick link above or the link below within this post will take you to the diagram.

See "Black Box Warning" update for 4/3/20.
My COVID-19 Running Notes @ Diagrams.net

Depending on feedback I will answer questions within the updated diagram.

Nightshade Vegetable Allergies

2017-08-13T09:42:00.000-04:00

In response to:

[Bess Rhoades has left a new comment on your post "Why I'm a Fan of Copper":

Dr. A- I do not know how to enter a question on this blog, so this is the best I could do. Could you please address what you believe about nightshade vegetable allergies- and their possible role in inflammatory process and perhaps even arthrities in certain individuals. I thought this was far fetched until I began reading. This article in particular caught my interest:

https://www.westonaprice.org/health-topics/food-features/nightshades/

Thank you]

Looking at your reference.

Paragraph 1: Claiming sensitivity to these plants without delineating a causal pathophysiology is always concerning to me and makes the content lack credibility.

Paragraph 3: If you have as claimed a sensitivity to a certain food, I don’t think it would be harmful to avoid them for a month or two, and monitor the improvement or lack thereof. I doubt with pretty good logic and science that nightshade plants "cause" heartburn. They may exacerbate symptoms but don’t cause relaxation of the lower esophageal sphincter, as far as I know at this time. (One of these days I will write up the causes of alluded to relaxation).

Paragraph 5: Potatoes causing dropsy. Anytime a human relies on a high carbohydrate low protein diet in tandem with a deficiency of other important nutrients, expect there to be body swelling.

I stopped reading after paragraph 6 as the author's arguments and evidence presentation were excessively weak and lacking in logic and definite pathophysiological cause, not to mention heavily infused with loose associations being put forth as evidence. Also the author, although listing references, didn’t associate them with the facts being quoted and therefore very difficult to verify his studies/articles/references.

Notes: Tomatoes have evidence of being anticancer.

In summary I would say that it's possible some people may have increased sensitivities to certain foods, but I would hesitate to say that 'nightshade' plants are dangerous as a group.

Mucuna Pruriens in Anxiety/Depression

2015-11-13T19:33:00.000-05:00

Question: AnonymousNovember 13, 2015 at 2:45 PM
What are your thoughts on the herbal supplement, mucuna pruriens, for anxiety/depression?

Answer: I have personally not been aware of this herb, Mucuna pruriens, till your question. After a quick research I found the following:

The major phenolic constituent of M. pruriens beans was found to be L-dopa (5%), along with 5-indole compounds, two of which were identified as tryptamine and 5-hydroxytryptamine.

The thought is that L-dopa being a precursor of dopamine, thence the different pharmacological effects. (Anti-diabetic, anti-inflammatory, neuroprotective, and anti-oxidant properties).

I would think that the benefit of this herb would be via 1- the increased production of adrenaline (from the precursor L-dopa), outside the brain, 2- the provision of a significant amount of precursors (tryptamine and 5-hydroxytryptamine), for serotonin peripherally and centrally, and 3- provision of L-dopa to the brain (as it crosses the blood brain barrier), which is a precursor for dopamine centrally. The increased production of adrenalin physiologically, in addition to increased production of serotonin and dopamine centrally should have a positive impact on depression.

In India, the seeds of M. pruriens have traditionally been used as a nervine tonic, and as an aphrodisiac for male virility.

It looks promising logically for anxiety but more so for depression, but I'm afraid I can't endorse its use at this time as I am not familiar with its dosing, its safety profile, purity of preparation, and studies where it has been used for anxiety or depression.

[Ref.- Lampariello LR, Cortelazzo A, Guerranti R, Sticozzi C, Valacchi G. The Magic Velvet Bean of Mucuna pruriens. Journal of Traditional and Complementary Medicine. 2012;2(4):331-339.]

How to Decide On How Much 5-HTP (5-Hydroxytryptophan) and L-Tyrosine to Take In Mild Depression? (Edited: 1/15/17)

2013-06-07T21:13:00.000-04:00

The question posed: “I am taking 5-HTP and L-Tyrosine supplements for mild depression and have been doing some research. I have read that a 10:1 ration (L-tyrosine to 5-HTP) is recommended so that no neurotransmitter is depleted. What are your thoughts? How about a 5:1 ratio? I know everyone is different but how would you recommend starting out and adjusting dosage?”

My answer: (run the following by your doctor first before applying)

I don’t agree with tying these two building blocks together in a ratio as posed because of the following: each one is involved in the production of different neurotransmitters, and everyone has a different magnitude of symptoms of depression which is commensurate with the neurotransmitter that is deficient. Therefore the symptoms and the response thereby to ingesting these precursors can be your guide on how much to take in the beginning and thereafter tailor accordingly.

If the exhibited symptoms include headache, poor sleep, inexplicable body pains, and/or memory issues then the anticipated deficiency is more in line with serotonin deficiency. Hence I would think 5-HTP is going to be needed for sure. I would start with a dose of 50 mg nightly after the evening meal and escalate a week later to 100 mg nightly and hold there for at least one month to see if the symptoms described here improve. It takes time to build up the amino acid pools in the body. This is assuming the 5-HTP is good quality and pure. If nausea arises, or if you become jittery, sweaty or get a rapid heart rate 30-60 minutes after (Edited: 1/15/17) intake of the 5-HTP in spite of taking it after a regular sized meal then you may be taking too much.

If the exhibited symptoms include sugar and starch craving, fatigue, preponderance of gloom, poor stamina, feeling cold more than normal people around you then the anticipated deficiency would be more in the adrenaline, and noradrenaline (neurotransmitter) arena. In this setting the tyrosine will be essential to production of the forementioned, as it is the precursor to both. As such I would go with a starting dose of 100 mg daily with a meal. This may be upped 100 mg every three days to a maximum of 1000 mg daily depending on side effects and therapeutic response. Once you get improvement then I would hold at that dose for 6 to 9 months then start weaning off over the following 3 months. I started low on the tyrosine as some patients may be deficient in this amino acid and on taking it in a large dose may result in hypotension, and or dizziness secondary to a higher production of adrenaline in a more than used to fashion. The body should be able to adjust to this over the following weeks, and if not I would do the escalation even more slowly.

Note: to produce neurotransmitters from precursors like you are targeting, there must be available certain vitamins which are part of certain enzymes and co-enzymes necessary for this production. Specifically I will mention vitamin C for production of serotonin and noradrenaline. Also copper and iron for production of noradrenaline. The amount I recommend is vitamin C 250 mg daily, copper 2 mg daily and iron 8-15 mg daily, or even better getting the equivalents in food (tomatoes, peanuts, red meat) (Edited: 1/15/17). The last two may be found in many multivitamin preparations. I would also recommend taking the multivitamin after the main meal of the day to enhance their absorption and decrease the possibility of nausea.

Note: do not take above supplements with anti-depressants.

A DIET FOR FIBROMYALGIA? FOODS ACCEPTABLE FOR FIBROMYALGIA AT THE RESTAURANT.

2012-12-20T11:18:00.000-05:00

Regarding the diet for Fibromyalgia, with a couple of exceptions, it is basically the one found here: http://thepillarsofhealth.blogspot.com/2008/04/appendix-diet.html

For Fibromyalgia I prefer that the patient not have any products containing white flour, because of its refinement and the ease with which it is absorbed into the blood stream as glucose, which will elicit an insulin response which will inhibit adrenalin output, which we don’t want.

A practical principle here is to avoid high glycemic index foods. A nice list is here: http://www.health.harvard.edu/newsweek/Glycemic_index_and_glycemic_load_for_100_foods.htm

Another point is that there should be emphasis on protein intake (fish, chicken, turkey, eggs, cheese, etc.), as there is the need to keep the amino acid pool satisfactorily stocked with the building blocks for energy hormones, and neurotransmitters. In addition amino acids can act as a source for slow production of glucose (which shouldn’t initiate an insulin secretion response – I have not verified this factoid). This production of glucose takes place in the liver in a process called gluconeogenesis.

Acceptable restaurants foods for Fibromyalgia:

·         Chicken paprikash without the dumplings or noodles. More sour cream or yoghurt and vegetables.

·         Salads topped with chicken, or steak.

·         Steak and eggs. For breakfast. Hold on the white bread.

Basically apply: no refined sugars and no white starches.

Smoking and Depression

2012-11-29T17:26:00.001-05:00

First, let us try and understand what cigarettes do as relates to depression.

According to the American Heart Association, nicotine addiction (I prefer calling it tobacco addiction because it is not only nicotine that is addictive in the tobacco), has historically been one of the hardest addictions to break, while the pharmacological and behavioral characteristics that determine tobacco addiction are similar to those determining addiction to heroin and cocaine.

Is there anything mystical about how cigarettes are addictive? No. It is all very organic, and physical. The tobacco contains two categories of chemicals that establish addiction in addition to the conditioned reflex aspect (Pavlovian), which also fortifies the addiction. This last part is more related to the whole process of the activity itself of the cigarette touching the lips, the action of inhalation, the smell of the cigarette, holding the cigarette, etc. As nicotine enters the body, it is distributed quickly through the bloodstream and crosses the blood–brain barrier reaching the brain within 10–20 seconds after inhalation. The elimination half-life of nicotine in the body is around two hours.^{^[i]}

Tobacco smoke contains, in addition to nicotine (the first category I alluded to above), the monoamine oxidase inhibitors harman and norharman (the second category I alluded to above). These second category compounds significantly decrease MAO activity in smokers. This was evidenced by positron emission tomography imaging that showed smokers have a much lower activity of peripheral and brain MAO-A (30%) and -B (40%) isozymes compared to non-smokers.^{^[ii]},^{^[iii]} MAO enzymes break down monoaminergic neurotransmitters such as dopamine, norepinephrine, and serotonin. It is thought that the powerful interaction between the MAOIs and the nicotine is responsible for most of the addictive properties of tobacco smoking.^{^[iv]} Therefore when the activity of MAO enzymes is impeded these neurotransmitters are higher in quantity (enhancing brain function artificially), but the flip side of this is when the tobacco is gone the MAO enzymes increase and hence decrease those neurotransmitters (at least temporarily. This translates into the withdrawal syndrome from tobacco in addition to worsening of any depression state present. The magnitude and duration of these phenomena will vary with how long and how much the person has been using tobacco, and how healthy the individual is. In other words a less healthy person will take longer to renovate their brain neurotransmitter production compared to a healthier person.

As such a treatment strategy for you: target increasing the neurotransmitters in the brain by all means possible which are safe if supervised:

Decrease MAO enzymes activity by taking a MAO enzyme inhibitor drug. An example of this kind of drug is phenelzine (Nardil). [As a last resort only].
Provide the building blocks for the neurotransmitters: i. Protein is the major component of almost all major currently recognized neurotransmitters. ii. Vitamin C is essential for the manufacture of certain neurotransmitters. iii. All the B-complexes play a significant role in the production of neurotransmitters and are of paramount significance for their function. iv. Good hydration. How this works is multifactorial and I won't go into here in biochemical/physiological detail. That being said, intake sufficient fluid to maintain urine color a very light light yellow. If you are sweating in your exercise routine then replace your losses with a fluid containing sodium chloride (salt), potassium and some magnesium. The last isn't as important as the first two, so if not present in the purchased fluid then no worries.
Stimulate the production of adrenaline peripherally to stimulate neurotransmission and neurotransmitters in the brain. This is done by regular exercise targeting sweating 10 minutes per session in the beginning and later increasing that according to what your body tells you. Do one day per week (minimum), per decade of your age. If you are 28 years old then minimum three days exercise per week. If you are 44 years old, then five days per week, and so on.
Avoid food substances that inhibit adrenaline production. Any food that leads to secretion of insulin in high quantities causes inhibition of adrenaline secretion. This would be all foods that are assimilated and absorbed rapidly into the blood stream as glucose (a simple sugar). Examples are all refined sugars and all white refined starch products. (Candy, candybars, pastries, pasta, lasagna, pizza, mashed potatoes, rice, etc.)
Provide an environment to your body which enhances production and conservation of these neurotransmitters. In other words, sufficient regular sleep. To the tune of 8 hours per 24 hours. Preferably in one block.
Stop smoking, start 7 mg patch nicotine (while awake) for two weeks, start the MAO enzyme inhibitor, all in addition to above.
You must be off escitalopram for 10 days prior to starting MAO enzyme inhibitor. (They interact).

Comments:

Overcoming the conditioned reflexes will take time. Think months to a year. So the craving triggered by memory will take a while to go away.
The physical organic aspect of the addiction goes away quicker.
Taking MAO enzyme inhibitors as an antidepressant medication is serious business and must be supervised closely by the prescribing physician. Avoid over the counter medications unless cleared by physician who is aware you are on a MAO enzyme inhibitor.
Tobacco smoke will enhance the activity of the escitalopram in an ongoing fashion. (answering your question above.
The nicotine content of popular American-brand cigarettes has slowly increased over the years, and one study found that there was an average increase of 1.6% per year between the years of 1998 and 2005. This was found for all major market categories of cigarettes.^{^[v]} So the sooner you quit the better.

References:

[i] http://en.wikipedia.org/wiki/Nicotine

[ii] Herraiz T, Chaparro C (2005). "Human monoamine oxidase is inhibited by tobacco smoke: beta-carboline alkaloids act as potent and reversible inhibitors". Biochem. Biophys. Res. Commun. 326 (2): 378–86.

[iii] Fowler JS, Volkow ND, Wang GJ, et al. (1998). "Neuropharmacological actions of cigarette smoke: brain monoamine oxidase B (MAO B) inhibition". J Addict Dis 17 (1): 23–34.

[iv] Villégier AS, Blanc G, Glowinski J, Tassin JP (September 2003). "Transient behavioral sensitization to nicotine becomes long-lasting with monoamine oxidases inhibitors". Pharmacol. Biochem. Behav. 76 (2): 267–74.

[v] Connolly, G. N; Alpert, H. R; Wayne, G. F; Koh, H (2007). "Trends in nicotine yield in smoke and its relationship with design characteristics among popular US cigarette brands, 1997–2005". Tobacco Control 16 (5): e5. doi:10.1136/tc.2006.019695. PMC 2598548. PMID 17897974.

Is it safe to take 200-300mg of 5-HTP a day for Depression? Is Rhodiola Rosea useful for depression?

2012-10-07T20:44:00.000-04:00

Depending on the actual bioavailability provided by different 5-HTP preparations I would say a good pure preparation of 100 mg daily should be a sufficient amount in this situation. Taking too much could end up in a serotonergic reaction (agitation, consciousness impairment, tachycardia, hallucinations, etc.)[1]. Therefore with a reliable preparation, as seen with ‘PureEncapsulations’ I would stick to 100 mg daily only.

Rhodiola Rosea: In Russia and Scandinavia, it has been used for centuries to cope with the cold Siberian climate and stressful life.[2] The theory is that is has a positive impact on serotonin, dopamine and acts as a monoamine oxidase inhibitor. This would affect depression in a positive way.[3] In light of what it can do and the lack of studies, and lack of standardization I would only use it with a high degree of caution and under direct supervision of your physician lest you trigger a sertonergic reaction as described above. I have never used this substance before but after reading about it, it does look interesting.

For depression: Are there any other herbs, amino acids, or vitamins you would recommend? I also like Copper 2-3 mg once daily with a meal (which can be in a multivitamin). Be cautious with other amino acids though as they can have some pretty significant effects and side effects. Sometimes I will also use St. Johns Wort at 300 to 900 mg daily in divided doses. This last is a weak serotonin reuptake inhibitor.

[1] http://www.nlm.nih.gov/medlineplus/ency/article/007272.htm

[2] http://en.wikipedia.org/wiki/Rhodiola_rosea

[3] Monoamine oxidase inhibition by Rhodiola rosea L. roots. [J Ethnopharmacol. 2009] - PubMed - NCBI . http://www.ncbi.nlm.nih.gov/pubmed/19168123. Accessed 10/7/2012 2012.

How to Raise GABA (Gamma-amino-butyric acid) in the Brain by Natural Means

2012-05-27T16:20:00.000-04:00

[Answering M.F.’s questions: You recently stressed that I need to increase the levels of GABA in my body to help with my persistent anxiety. Are there natural ways to do this through specific foods or even drinks, such as loose leaf tea (due to its precursor l-theanine)?]

Background: As a general rule, in promoting health I like to stay as close as possible to letting and assisting the body in building its own enzymes, hormones, different substances via its own machinery because of my fear of disrupting the body’s magnificent equilibrium. This fear encompasses different issues of feedback mechanisms, rate limiting steps, dependency issues, etc.

Without further ado: GABA (Gamma-amino-butyric acid) functions in brain tissue as an inhibitory neurotransmitter by altering transmembrane potential differences. Throughout the adult brain, where scientists have mostly studied the roles of glutamate and GABA, it has been established that both amino acids function primarily as signals transmitted between cells. Most of the cells transmitting either glutamate or GABA signals are neurons. After release, GABA diffuses a very short distance and binds to receptor proteins on the surface of the target neuron, which are specialized for sensing either GABA or glutamate via either glutamatergic or GABA receptors. GABA subsequently will be taken up, or transported out by carrier proteins. The uptake process requires energy and involves co-transport of GABA, which is neutral at physiological pH, together with two sodium ions and one chloride ion.[3],[5] The result of GABA stimulation of GABA receptors specifically serves to retard the stimulatory effects of glutamate throughout the brain.

Why is it important for anxiety? All anxiogenic agents act on the GABA-A receptor/chloride ion channel complex, implicating this neurotransmitter system in the pathogenesis of anxiety and panic attacks.[7] As such increasing GABA availability, and or increasing the efficiency/effect of, or sensitivity of GABA receptors should help alleviate the feelings of anxiety.

How to promote its availability: GABA (Gamma-amino-butyric acid) can be formed from glutamic acid in the presence of pyridoxal phosphate[1] (as a cofactor for glutamic acid decarboxylase – GAD).[2] The pyridoxal phosphate arises from vitamin B6 (pyridoxine). Therefore availability of B6 is necessary. Don't overdo. Too much B6 has neurotoxic effects. 10 mg per day is easily sufficient. Other factors that may promote healthy GABA metabolism would be physiological levels of sodium and chloride (salt), in an ample fluid medium. Practical translation: sufficient salt and water intake. Lyte-Hydrate well.

Valerian raises GAD (glutamic acid decarboxylase) activity[4] which may raise GABA (Gamma-amino-butyric acid) in the neuronal tissues which should have a calming effect. The extract also contains GABA[8] which may have a direct impact on GABA receptors.

Make sure the building block of GABA is available (glutamic acid): All meats, poultry, fish, eggs, dairy products, and kombu are excellent sources of glutamic acid. Some protein-rich plant foods also serve as sources.[1]

To my knowledge only certain pharmaceuticals (such as phenobarbitone) function as a GABA receptor modulator which enhances the target function of said receptors.

Theanine: is an amino acid present in green tea which appears to have stimulatory effects and inhibitory effects on glutamic acid. For calming one would desire the inhibitory effect. How it works seems unclear to date (5-28-12). As such I would think it would be okay to use although in this case it is functioning more as a pharmaceutical agent and not as a building block. Theanine is similar in molecular structure to glutamic acid and hence could be ‘pressuring’ glutamic acid and causing it to be more available for transforming into GABA. Here I am theorizing. Then again it could be occupying glutamatergic receptors without causing the usual excitatory activity which glutamic acid usually results in. Here I am theorizing again.

References:

[1] Rodwell VW. Chapter 30. Conversion of Amino Acids to Specialized Products. In: Bender DA, Botham KM, Weil PA, Kennelly PJ, Murray RK, Rodwell VW, eds. Harper's Illustrated Biochemistry. 29th ed. New York: McGraw-Hill; 2011. http://0-www.accessmedicine.com.library.ccf.org

[2] http://en.wikipedia.org/wiki/Glutamate_decarboxylase

[3] GABA as a Neurotransmitter and Neurogenic Signal - eLS - Barker - Wiley Online Library . http://0-onlinelibrary.wiley.com.library.ccf.org/doi/10.1038/npg.els.0000121/full. Accessed 5/13/2012 2012.

[4] R Awad, D Levac, P Cybulska, Z Merali, VL Trudeau, JT Arnason (2007) Effects of traditionally used anxiolytic botanicals on enzymes of the gamma-aminobutyric acid (GABA) system Can J Physiol Pharmacol 85: 933-942. Doi:10.1139/Y07-083.

[5] Nicotinic Acetylcholine Receptors - eLS - Lindstrom - Wiley Online Library . http://0-onlinelibrary.wiley.com.library.ccf.org/doi/10.1002/9780470015902.a0000245.pub2/full. Accessed 5/20/2012 2012.

[6] Russek, S. J. 2006. γ-Aminobutyric Acid (GABA) Receptors. eLS.

[7] Reus VI. Chapter 391. Mental Disorders. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012. http://0-www.accessmedicine.com.library.ccf.org/content.aspx?aID=9112222. Accessed May 27, 2012.

[8] http://en.wikipedia.org/wiki/Valerian_%28herb%29#Biochemical_composition

Why I'm a Fan of Copper

2012-04-29T14:51:00.001-04:00

[Answering M.F.’s questions: What is the importance of taking copper? Should everyone be taking 2mg of this supplement daily, separate from a multivitamin? Or does this apply only to a specific group of individuals? Also, is there an advantage to taking either the citrate or glycinate form in terms of absorption?]

What is the importance of taking copper? Copper is an integral part of numerous enzyme systems, including amine oxidases, ferroxidase (ceruloplasmin), cytochrome-c oxidase, superoxide dismutase, and dopamine hydroxylase. Copper is also a component of ferroprotein, a transport protein involved in the basolateral transfer of iron during absorption from the intestine. As such, copper plays a role in iron metabolism (important for blood formation), melanin synthesis (important for skin color), energy production, neurotransmitter synthesis, and nervous system function; the synthesis and cross-linking of elastin and collagen; and the scavenging of superoxide radicals.[1]

From my viewpoint, the most important aspects are for the insurance of presence of sufficient quantities of copper for the cross linking of elastin and collagen and the dopamine hydroxylase.

The cross linking of elastin and collagen is of immediate importance in the health of bones, joints, tendons, skin and hair among other things. Of paramount importance though is the dopamine hydroxylase. This is because this enzyme is necessary for the hydroxylation of dopamine to noradrenalin which is the precursor to adrenalin.[2] I consider adrenalin to be of supreme importance for health when generated physiologically naturally. Of note here is that vitamin C (ascorbic acid) is a cofactor for the hydroxylation of dopamine to noradrenalin.

Don't take more than the recommended 2-3 mg daily, as at higher levels toxicity may ensue. (More isn't better). 10 mg intake can be dangerous.[1] See table:

Deficiencies and Toxicities of Metals - from Harrison's Online via AccessMedicine

It has been seen that copper did have a positive impact on HDL (the cardioprotective cholesterol) and did lower oxidized LDL values. This last is the type that tends to form the clogging cholesterol within the walls of blood vessels (specifically arteries). The study showing this was somewhat short for my taste and wasn’t consistent in its results but the logical tie-in to the heart protective factors is solid.[3] This study used the glycinate form of copper.

Another study shows that patients suffering from diabetes mellitus have lower levels of copper in their serum compared to control patients.[4] Again the tie-in here is logical.

Should everyone be taking 2mg of this supplement daily, separate from a multivitamin? Individuals whose nutrition is deficient or low in copper intake should take a separate supplement. Dietary sources of copper include shellfish, liver, nuts, legumes, bran, and organ meats. For myself I prefer not to take a chance on not getting enough of this essential mineral and hence take it anyway separate from the copper from other sources. By taking it separately as a 2 mg pill/capsule in addition to a usual 2 mg in the multivitamin tablet then we cap at 4 mg per day plus nutritional sources. We stay well below the 10 mg/day toxic level.

Is there an advantage to taking either the citrate or glycinate form in terms of absorption? It would appear that, at least in animals the glycinate form will provide superior bioavailability of the nutrient, compared to the citrate. That being said I personally take the citrate form as I also take a multivitamin tablet three times weekly, in addition to regular food intake.[5]

References:

[1] SP Russell RM (2012) Chapter 74. Vitamin and Trace Mineral Deficiency and Excess. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. (ed), Harrison's Principles of Internal Medicine. 18th ed. edn., McGraw-Hill, New York, pp http://0-www.accessmedicine.com.library.ccf.org/content.aspx?aID=9099706.

[2] Molina PE. Chapter 6. Adrenal Gland. In: Molina PE, ed. Endocrine Physiology. 3rd ed. New York: McGraw-Hill; 2010. http://0-www.accessmedicine.com.library.ccf.org/content.aspx?aID=6169718. Accessed April 29, 2012.

[3] RA Disilvestro, EL Joseph, W Zhang, AE Raimo, YM Kim (2012) A randomized trial of copper supplementation effects on blood copper enzyme activities and parameters related to cardiovascular health Metabolism Doi:10.1016/j.metabol.2012.02.002.

[4] M Basaki, M Saeb, S Nazifi, HA Shamsaei (2012) Zinc, Copper, Iron, and Chromium Concentrations in Young Patients with Type 2 Diabetes Mellitus Biol Trace Elem Res Doi:10.1007/s12011-012-9360-6.

[5] Ammerman CB, Baker DH. Bioavailability of Nutrients for Animals: Amino Acids, Minerals, Vitamins. Chapter 7. Copper Bioavailability. Pp. 127-156. Link.

Chapter 10: Depression

2012-01-02T21:31:00.000-05:00

Opinion: It is time to relegate Freudian theories to the museum and to realize that emotions, feelings, mood and thinking are results of organic processes in the body and brain interacting with the environment. Healthy organic processes can handle bad memories.

We have repeatedly heard that depression is due to an imbalance of chemicals in the brain without specification of those chemicals and why they even became imbalanced. I will outline to you what I think is amiss and how to prevent and alleviate the condition of depression.
By not following The Pillars described in previous chapters, we run the risk of not having certain chemicals in our brains in sufficient amounts to function correctly. Specifically these chemical deficiencies are those, which are responsible for thinking, memory, feeling happy, libido, good sleeping and just overall energy. To name the main players I will mention serotonin, endorphins, TRH, GABA, adrenaline and thyroxin. Cortisol is also a player but I think that in depression it gets produced in a chaotic excess pattern more than that it is in a deficient state. So depression can ensue by not having good nutrition (vitamins included), not having enough physical activity, not sleeping regularly and not avoiding harmful substances, or a combination in varying degrees of some or all of the above.
Stress is another player that I would like to talk a little about. If a person is healthy and gets exposed to severe acute emotional stress then their reserves of the chemicals mentioned above will be drawn upon and they will be able to withstand the onslaught and not develop depression. But, if the stress is long enough, the reserves will be depleted and the depression syndrome will develop. On the other hand an unhealthy person can develop depression even without emotional stresses.
Another factor is that people who have abused their bodies with harmful substances which shut down the body’s own “machinery” for producing the chemicals above, will be much more likely to develop depression. An example of this is people who have been addicted to narcotics will have deconditioned endorphin-producing tissue. This will of course predispose them to depression but the degree of predisposition will vary with how much and how long they were addicted. Alcohol will hurt the body in a similar way. In general my advice for curing the common form of depression is to apply The Pillars Of Health judiciously and use antidepressant medicines temporarily as a helping tool. Once reasonable improvement has occurred then the antidepressants may be weaned off.
Supplements of 5-HTP, and tyrosine are beneficial in this context and will assist above curing process and assist the onboard antidepressant by supplying the building blocks for serotonin in the instance of 5-HTP, and adrenaline and noradrenaline in the instance of tyrosine. This must be done under your doctor’s supervision.

Does light or sunlight play a role in depression?

Light, especially sunlight definitely plays a role and this becomes most evident in the condition of seasonal affective disorder (SAD). The importance of light as a corrective treatment in SAD, with results superior to placebo has been established.[1]

What appears to happen in SAD, is production of the neurotransmitter serotonin is disrupted. It has been seen that the turnover (production and metabolism) of serotonin by the brain was lowest in winter, and more significantly the rate of production of serotonin by the brain was directly related to the prevailing duration of bright sunlight. The production rose rapidly with increased light intensity.[2] In a situation of lower production of brain serotonin then we can anticipate the presence of depressive symptoms of tiredness, dejectedness, appetite changes (possibly anorexia or maybe increased desire for carbohydrates) and so on.

I don't believe vitamin D plays a major role in SAD, although I would anticipate it may have a minor one, by virtue of its importance in calcium and phosphate absorption. It has been seen to have a positive impact on depression.[3] This stance should not be interpreted as belittling the role of vitamin D in health as I am a big proponent of its supplementation into our diets.

[Rev.1/2/2012]

References:

[1] B Byrne, GC Brainard (2008) Seasonal Affective Disorder and Light Therapy Sleep Medicine Clinics 3: 307 - 315. Doi:10.1016/j.jsmc.2008.01.012.

[2] G Lambert, C Reid, D Kaye, G Jennings, M Esler (2002) Effect of sunlight and season on serotonin turnover in the brain The Lancet 360: 1840 - 1842. Doi:10.1016/S0140-6736(02)11737-5.

[3] Women's mental health: depression and anxiety. Nursing Clinics of North America - Volume 44, Issue 3 (September 2009)

How to Raise Your Cardioprotective HDL [Rev. 12-22-11, 04-18-12, 05-17-16]

2011-12-22T09:17:00.052-05:00

Note: Revisions or additions are in red font.

What is HDL?

HDL stands for high density lipoprotein and its importance in being a key player in preventing atherosclerosis (artery clogging) is more and more evident.[1],[16] It has even been seen that when LDL, (the ‘bad' or 'lousy' cholesterol), is very low, it is the HDL which is the deciding parameter on whether or not heart attacks (and other events) occur.[2] I, for one, am very insistent with my patients in raising this factor.

How does it work?

HDL promotes the mobilization and clearance of excess cholesterol via the series of reactions collectively termed ‘‘reverse cholesterol transport.’’[3] This is where cholesterol in the wall of the artery (and elsewhere) is removed before it is incorporated into the wall (or elsewhere) pathologically and irreversibly (it is a normal/natural constituent of cell structures and substances). Another mechanism cited is that HDL possesses many antioxidant capabilities, and thereby pre-empting the oxidation reactions inherent in development of atherosclerosis.[3] Another mechanism is HDL stimulates endothelial nitric oxide production and thence increases vasodilatation (opening up of blood vessels) and heart muscle blood flow. HDL also significantly impacts the capacity of inflammatory white blood cells to enter and take up residence in the sub-endothelial spaces of arteries.[4][5] This last factor is a probable player in removal of cholesterol molecules by engulfing them and removing them to safer dispositions.

My personal conviction is that the first phenomenon of reverse cholesterol transport is the most important one. There are other described mechanisms outlined in the figure which I won't go into.[6]

Conceptually from Figure 1 in reference [6]

The actual steps to take for increasing HDL are as follows:

Increase healthy oils intake - olive oil, fish oil, coconut oil, butter and animal fats. Concerning the last two it applies to organic products and not those which come from animals enhanced by bovine growth hormones and whose products will contain supernatural levels of IGF (such as present in the USA). This last may be the factor which increases heart related events occurring in those consuming relatively high levels of animal fats in some people in the USA.[7] I say this because there is solid evidence that fat intake of animal origin is associated with lower cardiac mortality compared to the USA as in the French population[8] and the Eskimos[9]. Their food products are organic predominately. I (personally), target a 45% calorie quota for fats and oils of an overall calorie intake, and I emphasize the organic or natural status of said fats. 45% is mid-way between the French and Eskimos.[8],[9] Here I would like to add that I use calories as a practical measure only, as the scientific basis of their translation into body energy is very shaky at this point in time (6-17-12, 5-17-16).
Increase low glycemic index foods – in other words avoid sugars (sucrose and high fructose corn syrup), and foods containing starch. This may also be described as a low-carbohydrate diet, with a relatively high consumption of fat and protein.[10]
Fatty tissue weight loss if needed by controlling overall calorie intake as follows: if the person is at a healthy body mass index (BMI) then intake should be equal to calorie expenditure. If the BMI is high resulting from high body fat then intake should be less than expenditure. If the BMI is low then one should increase overall calorie intake.
Engage in more aerobic exercise regularly, daily.[16]
Tobacco and smoking cessation if applicable.[11],[16]
Ensure intake of good quality protein (preferably animal origin that hasn’t been treated with bovine growth hormone – BST). Target a minimum of 1 gram per kilo body weight per day. This is because protein is a building block for HDL. As mentioned previously HDL stands for high density lipoprotein.
With your physician’s consent and instruction – take niacin 500 – 2000 mg in the morning depending on how low your HDL is. This is also known as nicotinic acid. Be ready for the flushing and itching. This will occur 5 – 30 minutes after ingestion and happens in most people. Lasts around 10 – 45 minutes. Use the immediate release form. It is worth the flush. This medicine (which is also a vitamin) has been shown to decrease heart attack incidence. [6],[12],[13],[14],[15]
Take vitamin C (ascorbic acid) as a supplement orally to the tune of 250 mg daily.[11],[17]
Other agents are available that may raise HDL such as statins (unusually), fibrates and more novel agents in the pipe line[3]. That being said I am not too enthusiastic about all cholesterol ester transport protein inhibitors (CETP-I).[18] My lack of enthusiasm here is because of their mechanism of action. They work by essentially preventing HDL from reaching its end-point target environment, and as such will increase the level in the blood, but won't remove LDL. Bad idea. It astounds me how much money is being/was spent on developing such a non-nonsensical drug.
Of all current options, nicotinic acid is not only the most potent agent for raising HDL-C but is also effective in reducing key atherogenic lipid components including triglyceride-rich lipoproteins (mainly very low-density lipoproteins [VLDL] and VLDL remnants), LDL-C, and lipoprotein(a). The European Consensus Panel recommends that the minimum target for HDL-C should be 40 mg/dL (1.03 mmol/L).[6] I prefer a target of 60 mg/dL or higher.

References:
[1] P Natarajan, KK Ray, CP Cannon (2010) High-density lipoprotein and coronary heart disease: current and future therapies. J Am Coll Cardiol 55: 1283-1299. Doi:10.1016/j.jacc.2010.01.008.
[2] P Barter, AM Gotto, JC LaRosa, J Maroni, M Szarek, SM Grundy et alHDL Cholesterol, Very Low Levels of LDL Cholesterol, and Cardiovascular Events. N Engl J Med 357: 1301-1310.
[3] PT Peter (2009) Novel Therapies for Increasing Serum Levels of HDL. Endocrinology and metabolism clinics of North America 38: 151-170.
[4] X Li (2000) Protective effect of high density lipoprotein on endothelium-dependent vasodilatation. Int J Cardiol 73: 231 236. Doi:10.1016/S0167-5273(00)00221-7.
[5] B Levkau, S Hermann, G Theilmeier, M van der Giet, J Chun, O Schober et al (2004) High-Density Lipoprotein Stimulates Myocardial Perfusion In Vivo. Circulation 110: 3355-3359. Doi:10.1161/01.CIR.0000147827.43912.AE.
[6] MJ Chapman, G Assmann, JC Fruchart, J Shepherd, C Sirtori, European Consensus Panel on HDL-C (2004) Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid--a position paper developed by the European Consensus Panel on HDL-C. Curr Med Res Opin 20: 1253-1268. Doi:10.1185/030079904125004402.
[7] TT Fung, RM van Dam, SE Hankinson, M Stampfer, WC Willett, FB Hu Low-Carbohydrate Diets and All-Cause and Cause-Specific Mortality. Annals of Internal Medicine 153: 289-298. Doi:10.1059/0003-4819-153-5-201009070-00003.
[8] MH Criqui, BL Ringel (1994) Does diet or alcohol explain the French paradox? Lancet 344: 1719-1723.
[9] H Bang, J Dyerberg, N Hjøorne (1976) The composition of food consumed by Greenland Eskimos. Acta Med Scand 200: 69-73.
[10] GD Foster, HR Wyatt, JO Hill, AP Makris, DL Rosenbaum, C Brill et al (2010) Weight and Metabolic Outcomes After 2 Years on a Low-Carbohydrate Versus Low-Fat Diet. Annals of Internal Medicine 153: 147-157. Doi:10.1059/0003-4819-153-3-201008030-00005.
[11] J Hallfrisch, VN Singh, DC Muller, H Baldwin, ME Bannon, R Andres (1994) High plasma vitamin C associated with high plasma HDL- and HDL2 cholesterol. Am J Clin Nutr 60: 100-105.
[12] PL Canner, KG Berge, NK Wenger, J Stamler, L Friedman, RJ Prineas et al (1986) Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. Journal of the American College of Cardiology 8: 1245-1255.
[13] K. G. Berge1 Contact Information,P.L.Canner2 and Coronary Drug Project Research Group, (1) Mayo Clinic, 55905 Rochester, Minnesota,USA, (2) Maryland Medical Research Institute, Baltimore, Maryland,USA (1991) Coronary drug project: Experience with niacin. European Journal of Clinical Pharmacology: S49-S51; S49.
[14] JB Segal, J Eng, LJ Tamariz, EB Bass (2007) Review of the Evidence on Diagnosis of Deep Venous Thrombosis and Pulmonary Embolism. Ann Fam Med 5: 63-73. Doi:10.1370/afm.648.
[15] Clofibrate and niacin in coronary heart disease. (1975) JAMA 231: 360-381.
[16] Anonymous Association of High-Density Lipoprotein Cholesterol With Incident Cardiovascular Events in Women, by Low-Density Lipoprotein Cholesterol and Apolipoprotein B100 Levels . http://annals.org/content/155/11/742.abstract. Accessed 12/22/2011 2011.

[17] Jacques, PF. “Ascorbic acid, HDL, and total plasma cholesterol in the elderly.” Journal Of The American College Of Nutrition, v. 6 issue 2, 1987, p. 169-174.

[18] J Poss, M Bohm, U Laufs (2010) HDL and CETP in atherogenesis. Dtsch Med Wochenschr 135: 188-192. Doi:10.1055/s-0030-1247862.

If You Eat Too Late At Night Does Your Body Repair Stop

2011-11-24T19:25:00.000-05:00

My friend at Anti-Aging Games, Elizabeth Amini had a another question for me:

Is it true that your body repairs one organ at a time every hour at night and if you eat late, your body chooses to focus on digestion instead of repairs during that time period and whatever organ is supposed to be repaired isn't during that time? It seems suspicious that the body works on an arbitrary time slot that humans sliced up the day by. I've heard it from both Eastern and Western doctors.

Answer to first part of question:

The body in all its tissues (and its organ units) is in continual repair, night and day. The extent of repair and who is getting the most attention will vary with the extent of damage, exhaustion or use of that specific tissue or organ. All of the processes of repair will depend on the signals emanating from the tissues (organs) signaling the need. This will be in the form of chemicals (such as lactic acid or substance P for example), or neurologic signals. Other factors are the availability of the building blocks (such as amino acids), assisting substances (such as vitamin C), energy hormones (such as growth hormone), building hormones (again such as growth hormone), fuel for energy (fatty acids) and appropriate surrounding temperature. A major factor is whether or not that tissue is being involved in full scale repair or not is if said tissue is in use or not. When the tissue is active then the amount of repair is less and vice versa.

Since most tissues and organs are less active when a person is sleeping, then a large part of repair of all tissues will occur during the person’s sleep cycle. In addition, there is escalation of growth hormone secretion when the eyes are closed (especially in adults), which is a major player in repair. Therefore, sleep truly is ‘renovation time’.

The premise that the ‘body repairs one organ at a time every hour at night’, to me is without scientific basis and I don't think that any one organ has a specific hour to be repaired in. It is a continuous process.

Answer to second part of question:

By eating late the repair of the gastrointestinal tract is probably delayed because of it being busy with digestion and absorption. Some of the energy resources required for the digestion and absorption which would otherwise be dedicated to repair or replenishment may be diverted away from the repair arena. This would especially be true if the meal size is large. To what extent this occurs isn't known to me, but I seriously doubt that it is as absolute as described in the question. As such it is my conviction that it is healthier to have frequent small meals instead of large ones to have a continuous low drain on energy resources needed for repair, while at the same time having a continuous influx of building blocks and energy resources. This concept, along with exercise, is capitalized upon (knowingly or otherwise), by Bill Phillips, in his strategy for getting healthy in his book, Body-for-LIFE: 12 Weeks to Mental and Physical Strength (1999). So I would say it is okay to eat late as long as the meal size is small.

Does Alkalinizing The Body Through Ingesting Food and Fluids That ‘Alkalinize’ The Body Have a Positive Impact on Health?

2011-11-06T16:37:00.001-05:00

My friend at Anti-Aging Games, Elizabeth Amini (Founder & CEO, Anti-Aging Games, LLC) had a question for me:

Does alkalinizing the body through ingesting food and fluids that ‘alkalinize’ the body have a positive impact on health?

Answer:

I doubt it very much. The body’s pH (acidity/alkalinity index), and here referring to blood and tissue fluids, is tightly regulated by among other organ systems, the lungs and kidneys. These two systems do that in a very magnificent synchronized fashion maintaining this tight range through multiple redundant backup tactics.
The pH of blood should be 7.35 to 7.45 which is truly on the alkaline side, but this shouldn’t translate into drinking or eating alkaline is better for us. I believe this is trying to fine-tune things artificially too much to the exclusion of highly important nutrients such as healthy proteins.
Also in-taking a consistently alkaline fluid or solid would put a burden on the kidneys to counter balance excess alkalinity. It would also trend our breathing to be slower so as to retain more carbon dioxide, especially if the kidneys aren't getting sufficient water (whose pH by the way is 7.0).
In conclusion I would say: eat healthy protein sufficiently (not less than 70 grams per day for a healthy adult), eat healthy fats (hormone free, and non-synthetic) sufficiently to the tune of 40-45% of the conventionally measured calorie intake, unlimited vegetables (preferably not genetically modified and also grown in fertile ground that hasn’t been exhausted of its minerals), and use fruits as a dessert. No refined sugars at all and keep refined carbohydrates (pasta, lasagna, breads, etc.) below 100 grams per day. Drink enough refined-sugar-free fluids to ensure a urine color that is very light yellow with a daily minimum of 3 urinary bladder full micturitions (urinations).

The websites you had referred to are too unscientific in their presumptions.

How much fat to eat to absorb vitamin D and how many total calories per day to lose weight. (To Anonymous)

2011-11-06T15:06:00.000-05:00

In reply to your lovely questions I think it necessary to understand the premise of calorie (calorie=Kilocalorie) content of food: food calorie content is usually assessed by totaling the calories of the individual nutrients of a given food. For example the calorie production of protein is assessed to be 4 calories per gram, and that of fat as 9 calories per gram, and carbohydrates 4 calories per gram.[Food Energy [1]] These estimates for the individual food nutrients are done by direct calorimetry as follows:

Merck Manual - Home Edition [2]

This to me this is a very imprecise, unscientific way of estimating calorie content in food as it translates into energy or fat storage for the human body. The body is not a bomb calorimeter and as such translating or equating 1 gram of fat to 9 Calories of energy that will be stored as fat is pretty naive (on the part of the authorities, scientific or governmental). The support for my statement above is evidenced by more than one study, but my favorite is in a study published in the Annals of Internal Medicine in 2010 where it was clearly seen that successful weight loss can be achieved with either a low-fat low-calorie or low-carbohydrate unlimited calorie diet when coupled with behavioral treatment.[3] Focus here on unlimited calorie intake of fat and protein. Another study in support of my statement included the Atkins diet where it was seen: women assigned to follow the Atkins diet, which had the lowest carbohydrate intake, lost more weight and experienced more favorable overall metabolic effects at 12 months than women assigned to follow the Zone, Ornish, or LEARN diets.[4] Therefore a low-carbohydrate, high-protein, high-fat diet, with good amounts of vegetables and fruit is in my opinion the best recommendation for weight loss. That being said the fats must be hormone free (rBST), and non synthetic. (I am not a full supporter of the Atkins diet because of its exclusion in certain phases of all forms of carbohydrate including vegetables and fruit, and the other part is not addressing the kind of fats allowed that may or may not include synthetic fats and fats coming from animals treated with rBST. To be fair though the latter happened more than 2 decades after his initial publication of the Atkins Diet Revolution. I admire the gentleman immensely for breaking the ‘Fat Barrier’.)
My direct message to Anonymous: Do not count calories to lose weight but AVOID refined carbohydrates (refined sugars, flour, rice, potatoes, etc.). Feel free to have unlimited amounts of healthy oils and a minimum amount of protein (hormone free) of 80 grams per day. This can translate into eating 1-2 pieces of fried chicken daily or equivalent (as long as there are no mashed potatoes, breads, pasta, lasagna, etc.) and this should be amply sufficient for absorption of your vitamin D supplement. Additionally you may have unlimited amounts of vegetables and use fruit as your dessert. Please continue the exercise and target sleeping 7.5 to 8.5 hours per 24 hour cycle.
I do realize that the calorie count concept will be hard to get rid of but the science just isn’t in favor of limiting fats and protein.
Also an opinion of mine not yet proven: I fear low fat is more in favor of cancer evolution than not, unless the fat intake has come from animals treated with rBST. I fear the last will contain said hormone (in meats) or higher levels of insulin growth factors (in milk and its products) both which will encourage increase in cell size and number artificially. This seems to me to be dangerous ground to tread.
I hope this answers your questions. Stay the course of health, it is very very worth it.

References:
[1] http://en.wikipedia.org/wiki/Food_energy
[2] http://www.merckmanuals.com/home/disorders_of_nutrition/overview_of_nutrition/calories.html
[3] GD Foster, HR Wyatt, JO Hill, AP Makris, DL Rosenbaum, C Brill et al (2010) Weight and Metabolic Outcomes After 2 Years on a Low-Carbohydrate Versus Low-Fat Diet. Annals of Internal Medicine 153: 147-157. Doi:10.1059/0003-4819-153-3-201008030-00005.
[4] CD Gardner, A Kiazand, S Alhassan, S Kim, RS Stafford, RR Balise et al (2007) Comparison of the Atkins, Zone, Ornish, and LEARN Diets for Change in Weight and Related Risk Factors Among Overweight Premenopausal Women: The A TO Z Weight Loss Study: A Randomized Trial. JAMA 297: 969-977. Doi:10.1001/jama.297.9.969.

The Pillars of Health:The Prelude: Preview "Fat Intake and Weight Gain"

2011-07-03T11:01:00.000-04:00

The Pillars of Health:The Prelude: Preview "Fat Intake and Weight Gain"

Magnesium Low

2010-04-04T19:29:00.003-04:00

Answering Nazek:
Disorders of Magnesium Balance (1)
Introduction Magnesium is the most abundant intracellular divalent cation and, after calcium, the most common divalent cation in the body. The majority (99%) of magnesium residing inside cells. Consequently, plasma magnesium concentration does not reflect total body magnesium. Magnesium plays an important role in neuromuscular coupling, largely through its interaction with calcium. Disorders of magnesium primarily reflect hypomagnesemia, with cardiac arrhythmias and other features similar to those of low calcium. Among the causes of hypomagnesemia are malnutrition, chronic alcoholism, kidney abnormalities and malabsorption. [Is she taking any laxatives?]
Magnesium Intake and Distribution Magnesium is found in many foods, including green vegetables and meat products, and the normal diet is usually more than ample. Approximately 5 mg/kg per day of magnesium is required for normal magnesium balance. Factors that control gastrointestinal magnesium absorption are unclear, but about one-third of ingested magnesium is absorbed.
Magnesium Excretion The distal nephron (part of the kidney), however, is the major site of fine regulation of magnesium excretion. Loop-acting diuretics predictably have a potent magnesium-wasting effect. [Is she taking any ‘Water Pills?], [One-Alpha should only be given to patients suffering from kidney disease. Is that the case here?]
Role of Magnesium The major role of magnesium is as a cofactor for hundreds of identified enzymes that produce or require ATP, such as kinases, ATPase, and adenylyl cyclase. Disorders of magnesium may lead to impaired energy production, substrate utilization, and synthetic processes.
Hypomagnesemia (Low magnesium) ESSENTIALS OF DIAGNOSIS
• Plasma [Mg2+] <1.7 style="color: rgb(255, 102, 102);">The numbers given satisfy this criterion.] • Cardiac arrhythmias, refractory potassium deficiency. [What was her potassium level?] • Features suggestive of hypocalcemia: tetany, weakness, increased deep tendon reflexes, altered mental status, and seizures. [Are there any symptoms like these?]
[Please provide also the laboratory reference levels for any result mentioned as this varies between laboratories.]
References
1. Bongard FS, STAT!Ref, Teton Data Systems. Current critical care diagnosis & treatment. 3rd ed. New York ;London: McGraw-Hill; 2008.

[Above doesn’t replace the input of a medical professional who interviews the patient and carries out a physical examination followed by a discussion of care – that is the premier method of obtaining medical advice at this time of medical science development].