update on vitamin d and immune health 62bc4b2d83695

Update on Vitamin D and Immune Health


I recently tried to help a family from out of state with a young man diagnosed with COVID-19. With a major surge going on in his state the family was trying get him Remdesivir. I didn’t know his clinical condition but knew he was hospitalized and short of breath with symptoms of COVID-19.  They asked me if there was a way to get Remdesivir. I suggested the family work with the hospitalist and infectious disease physicians to request for the drug as I learned their governor had just released 99 cases for distribution. I also mentioned the role of antioxidants such as IV N-acetyl cysteine or IV Glutathione as well as IV vitamin C and of course Vitamin D as I’ve discussed in previous blogs. I also reviewed with them the role of dexamethasone should his course worsen as there have been studies showing a 35% reduction in death with severe cases requiring mechanical oxygen support. Unfortunately, I learned his condition deteriorated despite getting Remdesivir and then plasma from a COVID-19 survivor and Dexamethasone when those supplies ran out.  He suffered several heart attacks and continued to deteriorate even on a ventilator.  Because there are so many factors involved even with youth, previous health, and applying all the latest things we’ve learned in treating COVID-19 the results are far from predictable or necessarily favorable.  As Benjamin Franklin said “an ounce of prevention is worth more than a pound of cure” and here no cure can be assured.


So this young man’s prognosis really brought home to me the importance of prevention.  I briefly outlined the state of the art treatment that this young man had received including plasma from a COVID-19 survivor and I’ve mentioned vitamin D previously but I just had to tell you about a comprehensive, updated article on Vitamin D which included more evidence of its positive effects on immune health and updated information on COVID-19. The title of the paper is “Immunologic Effects of Vitamin D on Human Health and Disease” by Nipith Charoenngam. 


I’ve mentioned before that vitamin D is almost like a hormone. It is a lipid soluble vitamin, derived from a cholesterol derivative and it requires ultraviolet radiation to convert it the cholesterol derivative into the 25-hydroxyvitamin D. From there the body metabolizes into 1, 25 dihydroxyvitamin D  into its active form.  Vitamin D does so many things some of which I’ve mentioned before but is well documented in this paper with almost 200 references  and excellent illustrations. 

There was another recent that paper (“Vitamin D status and risk of all-cause and cause-specific mortality in a large cohort: results from the UK BioBank”)  showed a reduction in all cause mortality associated with vitamin D levels 45 to 60 nanmoles per liter. The article reviewed the vitamin D status and risk of all cause and cause specific mortality in a large population from the UK Biobank. After a median follow-up of about nine years. Over ten thousand deaths occurred including 18.1 percent due to cardiovascular disease and 56 percent due to cancer. The multivariate analysis revealed nonlinear inverse associations with a decrease in mortality risk appearing to level off at 60 Nana moles per liter of 25-hydroxyvitamin D for all cause and cardiovascular deaths and at 45 Nan moles per liter for cancer deaths.  Compared to participants with 25-hydroxy vitamin D levels below those cut offs, those with higher concentrations had a 17 percent lower risk for all cause mortality, a 23 percent lower risk for cardiovascular and an 11 percent lower risk for cancer mortality. So their conclusion was that higher 25 hydroxyvitamin D concentrations are non-linearly associated with lower risk of all cause cardiovascular disease and cancer mortality. The thresholds of 45 to 60 nanomoles per liter might represent an intervention target to reduce overall risk of premature death which needs further confirmation with large clinical trials . This study was a  retrospective study of very large number of patients actually over 365 thousand participants over almost 10 years where they looked at these patients and they were able to see this difference in vitamin D levels.

The first article we mentioned actually breaks down as an initial introduction on vitamin D , the causes and associated diseases of vitamin D , the physiology of vitamin D including it’s skeletal effects. After these foundational reviews it gets much more interesting about the effects of vitamin D on innate immunity and they mention that it also exerts direct antiviral activities against many respiratory viruses by disrupting viral envelopes and alters viability of host target cells. This process is especially robust in granulomatous inflammation such as TB fungal infections, sarcoidosis and some lymphomas.  Discussions also include the different types of cell types of B cells th1 th17 etcetera and natural killer cells but the most interesting thing in relationship to our current knowledge on COVID-19 complications is the section on endothelial function and Vascular permeability. Studies are mentioned that have shown that vitamin D modulate endothelial function and vascular permeability. The endothelium is the cells lining all the blood vessels. Many mechanisms were reviewed but the end result is that Vitamin D plays a direct role or upregulates or triggers other molecules to stabilizing the vascular endothelium and this may be the reason why vitamin D is associated with a lower risk of mortality in covid-19.   

Also in regards to nitric oxide, which is known to dilate or allow blood vessels to open and relax, studies have shown that 1, 25 dihydroxyvitamin D is a transcriptional regulator of endolethial.  nitric oxide synthase which causes upregulation of Enos gene expression and increases and the endometrial production of nitric oxide. So there’s a connection between nitric oxide and vitamin D3 levels and the activation of nitric oxide. 

So to summarize in regarding the endothelium,  it is evident that vitamin D and its metabolites extort beneficial effects on the vascular endothelium that are protective against vascular dysfunction and tissue injury as a result of local and systemic inflammation which is what exactly what we want to have in a patient with covid-19 if the current hypothesis is correct that COVID-19 can trigger significant damage to the endomethelium activating our immune and clotting systems so clots form everwhere else as well.   As the young man I mentioned, the virus triggered such a response in the immune system and direct damage to his endomethelium or the lining in all his blood vessels that several heart attacks occurred and likely clots plugging up the bronchi and aveloar sacs in the lungs.

There have been discussions about vaccines, immunity, and antibodies and vitamin D has an effect on adaptive immunity.  There have been questions whether T lymphocytes, a type of white blood cell,  helper T cells and memory T-cells remember this infection.  There is an effect of vitamin D on that  There is also an effect on the B lymphocytes and these B lymphocytes give rise to plasma cells and sees plasma cells that give rise to antibodies.

This article than goes into a number of other things including immune-related diseases like psoriasis , type 1 diabetes , multiple sclerosis, inflammatory bowel diseases  including  Crohn’s,  ulcerative colitis all showing benefit from higher Vitamin D levels.  The paper also reviews   randomized controlled trials that show a benefit in respiratory viral infections in reducing acute respiratory infections. 

Previously I told you about proposed explanations to the seasonal outbreak of viruses so here studies show levels of 25-hydroxy D which reaches the lowest levels in the winter and the association between low-level serum 25-hydroxyvitamin D and the incidence and severity of respiratory tract infections in children and adults. A prospective cohort study in healthy adults living in New England showed a two-fold reduction in the risk of developing acute respiratory tract infections in those with serum 25-hydroxyvitamin D levels of 38 nanograms per milliliter which is 95 millimoles per liter or more. So in this case they weren’t supplemented  but they followed those that had higher levels and it showed that there was a two-fold reduction in the risk of developing acute respiratory tract infections. Covid-19 is of course an acute respiratory tract infection.now it wasn’t there as part of those acute respiratory tract infections but it belongs to that group of acute respiratory tract infections and we see prospective that a higher vitamin D level is protective from those. Children that were Age 2 years or less were 1.7 Times higher likelihood of requiring hospitalization for an acute respiratory tract infection. So what is vitamin D  proposed to be doing?  It seems as though that when respiratory viruses enter into the respiratory epithelium via the specific entry receptors for example  ACE2  it causes cellular and tissue damages has and triggers the innate and adaptive immune systems both which then result in airway and systemic inflammation and in severe cases life-threatening sepsis or acute respiratory distress syndrome. The 1,25 hydroxyvitamin d, the active form of vitamin D not only has antiviral activities but it also modulates inflammatory responses to viral infection by stimulating cathelicidin release , modulation of a toll like receptor expression,  and natural killer cell function as well as suppressing overexpression of pro-inflammatory cytokines.

A recent meta-analysis of 25 randomized controlled trial showed that supplementation of vitamin D2 or D3 can protect against the development of acute respiratory tract infections compared to placebo, or those that weren’t supplemented with vitamin D.  They also mentioned in this paper that symptomatic infection morbidity and mortality observe an African Americans and obese individuals suggest the possible impact of vitamin D on the host response and susceptibility to infection as obese and black individuals are known to have an elevated risk for vitamin D deficiency. 

They also mentioned that it has been proposed that supplementation of vitamin D can reduce the risk and severity of covid-19 infection and there are a number of references to that . The author’s go further in saying although the efficacy of vitamin D is still unclear as a result of ongoing clinical trials are still pending,  it is advisable that one should maintain adequate vitamin D intake to attain the desirable serum  25-hydroxy vitamin D level of 40-60 nanograms per milliliter or a hundred to one hundred and fifty nanomoles per liter in order to minimize the risk and severity of covid-19 infection. 

It is well documented that worldwide on average approximately 40% of children and adults have circulating 25-hydroxyvitamin D levels of less than 20 nanograms per milliliter or 15 nanomoles per liter and approximately 60% have less than 30 nanograms per milliliter or 75 nanomoles per liter. Thus patients presenting to the hospital with covid-19 are likely to have a vitamin D deficiency or insufficiency. It is therefore reasonable to institute as a standard of care to give at least one single dose of 50,000 units of vitamin D2 to all covid-19 patients as soon as possible after being hospitalized. For patients who are intubated and are being fed by a G-tube, they should be treated with a liquid form of vitamin D. 

So as a prevention, vitamin D supplementation is recommended. Ideally, a baseline vitamin D level can be checked before supplementation, but as 40% of the general population and probably higher here in Northern California north of the 35 parallel, supplementation from 2,000 international units or 5000 international units may be started without checking initial levels but if 5000 international units are taken, vitamin D  levels should be checked after 2-3 months. The goal is a level between 40 nanograms per milliliter to 60 nanograms per milliter for immune optimization but some studies have suggested 60 to 80 nanograms per milliliter may have more of an association with decreased cancer risk.

Other supplements may also be helpful including nutrients that support the mitochondria which take a hit with oxidative stress and having optimal immune health requires a lot of energy. A supplement with complete curcumoid matrixes can be converted by bacteria to help focus and train the immune system.

So I take supplements including Vitamin D, nutrients like MitoMax and CurCuMax Complete to maintain optimal immune health and resiliency to guard against all infections, autoimmune disease and cancer. Not all supplements are created equal.  All Functional Health Formulas are pharmaceutical grade, Good Manufacturing Practice certified quality ingredients,  free of fillers, contaminates, impurities and tested for superior absorption and bioavailability. The formulas meet or exceeds cGMP quality standards.  I’d like to make this paper available to you along with information on our specially formulated supplements with this link. Of course, it is always nice to spend a few minues in nature expose to the sunlight to increase our Vitamin D production, too.

In an effort to serve our patients better during this challenging time of COVID-19, we have expanded our services to include shipping supplements directly to our patients in San Ramon, Turlock, and neighboring cities, as well as throughout the entire Bay Area as well as to all 50 states.  Please email us at info@jeffreymarkmd.com with any questions or requests.


Jeffrey Mark, M.D.

Helping clients with compassionate and comprehensive medical care for over 25 years with 4 board certifications in functional medicine, gastroenterology, internal medicine, and anti-aging/ regenerative medicine . IFMCP, ABIM Gastroenterology, NPAS Internal Medicine, ABAARM.

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