Anjanette Tan, MD, FACE, ECNU  •  
5 min read

Vitamin D Covid 19 - Low Vitamin D Associated with Higher Covid Positivity Rate

Author: Dr. Anjanette Tan

Medically reviewed by Anjanette Tan, MD, FACE, ECNU, Endocrinologist

When we speak of adding layers to our armamentarium against Covid infection, along with mass vaccination, hand washing, mask wearing, social distancing, I assert that we need to add vitamin D supplementation into this patchwork. Vitamin D Covid 19 is an important addition.

 What is Vitamin D?

Vitamin D is a hormone.  The production of vitamin D3 requires UVB light on the skin.  The rate of formation is dependent upon the intensity of UVB and the degree of skin pigmentation, as melanin blocks UVB from reaching the vitamin D precursor, 7-dehydrocholesterol (7-DHC).

 

There are very few natural food sources of vitamin D, except a little amount in fatty fish.  Food has to be artificially fortified with D.   Vitamin D2 is usually the kind used for fortification. Vitamin D3 is the kind found in fish and what the skin converts.  The difference between D2 and D3 is in the side chain in D3 that causes faster clearance from the circulation, leading to less conversion in the liver. 

 

The liver is the major source of 25(OH)D production.  Vitamin D2/D3 is hydroxylated in the liver by cytochrome P450 oxidases.The kidney then converts 25(OH)D into 1,25(OH)D through 1alpha-hydroxylase, regulated by parathyroid hormone (PTH).

 

Vitamin D1,25(OH) is known as the active vitamin D, binding to vitamin D receptors that are practically everywhere.  Vitamin D influences over 80 pathways that promote DNA repair, decrease oxidative stress and decrease cell death.  It is shown to exert a positive impact on metabolic processes and is anti-inflammatory.

 

Along with the vast applications and studies on the effects of vitamin D on the skeleton, there have also been many studies on its effects on the immune system.  Vitamin D has the ability to upregulate anti-inflammatory cytokines and downregulate damaging cytokines. This may possibly tamp down the “cytokine storm” that is shown to be a late effect of severe Covid-19.  Interestingly, there are also studies showing possible regulation of the ACE2 system, known to be the initial viral entry point, by vitamin D.

 

Is there clinical evidence for Vitamin D Covid 19? 

Researchers therefore looked into the correlation between vitamin D deficiency and SARS-CoV-2 positivity rates. 

 

Kaufman et al, in a retrospective, observational analysis, looked at vitamin D 25(OH) levels drawn from 191.779 patients from all 50 states.  It was found that SARS-CoV-2 positivity rate was higher in those who were vitamin D deficient (<20 ng/mL) compared with those who had adequate levels (30-34 ng/mL) and those whose values were 55 ng/mL and over.

 

SARS-CoV-2 positivity was strongly and inversely associated with circulating 25(OH)D levels, a relationship that persisted across latitudes, races/ethnicities, both sexes and age ranges.  This means that SARS-Cov-2 positivity was found to be higher in those who had lower vitamin D levels.

 

The risk of SARS-CoV-2 positivity continued to decline until the serum levels reached 55 ng/mL.

In light of these observational findings, do we venture to recommend vitamin D supplementation in our population? 

 

This is a study showing a clear association.  Even if we find correlation, I would caution that it does not prove causality.  We know that observational studies are often alleyways that lead us to avenues of more robust investigation. In the Covid era however, when infections, hospitalizations and deaths are at an all time high, time is of the essence.

 

Moreover, what is the harm in replacing vitamin D25(OH) up to a level that is well within the acceptable range between 30 to 100 ng/mL?

 

The Institute of Medicine and the Endocrine Society both have guidelines on what is an adequate amount to supplement without a doctor’s supervision. The upper limit has ranged between 4,000 IU (IOM) to 10,000 IU (Endocrine Society) daily among adults in those who are known to be deficient. Generally, 2000 IU/day may be needed to keep levels above 30 ng/mL.   

 

Vitamin D is a fat soluble vitamin.  It may accumulate, causing severe and symptomatic hypercalcemia.  However, in studies of long term supplementation, it has been established that long term doses of ergocalciferol (vitamin D2) 50,000 IU every 2 weeks for up to 6 years, kept vitamin D 25(OH) levels between 50-60 ng/mL. 

 

I would caution against supplementation without medical supervision in patients with renal insufficiency, history of kidney stones, sarcoidosis or granulomatous disorders. 

 

So here we have a plausible physiologic explanation, an observation of consistent association, no obvious harm in replacing what is deficient in the first place, cost effective measure to possibly reduce SARS-CoV-2 infection.  Every little bit helps. Please speak with your doctor regarding recommendations for your individual situation.

 Author: Anjanette Tan, MD, FACE, ECNU

 Sources:

1.     Vitamin D Metabolism, Mechanism of Action, and Clinical Applications. https://doi.org/10.1016/j.chembiol.2013.12.016

2.     SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels.  https://doi.org/10.1371/journal.pone.0239799.

3.     Evaluation, Treatment, and Prevention of Vitamin D Deficiency:an Endocrine Society Clinical Practice Guideline.  https://doi.org/10.1210/jc.2011-0385

4.     Vitamin D Toxicity--A Clinical Perspective.  https://doi.org/10.3389/fendo.2018.00550

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