Can Vitamin D Prevent COVID-19?

In the beginning of last year, I was reading the news that a Chinese hospital in Shanghai was successful in treating COVID-19 patients with high doses of vitamin C. Not much attention was given to the subject, but evidence is increasing recently that vitamin D supplementation could be crucial in the prevention and treatment of COVID-19.

Vitamins are substances that you need to ingest with your food in order to live. They are vital to your health. Vitamin D is different. There are small amounts present in your food, but the bulk part is actually produced by your body. Your skin is able to metabolize it under sun exposure. If you do not get enough sun, then you need to supplement it, since the dietary intake is not sufficient to cover your needs.

Vitamin D is also different from other vitamins in the way it works in your body. In a certain sense, it almost works like a hormone, being able to regulate several essential body functions. It is able to bind to a receptor on the cell membrane and enter even into the nucleus, this way affecting how the genes express themselves in relation to cell function.¹⁾Vitamin D and COVID 19: The Evidence for Prevention and Treatment of Coronavirus (SARS CoV 2) Youtube Numerous cells have receptors for Vitamin D. This includes immune cells, an important fact for our subject of COVID-19 prevention. It was shown that vitamin D is essential for the proper functioning of the immune system.²⁾F Sassi et.al. Vitamin D: Nutrient, Hormone, and Immunomodulator. Nutrients2018, 10(11), 1656; https://doi.org/10.3390/nu10111656
Xu, Y., Baylink, D.J., Chen, CS. et al. The importance of vitamin d metabolism as a potential prophylactic, immunoregulatory and neuroprotective treatment for COVID-19. J Transl Med 18, 322 (2020). https://doi.org/10.1186/s12967-020-02488-5

Vitamin D and Immunity

The flu season is peaking exactly at the end of the winter, when sun exposure is limited and the Vitamin D storage is depleted. Studies have shown that children with rickets caused by Vitamin D deficiency, are also more susceptible to tuberculosis. Also, the relationship between respiratory diseases and vitamin D deficiency is well established.³⁾H Brenner et.al. Vitamin D Insufficiency and Deficiency and Mortality from Respiratory Diseases in a Cohort of Older Adults: Potential for Limiting the Death Toll during and beyond the COVID-19 Pandemic? Nutrients 2020, 12(8), 2488; https://doi.org/10.3390/nu12082488
Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017; 356 doi: https://doi.org/10.1136/bmj.i6583
M Urashima et.al. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr. 2010 May;91(5):1255-60. DOI: 10.3945/ajcn.2009.29094

On average we spend only 7.6% of the day being outdoors,⁴⁾N. Klepeis et.al. The National Human Activity Pattern Survey (NHAPS): a resource for assessing exposure to environmental pollutants. Journal of Exposure Analysis and Environmental Epidemiology (2001) 11, 231-252 which means our sun exposure is very limited. Living above the 35th degree of latitude you do not have sufficient Vitamin D production in the winter. That includes any location of Tennessee and above. Europe is included entirely.

Studies have shown that people in the age of 77 to 82 years had less than half the capacity to produce Vitamin D in the skin compared to teenagers.⁵⁾J MacLaughlin, M F Holick. Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest. 1985 Oct;76(4):1536-8. DOI: 10.1172/JCI112134 Darker skin colors have significantly less absorption of vitamin D as well.⁶⁾O. M. Gutiérrez et.al. Racial differences in the relationship between vitamin D, bone mineral density, and parathyroid hormone in the National Health and Nutrition Examination Survey. Osteoporos Int. 2011 Jun; 22(6): 1745–1753. doi: 10.1007/s00198-010-1383-2

Vitamin D is a fat-soluble vitamin. It is therefore stored in the fat tissues, and the more fat reserves you have, the more Vitamin D you will need. For that reason, individuals with a BMI higher than 35 are more likely to be Vitamin D deficient, and larger doses will be needed for supplementation.⁷⁾J Wortsman et.al. Decreased bioavailability of vitamin D in obesity. The American Journal of Clinical Nutrition, Volume 72, Issue 3, September 2000, Pages 690–693, https://doi.org/10.1093/ajcn/72.3.690

It is interesting to notice that people with higher age, dark skin color and increased BMI are having an increased risk of dying from COVID-19. Those are exactly the same risk factors for Vitamin D deficiency. Is that coincidental, or is there a causative relationship?

Vitamin D and COVID-19 Infections

Before we start, one note about unit conversion. Some countries are measuring blood levels of vitamin D in nmol/l. In the US the commonly used unit is ng/ml, and we are using this unit throughout the article. If you want to convert to nmol/l, you need to multiply those values by 2.5.

Some scientists analyzed the COVID-19 cases compared to the latitude of each country. They found out that all the countries with higher mortality rates were located above the 35th-degree latitude, thus having insufficient sun exposure in the winter.⁸⁾J M Rhodes et.al. Editorial: low population mortality from COVID-19 in countries south of latitude 35 degrees North supports vitamin D as a factor determining severity. Aliment Pharmacol Ther. 2020 Jun;51(12):1434-1437. DOI: 10.1111/apt.15777 Another research looked at the mean vitamin D level of each country and found that those with higher vitamin D levels had significantly lower numbers for COVID-19 cases and deaths.⁹⁾P C Ilie et.al. The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality. Aging Clin Exp Res. 2020 May 6 : 1–4. doi: 10.1007/s40520-020-01570-8

In a research among elderly hospital patients was found that the mean vitamin D level of COVID-19 positive patient was 11 ng/ml compared to 21 ng/ml in the group who tested negative.¹⁰⁾V Baktash et.al. Vitamin D status and outcomes for hospitalised older patients with COVID-19. Postgraduate Medical Journal Published Online First: 27 August 2020. doi: 10.1136/postgradmedj-2020-138712 A study in Switzerland compared the vitamin D level of hospitalized patients and found that those who were hospitalized for COVID-19 infection had significantly lower vitamin D levels than those who were tested negative for COVID-19.¹¹⁾A D’Avolio. 25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2. Nutrients 2020, 12(5), 1359; https://doi.org/10.3390/nu12051359

That study was able to show a correlation between those two factors, but a correlation is not always causative. Some scientists found out that during an infection the serum vitamin D levels tend to drop, and stipulated the possibility that COVID-19 infection caused the vitamin D levels to drop, and not that the vitamin D deficiency has caused COVID-19.¹²⁾J Smolders et.al. Letter to the Editor: Vitamin D deficiency in COVID-19: Mixing up cause and consequence. Metabolism. 2021 Feb; 115: 154434. doi: 10.1016/j.metabol.2020.154434 Although the drop in vitamin D levels could be proven, it is though very moderate, and does not fully explain the drastic difference in vitamin D levels between those two groups.

To help us establish the causative effect, there were two studies done in Israel, that checked out people who had a prior Vitamin D test on record, and they found that those who had adequate Vitamin D levels before being exposed to COVID-19 were less likely to get infected.¹³⁾A Israel et.al. The link between vitamin D deficiency and Covid-19 in a large population. https://doi.org/10.1101/2020.09.04.20188268 The second study found that those who had Vitamin D levels below 30 ng/ml, were almost twice as much needing hospitalization compared to those with normal levels.¹⁴⁾E Merzon et.al. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study. FEBS J. 2020 Sep;287(17):3693-3702. DOI: 10.1111/febs.15495 A study in the US found that persons with vitamin D level below 25 ng/ml had twice as many COVID-19 infections compared to those above 55 ng/ml.¹⁵⁾H W Kaufman et.al. SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. https://doi.org/10.1371/journal.pone.0239252

Vitamin D for COVID-19 Treatment

Another research done in Spain went some further to find out whether vitamin D is an effective treatment option. They gave vitamin D injections to patients that were hospitalized for COVID-19 treatment. For those in the placebo group, 50% were submitted to the intensive care unit, while in the group treated with vitamin D, only 2% needed intensive care.¹⁶⁾M E Castillo et.al. “Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study” J Steroid Biochem Mol Biol. 2020 Oct; 203: 105751. doi: 10.1016/j.jsbmb.2020.105751 This is quite a significant improvement! As a result of the study, the hospital started wheeling out COVID-19 patients in recovery to the seaside.¹⁷⁾Coronavirus: Barcelona beach trip for recovering patients. BBC News, 3 June 2020

In a clinical trial done in India, they gave a dose of 60.000 UI of vitamin D3 for 7 days to patients being hospitalized for COVID-19. After 3 weeks 62.5% of those who received Vitamin D were cured compared to 20.8% in the control group.¹⁸⁾A Rastogi et.al. Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study). Postgraduate Medical Journal Published Online First: 12 November 2020. doi: 10.1136/postgradmedj-2020-139065 A meta analysis concluded that vitamin D supplementation can cut COVID-19 mortality in half.¹⁹⁾L Nikniaz et.al. The impact of vitamin D supplementation on mortality rate and clinical outcomes of COVID-19 patients: A systematic review and meta-analysis. https://doi.org/10.1101/2021.01.04.21249219

Scientists start to explain the many different mechanisms in which Vitamin D shows so much benefit in COVID-19 treatment. One major problem in severe patient is an overreaction of the immune system, leading to a cytokine storm. This exaggerated inflammatory response can cause multiple organ damage. Vitamin D seems to be capable of regulating the immune system to minimize cytokine storm in severe patients.²⁰⁾Xu, Y., Baylink, D.J., Chen, CS. et al. The importance of vitamin d metabolism as a potential prophylactic, immunoregulatory and neuroprotective treatment for COVID-19. J Transl Med 18, 322 (2020). https://doi.org/10.1186/s12967-020-02488-5

Vitamin D Supplementation

There is no consensus on which levels of vitamin D are ideal for supplementation. In 2010 the Institue of Medicine raised the recommended daily allowance from 200UI to 600UI per day. The Endocrine Society recommends supplementation of 1500 to 2000UI per day in order to raise blood levels consistently above 30 ng/ml. They deem it safe to supplement up to 4,000 UI per day without medical supervision.²¹⁾M F Holick et.al. Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism, Volume 96, Issue 7, 1 July 2011, Pages 1911–1930, https://doi.org/10.1210/jc.2011-0385

Vitamin D toxicity is though very rare. The first negative side effect of high doses is increased calcium uptake, which can cause calcium deposits in the arteries and other organs. This effect is starting to be observed only in persons with Vitamin D blood levels above 150 ng/ml. Vitamin D is considered the least toxic among the fat-soluble vitamins, so there is no concern about toxicity doing a short term application of high doses of vitamin D. Some specialists like Michael Holick suggest that supplementation of up to 10.000 UI per day is perfectly safe.²²⁾„Vitamin D – State of the art“ – Dr. Michael F. Holick in Vienna (English) https://www.youtube.com/watch?v=NuWC2d0mTbo

It is possible to produce up to 10,000 UI of vitamin D just with a few minutes of sun exposure. This will work though only between 10 am and 3 pm, using no sunscreen and having large parts of the skin exposed to the sun. Latitude, season, age and skin color are factors that can significantly influence the amount of vitamin D production. In order to find out the ideal sun exposure for you, download the app Dminder that is found in Google Play and the App Store alike.

Now what levels of vitamin D in the blood are adequate? Here again, most recommendations are way lower than they are supposed to be. If you are below 30 ng/ml (75 nmol/l) consider yourself deficient. An ideal level for a well-functioning immune system would be between 50 and 100 ng/ml (125-250 nmol/l).

There are many who advocate a wider use of Vitamin D supplementation to help control the COVID-19 pandemic. In an initiative, 200 scientists and doctors have called on governments around the world to recommend a widespread supplementation of at least 4,000UI per day.²³⁾Over 200 Scientists & Doctors Call For Increased Vitamin D Use To Combat COVID-19. VitaminDforAll For those who did not do any supplementation so far, they recommend taking 10,000UI daily for 2-3 weeks in order to raise the levels, and then maintain with 4,000UI per day. Most governments that far have ignored this call, but individuals are able to do their part to protect themselves. And the message is reaching the consumers. Vitamin D supplement sales increased by more than 30% during the last year.²⁴⁾J Grebow. Vitamin D made headlines over COVID-19 studies last year. Sales of vitamin D were also up in 2020. What will 2021 look like? 2021 Ingredient trends to watch for food, drinks, and dietary supplements. Nutritional Outlook, February 10, 2021 And even Dr. Fauci has stated that supplementing vitamin D may be beneficial, and takes supplements for himself.²⁵⁾Dr. Fauci says to take vitamin D if you’re deficient — here’s how to know. CNBC. September 26, 2020

We have stated already that obese people need higher intakes of vitamin D, since it gets absorbed by the fat tissue. Overweight person with a BMI between 26 and 30 should take 1.5x the dose of normal weight individuals, and obese persons with a BMI above 30 should triple the dose of vitamin D supplementation. Age, should be taken into consideration as well when establishing the correct dose of supplementation. Individuals above 70 years of age should consider doubling the dose of supplementation.

It is interesting to note that High Fructose Corn Syrup which is present in soft drinks and many other industrialized foods can inactivate Vitamin D.²⁶⁾V Douard et.al. Excessive fructose intake causes 1,25-(OH)(2)D(3)-dependent inhibition of intestinal and renal calcium transport in growing rats. Am J Physiol Endocrinol Metab. 2013 Jun 15;304(12):E1303-13. DOI: 10.1152/ajpendo.00582.2012 The same mechanism may not apply to table sugar, but an excess of any kind of sugar will reduce the effectiveness of the immune system.

Conclusion

In summary we have seen that vitamin D has a profound impact on our immune system and is essential in the prevention of COVID-19. Based on this fact, we highly recommend to test for adequate vitamin D levels, and correct with proper sun exposure or supplementation if levels are low. In questions of doubt, consult a nutritionist to define the ideal dose for you.

Although vitamin D is essential, it is by far not the only thing you can do to strengthen your immune system. We have prepared a 10 day immunity challenge that will cover several habits that are essential to keep your immunity in top shape. Participate now to find out what you can do to have maximum protection against the coronavirus that is circulating around the entire globe.