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Vitamin D Is Again In The Spotlight!

Can Vitamin D Help Reduce Coronavirus Infection Risk?

Maintaining adequate levels of Vitamin D is important to prevent rickets in children and osteoporosis in adults. More recently we saw the emergence of a growing interest in the potential anti-inflammatory effects of vitamin D in preventing diabetes, hypertension, multiple sclerosis, depression and other chronic medical conditions. And now vitamin D is in the spotlight again, with a possible role in reducing coronavirus infection risk.

What is vitamin D and what’s its role?

Vitamin D is essential for good health. How do we ensure an adequate amount? Sunlight on our skin is the best source. About 15 minutes a day of direct sunlight is sufficient for most people to maintain healthy levels. Darker skin and sunscreen lengthen the exposure time needed. People in northern latitudes -in winter- may not be able to make any Vitamin D from sunlight. In the absence of sunlight, food is the next source (fortified milk, orange juice and cereals; fatty fish like tuna and salmon; egg yolk and cheese; mushrooms). You can also get supplements; most daily multivitamin supplements contain enough Vitamin D.

Vitamin D exists in several forms, two of which are important to humans. Vitamin D2, called ergocalciferol, is made by plants. This type of vitamin D is most often found in dietary supplements and foods fortified with vitamin D. Vitamin D3 is made naturally by the skin when it is exposed to ultraviolet rays in sunlight. Neither vitamin D2 nor D3 is active in the body.

Both must be converted, first in the liver and then in the kidney, into the active form of vitamin D.

The main role of vitamin D is to regulate the amount of calcium circulating in the blood, essential for bone health. But vitamin D also plays a role in boosting our immune response against viral diseases and lowering inflammation. Its deficiency has been associated with increased risk of cardiac diseases, hypertension, and type 2 Diabetes. The Institute of Medicine¹ recommends that most adults get 600 international units of vitamin D from food or supplements daily, or 800 IU if they are aged 71 and older, to protect musculoskeletal health.

Are low vitamin D levels associated with an increased risk and severity of COVID-19 disease?

Of relevance now is that low vitamin D status may be exacerbated during the COVID-19 pandemic due to indoor living and hence reduced sun exposure.

Does it matter? It is possible, as there is emerging and growing evidence that vitamin D status may be relevant to the risk of developing COVID-19 infection and to the severity of the disease. A word of caution: the evidence is only observational and randomized clinical trials are needed to prove a causal association.

Let’s look at the available evidence:

• The deficiency of vitamin D is more prevalent among the higher risk groups for COVID-19 infection, such as the elderly, institutionalized, darker skin, obese, and with pre-existing conditions².

• An observational study³ at the University of Chicago Medicine, found that people who were vitamin D deficient before the pandemic began were 77% more likely to test positive for COVID-19 compared to people who had normal levels. The authors reviewed records of 4,300 patients, in their majority African American and Hispanics, many of them health care workers.

• In another study, Kenny⁴ and colleagues from Ireland reported that lower vitamin D levels appear to be associated with higher mortality from COVID-19 across countries in Europe. They also found that countries with a formal vitamin D fortification policy –even if they have less sunlight- appear to have the lowest rates of infection.

• In a recent preprint study, Ali Daneshkhah⁵ and colleagues from Northwestern University, Chicago, analyzing hospital data from China, France, Germany, Italy, Iran, South Korea, Spain, Switzerland, the United Kingdom, and the United States found a 16% higher risk of severe COVID-19 cases among patients with severe vitamin D deficiency compared to patients with normal vitamin D levels.

• A small South Asian study⁶ showed about an eightfold higher risk of having severe COVID-19 illness among those who entered the hospital with vitamin D deficiency compared with those who had normal vitamin D levels.

• Two studies^7,8 looking at patients from the UK Biobank found no correlation between vitamin D concentration and the risk of Covid-19 infection.

What is the mechanism supporting the possible association between vitamin D and risk of COVID-19?

A study published in the British Medical Journal three years ago⁹, which reviewed 25 randomized clinical trials, showed that vitamin D supplementation was associated with a significant reduction in upper and lower respiratory tract infections. The greatest effect of vitamin D supplementation was observed in those who were most vitamin D deficient. Although the study was not done in a COVID-19 setting, there is no reason to think vitamin D wouldn’t work the same in reducing the risk of coronary virus infections.  

Experts say healthy blood levels of vitamin D may give people with COVID-19 a survival advantage by helping them reduce the inflammatory response to the infection. Some patients develop what is called a cytokine storm which is when the immune system overreacts and attacks your body's own cells and tissues. In simple words, vitamin D can make the immune cells less inflammatory. Vitamin D is also known to interact with the angiotensin converting enzyme 2 (ACE2), a protein that is used by SARS-CoV-2 as an entry receptor. Vitamin D promotes local ACE2 formation in the lungs which may reduce the severity of acute respiratory distress syndrome.

Summary and Recommendations

Mechanistically, there is a link between vitamin D and respiratory tract infections.

Researchers from different countries have found that the sickest patients often have the lowest levels of vitamin D, and that countries with higher death rates had larger numbers of people with vitamin D deficiency than countries with lower death rates.

These associations have been identified in observational studies, in their majority not peer-reviewed, and as such authors caution that they are not causal and other factors may be involved. Brazil is a good example of having plenty of sun –and therefore we assume good vitamin D levels- and very high rates of COVID-19 infection and mortality. Randomized clinical trials are needed to confirm the role of vitamin D in coronavirus disease.

In the meantime you should go outside and get some sun, while maintaining social distancing guidelines. You should eat healthy foods that contain or are supplemented with vitamin D. Taking a multivitamin or a vitamin D supplement containing 1,000-2,000 IU/daily of vitamin D would be reasonable, especially if you are older and have limited access to sunlight. Be careful with the supplements since excess vitamin D can have side effects, the most serious being an increase in your calcium blood levels with negative consequences on your heart, blood vessels and kidneys. Remember that simple measures such as regular exercise, getting enough sleep and not smoking can help improve your resistance to infection.   

References

¹RossAC, Manson JE, Abrams SA, et al. The 2011 Report on Dietary Reference  Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know. J Clin Endocrinol Metab. 2011 Jan; 96(1): 53–58.

²Pearce SH, Cheetham TD. Diagnosis and management of vitamin D deficiency. BMJ. 2010; 340:b5664.

³Meltzer DO, Best TJ, Zhang H, Vokes T, Arora V, Solway J. Association of Vitamin D Deficiency and Treatment with COVID-19 Incidence. Posted May 13, 2020. doi: https://doi.org/10.1101/2020.05.08.20095893. medRxiv preprint.

⁴Laird E, Rhodes J and Kenny RA. Vitamin D and Inflammation: Potential Implications for Severity of Covid-19. Ir Med J; Vol 113; No. 5; P81.

⁵Daneshkhah A, Agrawal V, Eshein A, Subramanian H, Roy HK, Backman V. The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients. doi: https://doi.org/10.1101/2020.04.08.20058578.

⁶Alipio MM. Vitamin D supplementation could possibly improve clinical outcomes of patients infected with Coronavirus-2019 (COVID2019). Preprint. Electronic copy available at: https://ssrn.com/abstract=3571484.

⁷Hastie CE, Mackay DF, Ho F et al. Vitamin D concentrations and COVID-19 infection in UK Biobank. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 14 (2020) 561e565.

⁸Darling AL, Ahmadi KR, Ward KA, et al. Vitamin D status, body mass index, ethnicity and COVID-19: Initial analysis of the first-reported UK Biobank COVID-19 positive cases (n 580) compared with negative controls (n 723). Preprint. https://doi.org/10.1101/2020.04.29.20084277.

⁹Martineau AR, Jolliffe DA, Hooper RL et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017;356:i6583.