The Benefits of Vitamin D Supplementation for Athletes: Better Performance and Reduced Risk of COVID-19.

The COVID-19 pandemic is having major economic and personal consequences for collegiate and professional sports. Sporting events have been canceled or postponed, and even when baseball and basketball seasons resumed in the United States recently, no fans were in attendance. As play resumed, several players developed COVID-19, disrupting some of the schedules. A hypothesis now under scientific consideration is that taking vitamin supplements to raise serum 25-hydroxyvitamin D [25(OH)D] concentrations could quickly reduce the risk and/or severity of COVID-19. Several mechanisms have been identified through which vitamin D could reduce the risks of infection and severity, death, and long-haul effects of COVID-19: (1) inducing production of cathelicidin and defensins to reduce the survival and replication of the SARS-CoV-2 virus; (2) reducing inflammation and the production of proinflammatory cytokines and risk of the "cytokine storm" that damages the epithelial layer of the lungs, heart, vascular system, and other organs; and (3) increasing production of angiotensin-converting enzyme 2, thus limiting the amount of angiotensin II available to the virus to cause damage. Clinical trials have confirmed that vitamin D supplementation reduces risk of acute respiratory tract infections, and approximately 30 observational studies have shown that incidence, severity, and death from COVID-19 are inversely correlated with serum 25(OH)D concentrations. Vitamin D supplementation is already familiar to many athletes and sports teams because it improves athletic performance and increases playing longevity. Thus, athletes should consider vitamin D supplementation to serve as an additional means by which to reduce risk of COVID-19 and its consequences.

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Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths.

The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40-60 ng/mL (100-150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

Why vitamin D clinical trials should be based on 25-hydroxyvitamin D concentrations.

Many health benefits are attributed to vitamin D, with those findings supported mostly by observational outcome studies of relationships to serum 25-hydroxyvitamin D [25(OH)D]. However, many randomized controlled trials (RCTs) aiming to confirm those findings have failed, perhaps because serum 25(OH)D is an index of UVB exposure and non-vitamin D mechanisms or because disease reduces serum 25(OH)D content. But the most likely reason for that failure is inappropriate design, conduct, analysis, and interpretation of RCTs. Most RCTs used principles designed to test pharmaceutical drugs; that design incorporates the assumptions that the RCT is the sole source of the agent and that dose-response relationships are linear. However, neither assumption is true for vitamin D, since neither vitamin D dose-responses or health outcome-serum 25(OH)D concentration relationships are linear-larger changes being induced with low rather than high baseline 25(OH)D values. Here, we propose a hybrid observational approach to vitamin D RCT design, based primarily on serum 25(OH)D concentration, requiring an understanding of serum 25(OH)D concentration-health outcome relationships, measuring baseline 25(OH)D values, recruiting non-replete subjects, measuring serum 25(OH)D during the trial for adjustment of supplemental doses for achievement of pretrial selection of target 25(OH)D values, where possible, and analyzing health outcomes in relation to those data rather than solely to vitamin D dosages.