New studies find that vitamin D supplementation did not impact COVID-19 outcomes, but there’s more to the story

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Two recent studies investigating the effects of vitamin D supplementation on acute respiratory infection and COVID-19, found that supplementation did not reduce the incidence of disease. Vitamin D is understood to boost antiviral defenses against respiratory viruses such as influenza A and rhinovirus, with observation studies suggesting that low levels of 25-hydroxyvitamin D (25(OH)D) may be a risk factor for severe COVID-19.

Luke Huber, ND, vice president, scientific & regulatory affairs at the Council for Responsible Nutrition (CRN; Washington, D.C.) criticized what he calls “overly simplistic” media coverage about the study results. “Reporting on this research that suggests vitamin D levels are not relevant to COVID-19 outcomes ignores the large body of research on this connection and downplays critical limitations of these studies,” said Huber, in a press release. He points to an accompanying editorial¹ that highlights some of the studies’ limitations.

In the first study², 3100 subjects were randomized to receive either 3200 IU/day or 800 IU/day of vitamin D3 for six months if their blood 25-hydroxyvitamin D concentrations were <75 nmol/L. An additional 3100 received no test or supplementation for control. Despite the strengths of the study, such as a high prevalence (64.6%) of participants with inadequate 25-hydroxyvitamin D levels (<50 nmol/L) and good adherence to the protocol, a editorial accompanying the studies did point to some notable limitation. For example, during the study vaccination for COVID-19 began rolling out, and while only 1.2% of participants had been vaccinated, by the end of the study 89.1% (5523/6200) had received at least one dose, potentially affecting the results. Interestingly, in unvaccinated subjects COVID-19 was less frequent among those taking 3200 IU/day of vitamin D compared with the control group with no supplementation, however, these differences were not statistically significant.

The other study³ utilized cod liver oil as a surrogate for low dose (400 IU/day) vitamin D supplementation. Researchers randomized 34,741 participants to either 5 mL cod liver oil or 5 mL placebo oil daily for six months. Here too, vaccination status may have affected the outcome of the study, with 35% of participants vaccinated during the study, as well as adequate vitamin D levels (>50 nmol/L) at baseline among 86.3% of participants who were relatively young and healthy.

“Both research teams should be commended for having completed large and well-designed clinical trials during the covid-19 pandemic with its unforeseen logistical challenges,” said Peter Bergman, the author of the editorial commenting on the studies. “However, the null findings of the studies should be interpreted in the context of a highly effective vaccine rolled out during both studies.”

Bergman concludes that “these new trials remain compatible with the two large meta-analyses suggesting that vitamin D supplementation may be beneficial for vitamin D deficient individuals. A pragmatic approach for the clinician could be to focus on risk groups; those who could be tested before supplementation, including people with dark skin, or skin that is rarely exposed to the sun; pregnant women; and elderly people with chronic diseases. For those with inadequate vitamin D levels (<50 nmol/L), supplementation with 1000-2000 IU/day could be a safe, simple, and affordable way to restore vitamin D levels, improve bone health, and take advantage of any possible protective effect against respiratory tract infections.”

Reference

1. Bergman P “Can vitamin D protect against covid-19?” BMJ, vol. 378 (September 7, 2022), https://doi.org/10.1136/bmj.o1822
2. Jolliffe DA et al. “Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: phase 3 randomised controlled trial (CORONAVIT)” BMJ, vol. 378 (September 7, 2022); https://doi.org/10.1136/bmj-2022-071230
3. Brunvoll SH et al. “Prevention of covid-19 and other acute respiratory infections with cod liver oil supplementation, a low dose vitamin D supplement: quadruple blinded, randomised placebo controlled trial.” BMJ, vol. 378 (September 7, 2022); https://doi.org/10.1136/bmj-2022-071245