Each month, we parse thousands of new studies to select the most important, review them, and summarize them for our Examine Members. Unsurprisingly, we ended up reviewing a good number of COVID-19 studies. The most studied supplement in the context of this disease is vitamin D. The present article is a short report on landmark studies on COVID-19 and vitamin D published between July 2020 and April 2021.
A pilot randomized controlled trial found that ICU admission was needed by 50% of the COVID-19 patients not taking vitamin D, but by only 2% of those taking vitamin D.
A cohort study found that COVID-19 patients taking a supplement containing 150 mg of magnesium, 500 μg of B12, and 25 μg (1,000 IU) of D3 were less likely to require supplemental oxygen or ICU support than a control group.
A randomized controlled trial found a lack of benefit of 200,000 IU of vitamin D for those hospitalized due to COVID-19. The study, however, can't rule out primary prevention or efficacy when vitamin D is taken earlier.
Clinical evidence for vitamin D’s benefits is still very preliminary and inconsistent. Typically, many good studies need to be analyzed together for us to be confident that a supplement works. The results of the pilot study look very impressive, but the negative study casts doubt, and we need more research.
A meta-analysis associated vitamin D levels under 30 ng/mL with a 43% increase in odds of COVID-19 infection.
A systematic review and meta-analysis found that, while vitamin D deficiency was not associated with the risk of COVID-19 infection, people who had COVID-19 had lower vitamin D levels than those who did not have COVID-19.
One systematic review found that COVID-19 patients with a poor prognosis had lower levels of vitamin D than those with a good prognosis.
A retrospective cohort study found that people with vitamin D deficiency were more likely to die from COVID-19.
A restrospective cohort study found that vitamin D levels over 40 ng/ml may be the most protective for Black people, whereas level didn't seem to matter for White people.
A retrospective cohort study found a strong, inverse correlation between vitamin D levels and COVID-19 infection rate.
A retrospective cohort study associated higher vitamin D levels with lower mortality: ≥30 ng/mL (≥75 nmol/L) with 9.2% mortality; <30 ng/mL with 25.3% mortality.
Overall, lower vitamin D levels seem correlated with a higher risk of COVID-19 and its complications, but one of the meta-analyses casts some doubt on this. It’s also possible that people with lower vitamin D levels are more susceptible due to worse general nutrition, a higher rate of comorbidities, a higher level of systemic inflammation, or other confounding factors. We’ll learn more in the next few months as we keep reviewing and summarizing studies on this topic for our Members.
A review reported a notable correlation between lower vitamin D levels and both COVID-19 infection rate and poor COVID-19 outcomes. It hypothesized that vitamin D might reduce the risk of COVID-19 infection and death by improving innate immunity, maintaining cell junctions, modifying gene expression, and acting as an antimicrobial.
A narrative review reported that vitamin D supplementation may benefit patients with COVID-19 by reducing the macrophage-driven hyperinflammatory response in the lungs.
It’s very clear that vitamin D plays a significant role in immune function and regulation, but it’s not so clear how low vitamin D levels need to be for this to be relevant to COVID-19.
A narrative review associated vitamin D deficiency or insufficiency with worse COVID-19 outcomes. It also found that vitamin D supplements enhanced the immune response to COVID when combined with high-dose vitamin C. (But a five-day open-label randomized controlled trial found that high-dose intravenous vitamin C was unlikely to improve COVID-19 outcomes.)
While there isn’t clear evidence that vitamin D helps fight off COVID-19, this disease does seem less severe in people with adequate vitamin D levels. The benefits of vitamin D are plausible, but keep in mind that, in the past, mechanistic and observational evidence in favor of vitamin D was not always confirmed in clinical trials.
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- Vitamin D Supplementation and Cardiovascular Disease Risks in More Than 83 000 Individuals in 21 Randomized Clinical Trials: A Meta-analysis. JAMA Cardiol. (2019) Mahmoud Barbarawi, et al.