What does the evidence say about vitamin D and COVID-19?

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.

The takeaway

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.^[1] Still, one thing is clear:

VITAMIN D IS NOT A REPLACEMENT FOR AN APPROVED COVID-19 VACCINE.

Studies on COVID-19 and vitamin D

Vitamin D supplementation

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. (This study can’t rule out that vitamin D supplementation could have a preventive effect.)

In a randomized controlled trial, participants with mild or asymptomatic SARS-CoV-2 infections and vitamin d deficiency took placebo or 60,000 IU of vitamin D daily for 7 days, then the same dose for another 7 days, or a single dose if levels were high. The participants who took vitamin D had a notably shorter duration of SARS-CoV-2 infection.

In a retrospective cohort study, participants who received and 80,000 IU intravenous dose one month prior to infection or up to one week after infection were less likely to die than those who didn’t, though all participants received such doses regularly and their vitamin D status wasn’t known.

In a retrospective cohort study, the participants who had been receiving intravenous vitamin D every 2–3 months for the preceding year, but not the participants who received 80,000 IU of oral vitamin D within a few hours of COVID-19 diagnosis, were less likely to develop severe COVID-19 or die than those who had received no vitamin D.

In a retrospective cohort study, people with COVID-19 who received vitamin D upon hospitalization were less likely to die than those who didn’t.

In a prospective cohort study, people who survived were more likely to have been taking vitamin D than those who didn’t.

In a retrospective cohort study of participants with advanced chronic kidney disease, those who had received calcitriol were less likely to develop severe COVID-19 or die than those who didn’t.

Clinical evidence for vitamin D’s benefits is still very preliminary. 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 the observational studies have significant weaknesses and potential for confounding and bias. We need more good quality trials that provide data in different patient contexts to understand how supplementation can be useful.

Vitamin D levels

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.

Mechanisms

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.

General nutrition for 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.)

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