Vitamin D has long been linked with immune function, but a new report suggests that vitamin D supplementation can reduce a person’s risk of COVID-19 infection and mortality.
Jason B. Gibbons, PhD, of Johns Hopkins University and the United States Department of Veterans Affairs (VA), and colleagues, noted that about half of people in the US have a deficiency or insufficiency of vitamin D. Previous research has shown that people who are not getting enough vitamin D are at a higher risk of COVID-19 infection and severe disease.
Yet, Gibbons and his co-authors said there has been limited evidence available thus far with regard to whether giving people oral vitamin D supplements might have a protective benefit.
Hoping to help answer the question, the investigators accessed healthcare data of veterans in the VA system to identify patients who received either vitamin D2 or D3 supplementation before or during the pandemic, and then compared their COVID-19 outcomes to people who were not given the supplements. Patients receiving both vitamin D2 and D3 were dropped from the analysis, as were people who had their first dose of vitamin D supplementation during the pandemic, since the authors said those patients likely had not been taking the therapy long enough to achieve a benefit.
After exclusions, the investigators were left with a study population of 220,265 people who received vitamin D3 supplements, 34,710 people who received vitamin D2, and 407,860 patients who received neither.
The investigators found that patients who filled a vitamin D2 prescription were 28% less likely to be diagnosed with COVID-19, and patients who filled a vitamin D3 prescription were 20% less likely to become infected (hazard ratios [HR] = 0.72; 95% confidence interval [CI]: 0.65, 0.79; and HR = 0.80; 95% CI: 0.77, 0.83, respectively.) Likewise, 30-day mortality rates following COVID-19 were lower in patients receiving supplementation, though the authors cautioned that the reduction for people taking vitamin D2 did not reach statistical significance (vitamin D2 HR = 0.75; 95% CI: 0.55, 1.04; vitamin D3 HR = 0.67; 95% CI: 0.59, 0.75).
“These associated reductions in risk are substantial and justify more significant exploration and confirmation using [randomized controlled trials],” Gibbons and colleagues wrote. “This is particularly important given the high rates of vitamin D deficiency in the US population and COVID-19.”
The investigators also found notable differences across subgroups. Black patients, for instance, had a greater reduction in COVID-19 infection rates when taking vitamin D3 than did White patients. The authors noted that people with darker skin tend to have higher rates of vitamin D deficiency or insufficiency.
“[T]hese results suggest that expansion of vitamin D supplementation may potentially reduce racial disparities in COVID-19 outcomes,” the authors said.
Gibbons and colleagues also found that participants who received higher doses of vitamin D had greater benefits, and that veterans who had vitamin D blood levels between 0 and 19 ng/ml before supplementation had the largest decrease in infection risk.
The authors listed a number of limitations to their study. They said they were unable to control for factors such as socioeconomic status, obesity, and adherence to public health precautions. They added that it is possible a significant number of patients had undiagnosed cases of COVID-19.
Still, the investigators concluded that with a low cost and high potential benefit, vitamin D deserves further investigation as a COVID-19 mitigation strategy.
“The most substantial dose-response relation was found in patients with the lowest vitamin D serum levels,” they wrote. “As a widely available, inexpensive, and safe treatment, vitamin D3 could be a helpful tool for reducing the spread of COVID-19 infection and related mortality and reducing racial disparities in COVID-19 outcomes.”