Are Higher Vitamin D Levels Needed Against COVID-19 in the Black Population?

Higher vitamin D serum levels may be required in Black persons than in Whites to support the immune system and reduce risk of COVID-19, according to a large retrospective cohort study.

David Meltzer, MD, PhD, Department of Medicine, University of Chicago, Chicago, IL, and colleagues point out that definitions of vitamin D deficiency and supplementation guidelines have been largely derived from effects on bone health. Although bone conservation in Black populations has been found with lower vitamin D levels than commonly considered sufficient, the investigators find no evidence that immune function is better preserved with low vitamin levels in Blacks than in Whites.

“This is especially important currently because deficient vitamin D levels have been associated with increased COVID-19 incidence and worse outcomes, especially in Black, Hispanic, and other non-White populations, who have also borne a disproportionate burden of COVID-19,” Meltzer and colleagues indicate.

To examine the interface of vitamin D level and supplementation, race and ethnicity, and risk of COVID-19, the investigators revisited the electronic health record data from a previous study cohort of almost 5000 patients with 25-hydroxy vitamin D [25(OH)D] serum levels at the University of Chicago Medicine, who were later tested for COVID-19 between March 3 and December 30, 2020.

In this assessment of individuals with 25(OH) D serum levels obtained within 365 days but before 14 days of COVID-19 testing, data on demographics, co-morbidities, laboratory tests and medications were analyzed, andCOVID-19 test results considered in relation to the vitamin D levels. Participants were stratified for analysis based on having 25(OH)D levels of less than 20ng/ml (deficient), 20 to less than 30ng/ml (insufficient), 30 to less than 40ng/ml or 40ng/ml or greater.

Meltzer and colleagues found, as others have reported, that lower vitamin D levels (eg, <20ng/ml) are associated with increased risk of positivity for COVID-19.In addition, however, they found that the risk for positive testing is also increased for Black persons with vitamin D level of 30 to less than 40ng/ml compared to those with levels of 40ng/ml or greater.This was a continuous variable in Black persons, with each 1ng/ml increase for those with 30 to less than 40ng/ml associated with a 3% decrease in risk of positive COVID-19 test. There was no such decreased risk in White persons after a level of 30ng/ml.

"Emphasizing that we still do not know if the relationship between serum 25(OH)D levels and COVID-19 risk is causal, the results seem to suggest that for Black persons, level of 40ng/ml or above may confer lower risk than levels of 30-40ng/ml or below," Meltzer commented to Contagion.

"Another possible interpretation is that levels of 40ng/ml or below may not be as protective as higher levels in Black persons, and that if levels are in that lower range then supplementation may be useful," Meltzer said.

The association of higher vitamin D levels with lower rates of COVID-19 positivity was strongest in this study among those using vitamin D supplements—particularly in those taking supplementation closer to the time of testing. This supports the case for supplementation, according to the investigators, although not necessarily demonstrating direct correlation to measured serum levels.

"It has also been hypothesized that free vitamin D levels may be more important to immune function than vitamin D levels and that free levels may be more affected by vitamin D intake or synthesis in some individuals since vitamin D may not be easily mobilized form vitamin D binding protein in some circumstances," the investigators posit.

Supplementation may be helpful then, not just for raising levels, "but because supplementation itself may increase free vitamin D independent of the levels," Meltzer posited.

"Our results did suggest people reported as taking a daily supplement of >2001 IU were much less likely to test positive for COVID-19 as long as their 25(OH)D level was 20ng/ml or above.For 25(OH)D levels lower than that, one has to wonder if the patient was actually taking that supplement consistently," Meltzer said.

Although this retrospective cohort study suggests the relation between vitamin D supplementation, serum levels and COVID-19 risk, the investigators acknowledge that dose-effective supplementation for particular populations is better determined through randomized controlled trials.While the pharmaceutical industry is unlikely to fund trials of a non-prescription supplement, Meltzer indicated that his group and others are conducting trials with a variety of designs and funding sources.

"One of our studies is funded by NIH and includes doses of 400 IU/day, 4,000 IU/day, and 10,000 per day," Meltzer announced."Another study we are doing is funded by CURES within Reach and local foundations, and compares 400 IU and 4,000 IU and is being done virtually, with recruitment on the internet and the vitamin D mailed to participants."

Additional information about both of these studies at the University of Chicago is available here.