Vitamin D supplementation for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials

Systematic review and meta-analysis of 8 randomized controlled trials including 657 adults with confirmed COVID-19. Participants were hospitalized inpatients and outpatients from multiple countries, and some trials enrolled patients with baseline vitamin D deficiency.

Vitamin D was evaluated in multiple forms across 8 randomized controlled trials: calcifediol, calcitriol, and cholecalciferol. Regimens ranged from a calcifediol loading dose of 532 µg followed by 266 µg on days 3, 7, 14, 21, and 28, to calcitriol 0.5 µg daily for 14 days, and cholecalciferol given as single doses of 5,000 µg or repeated daily doses of 125-1,500 µg for 7-14 days. Comparators were placebo or standard care.

Vitamin D supplementation did not show a statistically significant overall benefit for mortality or other key clinical outcomes in adults with COVID-19. The review noted a non-significant trend toward lower mortality, with the most favorable signal seen for repeated dosing after diagnosis. Across studies, the evidence was low to moderate quality and heterogeneous, so firm conclusions about clinical benefit or optimal dosing could not be made.

The evidence base was small and heterogeneous, with different vitamin D forms, doses, timing, and patient settings across only 8 trials. Several studies were short, some enrolled vitamin D deficient patients while others did not, and the overall certainty of evidence was low to moderate, limiting confidence in pooled estimates and dose-response conclusions.