High‐dose vitamin D supplementation in patients with COVID‐19: A meta‐analysis of randomized controlled trials

Abstract The efficacy of administering high doses of vitamin D to patients diagnosed with COVID‐19 remains uncertain. We conducted a comprehensive search across multiple databases (PubMed, EMBASE, Cochrane Library, and ISI Web of Science) from inception until August 2022, with no limitations on language, to locate randomized controlled trials (RCTs) that investigated the impact of high‐dose vitamin D supplementation (defined as a single dose of ≥100,000 IU or daily dose of ≥10,000 IU reaching a total dose of ≥100,000 IU) on COVID‐19 patients. Risk ratios (RR) with 95% confidence intervals (CI) and weighted mean differences (WMD) with 95% CI were calculated. Our meta‐analysis included 5 RCTs with a total of 834 patients. High‐dose vitamin D supplementation did not show any significant benefits for mortality (I2 = 0.0%, p = .670; RR 1.092, 95% CI 0.685–1.742, p = .711) or intensive care unit (ICU) admission (I2 = 0.0%, p = .519; RR 0.707, 95% CI 0.454–1.102, p = .126) in COVID‐19 patients compared to the control group. However, it was found to be safe and well‐tolerated (I2 = 0.0%, p = .887; RR 1.218, 95% CI 0.930–1.594, p = .151). Subgroup analysis also showed no benefits in overall mortality, including for patients with vitamin D deficiency (I2 = 0.0%, p = .452; RR 2.441, 95% CI 0.448–13.312, p = .303) or compared to the placebo (I2 = 0.0%, p = .673; RR 1.666, 95% CI 0.711–3.902, p = .240). Our research indicates that there is no evidence to support the efficacy of high‐dose vitamin D supplementation in improving clinical outcomes among individuals with COVID‐19, in line with previous studies focused on contexts including rickets. Considering the limitations of the study, additional research may be required.