The effect of vitamin D supplementation on depressive symptoms in adults: A systematic review and meta‐analysis of randomized controlled trials

Systematic review and meta-analysis of 41 randomized controlled trials in 53,235 adults. Participants came from general and clinical populations, including major depressive disorder, perinatal depressive symptoms, seasonal affective disorder, and healthy individuals.

Vitamin D supplementation was tested, most commonly as oral cholecalciferol, with some trials using ergocalciferol or calcitriol and a few using intramuscular administration. Doses ranged from 400 to 500,000 IU per single dose and from 400 IU/day to approximately 14,000 IU/day, typically for daily administration over 5 days to 5 years.

Vitamin D supplementation was associated with a small-to-moderate reduction in depressive symptoms overall. The pooled effect at the end of supplementation was Hedges' g = -0.317, 95% CI [-0.405, -0.230], p < 0.001, with substantial heterogeneity (I2 = 88.16%). Effects were larger in major depressive disorder (g = -0.729, 95% CI [-1.100, -0.358]) and perinatal mothers (g = -0.930, 95% CI [-1.229, -0.632]), while healthy participants showed little to no benefit (g = 0.043, 95% CI [0.025, 0.061]). Larger effects were reported with shorter duration, higher daily doses, and in participants with clinically relevant depressive symptoms, but certainty was very low and heterogeneity and possible publication bias limit confidence.

Evidence certainty was very low, and the pooled results were highly heterogeneous. Subgroup findings were inconsistent across depression status, dose, duration, baseline vitamin D status, and concomitant calcium use, and publication bias was a concern. Ethnicity reporting was limited, and some trials included co-supplementation or allowed antidepressant use, adding potential confounding.