Efficacy of vitamin D supplementation in depression in adults: a systematic review.

Systematic review and meta-analysis of 6 randomized controlled trials in adults 18 years and older who were at risk of depression, had depressive symptoms, or had a primary diagnosis of depression. Trials were conducted in Norway, the United States, Australia, and Iran and included 1203 participants overall, with 71 participants who had depression.

Oral vitamin D supplementation was evaluated across 6 randomized trials, mainly as cholecalciferol, with regimens ranging from 1,500 IU/day to 20,000 IU twice weekly, 50,000 IU weekly, or 500,000 IU once yearly; one trial used calcitriol 0.25 g twice daily. Most comparisons were against placebo, and one depression trial tested vitamin D3 1,500 IU/day plus fluoxetine versus placebo plus fluoxetine.

Vitamin D supplementation did not show a significant overall benefit for depression symptoms. The pooled postintervention effect was small and nonsignificant in the classic meta-analysis (SMD = −0.14, 95% CI −0.41 to 0.13; P = .32), and the dichotomous outcome was also null (OR = 0.93, 95% CI 0.54 to 1.59; P = .79). Subgroup analyses by dose, sex, location, sampling, and population did not identify a clear effect. Adverse events were generally absent or similar to placebo, but overall evidence quality was low.

Evidence quality was low because of heterogeneity and risk of bias. The included trials used diverse populations, dosing regimens, and depression measures, and only a small number of participants had diagnosed depression, limiting direct applicability to depressed patients. Several studies also had incomplete or inconsistently reported arm-level details and variable follow-up durations.