Adverse health outcomes in vitamin D supplementation trials for depression: A systematic review

Vitamin D deficiency is a universal risk factor for adverse health outcomes. Since depression is consistently associated with low vitamin D levels as well as several adverse health outcomes, vitamin D supplementation may be especially relevant for depressed persons. This review examines the potential benefits of vitamin D for (somatic) health outcomes in randomised controlled supplementation trials for depression. Systematic literature search to assess whether adverse health outcomes, such as frailty, falls, or cognitive functioning, were included in vitamin D supplementation trials for depression, and whether these outcomes were affected by supplementation. The revised Cochrane tool for assessing risk of bias in randomised trials was used. Thirty-one trials were included. Adverse health outcomes were considered in five studies. Two studies reported some beneficial effect on an adverse health outcome. While depressed persons are at increased risk of vitamin D deficiency, supplementation trials hardly addressed the common negative health consequences of low vitamin D levels as secondary outcome measures. Well-designed trials of the effects of vitamin D supplementation in late-life depression should explore whether adverse health outcomes can be prevented or stabilised, and whether depression benefits from this improvement.