Review Vitamin D supplementation to reduce depression in adults: Meta-analysis of randomized controlled trials Usha Gowda M.H.N. a , Mutsa P. Mutowo M.P.H. a , Ben J. Smith Ph.D. a , Anita E. Wluka Ph.D. b , Andre M.N. Renzaho Ph.D. a, c, d, * a Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia b Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Melbourne, Victoria, Australia c Centre for International Health, Burnet Institute, Melbourne, Victoria, Australia d School of Social Sciences and Psychology, University of Western Sydney, Sydney, New South Wales, Australia article info Article history: Received 19 February 2014 Accepted 11 June 2014 Keywords: Depressive symptoms 25-Hydroxyvitamin D 3 Brain function Placebo Pooled effect abstract Objectives: The aim of this study was to estimate the weighted mean effect of vitamin D supple- mentation in reducing depressive symptoms among individuals aged 18 y diagnosed with depression or depressive symptoms. Methods: A meta-analysis of randomized controlled trials (RCTs) in which vitamin D supplementa- tion was used to reduce depression or depressive symptoms was conducted. Databases MEDLINE, EMBASE, psych INFO, CINAHL plus, and the Cochrane library were searched from inception to August 2013 for all publications on vitamin D and depression regardless of language. The search was further updated to May 2014 to include newer studies being published. Studies involving individuals aged 18 y who were diagnosed with depressive disorder based on both the Diagnostic and Statistical Manual of Mental Disorders or other symptom checklist for depression were included. Meta-analysis was performed using random effects model due to differences between the individual RCTs. Results: The analysis included nine trials with a total of 4923 participants. No significant reduction in depression was seen after vitamin D supplementation (standardized mean difference ¼ 0.28; 95% confidence interval, 0.14 to 0.69; P ¼ 0.19); however, most of the studies focused on in- dividuals with low levels of depression and sufficient serum vitamin D at baseline. The studies included used different vitamin D doses with a varying degree of intervention duration. Conclusions: Future RCTs examining the effect of vitamin D supplementation among individuals who are both depressed and vitamin D deficient are needed. Ó 2015 Elsevier Inc. All rights reserved. Introduction Mental health disorders are the leading cause of disability- adjusted life years (DALYs) in Australia and worldwide, accounting for 13% of all DALYs [1,2]. Among mental health dis- orders, depression remains the leading cause of disability worldwide, and contributes significantly to the global burden of disease [3]. Depression is estimated to affect 350 million in- dividuals and imposes a significant economic burden, not just on individuals with the disorder, but also on their families, com- munities, employers, and health care systems [3]. In addition to genetic, biological, environmental, and psy- chological factors, nutritional deficiency is reported to be an important factor contributing to depression [4]. Recent discovery that the brain possesses vitamin D receptors [5] suggests the possibility that mood and depressive disorders may be related to vitamin D deficiency and insufficiency [6]. Vitamin D is a unique neurosteroid hormone [5,7] and is involved in numerous brain processes including neuroimmunomodulation, neuroprotection, and brain development [8]. Several studies also have evaluated the relationship for vitamin D and other affective disorders such This study was funded by Australian Research Council Future Fellowship (FT110100345) research support funds. UG designed the study, drafted the article, and analyzed the data. MPM was the second reviewer involved in the data extraction and critical review of the manuscript. UG, AMNR, BJS, and AEW made substantial contribution in the intellectual input and critically reviewed the manuscript. All authors have approved submission of the article. The authors have no conflicts of interest to declare. * Corresponding author. Tel.: þ61 39 903 0802; fax: þ61 39 903 0556. E-mail address: andre.renzaho@monash.edu (A. M. N. Renzaho). http://dx.doi.org/10.1016/j.nut.2014.06.017 0899-9007/Ó 2015 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Nutrition journal homepage: www.nutritionjrnl.com Nutrition 31 (2015) 421–429