![]() Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and hypersecretion of the stress hormone cortisol due to decreased sensitivity of glucocorticoid receptors in the brain are common physiological abnormalities in patients with depression (Willner, Scheel-Krüger, and Belzung 2013). Biologically active vitamin D (1,25-dihydroxyvitamin D3), nuclear vitamin D receptor (VDR), and enzymes activating and metabolizing vitamin D are present in neurons, glial cells, and brain macrophages, and vitamin D is considered to have various autocrine or paracrine actions in the brain (Kalueff and Tuohimaa 2007). ![]() Low circulating vitamin D levels have been linked to depression in cross-sectional studies (Anglin et al. Following the discovery of vitamin D receptors in the brain, it has been suggested that vitamin D could regulate neurophysiological processes associated with depression as a neuroactive steroid (Eyles et al. ![]() In some countries, vitamin D supplementation on regular basis in the form of fish liver oil or synthesized vitamin D is recommended for specific populations that are vulnerable to vitamin D deficiency, such as young children and the elderly (Prentice 2008). Sources of vitamin D in the diet include oily fish, eggs, meat, mushrooms and fortified dairy products. Vitamin D is known for its role in bone ossification and is formed in the skin by endogenous synthesis by sunlight UVB radiation or obtained from dietary sources. Thus, adjunctive treatment options for those with depression require further investigation. Further, treatment relapses are common, and most patients require multiple antidepressant trials to achieve adequate response (Rush et al. 2018) but their therapeutic efficacy is not always sufficient for all individuals. Antidepressants can be an effective treatment for depression (Cipriani et al. Funding: Finnish Medical Foundation, grant 4120 and Juho Vainio Foundation, grant 202100353.ĭepression is the leading cause of disability worldwide, affecting more than 320 million people every year (World Health Organization 2017, 2020). PROSPERO registration number: CRD42020149760. Future research should investigate possible benefits of augmenting standard treatments with vitamin D in clinical depression. Notwithstanding high heterogeneity, vitamin D supplementation ≥ 2,000 IU/day appears to reduce depressive symptoms. ![]() RoB assessment was concerning in most studies. Results for main outcome ( n = 53,235) revealed a positive effect of vitamin D on depressive symptoms (Hedges’ g = −0.317, 95% CI, p < 0.001, I 2 = 88.16% GRADE: very low certainty). Analyses based on random-effects models were performed with the Comprehensive Meta-analysis Software. Forty-one RCTs ( n = 53,235) were included. Cochrane risk-of-bias tool (RoB 2) and GRADE were used to appraise studies. Databases Medline, PsycINFO, CINAHL and The Cochrane Library were searched to identify relevant articles in English published before April 2022. Light therapy, co-supplementation (except calcium) and bipolar disorder were exclusionary. General and clinical populations, and studies of ill individuals with systemic diseases were included. This meta-analysis investigated the efficacy of vitamin D in reducing depressive symptoms among adults in randomized placebo-controlled trials (RCT). Meta‐analyses investigating the effect of vitamin D on depression have been inconsistent. ![]() Neurosteroid and immunological actions of vitamin D may regulate depression-linked physiology. ![]()
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