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

Mikola T, Marx W, Lane MM, Hockey M, Loughman A, Rajapolvi S, Rocks T, O'Neil A, Mischoulon D, Valkonen-Korhonen M, Lehto SM, Ruusunen A (2022) Crit Rev Food Sci Nutr Jul 11;1-18. doi: 10.1080/10408398.2022.2096560.

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Abstract:

Neurosteroid and immunological actions of vitamin D may regulate depression-linked physiology. Meta-analyses investigating the effect of vitamin D on depression have been inconsistent.

This meta-analysis investigated the efficacy of vitamin D in reducing depressive symptoms among adults in randomized placebo-controlled trials (RCT). General and clinical populations, and studies of ill individuals with systemic diseases were included. Light therapy, co-supplementation (except calcium) and bipolar disorder were exclusionary. Databases Medline, PsycINFO, CINAHL and The Cochrane Library were searched to identify relevant articles in English published before April 2022. Cochrane risk-of-bias tool (RoB 2) and GRADE were used to appraise studies. Forty-one RCTs (n = 53,235) were included. Analyses based on random-effects models were performed with the Comprehensive Meta-analysis Software.

Results for main outcome (n = 53,235) revealed a positive effect of vitamin D on depressive symptoms (Hedges' g = -0.317, 95% CI [-0.405, -0.230], p < 0.001, I2 = 88.16%; GRADE: very low certainty). RoB assessment was concerning in most studies.

Notwithstanding high heterogeneity, vitamin D supplementation ≥ 2,000 IU/day appears to reduce depressive symptoms. Future research should investigate possible benefits of augmenting standard treatments with vitamin D in clinical depression.

PROSPERO registration number: CRD42020149760. Funding: Finnish Medical Foundation, grant 4120 and Juho Vainio Foundation, grant 202100353.

FAB RESEARCH COMMENT:

This new systematic review and meta-analysis - including 41 different clinical trials and over 53,000 participants - found that supplementation with Vitamin D led to improvements in depressive symptoms.

Previous reviews and meta-analyses have either been inconclusive, or found benefits primarily for individuals with clinical-level depression. See for example:

Importantly, this new meta-analysis showed that benefits for reducing depressive symptoms came from trials using fairly high dosages of Vitamin D - at 50mcg/day (2000 IU) or more.

By contrast, only 10mcg/day (400 IU) is currently recommended by the UK NHS for all adults - although recommended intakes in the US and Europe are higher (600-800 IU), and the Upper Safe level is 4000 IU.

Clinical trial evidence of benefits from Vitamin D supplementation in most areas is still limited - not least because of the many serious practical difficulties in designing and conducting appropriate trials.

The actions of Vitamin D depend critically on availability of other nutrients, such as calcium, magnesium, Vitamin K2 etc. Magnesium in particular is seriously lacking from modern, western-type diets, and strongly implicated in depression and anxiety, as well as many other health disorders. See for example:

Dai et al 2019 - Magnesium status and supplementation influence vitamin D status and metabolism

This makes the current finding of benefits for depressive symptoms all the more remarkable - although the researchers did note that findings were variable, and much of the evidence was of 'low quality' - so (as ever), more research is required.

See the related news article: