Gender Differences in Vitamin D and Depressive Symptoms: A Systematic Review

Research Article

Austin J Psychiatry Behav Sci. 2016; 3(2): 1052.

Gender Differences in Vitamin D and Depressive Symptoms: A Systematic Review

Day CMJ¹*, Kripalani M¹, Rees K², Weich S², Clarke A² and Stranges S³

¹South London and Maudsley NHS Trust, University Hospital Lewisham, UK

²Division of Health Sciences, University of Warwick Medical School, UK

³Department of Population Health, Luxembourg Institute of Health, Luxembourg

*Corresponding author: Day CMJ, Lady well Unit, South London and Maudsley NHS Trust, University Hospital Lewisham, London, UK

Received: June 02, 2016; Accepted: July 08, 2016; Published: July 12, 2016


Background: Both vitamin D insufficiency and depression are major public health concerns particularly in women. Recent animal and cross-sectional studies have suggested an association between low vitamin D levels and increased depressive symptoms with some evidence that vitamin D supplementation may be more beneficial in women.

Objective: (i) To examine the gender differences in the observational prospective association between vitamin D status (using serum levels) and depressive symptoms; (ii) to determine if vitamin D supplementation is more effective in women than in men.

Methods: MEDLINE, EMBASE, Web of Science & Knowledge, PsychInfo, the Cochrane Library and trial registers were searched with no language restrictions from inception to December 2015.

Results: 22 separate studies met the inclusion criteria, 5 observational prospective studies and 17 RCTs. The most robust cohort study found a significant association only in women. Only seven out of seventeen RCTs found a significant effect of vitamin D on depressive symptoms. Six of these were mixed-sex studies and one was a female only study that had the greatest effect size. The females included in these seven trials were mostly of childbearing age.

Conclusion: There is suggestive evidence of potential benefits of vitamin D supplementation in women of childbearing age with depressive symptoms. Further large randomized placebo-controlled secondary prevention trials in both men and women of childbearing age, with low vitamin D levels, are needed to investigate the relative efficacy of vitamin D supplementation in depression in men and women.

Keywords: Systematic review; Vitamin D; Depression; Gender differences; Randomized control studies; Observational studies; Prevention; Vitamin D; Gender differences; Female


RCT: Randomized Control Trial; BDI: Beck Depression Inventory; CES-D: Centre for Epidemiologic Studies –Depression Scale; SCID: Structured Clinical Interview for DSM Disorders; CIDI: Composite International Diagnostic Interview; NOS: Newcastle-Ottawa Quality Assessment Scale; ADL: Activities of Daily Living; SPPB: Short Physical Performance Battery; PTH: Parathyroid Hormone; HDRS: Hamilton Depression Rating Scale; POMS: Profile of Mood States; ANCOVA: Analysis of Covariance; SF-12 MCS: Mental Component of the Short Form 12 Health Survey; HADS: Hospital Anxiety and Depression Scale; MADRS: Montgomery-Asberg Depression Rating Scale; GDS: Geriatric Depression Scale.


Depression is the third most common cause of disease burden in the world for both men and women and is the leading cause of disease burden for women in the world [1]. Epidemiological data show that women are twice as likely as men, to develop depression during their childbearing years [2-4]. Furthermore, it is estimated that 1 billion people worldwide have either deficient or insufficient vitamin D levels [5], and some epidemiological data show that women may be more at risk of this than men [6-13] women. Vitamin D fortification of milk was mainstream in Europe in the early twentieth century; however this was banned in the 1950’s due to case reports of hypercalcaemia in children [5].

For both sexes, there is now epidemiological evidence of association of hypovitaminosis D with many non-skeletal health conditions [5,14] and more recently, cross-sectional and cohort studies have shown an association between low vitamin D levels and depression [15-17]. These epidemiological findings are corroborated by biological experimental evidence supporting a potential role of vitamin D in the pathogenesis of depression [18-20].

Given that women are at increased risk of depression and hypovitamonis D, there has already been some interest in the role of vitamin D in depression in women [21]. Some cross-sectional data show that the association between low vitamin D levels and depressive symptoms is stronger in women than in men [22,23]. It is not clear whether this is because women are, a priori, more at risk of hypovitaminosis D or whether there is a specific genderbased interaction between vitamin D and depression. Like the sex hormones, active vitamin D is a steroid hormone and there is evidence that oestrogen promotes the potency of vitamin D protective effects in animals and humans [24, 25].

One existing systematic review and meta-analysis [26] reported a modest significant effect of vitamin D supplementation on depressive symptoms in adults with depressive symptoms. Another metaanalysis [27] after eliminating studies with biological flaws also found benefit of vitamin D supplementation. In this systematic review, however we aim to investigate any sex-interaction in the association between vitamin D levels and depressive symptoms and in the effect of vitamin D supplementation on depressive symptoms, which has not been explored yet. From current evidence of micronutrient supplementation trials, where, supplementation is more effective in high-risk individuals [28], we hypothesise that the effect of vitamin D supplementation will be most clearly seen in (a) those with depressive symptoms at baseline of both sexes and (b) those who are vitamin D deficient. Furthermore, given the oestrogen promoted differences in local vitamin D metabolism, we hypothesize that both effects (a) and (b) will be greater in women than in men.

Materials and Methods

Search strategy and study selection

The following electronic databases were systematically searched with no language restrictions from their inception to December 2015; In MEDLINE; EMBASE; Web of Science; Web of knowledge; Web of Knowledge and Science (title); Psych Info; Cochrane Library and Meta RCT trial registers. Existing reviews and articles retrieved from the search terms were scanned for further studies and hand searching of various relevant journals was also performed. Due to the diverse nomenclature of vitamin D, extensive search strategies were created and tailored to individual databases. The search strategy for the various databases is shown in the appendix.

Studies met the inclusion criteria if they fulfilled the following criteria: