What Is the Role of Vitamin D in Depression?

Vitamin D has been hailed as the “sunshine” vitamin with many therapeutic attributes. The authors explore the association between vitamin D deficiency and increased risk of depression.

Depression is a common psychiatric disorder that affects 11.23% of the population in the western world.1 However, the rates of depression vary greatly by geographic location, age, and sex, as well as other factors. For example, depression prevalence is as low as 1% in young urban men in Spain and as high as 28% in middle-aged urban women in Ireland.2 It is a disabling disorder, and the search for optimal treatment for depression is ongoing. Current treatment options include pharmacotherapy, psychotherapy, physical therapies, and behavioral therapies. However, while these are generally effective, applicability and treatment responses are limited, and some treatments can have serious adverse effects. Despite the availability of treatment options, 43% of patients fail to show adequate response to treatment and more than 55% have ongoing symptoms.3,4

Several factors are associated with increased risk of depression. Vitamin D deficiency has been proposed as one such risk.5 To better understand the relationship between vitamin D and depression, we posed 3 questions:

1. Is vitamin D deficiency a risk factor for depression?
2. Does vitamin D deficiency cause depression?
3. Does vitamin D supplementation relieve depression symptoms?

Produced in the body when the body is exposed to sunlight, vitamin D has been hailed as the “sunshine” vitamin with many therapeutic attributes.6 Lack of sunlight has been linked with mood disorders-especially seasonal affective disorder.7 Therefore, there is a good rationale for investigating the association between vitamin D deficiency and increased risk of depression.

Using case-control and cross-sectional studies, we examined the association between serum vitamin D level and depressive symptoms in 31,424 adults.5 Our findings suggest an association between vitamin D deficiency and depression. Data from our comparison of the lowest versus the highest categories of serum vitamin D levels showed a 31% increased risk of depression for those in the lowest category (odds ratio = 1.31; 95% confidence interval [CI], 1.0 1.71; P = .05).5 We also looked at depression outcomes from 3 cohort studies. Subjects with the lowest serum level of vitamin D were twice as likely to have depression at follow-up (hazard radio = 2.21; 95% CI, 1.4 3.49; P < .001).

The evidence from observational studies showed a weak association between vitamin D deficiency and risk of depression. This association does not imply causation because it is not known whether vitamin D deficiency leads to depression or whether the reverse is true-depression causes vitamin D deficiency. To better understand the effect of vitamin D supplementation as a treatment option for depression, randomized controlled trials (RCTs) are needed.

We recently looked at findings from 6 RCTs of vitamin D oral supplementation in depression.8 The majority (72%) of the 1203 study participants were women. Vitamin D was associated with improvement in depression symptoms after 8 weeks of supplementation only in the group with depressive disorder, not in adults at risk for depression (at risk was defined as individuals who were elderly, female, obese, or had vitamin D deficiency).

A meta-analysis of the 6 RTCs showed no significant effect of vitamin D on depression symptoms. However, the quality of evidence in this review as assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was low, and therefore better-designed RCTs are needed before a more precise estimate of vitamin D supplementation in depression can be reached.

Although our study did not show a significant effect of vitamin D on depression symptoms, the reasons behind these finding may be related to a relatively small number of studies, small overall sample size given the high prevalence of both depression and vitamin D deficiency in adults, the various methods of assessing depression symptoms, and the fact that the majority of these studies included persons at risk for depression without having a diagnosis of depressive disorder. The results may be different when there is an adequate number of studies. Thus far, the evidence for using vitamin D in depression is lacking, and recommendations for the use of vitamin D supplementation in depression are not yet justified.

Summary

• The evidence for a cross-sectional association between vitamin D deficiency and depression is weak.
• Cohort studies of vitamin D deficiency showed an increased risk of depression at follow-up.
• Oral supplements of vitamin D showed no effect on depression symptoms.
• The quality of evidence for vitamin D and depression is poor.
• Well-designed, large clinical trials are needed to understand the effects of vitamin D on depression.

Disclosures:

Dr Samaan is Assistant Professor in the department of psychiatry and behavioural neurosciences, Faculty Associate in the department of clinical epidemiology and biostatistics, and a member of the Population Genomics Program in the Chanchlani Research Centre at McMaster University in Hamilton, Ontario. Dr Anglin is Assistant Professor in the department of psychiatry and behavioural neurosciences and the department of medicine, division of gastroenterology at McMaster University. Mr Li is a PhD student in the department of clinical epidemiology and biostatistics at McMaster University. Dr Thabane is Professor and Associate Chair in the department of clinical epidemiology and biostatistics at McMaster University and is Director of the Centre for Evaluation of Medicine and the System Linked Research Unit in Hamilton. The authors report no conflicts of interest concerning the subject matter of this article.

References:

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2. Veerman JL, Dowrick C, Ayuso-Mateos JL, et al. Population prevalence of depression and mean Beck Depression Inventory score. Br J Psychiatry. 2009;195:516-519.

3. Sicras-Mainar A, Maurino J, Cordero L, et al. Assessment of pharmacological strategies for management of major depressive disorder and their costs after an inadequate response to first-line antidepressant treatment in primary care. Ann Gen Psychiatry. 2012;11:22.

4. Colman I, Naicker K, Zeng Y, et al. Predictors of long-term prognosis of depression. CMAJ. 2011; 183:1969-1976.

5. Anglin RE, Samaan Z, Walter SD, McDonald SD. Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry. 2013;202:100-107.

6. Nair R, Maseeh A. Vitamin D: the “sunshine” vitamin. J Pharmacol Pharmacother. 2012;3:118-126.

7. Westrin A, Lam RW. Seasonal affective disorder: a clinical update. Ann Clin Psychiatry. 2007;19:239-246.

8. Li G, Mbuagbaw L, Samaan Z, et al. Efficacy of vitamin D supplementation in depression in adults: a systematic review. J Clin Endocrinol Metab. 2013 Dec 10; [Epub ahead of print].