https://onlinelibrary.wiley.com/doi/pdf/10.1002/wps.20672

The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta‐review of meta‐analyses of randomized controlled trials

Background: Growing evidence points to the role of vitamin D in the pathobiology and treatment of depression. However, the evidence is inconsistent in many aspects. The objectives of this narrative review were to evaluate the state of the evidence, synthesize the knowledge gaps, and formulate recommendations for more enhanced research in this growing area. Methods: Electronic searches of MEDLINE via PubMed, Cochrane Library, and Google Scholar databases were carried out from inception till February 2019 to identify relevant English language peer-reviewed articles. Abstracts generated were systematically screened for eligibility. Included articles were grouped under three broad themes: The association between vitamin D and depression, its biological underpinnings, and trials evaluating the efficacy of vitamin D supplementation in depression. Relevant data were extracted as per a structured proforma. Results: A total of 61 articles were included in the present review. Overall findings were that there is a relationship between vitamin D and depression, though the directionality of this association remains unclear. The association appears to be driven by the homeostatic, trophic, and immunomodulatory effects of vitamin D. Evidence from supplementation trials suggest a more robust therapeutic effect on subjects with major depression and concurrent vitamin D deficiency. Conclusion: Serum vitamin D levels inversely correlate with clinical depression, but the evidence is not strong enough to recommend universal supplementation in depression. Enriching depression treatment trials with subjects having concurrent vitamin D deficiency appears to be a potential step forward in identifying subgroups who may maximally benefit from this approach.

https://journals.sagepub.com/doi/pdf/10.4103/IJPSYM.IJPSYM_160_19

Vitamin D and Depression: A Critical Appraisal of the Evidence and Future Directions.

Evidence is accumulating that vitamin D may have beneficial effects on respiratory tract, autoimmune, neuro-degenerative, and mental diseases. The present umbrella review of systematic reviews (SRs) of cohort studies and randomised controlled trials (RCTs), plus single Mendelian randomisation studies aims to update current knowledge on the potential role of vitamin D in preventing and treating these extraskeletal diseases. Altogether, 73 SRs were identified. Observational data on primary prevention suggest an inverse association between vitamin D status and the risk of acute respiratory tract infections (ARI), dementia and cognitive decline, and depression, whereas studies regarding asthma, multiple sclerosis (MS), and type 1 diabetes mellitus (T1DM) are scarce. SRs of RCTs support observational data only for the risk of ARI. No respective RCTs are available for the prevention of chronic obstructive pulmonary disease (COPD), MS, and T1DM. SRs of RCTs indicate beneficial therapeutic effects in vitamin D-deficient patients with asthma and COPD, while effects on major depression and T1DM need to be further elucidated. Mendelian randomisation studies do not consistently support the results of SRs. Since several limitations of the included SRs and existing RCTs do not permit definitive conclusions regarding vitamin D and the selected diseases, further high-quality RCTs are warranted.

https://publikationen.sulb.uni-saarland.de/bitstream/20.500.11880/30230/1/nutrients-12-00969-v2.pdf

Role of Vitamin D in Preventing and Treating Selected Extraskeletal Diseases-An Umbrella Review.

Background The several meta-analyses of the effect of vitamin D on depression have produced inconsistent results and studies dealing with anxiety were not incorporated. There has been no comprehensive analysis of how results are affected by the nature of the sample or the dosage and duration of supplementation. The study is aimed to investigate whether vitamin D supplementation reduces negative emotions and to analyze the possible influence of sample and regimen. Method We conducted a systematic review and meta-analysis of randomized controlled trials comparing the effect of vitamin D and placebo on negative emotion. Databases were searched for relevant articles published before February 2019. Results The analysis covered 25 trials with a total of 7,534 participants and revealed an effect of vitamin D on negative emotion (Hedges' g = -0.4990, 95% CI [-0.8453, -0.1528], p = .0047, I2 = 97.7%). Subgroup analysis showed that vitamin D had an effect on patients with major depressive disorder and on subjects with serum 25(OH)D levels ≤50 nmol/L. The pooled data from trials of vitamin D supplementation lasting ≥8 weeks and dosage ≤4,000 IU/day indicated that vitamin D had an effect. Conclusions Our results support the hypothesis that vitamin D supplementation can reduce negative emotions. Patients with major depressive disorder and individuals with vitamin D deficiency are most likely to benefit from supplementation. But to interpret the results with high heterogeneity should still be cautious.

The effect of vitamin D supplement on negative emotions: A systematic review and meta‐analysis

While observational studies show an association between 25(OH)vitamin D concentrations and depressive symptoms, intervention studies, which examine the preventive effects of vitamin D supplementation on the development of depression, are lacking. To estimate the role of lowered 25(OH)vitamin D concentrations in the etiology of depressive disorders, we conducted a two-sample Mendelian randomization (MR) study on depression, i.e., “depressive symptoms” (DS, n = 161,460) and “broad depression” (BD, n = 113,769 cases and 208,811 controls). Six single nucleotide polymorphisms (SNPs), which were genome-wide significantly associated with 25(OH)vitamin D concentrations in 79,366 subjects from the SUNLIGHT genome-wide association study (GWAS), were used as an instrumental variable. None of the six SNPs was associated with DS or BD (all p > 0.05). MR analysis revealed no causal effects of 25(OH)vitamin D concentration, either on DS (inverse variance weighted (IVW); b = 0.025, SE = 0.038, p = 0.52) or on BD (IVW; b = 0.020, SE = 0.012, p = 0.10). Sensitivity analyses confirmed that 25(OH)vitamin D concentrations were not significantly associated with DS or BD. The findings from this MR study indicate no causal relationship between vitamin D concentrations and depressive symptoms, or broad depression. Conflicting findings from observational studies might have resulted from residual confounding or reverse causation.

https://www.mdpi.com/2072-6643/11/5/1085/pdf

Vitamin D and the Risk of Depression: A Causal Relationship? Findings from a Mendelian Randomization Study

Background: There is a need to develop and periodically evaluate new treatment strategies in major depression due to the high burden of nonresponse and inadequate response to antidepressants. Aim: We aimed to assess the effect of vitamin D supplementation on depression symptom scores among individuals with clinically diagnosed major depression. Materials and Methods: Electronic search of databases was carried out for published randomized controlled trials in English language, peer-reviewed journals from inception till August 2017. Outcome measure used for effect size calculation was depression symptom scores. Effect sizes for the trials were computed using standardized mean difference (Cohen's d), and I2 test was used to assess sample heterogeneity. Pooled mean effect sizes were derived using both fixed and random-effects model. Critical appraisal of studies was done using the Cochrane risk of bias assessment tool. Results: A total of four trials involving 948 participants were included in the study. In three trials, the intervention group received oral vitamin D supplementation whereas in one parenteral vitamin D was given. Pooled mean effect size for vitamin D supplementation on depressive symptom ratings in major depression was 0.58 (95% confidence interval, 0.45–0.72). The I2 value for heterogeneity was 0 suggesting low heterogeneity among studies. Egger plot intercept indicated minimal publication bias. Conclusion: Vitamin D supplementation favorably impacted depression ratings in major depression with a moderate effect size. These findings must be considered tentative owing to the limited number of trials available and inherent methodological bias noted in few of them.

F Vellekkatt

Papers

Efficacy of vitamin D supplementation in major depression: A meta-analysis of randomized controlled trials.