Vitamin D Supplementation Reduces Depressive Symptoms in Subjects with Major Depressive Disorder

by | Oct 11, 2022 | 2022, Brain Health, Depression, Vitamin D - Mental Health

Written by Taylor Woosley, Staff Writer. Significant findings of this systemic review and meta-analysis of 41 papers with a total of 53,235 participants show that subgroup analysis in participants with clinically relevant depressive symptoms (including subjects with MDD) yielded a moderate effect favoring vitamin D supplementation (Hedges’ g = −0.604, 95% CI −0.802 to −0.406, p < 0.001, I2 = 78.4%). 

depressed young manDepression affects more than 168 million people worldwide and is one of the major causes of disease burden globally1. Major depressive disorder (MDD) is characterized by persistent low mood, often accompanied by cognitive dysfunction, physical symptoms, and impaired social function2. More than 85% of patients with a first episode will relapse in the next 10 years, and most of the patients have suicidal thoughts3. Research has suggested that depression may have multifactorial origins involving dysfunction of multiple brain areas and alternation in biochemical functions such as gene expression4.

The potential influence of diet and supplementation, such as vitamin D, on mood has emerged as a major research interest in recent years5. Vitamin D, a group of closely related secosteroid hormones, is involved in a range of important physiological processes, such as in promoting cell growth, facilitating immunomodulation regulation, and being involved in neurotransmission and anti-inflammatory effects6. Deficiency of vitamin D is often associated with several neurological diseases, as the vitamin D receptor is expressed in several brain structures including the hippocampus, hypothalamus, and thalamus7. Several studies have indicated the role of vitamin D as a critical neurosteroid hormone involved in numerous brain processes, including brain neuroplasticity and neuroimmunomodulation8.

Mikola et al. conducted a systemic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of vitamin D supplementation on depressive symptoms. RCTS included focused on examining the efficacy of vitamin D or vitamin D-calcium-supplementation in reducing depressive symptoms versus placebo in adults. Furthermore, a variety of different subgroups, including individuals with MDD, were included in analysis to examine whether the supplementation effect differed based on intervention duration or vitamin D dosage.

A total of 41 text papers published between 1998 and 2021 were included in the analysis, with a total of 53,235 participants included in the studies. Approximately 84% of the subject group were women. Study durations varied between five days to five years and vitamin D dosage ranged from 400 to 500,000 IU, with calculated intervention days varying from 400 IU to around 14,000 IU. Significant findings of the systemic review and meta-analysis are as follows:

  • Results of the primary meta-analysis produced a small-to-moderate effect of vitamin D on symptoms of depression (Hedges’ g = −0.317, 95% CI −0.405 to −0.230, p < 0.001, I2 = 88.16%; GRADE: very low certainty).
  • Subgroup analyses show an effect favoring vitamin D supplementation observed in patients (n=1166) diagnosed with MDD (Hedges’ g = −0.729, 95% CI −1.100
  • to −0.358, p < 0.001, I2 = 82.3%). However, subgroup analyses in healthy people (total n = 47,400) yielded a minimal effect favoring placebo (Hedges’ g = 0.043, 95% CI 0.025 to 0.061, p < 0.001, I2 = 0%).
  • A small subset of trials featuring mothers with perinatal depressive symptoms (n=407) show a large effect for vitamin D supplementation (Hedges’ g = −0.930, 95% CI −1.229 to −0.632, p < 0.001, I2 = 44.6%).

Results of this study suggest that vitamin D supplementation may have beneficial effects on subjects, particularly for those with MDD and perinatal depressive symptoms. Future research should continue to explore what duration and dosage of vitamin D offers the most improvement of symptoms in individuals. Study limitations include the limited evidence for clinical populations such as those with MDD, the high degree of studies used, and the specificity to detect MDD symptoms may fluctuate between studies depending on the assessment tool.

Source: Mikola, Tuomas, Wolfgang Marx, Melissa M. Lane, Meghan Hockey, Amy Loughman, Sanna Rajapolvi, Tetyana Rocks et al. “The effect of vitamin D supplementation on depressive symptoms in adults: A systematic review and meta‐analysis of randomized controlled trials.” Critical Reviews in Food Science and Nutrition (2022): 1-18.

© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.

Click here to read the full text study.

Posted October 11, 2022.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

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