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Anti-depression medication about as good as big increase in vitamin D – meta-analysis of flawless data April 2014

Vitamin D and Depression: A Systematic Review and Meta-Analysis Comparing Studies with and without Biological Flaws

Nutrients 2014, 6(4), 1501-1518; doi:10.3390/nu6041501
Simon Spedding spedding at adam.com.au
Nutritional Physiology Research Centre, University of South Australia, City East Campus, North Tce, Adelaide, SA 5000, Australia
Received: 20 March 2014; in revised form: 4 April 2014 / Accepted: 4 April 2014 / Published: 11 April 2014

Efficacy of Vitamin D supplements in depression is controversial, awaiting further literature analysis. Biological flaws in primary studies is a possible reason meta-analyses of Vitamin D have failed to demonstrate efficacy. This systematic review and meta-analysis of Vitamin D and depression compared studies with and without biological flaws. The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The literature search was undertaken through four databases for randomized controlled trials (RCTs). Studies were critically appraised for methodological quality and biological flaws, in relation to the hypothesis and study design. Meta-analyses were performed for studies according to the presence of biological flaws.
The 15 RCTs identified provide a more comprehensive evidence-base than previous systematic reviews; methodological quality of studies was generally good and methodology was diverse.
A meta-analysis of all studies without flaws demonstrated a statistically significant improvement in depression with Vitamin D supplements (+0.78 CI +0.24, +1.27).
Studies with biological flaws were mainly inconclusive, with the meta-analysis demonstrating a statistically significant worsening in depression by taking Vitamin D supplements (−1.1 CI −0.7, −1.5).
Vitamin D supplementation (≥800 I.U. daily) was somewhat favorable in the management of depression in studies that demonstrate a change in vitamin levels, and the effect size was comparable to that of anti-depressant medication.

Emailed comment by the author

This time the paper is a meta-analysis with a difference. In fact two, I believe it may be the first meta-analysis about vitamin D and depression (the symptom not the disease). Perhaps more fundamentally, it compares vitamin D studies with and without biological flaws.

Biological flaws (with thanks to Robert Heaney)…I grade the flaws as ‘blindingly obvious’, ‘obvious’ and ‘more subtle’ ones.

  1. The ‘blindingly obvious’ – the IOM Institute of Medicine (calcium and vitamin D review) included two studies in the vitamin D section: one did not use vitamin D but used calcium in the intervention group, and in the other study the effect of seasonal change overwhelmed the dose of vitamin D such that the 25OHD actually decreased in the intervention group. So the study authors stated the trial was not an RCT.
  2. The ‘obvious’ – Many vitamin D studies did not measure 25OHD in the most participants, and used such small doses that no clinical effect was ever going to be apparent. The Womens Health Initiative is the best example as the effective dose of vitamin D was reduced to 200 IU (from 400 IU) by the low rate of compliance in the intervention group and the high rate of contamination in the controls.
  3. The ‘subtle’ flaws require a judgement as to whether ‘considering the dose used and the baseline 25OHD level, is it likely that a majority of the participants in the intervention group would have changed their vitamin D status from deficient to sufficient’.

The results of the systematic review and the meta-analysis were as WE would predict from understanding the mechanisms of vitamin D.

Studies without flaws show a positive effect on depression, whilst studies with flaws show a negative effect and a null result when all studies are considered together

Interestingly, this review found that previous systematic reviews of RCTs concluded there was insufficient evidence based, however these previous reviews only identified one to four of the 15 available valid RCTs about vitamin D and depression.

Huge range of dose sizes for the Depression Random Controlled Trials


Results: Decreased depression: studies which were not flawed.


 Download the PDF from VitaminDWiki

264 studies have cited this study as of April 2021

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Anti-depression medication about as good as big increase in vitamin D – meta-analysis of flawless data April 2014        
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