Meta-analysis: “Sunshine vitamin” may brighten mood

Vitamin D is known for its role in bone ossification, and most of this vitamin is made when skin is exposed to sunlight. Recently, a meta-analysis has reported that supplemental vitamin D can help alleviate depressive symptoms in adults.

Pooled data from 41 studies (n=53,235) revealed that taking vitamin D had a positive effect on depression symptoms (Hedges’ g, −0.317; p<0.001; I²=88.16%) and was both beneficial in adult patients with major depressive disorder (MDD; Hedges’ g, −0.729) and in women with perinatal depressive symptoms (Hedges’ g, −0.930). [Crit Rev Food Sci Nutr 2022;doi:10.1080/10408398.2022.2096560]

The beneficial effect on depressive symptoms seemed larger when supplements had been taken for less than 12 weeks as opposed to longer than 12 weeks.

“However, our result favoured placebo in the subset of healthy individuals without a diagnosis of depression or without other major psychiatric or physical conditions,” according to a group of researchers from the University of Eastern Finland in Kuopio, Finland.

“These findings could represent a floor effect: when the baseline levels of depressive symptoms are very low, a reduction in depressive symptoms is challenging to detect through statistical analysis. In addition, participants in the subset of trials with healthy subjects may have been more likely to have a sufficient vitamin D status at baseline. The benefits of raising sufficient serum vitamin D levels are likely to be small,” they pointed out.

Some experts suggest that vitamin D could regulate neurophysiological processes associated with depression as a neuroactive steroid, following the discovery of vitamin D receptors in the brain. Since then, there has been a glut of evidence showing the potential benefit of vitamin D supplementation in patients with depression. [Nutr Rev 2008;66:S153-S164; Br J Psychiatr 2013;202:100-107]

For one, vitamin D has been reported to act as an antagonist of glucocorticoids and to protect the vulnerable hippocampus in HPA axis dysregulation. The compound is also believed to regulate the formation and maturation of new neurons in the hippocampus, the secretion of serotonin and dopamine by neurons, and the mechanisms underlying synaptic plasticity via genomic and nongenomic pathways. [J Neurochem 2006;96:500-509; Neurosci Lett 2003;343:139-143; Genes Nutr 2018;13:19; Behav Brain Res 2019;356:156-169]

“Furthermore, the body’s innate and adaptive immune responses have also been shown to be partially dependent on circulating 25(OH)D levels,” the researchers said. [Immunology 2011;134:123-139]

In the present study, vitamin D supplementation had a similar small-to-moderate effect size on depressive symptoms in people with low (≤50 nmol/L) and sufficient (>50 nmol/L) serum levels of vitamin D at baseline, with the effect size estimate slightly larger in the former subset, they added.

“Moreover, vitamin D doses up to 2,000 IU/day had a similar small-to-moderate size effect as doses up to 4,000 IU/day, but doses of over 4,000 IU/day produced a larger effect,” according to the researchers.

“It should be noted, [however], that a high degree of heterogeneity was observed across most analyses except for those with healthy participants and with low overall risk of bias, and significant evidence of publication bias was detected,” they acknowledged.

The studies included in the new meta-analysis were from around the world and investigated the efficacy of vitamin D in alleviating depressive symptoms mostly in young to middle-age and older adult participants. There were major differences in the vitamin D doses used, but the typical dose ranged 50–100 micrograms per day.

“Future research should investigate the possible benefits of augmenting standard treatments with vitamin D in clinical depression,” the researchers said.