Antidepressants can effectively treat depression, but their benefits can be insufficient for some patients. The need for effective adjunctive treatments is urgent.

Although results of meta-analyses on the link between vitamin D and depression have historically been mixed, emerging research suggests vitamin D supplementation may help with depression.

 

Potential mechanisms

There are increased vitamin D receptors in the prefrontal and cingulate cortices, which are responsible for regulating mood. Vitamin D could also moderate mood via mitigating inflammation, and could protect against depression via its anti-inflammatory effects.

Menon V, Kar SK, Suthar N, et al. Vitamin D and depression: A critical appraisal of the evidence and future directions. Indian J Psychol Med. 2020;42(1):11–21.

 

“Vitamin D is a neuroactive steroid involved in brain development, synaptic plasticity, neuroprotection, neurotransmission, and neuroimmunomodulation,” wrote the authors of a study published in Psychoneuroendocrinology.

Di Nicola M, Dattoli L, Moccia L, et al. Serum 25-hydroxyvitamin D levels and psychological distress symptoms in patients with affective disorders during the COVID-19 pandemic. Psychoneuroendocrinology. 2020;122:104869.

 

Vitamin D metabolites have been shown to protect neural integrity in brain areas implicated in the pathophysiology of stress response and mood regulation, such as the prefrontal cortex, amygdala, and hippocampus.

Also, vitamin D appears to play a role in the modulation of neuroinflammatory pathways, whose dysfunctions have been linked to both altered stress response and depression” they continued.

 

Hypovitaminosis D

Levels of vitamin D are lower in patients with MDD or BD, but the nature of these associations is debated.

In the Psychoneuroendocrinology study, Italian researchers assessed psychological distress in a small cohort of MDD and euthymic BD patients locked down for 7 weeks due to the COVID-19 pandemic.

They found that decreased serum 25(OH)D levels and MDD diagnosis predisposed participants to the outbreak’s stressors. Participants exhibiting a longer duration of illness, those who lived alone, and those who smoked were also more likely to experience COVID-19-related distress.

 

Exploring the link

Scandinavian researchers publishing in Critical Reviews in Food Science and Nutrition attempted to shore up the inconsistencies of previous meta-analyses examining the link between vitamin D and depression.

Mikola T, Marx W, Lane MM, et al. The effect of vitamin D supplementation on depressive symptoms in adults: A systematic review and meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr. 2022.2022:1–18.

 

They assessed the efficacy of vitamin D supplementation vs placebo on depressive symptoms in general and MDD populations. They also looked at whether the antidepressive effect varied by intervention duration or vitamin D dosage.

The investigators found that vitamin D supplementation decreased depressive symptoms in MDD patients, as well as in women with perinatal depressive symptoms. In individuals without depression or other illnesses, the results favored placebo.

Vitamin D supplementation was more effective when taken for fewer than 12 weeks compared with more than 12 weeks. Dosages of up to 2,000 IU/day had a similar small-to-moderate effect compared with doses up to 4,000 IU/day, while dosages above 4,000 IU/day elicited a larger effect. Vitamin D supplementation did not improve depressive symptoms in participants over age 65.

There is not yet consensus about the optimal serum 25(OH)D concentration for alleviating symptoms of depression.

“Hypothetically, if vitamin D supplementation has direct causal therapeutic effects in the human central nervous system, the standard cutoff level of vitamin D deficiency may not be adequate in neuropsychiatric disorders,” the Critical Reviews in Food Science and Nutrition authors continued. “However, the evidence for this is not strong.“

The authors recommended that future randomized-controlled trials study the efficacy of reducing depressive symptoms in patients with MDD and perinatal depression at dosages of at least 2,000 IU/day.