The vitamin that affects mood—and may help with depression

By Naveed Saleh, MD, MS | Medically reviewed by Amanda Zeglis, DO, MBA
Published October 7, 2022

Key Takeaways

  • Adjunctive treatment for depression is a significant unmet need, with antidepressants not always effective.

  • Vitamin D deficiency is commonly seen in patients with major depressive disorder. Vitamin D receptors are located in regions of the brain responsible for mood, and vitamin D has anti-inflammatory effects that could moderate mood.

  • Supplementation of at least 2,000 IU daily could help alleviate depressive symptoms, according to recent research. Focused, randomized-controlled trials, however, are needed to verify this.

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

Experts hypothesize that vitamin D may play a role in depression for many reasons.

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.[]

“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.[]

"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."

Di Nicola, et al.

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

Vitamin D deficiency may also predict bipolar disorder (BD) in addition to major depressive disorder (MDD).

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.[]

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."

Mikola, et al.

“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.

What this means for you

Although more research needs to be done, low vitamin D levels are linked to depression. Vitamin D supplementation of at least 2,000 IU/day could help alleviate depressive symptoms, according to the research. Clinicians should stay apprised of ongoing research for further results on the effectiveness of supplementation in treating depression.

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