Effects of vitamin D supplementation on depression

By Scott Cunningham, MD, PhD
Published November 14, 2022

Key Takeaways

  • The circulating 25(OH)D level increased after 8 weeks of supplemental vitamin D, with a corresponding improvement in patients with mild-to-moderate depression.

Putting It Into Practice

Despite the findings of the current study, vitamin D supplementation in patients with depression is not without risk. In fact, the collective findings of studies involving vitamin D supplementation in patients with depression have been mixed.

Mendelian randomization studies have ruled out a causal association between vitamin D levels and depression, and concerns exist that indiscriminate use of vitamin D supplementation in patients with depression may trigger refractory or atypical depression.

Why this study matters

It is well-known that the serum vitamin D level is decreased in patients with depression compared with non-depressed controls.

Although the underlying mechanism leading to decreased vitamin D levels in depressed patients has not been established, it has been theorized that vitamin D receptors in the limbic system, cerebellum, and cortex have an effect by modulating intra-neuron levels of Ca++ in the brain.

The results of the current study suggest that “supra-normal” levels of vitamin D may thus be required to overcome the Ca++ effect, although immunoinflammatory processes may also be involved, albeit to a lesser degree.

Additional well-designed studies are warranted to determine whether vitamin D causes depression or vice versa, and the dose, duration, and safety of vitamin D supplementation.

Study design

This was an 8-week double-blind clinical trial involving 56 patients (18-60 years of age) with mild-to-moderate depression. The patients were randomized to receive 50,000 IU of cholecalciferol every 2 weeks or placebo. The serum 25(OH)D, iPTH, IL-1β, IL-6, and hs-CRP levels, as well as the Beck Depression Inventory II score were determined prior to and after treatment.

Results and conclusion

After the 8-week treatment with cholecalciferol, the serum 25(OH)D level was increased compared to placebo (40.83 vs. 5.14 mmol/L). The Beck Depression Inventory II score was decreased further in the treatment group than the placebo group (-11.75 vs. -3.61).

The IL-1β, IL-6, and hs-CRP levels were not significantly different between the treatment and placebo groups post-treatment.

Original Source

Kaviani M, Nikooyeh B, Etesam F, et al. Effects of vitamin D supplementation on depression and some selected pro-inflammatory biomarkers: A double-blind randomized clinical trial. BMC Psychiatry 2022; doi.org/10.1186/s12888-022-04305-3.

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