No Support for Vitamin D3 Supplementation to Prevent Depression Among Older Adults

vitamin D
vitamin D
Study findings do not support the use of vitamin D3 supplementation to prevent depression in adults.

Long-term supplementation with 25-hydroxyvitamin D (vitamin D3) did not significantly alter symptoms of late-life depression among the general population. These findings, from a randomized clinical trial, were published in JAMA.

Adults (n=18,353) aged 50 years or older were enrolled in the Vitamin D and Omega-3 Trial-Depression Endpoint Prevention (VITAL-DEP) clinical trial ( identifier NCT01169259) between 2011 and 2014. Participants were randomly assigned to receive either 2000 IU/day cholecalciferol (vitamin D3) and fish oil (n=9181) or a placebo (n=9172). Patients were followed through 2017 and assessed for depression using the 8-item Patient Health Questionnaire depression scale (PHQ-8); a score of 0 indicated minimal symptoms and a score of 24 indicated the most severe symptoms. A change in PHQ-8 score of 0.5 was considered the minimally important clinical change.

The 2 treatment groups were well balanced in terms of baseline characteristics. Mean participant age was 67.5±7.1 years, 49.2% of participants were women, 27% were minorities, and the mean baseline vitamin D3 level was 31.1 ng/mL. The majority of study participants (n=16,657) had no history of depression, and the rest of the participants had no treatment for depression during the previous 2 years. The participants had a median treatment duration of 5.3 years (interquartile range 5.0-5.7 years) and 90.5% completed the trial, with a 93.5% completion rate among participations who were alive at the study conclusion.

Reported incidence of depression or clinically relevant depressive symptoms were similar between the treatment and placebo cohorts (609 vs 625, respectively; adjusted hazard ratio 0.97; 95% CI, 0.87-1.09; P =.62). Throughout the study, the difference between treatment groups in PHQ-8 scores did not differ significantly from 0 (0.01 points; 95% CI, -0.04 to 0.05).

Reports of incident depression were similar between treatment and placebo cohorts (459 vs 461, respectively); reports of recurrent depression were also similar (150 vs 164, respectively). Overall risk for incident depression (HR, 0.99; 95% CI, 0.87-1.13) or recurrence of depression (HR, 0.95; 95% CI, 0.76-1.19) did not differ significantly between cohorts.

One limitation of this study was that low vitamin D3 has been associated with increased risk for depression during later life, however, only 11.6% of the study participants had levels below 20 ng/mL. It remains unclear whether a study population with lower baseline vitamin D3 levels would have a greater response to supplementation.

The conclusions drawn from these data were that among adults aged 50 years or greater with no clinically relevant depression symptoms, supplementation with vitamin D3 had no significant reduction for depressive symptoms or change in mood scores after 5 years.

“These findings do not support the use of vitamin D3 in adults to prevent depression,” the researchers concluded.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Okereke OI, Reynolds CF, Mischoulon D, et al. Effect of long-term vitamin D3 supplementation vs placebo on risk of depression or clinically relevant depressive symptoms and on change in mood scores. A randomized clinical trial. JAMA. 2020;324(5):471-480. doi: 10.1001/jama.2020.10224