Long-term vitamin D supplementation does not appear to protect against depression
No significant difference in risk for depression or clinically relevant symptoms was noted over 5.3 years in 18,353 at-risk patients randomly assigned to receive vitamin D3 or placebo.
An ancillary study of a large, industry-supported randomized trial found that long-term supplementation with vitamin D3 did not appear to affect later development of depression.
The Vitamin D and Omega-3 Trial-Depression Endpoint Prevention (VITAL-DEP), an ancillary study of VITAL, examined the effects of vitamin D3 supplementation on late-life depression risk and mood scores among 18,353 U.S. men and women ages 50 years or older. Of these patients, 16,657 were at risk for incident depression and 1,696 were at risk for recurrent depression, defined as having a history of depression but no depression treatment in the past two years. From November 2011 through March 2014, patients were randomly assigned to receive vitamin D3 (2,000 IU of cholecalciferol per day) and fish oil or placebo. Results on the effects of fish oil were not reported in this study.
Risk of depression or clinically relevant depressive symptoms and mean difference in mood scores were the primary outcomes. Mood was measured by the 8-item Patient Health Questionnaire depression scale (PHQ-8), which ranges from 0 (least symptoms) to 24 (most symptoms), with 0.5 point considered the minimal clinically important difference for change in scores. Study agents, matching placebo, and packaging were donated by Pharmavite LLC and Pronova BioPharma/BASF. The study results were published Aug. 4 by JAMA.
Mean patient age was 67.5 years, and 49.2% were women. A total of 9,181 patients were randomly assigned to receive vitamin D3 and fish oil, and 9,172 were assigned to receive matching placebo. Median treatment duration was 5.3 years. Overall, 93.5% of the patients who were alive at the end of the trial completed it. The researchers found no significant difference in risk for depression or clinically relevant symptoms between the vitamin D3 group and the placebo group (12.9 per 1,000 person-years vs. 13.3 per 1,000 person-years, respectively; adjusted hazard ratio, 0.97 [95% CI, 0.87 to 1.09]; P=0.62). Depression incidence and recurrence also did not differ significantly between groups, and no significant differences were seen for change in PHQ-8 mood scores over follow-up (mean difference, 0.01 point [95% CI, −0.04 to 0.05 point]).
Among other limitations, PHQ-8 scores were determined only once per year, and most patients had adequate levels of 25-hydroxyvitamin D at baseline, limiting generalizability, the authors noted. They concluded that treatment with vitamin D3 versus placebo did not lead to a statistically significant difference in depression incidence or recurrence, or in clinically relevant depressive symptoms or change in mood scores, in adults ages 50 years and older who had no clinically relevant depressive symptoms at baseline. “These findings do not support the use of vitamin D3 in adults to prevent depression,” the authors wrote.