Previous studies have demonstrated that low levels of vitamin D were associated with higher risk for depression in older adults; however, there have been few long-term trials assessing the effects of vitamin D supplementation on mood and risk for depression. In a recent study, Dr. Olivia Okereke and colleagues in the Department of Psychiatry at MGH assess the impact of vitamin D supplementation on risk for depression in a group of older adults taking part in the VITAL study.
The VITAL study is a completed randomized controlled trial of 25,871 men and women in the U.S. that investigated whether taking daily dietary supplements of vitamin D3 (2000 IU) or omega-3 fatty acids (Omacor® fish oil, 1 gram) reduces the risk for developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses. VITAL-DEP (Vitamin D and Omega-3 Trial-Depression Endpoint Prevention) is an ancillary study to the VITAL trial and included a subset of 18,353 participants who were aged 50 years or older.
In this cohort, there were 16,657 adults at risk for incident depression; these participants had no history of depression. 1696 of the participants were at risk for recurrent depression; these participants had a history of depression but had no current symptoms of clinical depression and received no treatment for depression within the past two years. Participants were randomized to receive vitamin D3 (2000 IU/day of cholecalciferol) and fish oil (n=9181) or placebo (n=9172). Depressive symptoms were assessed using the Patient Health Questionnaire – 8 items (PHQ-8).
Among the 18,353 randomized participants (mean age, 67.5 [SD, 7.1] years; 49.2% women), the median treatment duration was 5.3 years, and 90.5% completed the trial. Risk of depression or clinically relevant depressive symptoms did not differ between those receiving the vitamin D3 supplement versus those receiving placebo. There were no significant differences between groups in depression incidence or recurrence. Nor did the researchers observe any significant differences between treatment groups in terms of changes in mood scores over time.
To date, this is the largest long-term study of the effects of supplemental vitamin D3 on risk for depression. In this study of adults aged 50 years or older with no clinically relevant depressive symptoms at baseline, the findings do not support the use of vitamin D3 to prevent depression in the general adult population.
Although there has been much interest in antidepressant effects of vitamin D, most studies thus far have failed to show beneficial effects of vitamin D supplementation in terms of prevention of depressive illness. Although low levels of vitamin D significantly correlate with depressive symptoms, most studies have observed that vitamin D supplementation did not have a meaningful effect on depressive symptoms. Because the VITAL-DEP study did not find a causal effect of long-term supplemental vitamin D3 on depression risk, a possible explanation for findings from earlier studies is that lower levels of vitamin D may be the result of depression rather than its cause.
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Okereke OI, Reynolds CF 3rd, Mischoulon D, Chang G, Vyas CM, Cook NR, Weinberg A, Bubes V, Copeland T, Friedenberg G, Lee IM, Buring JE, Manson JE. 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 Aug 4;324(5):471-480.
Olivia Okereke, MD, MS is a Board-certified geriatric psychiatrist and Associate Professor of Psychiatry and Associate Professor of Epidemiology at Harvard Medical School and the Harvard T. H. Chan School of Public Health. She is Director of Geriatric Psychiatry and Director (Research) of the Geriatric Psychiatry Clinical and Research Program at Massachusetts General Hospital.
David Mischoulon, MD PhD is the Director of the Depression Clinical and Research Program (DCRP) at Massachusetts General Hospital (MGH), and the Joyce R. Tedlow Professor of Psychiatry at Harvard Medical School.
