New research findings help clarify mixed results from previous studies. Results from the largest clinical trial of its kind do not support the use of fish oil supplements—a source of omega-3 fatty acid—to help prevent depression. The findings are published in JAMA by a team led by investigators at Massachusetts General Hospital (MGH) and Brigham and Women’s Hospital (BWH). Experts have recommended omega-3 supplements for reducing the recurrence of depression in some high-risk patients, but there are no guidelines related to the use of these supplements for preventing depression in the general population. Also, studies on this topic have generated mixed results. To be more specific, the Vitamin D and Omega-3 Trial-Depression Endpoint Prevention (VITAL-DEP) was created to assess the efficacy of daily vitamin D and/or omega-3 supplementation in avoiding depression. A total of 18,353 persons aged 50 and older who were not depressed at the start of the study were randomly assigned to receive vitamin D and/or omega-3 supplements or matched placebos for a median of 5.3 years. “This study is a significant step. It requires many thousands of people to conduct this type of study of preventing depression in adults—something we call universal prevention—and the participants were taking randomized study pills for between 5 to 7 years on average,” says VITAL-DEP lead investigator and lead author Olivia I. Okereke, MD, MS, director of geriatric psychiatry at MGH and an associate professor of psychiatry at Harvard Medical School. “So, it is rare to see a long-term randomized trial of this kind.” Over the course of the trial, Okereke and her colleagues found no net benefit from omega-3 supplementation in terms of avoiding depression or enhancing mood. The risk of developing clinical depression at any point in time was given equal weight, as were general mood ratings throughout the course of the follow-up. While a little increase in the incidence of depression was within the statistical margin of error, Okereke claims that “there was no harmful or beneficial effect of omega-3 on overall course of mood during the roughly 5 to 7 years of follow-up.” “There are still health reasons for some people, under the guidance of their health care providers, to take omega-3 fish oil supplements. For example, these supplements increasingly have been found to have benefits for cardiac disease prevention and treatment of inflammatory conditions, in addition to being used for management of existing depressive disorders in some high-risk patients,” says senior author JoAnn E. Manson, MD, DrPH, chief of the Division of Preventive Medicine at BWH, a professor of medicine at Harvard Medical School, and director of the parent VITAL trial. “However, our findings indicate there is no reason for adults without depression in the general population to take fish oil supplements solely for the purpose of preventing depression or for maintaining a positive mood.” Reference: “Effect of Long-term Supplementation With Marine Omega-3 Fatty Acids vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood ScoresA Randomized Clinical Trial” by Olivia I. Okereke, MD, SM; Chirag M. Vyas, MBBS, MPH; David Mischoulon, MD, PhD; Grace Chang, MD, MPH; Nancy R. Cook, ScD; Alison Weinberg, MA; Vadim Bubes, PhD; Trisha Copeland, MS, RD; Georgina Friedenberg, MPH; I-Min Lee, MBBS, ScD; Julie E. Buring, ScD; Charles F. Reynolds III, MD and JoAnn E. Manson, MD, DrPH, 21 December 2021, JAMA.DOI: 10.1001/jama.2021.21187 Other authors include Chirag M. Vyas, MBBS, MPH, David Mischoulon, MD, PhD, Grace Chang, MD, MPH, Nancy R. Cook, ScD, Alison Weinberg, MA, Vadim Bubes, PhD, Trisha Copeland, MS, RD, Georgina Friedenberg, MPH, I-Min Lee, MBBS, ScD, Julie E. Buring, ScD, and Charles F. Reynolds III, MD. The study was supported by the National Institute of Mental Health.
