Omega-3 Fish Oil Supplements Do Not Help Prevent Depression

Summary: Study reveals there are no net benefits of omega-3 supplementation for preventing depression or boosting mood.

Source: Mass General

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 provide clarity, the Vitamin D and Omega-3 Trial-Depression Endpoint Prevention (VITAL-DEP) was designed to test the potential of daily vitamin D and/or omega-3 supplements for preventing depression. A total of 18,353 adults aged 50 years or older without depression at the start of the trial were randomized to receive vitamin D and/or omega-3 supplements or matching 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.”

Okereke and her colleagues observed no net benefit of omega-3 supplements for preventing depression or boosting mood over the course of the study. Equal attention was given to risk of developing a clinical depression at any point and to overall mood scores for the duration of follow-up.

While a small increase in risk of a depression was inside the statistical margin of significance, Okereke says “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.”

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.

Funding: The study was supported by the National Institute of Mental Health.

Abstract

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 Scores

Importance

Marine omega-3 fatty acid (omega-3) supplements have been used to treat depression but their ability to prevent depression in the general adult population is unknown.

Objective

To test effects of omega-3 supplementation on late-life depression risk and mood scores.

Design, Setting, and Participants

A total of 18 353 adults participated in the VITAL-DEP (Vitamin D and Omega-3 Trial-Depression Endpoint Prevention) ancillary study to VITAL, a randomized trial of cardiovascular disease and cancer prevention among 25 871 US adults. There were 16 657 at risk of incident depression (no previous depression) and 1696 at risk of recurrent depression (previous depression, but not for the past 2 years). Randomization occurred from November 2011 through March 2014; randomized treatment ended on December 31, 2017.

Interventions

Randomized 2 × 2 factorial assignment to vitamin D₃ (2000 IU/d), marine omega-3 fatty acids (1 g/d of fish oil, including 465 mg of eicosapentaenoic acid and 375 mg of docosahexaenoic acid) or placebo; 9171 were randomized to omega-3 and 9182 were randomized to matching placebo.

Main Outcomes and Measures

Prespecified coprimary outcomes were risk of depression or clinically relevant depressive symptoms (total of incident + recurrent cases); mean difference in mood score (8-item Patient Health Questionnaire [PHQ-8] depression scale).

Results

Among 18 353 participants who were randomized (mean age, 67.5 [SD, 7.1] years; 49.2% women), 90.3% completed the trial (93.5% among those alive at the end of the trial); the median treatment duration was 5.3 years. The test for interaction between the omega-3 and the vitamin D agents was not significant (P for interaction = .14). Depression risk was significantly higher comparing omega-3 (651 events, 13.9 per 1000 person-years) with placebo (583 events, 12.3 per 1000 person-years; hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P = .03). No significant differences were observed comparing omega-3 with placebo groups in longitudinal mood scores: the mean difference in change in PHQ-8 score was 0.03 points (95% CI, −0.01 to 0.07; P = .19). Regarding serious and common adverse events, the respective prevalence values in omega-3 vs placebo groups were major cardiovascular events (2.7% vs 2.9%), all-cause mortality (3.3% vs 3.1%), suicide (0.02% vs 0.01%), gastrointestinal bleeding (2.6% vs 2.7%), easy bruising (24.8% vs 25.1%), and stomach upset or pain (35.2% vs 35.1%).

Conclusions and Relevance

Among adults aged 50 years or older without clinically relevant depressive symptoms at baseline, treatment with omega-3 supplements compared with placebo yielded mixed results, with a small but statistically significant increase in risk of depression or clinically relevant depressive symptoms but no difference in mood scores, over a median follow-up of 5.3 years. These findings do not support the use of omega-3 supplements in adults to prevent depression.

Trial Registration

ClinicalTrials.gov Identifiers: NCT01696435 and NCT01169259