Summary: Large randomized trial finds no net benefit of omega-3 (fish oil) supplements for preventing depression or improving mood in adults.
Source: Mass General
Results from the largest clinical trial to date do not support taking fish oil (marine omega-3 fatty acid) supplements to prevent depression.
A research team led by investigators at Massachusetts General Hospital (MGH) and Brigham and Women’s Hospital (BWH) reports the findings in JAMA. The analysis comes from VITAL-DEP, an ancillary study to the VITAL trial, and addresses whether daily omega-3 supplementation reduces the risk of developing depression or improves mood in older adults.
Clinical and public interest in omega-3 supplements has been high: some prior work suggested benefit for specific high-risk groups, while other studies produced mixed or inconclusive results. To clarify the evidence, VITAL-DEP enrolled 18,353 adults aged 50 years or older who did not have clinically relevant depressive symptoms at baseline. Participants were randomly assigned to receive vitamin D, omega-3 supplements, both, or matching placebos, and they were followed for a median of 5.3 years.
“This is one of the rare, large-scale randomized studies of universal prevention for depression,” says lead author Olivia I. Okereke, MD, MS, director of geriatric psychiatry at MGH and an associate professor at Harvard Medical School. “Participants took study pills for roughly five to seven years on average, which provides a robust window to observe any preventive effects.”
The trial compared daily marine omega-3 fatty acid capsules (1 g/day, containing 465 mg eicosapentaenoic acid and 375 mg docosahexaenoic acid) with placebo. Of the 18,353 randomized participants, roughly half received omega-3 and half received placebo. Investigators tracked two coprimary outcomes: the risk of developing depression or clinically relevant depressive symptoms (including both incident and recurrent cases) and change in mood score measured by the 8-item Patient Health Questionnaire (PHQ-8).
Overall, the VITAL-DEP team observed no meaningful benefit of omega-3 supplementation for preventing depression or for improving longitudinal mood scores. While a small increase in depression risk among the omega-3 group reached statistical significance, the authors emphasize that there was no consistent harmful or beneficial effect on overall mood across the follow-up period.
JoAnn E. Manson, MD, DrPH, senior author and chief of the Division of Preventive Medicine at BWH, notes that these results pertain to the general adult population without current depression. “There remain valid medical reasons for some individuals to take omega-3 supplements under clinical guidance—such as for certain cardiac or inflammatory conditions, or for managing established depressive disorders in specific high-risk patients—but our findings do not support routine use of fish oil solely to prevent depression or to maintain a positive mood in adults without depression,” she says.
Key trial details: participants’ mean age was 67.5 years and 49.2% were women. Treatment lasted a median 5.3 years, with 90.3% completing the trial. Depression events numbered 651 in the omega-3 group (13.9 per 1,000 person-years) and 583 in the placebo group (12.3 per 1,000 person-years), yielding a hazard ratio of 1.13 (95% CI, 1.01–1.26; P = .03). The average change in PHQ-8 mood score did not differ materially between groups (mean difference 0.03 points; 95% CI, −0.01 to 0.07; P = .19). Serious adverse events and common side effects were similar in both groups.
The study team includes authors Chirag M. Vyas, David Mischoulon, Grace Chang, Nancy R. Cook, Alison Weinberg, Vadim Bubes, Trisha Copeland, Georgina Friedenberg, I-Min Lee, Julie E. Buring, Charles F. Reynolds III, and others. Funding was provided by the National Institute of Mental Health.
Funding: The study was supported by the National Institute of Mental Health.
About this depression research news
Author: Michael Morrison
Source: Mass General
Contact: Michael Morrison – Mass General
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Original Research: “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” by Olivia I. Okereke et al., published in JAMA. Closed access.
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 supplements have been investigated for treatment of depression, but evidence about their preventive value in the general adult population has been limited.
Objective To evaluate whether long-term daily omega-3 supplementation reduces late-life depression risk or improves mood scores.
Design, Setting, and Participants VITAL-DEP enrolled 18,353 adults as an ancillary study to the VITAL randomized trial of cardiovascular disease and cancer prevention. Participants were randomized between November 2011 and March 2014 and followed through December 31, 2017. Most participants had no prior depression; a smaller subgroup had a prior history but no recent symptoms.
Interventions Participants were randomized in a 2×2 factorial design to vitamin D3 (2000 IU/day), marine omega-3 (1 g/day fish oil, including 465 mg EPA and 375 mg DHA), both agents, or matching placebos. Approximately 9,171 participants received omega-3 and 9,182 received placebo.
Main Outcomes and Measures Copimary outcomes were the combined risk of incident or recurrent depression/clinically relevant depressive symptoms and change in mood score measured by the PHQ-8.
Results Over a median 5.3 years, treatment with omega-3 showed a small but statistically significant increase in depression events compared with placebo (hazard ratio 1.13; 95% CI, 1.01–1.26). No significant differences were seen in longitudinal mood scores. Rates of major adverse events were similar between groups.
Conclusions and Relevance Among adults aged 50 and older without baseline depressive symptoms, long-term omega-3 supplementation did not reduce depression risk or improve mood scores and therefore is not supported for routine use to prevent depression in the general population.
Trial Registration Clinical trial identifiers: NCT01696435 and NCT01169259.