Omega-3 Fatty Acids Protective Against Depressive Episodes?

Megan Brooks

August 19, 2022

New research is suggesting that there are "meaningful" associations between higher dietary intake of omega-3 fatty acids and lower risk for depressive episodes.

In a longitudinal study of more than 13,000 participants, consumption of omega-3 fatty acids (total and subtypes) was associated with a 2%-65% reduction in the risk for depressive episodes in patients with depressive episodes at baseline.

In addition, consumption of total fatty acids and alpha-linolenic acid was associated with a reduced risk for incident depressive episodes (9% and 29%, respectively).

"Our results showed an important protective effect from the consumption of omega-3," Maria de Jesus Mendes da Fonseca, University of the State of Rio de Janeiro, Brazil, and colleagues write.

The findings were published online August 7 in Nutrients.

Mixed Bag of Studies

Epidemiologic evidence suggests that deficient dietary omega-3 intake is a modifiable risk factor for depression and that individuals with low consumption of omega-3 food sources have more depressive symptoms.

However, the results are inconsistent, and few longitudinal studies have addressed this association, the investigators note

The new analysis included 13,879 adults (aged 39 to 65 years or older) participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) from 2008 to 2014.

Data on depressive episodes were obtained with the Clinical Interview Schedule Revised (CIS-R), and food consumption was measured with the Food Frequency Questionnaire (FFQ).

The target dietary components were total polyunsaturated fatty acids (PUFA) and the omega-3 fatty acids: alpha-linolenic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA).

The majority of participants had adequate dietary intake of omega-3 fatty acids, and none were taking omega-3 supplements.

In the fully adjusted model, consumption of fatty acids from the omega-3 family had a protective effect against maintenance of depressive episodes, showing "important associations, although the significance levels are borderline, possibly due to the sample size," the researchers report.

Maintenance of depressive episodes

Odds ratio (95%CI)


0.87 (0.70-1.03)

Alpha-linolenic acid

0.93 (0.62-1.39)


0.35 (0.10-1.09)


0.72 (0.49-1.01)


0.31 (0.10-1.13)


0.98 (0.94-1.04)


In regard to onset of depressive episodes, estimates from the fully-adjusted model suggest that a higher consumption of omega-3 acids (total and subtypes) is associated with lower the risk for depressive episodes — with significant associations for omega-3 and alpha-linolenic acid.

Incident of depressive episodes

Odds ratio (95%CI)


0.91 (0.84-.98)

Alpha-linolenic acid

0.71 (0.59-.91)


0.69 (0.39-1.20)


0.89 (0.75-1.05)


0.66 (0.33-1.25)


0.98 (0.95-1.00)


The investigators note that strengths of the study include "its originality, as it is the first to assess associations between maintenance and incidence of depressive episodes and consumption of omega-3, besides the use of data from the ELSA-Brasil Study, with rigorous data collection protocols and reliable and validated instruments, thus guaranteeing the quality of the sample and the data."

A study limitation, however, was that the ELSA-Brasil sample consists only of public employees, with the potential for a selection bias such as healthy worker phenomenon, the researchers note. Another was the use of the FFQ, which may underestimate daily intake of foods and depends on individual participant recall — all of which could possibly lead to a differential classification bias.

Interpret Cautiously

Commenting on the study for Medscape Medical News, David Mischoulon, MD, PhD, professor of psychiatry, Harvard Medical School, and director of the Depression Clinical and Research Program at Massachusetts General Hospital, Boston, Massachusetts, said that data on omega-3s in depression are "very mixed."

"A lot of the studies don't necessarily agree with each other. Certainly, in studies that try to seek an association between omega-3 use and depression, it's always complicated because it can be difficult to control for all variables that could be contributing to the result that you get," said Mischoulon, who is also a member of the Anxiety and Depression Association of America and was not involved in the research.

A caveat to the current study was that diet was assessed only at baseline, "so we don't really know whether there were any substantial dietary changes over time, he noted.

He also cautioned that it is hard to draw any firm conclusions from this type of study.

"In general, in studies with a large sample, which this study has, it's easier to find statistically significant differences. But you need to ask yourself: does it really matter? Is it enough to have a clinical impact and make a difference?" Mischoulon said.

The ELSA-Brasil study was funded by the Brazilian Ministry of Science, Technology, and Innovation and by the Ministry of Health. The investigators have reported no relevant financial relationships. Mischoulon has received research support from Nordic Naturals and heckel medizintechnik GmbH and honoraria for speaking from the Massachusetts General Hospital (MGH) Psychiatry Academy. He also works with the MGH Clinical Trials Network and Institute, which has received research funding from multiple pharmaceutical companies and the National Institute of Mental Health.

Nutrients. Published online August 7, 2022. Full article

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