A cross-sectional analysis published in The Journal of Nutrition found that higher plasma levels of omega-3 fatty acids — particularly EPA-rich, non-DHA omega-3s — were associated with significantly lower rates of depression and anxiety.

The study, led by researchers at the Fatty Acid Research Institute (FARI), evaluated 258,354 adults with plasma fatty acid measurements and 468,145 adults with detailed fish oil supplement use in the UK Biobank, representing the largest biomarker-based mental health analysis of its kind, researchers said.

Critical depression and anxiety outcomes were drawn from physician-diagnosed ICD-10 codes, not self-report. Statistical models adjusted for age, sex, ethnicity, BMI, smoking, diet, alcohol use, exercise, socioeconomic status, and other covariates.

The findings showed that individuals with the highest omega-3 status (i.e., Omega-3 Index) had 15–33% lower odds of a lifetime history of depression and 19–22% lower odds of a lifetime history of anxiety, compared to those with the lowest levels. The non-DHA omega-3 fraction — primarily EPA — showed some of the strongest associations with reduced risk.

The study also found that fish oil supplement users had 9–10% lower risk of a history of depression or anxiety, and 20% lower risk of recent anxiety, independent of fish intake.

“This study adds significant weight to the growing evidence that omega-3 fatty acids — especially EPA — may help protect mental health,” said Dr. Bill Harris, lead study author and president of the Fatty Acid Research Institute (FARI).

Study Highlights

• Higher plasma omega-3 levels (total omega-3s, DHA, and non-DHA omega-3s) were consistently associated with lower odds of historical depression and anxiety.
• Non-DHA omega-3s (a proxy for EPA) had some of the strongest inverse associations, suggesting a particularly important role for EPA in mental health.
• Fish oil supplement users showed significantly lower risk for depression and anxiety, independent of oily fish consumption.
• Oily fish intake was also associated with reduced risk, but with weaker dose-response relationships compared to biomarkers, likely due to limitations of dietary self-reporting.

“Our findings from more than a quarter-million adults show a clear and consistent link between higher omega-3 status and lower chance of having a history of both depression and anxiety,” said Harris. “When you consider the biological roles of EPA and DHA in inflammation, neuronal function, and neurotransmitter signaling, these associations make a great deal of sense.”

“The strength of this research lies in both its scale and its use of plasma omega-3 measurements,” said Nathan Tintle, PhD, co-author, bio-statistician, and executive director of FARI. “The biomarker data give us a much clearer picture than self-reported diet alone, and the consistency across multiple omega-3 metrics strengthens confidence in the overall conclusions.”