Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: systematic review and meta-analysis of randomised trials

Systematic review and meta-analysis of randomized trials in adults aged 18 years and older, excluding pregnant or seriously ill people. The evidence came from 32 RCTs and 33 comparisons across diverse settings, including participants with or without depression or anxiety and many with chronic illness, cognitive impairment, or mental health problems. Outcomes were assessed over at least 24 weeks.

This systematic review evaluated increasing long-chain omega-3 fatty acids, mainly EPA plus DHA, versus lower-dose or control regimens across randomized trials. LCn3 doses ranged from 300 to 3360 mg/day, most often given as capsules or medicinal oils, with some trials using enriched foods, dietary advice, or a combination approach. It also assessed alpha-linolenic acid at 2 g/day via enriched margarine and one higher total PUFA intervention delivered with dietary advice plus nuts.

Increasing long-chain omega-3 supplementation probably has little or no effect on preventing depression symptoms, and it probably has little or no effect on anxiety symptoms as well. For depression prevention, the pooled risk ratio was 1.01 (95% CI 0.92 to 1.10; I2 = 0%), and a sensitivity analysis restricted to better adherence suggested possible increased risk (RR 1.16, 95% CI 0.99 to 1.36). In people with existing depression, evidence for change in severity or remission was very uncertain; one small trial showed a mean difference of -0.94 on the GDS-15 (95% CI -2.27 to 0.39; n = 61). Increasing alpha-linolenic acid may slightly increase depression symptoms over 40 months, while evidence for total PUFA is very low quality and unclear.

Evidence was sparse for several outcomes, especially depression treatment, ALA, omega-6, and total PUFA. Many trials were small or of limited quality, adverse events were poorly reported, and intervention formats and populations were heterogeneous, limiting certainty and generalizability. Some conclusions rely on very low-quality evidence or single small studies.