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

Background: There is strong public belief that polyunsaturated fats protect against and ameliorate depression and anxiety. Aims: To assess effects of increasing omega-3, omega-6 or total polyunsaturated fat on prevention and treatment of depression and anxiety symptoms. Method: We searched widely (Central, Medline, Embase to April 2017, trials registers to September 2016, ongoing trials updated August 2019), including trials of adults with or without depression or anxiety, randomised to increased omega-3, omega-6 or total polyunsaturated fat for ≥24 weeks, excluding multi-factorial interventions. Inclusion, data extraction and risk of bias were assessed independently in duplicate, authors contacted for further data. We used random-effects meta-analysis, sensitivity analyses, subgrouping and GRADE assessment. Results: We included 31 trials assessing effects of long-chain omega-3 (n=41,470), one of alpha-linolenic acid (n=4837), one of total polyunsaturated fat (n=4997), none of omega-6. Meta-analysis suggested increasing long-chain omega-3 probably has little or no effect on risk of depression symptoms (RR 1.01, 95% CI 0.92-1.10, I2 0%, median dose 0.95g/d, duration 12 months) or anxiety symptoms (SMD 0.15, 95% CI 0.05-0.26, I2 0%, median dose 1.1g/d, duration 6 months, both moderate-quality evidence). Evidence of effects on depression severity and remission in those with existing depression were unclear (very low-quality evidence). Results did not differ by risk of bias, omega-3 dose, duration or nutrients replaced. Increasing alpha-linolenic acid by 2g/d may increase risk of depression symptoms very slightly over 40 months (number needed to harm=1000). Conclusions: Long-chain omega-3 supplementation probably has little or no effect in preventing depression or anxiety symptoms.