Abstract
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 and EMBASE to April 2017, trial registers to September 2016, ongoing trials updated to 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 multifactorial interventions. Inclusion, data extraction and risk of bias were assessed independently in duplicate, and authors contacted for further data. We used random-effects meta-analysis, sensitivity analyses, subgrouping and Grading of Recommendations, Assessment, Development and Evaluations (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) and none of omega-6. Meta-analysis suggested that increasing long-chain omega-3 probably has little or no effect on risk of depression symptoms (risk ratio 1.01, 95% CI 0.92–1.10, I2 = 0%, median dose 0.95 g/d, duration 12 months) or anxiety symptoms (standardised mean difference 0.15, 95% CI 0.05–0.26, I2 = 0%, median dose 1.1 g/d, duration 6 months; both moderate-quality evidence). Evidence of effects on depression severity and remission in 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 2 g/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.
Link to Full Text
Key Points
This meta-analysis is part of a series of systematic reviews commissioned by the World Health Organization (WHO) assessing health effects of omega-3, omega-6 and total PUFA. GRADE assessment of the meta-analytic data suggests that increasing LCn3 probably has little or no effect on risk of depression or anxiety symptoms in those without depression or anxiety at baseline (moderate-quality evidence), but effects on depression severity and risk of remission in depression were unclear. Increasing ALA may
increase risk of depression symptoms very slightly (1000 people would need to increase their ALA intake for one additional person to develop depression symptoms). Data on other outcomes and effects of increasing omega-6 and total PUFA were missing or of very low quality. Results did not differ by risk of bias, omega-3 dose, duration or nutrients replaced. Effects on depression severity and remission were unclear (very-low-quality evidence). Physicians should not recommend omega-3 supplements for reducing depression or anxiety risk, and evidence of effectiveness in existing depression is of very low quality. Further methodologically strong, long-term trials (that focus on robust randomisation, allocation concealment, and blinding of participants, trial staff and outcome assessors, as well as adequately checking adherence in both the intervention and control arms) are needed to drive practice in people with existing depression and anxiety.