Cited by 353Fatty Acid Research and HealthTreatment of Major DepressionTryptophan and brain disorders

Updated systematic review and meta-analysis of the effects of n−3 long-chain polyunsaturated fatty acids on depressed mood

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Appleton, Katherine M, Rogers, Peter J, Ness, Andrew R·2010·The American Journal of Clinical Nutrition

Abstract

Background The debate over a role for n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) in depressed mood continues. Objective The objective was to update a previous systematic review and meta-analysis of published randomized controlled trials investigating the effects of n-3 PUFAs on depressed mood and to explore potential sources of heterogeneity. Design Eight databases were searched for trials that randomly assigned participants to receive n-3 PUFAs/fish, measured depressed mood, used human participants, and included a comparison group up to April 2009. Results Thirty-five randomized controlled trials were identified; 17 were not included in the previous review. The pooled standardized difference in mean outcome of the 29 trials that provided data to allow pooling (fixed-effects model) was 0.10 SD (95% CI: 0.02, 0.17) in those who received n-3 PUFAs compared with placebo, with strong evidence of heterogeneity (I(2) = 65%, P < 0.01). The presence of funnel plot asymmetry suggested that publication bias was a likely source of this heterogeneity. Depressive symptom severity and participant diagnosis also explained some of the observed heterogeneity. Greater effects of n-3 PUFAs were found in individuals with more-severe depressive symptoms. In trials that enrolled individuals with a diagnosed depressive disorder, the combined mean difference was 0.41 (95% CI: 0.26, 0.55), although evidence of heterogeneity was also found (I(2) = 71%). In trials that enrolled individuals without a depressive diagnosis, no beneficial effects of n-3 PUFAs were found (largest combined mean difference: 0.22; 95% CI: -0.01, 0.44; I(2) = 0%). Conclusions Trial evidence of the effects of n-3 PUFAs on depressed mood has increased but remains difficult to summarize because of considerable heterogeneity. The evidence available provides some support of a benefit of n-3 PUFAs in individuals with diagnosed depressive illness but no evidence of any benefit in individuals without a diagnosis of depressive illness.

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  • A meta-analytic review of 35 randomized controlled trials found that omega-3 fatty acid supplementation is associated with a 0.41-0.57 SD difference in depression severity for individuals with MDD.

    “a recent meta-analytic review of 35 randomized controlled trials found that omega-3 fatty acid supplementation is associated with a 0.41-0.57SD difference in depression severity for individuals with MDD”

    From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Appleton, Rogers, & Ness, 2010

    The Participant diagnosis section (page not provided) reports pooled differences of 0.41 SD and 0.57 SD for trials enrolling people with a depressive disorder, not specifically MDD. The Results section (page not provided) identifies 35 trials across the review but says only 29 were included in the meta-analyses; the quoted effect sizes come from the depressive-disorder subgroup. (LLM, conf=0.90)

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2 of the 87 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Warren G, McKendrick M, Peet M. The role of essential fatty acids in chronic fatigue syndrome. Acta Neurol Scand 1999;99:112-6.
  2. Sheehan DV, Lecrubier Y, Harnett-Sheehan K, et al. The Mini In- ternational Neuropsychiatric Interview (MINI): the development and validation of a structured diagnostic psychiatric interview. J Clin Psy- chiatry 1998;59:22-33.

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Authors
Appleton, K. M., Rogers, P. J., & Ness, A. R.
Affiliations
Queen's University Belfast (GB)
Corresponding author
Appleton, Katherine M
Venue
The American Journal of Clinical Nutrition
Publisher
Elsevier BV
Published
2010-03
Volume
91
Issue
3
Pages
757-770
ISSN
0002-9165 (ISSN-L)
OpenAlex
W2135221710
Cited by
353
References
87
Citations by year
2026: 3 · 2025: 6 · 2024: 10 · 2023: 8 · 2022: 8 · 2021: 12 · 2020: 21 · 2019: 19 · 2018: 19 · 2017: 25 · 2016: 34 · 2015: 31 · 2014: 39 · 2013: 34 · 2012: 41
FWCI
4.19
Type
journal article
Language
en
Open access
Locations
  • American Journal of Clinical Nutrition (publishedVersion)
  • PubMed (publishedVersion)
  • Explore Bristol Research (submittedVersion)
  • Research Portal (Queen's University Belfast) (submittedVersion)
Funders
McGill University
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
n-3 long-chain polyunsaturated fatty acids, omega-3 fatty acids, fish oil supplementation, depressive mood, depression, depressive symptoms, treatment effect heterogeneity, publication bias
MeSH terms
Depression, Dietary Fats, Humans, Severity of Illness Index, Fatty Acids, Omega-3, Randomized Controlled Trials as Topic, Publication Bias

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