Omega-3, omega-6 and polyunsaturated fat for cognition: systematic review and meta-analysis of randomised trials

Julii S. Brainard, Oluseyi F. Jimoh, Katherine H. O. Deane, Priti Biswas, Daisy Donaldson, Katie Maas, Asmaa Abdelhamid, Lee Hooper, PUFAH group

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Objectives: Neurocognitive function may be influenced by polyunsaturated fat intake. Many older adults consume omega-3 supplements hoping to prevent cognitive decline. We assessed effects of increasing omega-3, omega-6, or total polyunsaturated fats on new neurocognitive illness and cognition. Design and inclusion criteria: We carried out a systematic review and meta-analysis of randomized controlled trials (RCTs) in adults, with duration ≥24 weeks, assessing effects of higher vs lower omega-3, omega-6, or total polyunsaturated fats and outcomes: new neurocognitive illness, newly impaired cognition, and/or continuous measures of cognition. 

Methods: We searched MEDLINE, Embase, Cochrane CENTRAL, and trials registers (final update of ongoing trials December 2018). We duplicated screening, data extraction, and risk of bias assessment. Neurocognitive measures were grouped to enable random effects meta-analysis. GRADE assessment, sensitivity analyses, and subgrouping by dose, duration, type of intervention, and replacement were used to interrogate our findings. 

Results: Searches generated 37,810 hits, from which we included 38 RCTs (41 comparisons, 49,757 participants). Meta-analysis suggested no or very little effect of long-chain omega-3 on new neurocognitive illness [risk ratio (RR) 0.98, 95% confidence interval (CI) 0.87-1.10, 6 RCTs, 33,496 participants, I 2 36%), new cognitive impairment (RR 0.99, 95% CI 0.92-1.06, 5 RCTs, 33,296 participants, I 2 0%) or global cognition assessed using the Mini-Mental State Examination (MD 0.10, 95% CI 0.03-0.16, 13 RCTs, 14,851 participants, I 2 0%), all moderate-quality evidence. Effects did not differ with sensitivity analyses, and we found no differential effects by dose, duration, intervention type, or replacement. Effects of increasing α-linolenic acid, omega-6, or total PUFA were unclear. 

Conclusions: This extensive trial data set enabled assessment of effects on neurocognitive illness and cognitive decline not previously adequately assessed. Long-chain omega-3 probably has little or no effect on new neurocognitive outcomes or cognitive impairment. Implications: Long-chain omega-3 supplements do not help older adults protect against cognitive decline.

Original languageEnglish
Pages (from-to)1439-1450.e21
JournalJournal of the American Medical Directors Association
Issue number10
Early online date15 Apr 2020
Publication statusPublished - 1 Oct 2020


  • Fatty acids, omega-3
  • cognition
  • dementia
  • fatty acids, omega-6
  • fatty acids, unsaturated
  • meta-analysis

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