The influence of n-3 polyunsaturated fatty acids on cognitive function in individuals without dementia: a systematic review and dose-response meta-analysis

Abstract

Background: Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been suggested as a cognitive enhancing agent, though their effect is doubtful. We aimed to examine the effect of n-3 PUFA on the cognitive function of middle-aged or older adults without dementia.

Methods: We reviewed randomized controlled trials of individuals aged 40 years or older. We systematically searched PubMed/MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Library databases. We used the restricted cubic splines model for non-linear dose-response meta-analysis in terms of the standardized mean difference with 95% confidence intervals.

Results: The current meta-analysis on 24 studies (n 9660; follow-up 3 to 36 months) found that the beneficial effect on executive function demonstrates an upward trend within the initial 12 months of intervention. This effect is prominently observed with a daily intake surpassing 500 mg of n-3 PUFA and up to 420 mg of eicosapentaenoic acid (EPA). Furthermore, these trends exhibit heightened significance in regions where the levels of blood docosahexaenoic acid (DHA) + EPA are not very low.

Conclusions: Supplementation of n-3 PUFA may confer potential benefits to executive function among the middle-aged and elderly demographic, particularly in individuals whose dietary DHA + EPA level is not substantially diminished.

Keywords: Cognitive function; Dose–response meta-analysis; Mild cognitive impairment; N-3 PUFA; Omega-3; Polyunsaturated fatty acids.

Fig. 1

Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) diagram

Fig. 2

Forest plots concerning the effect of n-3 polyunsaturated fatty acids on six cognitive domains using randomized controlled trials

Fig. 3

Dose–response meta-analyses for the association between n-3 polyunsaturated fatty acids (PUFA) and the global cognition. a Duration of intervention; b daily intake of n-3 PUFA; c total amount of n-3 PUFA taken during the study period; d daily intake of docosahexaenoic acid (DHA); e daily intake of eicosapentaenoic acid (EPA); f ratio of DHA to EPA taken

Fig. 4

Dose–response meta-analyses for the association between n-3 polyunsaturated fatty acids (PUFA) and the executive function. a Duration of intervention; b daily intake of n-3 PUFA; c total amount of n-3 PUFA taken during the study period; d daily intake of docosahexaenoic acid (DHA); e daily intake of eicosapentaenoic acid (EPA); f ratio of DHA to EPA taken

Fig. 5

Dose–response meta-analyses for the association between n-3 polyunsaturated fatty acids (PUFA) and the executive function based on the studies from countries where the blood level of docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) is not very low. a Duration of intervention; b daily intake of n-3 PUFA; c total amount of n-3 PUFA taken during the study period; d daily intake of DHA; e daily intake of EPA; f ratio of DHA to EPA taken