Nutr Rev. 2026 Mar 12:nuag019. doi: 10.1093/nutrit/nuag019. Online ahead of print.
ABSTRACT
CONTEXT: Omega-3 fatty acids are suggested to have protective effects against dementia and cardiovascular disease (CVD). Some evidence suggests that genetic elements, including the apolipoprotein E epsilon-4 (APOE-ε4) allele, may modify this association. However, the findings are inconsistent.
OBJECTIVE: In this study we sought to systematically review whether genetic variants modify the association between fish intake or omega-3 fatty acids and cognitive decline or CVD in community-dwelling adults aged 65 years and older.
DATA SOURCES: We searched the Embase, Medline, and Scopus electronic databases, along with the platform Web of Science, from inception to December 10, 2024.
DATA EXTRACTION: The search yielded 2349 papers. Title and abstract screening, along with full-text review, were independently performed by 2 reviewers. 15 studies met the inclusion criteria. Data extraction was completed by 1 reviewer and independently cross-checked by another. Risk of bias was assessed using standard tools.
DATA ANALYSIS: Due to substantial heterogeneity in the available evidence, instead of meta-analysis, a narrative review approach was adopted. A relatively small number of studies reported conflicting results for the dementia, Alzheimer disease (AD), and CVD outcomes; however, higher omega-3 biomarker levels/fish intake appeared to be associated with slower cognitive decline in APOE-ε4 carriers.
CONCLUSIONS: There is some limited evidence suggesting that APOE-ε4 may modify the association between omega-3 intake and cognitive decline in older adults, although the current body of research is inconsistent. This inconsistency highlights the need for additional research to better understand this association to support the development of personalized nutrigenetic-informed interventions to optimize health in later life.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration No. CRD42024623183.
PMID:41818679 | DOI:10.1093/nutrit/nuag019