Nutrigenetics, omega-3 and plasma lipids/lipoproteins/apolipoproteins with evidence evaluation using the GRADE approach: a systematic review

OBJECTIVES: Despite the uptake of nutrigenetic testing through direct-to-consumer services and healthcare professionals, systematic reviews determining scientific validity are limited in this field. The objective of this review was to: retrieve, synthesise and assess the quality of evidence (confidence) for nutrigenetic approaches related to the effect of genetic variation on plasma lipid, lipoprotein and apolipoprotein responsiveness to omega-3 fatty acid intake. DESIGN: A systematic review was conducted using three search engines (Embase, Web of Science and Medline) for articles published up until 1 August 2020. We aimed to systematically search, identify (select) and provide a narrative synthesis of all studies that assessed nutrigenetic associations/interactions for genetic variants (comparators) influencing the plasma lipid, lipoprotein and/or apolipoprotein response (outcomes) to omega-3 fatty acid intake (intervention/exposure) in humans—both paediatric and adult populations (population). We further aimed to assess the overall quality of evidence for specific priority nutrigenetic associations/interactions based on the following inclusion criteria: nutrigenetic associations/interactions reported for the same genetic variants (comparators) influencing the same plasma lipid, lipoprotein and/or apolipoprotein response (outcomes) to omega-3 fatty acid intake (intervention/exposure) in humans—both paediatric and adult populations (population) in at least two independent studies, irrespective of the findings. Risk of bias was assessed in individual studies. Evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach with a modification to further consider biological plausibility. RESULTS: Out of 1830 articles screened, 65 met the inclusion criteria for the narrative synthesis (n=23 observational, n=42 interventional); of these, 25 met the inclusion criteria for GRADE evidence evaluation. Overall, current evidence is insufficient for gene–diet associations related to omega-3 fatty acid intake on plasma apolipoproteins, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein (LDL)-cholesterol and LDL particle size. However, there is strong (GRADE rating: moderate quality) evidence to suggest that male APOE-E4 carriers (rs429358, rs7412) exhibit significant triglyceride reductions in response to omega-3-rich fish oil with a dose–response effect. Moreover, strong (GRADE rating: high quality) evidence suggests that a 31-SNP nutrigenetic risk score can predict plasma triglyceride responsiveness to omega-3-rich fish oil in adults with overweight/obesity from various ethnicities. CONCLUSIONS: Most evidence in this area is weak, but two specific nutrigenetic interactions exhibited strong evidence, with generalisability limited to specific populations. PROSPERO REGISTRATION NUMBER: CRD42020185087.