ObjectivesDespite 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.DesignA 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.ResultsOut 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.ConclusionsMost evidence in this area is weak, but two specific nutrigenetic interactions exhibited strong evidence, with generalisability limited to specific populations.PROSPERO registration numberCRD42020185087.

Background: There is a significant lack of consistency used to determine the scientific validity of nutrigenetic research. The aims of this study were to examine existing frameworks used for determining scientific validity in nutrition and/or genetics and to determine which framework would be most appropriate to evaluate scientific validity in nutrigenetics in the future.Methods: A systematic review (PROSPERO registration: CRD42021261948) was conducted up until July 2021 using Medline, Embase, and Web of Science, with articles screened in duplicate. Gray literature searches were also conducted (June-July 2021), and reference lists of two relevant review articles were screened. Included articles provided the complete methods for a framework that has been used to evaluate scientific validity in nutrition and/or genetics. Articles were excluded if they provided a framework for evaluating health services/systems more broadly. Citing articles of the included articles were then screened in Google Scholar to determine if the framework had been used in nutrition or genetics, or both; frameworks that had not were excluded. Summary tables were piloted in duplicate and revised accordingly prior to synthesizing all included articles. Frameworks were critically appraised for their applicability to nutrigenetic scientific validity assessment using a predetermined categorization matrix, which included key factors deemed important by an expert panel for assessing scientific validity in nutrigenetics.Results: Upon screening 3,931 articles, a total of 49 articles representing 41 total frameworks, were included in the final analysis (19 used in genetics, 9 used in nutrition, and 13 used in both). Factors deemed important for evaluating nutrigenetic evidence related to study design and quality, generalizability, directness, consistency, precision, confounding, effect size, biological plausibility, publication/funding bias, allele and nutrient dose-response, and summary levels of evidence. Frameworks varied in the components of their scientific validity assessment, with most assessing study quality. Consideration of biological plausibility was more common in frameworks used in genetics. Dose-response effects were rarely considered. Two included frameworks incorporated all but one predetermined key factor important for nutrigenetic scientific validity assessment.Discussion/Conclusions: A single existing framework was highlighted as optimal for the rigorous evaluation of scientific validity in nutritional genomics, and minor modifications are proposed to strengthen it further.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=261948, PROSPERO [CRD42021261948].