One Diet Does Not Fit All: A Systematic Review and Meta-Analysis of Gene–Diet Interactions Affecting Blood Lipid Profiles

Blood lipid responses to diet vary substantially between individuals, limiting the effectiveness of uniform dietary recommendations, and genetic variation may contribute to this heterogeneity through gene–diet interactions. This systematic review and meta-analysis evaluated nutrigenetic interactions affecting blood lipid traits. Web of Science Core Collection and MEDLINE were searched in April 2026 to identify human studies testing interactions between dietary exposures—including macronutrient composition, fat quantity, fat type polyunsaturated fatty acids (PUFA), monounsaturated fatty acids (MUFA), and saturated fatty acids (SFA), carbohydrate, and protein—and lipid-related genes. Interaction p-values were synthesized using a weighted Stouffer’s Z method with Benjamini–Hochberg false discovery rate correction. Twenty studies (n = 20), comprising approximately 9800 participants, met the inclusion criteria. The most consistent evidence was observed for CETP, APOE, and APOB, particularly in relation to broader macronutrient composition and fat-related exposures, while ABCA1 and APOA5 showed significant but more limited evidence. PUFA was the most consistent specific dietary exposure. In contrast, ABCG5, ABCG8, and CYP7A1 lacked sufficient data for meta-analysis, highlighting major gaps in the current literature. Overall, the findings support the view that lipid responses to diet are partly genotype-dependent, while also underscoring the need for larger, better harmonized studies to clarify and extend the current evidence base.