Effects of a Nutrigenetic Diet on Fat Mass Loss, Insulin Resistance, and Subclinical Inflammation in Adults with Abdominal Obesity: A Randomized Controlled Trial—The INNUPREC Study

Background: Abdominal obesity (AO) is involved in the development of cardiometabolic disorders, in which factors such as diet and genetics play crucial roles. In this context, interactions between genetic variants and dietary responses may influence metabolic processes associated with AO. Objective: This study aimed to evaluate the effects of a nutrigenetic diet incorporating 21 genetic variants related to lipid metabolism and cardiovascular risk on anthropometric and biochemical parameters and antioxidant capacity in adults with AO. Methods: An eight-week randomized controlled trial was conducted in 58 adults with AO, who were randomly assigned to either a nutrigenetics-guided diet or a standard diet. Participants in the nutrigenetic group underwent genotyping for 21 variants associated with lipid metabolism and cardiometabolic risk in the ABCA1, APOA1, APOA2, APOA5, APOB, APOC3, APOE, CETP, CDKN2B-AS1, CD36, FABP2, FTO, LIPC, LPL, MTTP, MTHFR, NFKB1, PON1, SIRT1, and ZPR1 genes. Anthropometric and biochemical measurements were performed. Antioxidant and oxidative stress biomarkers were measured using colorimetric assays and ELISA, respectively. Results: In baseline-adjusted ANCOVA models controlling for age and sex, with false discovery rate (FDR) correction, both groups achieved comparable reductions in body weight and fat mass under equivalent energy restriction. However, the nutrigenetic group demonstrated significantly greater improvements in insulin levels, HOMA-IR, and high-sensitivity C-reactive protein (hs-CRP) compared with the standard diet group. The nutrigenetic intervention also resulted in greater reductions in the prevalence of elevated TyG index (−20% vs. −10.8%) and HOMA-IR (−33.3% vs. −10.7%), along with a trend toward a greater increase in catalase activity. Conclusions: Compared with a standard dietary intervention, a nutrigenetic diet was associated with greater improvements in fasting insulin, estimated insulin resistance (HOMA-IR), and systemic inflammation (hs-CRP) in adults with AO.