Differential weight loss responses of APOA2 genotype carriers to diets of low carbohydrate and low fat: the DIETFITS randomized clinical trial

Authors: Lai, Chao Qiang; Parnell, Laurence; DAS, SAI KRUPA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; GARDNER, CHRISTOPHER - Stanford University; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Obesity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/24/2025
Publication Date: 5/1/2025
Citation: Lai, C., Parnell, L.D., Das, S., Gardner, C.D., Ordovas, J.M. 2025. Differential weight loss responses of APOA2 genotype carriers to diets of low carbohydrate and low fat: the DIETFITS randomized clinical trial. Obesity. 33(6):1048-1057. https://doi.org/10.1002/oby.24288.
DOI: https://doi.org/10.1002/oby.24288

Interpretive Summary: Different people often experience varying levels of success with the same diet, making it challenging to provide universally effective dietary advice. Precision nutrition aims to create personalized diet plans based on individual genetic profiles to promote better health. In a study involving 609 participants, researchers examined how different genetic versions of the APOA2 gene affected weight loss when following either a low-carbohydrate or low-fat diet. They found that individuals with one version of the gene (TT variant) lost more weight on a low-carbohydrate diet, while those with another version (C variant) initially lost weight on a low-fat diet but eventually started gaining weight again. These findings highlight the potential of precision nutrition to offer tailored dietary recommendations based on genetic makeup. By understanding how different genes interact with specific diets, it becomes possible to optimize weight loss and overall health more effectively. This approach can lead to more successful health outcomes and better use of resources in dietary planning.

Technical Abstract: Precision nutrition aims to tailor dietary advice based on individual genetic and environmental factors. Current evidence for the efficacy and feasibility of precision nutrition remains scarce. This study examined whether participants with different APOA2 genotypes at variant rs5082 in the DIETFITS study (n = 609) who met criteria for saturated fatty acid (SAT) intake had different weight loss outcomes in response to low-carbohydrate and low-fat diets over a 12-month period (n=309). Results indicate that although the genotype effect was not significant, the two healthy diets had different impacts on weight loss during the intervention. Participants with the TT genotype (n=258) lost more weight on the low-carbohydrate diet than on the low-fat diet throughout the trial. Conversely, C allele carriers (CT+CC, n=69) lost less weight on the low-fat diet than on the low-carbohydrate diet early in the intervention (3 months), but this difference vanished by 6 and 12 months. There was a significant gene by diet (GxD) interaction involving APOA2 genotype and SAT intake, affecting weight loss response late in the intervention (12 months) but not early in the trial. Importantly, among participants (n=264) who did not meet the criterion for consistent SAT intake, there were no significant differences in weight loss between APOA2 genotypes, and hence no GxD interaction was observed. This finding illustrates the implication of GxD interactions observed in observational studies on personalized nutrition and provides insights for the design of precision nutrition interventions.