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Same Food, Different Outcome: How Biology Shapes the Effects of Food on Health (Oral Session 3)

(OR03-03-25) Low Fat/Carbohydrate Diet, Fat- and Carbohydrate-Responsive Genotypes, and Coronary Artery Disease: A Prospective Study

Saturday, May 31, 2025
10:24 AM - 10:36 AM ET
Location: S220 B-D

    Presenting Author(s)

  • Xinming Xu, MBBS (she/her/hers)

    PhD candidate
    Institute of Nutrition, Fudan University
    Shanghai, Shanghai, China (People's Republic)

    Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

    • Co-Author(s)

  • XG

    Xiang Gao

    Fudan University

Objectives: This study aimed to explore the association between low-carbohydrate diet (LCD) (including overall, animal-based and vegetable-based)/low fat diet (LFD) based on the percentage of energy from carbohydrate, protein, and fat, stratified by fat- and carbohydrate-responsive genotypes, and coronary artery disease (CAD).

Methods: 24-hour online dietary intakes were collected from the UK Biobank on two or more occasions. Participants were classified as fat responders, carbohydrate responders, or non-responders based on a priori selection of ten single nucleotide polymorphisms (SNPs), which had been demonstrated to define fat- and carbohydrate-responsive genotypes. An additional three SNPs were included in secondary analysis. Cox proportional hazards models were applied to examine the association between LCD/LFD and CAD risk.

Results: Included were 101,498 participants (mean age[SD]=55.9[7.8] y, range 40-70 y) with at least two 24-hour dietary questionnaires and were free of pregnancy, ASCVD, type 2 diabetes and cancer. During a median follow-up of 10.5 years, 2584 CAD cases were identified. Among fat responders, the hazard ratio (HR) comparing the 10th to 1st deciles of vegetable LCD, based on the percentage of energy from carbohydrate, vegetable protein, and vegetable fat intake, was 0.54 (95% CI=0.32~0.93, Ptrend = 0.02). No significant trend was observed among carbohydrate responders, non-responders, or the overall population. In contrast, the HRs comparing the 10th to 1st deciles of LFD, based on the percentage of energy from carbohydrate, protein, and fat intake, showed significant positive trends among the overall population (1.19[95% CI=1.00~1.42], 10th vs 1st decile), fat responders (1.28[95% CI=1.00~1.64]), and non-responders (1.59[95% CI=1.00~2.51]), but not among carbohydrate responders (0.96[95% CI=0.72~1.28]). Secondary analysis yielded consistent results.

Conclusions: Participants with a fat-responsive genotype appeared to benefit more from adhering to vegetable LCD. High adherence to LFD was associated with higher CAD risk, particularly among fat-responsive and non-responsive participants. This underscores the importance of considering genetic predispositions when recommending dietary patterns for CAD prevention.

Funding Sources: Startup grant at Fudan University (IDF201026Y and JIF201068Y).