(P17-077-25) Low-Carbohydrate and Low-Fat Diets, Objective Biomarker Indices, and Coronary Heart Disease in US Men and Women

Objectives: The current study aimed to examine the associations of low-carbohydrate diet (LCD) and low-fat diet (LFD) patterns that emphasize different quality of carbohydrate, fat, and protein with coronary heart disease (CHD) risk in U.S. men and women. We also aimed to replicate the associations of these dietary patterns using plasma metabolomics.

Methods: We followed up 43,430 men in the Health Professionals Follow-Up Study (1986-2016), 64,164 women in the Nurses’ Health Study (1986-2018), and 92,189 women in the Nurses’ Health Study II (1991-2019) for CHD incidence. Five LCD and three LFD indices were derived and evaluated, each emphasizing different sources and qualities of macronutrients (animal products vs. plant-based foods, whole grains vs. refined carbohydrates, etc). We further examined the associations of LCD and LFD indices with plasma metabolomics profiles among 1,146 participants in Lifestyle Validation Study (LVS) and developed the multi-metabolite scores of LCD and LFD indices using elastic net regression.

Results: During 5,287,240 person-years of follow-up, we documented 19,407 CHD cases. The pooled multivariable-adjusted hazard ratios (HRs, 95% CIs) of CHD per 1-SD increment of diet scores were 1.02 (1.00, 1.04) for overall LCD, 1.03 (1.02, 1.05) for animal LCD, 0.98 (0.96, 0.99) for vegetable LCD, 1.05 (1.04, 1.07) for unhealthy LCD, and 0.94 (0.93, 0.96) for healthy LCD, and 0.97 (0.96, 0.99) for overall LFD, 1.04 (1.03, 1.06) for unhealthy LFD, and 0.94 (0.93, 0.96) for healthy LFD. Spline regression revealed linear dose-response associations between the diet scores and CHD, except for the vegetable LCD (P = 0.03 for non-linearity). Healthy and unhealthy LCD and LFD patterns have distinct impacts on plasma lipid species and other metabolites. Multi-metabolite scores of LCD and LFD indices (Spearman r = 0.57-0.66 in LVS, and 0.20-0.39 in NHS, NHSII, and HPFS) showed consistent associations with CHD risk.

Conclusions: These findings suggest that the associations of low-carbohydrate and low-fat diets with CHD, lipid profiles, and downstream metabolites largely depend on the quality of macronutrients. Prioritizing adherence to high-quality macronutrients is essential for promoting cardiovascular health, regardless of whether a low-carbohydrate or low-fat diet is followed.

Funding Sources: Supported by National Institutes of Health Grants