(P26-49-26) Peanut Consumption, Circulating Metabolites, and Coronary Heart Disease: A Two-Stage Prospective Metabolomic Study

Objectives: Peanut intake has been linked to cardiovascular benefits, but the underlying metabolic pathways remain unclear. We aimed to identify and validate circulating metabolites associated with peanut intake and coronary heart disease (CHD).

Methods: Discovery included 1,740 participants from a 1:1 matched case-control study of incident CHD nested within the Southern Community Cohort Study (SCCS), Shanghai Women’s Health Study (SWHS), and Shanghai Men’s Health Study (SMHS); validation was done in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO; N=2,315) and Hispanic Community Health Study/Study of Latinos (HCHS/SOL; N=5,164). Peanut and peanut butter intake was estimated from food frequency questionnaires or 24-h dietary recalls at baseline. Untargeted profiling of baseline blood metabolites was performed in selected participants without cancer or CVD. In discovery, peanut–metabolite associations were assessed by linear regression and metabolite–CHD associations by conditional logistic regression, adjusting for confounders including Healthy Eating Index. Significant findings (FDR < 0.1) were validated using linear and Cox regression in validation studies with similar adjustment.

Results: In discovery, 92 peanut-related metabolites were identified, of which 24 were linked to CHD risk (FDR < 0.1). In validation, 38 metabolites were replicated in relation with peanut intake (P  < 0.05 in PLCO or HCHS/SOL), mainly lipids (e.g., fatty acids, sphingolipids, and phospholipids); seven were further replicated for significant associations with CHD incidence/mortality, including S-carboxyethylcysteine, N-acetylphenylalanine, sphingomyelin (d18:1/24:1, d18:2/24:0), gamma-glutamylvaline (pooled standardized ORs: 1.15–1.25), and three unnamed metabolites (0.76–0.83). A signature derived from 38 validated peanut-related metabolites was associated with 16% lower CHD risk (standardized OR [95%CI]: 0.84 [0.73, 0.97]) in SCCS but not in SWHS/SMHS.

Conclusions: Peanut intake was associated with a distinct metabolite profile linked to lower CHD risk, providing mechanistic insights into cardiovascular benefits. Further research is needed to determine causal pathways linking peanut, metabolites, and disease across diverse populations.

Funding Sources: NIH; Vanderbilt-Ingram Cancer Center; The Peanut Institute