Dietary intake of phytosterols, particularly beta-sitosterol, may be associated with a lower risk of developing type 2 diabetes and cardiovascular disease, according to a 36-year prospective study of over 206,000 participants conducted by researchers at the Harvard T.H. Chan School of Public Health.
In the study, led by Fenglei Wang, PhD, and presented at Nutrition 2025, participants in the highest quintile of phytosterol intake had an 8% lower risk of type 2 diabetes (T2D) and a 9% lower risk of cardiovascular disease (CVD) compared with those in the lowest quintile.
"Similar associations were observed for [beta]-sitosterol, but not for campesterol or stigmasterol," noted Wang and colleagues.
Multilayered Investigation
The researchers employed a multilayered approach, examining associations not only with clinical outcomes, but also with plasma metabolic biomarkers, metabolomic profiles, and gut microbial characteristics.
Among the 206,277 participants (79% female) followed across the large U.S. cohorts, 20,167 incident cases of T2D and 15,806 cases of CVD were documented. Dietary intake of total phytosterols and three individual compounds—beta-sitosterol, campesterol, and stigmasterol—was assessed using validated food frequency questionnaires.
Biomarker and Metabolomic Profiles
In a subset of 40,807 participants with available plasma metabolic biomarker data, total phytosterol and beta-sitosterol intake were associated with favorable profiles, including lower concentrations of C-peptide and C-reactive protein (CRP), as well as beneficial metabolite profiles.
Metabolomic analysis in a subset of 11,402 participants revealed profiles associated with lower risk of T2D and CVD among individuals with higher phytosterol consumption.
Gut Microbiome Associations
In 465 participants with gut microbiome data, higher beta-sitosterol intake was associated with the presence of Faecalibacterium prausnitzii and its beta-sitosterol–degrading enzyme 3-oxosteroid 1-dehydrogenase (EC 1.3.99.4), along with a metabolomic signature indicating reduced risk of T2D.
Statistical Methods and Study Strengths
Associations were assessed using Cox proportional hazards models adjusted for potential confounders. The study's strengths included its large sample size, extended follow-up, and integration of dietary, clinical, metabolic, and microbial data.
Disclosures were not made available at the time of publishing.
This study was supported by funding from the National Institutes of Health and the American Heart Association.
Source: Nutrition 2025