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Bioactives for Brain and Cardiometabolic Health (Oral Session 23)

(OR23-05-25) Multi-layered Investigation of Dietary Phytosterol Intake in Relation to Risk of Type 2 Diabetes and Cardiovascular Disease

Tuesday, June 3, 2025
10:48 AM – 11:00 AM ET
Location: S220 B-D
Emerging Leaders in Nutrition Science Poster Competition

    Presenting Author(s)

  • FW

    Fenglei Wang, PhD (he/him/his)

    Research Associate
    Harvard T.H. Chan School of Public Health
    Boston, Massachusetts, United States

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

    • Co-Author(s)

  • Anne-Julie Tessier, RD, PhD (she/her/hers)

    Postdoctoral Fellow
    Harvard T.H. Chan School of Public Health
    Boston, Massachusetts, United States

  • AG

    Andrea J. Glenn

    Harvard T.H. Chan School of Public Health, United States

  • MG

    Marta Guasch-Ferré

    Harvard T.H. Chan School of Public Health, United States

  • QS

    Qi Sun, PhD

    Associate Professor
    Harvard T.H. Chan School of Public Health
    Boston, Massachusetts, United States

  • Frank B. Hu, MD, MPH, PhD

    Chair, Department of Nutrition Harvard T.H. Chan School of Public Health Fredrick J. Stare Professor of Nutrition and Epidemiology at Harvard T.H. Chan School of Public Health Professor of Medicine, Harvard Medical School and Brigham and Women’s Hospital
    Harvard T.H. Chan School of Public Health
    Boston, Massachusetts, United States

Objectives: Limited evidence exists on dietary phytosterol intake and cardiometabolic disease risk. We aimed to investigate the association of dietary phytosterol intake with the risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), along with the underlying plasma metabolic and metabolomic biomarkers and gut microbial features.

Methods: We followed 206,277 participants (79% women) from three large US prospective cohorts for up to 36 years. Validated food-frequency questionnaires were used to collect dietary intake data for total phytosterols and three individual phytosterols: β-sitosterol, campesterol, and stigmasterol. We applied Cox proportional hazards models to assess their associations with risk of T2D and CVD. In a subset of 40,807 participants with plasma metabolic biomarkers and 11,402 participants with plasma metabolomics data, we examined the association between phytosterol intake and metabolic biomarkers related to insulinemia, glycemia, lipids, and inflammation, as well as metabolomic profiles reflecting the risk of T2D and CVD. Additionally, we explored the gut microbial species and enzymes involved in these associations in a subset of 465 participants with gut microbiome data.

Results: During follow-up, we documented 20,167 incident cases of T2D and 15,806 cases of CVD. Higher intakes of total phytosterols were associated with a lower risk of T2D (HR comparing extreme quintiles = 0.92, 95% CI: 0.87-0.98, P-trend = 0.01) and CVD (HR = 0.91, 95% CI: 0.85-0.97, P-trend = 0.03). Similar associations were observed for β-sitosterol, but not for campesterol or stigmasterol. Total phytosterol and β-sitosterol were also associated with favorable plasma metabolic profiles, such as lower levels of C-peptide and CRP, and beneficial metabolite profiles. Moreover, we identified several gut microbial species, and their enzymes involved in these associations. For example, Faecalibacterium prausnitzii and its β-sitosterol-degrading enzyme 3-oxosteroid 1-dehydrogenase (EC1.3.99.4) were associated with higher β-sitosterol intake and a metabolite profile less likely to develop T2D.

Conclusions: A higher intake of phytosterol, particularly β-sitosterol, was associated with a lower risk of T2D and CVD. These associations were supported by multiple layers of evidence.

Funding Sources: National Institutes of Health, American Heart Association