Plasma Levels of Polyols Erythritol, Mannitol, and Sorbitol and Incident Coronary Heart Disease Among Women

Yoriko Heianza; Qi Sun; Xuan Wang; Saumya Tiwari; Jeramie D Watrous; Kathryn M Rexrode; Mona Alotaibi; Mohit Jain; Samia Mora; Walter C Willett; Lu Qi; JoAnn E Manson

doi:10.1093/eurjpc/zwae288

Plasma Levels of Polyols Erythritol, Mannitol, and Sorbitol and Incident Coronary Heart Disease Among Women

Eur J Prev Cardiol. 2024 Sep 4:zwae288. doi: 10.1093/eurjpc/zwae288. Online ahead of print.

Authors

Yoriko Heianza^{1

2}, Qi Sun^{2

3

4}, Xuan Wang¹, Saumya Tiwari⁵, Jeramie D Watrous⁵, Kathryn M Rexrode^{4

6}, Mona Alotaibi⁵, Mohit Jain⁵, Samia Mora^{7

8}, Walter C Willett^{2

3

4}, Lu Qi^{1

2

4}, JoAnn E Manson^{3

4

8}

Affiliations

¹ Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA.
² Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
³ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
⁴ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
⁵ Department of Pharmacology, University of California San Diego, La Jolla, CA.
⁶ Division of Women's Health, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
⁷ Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
⁸ Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

PMID: 39230875
DOI: 10.1093/eurjpc/zwae288

Abstract

Background and aims: Erythritol, a sugar alcohol (polyol), has recently been linked to the risks of major adverse cardiovascular events. We investigated whether plasma erythritol and other polyols (mannitol/sorbitol) were associated with the risk of incident coronary heart disease (CHD).

Methods: This prospective nested case-control study included 762 incident cases of CHD and 762 controls from the Nurses' Health Study. Plasma concentrations of polyols were measured at baseline (1989-90 or 2000-02). Associations of erythritol with cardiometabolic risk factors were also analyzed in the Women's Lifestyle Validation Study (n=728; blood collected in 2010-12).

Results: Higher erythritol levels were related to more adverse cardiometabolic risk factor status. The relative risk (RR) for CHD per 1-SD increment was 1.15 [95% CI: 1.04, 1.28] for erythritol and 1.16 [1.05, 1.28] for mannitol/sorbitol, after adjusting for diet quality, lifestyles, and adiposity. Compared with women in the lowest quartile, those in the highest quartile (Q4) of erythritol had a RR 1.55 [1.13, 2.14] for CHD. The RR in Q4 of erythritol was 1.61 [1.15, 2.24; p=0.006] when hypertension and dyslipidemia were further added to the model; the RR was 1.21 [0.86, 1.70] after adjustment for diabetes. For mannitol/sorbitol, the RR in the Q4 was 1.42 [1.05, 1.91; p=0.022] for CHD in the multivariable-adjusted model including diabetes.

Conclusions: Higher plasma erythritol and mannitol/sorbitol were related to elevated risks of CHD even after adjustment for diet, lifestyles, adiposity, and other risk factors. The unfavorable association of mannitol/sorbitol, but not erythritol, with CHD risk remained significant independently of diabetes/hyperglycemia.

Keywords: Coronary heart disease; Erythritol; Prospective cohort study; Risk factors; Sugar alcohols (polyols).

Plain language summary

The present study shows unfavorable associations of circulating erythritol and mannitol/sorbitol with long-term coronary heart disease (CHD) risk even after adjustments for overall diet quality, lifestyle factors, and several other traditional CHD risk factors among women at usual risk. In contrast to mannitol/sorbitol, the association between high erythritol levels and increased CHD risk was no longer significant upon additional inclusion of diabetes in the multivariable-adjusted model. Our findings from the two independent study populations of women without prior CHD suggest endogenous and exogenous erythritol levels are related to unfavorable cardiometabolic risk factor status.