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

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.

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.