Abstract MP28: Declines in Plasma Levels of Nonnutritive Sweetener Erythritol Are Related to Two-Year Improvements in Atherosclerotic Cardiovascular Disease Risk Estimates Among Adults With Overweight and Obesity

Background: A potential adverse relationship between the consumption of low-calorie sweeteners and cardiovascular disease (CVD) risk has been proposed. High levels of circulating erythritol, a sugar alcohol (polyol) used as one of the non-nutritive sweeteners, have been recently linked to increased risks of major adverse cardiovascular events. However, associations of temporal changes in plasma erythritol and other polyols with cardiometabolic risk remain unclear. Hypothesis: We tested whether changes in plasma levels of non-nutritive sweetener erythritol and other polyols in response to weight-loss dietary interventions were associated with improved atherosclerotic cardiovascular disease (ASCVD) risk estimates and atherogenic lipoproteins among adults with overweight and obesity. Methods: This study included 804 adults (mean BMI: 32.7 [SD 3.9] kg/m 2 ) without diabetes or unstable CVD at baseline who participated in a 2-year intervention of weight-loss diets, the POUNDS Lost trial. Metabolomic profiling was performed to measure plasma erythritol and its precursor erythronate, other sugar alcohols, and low-calorie sweeteners at baseline and 6 months after randomization. The primary outcome was the change in 10-year ASCVD risk scores calculated by the validated pooled cohort equations. Two-year changes in lipid profiles and cholesterol [Chol] in lipoprotein subfractions defined by the presence or absence of apolipoprotein CIII (apoCIII) were analyzed as secondary outcomes. Results: The mean estimated value of the 10-year ASCVD risk was 4.0% at baseline; 16% of the participants were at intermediate or high ASCVD risk (score ≥7.5%). Higher levels of erythritol (per 1 SD increment: β 1.1% [SE 0.2%], p <.0001) and erythronate (β 1.3% [0.2%], p <.0001), as well as other sugar alcohols, such as mannitol-sorbitol, myoinositol, arabitol-xylitol ( p <.0001 for all), and low-calorie sweetener saccharin ( p = 0.02), but not acesulfame ( p =0.8), were related to a higher ASCVD risk at baseline after adjusting for BMI. There was large variability in the changes in metabolite levels across participants; greater decreases in erythritol in response to the interventions were significantly related to greater reductions in ASCVD risk estimates at 6 months (per 1 SD reduction: β -0.2% [SE 0.1%]; p =0.023) and at 2 years (β -0.3% [0.1%]; p = 0.015) after adjusting for covariates, including BMI, the initial metabolite levels, and baseline ASCVD risk. The 6-month decrease in erythritol was associated with long-term (2-year) improvements in atherogenic lipids, including Chol in VLDL+LDL with apoCIII ( p <0.05). Conclusions: Higher plasma levels of erythritol and other sugar alcohols were associated with greater 10-year ASCVD risk scores among adults with overweight and obesity. Weight-loss diet-induced decreases in erythritol levels were related to improved ASCVD risk and atherogenic lipid profiles.