Declines in plasma erythritol and improvements in cardiovascular disease risk and atherogenic lipid profiles: a 2-year randomized weight-loss dietary intervention trial

Background: High circulating concentrations of sugar alcohols (polyols) have recently been linked to increased risks of cardiovascular events. Objectives: We investigated whether temporal changes in plasma concentrations of erythritol and other isomeric polyols (arabitol/xylitol and mannitol/sorbitol) in response to weight-loss dietary interventions were associated with improvements in atherosclerotic cardiovascular disease (ASCVD) risk estimates and atherogenic lipid profiles among adults with overweight or obesity. Methods: We performed an observational analysis using data from adults with overweight or obesity who participated in the 2-y Preventing Overweight Using Novel Dietary Strategies trial. Plasma erythritol, arabitol/xylitol, and mannitol/sorbitol were measured at baseline (n = 802, n = 805, and n = 803, respectively) and at 6 mo. Temporal changes were calculated among participants with measurements at both time points (n = 664, n = 669, and n = 668, respectively). The primary outcome was the 10-y ASCVD risk estimated using the validated pooled cohort equations. Two-year changes in cholesterol in lipoprotein subfractions with or without apolipoprotein C-III (apoC-III) were analyzed as secondary outcomes. Results: Higher baseline levels of erythritol [β per 1 standard deviation (SD): 1.1%; standard error (SE): 0.2%], arabitol/xylitol (β: 1.3%; SE: 0.2%), and mannitol/sorbitol (β: 1.1%; SE: 0.2%) were associated with higher ASCVD risk estimates (P < 0.001 for all). Greater decreases in erythritol, but not the other polyols, were significantly associated with reductions in ASCVD risk estimates at 6 mo (β: −0.16%; SE: 0.07% per 1 SD reduction; P = 0.023). Initial (6-mo) declines in plasma erythritol were associated with long-term (2-y) improvements in ASCVD risk (β: −0.26%; SE: 0.11%; P = 0.016) and reductions in cholesterol in very-low-density lipoprotein + low-density lipoprotein containing apoC-III. Conclusions: Declines in plasma erythritol concentrations in response to weight-loss dietary interventions are associated with improvements in ASCVD risk estimates and atherogenic lipid subtypes containing apoC-III. These findings highlight the potential role of changes in plasma erythritol concentrations in relation to improvements in cardiometabolic risk among adults with overweight or obesity.This trial was registered at clinicaltrials.gov as NCT00072995.