Declines in Plasma Erythritol and Improvements in Cardiovascular Risk and Atherogenic Lipid Profiles: A 2-Year Randomized Weight-Loss Dietary Intervention Trial.

BACKGROUND: High circulating levels of sugar alcohols (polyols) have recently been linked to increased risks of cardiovascular events. OBJECTIVES: We investigated whether temporal changes in plasma levels 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-year POUNDS Lost trial. Plasma erythritol, arabitol/xylitol, and mannitol/sorbitol were measured at baseline (n = 802, 805, and 803, respectively) and at 6 months. Temporal changes were calculated among participants with measurements at both time points (n = 664, 669, and 668, respectively). The primary outcome was the 10-year 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 SD 1.1% [SE 0.2%]), arabitol/xylitol (β 1.3% [0.2%]), and mannitol/sorbitol (β 1.1% [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 of ASCVD risk estimates at 6 months (β -0.16% [0.07%] per 1 SD reduction; p = 0.023). Initial (6-month) declines in plasma erythritol were associated with long-term (2-year) improvements in ASCVD risk (β -0.26% [0.11%]; p= 0.016) and reductions in cholesterol in VLDL+LDL containing apo-CIII. CONCLUSIONS: Declines in plasma erythritol levels in response to weight-loss dietary interventions were 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 levels in relation to improvements in cardiometabolic risk among adults with overweight or obesity. TRIAL REGISTRATION NUMBER: NCT00072995, https://clinicaltrials.gov/ct2/show/NCT00072995.