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.