Declines in Plasma Erythritol Levels and Improvements in Insulin Sensitivity and Glucose Metabolism: POUNDS Lost Trial

Erythritol is a non-nutritive sweetener that is also endogenously produced from glucose. We investigated whether declines in plasma erythritol and other sugar alcohols (polyols) in response to weight-loss dietary interventions were significantly associated with long-term improvements in glucose metabolism and insulin sensitivity. Plasma erythritol, mannitol/sorbitol, and arabitol/xylitol were repeatedly measured among adults with overweight or obesity who participated in the POUNDS Lost trial (n = 802 at baseline and n = 664 at 6 months). We analyzed associations of changes in erythritol, mannitol/sorbitol, and arabitol/xylitol from baseline to 6 months with changes in homeostasis model assessment of insulin resistance (HOMA-IR), fasting insulin, fasting glucose, and HbA1c at 6 months and 2 years of intervention.

Plasma erythritol levels were positively related to HOMA-IR, fasting insulin, and glycemic markers at baseline. Greater declines in plasma erythritol in response to the interventions were associated with greater reductions in HOMA-IR (p < 0.001) and fasting insulin (p < 0.001) at 6 months. Similar associations were found for changes in arabitol/xylitol, but not for mannitol/sorbitol. Every 1 SD reduction in plasma erythritol during the initial 6-month period was related to long-term (2-year) decreases in log-transformed HOMA-IR (β [SE] –0.07 [0.02], p = 0.008) and glycemic markers (β –1.0 [0.44] mg/dL, p = 0.025 for fasting glucose; β –0.05% [0.02%], p = 0.019 for HbA1c).

These findings suggest that reductions in endogenous erythritol levels may serve as a biomarker for metabolic improvement during weight-loss interventions. The observed associations indicate that dietary modifications leading to lower plasma polyol concentrations correlate with enhanced insulin sensitivity and reduced glycemic burden over extended periods. This relationship holds independent of the specific type of intervention, provided it results in significant weight loss.

The study highlights the potential utility of monitoring erythritol levels as an adjunctive metric for evaluating metabolic health outcomes in clinical trials involving obesity management. While these associations are statistically significant, they do not establish causation between erythritol reduction and metabolic improvement. Further mechanistic studies are required to elucidate the biological pathways linking polyol metabolism to insulin signaling.

This research note is provided for laboratory use only. The data presented herein describes findings from a clinical trial and should not be used for diagnostic, therapeutic, or prophylactic purposes in human subjects. All interpretations of these results must be conducted within the context of established medical guidelines and peer-reviewed literature.