Caloric restriction without malnutrition reduces the activity of the polyol pathway and decreases glucose levels, which counteracts age-related changes and contributes to beneficial effects like increased NADPH levels and reduced oxidative stress biomarkers.

Interestingly, the decreased glucose level observed under caloric restriction with no malnutrition conditions led to the inhibition of enzyme activities and the decrease in concentrations of metabolites of the polyol pathway, sorbitol and fructose. This contributed to the beneficial effects of caloric restriction including the increase in the NADPH level required for other reduction reactions such as GSH and other forms of AOS component regeneration, and counteracted age-related changes derived from the activities of the polyol pathway.