Reduction of glycation stress as a geroscience intervention: protocol for a pilot RCT in postmenopausal women.

Abstract

Advanced glycation end products (AGEs) drive metabolic dysfunction, inflammation, and age-related disease, and their accumulation accelerates after menopause. Preclinical studies show that GLYLO, a five-compound glycation-lowering formulation (alpha-lipoic acid, nicotinamide, pyridoxine, benfotiamine, and piperine), reduces AGE burden and improves metabolic health, but its translational relevance in humans is unknown. The Glycation Reduction and Aging: a Clinical Evaluation (GRACE) trial is a randomized, double-blind, placebo-controlled pilot study testing whether six months of GLYLO supplementation lowers circulating AGEs and methylglyoxal (MGO) in postmenopausal women (45-65 years) with elevated adiposity (BMI ≥ 25 kg/m² or waist circumference ≥88 cm) and elevated HbA1c (5.5-6.4%). Secondary and exploratory endpoints include HOMA-IR, body composition, and reproductive hormones, cognitive and physical function, retinal aging, and systemic inflammation. GRACE is designed to address a critical gap in geroscience by evaluating whether targeting glycation can mitigate early metabolic and functional decline in postmenopausal women. ClinicalTrials.gov identifier NCT06813261.