Combined treatment with L-Glutathione, D-Chiro-Inositol, Myo-inositol and N-Acetylcysteine reduces insulin resistance in overweight/obese patients with polycystic ovary syndrome

Abstract

Background: Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder frequently associated with insulin resistance and increased cardiometabolic risk. Objective:  To evaluate the effects of combined supplementation with L-glutathione, D-chiro-inositol, Myo-inositol, and N-acetylcysteine on metabolic and hepatic insulin-related parameters in overweight/obese women with PCOS. Methods:  Over 12 weeks, a total of 32 overweight/obese women with PCOS (mean BMI 30.72 ± 0.96 kg/m²) received daily oral integrative therapy comprising reduced L-glutathione (50 mg), D-chiro-inositol (500 mg), Myo-inositol (100 mg), and N-acetylcysteine (150 mg). The patients had received no hormonal or insulin-sensitizing treatments during the prior six months. Clinical and laboratory assessments were conducted before and after treatment, evaluating hormonal parameters during the follicular phase, as well as fasting glucose, insulin, C-peptide, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and the Hepatic Insulin Extraction index (calculated as insulin/ C-peptide). Results: After 12 weeks, significant reductions were observed in fasting glucose, fasting insulin, Homeostatic Model Assessment for Insulin Resistance (from 3.24 ± 0.31 to 2.23 ± 0.32; p=0.02), and the Hepatic Insulin Extraction index (from 5.78 ± 0.35 to 4.94 ± 0.44; p=0.006). No changes were observed in C-peptide levels. Subgroup analysis showed that these improvements remained significant in patients with a first-degree family history of type 2 diabetes mellitus, but not in patients without such a history.  Conclusions: Combined supplementation with L-glutathione, D-chiro-inositol, Myo-inositol, and N-acetylcysteine was associated with reductions in insulin resistance markers in overweight/obese women with PCOS, especially among those with a family history of diabetes. L-glutathione and N-acetylcysteine, through their antioxidant effects, may improve insulin-degrading enzyme expression and activity in the liver, thereby increasing hepatic insulin clearance and reducing compensatory hyperinsulinemia and insulin resistance.