The effects of 3 weeks of oral glutathione supplementation on whole body insulin sensitivity in obese males with and without type 2 diabetes: a randomized trial

Appl Physiol Nutr Metab. 2021 Sep;46(9):1133-1142. doi: 10.1139/apnm-2020-1099. Epub 2021 Mar 19.


The effect of oral glutathione (GSH) supplementation was studied in obese subjects with and without type 2 diabetes (T2DM) on measures of glucose homeostasis and markers of oxidative stress. Twenty subjects (10 patients with T2DM and 10 obese subjects) were recruited for the study, and randomized in a double-blinded placebo-controlled manner to consume either 1000 mg GSH per day or placebo for 3 weeks. Before and after the 3 weeks insulin sensitivity was measured with the hyperinsulinemic-euglycemic clamp and a muscle biopsy was obtained to measure GSH and skeletal muscle mitochondrial hydrogen peroxide (H2O2) emission rate. Whole body insulin sensitivity increased significantly in the GSH group. Skeletal muscle GSH was numerically increased (∼19%) in the GSH group; no change was seen in GSH to glutathione disulfide ratio. Skeletal muscle mitochondrial H2O2 emission rate did not change in response to the intervention and neither did the urinary excretion of the RNA oxidation product 8-oxo-7,8-dihydroguanosine or the DNA oxidation product 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), although 8-oxodG decreased as a main effect of time. Oral GSH supplementation improves insulin sensitivity in obese subjects with and without T2DM, although it does not alter markers of oxidative stress. The study has been registered in (NCT02948673). Novelty: Reduced glutathione supplementation increases insulin sensitivity in obese subjects with and without T2DM. H2O2 emission rate from skeletal muscle mitochondria was not affected by GSH supplementation.

Keywords: glutathion; glutathione; insulin sensitivity; mitochondria; mitochondries; oxidative stress; sensibilité à l’insuline; stress oxydatif.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Biomarkers / metabolism
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Dietary Supplements* / adverse effects
  • Glucose Tolerance Test
  • Glutathione / administration & dosage*
  • Glutathione / adverse effects
  • Glutathione / blood
  • Glutathione / metabolism
  • Glutathione Disulfide / metabolism
  • Humans
  • Hydrogen Peroxide / metabolism
  • Insulin Resistance / physiology*
  • Middle Aged
  • Mitochondria, Muscle / metabolism
  • Muscle, Skeletal / metabolism
  • Obesity / metabolism
  • Obesity / physiopathology*
  • Oxidative Stress
  • Oxygen Consumption


  • Biomarkers
  • Blood Glucose
  • Hydrogen Peroxide
  • Glutathione
  • Glutathione Disulfide

Associated data