{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T11:47:29Z","timestamp":1782906449682,"version":"3.54.5"},"reference-count":28,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH-NHLBI","award":["2R15HL143545-02"],"award-info":[{"award-number":["2R15HL143545-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Glutathione (GSH), the most abundant intracellular antioxidant, plays a central role in maintaining redox homeostasis, regulating immune responses, and protecting cellular integrity. In chronic diseases such as type 2 diabetes mellitus (T2DM), GSH deficiency is a consistent hallmark, contributing to oxidative stress, mitochondrial dysfunction, inflammation, and progressive organ damage. This review critically examines the efficacy and safety of GSH supplementation and precursor strategies, synthesizing evidence across mechanistic studies, clinical trials, and translational research. In T2DM, GSH augmentation has been linked to improved insulin sensitivity, reduced oxidative damage, and better microvascular outcomes, although findings remain preliminary and heterogeneous. Safety profiles across populations are highly favorable, with gastrointestinal discomfort being the most reported adverse effect and serious toxicities rare. Importantly, both acute and chronic studies reinforce the compatibility of GSH and its precursors with standard antiretroviral and antidiabetic therapies. Despite this encouraging data, significant research gaps remain. Standardization of biomarkers, dose\u2013response mapping, and long-term outcomes are urgently needed to move from proof-of-concept to clinical trials. Future directions include integrating mechanistic endpoints such as mitochondrial function and multi-omic profiling, exploring targeted delivery systems, and embedding implementation science to ensure real-world feasibility and equity. Collectively, the emerging evidence supports GSH-centered strategies as promising adjuncts for oxidative stress-driven chronic disease. Rigorous, well-designed trials are now required to define their definitive role in clinical care.<\/jats:p>","DOI":"10.3390\/nu18132132","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T10:41:01Z","timestamp":1782902461000},"page":"2132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of Glutathione Supplementation in Type 2 Diabetes &amp; Diabetes Complications"],"prefix":"10.3390","volume":"18","author":[{"given":"Stefanie","family":"Au","sequence":"first","affiliation":[{"name":"College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1860-3697","authenticated-orcid":false,"given":"John","family":"Dawi","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7842-2296","authenticated-orcid":false,"given":"Scarlet","family":"Affa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Chemistry, The College, UCLA, 405 Hilgard Avenue, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yura","family":"Misakyan","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham","family":"Chorbajian","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Hammi","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Dave","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyla","family":"Qumsieh","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2586-1160","authenticated-orcid":false,"given":"Vishwanath","family":"Venketaraman","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.3390\/antiox11051026","article-title":"Randomized Clinical Trial of How Long-Term Glutathione Supplementation Offers Protection from Oxidative Damage and Improves HbA1c in Elderly Type 2 Diabetic Patients","volume":"11","author":"Kalamkar","year":"2022","journal-title":"Antioxidants"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"162","DOI":"10.2337\/dc10-1006","article-title":"Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine","volume":"34","author":"Sekhar","year":"2011","journal-title":"Diabetes Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"154","DOI":"10.3390\/antiox11010154","article-title":"GlyNAC (Glycine and N-Acetylcysteine) Supplementation Improves Impaired Mitochondrial Fuel Oxidation and Lowers Insulin Resistance in Patients with Type 2 Diabetes: Results of a Pilot Study","volume":"11","author":"Sekhar","year":"2022","journal-title":"Antioxidants"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"165801","DOI":"10.1016\/j.bbadis.2020.165801","article-title":"Interplay between NADH oxidation by complex I, glutathione redox state and sirtuin-3, and its role in the development of insulin resistance","volume":"1866","year":"2020","journal-title":"Biochim. 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