Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial.
What this study found
GlyNAC produced broad, clinically meaningful improvements in older adults, whereas placebo did not. Over 16 weeks, insulin resistance fell substantially, with HOMA-IR down 31% at 2 weeks and 64% at 16 weeks, and fasting insulin down 34% and 65%, respectively. Inflammation and endothelial markers also improved, including IL-6 down 57% at 2 weeks and 78% at 16 weeks, TNF-alpha down 30% and 54%, hs-CRP down 25% and 41%, sICAM-1 down 27% and 57%, and sVCAM-1 down 21% and 44%. Oxidative stress and mitochondrial measures improved as well, with 8-OHdG decreasing by 57% at 2 weeks and 73% at 16…
- Study & population
- This was a randomized controlled clinical trial in older adults with overweight BMI criteria (> 27) and no major confounding diseases.
- Intervention
- Older adults received oral GlyNAC capsules containing glycine 100 mg/kg/day plus N-acetylcysteine 100 mg/kg/day once daily for 16 weeks.
- Key limitation
- The active arm was small, with only 12 older adults, which limits precision and generalizability.
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Open PDFOriginal abstract
BACKGROUND Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial. METHODS Twenty-four OA and 12 young adults (YA) were studied. OA was randomized to receive either GlyNAC (N = 12) or isonitrogenous alanine placebo (N = 12) for 16-weeks; YA (N = 12) received GlyNAC for 2-weeks. Participants were studied before, after 2-weeks, and after 16-weeks of supplementation to assess GSH concentrations, OxS, MFO, molecular regulators of energy metabolism, inflammation, endothelial function, IR, aging hallmarks, gait speed, muscle strength, 6-minute walk test, body composition, and blood pressure. RESULTS Compared to YA, OA had GSH deficiency, OxS, mitochondrial dysfunction (with defective molecular regulation), inflammation, endothelial dysfunction, IR, multiple aging hallmarks, impaired physical function, increased waist circumference, and systolic blood pressure. GlyNAC (and not placebo) supplementation in OA improved/corrected these defects. CONCLUSION GlyNAC supplementation in OA for 16-weeks was safe and well-tolerated. By combining the benefits of glycine, NAC and GSH, GlyNAC is an effective nutritional supplement that improves and reverses multiple age-associated abnormalities to promote health in aging humans. Clinical Trials Registration Number: NCT01870193.