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.

This was a randomized controlled clinical trial in older adults with overweight BMI criteria (> 27) and no major confounding diseases. In the active GlyNAC arm, 12 participants were randomized in a 1:1 comparison with placebo; the mean age was 71.4 ± 4.2 years and 8 were men and 4 were women. A young adult group was also included as a reference.

Older adults received oral GlyNAC capsules containing glycine 100 mg/kg/day plus N-acetylcysteine 100 mg/kg/day once daily for 16 weeks. The comparator was an isonitrogenous placebo of alanine 200 mg/kg/day.

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 weeks and palmitate oxidation improving from 146.8 ± 25.5 to 119.0 ± 11.9 (p=0.003). Waist circumference and systolic blood pressure decreased, and no adverse events were reported; overall, GlyNAC was safe and well tolerated and reversed multiple aging-related abnormalities.

The active arm was small, with only 12 older adults, which limits precision and generalizability. The study was single-center and short term at 16 weeks, so durability and broader clinical outcomes remain uncertain. Many outcomes were mechanistic and biomarker-based rather than hard clinical endpoints.