What are the effects of GlyNAC supplementation and withdrawal on various health markers in older adults, including glutathione levels, oxidative stress, mitochondrial function, inflammation, and insulin resistance?
Clin Transl Med · 2021 · PMID 33783984 · DOI 10.1002/ctm2.372
GlyNAC supplementation in older adults improved several markers of aging and health, but these benefits decreased after stopping the supplement.
The question
What are the effects of GlyNAC supplementation and withdrawal on various health markers in older adults, including glutathione levels, oxidative stress, mitochondrial function, inflammation, and insulin resistance?
What they tested
GlyNAC supplementation in older adults will improve naturally-occurring glutathione deficiency, mitochondrial impairment, oxidative stress, and insulin resistance, similar to observations in aged mice.
How they did it
This was a 36-week open-label pilot clinical trial involving eight older adults (OAs) and eight young adults (YAs). All participants underwent an initial pre-supplementation study. YAs were then released, while OAs received GlyNAC supplementation for 24 weeks, followed by a 12-week GlyNAC withdrawal period. Measurements included red blood cell (RBC) glutathione, mitochondrial fuel-oxidation (MFO), plasma biomarkers for oxidative stress, inflammation, endothelial function, glucose, and insulin, as well as gait speed, grip strength, 6-minute walk test, cognitive tests, genomic damage, glucose production and muscle protein breakdown rates, and body composition.
What they found
GlyNAC supplementation for 24 weeks in older adults corrected RBC-GSH deficiency, oxidative stress, and mitochondrial dysfunction. It also improved inflammation, endothelial dysfunction, insulin resistance, genomic damage, cognition, strength, gait speed, and exercise capacity, while lowering body fat and waist circumference. However, these benefits declined after stopping GlyNAC supplementation for 12 weeks.
| RBC-GSH deficiency | 0 | |
|---|---|---|
| Oxidative stress | 0 | |
| Mitochondrial dysfunction | 0 | |
| Inflammation | 1 | |
| Endothelial dysfunction | 1 | |
| Insulin resistance | 1 | |
| Genomic damage | 1 | |
| Cognition | 2 | |
| Strength | 2 | |
| Gait speed | 2 | |
| Exercise capacity | 2 | |
| Body fat | 1 | |
| Waist circumference | 1 |
This chart illustrates the reported effects of 24-week GlyNAC supplementation in older adults. A value of 0 indicates correction of a deficiency, 1 indicates a decrease/lowering, and 2 indicates an improvement.
What it means
GlyNAC supplementation for 24 weeks in older adults was well tolerated and demonstrated improvements across multiple health parameters, including reduced oxidative stress, corrected glutathione deficiency, improved mitochondrial function, decreased inflammation, insulin resistance, endothelial dysfunction, and genomic damage, as well as enhanced strength, gait speed, cognition, and body composition. These findings suggest GlyNAC could be a simple and viable method to promote health in aging humans, warranting further investigation.
Limitations
This was a pilot trial with a small sample size (eight older adults) and an open-label design, which may limit the generalizability and strength of the findings.
The paper at a glance
| Title | GlyNAC supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation and insulin resistance |
|---|---|
| Journal | Clin Transl Med |
| Year | 2021 |
| PMID | 33783984 ↗ |
| DOI | 10.1002/ctm2.372 ↗ |
| Topic | Immunity, inflammation & resilience |
Read the source: PubMed record (authors, abstract, full citation) ↗ · Publisher via doi.org ↗
Where Magellan uses this paper
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Glutathione
Randomized trials show that oral glutathione supplementation can genuinely raise body stores — a well-run 6-month trial found dose-dependent increases of about 30–35% in blood cells at 1,000 mg/day, along with a more than twofold rise in NK-cell activity — and lower oxidative-stress markers, answering historical…
GlyNAC (Glycine + N-Acetylcysteine)
In small clinical trials, mostly pilot and open-label studies plus one randomized placebo-controlled trial of 24 older adults from the same laboratory, GlyNAC supplementation corrected glutathione deficiency and improved markers of oxidative stress, mitochondrial function, inflammation, insulin resistance, muscle…
NOVOS Core is a multi-ingredient dietary supplement marketed for longevity that combines about a dozen…
Glutathione (GSH) is a tripeptide of glutamate, cysteine, and glycine synthesized inside virtually all…
Glycine is the smallest and simplest proteinogenic amino acid, synthesized endogenously but often in…
GlyNAC is a nutritional supplement combining two amino acids, glycine and N-acetylcysteine (NAC, a…
Research describes the compound or intervention studied. It is not a claim about any specific product.
Molecules & mechanisms in this paper
Each of these is named in the paper’s own words above. Open the monograph for the full mechanism and its other citations.
Cite this page
These citations point at this summary. To cite the original paper with its full author list, use the PubMed record or doi.org.
Magellan Longevity. (2026). What are the effects of GlyNAC supplementation and withdrawal on various health markers in older adults, including glutathione levels, oxidative stress, mitochondrial function, inflammation, and insulin resistance? [Plain-English summary of Clin Transl Med 2021, PMID 33783984, DOI 10.1002/ctm2.372]. Magellan Longevity. https://magellanlongevity.com/study/x8.html@misc{magellan_x8,
title = {What are the effects of GlyNAC supplementation and withdrawal on various health markers in older adults, including glutathione levels, oxidative stress, mitochondrial function, inflammation, and insulin resistance?},
author = {{Magellan Longevity}},
year = {2026},
howpublished = {\url{https://magellanlongevity.com/study/x8.html}},
note = {Plain-English summary of PubMed PMID 33783984; DOI 10.1002/ctm2.372; Clin Transl Med 2021. Reviewed by Gabriel Radu, DO},
urldate = {2026-08-11}
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