GlyNAC (Glycine + N-Acetylcysteine)

Synthetic combination (glycine plus N-acetylcysteine)
Evidence Level
Limited
3 Clinical Trials
6 Documented Benefits
2/5 Evidence Score

GlyNAC is a combination of the amino acid glycine and N-acetylcysteine (NAC), a stable source of cysteine. Together they supply two building blocks of glutathione, the body's main antioxidant inside cells. The combination was developed by Dr. Rajagopal Sekhar's team at Baylor College of Medicine, whose 16-week randomized trial in 24 older adults (about 7 g each of glycine and NAC daily for a 70 kg adult) reported higher glutathione, lower oxidative stress and inflammation markers, lower insulin resistance, faster gait speed and stronger grip compared with baseline, while the placebo group did not improve. A separate 114-person randomized trial in healthy older adults, run by a company that sells glycine and NAC products, gave up to 7.2 g/day for 2 weeks and found no rise in glutathione overall, its primary outcome. The evidence is promising but small, short and mostly from one team.

Studied Dose 100 mg/kg/day each of glycine and NAC (about 7 g of each for a 70 kg adult) for 16 weeks in the main trial; 2.4 to 7.2 g/day combined (1:1) for 2 weeks in a larger independent trial.
Active Compound Glycine (an amino acid) plus NAC (N-acetylcysteine, a cysteine source). Both are precursors of glutathione (gamma-glutamyl-cysteinyl-glycine), the main antioxidant inside cells.

Benefits

Gait speed and grip strength in older adults

In a 16-week randomized trial, 12 older adults (mean age 71) taking GlyNAC raised gait speed by about 19% (1.13 to 1.34 m/s) and grip strength by about 14%, while the 12 on an alanine placebo did not improve. The paper reports within-group changes rather than direct GlyNAC versus placebo tests, and it is a single small trial.

Glutathione levels in red cells and muscle

In the same trial, red blood cell glutathione rose about 225% and muscle glutathione about 164% in the GlyNAC group, reaching levels seen in young adults. A larger 2-week trial in 114 healthy older adults, run by a company that sells glycine and NAC, found no overall rise in glutathione.

Oxidative stress markers (TBARS, F2-isoprostanes)

Over 16 weeks, the lipid oxidation markers TBARS and F2-isoprostanes each fell about 72% in older adults taking GlyNAC, with no change on placebo. These results come from one small trial; the larger 2-week trial, run by Nestle scientists, did not raise glutathione overall.

Insulin resistance and glucose metabolism

In the 16-week trial, the insulin resistance index HOMA-IR fell about 64% and fasting insulin about 65% in the GlyNAC group, with no change on placebo. This large change comes from 12 people in one small trial and has not been independently confirmed.

Inflammatory markers (IL-6, TNF-alpha, CRP)

After 16 weeks on GlyNAC, IL-6 fell about 78%, TNF-alpha about 54% and hsCRP about 41% in older adults, with no change on placebo. These results come from one small single-team trial and need independent repeating.

Aging hallmark biomarkers

The main trial also measured lab markers linked to aging, such as mitochondrial fuel use, mitophagy, DNA damage and insulin resistance, and reported improvement in many of them after 16 weeks of GlyNAC. These are biomarker changes in 12 people in a single small trial, not proof of slower aging or longer life.

Mechanism of action

1

Glutathione building blocks

Glutathione is made from glutamate, cysteine and glycine. The Sekhar group proposes that older adults run short of cysteine and glycine, and that supplying them (cysteine as NAC) restores glutathione production.

2

Mitochondrial function

Glutathione helps protect mitochondria from oxidative damage. In the main trial, GlyNAC improved mitochondrial fatty acid oxidation in older adults, which the authors link to the strength and gait results.

3

Less oxidative damage

Glutathione neutralizes reactive oxygen species and supports glutathione peroxidase, limiting damage to fats, proteins and DNA. Lipid oxidation markers fell in the main trial.

4

Inflammatory signaling

Oxidative stress can activate NF-kB and raise inflammatory cytokines such as IL-6 and TNF-alpha. Restoring redox balance is the proposed reason these markers fell in the main trial.

5

Effects of glycine itself

Glycine also acts in the nervous system and is a building block of collagen and creatine, so some effects of GlyNAC may come from glycine rather than glutathione.

Clinical trials

1
GlyNAC in Older Adults: 16-Week Randomized Trial
PubMed

Randomized, placebo-controlled trial of GlyNAC (100 mg/kg/day each of glycine and NAC) vs isonitrogenous alanine placebo for 16 weeks; 12 young adults took GlyNAC for 2 weeks as a reference group (Kumar et al. 2023, J Gerontol A Biol Sci Med Sci).

24 older adults (12 GlyNAC, 12 placebo) and 12 young adults.

In the GlyNAC group, red cell glutathione rose about 225% and muscle glutathione about 164%; TBARS and F2-isoprostanes fell about 72%; IL-6 fell 78%, TNF-alpha 54% and HOMA-IR 64%; gait speed rose from 1.13 to 1.34 m/s and grip strength about 14%. The placebo group did not improve. Results are reported as within-group changes. No supplement-related adverse events. NIH-funded; no conflicts declared.

2
GlyNAC in Older Adults: 24-Week Open-Label Pilot
PubMed

Open-label pilot trial: GlyNAC for 24 weeks followed by 12 weeks off, with no placebo group (Kumar et al. 2021, Clin Transl Med).

8 older adults and 8 young adults (young adults studied at baseline only).

After 24 weeks, older adults had higher red cell glutathione and improvements in oxidative stress, mitochondrial function, inflammation, insulin resistance, strength, gait speed, cognition and waist size. Benefits declined after 12 weeks off GlyNAC. Very small and uncontrolled.

3
Independent Dose-Ranging GlyNAC Trial in Healthy Older Adults
PubMed

Randomized, controlled trial of GlyNAC at 2.4, 4.8 or 7.2 g/day (1:1) vs placebo for 2 weeks (Lizzo et al. 2022, Front Aging).

114 healthy older volunteers (mean age 65), plus 20 young adults for reference.

GlyNAC was safe and well tolerated but did not raise the glutathione redox ratio or total glutathione, the primary outcome (7.2 g vs placebo P=0.739 and P=0.278). A post hoc subgroup with high oxidative stress and low glutathione showed a rise on 4.8 to 7.2 g/day. Authors were employed by Nestle Health Science, which markets glycine and NAC products.

Side effects and drug interactions

Common Potential side effects

No supplement-related adverse events were reported in the 16-week trial, and the 2-week trial of up to 7.2 g/day found it safe and well tolerated.
Mild stomach upset or nausea and a sulfur smell from NAC are the most common complaints.
Loose stools can occur at high doses.
Pregnancy and breastfeeding: there are no safety data for these high combined doses; ask your doctor.
Long-term safety beyond 24 weeks has not been studied.

Important Drug interactions

Nitroglycerin and other nitrates: NAC may increase their blood-vessel-widening effect and headache.
Blood thinners and antiplatelet drugs: NAC may slow clotting at high doses; ask your doctor.
Activated charcoal: binds NAC; do not take them together.
Other medicines: no well-documented interactions at the doses studied, but tell your doctor you take it.

Frequently asked questions about GlyNAC (Glycine + N-Acetylcysteine)

What is GlyNAC?

GlyNAC is a combination of the amino acid glycine and N-acetylcysteine (NAC), a stable source of cysteine. Together they supply two building blocks of glutathione, the body's main antioxidant inside cells. The combination was developed by Dr.

What is GlyNAC used for?

GlyNAC is researched primarily for Longevity, Antioxidant, and Muscle & Recovery. In a 16-week randomized trial, 12 older adults (mean age 71) taking GlyNAC raised gait speed by about 19% (1.13 to 1.34 m/s) and grip strength by about 14%, while the 12 on an alanine placebo did not improve.

What is the recommended dosage of GlyNAC?

The clinically studied dose is 100 mg/kg/day each of glycine and NAC (about 7 g of each for a 70 kg adult) for 16 weeks in the main trial; 2.4 to 7.2 g/day combined (1:1) for 2 weeks in a larger independent trial. Always follow the product label and check with a healthcare provider for personal advice.

Is GlyNAC safe, and does it have side effects?

Side effects and cautions reported for GlyNAC include: No supplement-related adverse events were reported in the 16-week trial, and the 2-week trial of up to 7.2 g/day found it safe and well tolerated. Mild stomach upset or nausea and a sulfur smell from NAC are the most common complaints. It may also interact with some medications. GlyNAC is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does GlyNAC interact with any medications?

Possible interactions include: Nitroglycerin and other nitrates: NAC may increase their blood-vessel-widening effect and headache. Blood thinners and antiplatelet drugs: NAC may slow clotting at high doses; ask your doctor. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for GlyNAC?

NutraSmarts rates the evidence for GlyNAC as Limited (2 out of 5). It is backed by 3 study summaries and 3 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(3 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Kumar P, Liu C, Suliburk J, Hsu JW, Muthupillai R, Jahoor F, Minard CG, Taffet GE, Sekhar RV. 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. J Gerontol A Biol Sci Med Sci. 2023;78(1):75-89. doi: 10.1093/gerona/glac135.PubMedUsed to support: 16-week placebo-controlled RCT in 24 older adults (12 per arm) at 100 mg/kg/day each of glycine and NAC. Within the GlyNAC group, glutathione rose and TBARS (72%), IL-6 (78%), TNF-alpha (54%) and HOMA-IR (64%) fell, gait speed rose about 19% and grip strength about 14%; placebo did not improve. Results are within-group comparisons.
  2. Kumar P, Liu C, Hsu JW, Chacko S, Minard C, Jahoor F, Sekhar RV. Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial. Clin Transl Med. 2021;11(3):e372. doi: 10.1002/ctm2.372.PubMedUsed to support: 36-week open-label pilot in 8 older adults (24 weeks on GlyNAC, 12 weeks off): improvements in glutathione, oxidative stress, mitochondrial function, inflammation, insulin resistance, strength, gait speed and cognition that declined after stopping. No placebo group.
  3. Lizzo G, Migliavacca E, Lamers D, Frézal A, Corthesy J, Vinyes-Parès G, Bosco N, Karagounis LG, Hövelmann U, Heise T, von Eynatten M, Gut P. A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. Front Aging. 2022;3:852569. doi: 10.3389/fragi.2022.852569.PubMedUsed to support: Two-week RCT in 114 healthy older adults at 2.4, 4.8 or 7.2 g/day GlyNAC: safe and well tolerated, but no increase in glutathione redox ratio or total glutathione (primary outcome). A post hoc subgroup with high oxidative stress and low glutathione showed higher glutathione. Run by Nestle employees.