Abstraction Health

Glycine — Research Evidence

Source: PubMed / NCBI · human studies preferred · ranked by evidence qualityLast analyzed: May 24, 2026
🟡Moderate Evidence
20 studies·5 RCTs·15 reviews

The summary below was generated by an AI system (Claude) based on the studies listed. It is a synthesis tool, not a clinical opinion. Read individual studies for full context.

The available research on glycine supplementation spans multiple biological pathways and health outcomes, but the evidence base is uneven in quality and scope. The strongest signal comes from a randomized clinical trial (GlyNAC study) examining glycine combined with N-acetylcysteine in older adults, which found improvements in glutathione deficiency, oxidative stress, mitochondrial function, inflammation, and physical function — suggesting that glycine's role as a rate-limiting precursor for glutathione synthesis may have real clinical relevance, especially in aging populations. Glycine's structural role in collagen is well-established biochemically, and RCT evidence supports that vitamin C-enriched gelatin (which contains glycine) can augment collagen synthesis when taken before intermittent exercise, though this involved a multi-ingredient product rather than glycine in isolation. A systematic review on glycine's physiological effects in human adults provides some organized clinical evidence, but the overall picture is constrained by small sample sizes, short intervention durations, and heterogeneous study designs.

Across the reviewed literature, glycine emerges as a conditionally essential amino acid — meaning dietary intake may become insufficient under conditions of aging, high physiological stress, or elevated metabolic demand, even though the body can synthesize it. This conditional essentiality is supported indirectly by findings showing that endogenous glycine synthesis appears inadequate to meet total-body demands in older adults. Its roles as a precursor to creatine and glutathione are biochemically well-established and corroborated by mechanistic and clinical data in the reviewed studies. Reviews on bone broth, collagen, and glycine's multifarious benefits provide supporting context, though these are narrative reviews rather than controlled trials and carry inherent limitations in establishing causality.

Important caveats temper enthusiasm. The majority of claims about glycine — 137 out of 176 evaluated — were rated as having insufficient evidence, meaning much of what is discussed in the literature remains speculative or insufficiently tested in humans. Most studies are short-term, conducted in narrow populations (such as older adults or athletes), and many glycine-containing interventions use combination products (e.g., GlyNAC, gelatin plus vitamin C), making it difficult to attribute effects to glycine alone. Long-term safety data in supplemental doses are sparse, dose-response relationships are poorly characterized, and it remains unclear which populations would benefit most. The research on collagen synthesis, gut barrier support, and anti-inflammatory effects is promising but preliminary in humans.

Key findings

  • A randomized clinical trial of GlyNAC (glycine + N-acetylcysteine) in older adults found improvements in glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, and physical function, supporting glycine's role as a key substrate for glutathione synthesis.
  • Glycine is a well-established biochemical precursor to glutathione, creatine, and collagen — three molecules with broad relevance to aging, muscle function, and tissue integrity.
  • Glycine may be conditionally essential in older adults and under high physiological demand, as endogenous synthesis appears insufficient to meet total-body requirements in these contexts.
  • A systematic review on glycine's physiological effects in human adults provides organized but limited clinical evidence, with heterogeneous outcomes and small sample sizes across included studies.
  • Vitamin C-enriched gelatin supplementation (a glycine-rich source) before intermittent activity was shown in an RCT to augment collagen synthesis, though glycine's independent contribution cannot be isolated from this multi-ingredient product.

Evidence gaps

  • ?Most clinical evidence for glycine uses combination products (e.g., GlyNAC, gelatin + vitamin C), making it impossible to determine how much of the observed benefit is attributable to glycine alone versus co-ingredients.
  • ?Long-term supplementation trials in diverse human populations are lacking; existing studies are largely short-term and focused on older adults or athletes, leaving gaps for other demographics including those with chronic disease.
  • ?Optimal dosing and dose-response relationships for glycine supplementation across different health outcomes (e.g., sleep, gut health, muscle recovery) are poorly characterized in the current human evidence base.

Safety summary

Glycine is generally considered well-tolerated at supplemental doses used in the reviewed studies, with no serious adverse effects reported in the available RCTs. However, long-term safety data at higher supplemental doses remain limited, and formal tolerability trials specific to glycine are sparse in the reviewed literature.

Studies (20)

Effect of Acute and Chronic Oral l-Carnitine Supplementation on Exercise Performance Based on the Exercise Intensity: A Systematic Review.

Nutrients · 2021 · Mielgo-Ayuso J et al.
Systematic Review🟢
Key finding

Effect of Acute and Chronic Oral l-Carnitine Supplementation on Exercise Performance Based on the Exercise Intensity: A Systematic Review.

Funded by: Industry (inferred from affiliations)
COI: The authors declare no conflict of interest.
PMID: 34959912DOI: 10.3390/nu13124359
View on PubMed

Tolerability of different oral iron supplements: a systematic review.

Current medical research and opinion · 2013 · Cancelo-Hidalgo MJ et al.
Systematic Review🟢
Key finding

Tolerability of different oral iron supplements: a systematic review.

PMID: 23252877DOI: 10.1185/03007995.2012.761599
View on PubMed

Breastfeeding or breast milk for procedural pain in neonates.

The Cochrane database of systematic reviews · 2023 · Shah PS et al.
Systematic Review🟢
Key finding

Breastfeeding or breast milk for procedural pain in neonates.

COI: PSS is an Associate Editor for Cochrane Neonatal; however, he was not involved in the editorial process for this review. RT declares there is no conflict of interest. VS is an Associate Editor for Cochrane Neonatal; however, she was not involved in the editorial process for this review.
PMID: 37643989DOI: 10.1002/14651858.CD004950.pub4
View on PubMed

The effect of glycine administration on the characteristics of physiological systems in human adults: A systematic review.

GeroScience · 2024 · Soh J et al.
Systematic Review🟢
Key finding

The effect of glycine administration on the characteristics of physiological systems in human adults: A systematic review.

COI: No conflict of interest to declare.
PMID: 37851316DOI: 10.1007/s11357-023-00970-8
View on PubMed

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.

The journals of gerontology. Series A, Biological sciences and medical sciences · 2023 · Kumar P et al.
RCT🟡
Key finding

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.

Funded by: NIA NIH HHS
PMID: 35975308DOI: 10.1093/gerona/glac135
View on PubMed

Vitamin C-enriched gelatin supplementation before intermittent activity augments collagen synthesis.

The American journal of clinical nutrition · 2017 · Shaw G et al.
RCT🟡
Key finding

Vitamin C-enriched gelatin supplementation before intermittent activity augments collagen synthesis.

Funded by: NIA NIH HHS
PMID: 27852613DOI: 10.3945/ajcn.116.138594
View on PubMed

Metabolome-associated psychological comorbidities improvement in irritable bowel syndrome patients receiving a probiotic.

Gut microbes · 2024 · Martin FP et al.
RCT🟡
Key finding

Metabolome-associated psychological comorbidities improvement in irritable bowel syndrome patients receiving a probiotic.

COI: GB, BB, SC, JM, FPM, and OC are employees of Société des Produits Nestlé S.A., Switzerland. WJ, GX, and PB received research support from Société des Produits Nestlé, SA. PB holds the Richard Hunt-AstraZeneca Chair in Gastroenterology.
PMID: 38717445DOI: 10.1080/19490976.2024.2347715
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Collagen and Vitamin C Supplementation Increases Lower Limb Rate of Force Development.

International journal of sport nutrition and exercise metabolism · 2022 · Lis DM et al.
RCT🟡
Key finding

Collagen and Vitamin C Supplementation Increases Lower Limb Rate of Force Development.

PMID: 34808597DOI: 10.1123/ijsnem.2020-0313
View on PubMed

Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial.

Gut · 2019 · Chambers ES et al.
RCT🟡
Key finding

Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial.

Funded by: Biotechnology and Biological Sciences Research Council, Medical Research Council, Department of Health
COI: Competing interests: A patent application for ’Compounds and their effects on appetite control and insulin sensitivity' surrounding the use of inulin-propionate ester has been filed by GSF and DJM (WO2014020344). None of the other authors reported a conflict of interest related to the study.
PMID: 30971437DOI: 10.1136/gutjnl-2019-318424
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Folic acid versus 5- methyl tetrahydrofolate supplementation in pregnancy.

European journal of obstetrics, gynecology, and reproductive biology · 2020 · Ferrazzi E et al.
Review🟡
Key finding

Folic acid versus 5- methyl tetrahydrofolate supplementation in pregnancy.

COI: Declaration of Competing Interest This above unconditional support was funded by Zambon Italia Srl.
PMID: 32868164DOI: 10.1016/j.ejogrb.2020.06.012
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Creatine: endogenous metabolite, dietary, and therapeutic supplement.

Annual review of nutrition · 2007 · Brosnan JT et al.
Review🟡
Key finding

Creatine: endogenous metabolite, dietary, and therapeutic supplement.

PMID: 17430086DOI: 10.1146/annurev.nutr.27.061406.093621
View on PubMed

Bone Broth Benefits: How Its Nutrients Fortify Gut Barrier in Health and Disease.

Digestive diseases and sciences · 2025 · Matar A et al.
Review🟡
Key finding

Bone Broth Benefits: How Its Nutrients Fortify Gut Barrier in Health and Disease.

COI: Declarations. Conflict of interest: The authors have no relevant conflicts of interest.
PMID: 40180691DOI: 10.1007/s10620-025-08997-x
View on PubMed

Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review.

Oxidative medicine and cellular longevity · 2017 · Razak MA et al.
Review🟡
Key finding

Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review.

COI: The authors declare that they have no competing interests.
PMID: 28337245DOI: 10.1155/2017/1716701
View on PubMed

Glutathione and glutathione-dependent enzymes: From biochemistry to gerontology and successful aging.

Ageing research reviews · 2023 · Lapenna D
Review🟡
Key finding

Glutathione and glutathione-dependent enzymes: From biochemistry to gerontology and successful aging.

COI: Declaration of Competing Interest The author declares that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
PMID: 37683986DOI: 10.1016/j.arr.2023.102066
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Nutraceutical treatment and prevention of benign prostatic hyperplasia and prostate cancer.

Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica · 2019 · Cicero AFG et al.
Review🟡
Key finding

Nutraceutical treatment and prevention of benign prostatic hyperplasia and prostate cancer.

PMID: 31577095DOI: 10.4081/aiua.2019.3.139
View on PubMed

Unlocking the Therapeutic Potential of Marine Collagen: A Scientific Exploration for Delaying Skin Aging.

Marine drugs · 2024 · Rahman A et al.
Review🟡
Key finding

Unlocking the Therapeutic Potential of Marine Collagen: A Scientific Exploration for Delaying Skin Aging.

Funded by: Industry (inferred from affiliations)
COI: The authors declare no conflicts of interest.
PMID: 38667776DOI: 10.3390/md22040159
View on PubMed

Mitochondria as Nutritional Targets to Maintain Muscle Health and Physical Function During Ageing.

Sports medicine (Auckland, N.Z.) · 2024 · Broome SC et al.
Review🟡
Key finding

Mitochondria as Nutritional Targets to Maintain Muscle Health and Physical Function During Ageing.

COI: In the interest of full disclosure, SCB reports gifts from MitoQ Ltd. who manufacture MitoQ. JAH reports research funding received from Amazentis Inc. who manufacture the urolithin A supplement Mitopure. JW has received conference and travel support from Amazentis Inc. LGK was an employee of Nestlé Research and Nestlé Health Science and reports personal fees from Nestlé Health Science who manufacture n3-PUFAs, urolithin A, GlyNAC, and nicotinamide riboside including multivitamins such as B6 and B3.
PMID: 39060742DOI: 10.1007/s40279-024-02072-7
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Advances in delivery methods of

Bioengineered · 2022 · ElFar OA et al.
Review🟡
Key finding

Advances in delivery methods of

Funded by: Industry (inferred from affiliations)
COI: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
PMID: 35946342DOI: 10.1080/21655979.2022.2100863
View on PubMed

Glycine: The Smallest Anti-Inflammatory Micronutrient.

International journal of molecular sciences · 2023 · Aguayo-Cerón KA et al.
Review🟡
Key finding

Glycine: The Smallest Anti-Inflammatory Micronutrient.

Funded by: Instituto Politécnico Nacional
COI: The authors declare no conflict of interest.
PMID: 37510995DOI: 10.3390/ijms241411236
View on PubMed

Inflammation, vitamin B6 and related pathways.

Molecular aspects of medicine · 2017 · Ueland PM et al.
Review🟡
Key finding

Inflammation, vitamin B6 and related pathways.

PMID: 27593095DOI: 10.1016/j.mam.2016.08.001
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