GlyNAC

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    Last Updated: February 26, 2024

    GlyNAC is a term that describes co-administered glycine and n-acetylcysteine. The body of research on GlyNAC is small, but preliminary evidence shows promising effects for conditions with higher levels of oxidative stress, such as type 2 diabetes, HIV, and aging.

    GlyNAC is most often used for

    What is GlyNAC?

    GlyNAC is simply a term used to describe co-administered glycine and n-acetylcysteine (NAC). Like NAC, GlyNAC is thought to reduce oxidative stress by increasing levels of glutathione (the most abundant intracellular antioxidant).[1]

    What are GlyNAC’s main benefits?

    Preliminary research suggests that GlyNAC may reduce oxidative stress and improve metabolic health in conditions characterized by high levels of oxidative stress, such as type 2 diabetes (T2D), human immunodeficiency virus (HIV), and aging.[2][3] As is the case with n-acetylcysteine, these benefits are largely brought about by increasing intracellular levels of the antioxidant glutathione.[4]

    Before discussing specific outcomes, it’s worth underscoring that, as of 2024, most studies on GlyNAC follow the same general methodology. People in the treatment group, who all have some condition of interest (e.g., people with HIV, people with T2D, or older people), receive some quantity of GlyNAC daily; their biomarkers of oxidative stress and metabolic health are measured at baseline, after the treatment period, and several weeks after the treatment has ceased. These biomarkers are compared to those of a group without the condition of interest (e.g., people without HIV, people without T2D, or young people) who have not received the treatment. Generally speaking, GlyNAC is able to shift the biomarkers of the treatment group to more closely resemble (and sometimes equal) those of the non-treatment group, and these biomarkers then return to baseline (i.e., worsen) after treatment is discontinued. This study design is certainly useful, especially with small groups, but the literature would still benefit from more randomized controlled trials.

    With respect to specific outcomes, GlyNAC seems able to improve (i.e., reduce) fasting respiratory quotient, glucose oxidation, insulin resistance, and plasma free fatty acids in people with T2D.[5][1]

    In people with HIV, GlyNAC has been reported to improve fasting glucose levels, measures of oxidative stress like thiobarbituric acid reactive substances (TBARS) and F2-isoprostane, and scores on the physical and mental components of the SF-36, which evaluates quality of life.[6][3]

    One randomized trial in healthy older adults found that GlyNAC didn’t always raise blood levels of glutathione sulfhydryl (GSH), the reduced form of glutathione, and that GlyNAC’s ability to do so may be dependent on a person’s baseline GSH status (i.e., people with low GSH may benefit from GlyNAC, while people with normal levels of GSH may not).[7]

    What are GlyNAC’s main drawbacks?

    No notable side effects have been reported in the GlyNAC literature, although there have been some documented instances of NAC causing nausea, vomiting, and diarrhea.[8][9]

    When NAC or GlyNAC are taken intravenously, NAC overdose is possible, and can result in red blood cell breakdown (hemolysis), low blood platelet count (thrombocytopenia), kidney failure, and possibly death.[10]

    How does GlyNAC work?

    GlycNAC is thought to provide its benefits largely by increasing the production of GSH. GlyNAC is simply glycine and cysteine (in the form of n-acetylcysteine), which are two of the three substrates necessary for the synthesis of GSH (via two enzymes: glutamate cysteine ligase and glutathione synthase).[2]

    As well as acting as substrates from which GSH can be formed, glycine and cysteine also play their own role in many biochemical reactions, and thus should be kept at proper levels. Glycine contributes methyl groups (-CH3) to many chemical reactions (such as those involved in regulating gene expression), is a key component of cartilage, and is a neurotransmitter. Cysteine similarly donates sulfhydryl groups (-SH) to chemical reactions, binds to metal ions, and supports protein structure via the formation of disulfide bonds.[11][12]

    What are other names for GlyNAC

    Note that GlyNAC is also known as:
    • Glycine-NAC
    • Glycine-N-Acetylcysteine
    GlyNAC should not be confused with:
    • NAC
    • N-Acetylcysteine
    • Glycine

    Dosage information

    The most common dosage in the (limited) body of research is 1.33 and 0.81 mmol/kg/day (millimoles per kilogram of bodyweight per day) of glycine and cysteine (in the form of n-acetylcysteine, which is about 74% cysteine), respectively. This dosage is equivalent to about 100 and 133 mg per kilogram of body weight per day (mg/kg/day) of glycine and n-acetylcysteine, respectively.

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    Frequently asked questions

    What is GlyNAC?

    GlyNAC is simply a term used to describe co-administered glycine and n-acetylcysteine (NAC). Like NAC, GlyNAC is thought to reduce oxidative stress by increasing levels of glutathione (the most abundant intracellular antioxidant).[1]

    What are GlyNAC’s main benefits?

    Preliminary research suggests that GlyNAC may reduce oxidative stress and improve metabolic health in conditions characterized by high levels of oxidative stress, such as type 2 diabetes (T2D), human immunodeficiency virus (HIV), and aging.[2][3] As is the case with n-acetylcysteine, these benefits are largely brought about by increasing intracellular levels of the antioxidant glutathione.[4]

    Before discussing specific outcomes, it’s worth underscoring that, as of 2024, most studies on GlyNAC follow the same general methodology. People in the treatment group, who all have some condition of interest (e.g., people with HIV, people with T2D, or older people), receive some quantity of GlyNAC daily; their biomarkers of oxidative stress and metabolic health are measured at baseline, after the treatment period, and several weeks after the treatment has ceased. These biomarkers are compared to those of a group without the condition of interest (e.g., people without HIV, people without T2D, or young people) who have not received the treatment. Generally speaking, GlyNAC is able to shift the biomarkers of the treatment group to more closely resemble (and sometimes equal) those of the non-treatment group, and these biomarkers then return to baseline (i.e., worsen) after treatment is discontinued. This study design is certainly useful, especially with small groups, but the literature would still benefit from more randomized controlled trials.

    With respect to specific outcomes, GlyNAC seems able to improve (i.e., reduce) fasting respiratory quotient, glucose oxidation, insulin resistance, and plasma free fatty acids in people with T2D.[5][1]

    In people with HIV, GlyNAC has been reported to improve fasting glucose levels, measures of oxidative stress like thiobarbituric acid reactive substances (TBARS) and F2-isoprostane, and scores on the physical and mental components of the SF-36, which evaluates quality of life.[6][3]

    One randomized trial in healthy older adults found that GlyNAC didn’t always raise blood levels of glutathione sulfhydryl (GSH), the reduced form of glutathione, and that GlyNAC’s ability to do so may be dependent on a person’s baseline GSH status (i.e., people with low GSH may benefit from GlyNAC, while people with normal levels of GSH may not).[7]

    Is taking GlyNAC better than taking NAC alone?

    Theoretically, yes. Certain groups of people (such as older adults) can have both reduced glutathione levels and reduced cysteine and glycine levels.[14] Although both glycine and cysteine can be produced by the body, their levels seem to be highly influenced by diet, and it’s possible that endogenous production of these amino acids may not be sufficient in people with higher demand (such as people with high levels of oxidative stress).[15][16]

    What are GlyNAC’s main drawbacks?

    No notable side effects have been reported in the GlyNAC literature, although there have been some documented instances of NAC causing nausea, vomiting, and diarrhea.[8][9]

    When NAC or GlyNAC are taken intravenously, NAC overdose is possible, and can result in red blood cell breakdown (hemolysis), low blood platelet count (thrombocytopenia), kidney failure, and possibly death.[10]

    How does GlyNAC work?

    GlycNAC is thought to provide its benefits largely by increasing the production of GSH. GlyNAC is simply glycine and cysteine (in the form of n-acetylcysteine), which are two of the three substrates necessary for the synthesis of GSH (via two enzymes: glutamate cysteine ligase and glutathione synthase).[2]

    As well as acting as substrates from which GSH can be formed, glycine and cysteine also play their own role in many biochemical reactions, and thus should be kept at proper levels. Glycine contributes methyl groups (-CH3) to many chemical reactions (such as those involved in regulating gene expression), is a key component of cartilage, and is a neurotransmitter. Cysteine similarly donates sulfhydryl groups (-SH) to chemical reactions, binds to metal ions, and supports protein structure via the formation of disulfide bonds.[11][12]

    What is the role of glutathione in the body?

    Glutathione’s reduced form, GSH, is a relevant target for treatment because it’s one of the most critical endogenously-produced antioxidants in the body. GSH is found in high quantities in the fluid of the lungs, for example, where it helps reduce the reactive oxygen species produced by neutrophils responding to smoke and other oxidizing compounds you may inhale.[13] Within the cell, GSH helps to reduce reactive oxygen species, such as the superoxide and peroxide radicals. Additionally, it is found in many organelles, aiding in the regulation of mitochondrial life cycle and cell division.[13]

    Update History

    References

    1. ^Sekhar RVGlyNAC (Glycine and -Acetylcysteine) Supplementation Improves Impaired Mitochondrial Fuel Oxidation and Lowers Insulin Resistance in Patients with Type 2 Diabetes: Results of a Pilot Study.Antioxidants (Basel).(2022-Jan-13)
    2. ^Sekhar RVGlyNAC Supplementation Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Aging Hallmarks, Metabolic Defects, Muscle Strength, Cognitive Decline, and Body Composition: Implications for Healthy Aging.J Nutr.(2021-Dec-03)
    3. ^Sekhar RVSupplementing glycine and N-acetylcysteine (GlyNAC) rapidly improves health-related quality of life and lowers perception of fatigue in patients with HIV.AIDS.(2021-Jul-15)
    4. ^Best JH, Hoogwerf BJ, Herman WH, Pelletier EM, Smith DB, Wenten M, Hussein MARisk of cardiovascular disease events in patients with type 2 diabetes prescribed the glucagon-like peptide 1 (GLP-1) receptor agonist exenatide twice daily or other glucose-lowering therapies: a retrospective analysis of the LifeLink database.Diabetes Care.(2011-Jan)
    5. ^Sekhar RV, McKay SV, Patel SG, Guthikonda AP, Reddy VT, Balasubramanyam A, Jahoor FGlutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycineDiabetes Care.(2011 Jan)
    6. ^Badrinath S, Blasczyk R, Bade-Doeding CNon-expression of HLA-C*07:55N is caused by a premature stop codon in exon 3.Tissue Antigens.(2012-Feb)
    7. ^Giulia Lizzo, Eugenia Migliavacca, Daniela Lamers, Adrien Frézal, John Corthesy, Gerard Vinyes-Parès, Nabil Bosco, Leonidas G Karagounis, Ulrike Hövelmann, Tim Heise, Maximilian von Eynatten, Philipp GutA Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative DamageFront Aging.(2022 Mar 7)
    8. ^Rhodes K, Braakhuis APerformance and Side Effects of Supplementation with N-Acetylcysteine: A Systematic Review and Meta-Analysis.Sports Med.(2017-Aug)
    9. ^Micaely Cristina Dos Santos Tenório, Nayara Gomes Graciliano, Fabiana Andréa Moura, Alane Cabral Menezes de Oliveira, Marília Oliveira Fonseca GoulartN-Acetylcysteine (NAC): Impacts on Human HealthAntioxidants (Basel).(2021 Jun 16)
    10. ^Ghafar Ali Mahmoudi, Peyman Astaraki, Azita Zafar Mohtashami, Maryam AhadiN-acetylcysteine overdose after acetaminophen poisoningInt Med Case Rep J.(2015 Feb 27)
    11. ^Baker DH, Czarnecki-Maulden GLPharmacologic role of cysteine in ameliorating or exacerbating mineral toxicities.J Nutr.(1987-Jun)
    12. ^Sevier CS, Kaiser CAFormation and transfer of disulphide bonds in living cells.Nat Rev Mol Cell Biol.(2002-Nov)
    13. ^Forman HJ, Zhang H, Rinna AGlutathione: overview of its protective roles, measurement, and biosynthesis.Mol Aspects Med.(2009)
    14. ^Sekhar RV, Patel SG, Guthikonda AP, Reid M, Balasubramanyam A, Taffet GE, Jahoor FDeficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementationAm J Clin Nutr.(2011 Sep)
    15. ^Meléndez-Hevia E, De Paz-Lugo P, Cornish-Bowden A, Cárdenas MLA weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesisJ Biosci.(2009 Dec)
    16. ^Gersovitz M, Bier D, Matthews D, Udall J, Munro HN, Young VRDynamic aspects of whole body glycine metabolism: influence of protein intake in young adult and elderly malesMetabolism.(1980 Oct)