Glycine - Revision history

Dmitry Dzhagarov: /* GlyNAC (combination of glycine and N-acetylcysteine) */

2023-10-22T10:24:35Z

GlyNAC (combination of glycine and N-acetylcysteine)

← Older revision		Revision as of 10:24, 22 October 2023
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	=== GlyNAC (combination of glycine and N-acetylcysteine) ===		=== GlyNAC (combination of glycine and N-acetylcysteine) ===
	Cellular increases in oxidative stress and decline in mitochondrial function are identified as key defects in aging. Defects linked to oxidative stress and impaired mitochondrial fuel oxidation, such as inflammation, insulin resistance, endothelial dysfunction, and aging hallmarks, are present in older humans and are associated with declining strength and cognition, as well as the development of sarcopenic obesity. Investigations on the origins of elevated oxidative stress and mitochondrial dysfunction in older humans led to the discovery that deficiencies of the antioxidant tripeptide glutathione (γ-Glutamylcysteinylglycine) and its precursor amino acids glycine and cysteine may be contributory. Supplementation with GlyNAC (combination of glycine and N-acetylcysteine as a cysteine precursor) was found to improve/correct cellular glycine, cysteine, and glutathione deficiencies; lower oxidative stress; and improve mitochondrial function, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, and multiple aging hallmarks; and improve muscle strength, exercise capacity, cognition, and body composition.<ref name="GlyNAC"/><ref>Sekhar, R. V. (2021). GlyNAC supplementation improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, aging hallmarks, metabolic defects, muscle strength, cognitive decline, and body composition: Implications for healthy aging. The Journal of Nutrition, 151(12), 3606-3616. PMID: 34587244 DOI: [https://doi.org/10.1093/jn/nxab309 10.1093/jn/nxab309]</ref><ref>Kumar, P., Liu, C., Suliburk, J., Hsu, J. W., Muthupillai, R., Jahoor, F., ... & Sekhar, R. V. (2023). 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, 78(1), 75-89. PMID: 35975308 PMCID: PMC9879756 (available on 2023-08-17) DOI: 10.1093/gerona/glac135</ref><ref>Kumar, P., Liu, C., Hsu, J. W., Chacko, S., Minard, C., Jahoor, F., & Sekhar, R. V. (2021). 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. Clinical and Translational Medicine, 11(3), e372. PMID: 33783984 PMCID: PMC8002905 DOI: 10.1002/ctm2.372</ref> '''The mice that received GlyNAC lived 24% longer than those that did not receive GlyNAC'''.<ref name="GlyNAC"/>		Cellular increases in oxidative stress and decline in mitochondrial function are identified as key defects in aging. Defects linked to oxidative stress and impaired mitochondrial fuel oxidation, such as inflammation, insulin resistance, endothelial dysfunction, and aging hallmarks, are present in older humans and are associated with declining strength and cognition, as well as the development of sarcopenic obesity. Investigations on the origins of elevated oxidative stress and mitochondrial dysfunction in older humans led to the discovery that deficiencies of the antioxidant tripeptide glutathione (γ-Glutamylcysteinylglycine) and its precursor amino acids glycine and cysteine may be contributory. Supplementation with GlyNAC (combination of glycine and N-acetylcysteine as a cysteine precursor) was found to improve/correct cellular glycine, cysteine, and glutathione deficiencies; lower oxidative stress; and improve mitochondrial function, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, and multiple aging hallmarks; and improve muscle strength, exercise capacity, cognition, and body composition.<ref name="GlyNAC"/><ref>Sekhar, R. V. (2021). GlyNAC supplementation improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, aging hallmarks, metabolic defects, muscle strength, cognitive decline, and body composition: Implications for healthy aging. The Journal of Nutrition, 151(12), 3606-3616. PMID: 34587244 DOI: [https://doi.org/10.1093/jn/nxab309 10.1093/jn/nxab309]</ref><ref>Kumar, P., Liu, C., Suliburk, J., Hsu, J. W., Muthupillai, R., Jahoor, F., ... & Sekhar, R. V. (2023). 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, 78(1), 75-89. PMID: 35975308 PMCID: PMC9879756 (available on 2023-08-17) DOI: 10.1093/gerona/glac135</ref><ref>Kumar, P., Liu, C., Hsu, J. W., Chacko, S., Minard, C., Jahoor, F., & Sekhar, R. V. (2021). 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. Clinical and Translational Medicine, 11(3), e372. PMID: 33783984 PMCID: PMC8002905 DOI: 10.1002/ctm2.372</ref> '''The mice that received GlyNAC lived 24% longer than those that did not receive GlyNAC'''.<ref name="GlyNAC"/><ref>[https://youtu.be/c3O4RwODJNc GlyNac More Anti-Aging Proof!]</ref>

	Glycine is genetically associated with lower coronary heart disease risk and lower incidence of type 2 diabetes.<ref>Wittemans, L. B., Lotta, L. A., Oliver-Williams, C., Stewart, I. D., Surendran, P., Karthikeyan, S., ... & Langenberg, C. (2019). Assessing the causal association of glycine with risk of cardio-metabolic diseases. Nature communications, 10(1), 1060. PMID: 30837465 PMCID: PMC6400990 DOI: 10.1038/s41467-019-08936-1</ref> Glycine improved the endothelium function in aged rats possibly by enhancing eNOS expression and reducing the role of superoxide anion and contractile prostanoids that increase the nitric oxide bioavailability.<ref>Gómez-Zamudio, J. H., García-Macedo, R., Lázaro-Suárez, M., Ibarra-Barajas, M., Kumate, J., & Cruz, M. (2015). Vascular endothelial function is improved by oral glycine treatment in aged rats. Canadian Journal of Physiology and Pharmacology, 93(6), 465-473. PMID: 25988540 DOI: 10.1139/cjpp-2014-0393</ref><ref>Zakaria, E. R., Joseph, B., Hamidi, M., Zeeshan, M., Algamal, A., Sartaj, F., ... & Madan, D. (2019). Glycine improves peritoneal vasoreactivity to dialysis solutions in the elderly. Qatar Medical Journal, 2019(3), 19. PMID: 31903325 PMCID: PMC6929513 DOI: 10.5339/qmj.2019.19</ref>		Glycine is genetically associated with lower coronary heart disease risk and lower incidence of type 2 diabetes.<ref>Wittemans, L. B., Lotta, L. A., Oliver-Williams, C., Stewart, I. D., Surendran, P., Karthikeyan, S., ... & Langenberg, C. (2019). Assessing the causal association of glycine with risk of cardio-metabolic diseases. Nature communications, 10(1), 1060. PMID: 30837465 PMCID: PMC6400990 DOI: 10.1038/s41467-019-08936-1</ref> Glycine improved the endothelium function in aged rats possibly by enhancing eNOS expression and reducing the role of superoxide anion and contractile prostanoids that increase the nitric oxide bioavailability.<ref>Gómez-Zamudio, J. H., García-Macedo, R., Lázaro-Suárez, M., Ibarra-Barajas, M., Kumate, J., & Cruz, M. (2015). Vascular endothelial function is improved by oral glycine treatment in aged rats. Canadian Journal of Physiology and Pharmacology, 93(6), 465-473. PMID: 25988540 DOI: 10.1139/cjpp-2014-0393</ref><ref>Zakaria, E. R., Joseph, B., Hamidi, M., Zeeshan, M., Algamal, A., Sartaj, F., ... & Madan, D. (2019). Glycine improves peritoneal vasoreactivity to dialysis solutions in the elderly. Qatar Medical Journal, 2019(3), 19. PMID: 31903325 PMCID: PMC6929513 DOI: 10.5339/qmj.2019.19</ref>

Dmitry Dzhagarov at 11:43, 30 July 2023

2023-07-30T11:43:27Z

← Older revision		Revision as of 11:43, 30 July 2023
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	'''Glycine (aminoacetic acid)''' is most important and simple, nonessential amino acid in humans, animals, and many mammals.<ref>Razak, M. A., Begum, P. S., Viswanath, B., & Rajagopal, S. (2017). Multifarious beneficial effect of nonessential amino acid, glycine: a review. Oxidative medicine and cellular longevity, 2017:1716701. PMID: 28337245 PMCID: PMC5350494 DOI: 10.1155/2017/1716701</ref> Glycine is a precursor for several important compounds such as creatine, purines and glucose, and is involved in a wide range of metabolic pathways.<ref>Wang, W., Wu, Z., Dai, Z., Yang, Y., Wang, J., & Wu, G. (2013). Glycine metabolism in animals and humans: implications for nutrition and health. Amino acids, 45, 463-477. PMID: 23615880 DOI: 10.1007/s00726-013-1493-1</ref> Besides participating in synthesizing structural biomolecules, glycine serves as one of the predecessors of glutathione, one of the most important antioxidants in the human body.<ref>Sekhar, R. V., Patel, S. G., Guthikonda, A. P., Reid, M., Balasubramanyam, A., Taffet, G. E., & Jahoor, F. (2011). Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation–. The American journal of clinical nutrition, 94(3), 847-853. PMID: 21795440 PMCID: PMC3155927 DOI: 10.3945/ajcn.110.003483</ref><ref>Sekhar, R. V., McKay, S. V., Patel, S. G., Guthikonda, A. P., Reddy, V. T., Balasubramanyam, A., & Jahoor, F. (2011). Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Diabetes care, 34(1), 162-167. PMID: 20929994 PMCID: PMC3005481 DOI: 10.2337/dc10-1006</ref><ref>Ruiz-Ramírez, A., Ortiz-Balderas, E., Cardozo-Saldaña, G., Diaz-Diaz, E., & El-Hafidi, M. (2014). Glycine restores glutathione and protects against oxidative stress in vascular tissue from sucrose-fed rats. Clinical Science, 126(1), 19-29. PMID: 23742196 DOI: 10.1042/CS20130164</ref>		'''Glycine (aminoacetic acid)''' is most important and simple, nonessential amino acid in humans, animals, and many mammals.<ref>Razak, M. A., Begum, P. S., Viswanath, B., & Rajagopal, S. (2017). Multifarious beneficial effect of nonessential amino acid, glycine: a review. Oxidative medicine and cellular longevity, 2017:1716701. PMID: 28337245 PMCID: PMC5350494 DOI: 10.1155/2017/1716701</ref> Glycine is a precursor for several important compounds such as creatine, purines and glucose, and is involved in a wide range of metabolic pathways.<ref>Wang, W., Wu, Z., Dai, Z., Yang, Y., Wang, J., & Wu, G. (2013). Glycine metabolism in animals and humans: implications for nutrition and health. Amino acids, 45, 463-477. PMID: 23615880 DOI: 10.1007/s00726-013-1493-1</ref> Besides participating in synthesizing structural biomolecules, glycine serves as one of the predecessors of glutathione, one of the most important antioxidants in the human body,<ref>Sekhar, R. V., Patel, S. G., Guthikonda, A. P., Reid, M., Balasubramanyam, A., Taffet, G. E., & Jahoor, F. (2011). Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation–. The American journal of clinical nutrition, 94(3), 847-853. PMID: 21795440 PMCID: PMC3155927 DOI: 10.3945/ajcn.110.003483</ref><ref>Sekhar, R. V., McKay, S. V., Patel, S. G., Guthikonda, A. P., Reddy, V. T., Balasubramanyam, A., & Jahoor, F. (2011). Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Diabetes care, 34(1), 162-167. PMID: 20929994 PMCID: PMC3005481 DOI: 10.2337/dc10-1006</ref><ref>Ruiz-Ramírez, A., Ortiz-Balderas, E., Cardozo-Saldaña, G., Diaz-Diaz, E., & El-Hafidi, M. (2014). Glycine restores glutathione and protects against oxidative stress in vascular tissue from sucrose-fed rats. Clinical Science, 126(1), 19-29. PMID: 23742196 DOI: 10.1042/CS20130164</ref> and also supplementation that is important in avoiding the development of chronic inflammation.<ref>Aguayo-Cerón, K. A., Sánchez-Muñoz, F., Gutierrez-Rojas, R. A., Acevedo-Villavicencio, L. N., Flores-Zarate, A. V., Huang, F., ... & Romero-Nava, R. (2023). Glycine: The Smallest Anti-Inflammatory Micronutrient. International Journal of Molecular Sciences, 24(14), 11236. https://doi.org/10.3390/ijms241411236</ref>

	'''Glycine supplementation has been shown to extend lifespan in various animal models'''.<ref>Miller, R. A., Harrison, D. E., Astle, C. M., Bogue, M. A., Brind, J., Fernandez, E., ... & Strong, R. (2019). Glycine supplementation extends lifespan of male and female mice. Aging cell, 18(3), e12953. PMID: 30916479 PMCID: PMC6516426 DOI: 10.1111/acel.12953</ref> <ref name="GlyNAC" >Kumar, P., Osahon, O. W., & Sekhar, R. V. (2022). GlyNAC (glycine and N-acetylcysteine) supplementation in mice increases length of life by correcting glutathione deficiency, oxidative stress, mitochondrial dysfunction, abnormalities in mitophagy and nutrient sensing, and genomic damage. Nutrients, 14(5), 1114.		'''Glycine supplementation has been shown to extend lifespan in various animal models'''.<ref>Miller, R. A., Harrison, D. E., Astle, C. M., Bogue, M. A., Brind, J., Fernandez, E., ... & Strong, R. (2019). Glycine supplementation extends lifespan of male and female mice. Aging cell, 18(3), e12953. PMID: 30916479 PMCID: PMC6516426 DOI: 10.1111/acel.12953</ref> <ref name="GlyNAC" >Kumar, P., Osahon, O. W., & Sekhar, R. V. (2022). GlyNAC (glycine and N-acetylcysteine) supplementation in mice increases length of life by correcting glutathione deficiency, oxidative stress, mitochondrial dysfunction, abnormalities in mitophagy and nutrient sensing, and genomic damage. Nutrients, 14(5), 1114.

Dmitry Dzhagarov: /* The glycine cleavage system */

2023-05-05T20:02:47Z

The glycine cleavage system

← Older revision		Revision as of 20:02, 5 May 2023
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	=== The glycine cleavage system ===		=== The glycine cleavage system ===
	Glycine takes part in one-carbon metabolism as a methyl group provider through the glycine cleavage system.<ref name="fate" >Tian, S., Feng, J., Cao, Y., Shen, S., Cai, Y., Yang, D., ... & Gao, P. (2019). Glycine cleavage system determines the fate of pluripotent stem cells via the regulation of senescence and epigenetic modifications. Life Science Alliance, 2(5). PMID: 31562192 PMCID: PMC6765226 DOI: 10.26508/lsa.201900413</ref> The glycine cleavage system is a multienzyme complex consisting of four individual components: glycine decarboxylase, amino methyltransferase, glycine cleavage system protein H, and dihydrolipoamide dehydrogenase.<ref>Narisawa, A., Komatsuzaki, S., Kikuchi, A., Niihori, T., Aoki, Y., Fujiwara, K., ... & Kure, S. (2012). Mutations in genes encoding the glycine cleavage system predispose to neural tube defects in mice and humans. Human molecular genetics, 21(7), 1496-1503. PMID: 22171071 PMCID: PMC3298276 DOI: 10.1093/hmg/ddr585</ref> It has been revealed that '''glycine influenced stem cell pluripotency by controlling the synthesis of SAM S-adenosylmethionine ''' (a methyl donor in histone as well as DNA methylation<ref>Liu, Y., Cui, D. X., Pan, Y., Yu, S. H., Zheng, L. W., & Wan, M. (2022). Metabolic-epigenetic nexus in regulation of stem cell fate. World Journal of Stem Cells, 14(7), 490. PMID: 36157525 PMCID: PMC9350619 DOI: 10.4252/wjsc.v14.i7.490</ref>), thus promoting H3K4me3 modification, and open euchromatin.<ref name="fate"/><ref>Kang, P. J., Zheng, J., Lee, G., Son, D., Kim, I. Y., Song, G., ... & You, S. (2019). Glycine decarboxylase regulates the maintenance and induction of pluripotency via metabolic control. Metabolic engineering, 53, 35-47. PMID: 30779965 DOI: 10.1016/j.ymben.2019.02.003 </ref> This process is present in human and mouse ~~PSCs~~.<ref name="fate"/><ref>Zhang, J., Ratanasirintrawoot, S., Chandrasekaran, S., Wu, Z., Ficarro, S. B., Yu, C., ... & Daley, G. Q. (2016). LIN28 regulates stem cell metabolism and conversion to primed pluripotency. Cell stem cell, 19(1), 66-80. PMID: 27320042 DOI: 10.1016/j.stem.2016.05.009</ref>		Glycine takes part in one-carbon metabolism as a methyl group provider through the glycine cleavage system.<ref name="fate" >Tian, S., Feng, J., Cao, Y., Shen, S., Cai, Y., Yang, D., ... & Gao, P. (2019). Glycine cleavage system determines the fate of pluripotent stem cells via the regulation of senescence and epigenetic modifications. Life Science Alliance, 2(5). PMID: 31562192 PMCID: PMC6765226 DOI: 10.26508/lsa.201900413</ref> The glycine cleavage system is a multienzyme complex consisting of four individual components: glycine decarboxylase, amino methyltransferase, glycine cleavage system protein H, and dihydrolipoamide dehydrogenase.<ref>Narisawa, A., Komatsuzaki, S., Kikuchi, A., Niihori, T., Aoki, Y., Fujiwara, K., ... & Kure, S. (2012). Mutations in genes encoding the glycine cleavage system predispose to neural tube defects in mice and humans. Human molecular genetics, 21(7), 1496-1503. PMID: 22171071 PMCID: PMC3298276 DOI: 10.1093/hmg/ddr585</ref> It has been revealed that '''glycine influenced stem cell pluripotency by controlling the synthesis of SAM (S-adenosylmethionine ''' - a methyl donor in histone as well as DNA methylation<ref>Liu, Y., Cui, D. X., Pan, Y., Yu, S. H., Zheng, L. W., & Wan, M. (2022). Metabolic-epigenetic nexus in regulation of stem cell fate. World Journal of Stem Cells, 14(7), 490. PMID: 36157525 PMCID: PMC9350619 DOI: 10.4252/wjsc.v14.i7.490</ref>), thus promoting H3K4me3 modification, and open euchromatin.<ref name="fate"/><ref>Kang, P. J., Zheng, J., Lee, G., Son, D., Kim, I. Y., Song, G., ... & You, S. (2019). Glycine decarboxylase regulates the maintenance and induction of pluripotency via metabolic control. Metabolic engineering, 53, 35-47. PMID: 30779965 DOI: 10.1016/j.ymben.2019.02.003 </ref> This process is present in human and mouse pluripotent stem cells.<ref name="fate"/><ref>Zhang, J., Ratanasirintrawoot, S., Chandrasekaran, S., Wu, Z., Ficarro, S. B., Yu, C., ... & Daley, G. Q. (2016). LIN28 regulates stem cell metabolism and conversion to primed pluripotency. Cell stem cell, 19(1), 66-80. PMID: 27320042 DOI: 10.1016/j.stem.2016.05.009</ref>

	== References ==		== References ==

Dmitry Dzhagarov: /* Glycine improves sleep quality */

2023-05-05T19:58:16Z

Glycine improves sleep quality

← Older revision		Revision as of 19:58, 5 May 2023
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	=== Glycine improves sleep quality ===		=== Glycine improves sleep quality ===
	Glycine at a dose of 3 g/day before bedtime subjectively '''improves sleep quality''' and reduces sleepiness and fatigue during the day in individuals with insomniac tendencies or restricted sleep time. Glycine administration before bedtime also '''decreases core body temperature''' in human subjects.<ref>Kawai, N., Sakai, N., Okuro, M., Karakawa, S., Tsuneyoshi, Y., Kawasaki, N., ... & Nishino, S. (2015). The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. Neuropsychopharmacology, 40(6), 1405-1416. PMID: 25533534 PMCID: PMC4397399 DOI: 10.1038/npp.2014.326</ref>		Glycine at a dose of 3 g/day before bedtime subjectively '''improves sleep quality''' and reduces sleepiness and fatigue during the day in individuals with insomniac tendencies or restricted sleep time. Glycine administration before bedtime also '''decreases core body temperature''' in human subjects.<ref>Kawai, N., Sakai, N., Okuro, M., Karakawa, S., Tsuneyoshi, Y., Kawasaki, N., ... & Nishino, S. (2015). The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. Neuropsychopharmacology, 40(6), 1405-1416. PMID: 25533534 PMCID: PMC4397399 DOI: 10.1038/npp.2014.326</ref>

			=== The glycine cleavage system ===
			Glycine takes part in one-carbon metabolism as a methyl group provider through the glycine cleavage system.<ref name="fate" >Tian, S., Feng, J., Cao, Y., Shen, S., Cai, Y., Yang, D., ... & Gao, P. (2019). Glycine cleavage system determines the fate of pluripotent stem cells via the regulation of senescence and epigenetic modifications. Life Science Alliance, 2(5). PMID: 31562192 PMCID: PMC6765226 DOI: 10.26508/lsa.201900413</ref> The glycine cleavage system is a multienzyme complex consisting of four individual components: glycine decarboxylase, amino methyltransferase, glycine cleavage system protein H, and dihydrolipoamide dehydrogenase.<ref>Narisawa, A., Komatsuzaki, S., Kikuchi, A., Niihori, T., Aoki, Y., Fujiwara, K., ... & Kure, S. (2012). Mutations in genes encoding the glycine cleavage system predispose to neural tube defects in mice and humans. Human molecular genetics, 21(7), 1496-1503. PMID: 22171071 PMCID: PMC3298276 DOI: 10.1093/hmg/ddr585</ref> It has been revealed that '''glycine influenced stem cell pluripotency by controlling the synthesis of SAM S-adenosylmethionine ''' (a methyl donor in histone as well as DNA methylation<ref>Liu, Y., Cui, D. X., Pan, Y., Yu, S. H., Zheng, L. W., & Wan, M. (2022). Metabolic-epigenetic nexus in regulation of stem cell fate. World Journal of Stem Cells, 14(7), 490. PMID: 36157525 PMCID: PMC9350619 DOI: 10.4252/wjsc.v14.i7.490</ref>), thus promoting H3K4me3 modification, and open euchromatin.<ref name="fate"/><ref>Kang, P. J., Zheng, J., Lee, G., Son, D., Kim, I. Y., Song, G., ... & You, S. (2019). Glycine decarboxylase regulates the maintenance and induction of pluripotency via metabolic control. Metabolic engineering, 53, 35-47. PMID: 30779965 DOI: 10.1016/j.ymben.2019.02.003 </ref> This process is present in human and mouse PSCs.<ref name="fate"/><ref>Zhang, J., Ratanasirintrawoot, S., Chandrasekaran, S., Wu, Z., Ficarro, S. B., Yu, C., ... & Daley, G. Q. (2016). LIN28 regulates stem cell metabolism and conversion to primed pluripotency. Cell stem cell, 19(1), 66-80. PMID: 27320042 DOI: 10.1016/j.stem.2016.05.009</ref>

	== References ==		== References ==

Dmitry Dzhagarov: /* GlyNAC (combination of glycine and N-acetylcysteine) */

2023-05-05T18:07:35Z

GlyNAC (combination of glycine and N-acetylcysteine)

← Older revision		Revision as of 18:07, 5 May 2023
Line 21:		Line 21:

	=== GlyNAC (combination of glycine and N-acetylcysteine) ===		=== GlyNAC (combination of glycine and N-acetylcysteine) ===
	Cellular increases in oxidative stress and decline in mitochondrial function are identified as key defects in aging. Defects linked to oxidative stress and impaired mitochondrial fuel oxidation, such as inflammation, insulin resistance, endothelial dysfunction, and aging hallmarks, are present in older humans and are associated with declining strength and cognition, as well as the development of sarcopenic obesity. Investigations on the origins of elevated oxidative stress and mitochondrial dysfunction in older humans led to the discovery that deficiencies of the antioxidant tripeptide glutathione (γ-Glutamylcysteinylglycine) and its precursor amino acids glycine and cysteine may be contributory. Supplementation with GlyNAC (combination of glycine and N-acetylcysteine as a cysteine precursor) was found to improve/correct cellular glycine, cysteine, and glutathione deficiencies; lower oxidative stress; and improve mitochondrial function, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, and multiple aging hallmarks; and improve muscle strength, exercise capacity, cognition, and body composition.<ref name="GlyNAC"/><ref>Sekhar, R. V. (2021). GlyNAC supplementation improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, aging hallmarks, metabolic defects, muscle strength, cognitive decline, and body composition: Implications for healthy aging. The Journal of Nutrition, 151(12), 3606-3616. PMID: 34587244 DOI: [https://doi.org/10.1093/jn/nxab309 10.1093/jn/nxab309]</ref> ~~'''The mice that received GlyNAC lived 24% longer than those that did not receive GlyNAC'''.<ref name="GlyNAC"/>~~		Cellular increases in oxidative stress and decline in mitochondrial function are identified as key defects in aging. Defects linked to oxidative stress and impaired mitochondrial fuel oxidation, such as inflammation, insulin resistance, endothelial dysfunction, and aging hallmarks, are present in older humans and are associated with declining strength and cognition, as well as the development of sarcopenic obesity. Investigations on the origins of elevated oxidative stress and mitochondrial dysfunction in older humans led to the discovery that deficiencies of the antioxidant tripeptide glutathione (γ-Glutamylcysteinylglycine) and its precursor amino acids glycine and cysteine may be contributory. Supplementation with GlyNAC (combination of glycine and N-acetylcysteine as a cysteine precursor) was found to improve/correct cellular glycine, cysteine, and glutathione deficiencies; lower oxidative stress; and improve mitochondrial function, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, and multiple aging hallmarks; and improve muscle strength, exercise capacity, cognition, and body composition.<ref name="GlyNAC"/><ref>Sekhar, R. V. (2021). GlyNAC supplementation improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, aging hallmarks, metabolic defects, muscle strength, cognitive decline, and body composition: Implications for healthy aging. The Journal of Nutrition, 151(12), 3606-3616. PMID: 34587244 DOI: [https://doi.org/10.1093/jn/nxab309 10.1093/jn/nxab309]</ref><ref>Kumar, P., Liu, C., Suliburk, J., Hsu, J. W., Muthupillai, R., Jahoor, F., ... & Sekhar, R. V. (2023). 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, 78(1), 75-89. PMID: 35975308 PMCID: PMC9879756 (available on 2023-08-17) DOI: 10.1093/gerona/glac135</ref><ref>Kumar, P., Liu, C., Hsu, J. W., Chacko, S., Minard, C., Jahoor, F., & Sekhar, R. V. (2021). 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. Clinical and Translational Medicine, 11(3), e372. PMID: 33783984 PMCID: PMC8002905 DOI: 10.1002/ctm2.372</ref> '''The mice that received GlyNAC lived 24% longer than those that did not receive GlyNAC'''.<ref name="GlyNAC"/>

	<ref>Kumar, P., Liu, C., Suliburk, J., Hsu, J. W., Muthupillai, R., Jahoor, F., ... & Sekhar, R. V. (2023). 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, 78(1), 75-89. PMID: 35975308 PMCID: PMC9879756 (available on 2023-08-17) DOI: 10.1093/gerona/glac135</ref><ref>Kumar, P., Liu, C., Hsu, J. W., Chacko, S., Minard, C., Jahoor, F., & Sekhar, R. V. (2021). 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. Clinical and Translational Medicine, 11(3), e372. PMID: 33783984 PMCID: PMC8002905 DOI: 10.1002/ctm2.372</ref>

	Glycine is genetically associated with lower coronary heart disease risk and lower incidence of type 2 diabetes.<ref>Wittemans, L. B., Lotta, L. A., Oliver-Williams, C., Stewart, I. D., Surendran, P., Karthikeyan, S., ... & Langenberg, C. (2019). Assessing the causal association of glycine with risk of cardio-metabolic diseases. Nature communications, 10(1), 1060. PMID: 30837465 PMCID: PMC6400990 DOI: 10.1038/s41467-019-08936-1</ref> Glycine improved the endothelium function in aged rats possibly by enhancing eNOS expression and reducing the role of superoxide anion and contractile prostanoids that increase the nitric oxide bioavailability.<ref>Gómez-Zamudio, J. H., García-Macedo, R., Lázaro-Suárez, M., Ibarra-Barajas, M., Kumate, J., & Cruz, M. (2015). Vascular endothelial function is improved by oral glycine treatment in aged rats. Canadian Journal of Physiology and Pharmacology, 93(6), 465-473. PMID: 25988540 DOI: 10.1139/cjpp-2014-0393</ref><ref>Zakaria, E. R., Joseph, B., Hamidi, M., Zeeshan, M., Algamal, A., Sartaj, F., ... & Madan, D. (2019). Glycine improves peritoneal vasoreactivity to dialysis solutions in the elderly. Qatar Medical Journal, 2019(3), 19. PMID: 31903325 PMCID: PMC6929513 DOI: 10.5339/qmj.2019.19</ref>		Glycine is genetically associated with lower coronary heart disease risk and lower incidence of type 2 diabetes.<ref>Wittemans, L. B., Lotta, L. A., Oliver-Williams, C., Stewart, I. D., Surendran, P., Karthikeyan, S., ... & Langenberg, C. (2019). Assessing the causal association of glycine with risk of cardio-metabolic diseases. Nature communications, 10(1), 1060. PMID: 30837465 PMCID: PMC6400990 DOI: 10.1038/s41467-019-08936-1</ref> Glycine improved the endothelium function in aged rats possibly by enhancing eNOS expression and reducing the role of superoxide anion and contractile prostanoids that increase the nitric oxide bioavailability.<ref>Gómez-Zamudio, J. H., García-Macedo, R., Lázaro-Suárez, M., Ibarra-Barajas, M., Kumate, J., & Cruz, M. (2015). Vascular endothelial function is improved by oral glycine treatment in aged rats. Canadian Journal of Physiology and Pharmacology, 93(6), 465-473. PMID: 25988540 DOI: 10.1139/cjpp-2014-0393</ref><ref>Zakaria, E. R., Joseph, B., Hamidi, M., Zeeshan, M., Algamal, A., Sartaj, F., ... & Madan, D. (2019). Glycine improves peritoneal vasoreactivity to dialysis solutions in the elderly. Qatar Medical Journal, 2019(3), 19. PMID: 31903325 PMCID: PMC6929513 DOI: 10.5339/qmj.2019.19</ref>

Dmitry Dzhagarov: /* GlyNAC (combination of glycine and N-acetylcysteine) */

2023-05-05T18:03:55Z

GlyNAC (combination of glycine and N-acetylcysteine)

← Older revision		Revision as of 18:03, 5 May 2023
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	=== GlyNAC (combination of glycine and N-acetylcysteine) ===		=== GlyNAC (combination of glycine and N-acetylcysteine) ===
	Cellular increases in oxidative stress and decline in mitochondrial function are identified as key defects in aging. Defects linked to oxidative stress and impaired mitochondrial fuel oxidation, such as inflammation, insulin resistance, endothelial dysfunction, and aging hallmarks, are present in older humans and are associated with declining strength and cognition, as well as the development of sarcopenic obesity. Investigations on the origins of elevated oxidative stress and mitochondrial dysfunction in older humans led to the discovery that deficiencies of the antioxidant tripeptide glutathione (γ-Glutamylcysteinylglycine) and its precursor amino acids glycine and cysteine may be contributory. Supplementation with GlyNAC (combination of glycine and N-acetylcysteine as a cysteine precursor) was found to improve/correct cellular glycine, cysteine, and glutathione deficiencies; lower oxidative stress; and improve mitochondrial function, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, and multiple aging hallmarks; and improve muscle strength, exercise capacity, cognition, and body composition.<ref name="GlyNAC"/><ref>Sekhar, R. V. (2021). GlyNAC supplementation improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, aging hallmarks, metabolic defects, muscle strength, cognitive decline, and body composition: Implications for healthy aging. The Journal of Nutrition, 151(12), 3606-3616. PMID: 34587244 DOI: [https://doi.org/10.1093/jn/nxab309 10.1093/jn/nxab309]</ref>		Cellular increases in oxidative stress and decline in mitochondrial function are identified as key defects in aging. Defects linked to oxidative stress and impaired mitochondrial fuel oxidation, such as inflammation, insulin resistance, endothelial dysfunction, and aging hallmarks, are present in older humans and are associated with declining strength and cognition, as well as the development of sarcopenic obesity. Investigations on the origins of elevated oxidative stress and mitochondrial dysfunction in older humans led to the discovery that deficiencies of the antioxidant tripeptide glutathione (γ-Glutamylcysteinylglycine) and its precursor amino acids glycine and cysteine may be contributory. Supplementation with GlyNAC (combination of glycine and N-acetylcysteine as a cysteine precursor) was found to improve/correct cellular glycine, cysteine, and glutathione deficiencies; lower oxidative stress; and improve mitochondrial function, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, and multiple aging hallmarks; and improve muscle strength, exercise capacity, cognition, and body composition.<ref name="GlyNAC"/><ref>Sekhar, R. V. (2021). GlyNAC supplementation improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, aging hallmarks, metabolic defects, muscle strength, cognitive decline, and body composition: Implications for healthy aging. The Journal of Nutrition, 151(12), 3606-3616. PMID: 34587244 DOI: [https://doi.org/10.1093/jn/nxab309 10.1093/jn/nxab309]</ref> '''The mice that received GlyNAC lived 24% longer than those that did not receive GlyNAC'''.<ref name="GlyNAC"/>

	<ref>Kumar, P., Liu, C., Suliburk, J., Hsu, J. W., Muthupillai, R., Jahoor, F., ... & Sekhar, R. V. (2023). 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, 78(1), 75-89. PMID: 35975308 PMCID: PMC9879756 (available on 2023-08-17) DOI: 10.1093/gerona/glac135</ref><ref>Kumar, P., Liu, C., Hsu, J. W., Chacko, S., Minard, C., Jahoor, F., & Sekhar, R. V. (2021). 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. Clinical and Translational Medicine, 11(3), e372. PMID: 33783984 PMCID: PMC8002905 DOI: 10.1002/ctm2.372</ref>		<ref>Kumar, P., Liu, C., Suliburk, J., Hsu, J. W., Muthupillai, R., Jahoor, F., ... & Sekhar, R. V. (2023). 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, 78(1), 75-89. PMID: 35975308 PMCID: PMC9879756 (available on 2023-08-17) DOI: 10.1093/gerona/glac135</ref><ref>Kumar, P., Liu, C., Hsu, J. W., Chacko, S., Minard, C., Jahoor, F., & Sekhar, R. V. (2021). 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. Clinical and Translational Medicine, 11(3), e372. PMID: 33783984 PMCID: PMC8002905 DOI: 10.1002/ctm2.372</ref>

Dmitry Dzhagarov at 17:52, 5 May 2023

2023-05-05T17:52:33Z

← Older revision		Revision as of 17:52, 5 May 2023
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	PMID: 35268089 PMCID: PMC8912885 DOI: 10.3390/nu14051114 </ref><ref>Brind, J., Malloy, V., Augie, I., Caliendo, N., Vogelman, J. H., Zimmerman, J. A., & Orentreich, N. (2011). Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 rats. https://doi.org/10.1096/fasebj.25.1_supplement.528.2</ref><ref>Liu, Y. J., Janssens, G. E., McIntyre, R. L., Molenaars, M., Kamble, R., Gao, A. W., ... & Houtkooper, R. H. (2019). Glycine promotes longevity in Caenorhabditis elegans in a methionine cycle-dependent fashion. PLoS genetics, 15(3), e1007633. PMID: 30845140 PMCID: PMC6424468 DOI: 10.1371/journal.pgen.1007633</ref><ref>Johnson, A. A., & Cuellar, T. L. (2023). Glycine and aging: Evidence and mechanisms. Ageing Research Reviews, 101922. PMID: 37004845 DOI: 10.1016/j.arr.2023.101922</ref>		PMID: 35268089 PMCID: PMC8912885 DOI: 10.3390/nu14051114 </ref><ref>Brind, J., Malloy, V., Augie, I., Caliendo, N., Vogelman, J. H., Zimmerman, J. A., & Orentreich, N. (2011). Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 rats. https://doi.org/10.1096/fasebj.25.1_supplement.528.2</ref><ref>Liu, Y. J., Janssens, G. E., McIntyre, R. L., Molenaars, M., Kamble, R., Gao, A. W., ... & Houtkooper, R. H. (2019). Glycine promotes longevity in Caenorhabditis elegans in a methionine cycle-dependent fashion. PLoS genetics, 15(3), e1007633. PMID: 30845140 PMCID: PMC6424468 DOI: 10.1371/journal.pgen.1007633</ref><ref>Johnson, A. A., & Cuellar, T. L. (2023). Glycine and aging: Evidence and mechanisms. Ageing Research Reviews, 101922. PMID: 37004845 DOI: 10.1016/j.arr.2023.101922</ref>

	== GlyNAC (combination of glycine and N-acetylcysteine) ==		=== GlyNAC (combination of glycine and N-acetylcysteine) ===
	Cellular increases in oxidative stress and decline in mitochondrial function are identified as key defects in aging. Defects linked to oxidative stress and impaired mitochondrial fuel oxidation, such as inflammation, insulin resistance, endothelial dysfunction, and aging hallmarks, are present in older humans and are associated with declining strength and cognition, as well as the development of sarcopenic obesity. Investigations on the origins of elevated oxidative stress and mitochondrial dysfunction in older humans led to the discovery that deficiencies of the antioxidant tripeptide glutathione (γ-Glutamylcysteinylglycine) and its precursor amino acids glycine and cysteine may be contributory. Supplementation with GlyNAC (combination of glycine and N-acetylcysteine as a cysteine precursor) was found to improve/correct cellular glycine, cysteine, and glutathione deficiencies; lower oxidative stress; and improve mitochondrial function, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, and multiple aging hallmarks; and improve muscle strength, exercise capacity, cognition, and body composition.<ref name="GlyNAC"/><ref>Sekhar, R. V. (2021). GlyNAC supplementation improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, aging hallmarks, metabolic defects, muscle strength, cognitive decline, and body composition: Implications for healthy aging. The Journal of Nutrition, 151(12), 3606-3616. PMID: 34587244 DOI: [https://doi.org/10.1093/jn/nxab309 10.1093/jn/nxab309]</ref>		Cellular increases in oxidative stress and decline in mitochondrial function are identified as key defects in aging. Defects linked to oxidative stress and impaired mitochondrial fuel oxidation, such as inflammation, insulin resistance, endothelial dysfunction, and aging hallmarks, are present in older humans and are associated with declining strength and cognition, as well as the development of sarcopenic obesity. Investigations on the origins of elevated oxidative stress and mitochondrial dysfunction in older humans led to the discovery that deficiencies of the antioxidant tripeptide glutathione (γ-Glutamylcysteinylglycine) and its precursor amino acids glycine and cysteine may be contributory. Supplementation with GlyNAC (combination of glycine and N-acetylcysteine as a cysteine precursor) was found to improve/correct cellular glycine, cysteine, and glutathione deficiencies; lower oxidative stress; and improve mitochondrial function, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, and multiple aging hallmarks; and improve muscle strength, exercise capacity, cognition, and body composition.<ref name="GlyNAC"/><ref>Sekhar, R. V. (2021). GlyNAC supplementation improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, aging hallmarks, metabolic defects, muscle strength, cognitive decline, and body composition: Implications for healthy aging. The Journal of Nutrition, 151(12), 3606-3616. PMID: 34587244 DOI: [https://doi.org/10.1093/jn/nxab309 10.1093/jn/nxab309]</ref>

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	Because glycine residues occupy 1/3 of amino acid residues in collagen protein,<ref>Nassa, M., Anand, P., Jain, A., Chhabra, A., Jaiswal, A., Malhotra, U., & Rani, V. (2012). Analysis of human collagen sequences. Bioinformation, 8(1), 26. PMID: 22359431 PMCID: PMC3282272 DOI: 10.6026/97320630008026</ref> the supply of glycine may be a limiting factor for collagen synthesis and must be present in the diet in large amounts to satisfy the demands for collagen synthesis for prevention of '''osteoarthritis'''.<ref>de Paz-Lugo, P., Lupiáñez, J. A., & Meléndez-Hevia, E. (2018). High glycine concentration increases collagen synthesis by articular chondrocytes in vitro: acute glycine deficiency could be an important cause of osteoarthritis. Amino Acids, 50(10), 1357-1365. PMID: 30006659 PMCID: PMC6153947 DOI: 10.1007/s00726-018-2611-x</ref> An optimized form of glycine precursor '''glycinamide (2-aminoacetamide)''' increased collagen production much more effectively than glycine, especially synergistically in combination with ascorbic acid.<ref>Lee, J. E., & Boo, Y. C. (2022). Combination of Glycinamide and Ascorbic Acid Synergistically Promotes Collagen Production and Wound Healing in Human Dermal Fibroblasts. Biomedicines, 10(5), 1029. PMID: 35625765 PMCID: PMC9138459 DOI: 10.3390/biomedicines10051029</ref> Moreover, some '''2-aminoacetamide derivatives''' have good anti-inflammatory activity. Among them, compound '''f15''' showed the most prominent performance and blocked the excitation of nuclear factor κB (NF-кB) signaling pathway in a concentration-dependent manner. Furthermore, in-vivo experiment showed that '''f15''' reduced arthritic index in adjuvant-induced arthritis rats and '''inhibited the production of TNF-α and IL-1β''' in serum.<ref>Liu, T., Zhu, Y., Chen, S., Du, J., Xing, S., Dong, S., ... & Li, Z. (2022). Protective effects of (4-(1, 2, 4-oxadiazol-5-yl) phenyl)-2-aminoacetamide derivatives to adjuvant-induced arthritis rats by regulating the NF-κB signaling pathway. Inflammopharmacology, 30(6), 2417-2426. PMID: 36203113 DOI: 10.1007/s10787-022-01081-0</ref>		Because glycine residues occupy 1/3 of amino acid residues in collagen protein,<ref>Nassa, M., Anand, P., Jain, A., Chhabra, A., Jaiswal, A., Malhotra, U., & Rani, V. (2012). Analysis of human collagen sequences. Bioinformation, 8(1), 26. PMID: 22359431 PMCID: PMC3282272 DOI: 10.6026/97320630008026</ref> the supply of glycine may be a limiting factor for collagen synthesis and must be present in the diet in large amounts to satisfy the demands for collagen synthesis for prevention of '''osteoarthritis'''.<ref>de Paz-Lugo, P., Lupiáñez, J. A., & Meléndez-Hevia, E. (2018). High glycine concentration increases collagen synthesis by articular chondrocytes in vitro: acute glycine deficiency could be an important cause of osteoarthritis. Amino Acids, 50(10), 1357-1365. PMID: 30006659 PMCID: PMC6153947 DOI: 10.1007/s00726-018-2611-x</ref> An optimized form of glycine precursor '''glycinamide (2-aminoacetamide)''' increased collagen production much more effectively than glycine, especially synergistically in combination with ascorbic acid.<ref>Lee, J. E., & Boo, Y. C. (2022). Combination of Glycinamide and Ascorbic Acid Synergistically Promotes Collagen Production and Wound Healing in Human Dermal Fibroblasts. Biomedicines, 10(5), 1029. PMID: 35625765 PMCID: PMC9138459 DOI: 10.3390/biomedicines10051029</ref> Moreover, some '''2-aminoacetamide derivatives''' have good anti-inflammatory activity. Among them, compound '''f15''' showed the most prominent performance and blocked the excitation of nuclear factor κB (NF-кB) signaling pathway in a concentration-dependent manner. Furthermore, in-vivo experiment showed that '''f15''' reduced arthritic index in adjuvant-induced arthritis rats and '''inhibited the production of TNF-α and IL-1β''' in serum.<ref>Liu, T., Zhu, Y., Chen, S., Du, J., Xing, S., Dong, S., ... & Li, Z. (2022). Protective effects of (4-(1, 2, 4-oxadiazol-5-yl) phenyl)-2-aminoacetamide derivatives to adjuvant-induced arthritis rats by regulating the NF-κB signaling pathway. Inflammopharmacology, 30(6), 2417-2426. PMID: 36203113 DOI: 10.1007/s10787-022-01081-0</ref>

	== Glycine improves sleep quality ==		=== Glycine improves sleep quality ===
	Glycine at a dose of 3 g/day before bedtime subjectively '''improves sleep quality''' and reduces sleepiness and fatigue during the day in individuals with insomniac tendencies or restricted sleep time. Glycine administration before bedtime also '''decreases core body temperature''' in human subjects.<ref>Kawai, N., Sakai, N., Okuro, M., Karakawa, S., Tsuneyoshi, Y., Kawasaki, N., ... & Nishino, S. (2015). The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. Neuropsychopharmacology, 40(6), 1405-1416. PMID: 25533534 PMCID: PMC4397399 DOI: 10.1038/npp.2014.326</ref>		Glycine at a dose of 3 g/day before bedtime subjectively '''improves sleep quality''' and reduces sleepiness and fatigue during the day in individuals with insomniac tendencies or restricted sleep time. Glycine administration before bedtime also '''decreases core body temperature''' in human subjects.<ref>Kawai, N., Sakai, N., Okuro, M., Karakawa, S., Tsuneyoshi, Y., Kawasaki, N., ... & Nishino, S. (2015). The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. Neuropsychopharmacology, 40(6), 1405-1416. PMID: 25533534 PMCID: PMC4397399 DOI: 10.1038/npp.2014.326</ref>

Dmitry Dzhagarov at 17:50, 5 May 2023

2023-05-05T17:50:54Z

← Older revision		Revision as of 17:50, 5 May 2023
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	'''Glycine (aminoacetic acid)''' is most important and simple, nonessential amino acid in humans, animals, and many mammals.<ref>Razak, M. A., Begum, P. S., Viswanath, B., & Rajagopal, S. (2017). Multifarious beneficial effect of nonessential amino acid, glycine: a review. Oxidative medicine and cellular longevity, 2017:1716701. PMID: 28337245 PMCID: PMC5350494 DOI: 10.1155/2017/1716701</ref> Glycine is a precursor for several important compounds such as creatine, purines and glucose, and is involved in a wide range of metabolic pathways.<ref>Wang, W., Wu, Z., Dai, Z., Yang, Y., Wang, J., & Wu, G. (2013). Glycine metabolism in animals and humans: implications for nutrition and health. Amino acids, 45, 463-477. PMID: 23615880 DOI: 10.1007/s00726-013-1493-1</ref> Besides participating in synthesizing structural biomolecules, glycine serves as one of the predecessors of glutathione, one of the most important antioxidants in the human body.<ref>Sekhar, R. V., Patel, S. G., Guthikonda, A. P., Reid, M., Balasubramanyam, A., Taffet, G. E., & Jahoor, F. (2011). Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation–. The American journal of clinical nutrition, 94(3), 847-853. PMID: 21795440 PMCID: PMC3155927 DOI: 10.3945/ajcn.110.003483</ref><ref>Sekhar, R. V., McKay, S. V., Patel, S. G., Guthikonda, A. P., Reddy, V. T., Balasubramanyam, A., & Jahoor, F. (2011). Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Diabetes care, 34(1), 162-167. PMID: 20929994 PMCID: PMC3005481 DOI: 10.2337/dc10-1006</ref><ref>Ruiz-Ramírez, A., Ortiz-Balderas, E., Cardozo-Saldaña, G., Diaz-Diaz, E., & El-Hafidi, M. (2014). Glycine restores glutathione and protects against oxidative stress in vascular tissue from sucrose-fed rats. Clinical Science, 126(1), 19-29. PMID: 23742196 DOI: 10.1042/CS20130164</ref>		'''Glycine (aminoacetic acid)''' is most important and simple, nonessential amino acid in humans, animals, and many mammals.<ref>Razak, M. A., Begum, P. S., Viswanath, B., & Rajagopal, S. (2017). Multifarious beneficial effect of nonessential amino acid, glycine: a review. Oxidative medicine and cellular longevity, 2017:1716701. PMID: 28337245 PMCID: PMC5350494 DOI: 10.1155/2017/1716701</ref> Glycine is a precursor for several important compounds such as creatine, purines and glucose, and is involved in a wide range of metabolic pathways.<ref>Wang, W., Wu, Z., Dai, Z., Yang, Y., Wang, J., & Wu, G. (2013). Glycine metabolism in animals and humans: implications for nutrition and health. Amino acids, 45, 463-477. PMID: 23615880 DOI: 10.1007/s00726-013-1493-1</ref> Besides participating in synthesizing structural biomolecules, glycine serves as one of the predecessors of glutathione, one of the most important antioxidants in the human body.<ref>Sekhar, R. V., Patel, S. G., Guthikonda, A. P., Reid, M., Balasubramanyam, A., Taffet, G. E., & Jahoor, F. (2011). Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation–. The American journal of clinical nutrition, 94(3), 847-853. PMID: 21795440 PMCID: PMC3155927 DOI: 10.3945/ajcn.110.003483</ref><ref>Sekhar, R. V., McKay, S. V., Patel, S. G., Guthikonda, A. P., Reddy, V. T., Balasubramanyam, A., & Jahoor, F. (2011). Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Diabetes care, 34(1), 162-167. PMID: 20929994 PMCID: PMC3005481 DOI: 10.2337/dc10-1006</ref><ref>Ruiz-Ramírez, A., Ortiz-Balderas, E., Cardozo-Saldaña, G., Diaz-Diaz, E., & El-Hafidi, M. (2014). Glycine restores glutathione and protects against oxidative stress in vascular tissue from sucrose-fed rats. Clinical Science, 126(1), 19-29. PMID: 23742196 DOI: 10.1042/CS20130164</ref>

	'''Glycine supplementation has been shown to extend lifespan in various animal models'''.<ref>Miller, R. A., Harrison, D. E., Astle, C. M., Bogue, M. A., Brind, J., Fernandez, E., ... & Strong, R. (2019). Glycine supplementation extends lifespan of male and female mice. Aging cell, 18(3), e12953. PMID: 30916479 PMCID: PMC6516426 DOI: 10.1111/acel.12953</ref><ref>Kumar, P., Osahon, O. W., & Sekhar, R. V. (2022). GlyNAC (glycine and N-acetylcysteine) supplementation in mice increases length of life by correcting glutathione deficiency, oxidative stress, mitochondrial dysfunction, abnormalities in mitophagy and nutrient sensing, and genomic damage. Nutrients, 14(5), 1114.		'''Glycine supplementation has been shown to extend lifespan in various animal models'''.<ref>Miller, R. A., Harrison, D. E., Astle, C. M., Bogue, M. A., Brind, J., Fernandez, E., ... & Strong, R. (2019). Glycine supplementation extends lifespan of male and female mice. Aging cell, 18(3), e12953. PMID: 30916479 PMCID: PMC6516426 DOI: 10.1111/acel.12953</ref> <ref name="GlyNAC" >Kumar, P., Osahon, O. W., & Sekhar, R. V. (2022). GlyNAC (glycine and N-acetylcysteine) supplementation in mice increases length of life by correcting glutathione deficiency, oxidative stress, mitochondrial dysfunction, abnormalities in mitophagy and nutrient sensing, and genomic damage. Nutrients, 14(5), 1114.
	PMID: 35268089 PMCID: PMC8912885 DOI: 10.3390/nu14051114 </ref><ref>Brind, J., Malloy, V., Augie, I., Caliendo, N., Vogelman, J. H., Zimmerman, J. A., & Orentreich, N. (2011). Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 rats. https://doi.org/10.1096/fasebj.25.1_supplement.528.2</ref><ref>Liu, Y. J., Janssens, G. E., McIntyre, R. L., Molenaars, M., Kamble, R., Gao, A. W., ... & Houtkooper, R. H. (2019). Glycine promotes longevity in Caenorhabditis elegans in a methionine cycle-dependent fashion. PLoS genetics, 15(3), e1007633. PMID: 30845140 PMCID: PMC6424468 DOI: 10.1371/journal.pgen.1007633</ref><ref>Johnson, A. A., & Cuellar, T. L. (2023). Glycine and aging: Evidence and mechanisms. Ageing Research Reviews, 101922. PMID: 37004845 DOI: 10.1016/j.arr.2023.101922</ref>		PMID: 35268089 PMCID: PMC8912885 DOI: 10.3390/nu14051114 </ref><ref>Brind, J., Malloy, V., Augie, I., Caliendo, N., Vogelman, J. H., Zimmerman, J. A., & Orentreich, N. (2011). Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 rats. https://doi.org/10.1096/fasebj.25.1_supplement.528.2</ref><ref>Liu, Y. J., Janssens, G. E., McIntyre, R. L., Molenaars, M., Kamble, R., Gao, A. W., ... & Houtkooper, R. H. (2019). Glycine promotes longevity in Caenorhabditis elegans in a methionine cycle-dependent fashion. PLoS genetics, 15(3), e1007633. PMID: 30845140 PMCID: PMC6424468 DOI: 10.1371/journal.pgen.1007633</ref><ref>Johnson, A. A., & Cuellar, T. L. (2023). Glycine and aging: Evidence and mechanisms. Ageing Research Reviews, 101922. PMID: 37004845 DOI: 10.1016/j.arr.2023.101922</ref>

			== GlyNAC (combination of glycine and N-acetylcysteine) ==
			Cellular increases in oxidative stress and decline in mitochondrial function are identified as key defects in aging. Defects linked to oxidative stress and impaired mitochondrial fuel oxidation, such as inflammation, insulin resistance, endothelial dysfunction, and aging hallmarks, are present in older humans and are associated with declining strength and cognition, as well as the development of sarcopenic obesity. Investigations on the origins of elevated oxidative stress and mitochondrial dysfunction in older humans led to the discovery that deficiencies of the antioxidant tripeptide glutathione (γ-Glutamylcysteinylglycine) and its precursor amino acids glycine and cysteine may be contributory. Supplementation with GlyNAC (combination of glycine and N-acetylcysteine as a cysteine precursor) was found to improve/correct cellular glycine, cysteine, and glutathione deficiencies; lower oxidative stress; and improve mitochondrial function, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, and multiple aging hallmarks; and improve muscle strength, exercise capacity, cognition, and body composition.<ref name="GlyNAC"/><ref>Sekhar, R. V. (2021). GlyNAC supplementation improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, aging hallmarks, metabolic defects, muscle strength, cognitive decline, and body composition: Implications for healthy aging. The Journal of Nutrition, 151(12), 3606-3616. PMID: 34587244 DOI: [https://doi.org/10.1093/jn/nxab309 10.1093/jn/nxab309]</ref>

			<ref>Kumar, P., Liu, C., Suliburk, J., Hsu, J. W., Muthupillai, R., Jahoor, F., ... & Sekhar, R. V. (2023). 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, 78(1), 75-89. PMID: 35975308 PMCID: PMC9879756 (available on 2023-08-17) DOI: 10.1093/gerona/glac135</ref><ref>Kumar, P., Liu, C., Hsu, J. W., Chacko, S., Minard, C., Jahoor, F., & Sekhar, R. V. (2021). 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. Clinical and Translational Medicine, 11(3), e372. PMID: 33783984 PMCID: PMC8002905 DOI: 10.1002/ctm2.372</ref>

	Glycine is genetically associated with lower coronary heart disease risk and lower incidence of type 2 diabetes.<ref>Wittemans, L. B., Lotta, L. A., Oliver-Williams, C., Stewart, I. D., Surendran, P., Karthikeyan, S., ... & Langenberg, C. (2019). Assessing the causal association of glycine with risk of cardio-metabolic diseases. Nature communications, 10(1), 1060. PMID: 30837465 PMCID: PMC6400990 DOI: 10.1038/s41467-019-08936-1</ref> Glycine improved the endothelium function in aged rats possibly by enhancing eNOS expression and reducing the role of superoxide anion and contractile prostanoids that increase the nitric oxide bioavailability.<ref>Gómez-Zamudio, J. H., García-Macedo, R., Lázaro-Suárez, M., Ibarra-Barajas, M., Kumate, J., & Cruz, M. (2015). Vascular endothelial function is improved by oral glycine treatment in aged rats. Canadian Journal of Physiology and Pharmacology, 93(6), 465-473. PMID: 25988540 DOI: 10.1139/cjpp-2014-0393</ref><ref>Zakaria, E. R., Joseph, B., Hamidi, M., Zeeshan, M., Algamal, A., Sartaj, F., ... & Madan, D. (2019). Glycine improves peritoneal vasoreactivity to dialysis solutions in the elderly. Qatar Medical Journal, 2019(3), 19. PMID: 31903325 PMCID: PMC6929513 DOI: 10.5339/qmj.2019.19</ref>		Glycine is genetically associated with lower coronary heart disease risk and lower incidence of type 2 diabetes.<ref>Wittemans, L. B., Lotta, L. A., Oliver-Williams, C., Stewart, I. D., Surendran, P., Karthikeyan, S., ... & Langenberg, C. (2019). Assessing the causal association of glycine with risk of cardio-metabolic diseases. Nature communications, 10(1), 1060. PMID: 30837465 PMCID: PMC6400990 DOI: 10.1038/s41467-019-08936-1</ref> Glycine improved the endothelium function in aged rats possibly by enhancing eNOS expression and reducing the role of superoxide anion and contractile prostanoids that increase the nitric oxide bioavailability.<ref>Gómez-Zamudio, J. H., García-Macedo, R., Lázaro-Suárez, M., Ibarra-Barajas, M., Kumate, J., & Cruz, M. (2015). Vascular endothelial function is improved by oral glycine treatment in aged rats. Canadian Journal of Physiology and Pharmacology, 93(6), 465-473. PMID: 25988540 DOI: 10.1139/cjpp-2014-0393</ref><ref>Zakaria, E. R., Joseph, B., Hamidi, M., Zeeshan, M., Algamal, A., Sartaj, F., ... & Madan, D. (2019). Glycine improves peritoneal vasoreactivity to dialysis solutions in the elderly. Qatar Medical Journal, 2019(3), 19. PMID: 31903325 PMCID: PMC6929513 DOI: 10.5339/qmj.2019.19</ref>

Dmitry Dzhagarov at 14:33, 5 May 2023

2023-05-05T14:33:23Z

← Older revision		Revision as of 14:33, 5 May 2023
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			[[File:Glycine.jpg\|thumb\|
			{\| class="wikitable"
			\|-
			! Glycine (Aminoacetic acid, Aminoethanoic acid, Glycocoll)
			\|-
			\| Molecular Weight: 75.07
			\|-
			\| Chemical formula: C<sub>2</sub>H<sub>5</sub>NO<sub>2</sub>
			\|-
			\| Linear Formula: NH<sub>2</sub>CH<sub>2</sub>COOH
			\|-
			\| CASNo = 56-40-6, CASNo =
			(HCl): 6000-43-7
			\|-
			\| ATC code [https://icdcode.info/atc-ddd/index-b05cx03.html B05CX03]
			\|} ]]
	'''Glycine (aminoacetic acid)''' is most important and simple, nonessential amino acid in humans, animals, and many mammals.<ref>Razak, M. A., Begum, P. S., Viswanath, B., & Rajagopal, S. (2017). Multifarious beneficial effect of nonessential amino acid, glycine: a review. Oxidative medicine and cellular longevity, 2017:1716701. PMID: 28337245 PMCID: PMC5350494 DOI: 10.1155/2017/1716701</ref> Glycine is a precursor for several important compounds such as creatine, purines and glucose, and is involved in a wide range of metabolic pathways.<ref>Wang, W., Wu, Z., Dai, Z., Yang, Y., Wang, J., & Wu, G. (2013). Glycine metabolism in animals and humans: implications for nutrition and health. Amino acids, 45, 463-477. PMID: 23615880 DOI: 10.1007/s00726-013-1493-1</ref> Besides participating in synthesizing structural biomolecules, glycine serves as one of the predecessors of glutathione, one of the most important antioxidants in the human body.<ref>Sekhar, R. V., Patel, S. G., Guthikonda, A. P., Reid, M., Balasubramanyam, A., Taffet, G. E., & Jahoor, F. (2011). Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation–. The American journal of clinical nutrition, 94(3), 847-853. PMID: 21795440 PMCID: PMC3155927 DOI: 10.3945/ajcn.110.003483</ref><ref>Sekhar, R. V., McKay, S. V., Patel, S. G., Guthikonda, A. P., Reddy, V. T., Balasubramanyam, A., & Jahoor, F. (2011). Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Diabetes care, 34(1), 162-167. PMID: 20929994 PMCID: PMC3005481 DOI: 10.2337/dc10-1006</ref><ref>Ruiz-Ramírez, A., Ortiz-Balderas, E., Cardozo-Saldaña, G., Diaz-Diaz, E., & El-Hafidi, M. (2014). Glycine restores glutathione and protects against oxidative stress in vascular tissue from sucrose-fed rats. Clinical Science, 126(1), 19-29. PMID: 23742196 DOI: 10.1042/CS20130164</ref>		'''Glycine (aminoacetic acid)''' is most important and simple, nonessential amino acid in humans, animals, and many mammals.<ref>Razak, M. A., Begum, P. S., Viswanath, B., & Rajagopal, S. (2017). Multifarious beneficial effect of nonessential amino acid, glycine: a review. Oxidative medicine and cellular longevity, 2017:1716701. PMID: 28337245 PMCID: PMC5350494 DOI: 10.1155/2017/1716701</ref> Glycine is a precursor for several important compounds such as creatine, purines and glucose, and is involved in a wide range of metabolic pathways.<ref>Wang, W., Wu, Z., Dai, Z., Yang, Y., Wang, J., & Wu, G. (2013). Glycine metabolism in animals and humans: implications for nutrition and health. Amino acids, 45, 463-477. PMID: 23615880 DOI: 10.1007/s00726-013-1493-1</ref> Besides participating in synthesizing structural biomolecules, glycine serves as one of the predecessors of glutathione, one of the most important antioxidants in the human body.<ref>Sekhar, R. V., Patel, S. G., Guthikonda, A. P., Reid, M., Balasubramanyam, A., Taffet, G. E., & Jahoor, F. (2011). Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation–. The American journal of clinical nutrition, 94(3), 847-853. PMID: 21795440 PMCID: PMC3155927 DOI: 10.3945/ajcn.110.003483</ref><ref>Sekhar, R. V., McKay, S. V., Patel, S. G., Guthikonda, A. P., Reddy, V. T., Balasubramanyam, A., & Jahoor, F. (2011). Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Diabetes care, 34(1), 162-167. PMID: 20929994 PMCID: PMC3005481 DOI: 10.2337/dc10-1006</ref><ref>Ruiz-Ramírez, A., Ortiz-Balderas, E., Cardozo-Saldaña, G., Diaz-Diaz, E., & El-Hafidi, M. (2014). Glycine restores glutathione and protects against oxidative stress in vascular tissue from sucrose-fed rats. Clinical Science, 126(1), 19-29. PMID: 23742196 DOI: 10.1042/CS20130164</ref>

Dmitry Dzhagarov at 11:53, 5 May 2023

2023-05-05T11:53:22Z

← Older revision		Revision as of 11:53, 5 May 2023
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	Glycine serves as the acceptor for a methylation reaction catalyzed by glycine N-methyltransferase, which takes a methyl group from S-adenosyl-L-methionine and transfers it to glycine to form sarcosine (methylglycine) and S-adenosyl-L-homocysteine. Glycine N-methyltransferase prolongs life in flies when overexpressed.<ref>Tain, L. S., Jain, C., Nespital, T., Froehlich, J., Hinze, Y., Grönke, S., & Partridge, L. (2020). Longevity in response to lowered insulin signaling requires glycine N‐methyltransferase‐dependent spermidine production. Aging Cell, 19(1), e13043. PMID: 31721422 PMCID: PMC6974722 DOI: 10.1111/acel.13043</ref>		Glycine serves as the acceptor for a methylation reaction catalyzed by glycine N-methyltransferase, which takes a methyl group from S-adenosyl-L-methionine and transfers it to glycine to form sarcosine (methylglycine) and S-adenosyl-L-homocysteine. Glycine N-methyltransferase prolongs life in flies when overexpressed.<ref>Tain, L. S., Jain, C., Nespital, T., Froehlich, J., Hinze, Y., Grönke, S., & Partridge, L. (2020). Longevity in response to lowered insulin signaling requires glycine N‐methyltransferase‐dependent spermidine production. Aging Cell, 19(1), e13043. PMID: 31721422 PMCID: PMC6974722 DOI: 10.1111/acel.13043</ref>

	Because glycine residues occupy 1/3 of amino acid residues in collagen protein,<ref>Nassa, M., Anand, P., Jain, A., Chhabra, A., Jaiswal, A., Malhotra, U., & Rani, V. (2012). Analysis of human collagen sequences. Bioinformation, 8(1), 26. PMID: 22359431 PMCID: PMC3282272 DOI: 10.6026/97320630008026</ref> the supply of glycine may be a limiting factor for collagen synthesis and must be present in the diet in large amounts to satisfy the demands for collagen synthesis for prevention of '''osteoarthritis'''.<ref>de Paz-Lugo, P., Lupiáñez, J. A., & Meléndez-Hevia, E. (2018). High glycine concentration increases collagen synthesis by articular chondrocytes in vitro: acute glycine deficiency could be an important cause of osteoarthritis. Amino Acids, 50(10), 1357-1365. PMID: 30006659 PMCID: PMC6153947 DOI: 10.1007/s00726-018-2611-x</ref> An optimized form of glycine precursor '''glycinamide''' increased collagen production much more effectively than glycine, especially synergistically in combination with ascorbic acid.<ref>Lee, J. E., & Boo, Y. C. (2022). Combination of Glycinamide and Ascorbic Acid Synergistically Promotes Collagen Production and Wound Healing in Human Dermal Fibroblasts. Biomedicines, 10(5), 1029. PMID: 35625765 PMCID: PMC9138459 DOI: 10.3390/biomedicines10051029</ref>		[[File:Glycinamide (2-aminoacetamide) hydrochloride.jpg\|thumb\|Glycinamide (2-aminoacetamide) hydrochloride]]
			Because glycine residues occupy 1/3 of amino acid residues in collagen protein,<ref>Nassa, M., Anand, P., Jain, A., Chhabra, A., Jaiswal, A., Malhotra, U., & Rani, V. (2012). Analysis of human collagen sequences. Bioinformation, 8(1), 26. PMID: 22359431 PMCID: PMC3282272 DOI: 10.6026/97320630008026</ref> the supply of glycine may be a limiting factor for collagen synthesis and must be present in the diet in large amounts to satisfy the demands for collagen synthesis for prevention of '''osteoarthritis'''.<ref>de Paz-Lugo, P., Lupiáñez, J. A., & Meléndez-Hevia, E. (2018). High glycine concentration increases collagen synthesis by articular chondrocytes in vitro: acute glycine deficiency could be an important cause of osteoarthritis. Amino Acids, 50(10), 1357-1365. PMID: 30006659 PMCID: PMC6153947 DOI: 10.1007/s00726-018-2611-x</ref> An optimized form of glycine precursor '''glycinamide (2-aminoacetamide)''' increased collagen production much more effectively than glycine, especially synergistically in combination with ascorbic acid.<ref>Lee, J. E., & Boo, Y. C. (2022). Combination of Glycinamide and Ascorbic Acid Synergistically Promotes Collagen Production and Wound Healing in Human Dermal Fibroblasts. Biomedicines, 10(5), 1029. PMID: 35625765 PMCID: PMC9138459 DOI: 10.3390/biomedicines10051029</ref> Moreover, some '''2-aminoacetamide derivatives''' have good anti-inflammatory activity. Among them, compound '''f15''' showed the most prominent performance and blocked the excitation of nuclear factor κB (NF-кB) signaling pathway in a concentration-dependent manner. Furthermore, in-vivo experiment showed that '''f15''' reduced arthritic index in adjuvant-induced arthritis rats and '''inhibited the production of TNF-α and IL-1β''' in serum.<ref>Liu, T., Zhu, Y., Chen, S., Du, J., Xing, S., Dong, S., ... & Li, Z. (2022). Protective effects of (4-(1, 2, 4-oxadiazol-5-yl) phenyl)-2-aminoacetamide derivatives to adjuvant-induced arthritis rats by regulating the NF-κB signaling pathway. Inflammopharmacology, 30(6), 2417-2426. PMID: 36203113 DOI: 10.1007/s10787-022-01081-0</ref>

			== Glycine improves sleep quality ==
			Glycine at a dose of 3 g/day before bedtime subjectively '''improves sleep quality''' and reduces sleepiness and fatigue during the day in individuals with insomniac tendencies or restricted sleep time. Glycine administration before bedtime also '''decreases core body temperature''' in human subjects.<ref>Kawai, N., Sakai, N., Okuro, M., Karakawa, S., Tsuneyoshi, Y., Kawasaki, N., ... & Nishino, S. (2015). The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. Neuropsychopharmacology, 40(6), 1405-1416. PMID: 25533534 PMCID: PMC4397399 DOI: 10.1038/npp.2014.326</ref>

	== References ==		== References ==