Monday, December 30, 2013

Health Benefits of Glycine

1. Preface

Glycine is an amino acid, and it is generally considered non-essential because we can usually synthesize some glycine from amino acids serine and threonine and from some other compounds as well.

However, I have seen a compelling amount of evidence showing that body cannot necessarily produce enough glycine for optimal health, and therefore it might be beneficial to get generous amounts glycine from dietary sources.




2. Dietary requirements

A French-Spanish research group, in their review article (2009), wrote that humans can usually synthesize 3 grams of glycine, and they usually get 1.5-3.0 additional grams from the diet, so the total yield is 4.5-6 grams.

On the other hand, they stated that this amount doesn't satisfy the daily need of 10-13 grams for collagen synthesis in various tissues (bone, muscle, skin), and therefore glycine should be considered a semi-essential amino acid.[1]

"This result supports earlier suggestions in the literature that glycine is a semi-essential amino acid and that it should be taken as a nutritional supplement to guarantee a healthy metabolism" - (Meléndez-Hevia et al. 2009)




3. Health effects of glycine (animal studies)

"Glycine is recognized as an “inhibitory” neurotransmitter, and promotes natural sleep. Used as a supplement, it has helped to promote recovery from strokes and seizures, and to improve learning and memory. But in every type of cell, it apparently has the same kind of quieting, protective antistress action. The range of injuries produced by an excess of tryptophan and serotonin seems to be prevented or corrected by a generous supply of glycine. Fibrosis, free radical damage, inflammation, cell death from ATP depletion or calcium overload, mitochondrial damage, diabetes, etc., can be prevented or alleviated by glycine." - Ray Peat


Most of the glycine research has been conducted in rodent studies, usually by replacing a fraction of dietary protein with glycine or by using 1% glycine solution instead of normal drinking water.

In the animal studies I could find, the results were surprisingly good. Glycine
  • protects rats from diabetes-induced harmful effects on kidneys, eyes, blood sugar, immune function and total mortality[2]
  • slows tumor growth in rats and mice[3]
  • dramatically decreases the negative effects of sucrose and ethanol in rats[4]
  • prolongs the lifespan of rats, possibly by mimicking the effect of methionine restriction[5]
  • protects rats from the harmful effects of excess methionine[5]
  • protects dogs, rats and rabbits from ischemia (lack of oxygen in the tissue)[6]
  • protects rats and mice from endotoxin-induced damage[7]
  • protects rats from lethal sepsis[7]
  • protects rats from liver injury caused by methionine or choline restriction, alcohol, chemotherapy, bile duct ligation, partial hepatectomy, hemorrhagic shock, sepsis, Cyclosporin A or corn oil[8]
  • protects rats from kidney injury[35]
  • protects rats from hemorrhagic shock[9]
  • protects rats from acid reflux esophagitis[10]
  • protects rats from high blood pressure and vascular dysfunction caused by a low-protein diet (9% casein) during pregnancy[11]
  • protects chickens from body fat gain caused by a low-protein diet (supplemented w/glutamic acid)[11]
  • protects rats from hypercholesterolemia induced by casein and cholesterol[12]
  • protects rabbits from hypercholesterolemia and atherosclerosis induced by casein[12]
  • protects rats from hypercholesterolemia caused by methionine[5]
  • protects rats from lead toxicity[13]
  • protects rats from dental caries[14]
  • protects rats from experimental colitis, and gastric ulcers/lesions[15]
  • protects rats from experimental arthritis[16]
  • protects rats from Achilles tendon inflammation[17]
  • protects rats from pancreatitis[36]
  • protects ovariectomized rats from osteoporosis[27]
  • protects hamsters from chemotherapy-caused oral mucositis[34]
  • reduces platelet aggregation in rats[18]
  • reduces the birth defects caused by Tretinoin,  cadmium or hyperglycemia[19]
  • reduces the production of pro-inflammatory cytokines (TNF-α, IL-6) and increases adiponectin in mice[20]



4. Health effects of glycine (human studies)

However, not as many human studies have been conducted. As noted in some human trials...
  • Glycine might improve some health markers (HbA1c, IFN-gamma, TBARS, TNFalpha receptor) a little bit in patients with metabolic syndrome or diabetes, but the effect wasn't nearly as dramatic as in animal studies. Diabetic patients have 26% lower serum glycine levels than "normal" population.[21]
  • Combination of glycine and cysteine has been studied in diabetic patients, HIV patients and elderly persons. The combination has been shown to significantly increase glutathione synthesis, insulin sensitivity and mitochondrial fuel oxidation and to decrease NEFA levels, lipid peroxidation and F2 isoprostanes. These results are extremely interesting, and more data will be published in the future.[22]
  • Glycine powerfully protected from neurological damage caused by stroke. 1 or 2 grams of glycine a day taken sublingually for five days after the stroke decreased the risk of moderate to severe disability by 66%, cerebrospinal fluid lipid peroxides by 50% and mortality by 40% compared to placebo.[23]
  • Glycine might improve sleep quality.[24]
  • Glycine improved schizophrenia symptoms in large doses (usually 0.8g/kg/d), though it doesn't seem to augment the effect of clozapine.[25]
  • Glycine improved the absorption of aspirin, and dramatically decreases the gastrointestinal side effects.[26]

One large study, which hasn't been published in a scientific journal but has been reported on a news site, showed that glycine could relieve arthrosis, osteoporosis and related diseases very effectively:
The work of De Paz Lugo was developed at the Cellular Metabolism Institute (CMI) in Tenerife, where researchers studied the effect of the glycine supplement on the diet of a group of 600 volunteers affected by different diseases related to the mechanical structure of the organism such as arthrosis, physical injuries or osteoporosis. The patients analysed were aged 4-85, and the average age was 45. 
In all cases, there was a notable improvement in the symptomology. "Thefore -- according to De Paz Lugo -- we concluded that many degenerative diseases such as arthrosis can be treated as deficiency diseases due to the lack of glycine, since supplementing a diet with this amino acid leads to a notable improvement in symptomology without the need to take pain-killers."

Collagen protein is approximately 22% glycine by weight, so the health effects achieved by collagen supplementation could also be related to its' glycine content. Though, in some studies, collagen might have effects via a mechanism called oral tolerance (OT).

In rats and mice, collagen protects from osteoporosis[27], but similar effect wasn't found in humans. In humans it could be beneficial for osteoarthritis[27], rheumatoid arthritis[27], joint pain[27], pressure ulcer[28], hair loss[29], nails[29] and skin health (collagen content, elasticity, etc.)[30].

The effects on the skin and bone are logical, because these tissues contain high amounts of collagen/glycine. However, a large part of effects are probably related to the general anti-inflammatory properties of glycine.

French researcher reported that 25g of gelatin daily "rapidly relieves urinary symptoms" accompanying benign prostatic hyperplasia, and it was concluded that "gelatin can be very useful in the treatment of this disorder". Some impressive results have also been obtained with the combination of amino acids glycine, alanine and glutamic acid, which all are abundant in gelatin.[31]

Russian researchers have also reported that glycine might be beneficial for trigeminal neuralgia.[37]

Glycine has also failed to bring benefits for heart surgery and arterial stenosis, even though animal studies regarding cardiovascular system have been very promising.[38]



5. Mechanisms

The protective effects of glycine can be partially explained by glycine's inhibitory effects. Glycine can hyperpolarize certain immune cells via glycine-gated chloride channels, decreasing the amount of toxic mediators (TNF-α, IL-6) released in response to endotoxin and other stimuli.[32]

This is probably the best explanation why glycine gives a very strong protection against the possible harms of fructose and ethanol and probably fats as well.[32] By a similar mechanism, it's possible that glycine also protects from atherosclerosis and some other diseases but this hasn't been investigated in humans.[32]

It has also been suggested that some of glycine's positive effects are due to increased secretion of glucagon-like peptide-1 (GLP-1).[32] Since watching William Li's TED talk Can we eat to starve cancer?, I have also been thinking about the significance of glycine's anti-angiogenic effects. In some rodent studies, inhibition of angiogenesis has also protected animals from obesity.

Because of its liver-protecting properties, glycine might also increase the conversion of T4 to T3 in liver (via deiodinases). So far, this has only been studied in a rainbow trout study, with a positive result.[32]

In his book, Broda Barnes wrote that high-protein diets decrease thyroid function. Biologist Ray Peat's take on the subject is that insufficient protein intake is one of the main causes of low thyroid function, but muscle meats have a large amount of antimetabolic amino acids. Therefore he suggests that a large part of daily protein intake could be in the form of gelatin.

A popular health author Denise Minger has argued that the "harmfulness" of animal protein (or methionine) could actually be caused by the insufficient glycine intake on high-methionine diets that include muscle meat, milk and eggs. As shown above, some studies have demonstrated that glycine can decrease the possible harms of casein and methionine. Some animal proteins (scallop, cod) seem to have important health-promoting effects due to their high glycine and taurine content.[33]
"In conclusion, intake of scallop muscle as the sole dietary protein source completely prevented high-fat, high-sucrose-induced body mass gain and fat accretion without affecting lean body mass. Furthermore, scallop feeding improved plasma lipid profile in C57BL/6J mice compared to mice fed diets with protein from chicken, cod or crab. Correlation analyses revealed strong, highly significant inverse correlations between intake of taurine and glycine and body fat mass, as well as strong, highly significant correlations between glycine and especially taurine intake and improved plasma lipid profiles." (Tastesen et al. 2014)




6. Dietary sources of glycine

"[T]extbook writers from the 19th century on have rated gelatin a "poor quality protein." But in spite of its seeming limitations, gelatin was valued for its medicinal benefits for thousands of years and was long considered a panacea for everything from skin and joint disorders to digestive distress to heart ailments." Kaayla T. Daniel


Biologist Ray Peat has written that collagen makes up about 50% of the protein in an animal. Considering this information, we can assume that some traditional cultures probably had quite high glycine intake if they consumed skin and bones, and not only muscle meat.

The traditional way to achieve higher dietary intake of glycine would be to consume skin and bone broth, but some other foods such as ground meathead cheese and jello also contain some gelatin (cooked form of collagen).

The straightforward way to get more gelatin is to use a nutritional supplement. I usually mix 1-2 tablespoons of gelatin powder to my chocolate milk before heating* the drink. Some dietary supplement stores also sell glycine powder and capsules.

Magnesium (bis)glycinate supplements have 6:1 ratio of magnesium:glycine, so eating 350mg magnesium (as magnesium glycinate) daily should yield approximately 2 grams of (di)glycine.




7. Conclusions

"Dietary supplementation with an appropriate dose of glycine is effective in ameliorating metabolic disorders in patients with obesity, diabetes, cardiovascular disease, ischemia-reperfusion injuries, various inflammatory diseases, and cancers." (Wang et al. 2013)


The results of glycine studies have been mostly quite positive, and it's nice to see that it could possibly ameliorate a wide spectrum of health problems and protect against the health problems caused by dietary fat, fructose, ethanol and some types of animal protein. However, we do still need additional data from human trials.

In the paleosphere, a growing number of writers have been recommending the consumption of bone brothsskin and organs. Based on these findings, I think this is a good trend, compared to some previous recommendations of high consumption of lean meat.

In addition to glycine, we should also try to investigate the potential health effects of other amino acids and peptides. Especially taurine, histidine and carnosine might have potentially beneficial anti-inflammatory effects. I have investigated this issue a little bit in my article Good Proteins, Bad Proteins.






Notes

* I use microwave oven to heat the chocolate milk. However, in her article, Kaayla T. Daniel argues that microwaves can turn proline into poisonous d-proline and therefore "if you heat it [gelatin] in the microwave, it becomes toxic to the liver, kidneys and nervous system". She refers to this paper (Lubec et al).

However, I suspect that as usual, some misinterpretations might have happened. Paul Jaminet has written that some of he anti-microwave claims are based on quite poor science (Do Microwaves Destroy Flavonoids?).

According to one paper (pdf), the Lubec study was conducted "under pressure in 174 to 176°C". There is also another paper that doesn't seem to show that domestic microwaving would be more harmful than some other heating methods.




Slideshow (with a focus on metabolic syndrome)


Glycine: The Versatile Anti-inflammatory Nutrient (by Vladimir Heiskanen)






References

[0] Review articles

[x] Amino Acids. 2013 Sep;45(3):463-77. Glycine metabolism in animals and humans: implications for nutrition and health. Wang W, Wu Z, Dai Z, Yang Y, Wang J, Wu G.

[x] Curr Opin Clin Nutr Metab Care. 2003 Mar;6(2):229-40. L-Glycine: a novel antiinflammatory, immunomodulatory, and cytoprotective agent. Zhong Z, Wheeler MD, Li X, Froh M, Schemmer P, Yin M, Bunzendaul H, Bradford B, Lemasters JJ.

[x] Alcohol Clin Exp Res. 2005 Nov;29(1ai1 Suppl):162S-5S. Glycine as a therapeutic immuno-nutrient for alcoholic liver disease. Yamashina S, Ikejima K, Enomoto N, Takei Y, Sato N.

[x] Open Heart 2014;1:e000103. The cardiometabolic benefits of glycine: Is glycine an ‘antidote’ to dietary fructose? Mark F McCarty, James J DiNicolantonio "The plasma concentration of glycine in normally nourished individuals—around 200 µM—is near the Km for activation of these channels, implying that the severalfold increases in plasma glycine achievable with practical supplementation can be expected to further activate these channels in vivo."

[x] Front Mol Neurosci. 2009 Aug 20;2:9. Glycine and glycine receptor signalling in non-neuronal cells. den Eynden JV, Ali SS, Horwood N, Carmans S, Brône B, Hellings N, Steels P, Harvey RJ, Rigo JM.


[x] Cell Mol Life Sci. 2016 Apr 11. [Epub ahead of print] The role of glycine in regulated cell death. Weinberg JM, Bienholz A, Venkatachalam MA. [An extremely extensive review on the cellular effects of glycine.]

[x] Wikipedia - Gelatin#Medical and nutritional properties

[x] Examine.com - Glycine

[x] Chris Masterjohn - Beyond Good and Evil

[x] Raymond F. Peat - Gelatin, stress, longevity

[x] Kaayla T. Daniel - Why Broth is Beautiful: Essential Roles for Proline, Glycine and Gelatin

[x] Wise Choice Market - Benefits of Bone Broth

[x] The poor, misunderstood calorie - Protein dilemma ~ sleepy or smart. #Gelatin

[x] Sweetamine.com - The Breakthrough Science of Sweetamine

[x] YouTube - The anti-Inflammatory properties of the amino acid glycine part 1
[x] YouTube - Anti-Inflammatory characteristics of glycine Part 2





[1] Glycine dietary requirements

[x] J Biosci. 2009 Dec;34(6):853-72. A weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis. Meléndez-Hevia E, De Paz-Lugo P, Cornish-Bowden A, Cárdenas ML.

[x] Amino Acids. 2013 Sep;45(3):463-77. Glycine metabolism in animals and humans: implications for nutrition and health. Wang W, Wu Z, Dai Z, Yang Y, Wang J, Wu G.

[x] J Biosci. 2008 Dec;33(5):771-80. Branch-point stoichiometry can generate weak links in metabolism: the case of glycine biosynthesis. Melendez-Hevia E, Paz-Lugo PD. "A critical weak link is created in glycine biosynthesis by the stoichiometry of the reaction catalyzed by glycine hydroxymethyltransferase (EC 2.1.2.1), which converts serine into glycine plus one C1 unit: this produces an absolute dependence of the glycine production flux on the utilization of C1 units for other metabolic pathways that do not work coordinately with glycine use. It may not be possible, therefore, to ensure that glycine is always synthesized in sufficient quantities to meet optimal metabolic requirements."

[x] Br J Nutr. 1987 Sep;58(2):207-14. Urinary excretion of 5-oxoproline (pyroglutamic aciduria) as an index of glycine insufficiency in normal man. Jackson AA, Badaloo AV, Forrester T, Hibbert JM, Persaud C. 


[x] Drug Metab Rev. 2014 Apr 22. A new perspective on the importance of glycine conjugation in the metabolism of aromatic acids. Badenhorst CP, Erasmus E, van der Sluis R, Nortje C, van Dijk AA. "In this review it will be argued that the major role of glycine conjugation is to dispose of the end products of phenylpropionate metabolism. Furthermore, glucuronidation, which occurs in the endoplasmic reticulum, would not be ideal for the detoxification of free benzoate, which has been shown to accumulate in the mitochondrial matrix. Glycine conjugation, however, prevents accumulation of benzoic acid in the mitochondrial matrix by forming hippurate, a less lipophilic conjugate that can be more readily transported out of the mitochondria. Finally, it will be explained that the glycine conjugation of benzoate, a commonly used preservative, exacerbates the dietary deficiency of glycine in humans. Because the resulting shortage of glycine can negatively influence brain neurochemistry and the synthesis of collagen, nucleic acids, porphyrins, and other important metabolites, the risks of using benzoate as a preservative should not be underestimated."

[x] Amino Acids. 2017 Sep 20. doi: 10.1007/s00726-017-2490-6. Roles of dietary glycine, proline, and hydroxyproline in collagen synthesis and animal growth. Li P, Wu G. "Results of the recent studies indicate that endogenous synthesis of glycine, proline, and Hyp is inadequate for maximal growth, collagen production, or feed efficiency in pigs, chickens, and fish."




[2] Glycine and diabetic complications

[x] Comp Biochem Physiol C Toxicol Pharmacol. 2003 Apr;134(4):521-7. Effect of glycine in streptozotocin-induced diabetic rats. Alvarado-Vásquez N, Zamudio P, Cerón E, Vanda B, Zenteno E, Carvajal-Sandoval G.

[x] Mol Vis. 2012;18:439-48. Glycine therapy inhibits the progression of cataract in streptozotocin-induced diabetic rats. Bahmani F, Bathaie SZ, Aldavood SJ, Ghahghaei A.

[x] Rev Alerg Mex. 2006 Nov-Dec;53(6):212-6. Effect of glycine on the immune response of the experimentally diabetic rats. Lezcano Meza D, Terán Ortiz L, Carvajal Sandoval G, Gutiérrez de la Cadena M, Terán Escandón D, Estrada Parra S.

[x] Rev Med Chil. 2010 Oct;138(10):1246-52. [Effects of glycine on auditory evoked potentials among diabetic patients with auditory pathway neuropathy]. [Article in Spanish] Muñoz-Carlin Mde L, Rodríguez-Moctezuma JR, Gómez Latorre JG, Montes-Castillo ML, Juárez-Adauta S.

[x] Life Sci. 2006 Jun 13;79(3):225-32. Oral glycine administration attenuates diabetic complications in streptozotocin-induced diabetic rats. Alvarado-Vásquez N, Lascurain R, Cerón E, Vanda B, Carvajal-Sandoval G, Tapia A, Guevara J, Montaño LF, Zenteno E.

[x] Journal of Kerman University of Medical Sciences 2014;21 Assessment of Oral Glycine and Lysine Therapy on Receptor for Advanced Glycation End Products and Transforming Growth Factor Beta Expression in the Kidney of Streptozotocin-Induced Diabetic Rats in Comparison with Normal Rats. Somayeh Sadat Heidary, M.Sc., et al.


[x] Journal of Experimental & Clinical Medicine 2013;5:109-114 Effect of Glycine on Protein Oxidation and Advanced Glycation End Products Formation Salinas Arreortua Noe, García Lorenzana Mario, Genoveva Durán Reyes, Villagómez Jasso Edgar Iván, Alarcón Aguilar Francisco Javier, Gómez Olivares José Luis "The experimental data demonstrate that glycine reduced glucose, HbA1C, and fructosamine levels in blood. Even more, glycine significantly reduced AGE-BSA conformation, but the reduction of protein oxidation occurred only in the kidneys."




[3] Glycine, cancer, angiogenesis and cachexia

[x] Cancer Biol Ther. 2003 Mar-Apr;2(2):173-8. Dietary glycine inhibits angiogenesis during wound healing and tumor growth. Amin K, Li J, Chao WR, Dewhirst MW, Haroon ZA.

[x] Carcinogenesis. 1999 Nov;20(11):2075-81. Dietary glycine prevents the development of liver tumors caused by the peroxisome proliferator WY-14,643. Rose ML, Cattley RC, Dunn C, Wong V, Li X, Thurman RG.


[x] Carcinogenesis. 1997 Aug;18(8):1453-6. Kupffer cells are causally responsible for the mitogenic effect of peroxisome proliferators. Rose ML, Germolec DR, Schoonhoven R, Thurman RG.

[x] Carcinogenesis. 1999 May;20(5):793-8. Dietary glycine inhibits the growth of B16 melanoma tumors in mice. Rose ML, Madren J, Bunzendahl H, Thurman RG.

[x] Clin Nutr. 2013 Jun 26. pii: S0261-5614(13)00185-4. Glycine administration attenuates skeletal muscle wasting in a mouse model of cancer cachexia. Ham DJ, Murphy KT, Chee A, Lynch GS, Koopman R.


[x] Amino Acids. 2016 Jun 28. Glycine inhibits angiogenesis in colorectal cancer: role of endothelial cells. Bruns H, Kazanavicius D, Schultze D, Saeedi MA, Yamanaka K, Strupas K, Schemmer P.

[x] Nutr Cancer. 2001;40(2):197-204. Endothelial cells contain a glycine-gated chloride channel. Yamashina S, Konno A, Wheeler MD, Rusyn I, Rusyn EV, Cox AD, Thurman RG. "Importantly, glycine diminished serum-stimulated proliferation and migration of endothelial cells. Collectively, these data indicate that the inhibitory effect of glycine on growth and migration of endothelial cells is due to activation of a glycine-gated Cl- channel. This hyperpolarizes the cell membrane and blocks influx of Ca2+, thereby minimizing growth factor-mediated signaling."

[x] J Gastroenterol Hepatol. 2007 Jun;22 Suppl 1:S62-4. Glycine as a potent anti-angiogenic nutrient for tumor growth. Yamashina S, Ikejima K, Rusyn I, Sato N.

[x] Trends Biochem Sci. 2014 Apr;39(4):191-198. Serine and glycine metabolism in cancer. Amelio I, Cutruzzolá F, Antonov A, Agostini M, Melino G. [Ray Peat: "When tumors aren't getting enough sugar and fat, they cause proteins to be broken down, and glutamine, glycine, and serine can be used for energy. But when glycine is present in the diet, it has various anti-tumor effects."]

[x] Cell Rep. 2014 May 22;7(4):1248-58. Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells. Labuschagne CF, van den Broek NJ, Mackay GM, Vousden KH, Maddocks OD. "Although serine and glycine can be interconverted and either might be used for nucleotide synthesis and one-carbon metabolism, we show that exogenous glycine cannot replace serine to support cancer cell proliferation."

[x] Asia Pac J Clin Nutr. 2014 Sep;23(3):429-36. Plasma and tissue free amino acid profiles and their concentration correlation in patients with lung cancer. Zhao Q, Cao Y, Wang Y, Hu C, Hu A, Ruan L, Bo Q, Liu Q, Chen W, Tao F, Ren M, Ge Y, Chen A, Li L. "Within the PFAAs, the concentrations of five amino acids (tryptophan, glycine, citrulline, ornithine and proline) were significantly decreased, while that of phenylalanine was markedly increased compared with control subjects. Within the TFAAs, the concentrations of three amino acids (taurine, glutamic acid and glycine) were increased, while the concentrations of two amino acids (lysine and ornithine) were decreased significantly in lung cancer tissues compared with the paracarcinomous tissues."

[x] Amino Acids. 2014 Apr;46(4):969-76. Glycine inhibits angiogenic signaling in human hepatocellular carcinoma cells. Bruns H, Petrulionis M, Schultze D, Al Saeedi M, Lin S, Yamanaka K, Ambrazevičius M, Strupas K, Schemmer P.




[4] Glycine protects from sugar and ethanol (animal studies)

[x] Am J Physiol Regul Integr Comp Physiol. 2004 Dec;287(6):R1387-93. Glycine intake decreases plasma free fatty acids, adipose cell size, and blood pressure in sucrose-fed rats. El Hafidi M, Pérez I, Zamora J, Soto V, Carvajal-Sandoval G, Baños G.

[x] Can J Physiol Pharmacol. 2011 Nov 24. [Epub ahead of print] Effect of glycine on the cyclooxygenase pathway of the kidney arachidonic acid metabolism in a rat model of metabolic syndrome. Pérez-Torres I, Ibarra B, Soria-Castro E, Torrico-Lavayen R, Pavón N, Diaz-Diaz E, Flores PL, Infante O, Baños G.

[x] Cell Biochem Funct. 2004 Mar-Apr;22(2):123-8. Protective effect of glycine supplementation on the levels of lipid peroxidation and antioxidant enzymes in the erythrocyte of rats with alcohol-induced liver injury. Senthilkumar R, Sengottuvelan M, Nalini N.

[x] Clin Sci (Lond). 2014 Jan 1;126(1):19-29. Glycine restores glutathione and protects against oxidative stress in vascular tissue from sucrose-fed rats. Ruiz-Ramírez A, Ortiz-Balderas E, Cardozo-Saldaña G, Diaz-Diaz E, El-Hafidi M.

[x] Internet Journal of Pharmacology 2003;2:1-12 Glycine Modulates Lipid And Lipoprotein Levels In Rats With Alcohol Induced Liver Injury. Senthilkumar, Rajagopal; Nalini, Namasivayam "[glycine] reduced the levels of tissue and serum cholesterol, triglycerides and lipoproteins significantly as compared with the unsupplemented alcohol treated rats. [...] alcohol treated rat brain demonstrated edema, which was markedly reduced on treatment with glycine."

[x] Amino Acids. 2014 Mar 23. [Epub ahead of print] Scallop protein with endogenous high taurine and glycine content prevents high-fat, high-sucrose-induced obesity and improves plasma lipid profile in male C57BL/6J mice. Tastesen HS, Keenan AH, Madsen L, Kristiansen K, Liaset B. (via ergo-log)


[x] Curr Drug Deliv. 2016;13(1):158-69. Effect of Glycine on Adipocyte Hypertrophy in a Metabolic Syndrome Rat Model. López YR, Pérez-Torres I1, Zúñiga-Muñoz A, Lans VG, Díaz-Díaz E, Castro ES, Espejel RV.

[x] Neurochem Int. 2016 Apr 4. pii: S0197-0186(16)30049-3. Glycine inhibits ethanol-induced oxidative stress, neuroinflammation and apoptotic neurodegeneration in postnatal rat brain. Amin FU, Shah SA, Kim MO.

[x] Oncotarget. 2016 Oct 23. doi: 10.18632/oncotarget.12831. Glycine protects against high sucrose and high fat-induced non-alcoholic steatohepatitis in rats. Zhou X, Han D, Xu R, Wu H, Qu C, Wang F, Wang X, Zhao Y.




[5] Glycine, methionine, lifespan and cholesterol levels

[x] The FASEB Journal. 2011;25:528.2. Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 rats. Brind J, Malloy V, Augie I, Caliendo N, Vogelman JH, Zimmerman JA, Orentreich N. "We propose that more efficient Met clearance via GNMT with GS could be reducing chronic Met toxicity due to rogue methylations from chronic excess methylation capacity or oxidative stress from generation of toxic by-products such as formaldehyde."

[x] J Nutr Sci Vitaminol (Tokyo). 1987 Jun;33(3):195-205. Effect of dietary glycine on methionine metabolism in rats fed a high-methionine diet. Sugiyama K, Kushima Y, Muramatsu K.

[x] Proc Soc Exp Biol Med. 1949 Feb;70(2):327-30. The effect of feeding excess glycine, L-arginine, and DL-methionine to rats on a casein diet. ROTH JS, ALLISON JB.

[x] Biosci Biotechnol Biochem. 2006 Oct;70(10):2403-9. Suppression of methionine-induced hyperhomocysteinemia by glycine and serine in rats. Fukada S, Shimada Y, Morita T, Sugiyama K.

[x] Arch Biochem Biophys. 1993 Feb 1;300(2):598-607. Methionine toxicity in the rat in relation to hepatic accumulation of S-adenosylmethionine: prevention by dietary stimulation of the hepatic transsulfuration pathway. Regina M, Korhonen VP, Smith TK, Alakuijala L, Eloranta TO.

[x] Fukada, Shin-ichiro, Tatsuya Morita, and Kimio Sugiyama. "Effects of various amino acids on methionine-induced hyperhomocysteinemia in rats." Bioscience, biotechnology, and biochemistry 72.7 (2008): 1940-1943.


[x] Circ Res. 1959 Mar;7(2):224-7. Effect of taurine, glycine and beta-sitosterols on serum and tissue cholesterol in the rat and rabbit. HERRMANN RG. "Glycine was without any significant effect."

[x] Nahrung. 1980;24(7):663-71. The hypolipaemic action of a glycine rich diet in rats. Aust L, Poledne R, Elhabet A, Noack R.

[x] J Nutr Sci Vitaminol (Tokyo). 1986 Aug;32(4):413-23. Relationship between amino acid composition of diet and plasma cholesterol level in growing rats fed a high cholesterol diet. Sugiyama K, Ohkawa S, Muramatsu K.

[x] J Nutr Sci Vitaminol (Tokyo). 1990 Feb;36(1):45-54. Effects of dietary methionine and glycine on serum lipoprotein profiles and fecal sterol excretion in normal and hepatoma-bearing rats. Yagasaki K, Machida-Takehana M, Funabiki R.

[x] J Nutr Sci Vitaminol (Tokyo). 1986 Dec;32(6):643-51. Effects of dietary methionine, cystine, and glycine on endogenous hypercholesterolemia in hepatoma-bearing rats. Yagasaki K, Machida M, Funabiki R.

[x] J Nutr Sci Vitaminol (Tokyo). 1990 Oct;36 Suppl 2:S165-8. Effects of dietary supplemented amino acids on endogenous hypercholesterolemia in rats. Yagasaki K, Funabiki R.

[x] J Nutr Sci Vitaminol (Tokyo). 1990 Oct;36 Suppl 2:S105-10. Significance of the amino acid composition of dietary protein in the regulation of plasma cholesterol. Sugiyama K, Muramatsu K. "diets high in methionine and low in cystine and glycine content tend to increase the plasma cholesterol level and diets of opposite amino acid content tend to decrease the plasma cholesterol level."

[x] Br J Nutr. 2005 Sep;94(3):321-30. Dietary proteins with high isoflavone content or low methionine-glycine and lysine-arginine ratios are hypocholesterolaemic and lower the plasma homocysteine level in male Zucker fa/fa rats. Gudbrandsen OA, Wergedahl H, Liaset B, Espe M, Berge RK.

[x] Br J Nutr. 1997 Sep;78(3):459-67. Influence of dietary protein and fat on serum lipids and metabolism of essential fatty acids in rats. Ratnayake WM, Sarwar G, Laffey P. "Gelatin was hypocholesterolaemic and also suppressed the liver phospholipid levels of AA and DHA (reported for the first time)."

[x] Agricultural and Biological Chemistry Vol. 53 (1989) No. 6 P 1647-1652 Comparison between the Plasma Cholesterol-lowering Effects of Glycine and Taurine in Rats Fed on High Cholesterol Diets Kimio SUGIYAMA, Akio OHISHI, Yukari OHNUMA, Keiichiro MURAMATSU "The plasma cholesterol-lowering effect of Gly could not be fully explained by the stimulation of fecal bile acid excretion, whereas the effect of Tau appeared to be associated with the fecal bile acid excretion."

[x] Food Science and Technology Research Vol. 19 (2013) No. 6 p. 1149-1153 Effects of Collagen Peptide Ingestion on Blood Lipids in Rats Fed a High-Lipid and High-Sucrose Diet Yoh-ichi KOYAMA, Masashi KUSUBATA "0.2 g/kg body weight collagen peptide was administered for 29 days to male Crlj:CD (SD) rats fed a high-lipid and high-sucrose diet [...] total cholesterol, particularly LDL, was significantly lower in rats given collagen peptide than in control rats"


[x] Nutrition Research Volume 19, Issue 12, December 1999, Pages 1777–1789 Dietary taurine or glycine supplementation reduces plasma and liver cholesterol and triglyceride concentrations in rats fed a cholesterol-free diet Taesun Park, Ph.D., Jooyeon Oh, M.S., Kyungshin Lee, M.S. "Both TSD and GSD significantly lowered the plasma levels of total cholesterol (40% decrease in TSD, p<0.001 and 27% decrease in GSD, p<0.001, respectively)"




[6] Glycine and ischemia-reperfusion injury (skeletal muscle, heart, intestine, kidneys, liver)

[x] Surgery. 2001 Feb;129(2):231-5. Glycine preserves function and decreases necrosis in skeletal muscle undergoing ischemia and reperfusion injury. Ascher E, Hanson JN, Cheng W, Hingorani A, Scheinman M.

[x] Br J Pharmacol. 2012 Apr;165(7):2059-72. Glycine, a simple physiological compound protecting by yet puzzling mechanism(s) against ischaemia-reperfusion injury: current knowledge. Petrat F, Boengler K, Schulz R, de Groot H.

[x] Eur Surg Res. 2011;46(4):180-7. Protection from glycine at low doses in ischemia-reperfusion injury of the rat small intestine. Petrat F, Drowatzky J, Boengler K, Finckh B, Schmitz KJ, Schulz R, de Groot H.


[x] J Vasc Surg. 2003 Nov;38(5):1113-20. Protective effect of glycine in mesenteric ischemia and reperfusion injury in a rat model. Kallakuri S, Ascher E, Pagala M, Gade P, Hingorani A, Scheinman M, Mehraein K, Jacob T.

[x] Am J Physiol Renal Physiol. 2002 Mar;282(3):F417-23. Protective effect of glycine on renal injury induced by ischemia-reperfusion in vivo. Yin M, Zhong Z, Connor HD, Bunzendahl H, Finn WF, Rusyn I, Li X, Raleigh JA, Mason RP, Thurman RG.

[x] Microcirculation. 2011 Apr;18(3):205-13. Glycine and taurine equally prevent fatty livers from Kupffer cell-dependent injury: an in vivo microscopy study. Bruns H, Watanpour I, Gebhard MM, Flechtenmacher C, Galli U, Schulze-Bergkamen H, Zorn M, Büchler MW, Schemmer P.

[x] J Gastroenterol Hepatol. 2011 Jan;26(1):194-200. Glycine maintains mitochondrial activity and bile composition following warm liver ischemia-reperfusion injury. Sheth H, Hafez T, Glantzounis GK, Seifalian AM, Fuller B, Davidson BR.


[x] J Physiol. 2004 Aug 1;558(Pt 3):873-82. Glycine protects cardiomyocytes against lethal reoxygenation injury by inhibiting mitochondrial permeability transition. Ruiz-Meana M, Pina P, Garcia-Dorado D, Rodríguez-Sinovas A, Barba I, Miró-Casas E, Mirabet M, Soler-Soler J.

[x] Hepatology. 1993 Jan;17(1):91-8. Glycine protects hepatocytes from injury caused by anoxia, cold ischemia and mitochondrial inhibitors, but not injury caused by calcium ionophores or oxidative stress. Marsh DC, Vreugdenhil PK, Mack VE, Belzer FO, Southard JH. "Of the amino acids tested, only alanine (10 mmol/L) and the combination of alanine (3 mmol/L) and serine (3 mmol/L) were as effective as glycine in preventing lactate dehydrogenase release in the hypothermic preservation model."

[x] FASEB J. 1990 Dec;4(15):3347-54. Structural requirements for protection by small amino acids against hypoxic injury in kidney proximal tubules. Weinberg JM, Venkatachalam MA, Garzo-Quintero R, Roeser NF, Davis JA. "Kidney proximal tubules are resistant to hypoxic injury if glycine or L-alanine is present in their incubation medium. Protection does not depend on the concentration or turnover of ATP in cells. We have investigated structure-function relationships that govern this protective activity. Among more than 45 amino acids and analogs examined, only glycine, L-alanine, D-alanine, beta-alanine, and the neuronal glycine binding site agonist, 1-aminocyclopropane-1-carboxylic acid, were active. The protective effect could not be explained by amino acid metabolism."

[x] Transplantation. 2008 May 15;85(9):1300-10. Perioperative glycine treatment attenuates ischemia/reperfusion injury and ameliorates smooth muscle dysfunction in intestinal transplantation. Schaefer N, Tahara K, Schuchtrup S, Websky MV, Overhaus M, Schmidt J, Wirz S, Abu-Elmagd KM, Kalff JC, Hirner A, Türler A.




[7] Glycine, endotoxemia, Kupffer cells, TLR4

[x] Am J Physiol. 1996 Jul;271(1 Pt 1):G97-103. A diet containing glycine improves survival in endotoxin shock in the rat. Ikejima K, Iimuro Y, Forman DT, Thurman RG.

[x] Am J Physiol. 1997 Jun;272(6 Pt 1):G1581-6. Kupffer cells contain a glycine-gated chloride channel. Ikejima K, Qu W, Stachlewitz RF, Thurman RG.


[x] World J Gastroenterol. 2012 May 28;18(20):2576-81. Effects of glycine on phagocytosis and secretion by Kupffer cells in vitro. Wu HW, Yun KM, Han DW, Xu RL, Zhao YC.

[x] Am J Surg. 2008 Jul;196(1):139-48. Glycine attenuates endotoxin-induced liver injury by downregulating TLR4 signaling in Kupffer cells. Xu FL, You HB, Li XH, Chen XF, Liu ZJ, Gong JP.

[x] Am J Physiol Lung Cell Mol Physiol. 2000 Aug;279(2):L390-8. Dietary glycine blunts lung inflammatory cell influx following acute endotoxin. Wheeler MD, Rose ML, Yamashima S, Enomoto N, Seabra V, Madren J, Thurman RG.

[x] Crit Care Med. 2001 Jun;29(6):1201-6. Glycine attenuates hepatocellular depression during early sepsis and reduces sepsis-induced mortality. Yang S, Koo DJ, Chaudry IH, Wang P.


[x] Br Poult Sci. 2009 Jul;50(4):479-86. Effects of dietary glycine supplementation and fish meal on inflammatory responses in broiler chicks. Takahashi K, Takagi K, Akiba Y. "4. Supplementing the CS diet with Gly resulted in smaller increases in the plasma concentrations of NO(x), Cer and AGP after LPS injection than were observed for chicks fed on the CS diet alone. In addition, 2 h after LPS challenge the expression of encoding inflammatory response-related substances was lower in the spleens of those chicks fed on the Gly-supplemented diet than in those fed the CS diet. 5. Supplementation of the FM diet with Gly reduced the plasma AGP concentration and IL-1 beta and TL1A expression. 6. These results suggest that modulation of inflammatory responses by dietary Gly supplementation is affected by dietary composition; Gly supplementation has different effects on the cytokine responses dependent on the diet."

[x] J Surg Res. 2013 Jul;183(1):e7-e21. Effects of glycine, pyruvate, resveratrol, and nitrite on tissue injury and cytokine response in endotoxemic rats. Hamburger T, Broecker-Preuss M, Hartmann M, Schade FU, de Groot H, Petrat F.

[x] Am J Physiol. 1998 Oct;275(4 Pt 1):G862-7. A choline-rich diet improves survival in a rat model of endotoxin shock. Rivera CA, Wheeler MD, Enomoto N, Thurman RG. "Feeding glycine, which prevents macrophage activation via a chloride channel, in addition to choline was even more effective than feeding choline alone, suggesting that glycine and choline act via distinct sites. These data are consistent with the hypothesis that choline diminishes endotoxin shock by preventing macrophage activation."

[x] Liver Int. 2003 Aug;23(4):276-82. Glycine modulates cytokine secretion, inhibits hepatic damage and improves survival in a model of endotoxemia in mice. Bruck R, Wardi J, Aeed H, Avni Y, Shirin H, Avinoach I, Shahmurov M, Hershkoviz R. "The serum aminotransferase levels in the glycine-treated mice decreased to ∼10% of the values in the control mice who did not receive glycine [...] As a result of glycine administration, the survival rate was 100% in the treatment group compared to 30% in the control mice."





[8] Glycine protects from liver injury and fatty liver (animal studies)

[x] Am J Surg. 2008 Jul;196(1):139-48. Glycine attenuates endotoxin-induced liver injury by downregulating TLR4 signaling in Kupffer cells. Xu FL, You HB, Li XH, Chen XF, Liu ZJ, Gong JP.

[x] Eur Rev Med Pharmacol Sci. 2012 Jun;16(6):728-36. Glycine alleviates liver injury induced by deficiency in methionine and or choline in rats. Barakat HA, Hamza AH.

[x] Pol J Pharmacol. 2003 Jul-Aug;55(4):603-11. Glycine modulates hepatic lipid accumulation in alcohol-induced liver injury. Senthilkumar R, Viswanathan P, Nalini N.

[x] Cell Biochem Funct. 2004 Mar-Apr;22(2):123-8. Protective effect of glycine supplementation on the levels of lipid peroxidation and antioxidant enzymes in the erythrocyte of rats with alcohol-induced liver injury. Senthilkumar R, Sengottuvelan M, Nalini N.

[x] Clin Exp Pharmacol Physiol. 2004 Jul;31(7):456-61. Effect of glycine on tissue fatty acid composition in an experimental model of alcohol-induced hepatotoxicity. Senthilkumar R, Nalini N.

[x] Pol J Pharmacol. 2004 Jan-Feb;56(1):121-8. Glycine prevents hepatic fibrosis by preventing the accumulation of collagen in rats with alcoholic liver injury. Senthilkumar R, Nalini N.

[x] Pharmazie. 2004 Jan;59(1):55-60. Effect of glycine on oxidative stress in rats with alcohol induced liver injury. Senthilkumar R, Viswanathan P, Nalini N. "Alcohol treated rat brain demonstrated oedma, which was significantly lowered on treatment with glycine"

[x] Amino Acids. 2011 Apr;40(4):1139-50. Dietary glycine protects from chemotherapy-induced hepatotoxicity. Mikalauskas S, Mikalauskiene L, Bruns H, Nickkholgh A, Hoffmann K, Longerich T, Strupas K, Büchler MW, Schemmer P.

[x] Clin Chim Acta. 2013 May;420:150-4. Glycine ameliorates liver injury and vitamin D deficiency induced by bile duct ligation. Chen CY, Wang BT, Wu ZC, Yu WT, Lin PJ, Tsai WL, Shiesh SC.


[x] World J Gastroenterol. 2008 Oct 21;14(39):5996-6003. Dietary glycine blunts liver injury after bile duct ligation in rats. Froh M, Zhong Z, Walbrun P, Lehnert M, Netter S, Wiest R, Conzelmann L, Gabele E, Hellerbrand C, Scholmerich J, Thurman RG.

[x] Liver Int. 2003 Aug;23(4):276-82. Glycine modulates cytokine secretion, inhibits hepatic damage and improves survival in a model of endotoxemia in mice. Bruck R, Wardi J, Aeed H, Avni Y, Shirin H, Avinoach I, Shahmurov M, Hershkoviz R.

[x] Free Radic Biol Med. 2001 Nov 15;31(10):1236-44. Dietary glycine inhibits activation of nuclear factor kappa B and prevents liver injury in hemorrhagic shock in the rat. Mauriz JL, Matilla B, Culebras JM, González P, González-Gallego J.

[x] J Exp Integr Med. 2014; 4(3): 180-186 Attenuation of carbon tetrachloride-induced hepatic fibrosis by glycine, vitamin E and vitamin C. Aziza A. Saad, El-Hassan M. Mokhamer, Mohamed A. Abdel Mohsen, Geylan A. Fadaly.

[x] J Invest Surg. 2010 Feb;23(1):12-20. Glycine pretreatment ameliorates liver injury after partial hepatectomy in the rat. Benko T, Frede S, Gu Y, Best J, Baba HA, Schlaak JF, de Groot H, Fandrey J, Rauen U.

[x] Crit Care Med. 2001 Jun;29(6):1201-6. Glycine attenuates hepatocellular depression during early sepsis and reduces sepsis-induced mortality. Yang S, Koo DJ, Chaudry IH, Wang P.

[x] J Pharmacol Exp Ther. 2001 Dec;299(3):858-65. Cyclosporin A causes a hypermetabolic state and hypoxia in the liver: prevention by dietary glycine. Zhong Z, Li X, Yamashina S, von Frankenberg M, Enomoto N, Ikejima K, Kolinsky M, Raleigh JA, Thurman RG.

[x] Carcinogenesis. 1999 Nov;20(11):2095-100. Corn oil rapidly activates nuclear factor-kappaB in hepatic Kupffer cells by oxidant-dependent mechanisms. Rusyn I, Bradham CA, Cohn L, Schoonhoven R, Swenberg JA, Brenner DA, Thurman RG.

[x] Eur Surg Res. 2006;38(6):503-12. Different protection mechanisms after pretreatment with glycine or alpha-lipoic acid in a rat model of warm hepatic ischemia. Duenschede F, Westermann S, Riegler N, Miesner I, Erbes K, Ewald P, Kircher A, Schaefer H, Schneider J, Schad A, Dutkowski P, Kiemer AK, Junginger T. "Protection by glycine is likely to result from a reduction in adverse TNFalpha effects."

[x] Liver Int. 2007 Nov;27(9):1249-54. Glycine reduces hepatic warm ischaemia-reperfusion injury by suppressing inflammatory reactions in rats. Yamanouchi K, Eguchi S, Kamohara Y, Yanaga K, Okudaira S, Tajima Y, Kanematsu T.

[x] Res Commun Mol Pathol Pharmacol. 2007-2008;120-121(1-6):93-104. Glycine affects valproate hepatotoxicity. Junius L, Brune T, Deters M, Schulze J, Siegers CP.


[x] Toxicology. 1998 Jun 26;128(1):63-72. Influence of glycine on the damage induced in isolated perfused rat liver by five hepatotoxic agents. Deters M, Siegers CP, Strubelt O.

[x] Am J Physiol Gastrointest Liver Physiol. 2016 Sep 22:ajpgi.00465.2015. Glycine prevents metabolic steatohepatitis in diabetic KK-Ay mice through modulation of hepatic innate immunity. Takashima S, Ikejima K, Arai K, Yokokawa J, Kon K, Yamashina S, Watanabe S.

[x] Oncotarget. 2016 Oct 23. doi: 10.18632/oncotarget.12831. Glycine protects against high sucrose and high fat-induced non-alcoholic steatohepatitis in rats. Zhou X, Han D, Xu R, Wu H, Qu C, Wang F, Wang X, Zhao Y.




[9] Glycine protects from hemorrhagic shock (animal studies)

[x] Shock. 1999 Jul;12(1):54-62. Glycine improves survival after hemorrhagic shock in the rat. Zhong Z, Enomoto N, Connor HD, Moss N, Mason RP, Thurman RG.

[x] Free Radic Biol Med. 2001 Nov 15;31(10):1236-44. Dietary glycine inhibits activation of nuclear factor kappa B and prevents liver injury in hemorrhagic shock in the rat. Mauriz JL, Matilla B, Culebras JM, González P, González-Gallego J.




[10] Glycine and reflux esophagitis (GERD)

[x] Med Sci Monit. 2012 Jan;18(1):BR9-15. Orally administered L-arginine and glycine are highly effective against acid reflux esophagitis in rats. Nagahama K, Nishio H, Yamato M, Takeuchi K.




[11] Glycine and low-protein diet

[x] Clin Sci (Lond). 2002 Dec;103(6):633-9. Increased systolic blood pressure in rats induced by a maternal low-protein diet is reversed by dietary supplementation with glycine. Jackson AA, Dunn RL, Marchand MC, Langley-Evans SC.

[x] J Physiol. 2004 Jan 15;554(Pt 2):497-504. Glycine rectifies vascular dysfunction induced by dietary protein imbalance during pregnancy. Brawley L, Torrens C, Anthony FW, Itoh S, Wheeler T, Jackson AA, Clough GF, Poston L, Hanson MA.

[x] Namroud, N. F., et al. "Effects of glycine and glutamic acid supplementation to low protein diets on performance, thyroid function and fat deposition in chickens." South African Journal of Animal Science 40.3 (2010): 238-244.




[12] Glycine protects from casein (animal studies)

[x] Atherosclerosis. 1982 Jun;43(2-3):381-91. Reduction of casein-induced hypercholesterolaemia and atherosclerosis in rabbits and rats by dietary glycine, arginine and alanine. Katan MB, Vroomen LH, Hermus RJ. "when we fed rats semi-purified diets containing cholesterol, and casein, casein plus glycine, or soy isolate, we obtained mean serum cholesterol levels of 10.4 mmol/l in the casein group, 4.9 in the casein-plus-glycine group and 3.5 in the soy group."

[x] Z Ernahrungswiss. 1987 Sep;26(3):161-4. Dietary glycine and cholesterol metabolism in rats. Beynen AC, Lemmens AG. "by adding glycine to a semipurified casein diet, so that the level of glycine was similar to that in a diet containing soy protein. [...] did not affect the casein-induced concentrations of cholesterol"

[x] J Nutr Sci Vitaminol (Tokyo). 1989 Aug;35(4):323-32. Effects of addition of sulfur-containing amino acids and glycine to soybean protein and casein on serum cholesterol levels of rats. Tanaka K, Sugano M. "When 2.0% Gly was added to cholesterol-enriched diets containing 20% protein, serum cholesterol decreased significantly only when the protein source was casein and the level attained was comparable to that observed in rats fed soybean protein."

[x] J Nutr. 1997 Mar;127(3):470-7. Cholesterol-lowering effects of soybean, potato and rice proteins depend on their low methionine contents in rats fed a cholesterol-free purified diet. Morita T, Oh-hashi A, Takei K, Ikai M, Kasaoka S, Kiriyama S. "There was a significant negative correlation between serum cholesterol concentration and fecal total steroid excretion (r = -0.490, P = 0.01). However, a stronger positive correlation was observed between serum cholesterol concentration and dietary methionine concentration (r = 0.674, P = 0.0003) or methionine:glycine ratios (r = 0.656, P = 0.0005). In a separate experiment in rats fed diets containing amino acid mixtures simulating the RP, PP and SP diets, serum total cholesterol concentrations were lower than in rats fed simulated casein."

[x] Bratisl Lek Listy. 2005;106(6-7):231-4. Health benefits and risks of plant proteins. Krajcovicova-Kudlackova M, Babinska K, Valachovicova M. "Vegetarians have a significantly higher intake of non-essential amino acids arginine and pyruvigenic amino acids glycine, alanine, serine."




[13] Glycine and lead toxicity

[x] J Toxicol. 2011;2011:430539. Effect of glycine on lead mobilization, lead-induced oxidative stress, and hepatic toxicity in rats. Alcaraz-Contreras Y, Garza-Ocañas L, Carcaño-Díaz K, Ramírez-Gómez XS.




[14] Glycine and dental caries

[x] J Dent Res. 1975 Sep-Oct;54(5):987-92. Effect of dietary supplementation of glycine on caries development and lipids in rat molars. Das SK, Harris RS.




[15] Glycine and intestinal function

[x] Gastroenterology. 2003 Sep;125(3):775-85. Dietary glycine prevents chemical-induced experimental colitis in the rat. Tsune I, Ikejima K, Hirose M, Yoshikawa M, Enomoto N, Takei Y, Sato N.

[x] Pathophysiology. 2000 Apr;7(1):69-73. Protection of gastric mucosal integrity by gelatin and simple proline-containing peptides. Samonina G, Lyapina L, Kopylova G, Pastorova V V, Bakaeva Z, Jeliaznik N, Zuykova S, Ashmarin I I.

[x] Res Commun Mol Pathol Pharmacol. 1997 Aug;97(2):185-98. Studies on the antisecretory, gastric anti-ulcer and cytoprotective properties of glycine. Tariq M, Al Moutaery AR. "Pretreatment with glycine significantly protected animals against stress-, indomethacin- and necrotizing agents induced gastric lesions."

[x] Scand J Gastroenterol. 1995 Sep;30(9):854-60. Antioxidants inhibit ethanol-induced gastric injury in the rat. Role of manganese, glycine, and carotene. Ligumsky M, Sestieri M, Okon E, Ginsburg I.

[x] Int J Colorectal Dis. 2011 May;26(5):561-8. L-arginine and glycine supplementation in the repair of the irradiated colonic wall of rats. de Aguiar Picanço E, Lopes-Paulo F, Marques RG, Diestel CF, Caetano CE, de Souza MV, Moscoso GM, Pazos HM. "The present results suggest that glycine supplementation had a superior effect on the irradiated colon wall compared to L-arginine supplementation since it was able to maintain the thickness of the wall and the epithelial surface of the mucosa"

[x] Am J Physiol. 1982 Feb;242(2):G85-8. Stimulation of gastric acid secreted by glycine and related oligopeptides in humans. Wald A, Adibi SA.

[x] J Cell Sci. 1994 Feb;107 ( Pt 2):413-24. Developmental expression of mucin genes MUC1 and MUC2. Chambers JA, Hollingsworth MA, Trezise AE, Harris A. "Mucous glycoproteins, mucins, contain a high percentage of serine, threonine, proline, alanine and glycine[...]"

[x] J Nutr. 2014 Aug 13. pii: jn.114.194001. [Epub ahead of print] Glycine Stimulates Protein Synthesis and Inhibits Oxidative Stress in Pig Small Intestinal Epithelial Cells. Wang W, Wu Z, Lin G, Hu S, Wang B, Dai Z, Wu G.

[x] Poult Sci. 2013 Oct;92(10):2724-31. Supplemental glycine and threonine effects on performance, intestinal mucosa development, and nutrient utilization of growing broiler chickens. Ospina-Rojas IC, Murakami AE, Oliveira CA, Guerra AF. "Glycine can directly or indirectly influence the proper function of the intestinal mucosa[...]"

[x] J Surg Res. 2014 Jun 13. [Epub ahead of print] Glycine selectively reduces intestinal injury during endotoxemia. Effenberger-Neidnicht K, Jägers J, Verhaegh R, de Groot H.

[x] Int J Colorectal Dis. 2007 Dec;22(12):1523-9. Role of L-glutamine and glycine supplementation on irradiated colonic wall. Diestel CF, Marques RG, Lopes-Paulo F, Paiva D, Horst NL, Caetano CE, Portela MC.


[x] Bull Exp Biol Med. 2009 Mar;147(3):308-11. Effect of glycine on the microcirculation in rat mesenteric vessels. Podoprigora GI, Nartsissov YR.

[x] Biol Pharm Bull. 1995 Dec;18(12):1653-6. Inhibitory effect of glycine on ethanol absorption from gastrointestinal tract. Akao T, Kobashi K.

[x] Life Sci. 1974 Feb 1;14(3):557-65. Reduction of acute alcoholic intoxication by alpha amino acids: glycine and serine. Blum K, Wallace JE, Friedman RN. "These findings provide evidence that glycine and serine-induced protection against the described motor impairments caused by ethanol may be due to a suppression of the rate of absorption of ethanol from the gastrointestinal tract."

[x] Gut. 1970 Sep;11(9):768-72. Effect of glycine and glucose on sodium and water adsorption in patients with cholera. Nalin DR, Cash RA, Rahman M, Yunus M "a solution containing both glucose and glycine provides more effective therapy than solutions containing either glucose or glycine alone." [diarrhea volume decreased by 39%]

[x] Arch Dis Child. 1986 Apr;61(4):372-6. Glycine supplemented oral rehydration solutions for diarrhoea. Vesikari T, Isolauri E "The patients receiving ORS60-Gly60 had similar stool and urine volumes as those receiving standard ORS60. It is concluded that excess glycine in relation to sodium in an ORS may lead to osmotic diarrhoea, and a high amount of absorbed glycine may result in osmotic diuresis with poor net rehydration."

[x] BMJ. 1994 Mar 5;308(6929):624-6. Management of acute diarrhoea in diabetic patients using oral rehydration solutions containing glucose, rice, or glycine. Haider R, Azad Khan AK, Roy SK, Dewan N, Alam AN, Mahalanabis D.




[16] Glycine and experimental arthritis

[x] Infect Immun. 2001 Sep;69(9):5883-91. Dietary glycine prevents peptidoglycan polysaccharide-induced reactive arthritis in the rat: role for glycine-gated chloride channel. Li X1, Bradford BU, Wheeler MD, Stimpson SA, Pink HM, Brodie TA, Schwab JH, Thurman RG.

[x] Int Immunopharmacol. 2007 Dec 15;7(13):1784-92. Anti-inflammatory effects of orally ingested lactoferrin and glycine in different zymosan-induced inflammation models: evidence for synergistic activity. Hartog A, Leenders I, van der Kraan PM, Garssen J.




[17] Glycine and Achilles tendinitis

[x] Anat Rec (Hoboken). 2014 Aug 23. Glycine Improves Biochemical and Biomechanical Properties Following Inflammation of the Achilles Tendon. Vieira CP, Oliveira LP, Guerra FD, Almeida MD, Marcondes MC, Pimentel ER.

[x] Connect Tissue Res. 2014 Nov 21:1-9. Green tea and glycine aid in the recovery of tendinitis of the Achilles tendon of rats. Vieira CP, Guerra FD, de Oliveira LP, Almeida MS, Marcondes MC, Pimentell ER.




[18] Glycine and platelet aggregation

[x] Amino Acids. 2013 Mar;44(3):925-31. Glycine reduces platelet aggregation. Schemmer P, Zhong Z, Galli U, Wheeler MD, Xiangli L, Bradford BU, Conzelmann LO, Forman D, Boyer J, Thurman RG. "Dietary glycine significantly increased bleeding time about twofold compared to valine-treated controls. Furthermore, the amplitude of platelet aggregation stimulated with ADP or collagen was significantly decreased in whole blood drawn from rats fed 2.5 or 5 % dietary glycine by over 50 %."




[19] Glycine and birth defects

[x] Birth Defects Res A Clin Mol Teratol. 2006 Oct;76(10):731-8. Reduction of all-trans-retinoic acid-induced teratogenesis in the rat by glycine administration. Martínez-Angoa A, Parra-Hernández E, Madrigal-Bujaidar E, Chamorro-Cevallos G, Carvajal-Sandoval G, Zamudio-Cortes P.

[x] Reprod Toxicol. 2007 Jan;23(1):92-7. Glycine reduces cadmium-induced teratogenic damage in mice. Paniagua-Castro N1, Escalona-Cardoso G, Chamorro-Cevallos G.

[x] J Pharm Pharmacol. 2008 Jul;60(7):895-900. Glycine decreases developmental damage induced by hyperglycaemia in mouse embryos. Martínez-Galero E, Paniagua-Castro N, Pérez-Pastén R, Madrigal-Bujaidar E, Chamorro-Cevallos G.




[20] Glycine, pro-inflammatory cytokines and adiponectin

[x] Eur J Pharmacol. 2008 Dec 3;599(1-3):152-8. Glycine regulates the production of pro-inflammatory cytokines in lean and monosodium glutamate-obese mice. Alarcon-Aguilar FJ, Almanza-Perez J, Blancas G, Angeles S, Garcia-Macedo R, Roman R, Cruz M.

[x] Biomed Pharmacother. 2010 Oct;64(8):534-40. Glycine regulates inflammatory markers modifying the energetic balance through PPAR and UCP-2. Almanza-Perez JC, Alarcon-Aguilar FJ, Blancas-Flores G, Campos-Sepulveda AE, Roman-Ramos R, Garcia-Macedo R, Cruz M.

[x] Eur J Pharmacol. 2008 Jun 10;587(1-3):317-21. Glycine increases mRNA adiponectin and diminishes pro-inflammatory adipokines expression in 3T3-L1 cells. Garcia-Macedo R, Sanchez-Muñoz F, Almanza-Perez JC, Duran-Reyes G, Alarcon-Aguilar F, Cruz M.




[21] Glycine, metabolic syndrome and insulin levels (human trials) + studies showing low glycine levels in diabetic patients

[x] J Endocrinol Invest. 2008 Aug;31(8):694-9. Glycine treatment decreases proinflammatory cytokines and increases interferon-gamma in patients with type 2 diabetes. Cruz M, Maldonado-Bernal C, Mondragón-Gonzalez R, Sanchez-Barrera R, Wacher NH, Carvajal-Sandoval G, Kumate J.

[x] Can J Physiol Pharmacol. 2013 Oct;91(10):855-60. Oral supplementation with glycine reduces oxidative stress in patients with metabolic syndrome, improving their systolic blood pressure. Díaz-Flores M, Cruz M, Duran-Reyes G, Munguia-Miranda C, Loza-Rodríguez H, Pulido-Casas E, Torres-Ramírez N, Gaja-Rodriguez O, Kumate J, Baiza-Gutman LA, Hernández-Saavedra D.

[x] Glycine supplementation to improve insulin sensitivity in humans by Boni Epse Attobla, Marie-Hippolyte, M.S., THE UNIVERSITY OF ALABAMA AT BIRMINGHAM, 2014

[x] Martinez-Abundis E, Kam-Ramos AM, Hernandez-Salazar E, Gonzalez-Ortiz. Effect of glycine on insulin secretion, fasting and postprandial glucose levels in patients with type 2 diabetes mellitus. 18th International Diabetes Federation Congress, Paris, August 24-29, 2003;abstract 758. [Lahey: "In a small double-blind study, glycine improved blood sugar control in type 2 diabetics.21 Researchers began by giving participants 1 gram of glycine a day, before breakfast, titrating the dose up to 5 grams. The results showed reductions in hemoglobin A1C, but no change in fasting glucose or insulin secretion."]


[x] Horm Metab Res. 2001 Jun;33(6):358-60. Effect of glycine on insulin secretion and action in healthy first-degree relatives of type 2 diabetes mellitus patients. González-Ortiz M, Medina-Santillán R, Martínez-Abundis E, von Drateln CR.

[x] Am J Clin Nutr. 2002 Dec;76(6):1302-7. The metabolic response to ingested glycine. Gannon MC, Nuttall JA, Nuttall FQ. "When glycine was ingested with glucose, the plasma glucose area response was attenuated by > 50%"

[x] PLoS One. 2010 Dec 10;5(12):e15234. Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type 2 diabetic obese African-American women. Fiehn O, Garvey WT, Newman JW, Lok KH, Hoppel CL, Adams SH. [see Table 2]

[x] PLoS One. 2013 Dec 31;8(12):e84034. Serum glycine is associated with regional body fat and insulin resistance in functionally-limited older adults. Lustgarten MS, Price LL, Phillips EM, Fielding RA. "Glycine was found to be significantly negatively associated with HOMA-IR and, IMAT and abdominal adiposity."

[x] Can J Physiol Pharmacol. 2004 Jul;82(7):506-14. Amino acid metabolism in the Zucker diabetic fatty rat: effects of insulin resistance and of type 2 diabetes. Wijekoon EP, Skinner C, Brosnan ME, Brosnan JT. "At the insulin-resistant stage, the plasma concentrations of the gluconeogenic amino acids aspartate, serine, glutamine, glycine, and histidine were decreased [...] It is evident that insulin resistance alone is capable of bringing about many of the changes in amino acid metabolism observed in type 2 diabetes."

[x] Br J Nutr. 2012 Jul 14;108(1):57-61. Histidine and arginine are associated with inflammation and oxidative stress in obese women. Niu YC, Feng RN, Hou Y, Li K, Kang Z, Wang J, Sun CH, Li Y. "Among the amino acids determined, serum histidine, arginine, threonine, glycine, lysine and serine were found to be significantly lower in obese women as compared to non-obese controls (P < 0·001). The difference was the greatest for histidine (P < 0·001)."

[x] PLoS One. 2010 May 28;5(5):e10883. alpha-hydroxybutyrate is an early biomarker of insulin resistance and glucose intolerance in a nondiabetic population. Gall WE, Beebe K, Lawton KA, Adam KP, Mitchell MW, Nakhle PJ, Ryals JA, Milburn MV, Nannipieri M, Camastra S, Natali A, Ferrannini E; RISC Study Group. "Similarly, levels of the amino acid glycine were observed to trend downward with IR"


[x] Diabetes. 2016 May 3. pii: db151272. A glycine-insulin autocrine feedback loop enhances insulin secretion from human β-cells and is impaired in type 2 diabetes. Yan-Do R, Duong E, Manning Fox JE, Dai X, Suzuki K, Khan S, Bautista A, Ferdaoussi M, Lyon J, Wu X, Cheley S, MacDonald PE, Braun M. "GlyRα1 expression and glycine-induced currents are reduced in T2D β-cells"






[22] Beneficial effects of glycine+cysteine (human trials)

[x] Diabetes Care. 2011 Jan;34(1):162-7. Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Sekhar RV, McKay SV, Patel SG, Guthikonda AP, Reddy VT, Balasubramanyam A, Jahoor F. [dose was 100mg/kg/d, according to the calculation of the author of this paper]

[x] Am J Clin Nutr. 2011 Sep;94(3):847-53. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. Sekhar RV, Patel SG, Guthikonda AP, Reid M, Balasubramanyam A, Taffet GE, Jahoor F.

[x] Aging Cell. 2013 Jun;12(3):415-25. Impaired mitochondrial fatty acid oxidation and insulin resistance in aging: novel protective role of glutathione. Nguyen D, Samson SL, Reddy VT, Gonzalez EV, Sekhar RV.

[x] J Clin Endocrinol Metab. 2014 Jan;99(1):169-77. Effect of increasing glutathione with cysteine and glycine supplementation on mitochondrial fuel oxidation, insulin sensitivity, and body composition in older HIV-infected patients. Nguyen D, Hsu JW, Jahoor F, Sekhar RV.

[x] AIDS. 2015 Sep 10;29(14):1899-900. Increasing glutathione concentrations with cysteine and glycine supplementation lowers inflammation in HIV patients. Sekhar RV, Liu CW, Rice S.




[23] Glycine and stroke (human and animal studies)

[x] Cerebrovasc Dis. 2000 Jan-Feb;10(1):49-60. Neuroprotective effects of glycine for therapy of acute ischaemic stroke. Gusev EI, Skvortsova VI, Dambinova SA, Raevskiy KS, Alekseev AA, Bashkatova VG, Kovalenko AV, Kudrin VS, Yakovleva EV.

[x] Conf Proc IEEE Eng Med Biol Soc. 2012;2012:2651-4. Assessment of microcirculatory effects of glycine by intravital microscopy in rats. Podoprigora GI, Blagosklonov O, Angoué O, Boulahdour H, Nartsissov YR. "Glycine had a vasodilatory effect on microvessels in the rat brain and mesenterium. The diameter of pial arterioles increased after glycine application especially markedly (up to 250% of initial size). These changes were not observed when physiological saline was used. Even a very small amount of glycine (a drop on the needle) was sufficient to stop the early stages of histamine-induced blood stasis development in 3-5 s in mesenterial microvessels. The vasodilatory effect of glycine on the pial microcirculation correlates with its reported positive therapeutic effect in cerebral ischemic stroke."

[x] J Nutr. 2015 Apr;145(4):720-8. Dietary intakes of glutamic Acid and glycine are associated with stroke mortality in Japanese adults. Nagata C, Wada K, Tamura T, Kawachi T, Konishi K, Tsuji M, Nakamura K. [In the highest quartile of glycine intake, glycine comprised 4.9% of total protein, whereas in the lowest quartile, glycine comprised 4.2% of total protein intake (a 17% difference). It seems that the correlation between glycine and mortality disappears in the age-adjusted model.]

[x] Pharmacological Research 31 (1995) Correction by glycine and piracetam of the alterations in neurotransmitter amino acids and high integrative functions of brain after focal cortex ischemia. Romanova, G. A., V. S. Kudrin, and L. A. Malikova. "Treatment of ischemic rats by daily administration per os glycine (500 mg/kg) and piracetam (500 mg/kg) was promoted to recovery of disturbed brain functions and was corrected of neurotransmitter amino acids metabolic changes.

[x] Bull Exp Biol Med. 2005 Jun;139(6):675-7. Effect of glycine on microcirculation in pial vessels of rat brain. Podoprigora GI, Nartsissov YR, Aleksandrov PN.

[x] Bull Exp Biol Med. 2012 May;153(1):44-7. Mechanism underlying the protective effect of glycine in energetic disturbances in brain tissues under hypoxic conditions. Selin AA, Lobysheva NV, Vorontsova ON, Tonshin AA, Yaguzhinsky LS, Nartsissov YR.

[x] J Neurochem. 2015 May;133(3):397-408. Glycine bidirectionally regulates ischemic tolerance via different mechanisms including NR2A-dependent CREB phosphorylation. Chen Z, Hu B, Wang F, Du L, Huang B, Li L, Qi J, Wang X. "Low doses of glycine (L-Gly) significantly decreased hippocampal ischemic LTP (i-LTP), infarct volume, and neurological deficit scores which were administered before ischemia was induced in rats, whereas high doses of glycine exerted deteriorative effects under the same condition. These findings suggested that exogenous glycine may induce IT in a dose-dependent manner. Furthermore, L-Gly-dependent neuronal protection was inversed by L689, a selective NMDAR glycine site antagonist both in vitro (abolished i-LTP depression) and in vivo (increased infarct size reduction), but not glycine receptor (GlyR) inhibitor strychnine."

[x] Pediatr Int. 2016 Sep 10. Amelioration of Brain Damage by Glycine in Neonatal Rat Brain Following Hypoxia-Ischemia. Mori H, Momosaki K, Kido J, Naramura T, Tanaka K, Matsumoto S, Nakamura K, Mitsubuchi H, Endo F, Iwai M.



[24] Glycine and sleep (short-term human studies)

[x] Sleep and Biological rhythms, 2007 5(2), 126-131. Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Yamadera W, Inagawa K, Chiba S, Bannai M, Takahashi M, Nakayama K

[x] Sleep and Biological Rhythms 2006 4(1), 75-77. Subjective effects of glycine ingestion before bedtime on sleep quality. Inagawa K, Hiraoka T, Kohda T, Yamadera W, Takahashi M.


[x] Front Neurol. 2012 Apr 18;3:61. The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. Bannai M, Kawai N, Ono K, Nakahara K, Murakami N.

[x] Neuropsychopharmacology. 2014 Dec 23. The Sleep-Promoting and Hypothermic Effects of Glycine are Mediated by NMDA Receptors in the Suprachiasmatic Nucleus. Kawai N, Sakai N, Okuro M, Karakawa S, Tsuneyoshi Y, Kawasaki N, Takeda T, Bannai M, Nishino S. "In acute sleep disturbance, oral administration of glycine induced non-rapid eye movement (REM) sleep and shortened NREM sleep latency with a simultaneous decrease in core temperature. [...]Pretreatment with N-methyl-D-aspartate (NMDA) receptor antagonists AP5 and CGP78608 but not the glycine receptor antagonist strychnine inhibited the CBF increase caused by glycine injection into the brain."





[25] Glycine and psychiatric diseases (schizophrenia, depression, psychosis and OCD)

[x] Int J Neuropsychopharmacol. 2001 Dec;4(4):385-91. Adjunctive high-dose glycine in the treatment of schizophrenia. Javitt DC, Silipo G, Cienfuegos A, Shelley AM, Bark N, Park M, Lindenmayer JP, Suckow R, Zukin SR.

[x] Arch Gen Psychiatry. 1999 Jan;56(1):29-36. Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia. Heresco-Levy U, Javitt DC, Ermilov M, Mordel C, Silipo G, Lichtenstein M.

[x] Br J Psychiatry. 1996 Nov;169(5):610-7. Double-blind, placebo-controlled, crossover trial of glycine adjuvant therapy for treatment-resistant schizophrenia. Heresco-Levy U, Javitt DC, Ermilov M, Mordel C, Horowitz A, Kelly D.

[x] Am J Psychiatry. 1994 Aug;151(8):1234-6. Amelioration of negative symptoms in schizophrenia by glycine. Javitt DC, Zylberman I, Zukin SR, Heresco-Levy U, Lindenmayer JP.

[x] Biol Psychiatry. 2004 Jan 15;55(2):165-71. High-dose glycine added to olanzapine and risperidone for the treatment of schizophrenia. Heresco-Levy U, Ermilov M, Lichtenberg P, Bar G, Javitt DC.

[x] Am J Psychiatry. 2005 Sep;162(9):1738-40. Relation of plasma glycine, serine, and homocysteine levels to schizophrenia symptoms and medication type. Neeman G, Blanaru M, Bloch B, Kremer I, Ermilov M, Javitt DC, Heresco-Levy U.

[x] Am J Psychiatry. 1994 Aug;151(8):1234-6. Amelioration of negative symptoms in schizophrenia by glycine. Javitt DC, Zylberman I, Zukin SR, Heresco-Levy U, Lindenmayer JP.

[x] Am J Psychiatry. 1999 Jan;156(1):145-7. Effect of clozapine and adjunctive high-dose glycine in treatment-resistant schizophrenia. Potkin SG, Jin Y, Bunney BG, Costa J, Gulasekaram B.


[x] Eur Neuropsychopharmacol. 1995;5 Suppl:71-5. Plasma concentrations of excitatory amino acids, serine, glycine, taurine and histidine in major depression. Altamura C, Maes M, Dai J, Meltzer HY. "Significantly lower plasma glycine values and a higher serine/glycine ratio were observed in the depressed group. No significant differences in glutamine, histidine, serine or aspartate levels could be detected between the study groups."

[x] Eur Neuropsychopharmacol. 2013 Aug;23(8):931-40. Glycine treatment of the risk syndrome for psychosis: report of two pilot studies. Woods SW, Walsh BC, Hawkins KA, Miller TJ, Saksa JR, D'Souza DC, Pearlson GD, Javitt DC, McGlashan TH, Krystal JH. "We conclude that glycine was associated with reduced symptoms with promising effect sizes in two pilot studies and a possibility of improvement in cognitive function."


[x] Neural Plast. 2009;2009:768398. High-dose glycine treatment of refractory obsessive-compulsive disorder and body dysmorphic disorder in a 5-year period. Cleveland WL, DeLaPaz RL, Fawwaz RA, Challop RS.

[x] J Psychiatr Res. 2009 Mar;43(6):664-70. Adjunctive glycine in the treatment of obsessive-compulsive disorder in adults. Greenberg WM, Benedict MM, Doerfer J, Perrin M, Panek L, Cleveland WL, Javitt DC.





[26] Glycine and aspirin

[x] Acta Pol Pharm. 2014 Jan-Feb;71(1):139-43. Interaction analysis of aspirin with selective amino acids. Murtaza G, Karim S, Najam-ul-Haq M, Ahmad M, Ismail T, Khan SA, Bin Asad MH, Hussain I.

[x] Adv Ther. 2003 Sep-Oct;20(5):237-45. Acetylsalicylic acid tablets with glycine improve long-term tolerability in antiplatelet drug therapy: results of a noninterventional trial. Kusche W, Paxinos R, Haselmann J, Schwantes U, Breddin HK. "After treatment with Gly-ASA, the mean percentage of patients without GI complaints increased more than 2-fold, from 28.2% to 60.6%. Furthermore, the mean percentage of patients reporting any GI symptoms as "always" present decreased from 8.5% to 0.5%. Gly-ASA tolerability was rated "excellent" or "good" by 98% of the patients."

[x] Arzneimittelforschung. 1991 Aug;41(8):812-4. [The effect of glycine on the gastroduodenal tolerability of acetylsalicylic acid. An endoscopic, controlled double-blind study in healthy subjects]. [Article in German] Müller P, Dammann HG, Bergdolt H, Simon B. "Both ASA-preparations induced comparable gastroduodenal damages during the whole test period: The lesions score of both groups on day 7, 14 and day 28 was almost identical. In contrast to plain ASA, where 9 of 10 volunteers reported gastrointestinal side effects, all subjects receiving ASA in combination with glycine did not complain from any dyspeptic symptoms, i.e. epigastric pain etc."

[x] Hum Exp Toxicol. 1990 Nov;9(6):389-95. Depletion of plasma glycine and effect of glycine by mouth on salicylate metabolism during aspirin overdose. Patel DK, Ogunbona A, Notarianni LJ, Bennett PN.

[x] Proglyta.com - Aspirin and Blindness? "Aspirin is an anti-inflammatory drug, so one would expect it to help. How does that fit into the inflammation story? When a cell is injured, it sends out signals—called prostaglandins—to recruit and activate inflammatory cells—some sort of macrophages that start destroying the local environment in an effort to stop infection. A glycine deficiency makes the macrophages hypersensitive to these prostaglandins. But a deficiency in the widespread micronutrient salicylic acid makes the wounded cells make too much prostaglandin. The key enzyme in making prostaglandins is called cyclooxygenase, or COX, and salicylic acid is a natural COX inhibitor. Aspirin also breaks down in the body to salicylic acid."

[x] Med Klin (Munich). 1990 Jul 15;85(7):429-31. [Gastrointestinal tolerance of 30 mg versus 300 mg acetylsalicylic acid daily. An endoscopically controlled double-blind study of healthy subjects]. [Article in German] Müller P, Dammann HG, Marinis E, Simon B. "Our data suggest that extremely low doses of ASS are almost harmless to the human gastroduodenal mucosa."

[x] Schweiz Med Wochenschr. 1996 Dec 7;126(49):2127-9. [Successful therapy of salicylate poisoning using glycine and activated charcoal]. [Article in German] Mühlebach S, Steger P, Conen D, Wyss PA.




[27] Glycine or collagen for bones/joints

[x] Nutrition. 2005 Nov-Dec;21(11-12):1120-6. Increase in bone mineral density through oral administration of shark gelatin to ovariectomized rats. Nomura Y, Oohashi K, Watanabe M, Kasugai S.

[x] Int J Med Sci. 2009 Oct 9;6(6):312-21. Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: a clinical trial. Crowley DC, Lau FC, Sharma P, Evans M, Guthrie N, Bagchi M, Bagchi D, Dey DK, Raychaudhuri SP.

[x] Arthritis Rheum. 2008 Jul 15;59(7):905-10. A randomized, double-blind, multicenter, controlled clinical trial of chicken type II collagen in patients with rheumatoid arthritis. Zhang LL, Wei W, Xiao F, Xu JH, Bao CD, Ni LQ, Li XF.

[x] Curr Med Res Opin. 2008 May;24(5):1485-96. 24-Week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain. Clark KL, Sebastianelli W, Flechsenhar KR, Aukermann DF, Meza F, Millard RL, Deitch JR, Sherbondy PS, Albert A.

[x] Complement Ther Med. 2012 Jun;20(3):124-30. Effect of collagen hydrolysate in articular pain: a 6-month randomized, double-blind, placebo controlled study. Bruyère O, Zegels B, Leonori L, Rabenda V, Janssen A, Bourges C, Reginster JY.

[x] Osteoporos Int. 2012 Jul;23(7):1909-19. Hydrolyzed collagen improves bone status and prevents bone loss in ovariectomized C3H/HeN mice. Guillerminet F, Fabien-Soulé V, Even PC, Tomé D, Benhamou CL, Roux C, Blais A.

[x] Bone. 2010 Mar;46(3):827-34. Hydrolyzed collagen improves bone metabolism and biomechanical parameters in ovariectomized mice: an in vitro and in vivo study. Guillerminet F1, Beaupied H, Fabien-Soulé V, Tomé D, Benhamou CL, Roux C, Blais A.

[x] J Nutr Sci Vitaminol (Tokyo). 2001 Feb;47(1):84-6. Ingestion of gelatin has differential effect on bone mineral density and body weight in protein undernutrition. Koyama Y, Hirota A, Mori H, Takahara H, Kuwaba K, Kusubata M, Matsubara Y, Kasugai S, Itoh M, Irie S. "CHs dose-dependently promoted the longitudinal bone growth and height of the growth plate in adolescent male rats, whereas gelatin failed to affect longitudinal bone growth."

[x] J Med Food. 2010 Dec;13(6):1385-90. A food supplement of hydrolyzed collagen improves compositional and biodynamic characteristics of vertebrae in ovariectomized rats. de Almeida Jackix E, Cúneo F, Amaya-Farfan J, de Assunção JV, Quintaes KD. "CH supplementation at the higher level in the ovariectomized rat had an unequivocal contribution in the conservation or preservation of vertebral mass, protein content, and mechanical strength not seen when gelatin was used as a supplement. Similar treatment of the intact rat with the CH, however, appeared to have the opposite effect."

[x] Maturitas. 2010 Mar;65(3):253-7. Effect of dietary supplementation with collagen hydrolysates on bone metabolism of postmenopausal women with low mineral density. Cúneo F, Costa-Paiva L, Pinto-Neto AM, Morais SS, Amaya-Farfan J. "CH consumption did not produce any effects on bone metabolism as measured by biochemical indices of bone remodeling in postmenopausal women."


[x] Bone. 2009 May;44(5):942-7. Effects of cod bone gelatin on bone metabolism and bone microarchitecture in ovariectomized rats. Han X, Xu Y, Wang J, Pei X, Yang R, Li N, Li Y. "our data confirmed that the cod bone gelatin treatment at 3 g/kg is effective in the prevention of estrogen deficient bone loss by modulating the expression of RANKL and OPG and suppressing the release of proinflammatory cytokines."

[x] J Med Food. 2013 May;16(5):447-53. Porcine skin gelatin hydrolysate promotes longitudinal bone growth in adolescent rats. Leem KH, Lee S, Jang A, Kim HK.

[x] Amino Acids. 2015 Nov 12. [Epub ahead of print] Estrogen-like osteoprotective effects of glycine in in vitro and in vivo models of menopause. Kim MH, Kim HM, Jeong HJ. "Therefore, we suggest that glycine may be useful for the treatment of menopause."




[28] Glycine (collagen) and ulcers/wounds

[x] Adv Skin Wound Care. 2006 Mar;19(2):92-6. Pressure ulcer healing with a concentrated, fortified, collagen protein hydrolysate supplement: a randomized controlled trial. Lee SK, Posthauer ME, Dorner B, Redovian V, Maloney MJ.

[x] Am J Vet Res. 2000 Dec;61(12):1574-8. Effects of a hydrolyzed collagen dressing on the healing of open wounds in dogs. Swaim SF, Gillette RL, Sartin EA, Hinkle SH, Coolman SL.

[x] Mar Drugs. 2011;9(5):696-711. Oral administration of skin gelatin isolated from Chum salmon (Oncorhynchus keta) enhances wound healing in diabetic rats. Zhang Z, Zhao M, Wang J, Ding Y, Dai X, Li Y.


[x] Pharmatherapeutica. 1985;4(4):227-30. L-cysteine, glycine and dl-threonine in the treatment of hypostatic leg ulceration: a placebo-controlled study. Harvey SG, Gibson JR, Burke CA "The results revealed that the degree of healing and decrease of pain were significantly better in the group of patients receiving the amino acid combination."




[29] Glycine (gelatin) for hair and fingernails

[x] Nadav Pam: Medical evidences of the therapeutic effect of edible gelatin on telogen effluvium and androgenetic alopecia in both men and women (2013)

[x] Review of the therapeutic effect of gelatin as a dietary supplement for fingernail changes and fingernail disorders. Zeev Pam M.D.




[30] Glycine or collagen for skin health

[x] Skin Pharmacol Physiol. 2014;27(1):47-55. Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology: a double-blind, placebo-controlled study. Proksch E, Segger D, Degwert J, Schunck M, Zague V, Oesser S.

[x] J Cosmet Laser Ther. 2013 Nov 18. [Epub ahead of print] Effects of collagen tripeptide supplement on skin properties: A prospective, randomized, controlled study. Choi SY, Ko EJ, Lee YH, Kim BG, Shin HJ, Seo DB, Lee SJ, Kim BJ, Kim MN.

[x] Efficacy Study of Skingain™ ‐ A Product Containing Collagen 1 and a Marine Hydrolysate. Mortensen AW, Strand R

[x] Biosci Biotechnol Biochem. 2009 Apr 23;73(4):930-2. Effects of collagen peptide ingestion on UV-B-induced skin damage. Tanaka M, Koyama Y, Nomura Y.

[x] Skin Pharmacol Physiol. 2014;27(3):113-9. Oral intake of specific bioactive collagen peptides reduces skin wrinkles and increases dermal matrix synthesis. Proksch E, Schunck M, Zague V, Segger D, Degwert J, Oesser S.

[x] Biochem Biophys Res Commun. 2015 Jan 9;456(2):626-30. Oral collagen-derived dipeptides, prolyl-hydroxyproline and hydroxyprolyl-glycine, ameliorate skin barrier dysfunction and alter gene expression profiles in the skin. Shimizu J, Asami N, Kataoka A, Sugihara F, Inoue N, Kimira Y, Wada M, Mano H.

[x] Photodermatol Photoimmunol Photomed. 2013 Aug;29(4):204-11. Collagen hydrolysate intake improves the loss of epidermal barrier function and skin elasticity induced by UVB irradiation in hairless mice. Oba C, Ohara H, Morifuji M, Ito K, Ichikawa S, Kawahata K, Koga J. "Repeated UVB irradiation decreased skin elasticity and dermal hyaluronic acid (HA) content in control mice, whereas collagen hydrolysate significantly suppressed both the increase in TEWL and the decrease in stratum corneum water content and improved skin elasticity and dermal HA content."




[31] Glycine (or gelatin) and benign prostatic hypertrophy

[x] Experientia 1973;29:313-4 Palliative effect of gelatine in benign prostatic hypertrophy E. Aschheim

[x] J Maine Med Assoc. 1958 Mar;49(3):99-101 passim. Palliative treatment of benign prostatic hypertrophy; value of glycine-alanine-glutamic acid combination. FEINBLATT HM, GANT JC.




[32] Glycine: protective mechanisms

[x] Am J Physiol. 1997 Jun;272(6 Pt 1):G1581-6. Kupffer cells contain a glycine-gated chloride channel. Ikejima K, Qu W, Stachlewitz RF, Thurman RG.

[x] Am J Physiol Gastrointest Liver Physiol. 2002 Oct;283(4):G856-63. Molecular evidence for a glycine-gated chloride channel in macrophages and leukocytes. Froh M, Thurman RG, Wheeler MD.

[x] FASEB J. 2000 Mar;14(3):476-84. Glycine-gated chloride channels in neutrophils attenuate calcium influx and superoxide production. Wheeler M, Stachlewitz RF, Yamashina S, Ikejima K, Morrow AL, Thurman RG.

[x] Supplemental Glycine as an “Antidote” to Fructose - Do GLP-1 and Glucagon Mediate This Protection? Mark F. McCarty, James J. DiNicolantonio

[x] Infect Immun. 2001 Sep;69(9):5883-91. Dietary glycine prevents peptidoglycan polysaccharide-induced reactive arthritis in the rat: role for glycine-gated chloride channel. Li X1, Bradford BU, Wheeler MD, Stimpson SA, Pink HM, Brodie TA, Schwab JH, Thurman RG.

[x] J Hepatol. 2008 Jun;48(6):983-92. Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin. Bergheim I, Weber S, Vos M, Krämer S, Volynets V, Kaserouni S, McClain CJ, Bischoff SC.

[x] Diabetes. 2010 Feb;59(2):347-57. Depletion of liver Kupffer cells prevents the development of diet-induced hepatic steatosis and insulin resistance. Huang W, Metlakunta A, Dedousis N, Zhang P, Sipula I, Dube JJ, Scott DK, O'Doherty RM. "As expected, a high-fat or high-sucrose diet induced steatosis and hepatic insulin resistance. However, these metabolic abnormalities were prevented when liver was depleted of KCs. In vitro, KCs recapitulated the in vivo effects of diet by increasing hepatocyte triglyceride accumulation and fatty acid esterification, and decreasing fatty acid oxidation and insulin responsiveness. To address the mechanisms(s) of KC action, we inhibited a panel of cytokines using neutralizing antibodies. Only neutralizing antibodies against tumor necrosis factor-alpha (TNFalpha) attenuated KC-induced alterations in hepatocyte fatty acid oxidation, triglyceride accumulation, and insulin responsiveness."

[x] Methods Mol Biol. 2008;447:199-212. Isolation of Kupffer cells from rats fed chronic ethanol. McMullen MR, Pritchard MT, Nagy LE. "Kupffer cells, the resident macrophages of the liver, are critical to the onset of ethanol-induced liver injury. Activation of Kupffer cells leads to an increased production of proinflammatory cytokines, such as tumor necrosis factor-alpha and also reactive oxygen species, a process mediated in part by changes in lipopolysaccharide-induced TLR4-dependent signal transduction."

[x] Hepatology. 1994 Aug;20(2):453-60. Inactivation of Kupffer cells prevents early alcohol-induced liver injury. Adachi Y, Bradford BU, Gao W, Bojes HK, Thurman RG.

[x] Diabetes. 2007 Aug;56(8):1986-98. Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance. Tsukumo DM, Carvalho-Filho MA, Carvalheira JB, Prada PO, Hirabara SM, Schenka AA, Araújo EP, Vassallo J, Curi R, Velloso LA, Saad MJ. "Here, we show that C3H/HeJ mice, which have a loss-of-function mutation in TLR4, are protected against the development of diet-induced obesity. In addition, these mice demonstrate decreased adiposity, increased oxygen consumption, a decreased respiratory exchange ratio, improved insulin sensitivity, and enhanced insulin-signaling capacity in adipose tissue, muscle, and liver compared with control mice during high-fat feeding."

[x] Atherosclerosis. 2010 Apr;209(2):314-20. Toll like receptor 4 in atherosclerosis and plaque destabilization. den Dekker WK, Cheng C, Pasterkamp G, Duckers HJ.

[x] Med Hypotheses. 2009 Aug;73(2):263-4. The hyperpolarizing impact of glycine on endothelial cells may be anti-atherogenic. McCarty MF, Barroso-Aranda J, Contreras F.

[x] Nutr Cancer. 2001;40(2):197-204. Endothelial cells contain a glycine-gated chloride channel. Yamashina S, Konno A, Wheeler MD, Rusyn I, Rusyn EV, Cox AD, Thurman RG. "Importantly, glycine diminished serum-stimulated proliferation and migration of endothelial cells. Collectively, these data indicate that the inhibitory effect of glycine on growth and migration of endothelial cells is due to activation of a glycine-gated Cl- channel. This hyperpolarizes the cell membrane and blocks influx of Ca2+, thereby minimizing growth factor-mediated signaling."


[x] Atherosclerosis. 1982 Jun;43(2-3):381-91. Reduction of casein-induced hypercholesterolaemia and atherosclerosis in rabbits and rats by dietary glycine, arginine and alanine. Katan MB, Vroomen LH, Hermus RJ. "when we fed rats semi-purified diets containing cholesterol, and casein, casein plus glycine, or soy isolate, we obtained mean serum cholesterol levels of 10.4 mmol/l in the casein group, 4.9 in the casein-plus-glycine group and 3.5 in the soy group."

[x] Clin Exp Immunol. 2012 Feb;167(2):269-74. Cysteine, histidine and glycine exhibit anti-inflammatory effects in human coronary arterial endothelial cells. Hasegawa S, Ichiyama T, Sonaka I, Ohsaki A, Okada S, Wakiguchi H, Kudo K, Kittaka S, Hara M, Furukawa S.

[x] Riley, W. W., et al. Influence of dietary arginine and glycine content on thyroid function and growth of juvenile rainbow trout, Oncorhynchus mykiss (Walbaum). Aquaculture Nutrition 2.4 (1996): 235-242


[x] J Neurosci Res. 2010 Aug 15;88(11):2420-30. The inhibitory neurotransmitter glycine modulates macrophage activity by activation of neutral amino acid transporters. Carmans S, Hendriks JJ, Thewissen K, Van den Eynden J, Stinissen P, Rigo JM, Hellings N. "We demonstrate that glycine does not affect the production of reactive oxygen species but stimulates myelin phagocytosis and the production of the proinflammatory mediators nitric oxide (NO) and tumor necrosis factor (TNF)-alpha by rat macrophages. These effects of glycine are not mediated by the glycine receptor (GlyR) or by glycine transporters (GlyTs), as neither the GlyR antagonist strychnine nor the antagonist of GlyT1 (ALX5407) reverses the observed effects. In contrast, 2-aminoisobutyric acid, a substrate of neutral amino acid transporters (NAATs), inhibits the glycine-mediated enhancement of myelin phagocytosis as well as of NO and TNF-alpha production. In conclusion, our findings demonstrate that glycine modulates macrophage function through activation of NAATs."




[33] Health effects of fish/scallop protein


[x] Biochim Biophys Acta. 2009 Apr;1791(4):254-62. Fish protein hydrolysate elevates plasma bile acids and reduces visceral adipose tissue mass in rats. Liaset B, Madsen L, Hao Q, Criales G, Mellgren G, Marschall HU, Hallenborg P, Espe M, Frøyland L, Kristiansen K.

[x] J Nutr. 2004 Jun;134(6):1320-7. Fish protein hydrolysate reduces plasma total cholesterol, increases the proportion of HDL cholesterol, and lowers acyl-CoA:cholesterol acyltransferase activity in liver of Zucker rats. Wergedahl H1, Liaset B, Gudbrandsen OA, Lied E, Espe M, Muna Z, Mørk S, Berge RK.

[x] Int J Mol Med. 2012 Feb;29(2):311-8. Dietary sardine protein lowers insulin resistance, leptin and TNF-α and beneficially affects adipose tissue oxidative stress in rats with fructose-induced metabolic syndrome. Madani Z, Louchami K, Sener A, Malaisse WJ, Ait Yahia D.

[x] Physiol Genomics. 2010 Feb 4;40(3):189-94. Fish nutrients decrease expression levels of tumor necrosis factor-alpha in cultured human macrophages. Rudkowska I, Marcotte B, Pilon G, Lavigne C, Marette A, Vohl MC.

[x] Lipids Health Dis. 2013 Oct 7;12:143. A fish protein hydrolysate alters fatty acid composition in liver and adipose tissue and increases plasma carnitine levels in a mouse model of chronic inflammation. Bjørndal B, Berge C, Ramsvik MS, Svardal A, Bohov P, Skorve J, Berge RK.

[x] J Biol Chem. 2011 Aug 12;286(32):28382-95. Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome. Liaset B, Hao Q, Jørgensen H, Hallenborg P, Du ZY, Ma T, Marschall HU, Kruhøffer M, Li R, Li Q, Yde CC, Criales G, Bertram HC, Mellgren G, Ofjord ES, Lock EJ, Espe M, Frøyland L, Madsen L, Kristiansen K. "Bile acids (BAs)3 are synthesized in the liver from cholesterol. After their synthesis, they are conjugated to the amino acids taurine or glycine in a species-dependent manner (1). Conjugation of bile acids increases their solubility and facilitates their secretion into bile (2). [...] the dietary levels of these amino acids might be crucial for BA conjugation and secretion [...] In conclusion, we provide compelling evidence that plasma bile acid levels can be modulated by the dietary protein source in high fat-treated rats. Increased levels of plasma BAs were associated with a significant reduction in diet-induced obesity and resulted in increased whole body energy expenditure and dissipation of energy in the form of heat."


[x] PLoS One. 2013 Oct 4;8(10):e77274. Beneficial effects of cod protein on inflammatory cell accumulation in rat skeletal muscle after injury are driven by its high levels of arginine, glycine, taurine and lysine. Dort J, Leblanc N, Maltais-Giguère J, Liaset B, Côté CH, Jacques H.

[x] Appl Physiol Nutr Metab. 2012 Jun;37(3):489-98. Beneficial effects of cod protein on skeletal muscle repair following injury. Dort J, Sirois A, Leblanc N, Côté CH, Jacques H.

[x] Nutr Metab Cardiovasc Dis. 2009 Dec;19(10):690-6. Consumption of cod and weight loss in young overweight and obese adults on an energy reduced diet for 8-weeks. Ramel A, Jonsdottir MT, Thorsdottir I.


[x] Amino Acids. 2014 Mar 23. [Epub ahead of print] Scallop protein with endogenous high taurine and glycine content prevents high-fat, high-sucrose-induced obesity and improves plasma lipid profile in male C57BL/6J mice. Tastesen HS, Keenan AH, Madsen L, Kristiansen K, Liaset B. (via ergo-log)




[34] Glycine and chemotherapy-induced oral mucositis

[x] Natural Science, 5, 972-978. (2013) Glycine supplementation reduces the severity of chemotherapy-induced oral mucositis in hamsters. Sá, O. , Lopes, N. , Alves, M. , Lalla, R. , Oliva, M. and Caran, E. "As compared to control animals, glycine-treated animals demonstrated a highly significant reduction in clinical severity of oral mucositis, neutrophil infiltrate, and MDA levels (p < 0.001 for all)."





[35] Glycine and kidneys


[x] Toxicology. 2006 Jun 15;223(3):202-8. Protection of renal tubular cells against the cytotoxicity of cadmium by glycine. Tang W, Xie J, Shaikh ZA.

[x] Am J Physiol. 1998 Oct;275(4 Pt 2):F595-604. Cyclosporin A increases hypoxia and free radical production in rat kidneys: prevention by dietary glycine. Zhong Z, Arteel GE, Connor HD, Yin M, Frankenberg MV, Stachlewitz RF, Raleigh JA, Mason RP, Thurman RG. "it is concluded that cyclosporin A causes renal injury by mechanisms involving hypoxia-reoxygenation, effects which can be prevented effectively by dietary glycine"

[x] Transplantation. 1997 Jun 15;63(11):1661-7. Prevention of cyclosporine-induced nephrotoxicity with dietary glycine. Thurman RG, Zhong Z, von Frankenberg M, Stachlewitz RF, Bunzendahl H.

[x] Am J Physiol. 1993 Jan;264(1 Pt 2):F94-9. Glycine protection against hypoxic but not phospholipase A2-induced injury in rat proximal tubules. Wetzels JF, Wang X, Gengaro PE, Nemenoff RA, Burke TJ, Schrier RW.

[x] J Lab Clin Med. 1993 Feb;121(2):263-7. Infusion of glycine does not attenuate in vivo ischemic acute renal failure in the rat. Wetzels JF, Yu L, Shanley PF, Burke TJ, Schrier RW.

[x] Kidney Int. 1993 Jun;43(6):1226-8. Glycine reduces early renal parenchymal uptake of cisplatin. Heyman SN, Spokes K, Egorin MJ, Epstein FH.

[x] Kidney Int. 1991 Aug;40(2):273-9. Protective action of glycine in cisplatin nephrotoxicity. Heyman SN, Rosen S, Silva P, Spokes K, Egorin MJ, Epstein FH.


[x] Clin Exp Pharmacol Physiol. 2002 May-Jun;29(5-6):449-54. Effects of glycine on glomerular filtration rate and segmental tubular handling of sodium in conscious rats. Thomsen K, Nielsen CB, Flyvbjerg A. "glycine increases ERPF and GFR and it also inhibits proximal and distal nephron Na+ reabsorption"




[36] Glycine and pancreatic damage (acute pancreatitis)

[x] Pancreatology. 2011;11(1):57-67. Prophylactic glycine administration attenuates pancreatic damage and inflammation in experimental acute pancreatitis. Ceyhan GO, Timm AK, Bergmann F, Günther A, Aghdassi AA, Demir IE, Mayerle J, Kern M, Lerch MM, Büchler MW, Friess H, Schemmer P. "Therefore, glycine seems to be a promising tool for prophylactic treatment of [acute pancreatitis]."




[37] Glycine and trigeminal neuralgia


[x] Zh Nevropatol Psikhiatr Im S S Korsakova. 1991;91(4):105-6. [Glycine in the treatment of trigeminal neuralgia]. [Article in Russian] Megdiatov RS, Karlov VA, Savchenko IuN, Khokhlov AP. "As many as 98 patients suffering from trigeminal neuralgia were given myeglynol (glycine) in a dose of 110 mg/kg a day for 4-5 weeks. A noticeable effect manifesting in the counteracting painful paroxysms was attained in more than 86% of cases. The drug was administered alone at the disease onset. The treatment effect of myeglynol may be related to its capacity to decrease to normal the high concentration of formaldehyde in the blood serum of patients suffering from trigeminal neuralgia."




[38] Glycine and cardiovascular system

[x] Burns. 2013 Jun;39(4):729-35. Effects of glycine supplementation on myocardial damage and cardiac function after severe burn. Zhang Y, Lv SJ, Yan H, Wang L, Liang GP, Wan QX, Peng X.


[x] J Physiol. 2004 Aug 1;558(Pt 3):873-82. Glycine protects cardiomyocytes against lethal reoxygenation injury by inhibiting mitochondrial permeability transition. Ruiz-Meana M, Pina P, Garcia-Dorado D, Rodríguez-Sinovas A, Barba I, Miró-Casas E, Mirabet M, Soler-Soler J.

[x] Can J Physiol Pharmacol. 2015 Jun;93(6):465-73. Vascular endothelial function is improved by oral glycine treatment in aged rats. Gómez-Zamudio JH, García-Macedo R, Lázaro-Suárez M, Ibarra-Barajas M, Kumate J, Cruz M. "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."


[x] Int J Clin Exp Pathol. 2013 Apr 15;6(5):821-30. Print 2013. Effects of glycyl-glutamine dipeptide supplementation on myocardial damage and cardiac function in rats after severe burn injury. Zhang Y, Yan H, Lv SG, Wang L, Liang GP, Wan QX, Peng X.

[x] Zhonghua Shao Shang Za Zhi. 2007 Aug;23(4):244-8. [Protective effects of glycyl-glutamine dipeptide supplement on the heart function in burn rats]. [Article in Chinese] Lv SJ, Zhang Y, Sun Y, Wu W, You ZY, Wang SL, Peng X.


[x] JPEN J Parenter Enteral Nutr. 2007 May-Jun;31(3):173-80. Glycine does not add to the beneficial effects of perioperative oral immune-enhancing nutrition supplements in high-risk cardiac surgery patients. Tepaske R, te Velthuis H, Oudemans-van Straaten HM, Bossuyt PM, Schultz MJ, Eijsman L, Vroom M. [150-300g of glycine before heart surgery --> no benefit]

[x] Acute Card Care. 2006;8(1):58-64. Oral administration of glycine in the prevention of restenosis after coronary angioplasty. A double blind placebo controlled randomized feasibility trial evaluating safety and efficacy of glycine in the prevention of restenosis after angioplasty. Khan M, Ron Van Der Wieken L, Riezebos RK, Tijssen JG, Kiemeneij F, Slagboom T, Laarman GJ. "Chronic oral administration of glycine was safe and feasible and had similar side effects compared to placebo. However, chronic oral administration of glycine did not lead to a significant reduction in restenosis rates at six months after elective PCI."

[x] J Am Heart Assoc. 2015 Dec 31;5(1). pii: e002621. Plasma Glycine and Risk of Acute Myocardial Infarction in Patients With Suspected Stable Angina Pectoris. Ding Y, Svingen GF, Pedersen ER, Gregory JF, Ueland PM, Tell GS, Nygård OK. "Plasma glycine was higher in women than in men and was associated with a more favorable baseline lipid profile and lower prevalence of obesity, hypertension, and diabetes mellitus (all P<0.001). After multivariate adjustment for traditional coronary heart disease risk factors, plasma glycine was inversely associated with risk of AMI (hazard ratio per SD: 0.89; 95% CI, 0.82-0.98; P=0.017)."

[x] Biochem Pharmacol. 2016 Nov 8. pii: S0006-2952(16)30395-1. Glycine Prevents Pressure Overload Induced Cardiac Hypertrophy Mediated by Glycine Receptor. Lu Y, Zhu X, Li J, Fang R, Wang Z, Zhang J, Li K, Li X, Bai H, Yang Q, Ben J, Zhang H, Chen Q.

[x] Cardiovasc Res. 2017 Jan;113(1):52-60. Remote ischemic conditioning provides humoural cross-species cardioprotection through glycine receptor activation. José Alburquerque-Béjar J, Barba I, Valls-Lacalle L, Ruiz-Meana M1, Pecoraro M, Rodríguez-Sinovas A, García-Dorado D.



[Extra] Harmful effects from glycine (note: in these studies, glycine wasn't administered orally)

[x] Mol Cell Biochem. 2014 Apr 17. Glycine aggravates ischemia reperfusion-induced acute kidney injury through N-Methyl-D-Aspartate receptor activation in rats. Arora S, Kaur T, Kaur A, Singh AP. [intraperitoneal injection]


[x] Life Sci. 2011 Aug 15;89(7-8):276-81. Glycine intrastriatal administration induces lipid and protein oxidative damage and alters the enzymatic antioxidant defenses in rat brain. Seminotti B, Knebel LA, Fernandes CG, Amaral AU, da Rosa MS, Eichler P, Leipnitz G, Wajner M.

[x] Mol Cell Biochem. 2014 Oct;395(1-2):125-34. Evidence that glycine induces lipid peroxidation and decreases glutathione concentrations in rat cerebellum. Moura AP, Grings M, Marcowich GF, Bumbel AP, Parmeggiani B, de Moura Alvorcem L, Wajner M, Leipnitz G.

[x] Acta Anaesthesiol Scand. 2006 Feb;50(2):261-2; author reply 262. Glycine is toxic. Hahn RG. "All these comparatives point in the same direction – glycine is the worst irrigating fluid that you can use."

[x] Indian J Anaesth. 2015 May;59(5):318-9. Glycine induced acute transient postoperative visual loss. Pramod A, Rajagopal S, Iyer VP, Murthy HS. "We report a case of transient postoperative blindness following use of large quantities of glycine delivered through a rotatory pump set at an inappropriately high pressure. [...] Her vision showed signs of improvement and returned to normal within 20 h of the procedure."


[x] Acta Anaesthesiol Scand. 1995 Feb;39(2):214-9. Eye symptoms, visual evoked potentials and EEG during intravenous infusion of glycine. Hahn RG, Andersson T, Sikk M.

[x] Indian J Anaesth. 2015 Aug;59(8):531. Glycine induced retinotoxicity is avoidable. Choudhary D, Sethi P, Sharma V, Bhatia PK.


[x] Urol Int. 2013;91(3):249-55. Glycine 1.5% for irrigation should be abandoned. Hahn RG.

[x] Toxicol Pathol. 1987;15(2):194-7. Effect of glycine on the induction of orotic aciduria and urinary bladder tumorigenesis in the rat. Vasudevan S, Laconi E, Abanobi SE, Rao PM, Rajalakshmi S, Sarma DS. "Administration of glycine (2.5 mmoles/100 g) to rats resulted in a 100-fold increase in urinary OA excretion [...] Attempts to determine whether increased exposure of urinary bladder to high concentrations of OA will influence bladder tumorigenesis revealed that chronic administration of glycine (2.5 mmoles/100 g, ip, daily, 5 days a week for 20 weeks) resulted in a 44% increased incidence of hyperplastic, preneoplastic, and neoplastic lesions. Some of these rats also exhibited stones in urinary bladders."

[x] Mol Neurobiol. 2015 Oct 26. [Epub ahead of print] Intracerebral Glycine Administration Impairs Energy and Redox Homeostasis and Induces Glial Reactivity in Cerebral Cortex of Newborn Rats. Moura AP, Parmeggiani B, Grings M, Alvorcem LM, Boldrini RM, Bumbel AP, Motta MM, Seminotti B, Wajner M, Leipnitz G.


[x] Metab Brain Dis. 2016 Jun 23. Glycine and hyperammonemia: potential target for the treatment of hepatic encephalopathy. Kristiansen RG, Rose CF, Ytrebø LM. "Lowering glycine levels has demonstrated to be beneficial in lowering ammonia and well as resolving encephalopathy."

[x] Mol Neurobiol. 2017 Jan 3. Glycine Administration Alters MAPK Signaling Pathways and Causes Neuronal Damage in Rat Brain: Putative Mechanisms Involved in the Neurological Dysfunction in Nonketotic Hyperglycinemia. Moura AP, Parmeggiani B, Gasparotto J, Grings M, Fernandez Cardoso GM, Seminotti B, Moreira JC, Gelain DP, Wajner M, Leipnitz G
.




[Extra] Glycine and gingival inflammation

[x] Clinical and Developmental Immunology 2013;2013:80836 Potential Immune Modularly Role of Glycine in Oral Gingival Inflammation Teresa Schaumann, et al.


[x] J Periodontal Res. 2005 Feb;40(1):43-7. Chronic glycine treatment inhibits ligature-induced periodontal disease in Wistar rats. Breivik T, Gundersen Y, Fonnum F, Vaagenes P, Opstad PK.




[Extra] Glycine and brain, nerves and spinal cord

[x] J Clin Psychopharmacol. 2006 Dec;26(6):595-9. Cerebral metabolic effects of intravenous glycine in healthy human subjects. Neumeister A, Carson R, Henry S, Planeta-Wilson B, Binneman B, Maguire RP, Luckenbaugh DA, D'Souza C, Krystal JH, Frost JJ.


[x] Indian J Physiol Pharmacol. 2010 Oct-Dec;54(4):355-60. Glycine enhances glutamate-induced excitation in ventromedial hypothalamic neurons in awake rats. Mallick HN, Kondoh T, Nishijo H, Ono T, Torii K.

[x] Amino Acids. 2012 Jun;42(6):2129-37. Pharmacokinetics and cerebral distribution of glycine administered to rats. Kawai N, Bannai M, Seki S, Koizumi T, Shinkai K, Nagao K, Matsuzawa D, Takahashi M, Shimizu E.

[x] J Pharmacol Exp Ther. 2012 Apr;341(1):196-204. Microinjection of glycine into the ventral tegmental area selectively decreases ethanol consumption. Li J, Nie H, Bian W, Dave V, Janak PH, Ye JH.

[x] Psychiatry Clin Neurosci. 2011 Mar;65(2):142-9. Oral administration of glycine increases extracellular serotonin but not dopamine in the prefrontal cortex of rats. Bannai M, Kawai N, Nagao K, Nakano S, Matsuzawa D, Shimizu E.

[x] Biol Psychiatry. 2001 May 15;49(10):876-85. Chronic high-dose glycine nutrition: effects on rat brain cell morphology. Shoham S, Javitt DC, Heresco-Levy U. "A reduction in density of class B, N-type Ca(2+) channels in specific brain regions may represent one general adaptation to long-term, high-dose glycine treatment."

[x] Neuropsychopharmacology. 2001 Mar;24(3):330-2. Glycine reduces novelty- and methamphetamine-induced locomotor activity in neonatal ventral hippocampal damaged rats. Kato K, Shishido T, Ono M, Shishido K, Kobayashi M, Niwa S.


[x] Ulus Travma Acil Cerrahi Derg. 2009 Mar;15(2):103-8. Effects of glycine on electrical and histological properties of a rat peripheral nerve injury model. Padilla-Martin K, Baltazar-Rendon B, Gonzalez-Maciel A, Nuno-Licona A, Uribe-Escamilla R, Hernandez-Romero A, Ramos A, Alfaro-Rodriguez A. "According to our results, glycine was effective in the morphologic regeneration and functional recovery of the sciatic nerve post-injury in Wistar rats with one month administration."

[x] Neurosurgery. 1979 Feb;4(2):152-6. Effects of glycine administration on canine experimental spinal spasticity and the levels of glycine, glutamate, and aspartate in the lumbar spinal cord. Smith JE, Hall PV, Galvin MR, Jones AR, Campbell RL.

[x] Pain. 2009 Nov;146(1-2):199-204. Intrathecal glycine for pain and dystonia in complex regional pain syndrome. Munts AG, van der Plas AA, Voormolen JH, Marinus J, Teepe-Twiss IM, Onkenhout W, van Gerven JM, van Hilten JJ. "there were no significant differences between ITG and placebo treatment in any of the outcomes"

[x] Int J Neuropsychopharmacol. 1999 Mar;2(1):35-40. High dose glycine nutrition affects glial cell morphology in rat hippocampus and cerebellum. Shoham S, Javitt DC, Heresco-Levy U. "Adult rats were randomized to receive, for 2 wk, no dietary supplementation or supplementation with 0.8 or 3.2 g/kg per day Gly. [...] No evidence of neuronal or microglial pathology was found. Although astrocyte proliferation was not evident in Gly-treated rats, GFAP-like immunoreactivity was dose-dependently increased in the hippocampus (p<0.01), whereas in cerebellum, a dose dependent decrease in density of astocytic fibres was demonstrated (p<0.01)."

[x] Mol Brain. 2016 May 26;9(1):59. Glycine confers neuroprotection through microRNA-301a/PTEN signaling. Chen J, Zhuang Y, Zhang ZF, Wang S, Jin P, He C, Hu PC, Wang ZF, Li ZQ, Xia GM, Li G, Wang Y, Wan Q. "glycine is an upstream regulator of microRNA-301a"

[x] Sci Rep. 2016 Oct 3;6:34459. Glycine triggers a non-ionotropic activity of GluN2A-containing NMDA receptors to confer neuroprotection. Hu R, Chen J, Lujan B, Lei R, Zhang M, Wang Z, Liao M, Li Z, Wan Y, Liu F, Feng H, Wan Q.




[Extra] Glycine and seizures

[x] Neurochem Res. 1984 Dec;9(12):1711-8. Glycine potentiates the action of some anticonvulsant drugs in some seizure models. Toth E, Lajtha A.

[x] Eur J Pharmacol. 1981 May 22;71(4):495-8. Antagonism of L-glycine to seizures induced by L-kynurenine, quinolinic acid and strychnine in mice. Lapin IP.

[x] Cell Mol Neurobiol. 2009 Mar;29(2):253-61. Glycine provokes lipid oxidative damage and reduces the antioxidant defenses in brain cortex of young rats. Leipnitz G, Solano AF, Seminotti B, Amaral AU, Fernandes CG, Beskow AP, Dutra Filho CS, Wajner M. "Patients affected by nonketotic hyperglycinemia (NKH) usually present severe neurological symptoms and suffer from acute episodes of intractable seizures with leukoencephalopathy[...]"

[x] Neurochem Res. 1983 Mar;8(3):291-302. Anticonvulsant effects of some inhibitory neurotransmitter amino acids. Toth E, Lajtha A, Sarhan S, Seiler N.


[x] Mov Disord. 1988;3(3):222-32. Therapeutic trial with glycine in myoclonus. Truong DD, Fahn S.




[Extra] Glycine, taurine and asthma

[x] Eur Respir J. 2004 Apr;23(4):565-8. Amino acids and asthma: a case-control study. Fogarty A, Broadfield E, Lewis S, Lawson N, Britton J. "there was no difference between cases and controls in any of the other amino acids tested, with the exception of plasma glycine, which was associated with a strongly reduced risk of asthma (odds ratio for the highest tertile compared to lowest 0.30"


[x] FASEB J. 2011 May;25(5):1706-17. Novel expression of a functional glycine receptor chloride channel that attenuates contraction in airway smooth muscle. Yim PD, Gallos G, Xu D, Zhang Y, Emala CW.

[x] Eur J Pharmacol. 2001 Nov 9;431(1):111-7. Effects of taurine on pulmonary responses to antigen in sensitized Brown-Norway rats. Cortijo J, Blesa S, Martinez-Losa M, Mata M, Seda E, Santangelo F, Morcillo EJ.





[Extra] "Glycinergic" drugs

[x] Life Sci. 2013 Mar 21;92(10):576-81. Glycinamide, a glycine pro-drug, induces antinociception by intraperitoneal or oral ingestion in ovariectomized rats. Beyer C, Komisaruk BK, González-Flores O, Gómora-Arrati P.


[x] Eur J Pharmacol. 2009 Aug 15;616(1-3):256-64. Renal ischemia/reperfusion injury in rats is attenuated by a synthetic glycine derivative. Bi W, Wang F, Bi Y, Wang T, Xue P, Zhang Y, Gao X, Liu S, Wang Z, Li M, Baudy-Floc'h M, Robinson SC, Ngerebara N, Bi L.




[Extra] Glycine in dentistry (air-polishing)

[x] Corbella, S. "Adjunctive glycine powder air-polishing for the treatment of peri-implant mucositis: an observational clinical trial." (2014). "In the test group (with glycine powder), a significant reduction of probing depth was observed. Air-abrasive system with glycine powder can be considered as viable treatment option for peri-implant mucositis as an adjunct to professional oral hygiene maneuvers. Moreover, glycine may have an important effect on the mucosal health, with a consequent reduction of probing depth."

[x] J Clin Periodontol. 2008 Apr;35(4):324-32. Effect of glycine powder air-polishing on the gingiva. Petersilka G, Faggion CM Jr, Stratmann U, Gerss J, Ehmke B, Haeberlein I, Flemmig TF. "The data indicated that GPAP results in less gingival erosion than SBAP or hand instrumentation, further supporting the safety of this new debridement technique."

[x] J Periodontol. 2007 Jun;78(6):1002-10. Subgingival debridement efficacy of glycine powder air polishing. Flemmig TF, Hetzel M, Topoll H, Gerss J, Haeberlein I, Petersilka G. "GPAP for 5 seconds per surface is effective in removing most of the subgingival biofilm in periodontal pockets with an APD < or =3 mm."

[x] J Periodontol. 2012 Apr;83(4):444-52. Randomized controlled trial assessing efficacy and safety of glycine powder air polishing in moderate-to-deep periodontal pockets. Flemmig TF, Arushanov D, Daubert D, Rothen M, Mueller G, Leroux BG. "The results indicate that SubGPAP is more efficacious in removing subgingival biofilm in moderate-to-deep periodontal pockets than SRP. Furthermore, full-mouth GPAP may result in a beneficial shift of the oral microbiota and appears to be well tolerated."

[x] Int J Dent Hyg. 2015 Aug;13(3):177-83. Efficacy of glycine powder air polishing in comparison with sodium bicarbonate air polishing and ultrasonic scaling - a double-blind clinico-histopathologic study. Simon CJ, Munivenkatappa Lakshmaiah Venkatesh P, Chickanna R. "GPAP results in clinically significant improvement in plaque and gingival index scores and histologically causes less gingival erosion than SBAP or ultrasonic instrumentation, further supporting the safety of this debridement technique in periodontal maintenance therapy."




[Extra] Glycine receptor in human sperm (acrosome reaction)

[x] Biol Reprod. 1995 Sep;53(3):676-83. Studies of porcine and human sperm suggesting a role for a sperm glycine receptor/Cl- channel in the zona pellucida-initiated acrosome reaction. Melendrez CS, Meizel S.

[x] Reproduction. 2008 Oct;136(4):387-90. Identification and spatial distribution of glycine receptor subunits in human sperm. Kumar P, Meizel S.

[x] Biol Reprod. 2002 Jan;66(1):91-7. A role for the human sperm glycine receptor/Cl(-) channel in the acrosome reaction initiated by recombinant ZP3. Bray C, Son JH, Kumar P, Harris JD, Meizel S.




[Extra] Glycine and opiate addiction (in mice)

[x] Arch Pharm Res. 2003 Dec;26(12):1074-8. Inhibitory effects of glycine on morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity in mice. Shin KW, Hong JT, Yoo HS, Song S, Oh KW. "Accordingly, the inhibition by glycine of the morphine-induced hyperactivity, reverse tolerance and dopamine receptor supersensitivity suggests that glycine might be useful for the treatment of morphine addiction."





[Extra] Other references

[x] BJU Int. 2005 Dec;96(9):1403-8. Effect of glycine on recovery of bladder smooth muscle contractility after acute urinary retention in rats. Hong SK, Son H, Kim SW, Oh SJ, Choi H.

[x] Exp Eye Res. 1993 Nov;57(5):623-8. Decrease in glycation of lens proteins by lysine and glycine by scavenging of glucose and possible mitigation of cataractogenesis. Ramakrishnan S, Sulochana KN.

[x] Amino Acids. 2008 Aug;35(2):451-6. Effects of orally administered glycine on myofibrillar proteolysis and expression of proteolytic-related genes of skeletal muscle in chicks. Nakashima K, Yakabe Y, Ishida A, Katsumata M. "These results indicate that orally administered glycine suppresses myofibrillar proteolysis and expression of proteolytic-related genes of skeletal muscle by decreasing the plasma corticosterone concentration in chicks."

[x] Gene Regul Syst Bio. 2007 Oct 14;1:217-26. Signaling mechanisms of endogenous angiogenesis inhibitors derived from type IV collagen. Sudhakar A, Boosani CS.

[x] Toxicology. 2007 Oct 8;239(3):147-55. The effect of dietary glycine on the hepatic tumor promoting activity of polychlorinated biphenyls (PCBs) in rats. Bunaciu RP, Tharappel JC, Lehmler HJ, Kania-Korwel I, Robertson LW, Srinivasan C, Spear BT, Glauert HP. "But the data overall indicate that Kupffer cells likely do not contribute to the tumor promoting activities of PCB-77 and PCB-153."

[x] Physiol Behav. 2010 Sep 1;101(2):237-44. No long-term weight maintenance effects of gelatin in a supra-sustained protein diet. Hochstenbach-Waelen A1, Westerterp KR, Soenen S, Westerterp-Plantenga MS.

[x] J Psychopharmacol. 2011 Dec;25(12):1632-8. High-dose glycine impairs the prepulse inhibition measure of sensorimotor gating in humans. O'Neill BV, Croft RJ, Mann C, Dang O, Leung S, Galloway MP, Phan KL, Nathan PJ.

[x] Eur J Biochem. 1998 Feb 1;251(3):597-604. Cycloheximide sensitivity of orotic acid biosynthesis induced by ammonia and glycine administration. Vasudevan S, Laconi E, Rao PM, Rajalakshmi S, Sarma DS, La Piana G, Fransvea E, Marzulli D, Lofrumento NE.

[x] J Toxicol Pathol. 2013 Dec;26(4):405-12. A 4-week Repeated Dose Toxicity Study of Glycine in Rats by Gavage Administration. Shibui Y, Miwa T, Yamashita M, Chin K, Kodama T.

[x] Pharmacol Biochem Behav. 2011 Apr;98(2):234-40. Effects of the alpha- and gamma-polymorphs of glycine on the behavior of catalepsy prone rats. Markel AL, Achkasov AF, Alekhina TA, Prokudina OI, Ryazanova MA, Ukolova TN, Efimov VM, Boldyreva EV, Boldyrev VV.

[x] Drug Metab Dispos. 1992 Mar-Apr;20(2):234-40. Availability of glycine and coenzyme A limits glycine conjugation in vivo. Gregus Z, Fekete T, Varga F, Klaassen CD.

[x] Toxicol Lett. 2013 Jul 4;220(2):181-6. Attenuation of subchronic formaldehyde inhalation toxicity with oral administration of glutamate, glycine and methionine. Katsnelson BA, Degtyareva TD, Privalova LI, Minigaliyeva IA, Slyshkina TV, Ryzhov VV, Beresneva OY.

[x] Hepatobiliary Pancreat Dis Int. 2005 Feb;4(1):37-40. Protective effects of glycine pretreatment on brain-death donor liver. Zhang SJ, Shi JH, Tang Z, Wu Y, Chen S.

[x] J Clin Endocrinol Metab. 2005 Mar;90(3):1594-8. Low serine hydroxymethyltransferase activity in the human placenta has important implications for fetal glycine supply. Lewis RM, Godfrey KM, Jackson AA, Cameron IT, Hanson MA.

[x] Transplantation. 2000 Mar 15;69(5):773-80. Inhibition of chronic rejection of aortic allografts by dietary glycine. Yin M, Rusyn I, Schoonhoven R, Graves LM, Rusyn EV, Li X, Li F, Cox AD, Harding TW, Bunzendahl H, Swenberg JA, Thurman RG. "These results indicate that dietary glycine minimizes histopathological changes of chronic rejection by reducing the immune response and, in part, by minimizing proliferation and migration of smooth muscle cells."

[x] Am J Physiol. 1999 Apr;276(4 Pt 1):G924-32. Intravenous glycine improves survival in rat liver transplantation. Schemmer P, Bradford BU, Rose ML, Bunzendahl H, Raleigh JA, Lemasters JJ, Thurman RG.

[x] World J Gastroenterol. 2003 Oct;9(10):2374-6. Effects of glycine on plasma and liver tissue changes of TNF-alpha, ET-1 and nitric oxide contents in rats with obstructive jaundice. Fang HQ1, Liu YB, Li HJ, Peng SY, Wu YL, Xu B, Wang JW, Li JT, Wang XB.

[x] Chest. 2000 Oct;118(4):1150-7. Chicken soup inhibits neutrophil chemotaxis in vitro. Rennard BO, Ertl RF, Gossman GL, Robbins RA, Rennard SI.

[x] Comp Biochem Physiol Comp Physiol. 1992 May;102(1):147-9. The effect of glycine administration on taurine concentration in the rat liver. Galindo JD, Cremades A, Monserrat F, Peñafiel R.

[x] Biochem Int. 1990 Nov;22(4):649-57. Glycine administration decreases hepatic taurine content in mice. Peñafiel R, Galindo JD, Cremades A, Monserrat F.

[x] J Nutr. 1992 Nov;122(11):2066-73. Cysteine and glycine supplementation modulate the metabolic response to tumor necrosis factor alpha in rats fed a low protein diet. Grimble RF, Jackson AA, Persaud C, Wride MJ, Delers F, Engler R.

[x] Acta Pol Pharm. 2012 Nov-Dec;69(6):1303-6. Effect of Gly-Gly-His, Gly-His-Lys and their copper complexes on TNF-alpha-dependent IL-6 secretion in normal human dermal fibroblasts. Gruchlik A1, Jurzak M, Chodurek E, Dzierzewicz Z. "Because of the anti-inflammatory properties, the copper-peptides could be used on the skin surface instead of corticosteroids or non-steroidal anti-inflammatory drugs, which have more side effects. Our observations provide some new information about the role of these tripeptides in skin inflammation."

[x] J Mol Evol. 2014 Jun;78(6):307-9. Genetic code evolution started with the incorporation of glycine, followed by other small hydrophilic amino acids. Bernhardt HS, Patrick WM. "We propose that glycine was the first amino acid to be incorporated into the genetic code, followed by serine, aspartic and/or glutamic acid-small hydrophilic amino acids that all have codons in the bottom right-hand corner of the standard genetic code table."

[x] J Biol Phys. 2015 Sep 15. [Epub ahead of print] Survivability and reactivity of glycine and alanine in early oceans: effects of meteorite impacts. Umeda Y, Fukunaga N, Sekine T, Furukawa Y, Kakegawa T, Kobayashi T, Nakazawa H.

[x] Ter Arkh. 1999;71(11):58-61. [Comparative efficacy of combined therapy with preductal and amino acid composition in elderly patients with coronary heart disease and class II-III angina]. [Article in Russian] Zaslavskaia RM, Kelimberdieva ES, Komissarova IA, Teĭblium MM, Goncharov LF, Goncharova ZF, Akhmetov KZh.

[x] Schilling, M., et al. "Glycine inhibits phospholipolysis of hypoxic membranes." Tx Med 6 (1994): 140-143.

[x] Fertil Steril. 2008 Oct;90(4 Suppl):1460-9. Epub 2007 Dec 11. Dietary glycine does not affect physiological angiogenesis and reproductive function, but inhibits apoptosis in endometrial and ovarian tissue by down-regulation of nuclear factor-kappaB. Laschke MW, Schwender C, Scheuer C, Vollmar B, Menger MD. "ANIMAL(S): Syrian golden hamsters." "Furthermore, glycine acts antiapoptotic in endometrial and ovarian tissue through down-regulation of NF-κB expression. Thus, glycine may be used as a therapeutic agent for disorders involving inflammation or pathological angiogenesis without inducing serious side effects in the female reproductive tract. Future studies may further clarify whether the observed antiapoptotic effect of glycine reduces ovarian tissue damage during cryopreservation and transplantation to increase the success rates of modern fertility preservation techniques."
[x] J Agric Food Chem. 2005 Apr 20;53(8):3259-64. Addition of glycine reduces the content of acrylamide in cereal and potato products. Bråthen E, Kita A, Knutsen SH, Wicklund T.

[x] Am J Obstet Gynecol. 2007 Jan;196(1):65.e1-5. Intermediate metabolism in association with the amino acid profile during the third trimester of normal pregnancy and diet-controlled gestational diabetes. Pappa KI, Vlachos G, Theodora M, Roubelaki M, Angelidou K, Antsaklis A. "Of the 21 amino acids, only methionine, glycine, alanine, citrulline, and ornithine levels were found at significantly higher levels in the NP group"

[x] Sci Rep. 2015 May 22;5:10434. Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defects. Hashizume O, Ohnishi S, Mito T, Shimizu A, Iashikawa K, Nakada K, Soda M, Mano H, Togayachi S, Miyoshi H, Okita K, Hayashi J. "These observations indicated that epigenetic downregulation of both GCAT and SHMT2 with aging (Fig. 3a) was at least partly responsible for the age-associated respiration defects found in elderly fibroblasts (Fig. 1a) by inducing a decrease in glycine production and a resultant decrease in mitochondrial translation. This possibility was supported by our observations that adding glycine to the medium for 10 days restored the reduced respiratory function of TIG102 (Supplementary Fig. 6), suggesting that glycine treatment can effectively prevent elderly fibroblasts from expressing age-associated respiration defects." [ScienceDaily: Scientists reverse aging in human cell lines and give theory of aging a new lease of life]


[x] Int J Sports Med. 1999 Jul;20(5):315-21. The effect of arginine or glycine supplementation on gastrointestinal function, muscle injury, serum amino acid concentrations and performance during a marathon run. Buchman AL, O'Brien W, Ou CN, Rognerud C, Alvarez M, Dennis K, Ahn C.

[x] Psychiatry Res. 2009 Aug 30;173(2):143-9. Oral glycine administration increases brain glycine/creatine ratios in men: a proton magnetic resonance spectroscopy study. Kaufman MJ, Prescot AP, Ongur D, Evins AE, Barros TL, Medeiros CL, Covell J, Wang L, Fava M, Renshaw PF. 

[x] Psychopharmacology (Berl). 2007 Nov;195(1):85-93. High-dose glycine inhibits the loudness dependence of the auditory evoked potential (LDAEP) in healthy humans. O'Neill BV, Croft RJ, Leung S, Oliver C, Phan KL, Nathan PJ.

[x] Scand J Clin Lab Invest. 2007;67(2):143-53. Capacity of glycine to modulate early inflammatory disturbances after serious gunshot injuries in the pig. Gundersen Y, Vaagenes P, Os Ø, Pillgram-Larsen J, Sundnes KO, Opstad PK.

[x] Am J Physiol Endocrinol Metab. 2016 Apr 19:ajpendo.00468.2015. Glycine restores the anabolic response to leucine in a mouse model of acute inflammation. Ham DJ, Caldow MK, Chhen V, Chee A, Wang X, Proud CG, Lynch GS, Koopman R.

[x] Am J Physiol Regul Integr Comp Physiol. 2016 May 25:ajpregu.00043.2016. Glycine Enhances Muscle Protein Mass Associated with Maintaining Akt-mTOR-FOXO1 Signaling and Suppressing TLR4 and NOD2 Signaling in Piglets Challenged with LPS. Liu Y, Wang X, Wu H, Chen S, Zhu H, Zhang J, Hou Y, Hu CA, Zhang G. "We found that 1.0% or 2.0% glycine increased protein/DNA ratio, protein content and RNA/DNA ratio in gastrocnemius or longissimus dorsi (LD) muscles."

[x] J Nutr. 2016 Oct 26. pii: jn231266. Glycine Regulates Protein Turnover by Activating Akt/mTOR and by Inhibiting MuRF1 and Atrogin-1 Gene Expression in C2C12 Myoblasts. Sun K, Wu Z, Ji Y, Wu G. "Our results indicate that glycine is a functional amino acid that improves muscle cell growth."

[x] Curr Opin Clin Nutr Metab Care. 2017 Jul;20(4):237-242. Glycine metabolism in skeletal muscle: implications for metabolic homeostasis. Koopman R, Caldow MK, Ham DJ, Lynch GS. "Recent studies demonstrate that supplemental glycine effectively protects muscles in a variety of wasting models, including cancer cachexia, sepsis, and reduced caloric intake. The underlying mechanisms responsible for the effects of glycine remain unclear but likely involve receptor-mediated responses and modulation of intracellular metabolism."

28 comments:

  1. Is it important to heat gelatin?

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    Replies
    1. No, but I don't like the taste if the gelatin isn't dissolved.

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    2. It's totally unnecessary to microwave or actually heat the gelatin itself, however. If you follow the directions on the package (at least on Knox's Gelatine here in the US), you need to put in bit of cool water into a bowl or mug first, and sprinkle on the gelatin, then let it sit for a minute. THEN you add the hot water -- the directions say "boiling water," but I find that water out of an electric coffeemaker works just fine. You add it to the gelatin suspended on the surface of the water, and stir; it dissolves quickly. If you don't sprinkle the gelatin on the surface of cool water first and just add hot water to dry gelatin, it clumps thickly and never completely dissolves. In any case, there's no need to put the gelatin itself into the microwave -- you can microwave the water if you want, but as I say, a coffeemaker or tea kettle will heat the water just fine.

      Delete
    3. Tea is not a wonder cure-all like many health claims out there try to boast. It has been said to help everything from a cold to cancer. And while most studies are very promising about its benefits, you'll find conflicting studies as well.Moraz Skin Care

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  2. Great information to think about. Thanks. I ended up here by following the link you posted in the Longecity forums.

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  3. I'm dealing with serious health problems involving glutamate excitotoxicity. GABA agonists are very helpful. Taurine is helpful. Theoretically, it seems that glycine ought to be helpful, too. But glycine has a clear excitatory effect on my brain, making everything much worse.

    (I also have a terrible reaction to gelatin and bone broth, though it is unclear whether this is due to the glycine or the glutamate -- or both, or something else.)

    I have been trying to get to the bottom of this for a long time, but it is hard to find anyone talking about this aspect of glycine. The only person I've found is autism researcher Amy Yasko. Here is a summary of her view:

    "Glycine is a fair-weather friend. If more glutamate is around it will pal up with the glutamate and cause more excitotoxin activity. If more GABA is around it will pal up with GABA and be more calming. My experience is that early on most [autistic] children have more glutamate and do not tolerate high doses of any source of glycine. Over time they are able to tolerate it as the balance between glutamate and GABA is more ideal."

    I am very interested in your thoughts!

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    Replies
    1. Hi Anonymous,

      Unfortunately, I have _very little_ knowledge on glycine's effects on neurons. I hope you find the answers by yourself, because I think that I'm not able to help.

      Thanks for informing about Yasko's point of view, it sounds quite interesting.

      So far, two commenters at 180DegreeHealth have mentined that they are getting adverse effects from glycine: http://180degreehealth.com/thyroid-inflammation-metabolic-syndrome-suprising-power-context/

      Here's one part of my answer on one comment:

      "What I find interesting that some neurology researchers have been studying “glycine antagonists” for acute treatment of stroke, because they see glycine as an potential cause excitotoxicity.

      However, it seems that many of “glycine antagonists” have failed, while real glycine seems to have protective effects against stroke

      http://www.ncbi.nlm.nih.gov/pubmed/11277826 “This glycine antagonist joins the growing list of neuroprotectants that have not shown improved outcomes for patients with acute stroke, despite promising preclinical results.”

      http://www.ncbi.nlm.nih.gov/pubmed/10629347 Reduced mortality, risk of disability and lipid peroxidation in the glycine treatment groups (low dose)."

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    2. To anonymous - could you please say more about both glutamate and GABA (what are they, how do they get into our system) and how they react with glycine? It's been interesting that for both my daughter and me taking some glycine at bedtime, far from resulting in more restful sleep, can lead to extreme restlessness and vivid dreams. I'm taking glycine (up to 5g daily) now in the mornings and afternoons to avoid this.

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    3. Oh, btw, my reason for taking glycine is primarily to combat possible inflammation whilst my daughter is focused more on muscle strength and development.

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  4. Do you think that 8g/day would be a good amount for allowing the intestine to heal? I know I have intestinal permiabilty to some degree because I have very visible feedback on the skin of my hands that corresponds exactly to certian foods I eat.

    ReplyDelete
    Replies
    1. Hi,

      8g/day is what Joel Brind (Sweetamine) recommends. I think it's probably a good dose. I'm personally using 2-6 grams of glycine daily and 1 gram of histidine daily.

      I have noticed that glycine powder has a disgusting taste when you consume high amounts. I usually put my glycine powder into "double 00" capsules (Now Foods).

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  5. "Magnesium (bis)glycinate supplements have 6:1 ratio of magnesium:glycine, so eating 350mg magnesium (as magnesium glycinate) daily should yield approximately 2 grams of (di)glycine"

    So your saying when measuring out magnesium glycinate powder we should multiply x 6? For example if I wanted to include 400 mg of magnesiurm from magnesium glycinate that I shouild take 2400 mg of the powder?

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    Replies
    1. I think that 2800mg of the powder is the correct answer. It would contain 2400mg of glycine and 400mg of magnesium. :)

      Delete
  6. Glycine isn't without it's negatives. It has been shown to increase oxalates, both anecdotally and in studies:

    http://www.ncbi.nlm.nih.gov/pubmed/8140673

    And see Ty's posts here:

    http://180degreehealth.com/glycine-insulin-resistance/

    ???

    ReplyDelete
    Replies
    1. Hi Kelly,

      I'm sorry for a late answer. I just didn't notice your message when you posted it...

      The study you are linking doesn't show that glycine would increase oxalates:

      "There were no significant changes in the urinary excretion of oxalate, calcium, or citrate. [...] These results provide no biochemical evidence of an increased risk of renal lithiasis due to glycine irrigation during transurethral operations."

      But I acknowledge that some people seem to have some problems with glycine. I think it should be used with caution, if any symptoms appear.

      Delete
  7. Hello,

    Which local brand of gelatin you are using? I am living in Helsinki.

    ReplyDelete
    Replies
    1. Hi imran,

      Nowadays I don't use gelatin often, but I used to use Dr. Oetker's "liivatejauhe" (65g; sold in food stores) or Now Foods Beef Gelatin (1 pound; ordered from iHerb).

      I have also been using glycine powder from Aminopörssi (located in Konala, Helsinki; hey also have a webstore).

      Delete
  8. love your material and research ethic

    You are providing valuable material

    I am in NEVADA USA age is 70

    I like the GLYCINE article and will definite use as supplement

    THANK YOU

    ReplyDelete
  9. Thank you so much for your mindful aggregation and analysis of the available info on glycine ingestion.

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  10. Thanks for the great article.Just started using Glycine power. Testing it's effects on post-workout inflammation. Playing with daily and post-workout doses. Lower dose morning and higher post training. Too early to tell yet. If you have any suggestions it would be greatly appreciated.

    Thank you!

    ReplyDelete
  11. Hey Vladimir, great blog! I came upon this blog on glycine while doing some research on a blog of my own and it definitely belonged in the first spot on google search. I like how succinct and heavily referenced it is. I have some additional info for you:

    One of the major mechanisms by which glycine can affect health is via the conjugation of bile acids. Both glycine and taurine, which you also mention, are required for conjugation of bile acids, which prevents them from destroying cells in the gall bladder and digestive tract. Glycine conjugation is the major pathway in humans and taurine conjugation is the major pathway in rats.

    An interesting thing to point out here is that glycine synthesis occurs via a few routes, but 2 of the primary ways that don't involve serine involve the methylation process. Specifically, glycine can be made via 5, 10 MTHF which is in the folate cycle and from sarcosine in the choline cycle.

    It's also interesting to note that bile salts require phosphatidylcholine to prevent mucosal injury. PC is upstream from both choline and glycine in the choline cycle, so adequate choline intake improves glycine synthesis, or more accurately, prevents glycine deficiency. This is probably a bigger issue for people with MTHFR SNPs that may decrease glycine synthesis via that route.

    On the choline cycle side of things, there is a SNP in the choline dehydrogenase enzyme that decreases the conversion of choline to trimethylglycine which is the step prior to the one that powers methylation. Trimethylglycine(TMG) is just like the name suggests, a glycine with 3 methyl groups. The gradual removal of these 3 methyl groups eventually produces glycine, but if you have the SNP that reduces your ability to make TMG you will also synthesize less glycine via this route.

    Here's a figure showing this route...

    http://www.nature.com/ncomms/2016/160129/ncomms10558/fig_tab/ncomms10558_F3.html

    There's a lot more to it, but I don't want to clog up your comments section. Thanks for the great blog, it was definitely informative.

    ReplyDelete
  12. Dr Anthony Samsel's extensive research found that gelatin is contaminated with glyphosate, which in fact blocks the uptake of glycine, so eating gelatin could reduce glycine in our body. See https://www.youtube.com/watch?v=BPhfJx0o38o

    ReplyDelete
  13. Hi, I didn't find the key line shown in this study
    Respond to molenaara@hotmail.com if possible

    [x] Trends Biochem Sci. 2014 Apr;39(4):191-198. Serine and glycine metabolism in cancer. Amelio I, Cutruzzolá F, Antonov A, Agostini M, Melino G. [Ray Peat: "When tumors aren't getting enough sugar and fat, they cause proteins to be broken down, and glutamine, glycine, and serine can be used for energy. But when glycine is present in the diet, it has various anti-tumor effects."]

    ReplyDelete
    Replies
    1. Hi Anonymous,

      That was a quote by biologist Ray Peat. It's not a citation from the actual paper, therefore the [square brackets]. :-)

      Delete
  14. Thank you for sharing great thoughts here. Indeed, amino acids are beneficial in lots of ways.

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  15. Could you take a Taurine and Glycine supplement at the same time or would they cancel out each one's benefit?

    ReplyDelete
  16. This is the first time i read this type of blog...Thanks for sharing this blog..

    ReplyDelete