glycine_molecule_big

The amino acid and neurotransmitter glycine has interested me for awhile, especially due to its high presence in gelatinous foods and its ability to excite or inhibit neurons depending on the surrounding physiological conditions. For example, in the forebrain, it is an N-methyl-D-aspartate (NMDA) receptor coagonist, promoting the excitatory actions of glutamate, while also being the major inhibitory neurotransmitter in the brainstem and spinal cord, regulating motor and sensory function.

It’s hard to talk about glycine in a nutritional context without discussing gelatin, which represents the majority of my relationship with glycine. Glycine comprises about 20% of gelatin whereas it’s relatively low in meat, and in the standard Western diet where mainly muscle meat is consumed and animal collagen neglected, it’s important to know the role it plays in our health.

I first learned about gelatin’s intestinal benefits in 2013 while exploring the Paleo, GAPS, and Keto worlds, and initially experimented with homemade bone broth (which is quite palatable and remembering it makes me crave some), then Great Lakes Gelatin, and most recently, Great Lakes Collagen Hydrolysate, which I favor because it doesn’t congeal and is barely noticeable when added to drinks. I like to put it in my fresh-squeezed lemonade or just plain water.

Glycine is a large reason for gelatin’s gut benefits. Glycine is taken up into intestinal cells and “nurtures” them by managing cellular requirements, fighting oxidative stress, protecting intracellular glutathione, and repairing gut irritation and damage. It protects against ulcers by decreasing excessive acid secretion caused by chemicals and stress (Tariq, et al., 1997), but it also stimulates healthy, adequate levels of gastric acid secretion (Wald, et al., 1982; Meerza, et al., 2017).

glycine_cortisol_insulin

Chronic stress damages the intestinal wall by way of prolonged glucocorticoid release, contributing to “leaky gut”. Glycine has a potent anti-stress effect, reducing plasma cortisol by up to 80% compared to controls (Nakashima, et al., 2008).

Collagen intake significantly improves skin quality, significantly reducing wrinkles such as around the eyes over just 8 weeks of ingestion, with long-lasting effects observed 4 weeks after cessation (Proksch, et al., 2014).

glycine_endotoxin

Glycine downregulates the TLR4 signaling pathway of endotoxin, a mediator of inflammation that is released by bacterial cell membranes. Glycine reduces endotoxic liver damage and inflammatory cytokines TNF-alpha and NF-kappaB induced by endotoxin, and promotes anti-inflammatory cytokines like interleukin 10, improving the survival rates of mice during endotoxemic shock (Bruck, et al., 2003; Xu, et al., 2008). 

The endotoxin-like peptidoglycan polysaccharide (PG-PS) causes rheumatoid arthritis by activating an inflammatory immune reaction causing macrophages to release cytokines. Glycine interacts directly with these macrophages to stop inflammation, thus treating PG-PS-induced arthritis (Li, et al., 2001).

Glycine inhibits the growth of new blood vessels in colon cancer (Bruns, et al., 2016). Polyunsaturated fats (e.g. corn oil, omega-6) and peroxisomal proliferators promote tumors by increasing cell proliferation. Dietary glycine suppresses cellular proliferation by both agents. In mice with melanoma tumors, glycine-treated mice had tumors weighing 65% less and with 70% fewer arteries than mice not fed glycine (Rose, et al., 1999).

Glycine infusion significantly increases vasopressin (antidiuretic hormone) by a mean of 60% above baseline (Hahn, et al., 1991). Vasopressin deficiency is seen in schizophrenia (Rubin, et al., 2014), insomnia, diabetes insipidus (Barbot, et al., 2018), bed wetting (Aikawa, et al., 1998), dysautonomia, postural orthostatic tachycardia syndrome, and adrenal insufficiency, so glycine can be of possible therapeutic value in all of these conditions. Intranasal vasopressin improves social deficits in autistic children (Parker, et al., 2019) and improves sleep in the elderly by inhibiting the hypopituitary-adrenal system and decreasing cortisol (Perras, et al., 1999; Perras, et al., 2003). High-dose glycine resulted in a 30% decrease in the negative symptoms of schizophrenia, thought to be mediated by its modulation of the aberrant glutaminergic functioning observed in schizophrenics (Heresco-Levy, et al., 1999).

Glycine is protective against the effects of sugar-induced metabolic syndrome due to its protective effects on liver mitochondria that metabolize sucrose. In patients with metabolic syndrome, treatment with 15 grams daily of glycine prevents fatty liver, hypertension, normalizes serum triglycerides and insulin levels, prevents stomach fat increase, and boosts the antioxidant glutathione (McCarty and DiNicolantonio 2014). In obese mice, a 40% caloric deficit combined with glycine accelerated whole-body fat loss (by 14%) while preserving lean mass (by 27%) and muscle mass, compared to caloric restricted mice treated with alanine (Caldow, et al., 2016). 

Perhaps the most profound known property of glycine is its ability to reverse aging in human mitochondria. Aging causes cumulative defects in cellular respiration that eventually lead to death. Researchers looked for genes that could epigenetically mediate these changes and found two, CGAT and SHMT2, that also happen to regulate glycine production in mitochondria. By altering these genes, mitochondrial function can be restored. After 10 days of treating a 97 year-old cell culture with glycine, its age-associated respiration defects were reversed. The implications of this in a clinical context have yet to be explored (Hashizume, et al., 2015).

Glycine has the potential to treat obsessive-compulsive disorder and body dysmorphic disorder. In a case study of a young man with treatment-resistant OCD and BDD that rendered him house-bound, treatment with glycine led to such a profound improvement in symptoms that he resumed his education and social life (Cleveland, et al., 2009). 

Fake skeptics who subscribe to “evidence-based medicine” usually scoff at anything that isn’t a randomized double-blind placebo-controlled peer-reviewed trial, like their beloved SSRIs and antibiotics that, coincidentally, completely failed this young man. I think it’s quite funny how “evidence-based” practices are increasingly revealed to be driven by fraudulent and fabricated data (Garmendia, et al., 2019), SSRIs being one such example (Ioannidis, 2008; Ioannidis, 2016), while inexpensive amino acids and other easy, simple interventions can rescue people from seemingly hopeless plights. How many people have died and will continue to die because the authorities meant to help them neglect or harm instead, and the idea of empowering yourself outside the Overton window is so culturally vilified? In light of this, it’s important to build a trust of one’s own faculties over the coercive narcissism of various authoritarian industries and their ulterior motives. A cautious, adaptive, modest, but radical, empiricism.

Glycine Supplementation

Works Cited

Aikawa, Tsutomu, et al. “The Arginine-Vasopressin Secretion Profile of Children with Primary Nocturnal Enuresis.” European Urology, vol. 33, no. Suppl. 3, 1998, pp. 41–44., doi:10.1159/000052242.

Barbot, Mattia, et al. “Cardiovascular Autonomic Dysfunction in Patients with Idiopathic Diabetes Insipidus.” Pituitary, vol. 21, no. 1, 2017, pp. 50–55., doi:10.1007/s11102-017-0846-2.

Bruck, Rafael, et al. “Glycine Modulates Cytokine Secretion, Inhibits Hepatic Damage and Improves Survival in a Model of Endotoxemia in Mice.” Liver International, vol. 23, no. 4, 2003, pp. 276–282., doi:10.1034/j.1600-0676.2003.00839.x.

Bruns, Helge, et al. “Glycine Inhibits Angiogenesis in Colorectal Cancer: Role of Endothelial Cells.” Amino Acids, vol. 48, no. 11, 2016, pp. 2549–2558., doi:10.1007/s00726-016-2278-0.

Caldow, Marissa K., et al. “Glycine Supplementation during Calorie Restriction Accelerates Fat Loss and Protects against Further Muscle Loss in Obese Mice.” Clinical Nutrition, vol. 35, no. 5, 2016, pp. 1118–1126., doi:10.1016/j.clnu.2015.08.013.

Christie, Graham R., et al. “Glycine Supply to Human Enterocytes Mediated by High-Affinity Basolateral GLYT1.” Gastroenterology, vol. 120, no. 2, 2001, pp. 439–448., doi:10.1053/gast.2001.21207.

Cleveland, W. Louis, et al. “High-Dose Glycine Treatment of Refractory Obsessive-Compulsive Disorder and Body Dysmorphic Disorder in a 5-Year Period.” Neural Plasticity, vol. 2009, 2009, pp. 1–25., doi:10.1155/2009/768398.

Garmendia, Craig A., et al. “Evaluation of the Inclusion of Studies Identified by the FDA as Having Falsified Data in the Results of Meta-Analyses.” JAMA Internal Medicine, vol. 179, no. 4, 2019, p. 582., doi:10.1001/jamainternmed.2018.7661.

“Gelatin, Glycine, and Metabolism.” Gelatin, Glycine, and Metabolism – Functional Performance Systems (FPS), www.functionalps.com/blog/2012/03/12/gelatin-glycine-and-metabolism/.

“GlaxoSmithKline to Plead Guilty and Pay $3 Billion to Resolve Fraud Allegations and Failure to Report Safety Data.” The United States Department of Justice, 22 May 2015, http://www.justice.gov/opa/pr/glaxosmithkline-plead-guilty-and-pay-3-billion-resolve-fraud-allegations-and-failure-report.

Hahn, Robert G., et al. “Vasopressin and Cortisol Levels in Response to Glycine Infusion.” Scandinavian Journal of Urology and Nephrology, vol. 25, no. 2, 1991, pp. 121–123., doi:10.3109/00365599109024545.

Hashizume, Osamu, et al. “Epigenetic Regulation of the Nuclear-Coded GCAT and SHMT2 Genes Confers Human Age-Associated Mitochondrial Respiration Defects.” Scientific Reports, vol. 5, no. 1, 2015, doi:10.1038/srep10434.

Heresco-Levy, Uriel, et al. “Efficacy of High-Dose Glycine in the Treatment of Enduring Negative Symptoms of Schizophrenia.” Archives of General Psychiatry, vol. 56, no. 1, 1999, p. 29., doi:10.1001/archpsyc.56.1.29.

Ioannidis, John Pa. “Effectiveness of Antidepressants: an Evidence Myth Constructed from a Thousand Randomized Trials?” Philosophy, Ethics, and Humanities in Medicine, vol. 3, no. 1, 2008, p. 14., doi:10.1186/1747-5341-3-14.

Ioannidis, John P.a. “The Mass Production of Redundant, Misleading, and Conflicted Systematic Reviews and Meta-Analyses.” The Milbank Quarterly, vol. 94, no. 3, 2016, pp. 485–514., doi:10.1111/1468-0009.12210.

Li, X., et al. “Dietary Glycine Prevents Peptidoglycan Polysaccharide-Induced Reactive Arthritis in the Rat: Role for Glycine-Gated Chloride Channel.” Infection and Immunity, vol. 69, no. 9, 2001, pp. 5883–5891., doi:10.1128/iai.69.9.5883-5891.2001.

Mccarty, Mark F, and James J Dinicolantonio. “The Cardiometabolic Benefits of Glycine: Is Glycine an ‘Antidote’ to Dietary Fructose?” Open Heart, vol. 1, no. 1, 2014, doi:10.1136/openhrt-2014-000103.

Nakashima, K., et al. “Effects of Orally Administered Glycine on Myofibrillar Proteolysis and Expression of Proteolytic-Related Genes of Skeletal Muscle in Chicks.” Amino Acids, vol. 35, no. 2, 2007, pp. 451–456., doi:10.1007/s00726-007-0573-5.

Parker, Karen J., et al. “A Randomized Placebo-Controlled Pilot Trial Shows That Intranasal Vasopressin Improves Social Deficits in Children with Autism.” Science Translational Medicine, vol. 11, no. 491, 2019, doi:10.1126/scitranslmed.aau7356.

Perras, Boris, et al. “Beneficial Treatment of Age-Related Sleep Disturbances With Prolonged Intranasal Vasopressin.” Journal of Clinical Psychopharmacology, vol. 19, no. 1, 1999, pp. 28–36., doi:10.1097/00004714-199902000-00007.

Perras, Boris, et al. “Improvement of Sleep and Pituitary-Adrenal Inhibition After Subchronic Intranasal Vasopressin Treatment in Elderly Humans.” Journal of Clinical Psychopharmacology, vol. 23, no. 1, 2003, pp. 35–44., doi:10.1097/00004714-200302000-00007.

Proksch, E., et al. “Oral Intake of Specific Bioactive Collagen Peptides Reduces Skin Wrinkles and Increases Dermal Matrix Synthesis.” Skin Pharmacology and Physiology, vol. 27, no. 3, 2014, pp. 113–119., doi:10.1159/000355523.

“Protective Glycine.” Protective Glycine – Functional Performance Systems (FPS), www.functionalps.com/blog/2012/06/29/protective-glycine/.

Razak, Meerza Abdul, et al. “Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review.” Oxidative Medicine and Cellular Longevity, vol. 2017, 2017, pp. 1–8., doi:10.1155/2017/1716701.

Rose, Michelle L., et al. “Dietary Glycine Inhibits the Growth of B16 Melanoma Tumors in Mice.” Carcinogenesis, vol. 20, no. 5, 1999, pp. 793–798., doi:10.1093/carcin/20.5.793.

Rubin, Leah H., et al. “Reduced Levels of Vasopressin and Reduced Behavioral Modulation of Oxytocin in Psychotic Disorders.” Schizophrenia Bulletin, vol. 40, no. 6, 2014, pp. 1374–1384., doi:10.1093/schbul/sbu027.

Tariq, M, and A R Al Moutaery. “Studies on the Antisecretory, Gastric Anti-Ulcer and Cytoprotective Properties of Glycine.” Research Communications in Molecular Pathology and Pharmacology, U.S. National Library of Medicine, Aug. 1997, http://www.ncbi.nlm.nih.gov/pubmed/9344231.

Wald, A., and S. A. Adibi. “Stimulation of Gastric Acid Secreted by Glycine and Related Oligopeptides in Humans.” American Journal of Physiology-Gastrointestinal and Liver Physiology, vol. 242, no. 2, 1982, doi:10.1152/ajpgi.1982.242.2.g85.

Xu, Fa Liang, et al. “Glycine Attenuates Endotoxin-Induced Liver Injury by Downregulating TLR4 Signaling in Kupffer Cells.” The American Journal of Surgery, vol. 196, no. 1, 2008, pp. 139–148., doi:10.1016/j.amjsurg.2007.09.045.

Yamashina, Shunhei, et al. “Glycine as a Potent Anti-Angiogenic Nutrient for Tumor Growth.” Journal of Gastroenterology and Hepatology, vol. 22, no. s1, 2007, doi:10.1111/j.1440-1746.2006.04655.x.

Zheng, Gen, et al. “Chronic Stress and Intestinal Barrier Dysfunction: Glucocorticoid Receptor and Transcription Repressor HES1 Regulate Tight Junction Protein Claudin-1 Promoter.” Scientific Reports, vol. 7, no. 1, 2017, doi:10.1038/s41598-017-04755-w.

One thought on “Glycine’s Myriad Health Benefits: Anti-Aging, Anti-Cancer, Anti-Stress

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.