Glycine: The Versatile Anti-inflammatory NutrientVladimir Heiskanen

Vladimir “Valtsu” Heiskanen

+ Valtsu’s (my English blog)+ Guest posts @ 180DegreeHealth and veteraaniurheilija

1 Glycine: Basics2 Essentiality of glycine3 Metabolic syndrome and glycine4 Stroke and glycine5 Glycine and other diseases6 Dietary sources of glycine

Glycine: Basics (1.1)- The smallest amino acid

carboxyl groupamino group

“side-chain”

side-chain of lysine(without the “g”)

side-chain of histidine

Glycine: Basics (1.2)- One of the 20 common amino acids that make up proteins

- A “non-essential amino-acid” (can be synthesized from other compounds)

Glycine: Basics (1.3)- Body uses glycine for the production of

* Collagen protein (most abundant protein in mammals)

* Other stuff: porphyrins, purine bases, creatine, glutathione, bile salts,hippuric acid

Essentiality of glycine (2.1)- French and Spanish researchers analyzed glycine metabolism and concluded (2009):

“the amount of glycine available from synthesis, about 3 g/day, together with that available from the diet, in the range 1.5-3.0 g/day, may fall significantly short of the amount needed for all metabolic uses, including collagen synthesis by about 10 g per day for a 70 kg human. 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.”

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.

Essentiality of glycine (2.2)A recent review article had a similar conclusion (2013):

“this nutrient has been used to: (1) prevent tissue injury; (2) enhance anti-oxidative capacity; (3) promote protein synthesis and wound healing; (4) improve immunity; and (5) treat metabolic disorders in obesity, diabetes, cardiovascular disease, ischemia-reperfusion injuries, cancers, and various inflammatory diseases. These multiple beneficial effects of glycine, coupled with its insufficient de novo synthesis, support the notion that it is a conditionally essential and also a functional amino acid for mammals (including pigs and humans).”

Amino Acids. 2013 Sep;45(3):463-77. doi: 10.1007/s00726-013-1493-1. Epub 2013 Apr 25. Glycine metabolism in animals and humans: implications for nutrition and health. Wang W, Wu Z, Dai Z, Yang Y, Wang J, Wu G.

Metabolic Syndrome and Glycine (3.1)

Q: How does sugar/fat/alcohol cause metabolic syndrome?A: By causing inflammation.

Q: How do they cause inflammation?A: By increasing the amount of endotoxin in the bloodstream.

Q: What is “endotoxin”?A: Endotoxin refers to bacterial lipopolysaccharides (LPS). Immune system becomes activated when these LPS molecules get from the gut into the bloodstream.

Metabolic Syndrome and Glycine (3.2)

Q: How does immune system it get activated by endotoxin (LPS)?A: Endotoxin is recognized by toll-like receptor 4 (TLR4). This leads to immune activation and some harmful consequences such as

* Production of pro-inflammatory cytokines (TNF-α, IL-6)* Increased cortisol activation (HSD-11β)

Q: What does that mean?A: We can prevent metabolic syndrome by decreasing endotoxin or inflammation. Rats become almost immune to metabolic syndrome, when the inflammation response is inhibited, or when you prevent endotoxemia with antibiotics. On the other hand, you don’t need sugar, fat and alcohol to cause the problems. You can simply inject some endotoxin (LPS) into the rats, and they develop inflammation, fatty liver, obesity and insulin resistance.

Sugar, Fat,Alcohol

Bacterial endotoxin (LPS) in blood

Inflammation!

Insulin resistance, abdominal obesity, hypertension, liver damage...

Metabolic Syndrome and Glycine (3.3)

Q: Wow.A: The most important thing is to eat a healthy diet. Most people acknowledge that antioxidants and vitamins are important, but it’s important to consider that some amino acids such as glycine and histidine, have very powerful anti-inflammatory effects.

Metabolic Syndrome and Glycine (3.4)

- Addition of 30% sucrose to rats’ drinking water -> abdominal obesity and high blood pressure, triglycerides and NEFA (in 20 weeks). These effects are almost completely reversed by 1% glycine (in 4 weeks).

Am J Physiol Regul Integr Comp Physiol. 2004 Dec;287(6):R1387-93. Epub 2004 Aug 26. 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.

Metabolic Syndrome and Glycine (3.5)

- High dose of glycine reverses most of the damage caused by high amounts of alcohol:

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.

Metabolic Syndrome and Glycine (3.6)- Glycine for humans with metabolic syndrome (5-15 grams/day):

“A1C levels of patients given glycine were significantly lower after 3 months of treatment than those of the placebo group.”

“A significant reduction in TNF-receptor I levels was observed in patients given glycine compared with placebo.”

“Individuals treated with glycine showed a 25% decrease in TBARS compared with the placebo-treated group.”

“Systolic blood pressure (SBP) also showed a significant decrease in the glycine-treated men (p = 0.043).”

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.

Can J Physiol Pharmacol. 2013 Oct;91(10):855-60. doi: 10.1139/cjpp-2012-0341. Epub 2013 Jun 17. 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.

Metabolic Syndrome and Glycine (3.7)- Glycine+cysteine for 2 weeks: Restores many important metabolic markers of elderly humans (glutathione, mitochondrial fuel oxidation, F2-isoprostanes, NEFA):

Aging Cell. 2013 Jun;12(3):415-25. doi: 10.1111/acel.12073. Epub 2013 Apr 19. 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.

Am J Clin Nutr. 2011 Sep;94(3):847-53. doi: 10.3945/ajcn.110.003483. Epub 2011 Jul 27. 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.

Metabolic Syndrome and Glycine (3.8)Q: Why does glycine have these beneficial effects? Is it needed for the synthesis of some anti-inflammatory proteins, or something..?

A: No. Many cell types have glycine-gated chloride channels. Glycine modulates the function of immune cells and endothelial cell via these channels.

But yes, some of the benefits are probably related to synthesis of collagen and glutathione.

Stroke and glycine (4.1)In a double-blind placebo study (n=200), 1.0-2.0 grams/d of sublingual glycine protected powerfully from stroke.

Compared to placebo, the people receiving glycine had:- 66% decreased risk of moderate/severe disability- 50% lower levels of cerebrospinal fluid lipid peroxides- 40% lower mortality

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.

source: http://medical-dictionary.thefreedictionary.com/sublingual

Glycine and other diseases: Human trials (5.1)

- High-dose glycine is commonly used for schizophrenia with good results (~60 grams a day).

- Glycine (3 grams) improves sleep quality in some subjects

- Glycine and cysteine seem to be beneficial for HIV-patients as well

- An unpublished study showing significant benefit for osteoporosis, arthrosis, physical injuries etc… ( http://www.eurekalert.org/pub_releases/2007-08/udg-tas073107.php )

Glycine and other diseases: Animal studies (5.2)

Glycine protects animals (rats/mice/chicken/rabbits) from:

- Diabetes- Tumor growth, cancer cachexia and chemotherapy- Methionine and casein (“animal protein”)- Endotoxin and sepsis- Liver damage- Ischemia and hemorrhagic shock

- Acid reflux esophagitis- Protein deficiency- Hypercholesterolemia (in some cases)- Lead and cadmium toxicity- Dental caries- Gastric ulcers/lesions and colitis- Platelet aggregation- Birth defects...and death (by increasing lifespan)

Dietary sources of glycine (6.1)

1) Glycine powder*2) Gelatin3) Collagen

Image sources: http://www.aminoporssi.fi/pure_glycine http://www.kauppahalli24.fi/oetker-65g-liivatejau http://www.iherb.com/product-reviews/Now-Foods-Real-Food-Beef-Gelatin-Powder-1-lb-454-g/400/?fr=2 https://www.terveysmarket.fi/tuoteryhmat/210-kollageenituotteet/tuote/1135-skingain-beauty-booster-kollageenituote/

Dietary sources of glycine (6.2)

4) Magnesium (bis)glycinate

5) Real food:- head cheese- ground meat- bone broth- etc.

http://www.valioravinto.fi/kelasin-magnesium

Thanks for listening!

Questions..?