Glycine

DESCRIPTION

Glycine is a protein amino acid found in the protein of all life forms. It is the simplest amino acid in the body and the only protein amino acid that does not have chirality. Although most glycine is found in proteins, free glycine is found in body fluids as well as in plants. The normal diet contributes approximately 2 grams of glycine daily.

Glycine is not considered an essential amino acid, i. e., the cells in the body can synthesize sufficient amounts of glycine to meet physiological requirements. However, glycine is of major importance in the synthesis of proteins, peptides, purines, adenosine triphosphate (ATP), nucleic acids, porphyrins, hemoglobin, glutathione, creatine, bile salts, one-carbon fragments, glucose, glycogen, and L-serine and other amino acids. Glycine is also a neurotransmitter in the central nervous system (CNS). Glycine and gamma-aminobutyric acid (GABA) are the major inhibitory neurotransmitters in the CNS. Recently, a glycine-gated chloride channel has been identified in neurophils that can attenuate increases in intracellular calcium ions and diminish oxidant damage mediated by these white blood cells. Thus, glycine may be a novel antioxidant.

Glycine is also known as amino acetic acid, aminoethanolic acid, glycocoll, glycinium and sucre de gelatine. Its IUPAC abbreviation is Gly and its one-letter abbreviation, used when spelling out protein structures, is G. It is a neutral amino acid. Glycine is a solid water-soluble substance that has a sweetish taste. Its structural formula is:

Glycine

ACTIONS AND PHARMACOLOGY

ACTIONS

Supplemental glycine may have antispastic activity. Very early findings suggest it may also have antipsychotic activity as well as antioxidant and anti-inflammatory activities.

MECHANISM OF ACTION

In the CNS, there exist strychnine-sensitive glycine binding sites as well as strychnine-insensitive glycine binding sites. The strychnine-insensitive glycine-binding site is located on the NMDA receptor complex. The strychnine-sensitive glycine receptor complex is comprised of a chloride channel and is a member of the ligand-gated ion channel superfamily. The putative antispastic activity of supplemental glycine could be mediated by glycine's binding to strychnine-sensitive binding sites in the spinal cord. This would result in increased chloride conductance and consequent enhancement of inhibitory neurotransmission.

The ability of glycine to potentiate NMDA receptor-mediated neurotransmission raised the possibility of its use in the management of neuroleptic-resistant negative symptoms in schizophrenia.

Animal studies indicate that supplemental glycine protects against endotoxin-induced lethality, hypoxia-reperfusion injury after liver transplantation, and D-galactosamine-mediated liver injury. Neutrophils are thought to participate in these pathologic processes via invasion of tissue and releasing such reactive oxygen species as superoxide. In vitro studies have shown that neutrophils contain a glycine-gated chloride channel that can attenuate increases in intracellular calcium and diminsh neutrophil oxidant production. This research is ealy-stage, but suggests that supplementary glycine may turn out to be useful in processes where neutrophil infiltration contributes to toxicity, such as ARDS.

PHARMACOKINETICS

Following ingestion of glycine, the amino acid is absorbed from the small intestine via an active transport mechanism. From the small intestine, glycine is transported to the liver by means of the portal circulation where a portion enters into one of several metabolic pathways. Glycine not metabolized in the liver enters the systemic circulation and is distributed to various tissues in the body. Glycine readily crosses the blood-brain barrier.

INDICATIONS AND USAGE

Glycine may be indicated to help alleviate the symptoms of spasticity. An indication for potentiating some anti-convulsant drugs and preventing some seizures could emerge, as could an indication for its use in managing schizophrenia. Research in progress also suggests usefulness in some cancers. There is no evidence to support use of glycine as an ergogenic aid, and it is too early to say whether it can play any useful role in lipid metabolism. There are no well-designed clinical trials to support its use in benign prostate hypertrophy.

RESEARCH SUMMARY

Glycine first attracted interest in the medical research community for its reputed ability to dampen reflex excitability in the CNS. A pilot study of its effects on severe chronic leg spasticity (most of the subjects were suffering from chronic multiple sclerosis) yielded improvement in spasticity and mobility of the lower limbs, rated at about 25% overall. The dose used was 1 gram daily for six months to a year. All patients noted some benefits, and no adverse events were recorded. Other researchers have since reported that glycine can potentiate some but not all anticonvulsant drugs in some animal models. It has also been shown to prevent some experimentally produced seizures.

The effects of oral glycine (200 mg/kg/day) were tested in two siblings suffering from 3-phosphoglycerate dehydrogenase deficiency, an inborn error of L-serine biosynthesis. A significant amount of glycine is made from L-serine. Among the features of this disorder are intractable seizures. L-serine in doses up to 500 mg/kg/day failed to control the seizures, but oral glycine completely stopped them, and electroencephalographic abnormalities resolved after six months of treatment.

High-dose glycine may be beneficial in the management of enduring negative symptoms of schizophrenia. Twenty-two treatment-resistant schizophrenic patients participated in a double-blind, placebo-controlled, six-week, crossover treatment trial with 0.8 grams per kilogram daily of glycine added to their ongoing antipsychotic medication. Glycine intake ranged from 40 to 90 grams daily. Only mild gastrointestinal side effects (nausea and vomiting) were reported in one patient taking glycine. Patients taking glycine experienced significantly diminished negative symptoms. Followup studies are planned.

Recent animal studies suggest that glycine may have some anti-cancer properties. In one recent study, 51 weeks of glycine supplementation did not stop early foci formation of cancer but reduced formation of small liver tumors by 23%, medium-sized tumors by 64% and large tumors by nearly 80% in rats given an agent that is a peroxisome proliferator and liver carcinogen.

In another recent study, dietary glycine inhibited B16 melanoma tumors in mice. Glycine-supplemented mice had tumors that were 50 to 70% smaller in size than those in controls. The protective mechanism in this case appeared to be inhibition of angiogenesis effected by suppressed endothelial-cell proliferation. Tumors in mice fed glycine had 70% fewer arteries than were present in the tumors of controls.

Whether very preliminary data suggesting some positive effects of glycine on lipid metabolism will be mirrored in human research remains to be seen.

Partly because glycine is a precursor of creatine, some have assumed that it might have some of the same ergogenic potential that has been claimed for creatine. This, so far, has not been demonstrated. Glycine is claimed to be beneficial for benign prostatic hypertrophy based on a dated clinical study that has never been confirmed.

CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS

CONTRAINDICATIONS

Glycine supplementation is contraindicated in those hypersensitive to any component of the preparation. It is also contraindicated in those who are anuric (some glycine gets converted to ammonia).

PRECAUTIONS

Glycine supplementation should be avoided by pregnant women and nursing mothers. Because of some conversion of glycine to ammonia, those with hepatic impairment should avoid glycine supplementation unless prescribed.

ADVERSE REACTIONS

Doses of 1 gram daily are very well tolerated. Mild gastrointestinal symptoms are infrequently noted. In one study doses of 90 grams daily were also well tolerated.

INTERACTIONS

Antispastic drugs. Theoretically, supplemental glycine might have additive effects when used in conjunction with baclofen, diazepam, dantrolene sodium and tizanidine.

No other drug, nutritional supplement, food or herb interactions are known.

OVERDOSAGE

There are no reports of overdosage in humans. The majority of mice receiving 3 to 4.5 grams per kilogram by intravenous infusion experienced bradycardia, prolongation of the PQ interval, QRS duration and death.

DOSAGE AND ADMINISTRATION

Glycine is available in 500 milligram tablets and capsules. Those who supplement use up to 1 gram daily in divided doses. Doses used for management of schizophrenia have ranged from 40 to 90 grams daily.

HOW SUPPLIED

Capsules — 500 mg, 600 mg

Irrigation Solution — 1.5%

Powder

Tablets — 500 mg, 600 mg

LITERATURE

Barbeau A. Preliminary study of glycine administration in patients with spasticity. Neurol. 1974; 24:392.

de Kooning JT, Duran M, Dorling L, et al. Beneficial effects of L-serine and glycine in the management of seizures in 3-phosphoglycerate dehydrogenase deficiency. Ann Neurol. 1998; 44:261-265.

Heresco-Levy U, Javitt DC, Ermilov M, et al. Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia. Arch Gen Psychiatry. 1999; 56:29-36.

Olsson J, Hahn RG. Glycine toxicity after high-dose i.v. infusion of 1.59 % glycine in the mouse. Br J Anaest. 1999; 82:250-254.

Rose ML, Cattley RC, Dunn C, et al. Dietary glycine prevents the development of liver tumors caused by the peroxisome proliferator WY-14, 643. Carcinogenesis. 1999; 20:2075-2081.

Rose ML, Madren J, Bunzendahl H, Thurman RG. Dietary glycine inhibits the growth of B16 melanoma tumors in mice. Carcinogenesis. 1999; 20:793-798

Simpson RK Jr, Gondo M, Robertson CS, Goodman JC. The influence of glycine and related compounds on spinal cord injury-related spasticity. Neurochem Res. 1995; 20:1203-1210.

Simpson RK Jr, Robertson CS, Goodman JC. The role of glycine in spinal shock. 1996; 19:215-224.

Smith JE, Hall PV, Galvin MR, et al. Effects of glycine administration on canine experimental spinal spasticity and the levels of glycine, glutamate, and aspartate in the lumbar spinal cord. Neurosurg. 1979; 4:153-156.

Toth E, Lajtha A. Glycine potentiates the action of some anticonvulsant drugs in some seizure models. Neurochem Res. 1984; 9:1711-1718.

Wheeler M, Stachlewitz RT, Yamashina S, et al. Glycine-gated channels in neutrophils attenuate calcium influx and superoxide production. FASEB J. 2000; 14:476-484.

Wheeler MD, Ikejema K, Mol Life Sci. Enomoto N, et al. Glycine: a new anti-inflammatory immunonutrient. Cell Mol Life Sci.1999; 56:843-856.

Yagasaki K, Funabiki R. Effects of dietary supplemented amino acids on endogenous hypercholesterolemia in rats. J Nutr Sci Vitaminol. 1990; 36 Suppl 12:S165-S168.