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Glycine

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Glycine is the simplest of the 20 different amino acids used as building blocks to make proteins for your body. It works in concert with glutamine, a substance that plays a major role in brain function. Glycine has shown some promise as an aid in the treatment of schizophrenia and may have other uses related to the brain as well, such as enhancing mental function .

Requirements/Sources

Your body is able to make glycine using another amino acid, serine. Because you can manufacture glycine, you do not really have to consume any, so it is called a "nonessential amino acid." Most of us get about 2 g of glycine a day from the foods we regularly eat anyway. This dietary glycine comes mostly from high-protein foods like meat, fish, dairy products, and legumes. For treating certain disease conditions, however, much larger amounts than are normally consumed have been advocated; such high doses can only be obtained by taking supplements.

Therapeutic Dosages

Dosages of oral glycine used in clinical trials for therapeutic purposes range from 2 to 60 g daily.

Therapeutic Uses

Several studies have evaluated glycine as a supportive treatment for schizophrenia . 1,2,4-6,22-26 According to some, but not all, of these studies, high doses of glycine (from 15 to 60 g daily) might augment the effectiveness of medications used for this condition. The one notable exception is clozapine (Clozaril); one study suggest that glycine may actually decrease the effectiveness of this drug (see Safety Issues below).
One large double-blind study suggests that low doses of glycine may be helpful for limiting the spreading brain damage that occurs during stroke . 7 However, there are also theoretical concerns that glycine could increase such damage (see Safety Issues ), so you should not try this treatment except under physician supervision.
A small double-blind study found evidence that glycine may help improve long-term blood sugar control in people with type 2 diabetes. 24
One small study weakly suggests that glycine may enhance memory and mental function . 11
Glycine alone and in combination with other amino acids has shown a bit of promise for enhancing wound healing. 13
Animal studies suggest that dietary glycine may protect against chemically induced damage to the liver or kidneys. 14-16
Other studies in laboratory animals suggest that dietary glycine may prevent tumor formation and growth in the livers of mice and rats. 17,18 However, it is too early to say whether glycine has cancer preventive effects in humans.
Manufacturers advertising glycine supplements have made a number of additional claims for it, including prevention of epileptic seizures , reducing acid in the stomach, multiple sclerosis , boosting the immune system , and calming the mind. It is also proposed as a sports supplement , said to work in this capacity by increasing release of human growth hormone (HGH). As yet, there is no real scientific evidence that glycine works for any of these purposes.
Because it has a sweet taste, glycine has also been recommended as a sugar substitute for people with diabetes.

What Is the Scientific Evidence for Glycine?

Schizophrenia

Glycine might enhance the effectiveness of drugs used for schizophrenia , especially those in the older phenothiazine category. It has also shown equivocal promise for the drugs risperidone and olanzapine. However, it may not be helpful for people using clozapine .
Phenothiazine drugs are most effective for the "positive" symptoms of schizophrenia, such as hallucinations and delusions. (Such symptoms are called "positive" because they indicate the presence of abnormal mental functions, rather than the absence of normal mental functions.) In general, however, these medications are less helpful for the "negative" symptoms of schizophrenia, such as apathy, depression, and social withdrawal. Glycine might be of benefit here.
A double-blind, placebo-controlled trial enrolled 22 participants who continued to experience negative symptoms of schizophrenia despite standard therapy. 1 The results showed that the use of glycine significantly improved negative symptoms. In addition, glycine also appeared to reduce some of the side effects caused by the prescription drugs. No changes were seen in positive symptoms (for instance, hallucinations), but it is not possible to tell whether that is because these symptoms were already being controlled by prescription medications or if glycine simply has no effect on those particular symptoms of of schizophrenia.
Three earlier double-blind, placebo-controlled clinical trials of glycine together with standard drugs for schizophrenia also found it to be helpful for negative symptoms. 2,4,5 All of these studies used very small groups (from 12 to 18 people), so much larger trials are still needed to verify glycine's effectiveness.
The trials just discussed were conducted before atypical antipsychotics were widely available. These drugs cause fewer side effects and also provide benefits for the negative symptoms of schizophrenia along with the positive. One study found that glycine augmented the effectiveness of two of these drugs: olanzapine and risperidone. 23 However, another study suggests that adding glycine to the atypical antipsychotic clozapine may not be a good idea. 6 In this study, glycine was found to reduce the benefits of clozapine. Two other double-blind, placebo-controlled trials of glycine and clozapine simply failed to find benefit. 22,25 Another recent study, not specifically limited to clozapine, also failed to find benefit with glycine. 26

Stroke

Glycine's potential usefulness for treating individuals who have undergone strokes was investigated in a double-blind, placebo-controlled study with 200 participants. 7 The results suggest that glycine can protect against the spreading damage to the brain that usually follows a stroke. Participants were given either 1 to 2 g of glycine sublingually (dissolved under the tongue) or placebo treatment for a period of 5 days. The results suggest that glycine can prevent neural damage. This appears to be an impressive result, but further research is necessary.
Although other researchers using glycine for brain disorders have reported that such small doses of glycine would not be sufficient to cross the blood-brain barrier, 1 measurements of amino acids in the cerebrospinal fluid during the above study suggest that it did enter the brain. However, there are potential concerns that high-dose glycine could increase stroke damage (see Safety Issues below).

Safety Issues

No serious adverse effects from using glycine have been reported, even at doses as high as 60 g per day. One participant in the 22-person trial described above developed stomach upset and vomiting, but it ceased when the glycine was discontinued.
In contradiction to the study on strokes mentioned above, theoretical concerns have been raised that suggest glycine might actually increase brain injury in strokes. 19 In fact, drugs that block glycine have been investigated as treatments to limit stroke damage. 12,20 However, the authors of the study on strokes described above make an argument that suggests the overall effect of glycine is protective. 7 Until this controversy is settled, prudence suggests not using glycine following a stroke, except on the advice of a physician.
In addition, as noted above, it is possible that use of glycine could reduce the benefits of clozapine.
Maximum safe doses for young children, pregnant or nursing women, or people with liver or kidney disease are not known.

Interactions You Should Know About

If you are taking:
  • Clozapine : Do not take glycine except on the advice of a physician.

References

1 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.

2 Heresco-Levy U, Javitt DC, Ermilov M, et al. Double-blind, placebo-controlled, crossover trial of glycine adjuvant therapy for treatment-resistant schizophrenia. Br J Psychiatry . 1996;169:610-617.

3 Javitt DC, Balla A, Sershen H, et al. A.E. Bennett Research Award. Reversal of phencyclidine-induced effects by glycine and glycine transport inhibitors. Biol Psychiatry . 1999;45:668-679.

4 Javitt DC, Zylberman I, Zukin SR, et al. Amelioration of negative symptoms in schizophrenia by glycine. Am J Psychiatry . 1994;151:1234-1236.

5 Semba J. Glycine therapy of schizophrenia; its rationale and a review of clinical trials [translated from Japanese]. Nihon Shinkei Seishin Yakurigaku Zasshi . 1998;18:71-80.

6 Potkin SG, Jin Y, Bunney BG, et al. Effect of clozapine and adjunctive high-dose glycine in treatment-resistant schizophrenia. Am J Psychiatry . 1999;156:145-147.

7 Gusev EI, Skvortsova VI, Dambinova SA, et al. Neuroprotective effects of glycine for therapy of acute ischaemic stroke. Cerebrovasc Dis . 2000;10:49-60.

8 Fries MH, Rinaldo P, Schmidt-Sommerfeld E, et al. Isovaleric acidemia: response to a leucine load after three weeks of supplementation with glycine, L-carnitine, and combined glycine-carnitine therapy. J Pediatr . 1996;129:449-452.

9 Itoh T, Ito T, Ohba S, et al. Effect of carnitine administration on glycine metabolism in patients with isovaleric acidemia: significance of acetylcarnitine determination to estimate the proper carnitine dose. Tohoku JExp Med . 1996;179:101-109.

10 de Koning TJ, Duran M, Dorland 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.

11 File SE, Fluck E, Fernandes C. Beneficial effects of glycine (Bioglycin) on memory and attention in young and middle-aged adults. J Clin Psychopharmacol . 1999;19:506-512.

12 Sopala M, Schweizer S, Schafer N, et al. Neuroprotective activity of a nanoparticulate formulation of the glycineB site antagonist MRZ 2/576 in transient focal ischaemia in rats. Arzneimittelforschung . 2002;52:168-74.

13 Harvey SG, Gibson JR, Burke CA. L-cysteine, glycine and dl-threonine in the treatment of hypostatic leg ulceration: a placebo-controlled study. Pharmatherapeutica . 1985;4:227-230.

14 Yin M, Ikejima K, Arteel GE, et al. Glycine accelerates recovery from alcohol-induced liver injury. J Pharmacol Exp Ther . 1998;286:1014-1019.

15 Thurman RG, Zhong Z, von Frankenberg M, et al. Prevention of cyclosporine-induced nephrotoxicity with dietary glycine. Transplantation . 1997;63:1661-1667.

16 Zhong Z, Arteel GE, Connor HD, et al. Cyclosporin A increases hypoxia and free radical production in rat kidneys: prevention by dietary glycine. Am J Physiol . 1998;275:F595-RF604.

17 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.

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

19 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.

20 Tatlisumak T, Takano K, Meiler MR, Fisher M. A glycine site antagonist ZD9379 reduces number of spreading depressions and infarct size in rats with permanent middle cerebral artery occlusion. Acta Neurochir Suppl . 2000;76:331-333.

21 Javitt DC. Management of negative symptoms of schizophrenia. Curr Psychiatry Rep . 2001;3:413-417.

22 Evins AE, Fitzgerald SM, Wine L, et al. Placebo-controlled trial of glycine added to clozapine in schizophrenia. Am J Psychiatry . 2000;157:826-828.

23 Heresco-Levy U, Ermilov M, Lichtenberg P, et al. High-dose glycine added to olanzapine and risperidone for the treatment of schizophrenia. Biol Psychiatry. 2004;55:165-71.

24 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.

25 Diaz P, Bhaskara S, Dursun SM, et al. Double-blind, Placebo-Controlled, Crossover Trial of Clozapine Plus Glycine in Refractory Schizophrenia Negative Results. J Clin Psychopharmacol . 2005;25:277-278.

26 . Buchanan RW, Javitt DC, Marder SR, et al. The cognitive and negative symptoms in schizophrenia trial (CONSIST): the efficacy of glutamatergic agents for negative symptoms and cognitive impairments. Am J Psychiatry. 2007;164:1593-1602.

Revision Information

This content is reviewed regularly and is updated when new and relevant evidence is made available. This information is neither intended nor implied to be a substitute for professional medical advice. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with questions regarding a medical condition.

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