• Approach to the Patient

    Glycine has been marketed as a memory and brain function enhancing supplement. The basis for this hypothesis involves its coagonist effects on glutamate brain pathways, specifically the N-methyl-D-aspartate (NMDA)–receptor. However, direct clinical evidence for this use is limited to one pilot trial. It may be advisable to steer patients toward ginkgo instead; ginkgo at least has some meaningful research to support this use. (See the Ginkgo article for more information.)

    Building on evidence that NMDA antagonists cause schizophrenia-like symptoms, glycine has been tried as a treatment for the negative symptoms of schizophrenia (e.g., flat affect and withdrawal), with some success. Effects on NMDA are also the basis of studies investigating the use of glycine to reduce ischemic damage in strokes. However, it is also possible that high-dose glycine could increase stroke damage. (See Safety Issues.)

    Your patients may have encountered numerous additional claims regarding glycine, such as that it can improve memory and mental alertness, treat ADHD symptoms, aid sports performance, help control diabetes and reduce anxiety. However, there is little or no evidence at all that it is effective for these uses.

    Common Uses

    • Post-CVA Treatment [+3]
    • Schizophrenia [+2]

    (Higher numbers indicate stronger evidence; X modifier indicates contradictory results. See the Introduction for details of the rating scale.)

    Post-CVA Treatment +3

    A double-blind, placebo-controlled trial of 200 individuals within 6 hours of CVA onset evaluated the potential benefits of sublingual glycine at 0.5 g, 1 g, or 2 g daily over a 5-day period.1 The results showed that 1 to 2 g daily significantly improved outcome.

    However, there are concerns that high-dose glycine could potentially increase CVA damage (see Safety Issues).

    Schizophrenia +2

    It is generally thought that phenothiazine antipsychotic drugs are most effective for the “positive” symptoms of schizophrenia, such as hallucinations and delusions, rather than the “negative” symptoms such as apathy, depression, and social withdrawal. Glycine has been proposed as a treatment for the latter category of symptoms.

    In a placebo-controlled, double-blind, crossover trial, 22 schizophrenics who were not well-managed by medications alone were randomly assigned to receive either 0.8 g/kg body weight of glycine or placebo for 6 weeks, along with standard antipsychotics.2 The groups were then switched after a 2-week placebo washout period. Significant improvements in negative symptoms were seen with glycine as compared to placebo. In addition, the benefits appeared to continue for another 8 weeks after glycine was discontinued. No changes were seen in positive symptoms.

    Three smaller double-blind, placebo-controlled clinical trials also found glycine to be helpful for negative symptoms of schizophrenia.2–5

    Atypical antidepressants may have more intrinsic effect on negative symptoms of schizophrenia than the older drugs. One study found that glycine nonetheless augmented the effectiveness of olanzapine and risperidone.19 However, studies involving clozapine have either found no augmentation or an actual reduction in efficacy.6,20

    Other Proposed Uses

    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.

    A pilot study suggests that glycine may improve memory.16

    Preliminary clinical studies have found that glycine may be useful for treatment of 3-phosphoglycerate dehydrogenase deficiency and isovaleric acidemia.7,8,9

    Animal studies suggest that dietary glycine may protect against chemically induced hepatic or renal damage.10,11,12 Other animal studies suggest that glycine may have antitumor effects.13,14

    Manufacturers have made a number of additional claims for the benefits of glycine supplements, including anticonvulsive effects, enhancing mental alertness, treating ADHD , reducing muscle spasms, enhancing immune system function, and reducing anxiety . 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 for any of these uses.

    Finally, because it has a sweet taste, glycine has been used as a sugar substitute.

    Mechanism of Action

    Impaired NMDA (N-methyl-D-aspartate) receptor-mediated glutamatergic neurotransmission may contribute to the negative symptoms of schizophrenia.2,3 Glycine, an obligatory coagonist, may augment such neurotransmission.

    Glycine’s benefits in CVA may be related to interaction with inhibitory glycine and GABA receptors.1

    Dosage

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

    Safety Issues

    No serious adverse effects of glycine have been reported, even at doses as high as 60 g/day. One participant in the 22-person trial described above developed gastric distress and vomiting, but these ceased when the glycine was discontinued.2

    Theoretical concerns have been raised that glycine might increase cerebral injury in CVA by increasing levels of glutamate 5; glycine antagonists have been investigated as treatments to limit the spread of ischemic injury.17,18 However, the authors of the study on CVAs suggest that the potentiating action of glycine on NMDA receptors has a saturation limit, and that protective effects predominate.1

    Maximum safe dosages in individuals with severe hepatic or renal disease are not known.

    Safety in Young Children and Pregnant or Lactating Women

    Maximum safe dosages for pregnant or lactating women, or young children, have not been established.

    Drug Interactions

    Glycine may impair the effectiveness of clozapine.22

    Gusev EI, Skvortsova VI, Komissarova IA, et al. Neuroprotective effects of glycine in the acute period of ischemic stroke [translated from Russian]. Zh Nevrol Psikhiatr Im S S Korsakova. 1999;99:12-20.

    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.

    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.

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

    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.

    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.

    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.

    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 J Exp Med. 1996;179:101-109.

    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;44:261265.

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

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

    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.

    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, et al. Dietary glycine inhibits the growth of B16 melanoma tumors in mice. Carcinogenesis. 1999;20:793-798.

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

    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.

    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;52:168-174.

    Tatlisumak T, Takano K, Meiler MR, et al. 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.

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

    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.

    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.

    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

    Last reviewed July 2012 by EBSCO CAM Review Board

    Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.

  • Approach to the Patient

    Glycine has been marketed as a memory and brain function enhancing supplement. The basis for this hypothesis involves its coagonist effects on glutamate brain pathways, specifically the N-methyl-D-aspartate (NMDA)–receptor. However, direct clinical evidence for this use is limited to one pilot trial. It may be advisable to steer patients toward ginkgo instead; ginkgo at least has some meaningful research to support this use. (See the Ginkgo article for more information.)

    Building on evidence that NMDA antagonists cause schizophrenia-like symptoms, glycine has been tried as a treatment for the negative symptoms of schizophrenia (e.g., flat affect and withdrawal), with some success. Effects on NMDA are also the basis of studies investigating the use of glycine to reduce ischemic damage in strokes. However, it is also possible that high-dose glycine could increase stroke damage. (See Safety Issues.)

    Your patients may have encountered numerous additional claims regarding glycine, such as that it can improve memory and mental alertness, treat ADHD symptoms, aid sports performance, help control diabetes and reduce anxiety. However, there is little or no evidence at all that it is effective for these uses.

    Common Uses

    • Post-CVA Treatment [+3]
    • Schizophrenia [+2]

    (Higher numbers indicate stronger evidence; X modifier indicates contradictory results. See the Introduction for details of the rating scale.)

    Post-CVA Treatment +3

    A double-blind, placebo-controlled trial of 200 individuals within 6 hours of CVA onset evaluated the potential benefits of sublingual glycine at 0.5 g, 1 g, or 2 g daily over a 5-day period.1 The results showed that 1 to 2 g daily significantly improved outcome.

    However, there are concerns that high-dose glycine could potentially increase CVA damage (see Safety Issues).

    Schizophrenia +2

    It is generally thought that phenothiazine antipsychotic drugs are most effective for the “positive” symptoms of schizophrenia, such as hallucinations and delusions, rather than the “negative” symptoms such as apathy, depression, and social withdrawal. Glycine has been proposed as a treatment for the latter category of symptoms.

    In a placebo-controlled, double-blind, crossover trial, 22 schizophrenics who were not well-managed by medications alone were randomly assigned to receive either 0.8 g/kg body weight of glycine or placebo for 6 weeks, along with standard antipsychotics.2 The groups were then switched after a 2-week placebo washout period. Significant improvements in negative symptoms were seen with glycine as compared to placebo. In addition, the benefits appeared to continue for another 8 weeks after glycine was discontinued. No changes were seen in positive symptoms.

    Three smaller double-blind, placebo-controlled clinical trials also found glycine to be helpful for negative symptoms of schizophrenia.2–5

    Atypical antidepressants may have more intrinsic effect on negative symptoms of schizophrenia than the older drugs. One study found that glycine nonetheless augmented the effectiveness of olanzapine and risperidone.19 However, studies involving clozapine have either found no augmentation or an actual reduction in efficacy.6,20

    Other Proposed Uses

    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.

    A pilot study suggests that glycine may improve memory.16

    Preliminary clinical studies have found that glycine may be useful for treatment of 3-phosphoglycerate dehydrogenase deficiency and isovaleric acidemia.7,8,9

    Animal studies suggest that dietary glycine may protect against chemically induced hepatic or renal damage.10,11,12 Other animal studies suggest that glycine may have antitumor effects.13,14

    Manufacturers have made a number of additional claims for the benefits of glycine supplements, including anticonvulsive effects, enhancing mental alertness, treating ADHD , reducing muscle spasms, enhancing immune system function, and reducing anxiety . 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 for any of these uses.

    Finally, because it has a sweet taste, glycine has been used as a sugar substitute.

    Mechanism of Action

    Impaired NMDA (N-methyl-D-aspartate) receptor-mediated glutamatergic neurotransmission may contribute to the negative symptoms of schizophrenia.2,3 Glycine, an obligatory coagonist, may augment such neurotransmission.

    Glycine’s benefits in CVA may be related to interaction with inhibitory glycine and GABA receptors.1

    Dosage

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

    Safety Issues

    No serious adverse effects of glycine have been reported, even at doses as high as 60 g/day. One participant in the 22-person trial described above developed gastric distress and vomiting, but these ceased when the glycine was discontinued.2

    Theoretical concerns have been raised that glycine might increase cerebral injury in CVA by increasing levels of glutamate 5; glycine antagonists have been investigated as treatments to limit the spread of ischemic injury.17,18 However, the authors of the study on CVAs suggest that the potentiating action of glycine on NMDA receptors has a saturation limit, and that protective effects predominate.1

    Maximum safe dosages in individuals with severe hepatic or renal disease are not known.

    Safety in Young Children and Pregnant or Lactating Women

    Maximum safe dosages for pregnant or lactating women, or young children, have not been established.

    Drug Interactions

    Glycine may impair the effectiveness of clozapine.22

    Gusev EI, Skvortsova VI, Komissarova IA, et al. Neuroprotective effects of glycine in the acute period of ischemic stroke [translated from Russian]. Zh Nevrol Psikhiatr Im S S Korsakova. 1999;99:12-20.

    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.

    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.

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

    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.

    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.

    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.

    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 J Exp Med. 1996;179:101-109.

    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;44:261265.

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

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

    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.

    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, et al. Dietary glycine inhibits the growth of B16 melanoma tumors in mice. Carcinogenesis. 1999;20:793-798.

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

    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.

    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;52:168-174.

    Tatlisumak T, Takano K, Meiler MR, et al. 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.

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

    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.

    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.

    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

    Last reviewed July 2012 by EBSCO CAM Review Board

    Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.