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