Glycine is a nonessential amino acid and is derived (in the body) from serine. Typically, a person may consume roughly 2 g of glycine as part of a standard diet (rich in meat, fish,
Table 32-1. Dosing Review for Select Amino Acids
Gastrointestinal-related conditions: Typical doses are 4 g, swished and swallowed (can be taken several times per day) Immune function: Most studies have shown benefit using doses from 3 to 6 g per day Typical doses start at 4 g per day and are increased by 4 g per day Typical dose is 125 mg per day, with food Alzheimer's disease: 1,500-4,000 mg, in divided doses, per day
Age-related memory impairment: 1,500-2,000 mg per day Stroke recovery: 1,500 mg per day Age-related depression: 1,500-3,000 mg, in divided doses, per day
Typical doses range from 3 to 20 g per day, in divided doses 150-200 mg per day 100-150 mg=kg per day
Notes: There are no recommended daily allowances for any of the amino acids in this chart. See "Conclusions" in the text for information about the importance of vitamin B6.
legumes, and dairy products). Glycine is transported easily into the brain and acts primarily as an inhibitory neurotransmitter. Brain concentrations of glycine are mainly stable with an adequate diet; however, supplemental intake can bolster central nervous system concentrations.18
Glycine binds avidly with receptors in the locus ceruleus, a group of cell bodies located in the pons of the midbrain, and inhibits noradrenergic cell discharge. The locus ceruleus contains mainly norepinephrine neurons and is considered to be a key brain center for anxiety, arousal, fear, and vigilance. Norepinephrine released from the locus ceruleus affects other parts of the brain (namely the nucleus accumbens), which can then lead to more feelings of anxiety and panic as well as an increased sense of energy. The locus ceruleus may be up-regulated in addictive states as well.
Addictions, Stress, Anxiety, and Insomnia
Glycine, because of its effects on this one area of the brain, can be used as an adjunctive treatment in several conditions. In people suffering from drug and alcohol dependency, it is thought that this area of the brain is periodically up-regulated, leading to excessive norepinephrine release. People who become dependent on substances may use drugs or alcohol to satisfy the cravings created by an up-regulated locus ceruleus. Other conditions in which glycine can be useful for down-regulation of the locus ceruleus are panic disorders, nervous tension, anxiety, substance withdrawal, and insomnia (which is marked by awakening with anxiety). Glycine also interacts in an inhibitory action with motor neurons in the spinal cord and can have a calming effect on muscle spasms, muscle twitching, guarding, and rigidity that results from excessive spinal reflex activity. Glycine can inhibit spasms associated with the urinary and reproductive systems as well.19
The realm of amino acids and their treatments is of course not limited to those included in this chapter. We encourage readers to investigate the many other amino acids available for treating a multitude of other medical conditions. Some of these include: Alanine—blood-sugar regulation
Branched chain amino acids (leucine, isoleucine, and valine)—postoperative conditions, liver disease
Citrulline—cholesterol and cancer; as a precursor to nitric oxide
Cysteine and glutathione—as detoxification and anti-aging agents
Methionine—cystitis and allergy
Ornithine—as a potential growth-hormone imitator
Proline and hydroxyproline—telopeptides, collagen, and aging Serine—psychiatric disorders, mood, and memory Threonine—immune system function, precursor to phosphatidylserine Tyrosine—antidepressant
Glycine works as an agonist at another type of receptor site in the central nervous system: the N-methyl-D-aspartate (NMDA) receptor. NMDA receptors are associated with memory and learning20 and are thought to play a role in both the negative and positive symptoms of schizophrenia.21 Schizophrenia is thought to be associated with underactivity of glutamatergic receptors, especially the NMDA type. In schizophrenic patients, those who have demonstrated resistance to therapy using singular antipsychotic medications have experienced a decreased amount of schizophrenic symptoms with glycine treatment.22 Glycine was also shown to reduce depressive and cognitive symptoms in these patients. In the study with the patients who were resistant to singular antipsychotics, the investigators noted that the greatest symptomatic improvements were made in subjects with the lowest baseline serum glycine amounts. However, another investigation revealed that, when used with the atypical neuroleptic drug clozapine, glycine demonstrated no statistically significant change in symptoms or cognitive functioning,23 while another study showed that patients treated with clozapine without glycine (in comparison to another group treated with both) fared better in terms of symptom reduction.24 These investigators concluded, based on their findings, that glycine may interfere with atypical neuroleptics such as clozapine.
Dimethylglycine (DMG) is a methylated form of the amino acid glycine. DMG is produced in the body, but exists for only a few seconds before undergoing conversion. (It is formed from betaine as homocysteine is methylated).25 Acting as a methyl group donor, DMG has a reputation for benefiting children with autism, who have symptomatic improvement within days of taking the supplement. Other research shows that DMG also has an immune-enhancing effect. Both humoral and cell-mediated immune responses are increased with DMG supplementation.26 DMG is absorbed in the small intestine and metabolized in the liver to mono-methylglycine or "sarcosine," which, in turn, is converted into glycine. DMG has been shown to have anticonvulsant effects in patients with mixed complex partial and grand mal seizures.27 Some research has investigated DMG for improvement of oxygen utilization, liver function, and athletic performance.28
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