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Glycine

glycine

The Humble Glycine!

The smallest of the amino acids, glycine plays a role in collagen formation, as an inhibitory neurotransmitter and is an essential co agonist of the NMDA receptor.

Despite glycine’s inclusion in the diet, supplementation would appear to have benefits. Glycine has been shown to improve sleep quality and reduce lack of sleep related fatigue which enhances cognition.

Aside from its biological role, glycine is frequently added to mineral supplements, such as magnesium, to increase absorption and bioavailability. This process is often referred to as amino acid chelation.

Dosing

The three studies assessing sleep quality have used 3 grams of glycine, typically an hour before sleep. [1][2][3] In treatments for schizophrenia (alongside antipsychotics), doses as high as 0.8g/KG have been used [5][6][7].

Structure

Glycine Molecule

The Glycine Molecule

The molecular formula for glycine is C2H5NO2.Glycine is the smallest and simplest of the amino acids, possessing a hydrogen atom for a side chain and thus does not have the typical L or D form enantiomers found in other amino acids.

Benefits

Potential Obsessive Compulsive Disorder (OCD)

A case study has been documented following a single male over a five year period[4]. From age 17 the person, referred to as “O” in the literature, was diagnosed with OCD and body dysmorphic disorder (BDD) and became housebound.  Traditional SSRI treatment was ineffective and “O”s mental state was severely worsened by antibiotic treatment at aged 22.

A deficiency of NMDAR signal transduction was considered as possible cause of symptoms and glycine was administered over a 5 year period. “O” was given 0.8g/KG glycine per day which was approximately 50-60g. Over a period of 5 years, “O”s condition dramatically improved after 23 days at the recommended dose.

The entire case has been documented and is available to read online (see ref 4).  In short, “O” was able to resume education and a social life following the glycine protocol. Partial relapse was noted in periods of cessation.

Potential Supplementary Schizophrenia Treatment

schizophrenic1

A double blind placebo controlled crossover trial lasting for 6 weeks was undertaking, featuring 17 patients. A dose of 0.8g/KG glycine was found to augment traditional drug treatment and reduce schizophrenic symptoms by 23% (+/- 8%) [5]. As seen above, symptoms returned following cessation. Though a seemingly impractical dose of around 50g, the glycine treatment was well tolerated.

Another study involving 14 patients suffering from schizophrenia found glycine was able to reduce negative symptoms relative to placebo. [6] As did a study conducted in 1999 involving 22 treatment resistant schizophrenics[7].

Sleep Quality and Daytime Fatigue

3 studies to date have been conducted with glycine and its effects on sleep. The three we were able to find have been published by the same group of researchers. It should be noted that the studies were conducted by researchers who work for Ajinomoto, a Japanese food and Chemical Corporation which manufactures glycine. [8] That said, the research presented is peer reviewed.

The first study conducted in 2006 involving participants with complaints of poor sleep quality used 3g of glycine, or placebo prior to sleep. Subjective assessments of sleep quality were recorded, with participants noting they felt “liveliness” “peppiness” and “clear headedness”, more so than placebo. [1]

glycine sat

The second study in 2007 involving some of the same researchers, tested 3g of glycine with participants reporting poor sleep.  Again, participants noted improved subjective sleep quality and less time taken to fall asleep. The participants also noted less daytime sleepiness and had improved memory performance on a cognitive task the following day. Polysomnography changes noted glycine lowered onset to slow wave sleep, but interestingly did not affect sleep architecture. [2]

glycine sat 2

Much the same as the first study, participants got a good night’s sleep following glycine ingestion prior to bedtime. Polysomnography (sleep study measuring sleep phases) was performed and noted no change in regular patterns. In other words, glycine got the participants to sleep faster, without affecting the ratio of REM/Non-REM sleep, as some sedatives and hypnotics do.

The third study published in 2012 tested the effects of glycine on partial sleep deprivation in healthy volunteers who were not suffering from poor sleep. Participants were restricted to ¼ less sleep (average 5.5 hours) for 3 consecutive nights. Each night, 3g of glycine or placebo (malt sugar) was consumed 30 minutes prior to retiring.  Researchers found glycine improved feelings of fatigue and sleepiness and improved performance in a vigilance test, though it must be noted the sample size used was small. [3]

Mechanism Of Action

The Glycinergic System

Similar to the GABAergic system, glycine is a neurotransmitter which has its own signalling system. That is to say. glyine impacts glycine receptors. Glycine is an important inhibitory neurotransmitter which impacts postsynaptic potential by opening chloride channels. [9]

NMDA Receptor Coagonist

Glycine is required for activation of the NMDA receptor.[10] Deficits in NMDA neurotransmission are thought to play a role in schizophrenia, as it’s observed that NMDA antagonists (such as PCP) can induce schizophrenic symptoms in healthy volunteers.

Supporting Circadian Rhythm

glycinemela

An animal study administering glycine to rodents showed glycine does not affect plasma melatonin concentrations and that glycine isn’t thought to act by increasing melatonin secretion, though glycine administration does induce a drop in core body temperature via NMDA receptor activation in the suprachiasmatic nucleus (SCN), an area of the brain responsible for maintaining circadian rhythm. [3]

Researchers also measured mRNA expression of Bmal1 and Per2, two “core clock genes” that act as pacemakers for circadian rhythm in mammalian brains. Glycine did not affect expression of these genes [3] relative to placebo.

glycine AVP

Glycine was found, however, to increase Vasopressin and VIP expression in the SCN. These two neuropeptides are associated with circadian rhythm and have effects on blood pressure, digestive motility, temperature regulation and cortisol release.

Safety

Glycine is remarkably well tolerated [1][2][3], even in high doses[5][6][7]. The most noted side effect is nausea, due to glycine’s ability to increase stomach PH. It should be noted doses used were in excess of 50g.

References

[1] http://onlinelibrary.wiley.com/doi/10.1111/j.1479-8425.2006.00193.x/abstract

[2] http://onlinelibrary.wiley.com/doi/10.1111/j.1479-8425.2007.00262.x/abstract

[3] http://www.ncbi.nlm.nih.gov/pubmed/22529837

[4] http://www.hindawi.com/journals/np/2009/768398/

[5] http://www.ncbi.nlm.nih.gov/pubmed/14732596

[6] http://www.ncbi.nlm.nih.gov/pubmed/8037263?dopt=Abstract

[7] http://www.ncbi.nlm.nih.gov/pubmed/9892253

[8] http://www.ajiaminoscience.com/products/manufactured_products/l-amino_acids/Glycine.aspx

[9] http://www.ncbi.nlm.nih.gov/pubmed/16381810

[10] http://www.ncbi.nlm.nih.gov/pubmed/1699248

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