Glycine is a small, nonessential amino acid. It is relatively ubiquitous in our muscle tissue and skin, and it plays an important role in the regulation and support of many critical pathways. Previously considered to be biologically inert, unexpected findings in a study using glycine as a placebo to investigate the function of other amino acids on the brain led to a study on the effects of glycine on human sleep quality and patterns.[5]
Comment: Glycine is classified as "nonessential" because the body can produce it, however it may be more accurate to classify it as "conditionally essential", meaning that if a person has impaired health, they won't be able to synthesize enough for their needs.
An alternative perspective could be that it's so essential to the body that, like cholesterol, the body can synthesize it in the absence of dietary intake, but functions dramatically better with it included in the diet.
Glycine undergoes passive diffusion through the blood-brain barrier and acts primarily on N-methyl-D-aspartate receptors (NMDA).[5] Its actions on the NMDA receptor are believed responsible for inhibiting muscle activity during rapid eye movement (REM) sleep,[6] and for lowering core body temperature to facilitate sleep.[7, 8] Oral glycine administration also increases serotonin levels without increasing dopamine levels [5] to help normalize circadian rhythms.
In addition to helping objectively normalize the physiology of sleep,[8] oral glycine supplementation ameliorates the subjective symptoms of sleep deprivation.[9] On testing, subjects report improved sleep satisfaction and decreased daytime sleepiness and cognitive impairment.[2, 9]
A pinch of glycine powder under the tongue can give immediate relief from "spinning thoughts" or over-thinking, which is a common complaint among insomniac patients and contributes to difficult sleep onset.[9] Indeed, oral glycine powder at bedtime ameliorates all subjective symptoms of sleep deprivation, from morning fatigue to eye strain and feelings of unease and difficulty concentrating, as well as improving memory recognition.[10, 11]
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Glycine and Mental Health
Glycine — this smallest and simplest of amino acids was first thought to be inert in its effects on physiology.[6] But study in recent years shows this little molecule to be a powerhouse! We have already discussed the impact of glycine on normalizing sleep by acting on the NMDA receptors.[12, 13, 14, 15] Through the same mechanism, oral glycine supplementation also helps normalize the brain chemistry of addiction and prevent relapse.
Glycine is critically involved in regulating ethanol (alcohol) consumption.[13] Elevating concentrations of glycine in the signalling junction between neurons has consistently been demonstrated to reduce alcohol intake,[13] and inhibit drug-seeking for cocaine and amphetamines.[14, 15] The mechanism of these effects is still poorly understood, but evidence suggests that increased glycine levels also attenuate the effects of amphetamines on the brain.[14]
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We do know, however, that changes to glycine levels in the brain correspond with improved attention, memory, impulsivity, emotional memory, and intellectual learning memory.
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Glycine's therapeutic uses to treat addictions go yet a step further. There is evidence that supplemental glycine helps reduce liver toxicity from chronic alcohol consumption and expedites recovery from alcohol-induced liver injury.
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Since the late 1980s, there has been an understanding that glycine therapy is useful to treat negative symptoms of schizophrenia, such as depression and loss of mental fluency or flexibility.[24] Recent double-blinded, placebo-controlled trials consistently support the conclusions that adding oral glycine to the pharmacologic protocols markedly improves negative symptoms and cognitive troubles, and may even improve psychotic symptoms in some cases.
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Examining regulation of NMDA receptors and amino-acid balance has led to potential implications with respect to ADHD and autism,[31] and greater understanding of the neurochemistry of posttraumatic stress disorder and Parkinson's.
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Ischemia (loss of blood supply) is a major cause of death in trauma, surgery, and organ replacement. Glycine significantly reduces tissue damage and loss in these cases, though the mechanism is not fully understood. What is clear is that glycine has direct cell-protective effects.[35] It protects against the damage of the inflammatory response, which is triggered as bloodflow returns to ischemic areas (ischemic reperfusion injury).[35, 36] These cell-protective and anti-inflammatory effects are not limited to tissue trauma due to ischemia. In fact, the anti-inflammatory benefits of glycine have been applied to the prevention and treatment of other inflammatory conditions.
Inflammation is the primary mechanism in arthritis. Animal studies indicate that oral glycine supplementation can mitigate this inflammatory process,[5] and mechanistic study suggests these effects have multiple potential therapeutic applications in humans as well.[37, 38] Conditions such as ulcerative colitis,[39] inflammatory pain,[40] muscle wasting in cancer,[41] and even inflammatory contributors to obesity [42, 43, 44] show improvement with glycine supplementation.
The safety of glycine supplementation has been clearly established. Surgeons routinely utilize an irrigation solution of glycine during procedures, delivering relatively high-dose glycine without adverse effects. Clinical trials have investigated oral glycine supplementation in humans quite thoroughly, indicating that long-term oral doses of 31 g/d [44] and 50 g/d [5] yield no adverse events. Short-term studies of 200 mg/kg daily of IV glycine also yielded no adverse effects.[5] While more study is required to fully elucidate the full breadth and potential of therapeutic glycine, the mounting body of evidence is certainly exciting.
