Glycine is a non-essential amino acid that plays an integral role in excitatory and inhibitory neurotransmission via N-methyl-D-aspartate type glutamate receptors and glycine receptors. Studies have found that glycine intake before bedtime can significantly improve subjective sleep quality in individuals with insomnia. 

The effects of glycine intake (3 g) before bedtime on subjective sleep quality were studied in human volunteers with persistently poor sleep quality. The results showed that glycine improved subjective sleep quality and sleep efficiency (sleep time/bed time), shortened PSG sleep onset latency and slow-wave sleep latency, while sleep structure was not changed. Glycine reduced daytime sleepiness and improved performance on memory recognition tasks. Therefore, large amounts of glycine intake before bedtime appear to produce subjective and objective improvements in sleep quality in a manner different from traditional hypnotic drugs such as benzodiazepines.

Mechanism

Oral administration of glycine to rats significantly increased plasma and cerebrospinal fluid glycine concentrations and significantly reduced core body temperature while increasing skin blood flow. A decrease in core body temperature may be a potential mechanism by which glycine affects sleep, as it is known that core body temperature decreases at the onset of sleep. In addition, core body temperature in humans remains low during sleep.

In acute sleep disorders, oral glycine induces non-rapid eye movement (REM) sleep and shortens NREM sleep latency, with a decrease in core temperature. Oral and intracerebroventricular injections of glycine increase skin blood flow (CBF) at the plantar surface in a dose-dependent manner, leading to heat loss. Pretreatment with the N-methyl-D-aspartate (NMDA) receptor antagonists AP5 and CGP78608, but not the glycine receptor antagonist strychnine. After glycine administration, induction of c-Fos expression was observed in hypothalamic nuclei, including the medial preoptic area (MPO) and suprachiasmatic nucleus (SCN) shell. Bilateral microinjection of glycine into the SCN increased CBF in a dose-dependent manner, whereas no effect was observed when glycine was injected into the MPO and dorsal subventricular zone. In addition, microinjection of D-serine into the SCN also increased CBF, and these effects were blocked in the presence of L-701324. SCN ablation completely abolished the somnogenic and cooling effects of glycine. These data suggest that exogenous glycine promotes sleep through peripheral vasodilation by activating NMDA receptors in the SCN shell.

References:

[1] MAKOTO BANNAI  Nobuhiro K. New Therapeutic Strategy for Amino Acid Medicine: Glycine Improves the Quality of Sleep[J]. Journal of pharmacological sciences, 2012, 118 2: Pages 145-148. DOI:10.1254/jphs.11R04FM.

[2] W. YAMADERA. Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes[J]. Sleep and Biological Rhythms, 2007, 5 1: 126-131. DOI:10.1111/J.1479-8425.2007.00262.X.

[3] NOBUHIRO KAWAI. The Sleep-Promoting and Hypothermic Effects of Glycine are Mediated by NMDA Receptors in the Suprachiasmatic Nucleus[J]. Neuropsychopharmacology, 2014, 40 6: 1405-1416. DOI:10.1038/npp.2014.326.