Glycine is a dietary amino acid that serves as both a constitutional amino acid (used to create protein structures such as enzymes) and as a neurotransmitter/neuromodulator.
Is it safe? Are there side effects?
Yes, glycine is classified as GRAS (generally regarded as safe) by the FDA.
Structure & Synthesis
Glycine in neurons is largely produced from conversion of the amino acid serine, by serine transhydroxy-methylase. (Figure 1).
Figure 1. Glycine biosynthethesis
Mechanisms of Action
As a neurotransmitter glycine is a unique in that it acts at both excitatory and inhibitory neural signaling (most neurotransmitters tend to affect one or the other at any given time). In terms of inhibitory neurotransmission glycine binds to dedicated glycine receptors, for excitatory neurotransmission, glycine binds to NMDA receptors, and increases its normal activity profile.
In terms of sleep specifically, a 2015 paper demonstrating that glycine-mediated upregulation of NMDA receptor activity in the suprachiasmatic nucleus was directly responsible for sleep induction.
Effect of glycine on Sleep
Glycine has been shown to improve both subjective and objective measures of sleep quality, as well as objective measures of reaction time. Glycine has also been observed to shorten EEG measured latency to sleep onset and to slow wave sleep, but without changes in the sleep architecture (meaning then REM and non-REM sleep durations were unchanged). And finally, glycine lessened subjective measures of daytime tiredness and increased performance in a task of psychomotor vigilance and attention. This indicates not only that glycine improves important measures of sleep, but also that this improved sleep leads to enhanced cognitive performance in individuals who experience disrupted sleep.
A follow up study replicated the effects of glycine on subjective sleep quality, demonstrating that sleep quality and fatigue, as mesured by the St. Mary’s Hospital Sleep Questionnaire and Space-Aeromedicine Fatigue Checklist, were improved and reduced, respectively, by glycine ingestion prior to sleep. Glycine significantly improved the following elements: “fatigue”, “liveliness and peppiness”, and “clear-headedness”. These results suggest that glycine produced a good subjective feeling after awakening from sleep.
A 2012 study investigated more in-depth the cognitive benefits, after glycine administration. Reaction time in a psychomotor vigilance task was consistenly improved one day and even two days after glycine administration. This is consistent with reduced psychomotor fatigue as a result of the improved sleep quality associated with glycine use. And interestingly, it demonstrates that the cognitive benefits are strong enough to be measured up to two days after the enhanced night of sleep.
Figure 2. Improvements in reaction times during tasks of psychomotor vigilance are consistently improved up to two days after glycine enhanced sleep.