Glycine — a simple amino acid for better sleep?

Aim of the study: Functional decline of physiological systems during ageing leads to age-related diseases. Dietary glycine increases healthy lifespan in model organisms and might decrease inflammation in humans, suggesting its geroprotective potential.

Results: Glycine was administered to healthy and diseased populations (18 and 34 studies) for up to 14 days and 4 months, respectively. The nervous system demonstrated the most positive effects, including improved psychiatric symptoms from longer-term glycine administration in psychiatric populations. While longer-term glycine administration improved sleep in healthy populations, these studies had small sample sizes with a high risk of bias. Larger and long-term studies with more robust study designs in healthy populations to examine the effects of glycine administration on preventing, delaying or reversing the ageing process are warranted.

Aim of the study: Glycine is a non-essential amino acid that has indispensable roles in both excitatory and inhibitory neurotransmission via N-methyl-D-aspartate type glutamate receptors and glycine receptors, respectively. We recently reported that glycine ingestion before bedtime significantly ameliorated subjective sleep quality in individuals with insomniac tendencies.

Results: The decline in the core body temperature might be a mechanism underlying glycine's effect on sleep, as the onset of sleep is known to involve a decrease in the core body temperature. Moreover, a low core body temperature is maintained during sleep in humans. Pharmacological studies investigating the mechanisms of glycine on sleep were also performed. In this review, we will describe both our recent findings regarding how and where orally administered glycine acts and findings from our rat study and human trials.

Aim of the study: The use of glycine as a therapeutic option for improving sleep quality is a novel and safe approach. However, despite clinical evidence of its efficacy, the details of its mechanism remain poorly understood.

Results: Bilateral microinjection of glycine into the SCN elevated CBF in a dose-dependent manner, whereas no effect was observed when glycine was injected into the MPO and dorsal subparaventricular zone. In addition, microinjection of D-serine into the SCN also increased CBF, whereas these effects were blocked in the presence of L-701324. SCN ablation completely abolished the sleep-promoting and hypothermic effects of glycine. These data suggest that exogenous glycine promotes sleep via peripheral vasodilatation through the activation of NMDA receptors in the SCN shell.

Aim of the study: Glycine is a conditionally essential amino acid with plausible roles in sleep regulation through thermoregulatory and glycinergic/N-methyl-D-aspartate signaling pathways. Collagen is rich in glycine and thus, collagen-based supplements may represent a practical dietary source of glycine and could plausibly influence sleep-related outcomes.

Results: All 3 glycine sleep trials reported benefits on at least 1 sleep-related outcome. Among collagen peptide trials, 1 placebo-controlled trial reported fewer polysomnographic awakenings, 1 placebo-controlled trial reported lower fatigue scores, and active-comparator studies with alpha-lactalbumin did not show superiority of collagen peptides for sleep-related outcomes. Overall, current evidence supports biological plausibility for glycine as a candidate mechanism that may contribute to collagen-related sleep effects, but mediation has not been directly tested. Larger mechanistic trials with standardized sleep outcomes are needed.

Aim of the study: This narrative review synthesizes evidence on how vitamins, minerals, and amino acids modulate sleep through neurobiological, circadian, and epigenetic pathways. B-group vitamins (B6, B12, folate) are cofactors in the synthesis of serotonin and gamma-aminobutyric acid (GABA).

Results: Tryptophan and other amino acids stimulate the formation of serotonin/melatonin to reduce sleep latency, and inhibitory amino acids (glycine, GABA) increase central nervous system inhibition to facilitate sleeping. Epigenetic mechanisms that operate on nutrient signals, especially methylation of clock genes using the vitamins folate and B12, are becoming appreciated. Taken together, these mechanisms affect the process of sleep latency, duration, and architecture. The review notes the prospect of more personalized nutritional interventions (possibly personalized by genotyping) in optimizing sleep, but notes that further research is necessary in the form of larger controlled trials.