A Small Molecule with a Big Impact on Sleep - Glycine

Glycine has a calming effect on the brain — it helps you wind down and prepare for sleep. Its role as an inhibitory neurotransmitter has been unfolding over many years of ongoing research. Easily one of the most versatile amino acids, glycine serves as a building block to proteins (collagen, the most abundant protein in our body, is one-third glycine), and is heavily utilised for the production of heme, DNA and RNA synthesis, glutathione formation, and for enriching the body’s capacity for methylation reactions [1, 2].

The Scale of the Sleep Problem

People need sleep. It is our basic human need. Too many of us experience sleep problems — lying there restless, counting sheep, watching the hostile glow of the clock, fearing the absence of sleep. Sleep issues have become a pervasive health problem, and research shows that lack of sleep affects everything from mental competence to increased risk of chronic diseases and cancer.

If you are experiencing persistent sleep difficulties and want to understand the hormonal picture behind them, our Sleep Hormone Test (UDH I) measures melatonin (as its urinary metabolite MT6s) alongside cortisol and other key hormones involved in the sleep-wake cycle — providing a clear biochemical picture of what may be driving your insomnia.

How Glycine Promotes Sleep

Glycine Promotes Sleep Without Altering Sleep Architecture

When human volunteers who had continuously experienced unsatisfactory sleep were given 3 g glycine before bedtime, their sleep improved [3]. Using polysomnography, glycine was shown to shorten the amount of time to fall asleep and stabilise sleep state, with no alterations in sleep architecture — unlike traditional hypnotic drugs. Glycine promoted normal nocturnal sleep cycles, from deeper to shallower with very few interruptions.

Glycine Lowers Core Body Temperature

Glycine taken orally has easy access to the brain — it readily crosses the blood-brain barrier via glycine transporters [4]. Once in the brain, glycine targets glutamate NMDA receptors in the suprachiasmatic nucleus (SCN) — the 24-hour biological clock in the central nervous system that controls when we want to be asleep and awake.

By modulating NMDA receptors in the SCN, glycine induces vasodilation throughout the body to promote lowering of core body temperature [5]. Sleep and body temperature are intertwined — body temperature decreases before the onset of sleep and continues to decrease throughout the night, reaching its nadir about 2 hours after sleep onset, and gradually rising as a person wakes [6]. Glycine’s effect on thermoregulation is similar to that of common prescription sleep medications that also work by reducing core body temperature [7, 8].

Additional mechanisms that glycine may rely on to promote sleep include inhibiting orexin neurons — the “wakefulness” neurons, the absence of which is implicated in narcolepsy [9].

Glycine’s Impact on Daytime Function

Glycine Improves Daytime Performance

Unlike many sleep aids out there, nutraceutical or pharmaceutical, that promote sleep and leave you groggy the next day, glycine actually corrects feelings of fatigue and sleepiness during the day.

Sleep-restricted volunteers receiving glycine showed improved reaction times in the psychomotor vigilance test compared to the placebo group and reported feeling refreshed after waking [10]. This is a remarkable distinction from most sleep aids.

Glycine Regulates Daytime Wakefulness via the HPA Axis

Glycine was found to contribute to yet another circadian process — stimulating the expression of arginine vasopressin, a neuropeptide produced in the SCN. Arginine vasopressin serves as an output signal of the hypothalamic biological clock, an important modulator of circadian processes involving the HPA and HPG axes and the autonomic nervous system [11]. Specifically to the HPA axis, arginine vasopressin synergises signalling with corticotropin releasing hormone (CRH) to facilitate the release of ACTH, ultimately triggering cortisol production from the adrenal glands and contributing to the state of wakefulness [12].

Because glycine’s sleep-promoting effects are so closely tied to cortisol and HPA axis rhythms, assessing your diurnal cortisol pattern can be a valuable companion to understanding your sleep difficulties. Our All Day Cortisol Test (4-Point LCMS) measures cortisol at four time points across the day — capturing the full diurnal rhythm and identifying whether a dysregulated cortisol pattern is contributing to your sleep and wakefulness issues.

Sleep as Neural Sanitisation

Sleep is not just a time to rest — it is an active process of clearing out toxins and repairing brain cells damaged by free radicals [13]. During sleep, waste products of brain metabolic processes are removed from the tiny spaces between brain cells where they can accumulate [14]. Sleep is a kind of power cleanse that restores and rejuvenates our brain for optimal function [15]. Considering glycine’s prominent role in detoxification processes, future research may reveal additional ways in which glycine supports a healthy brain.

For those who want to explore the full neurotransmitter picture alongside their sleep hormones — including glycine’s inhibitory counterparts GABA, serotonin and dopamine — our Neurotransmitters Tests measures key neurotransmitters alongside urine hormones in a single at-home collection, with specialist interpretation included.

Originally by Dr. Kate Placzek, ZRT Laboratory. Reproduced with permission. Last reviewed: May 2026.

References

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