More than 40% of Australians surveyed report sleep onset/maintenance concerns and daytime symptoms consistent with a clinical diagnosis of chronic insomnia. Impaired concentration, irritability and fatigue are symptoms that commonly manifest as a result of poor sleep,¹ highlighting the need for effective strategies to treat sleep and mood disturbances.

As one of the main inhibitory neurotransmitters, glycine is gaining recognition as a safe, evidence-based alternative for improving sleep quality as it positively affects sleep physiology through two main mechanisms. Glycine appears to influence circadian activity firstly through mechanisms in the suprachiasmatic nucleus (SCN) and secondly in the ventromedial medulla (VMM). The SCN, as the master circadian clock located within the hypothalamus, controls the timing of the sleep-wake cycle and coordinates this with circadian rhythms in other brain areas.² For instance, core body temperature slightly drops around sleep.³ In SCN shell neurons, glycine activates N-methyl-D aspartate (NMDA) receptors to induce peripheral vasodilation (hypothermic effect).⁴ In the VMM, glycine contributes to the regulation of sleep via glycine/gamma-aminobutyric acid (GABA) neurons. Here glycine is involved in inducing muscle atonia during REM sleep, important for sleep maintenance.⁵

Unlike conventional medications for insomnia (i.e., benzodiazepines), glycine’s application is not limited by concerns surrounding dependence,⁶ or the problematic side effects of daytime drowsiness⁷ and cognitive deficits.⁸ In fact, research studies using therapeutic doses of glycine have demonstrated positive effects on subjective daytime measures of sleep quality.

Glycine Modulates Suprachiasmatic Nucleus (SCN) Function

In a two-part study, the effects of glycine in sleep were investigated in both humans and animals, respectively. The first part of the trial involved a single-blind, randomised, crossover study in human subjects. Glycine (3 g) or placebo was ingested 30 minutes before bedtime on three consecutive nights by seven sleep-restricted healthy males (mean age 40.6 years). A visual analog scale (VAS), questionnaire and computerised performance test were utilised to evaluate the impact of glycine on daytime sleepiness, fatigue and performance. VAS data and questionnaire responses showed a significant reduction in fatigue and tendency towards reduced daytime sleepiness with glycine. Significant improvements in psychomotor vigilance test performance were also observed.⁹

In the second part of the trial, researchers measured plasma melatonin and circadian modulated-gene expression to determine glycine’s impact on circadian rhythms in rat SCN. Although these remained largely unchanged, orally administered glycine (2 g/kg body weight [BW]) induced an increase in the neuropeptides arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP).⁹ As AVP and VIP function as circadian synchronisers,¹⁰ the results suggest modulation of SCN function. Taken together, both parts of this study suggest glycine ingestion around bedtime may attenuate daytime impairments in subjective alertness and neurobehavioural function induced by acute and modest sleep restriction.⁹

Glycine Improves Subjective and Objective Sleep Quality

In another single-blind, randomised, crossover study, glycine (3 g) taken within the hour prior to bedtime improved subjective and objective sleep quality, correlated with polysomnographic (PSG) changes compared to placebo. After glycine intervention, the eight healthy volunteers (mean age 40.5 years) with Pittsburgh sleep quality index (PSQI) scores reflecting continuous unsatisfactory sleep quality, demonstrated significant improvements in sleep quality and sleep efficacy, supported by shortened PSG latency to sleep onset and slow wave sleep (SWS).

While changes in the ratio of each sleep stage length within the sleep period (i.e., sleep architecture) were not altered by glycine, hypnograms traced a normal stable nocturnal sleep cycle from deeper to shallower sleep with very few interruptions. Less daytime sleepiness and improved performance on memory recognition tasks were also shown to occur with the ingestion of glycine.¹¹ These observations directly contrast the mechanism and side effects of daytime drowsiness⁷ and impaired cognitive function⁸ typically experienced with traditional hypnotic drugs (i.e., benzodiazepines), suggesting that glycine offers a safer, alternative approach to improving sleep quality.

Waking Up Easy With Glycine

Glycine has also been shown to significantly improve subjective feel-good measures after waking in an earlier double-blind, randomised, crossover trial. Female volunteers (n=15, mean age 31.3 years) experiencing dissatisfaction with their quality of sleep ingested glycine (3 g) or placebo within the hour before bedtime on four consecutive nights. Subjective sleep and fatigue ratings indicated significant improvements in participant ‘fatigue’, ‘liveliness and peppiness’, and ‘clear-headedness’ with supplemental glycine.¹² These findings suggest that glycine can promote refreshing sleep quality, alleviating complaints commonly associated with the effects of poor sleep, such as grogginess, sluggishness and irritability.

Better Sleep, Better Health

Clinical evidence demonstrates that glycine (typically 3 g) safely improves sleep quality in those with unsatisfactory or disturbed sleep. These effects appear to be largely mediated by its supportive influence on both REM and NREM sleep stages, especially its thermoregulatory effects in sleep at the level of the SCN. With statistics and a growing body of scientific research converging to underscore the connection between inadequate sleep and mental health concerns,¹³ interventions that improve sleep quality not only enhance daytime energy levels and vitality but also have wide-reaching impacts that can better overall health and quality of life.¹⁴

References

1. Reynolds AC, Appleton SL, Gill TK, Adams RJ. Chronic insomnia disorder in Australia: a report to the Sleep Health Foundation [Internet]. North Strathfield: Sleep Health Foundation; 2019 [cited 2022 Jul 12]. 22 p. Available from: https://www.sleephealthfoundation.org.au/pdfs/Special_Reports/SHF_Insomnia_Report_2019_Final_SHFlogo.pdf

2. Moore RY. Suprachiasmatic nucleus in sleep-wake regulation. Sleep Med. 2007 Dec;8 Suppl 3:27-33. DOI: 10.1016/j.sleep.2007.10.003

3. Okamoto-Mizuno K, Mizuno K. Effects of thermal environment on sleep and circadian rhythm. J Physiol Anthropol. 2012 May;31:14. DOI: 10.1186/1880-6805-31-14

4. Kawai N, Sakai N, Okuro M, Karakawa S, Tsuneyoshi Y, Kawasaki N, et al. The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. Neuropsychopharmacology. 2015 May;40(6):1405-1416. DOI: 10.1038/npp.2014.326

5. Uchida S, Soya S, Saito YC, Hirano A, Koga K, Tsuda M, et al. A discrete glycinergic neuronal population in the ventromedial medulla that induces muscle atonia during REM sleep and cataplexy in mice. J Neurosci. 2021 Feb;41(7):1582-1596. DOI: 10.1523/JNEUROSCI.0688-20.2020

6. O'Brien CP. Benzodiazepine use, abuse, and dependence. J Clin Psychiatry. 2005;66 Suppl 2:28-33.

7. Johnson B, Streltzer J. Risks associated with long-term benzodiazepine use. Am Fam Physician. 2013 Aug;88(4):224-226.

8. Stewart SA. The effects of benzodiazepines on cognition. J Clin Psychiatry. 2005;66 Suppl 2:9-13.

9. Bannai M, Kawai N, Ono K, Nakahara K, Murakami N. The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. Front Neurol. 2012;3:61. DOI: 10.3389/fneur.2012.00061

10. Ono D, Honma KI, Honma S. Roles of neuropeptides, VIP and AVP, in the mammalian central circadian clock. Front Neurosci. 2021;15:650154. DOI: 10.3389/fnins.2021.650154

11. Yamadera W, Inagawa K, Chiba S, Bannai M, Takahashi M, Nakayama K. Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep Biol Rhythms. 2007 Mar;5:126-131. DOI: 10.1111/j.1479-8425.2007.00262.x

12. Inagawa K, Hiraoka T, Kohda T, Yamadera W, Takahasi. Subjective effects of glycine ingestion before bedtime on sleep quality. Sleep Biol Rhythms. 2006 Feb;4:75-77. DOI: 10.1111/j.1479-8425.2006.00193.x

13. Sleep Foundation. Seattle WA: OneCare Media; 2022. Mental health and sleep [Internet]; 2022 [cited 2022 Jul 12]. Available from: https://www.sleepfoundation.org/mental-health

14. Lee S, Kim JH, Chung JH. The association between sleep quality and quality of life: a population-based study. Sleep Med. 2021 Aug;84:121-126. DOI: 10.1016/j.sleep.2021.05.022

The information contained within is intended to be used as an educational tool and it is not intended to be used to diagnose, treat, cure or prevent any disease, nor should it be used for therapeutic purposes or as a substitute for your own health professional's advice.