Subjective effects of glycine ingestion before bedtime on sleep quality

Inagawa, Kentaro; Hiraoka, Takenori; Kohda, Tohru; Yamadera, Wataru; Takahashi, Michio

doi:10.1111/j.1479-8425.2006.00193.x

Cited by 27 publications

(34 citation statements)

References 4 publications

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“…Despite evidence from human trials that glycine intake before bedtime improves sleep quality both subjectively and objectively (Bannai et al, 2012;Inagawa et al, 2006;Yamadera et al, 2007), details of its mechanism remain poorly understood. We have revealed the site of action of glycine that promotes sleep and a novel mechanism for regulating sleep and temperature.…”

Section: Discussionmentioning

confidence: 99%

“…The beneficial effects of glycine on subjective and objective sleep quality have been reported in subjects with insomniac tendencies (Inagawa et al, 2006;Yamadera et al, 2007). Therefore, in this sleep study, the rats were subjected to mild sleep disturbance in a new cage environment.…”

Section: Glycine Induces Nrem Sleep Accompanied By a Decrease In Corementioning

confidence: 99%

“…Because glutamatergic neurotransmission has been implicated in schizophrenia pathophysiology, oral administration of high-dose glycine-a mean dose of B60 g/day-has been reported to significantly improve cognition and reduce the negative symptoms of schizophrenia (Coyle and Tsai, 2004;Heresco-Levy et al, 1999). Conversely, low-dose glycine at a dose of 3 g/day before bedtime subjectively improves sleep quality and reduces sleepiness and fatigue during the day in individuals with insomniac tendencies or restricted sleep time (Bannai et al, 2012;Inagawa et al, 2006). A polysomnographic study also revealed that the same dose of glycine stabilizes sleep state and shortens the latency to slow-wave sleep, with no alterations in sleep architecture (Yamadera et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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The Sleep-Promoting and Hypothermic Effects of Glycine are Mediated by NMDA Receptors in the Suprachiasmatic Nucleus

Kawai

Sakai

Okuro

et al. 2014

Neuropsychopharmacol

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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. In this study, we investigated the site of action and sleep-promoting mechanisms of glycine in rats. In acute sleep disturbance, oral administration of glycine-induced non-rapid eye movement (REM) sleep and shortened NREM sleep latency with a simultaneous decrease in core temperature. Oral and intracerebroventricular injection of glycine elevated cutaneous blood flow (CBF) at the plantar surface in a dose-dependent manner, resulting in heat loss. Pretreatment with N-methyl-D-aspartate (NMDA) receptor antagonists AP5 and CGP78608 but not the glycine receptor antagonist strychnine inhibited the CBF increase caused by glycine injection into the brain. Induction of c-Fos expression was observed in the hypothalamic nuclei, including the medial preoptic area (MPO) and the suprachiasmatic nucleus (SCN) shell after glycine administration. 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.

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Section: Discussionmentioning

confidence: 99%

Section: Glycine Induces Nrem Sleep Accompanied By a Decrease In Corementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Sleep-Promoting and Hypothermic Effects of Glycine are Mediated by NMDA Receptors in the Suprachiasmatic Nucleus

Kawai

Sakai

Okuro

et al. 2014

Neuropsychopharmacol

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“…We recently reported that glycine ingestion before bedtime significantly improves subjective sleep quality among people with insomniac tendencies (Inagawa et al 2006;Yamadera et al 2007). Additionally, orally administered glycine has been shown to cross the blood-brain barrier (BBB) and accumulate in the cerebrospinal fluid (CSF) in rodents and humans (Richter and Wainer 1971;Lajtha 1981, 1986).…”

Section: Introductionmentioning

confidence: 97%

Pharmacokinetics and cerebral distribution of glycine administered to rats

et al. 2011

Self Cite

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High doses of glycine have been reported to improve negative schizophrenic symptoms, suggesting that ingested glycine activates glutamatergic transmission via N-methyl-D-aspartate (NMDA) receptors. However, the pharmacokinetics of administered glycine in the brain has not been evaluated. In the present study, the time- and dose-dependent distributions of administered glycine were investigated from a pharmacokinetic viewpoint. Whole-body autoradiography of radiolabeled glycine was performed, and time-concentration curves for glycine and serine in plasma, cerebrospinal fluid (CSF), and brain tissues were obtained. Furthermore, pharmacokinetic parameters were calculated. For a more detailed analysis, the amount of glycine uptake in the brain was evaluated using the brain uptake index method. Radiolabeled glycine was distributed among periventricular organs in the brain. Oral administration of 2 g/kg of glycine significantly elevated the CSF glycine concentration above the ED50 value for NMDA receptors. The glycine levels in CSF were 100 times lower than those in plasma. Glycine levels were elevated in brain tissue, but with a slower time-course than in CSF. Serine, a major metabolite of glycine, was elevated in plasma, CSF, and brain tissue. Glycine uptake in brain tissue increased in a dose-dependent manner. Time-concentration curves revealed that glycine was most likely transported via the blood-CSF barrier and activated NMDA receptors adjacent to the ventricles. The pharmacokinetic analysis and the brain uptake index for glycine suggested that glycine was transported into brain tissue by passive diffusion. These results provide further insight into the potential therapeutic applications of glycine.

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“…We have recently found that glycine improves sleep quality in humans who have repeated complains about sleep (4,5). This treatment is a novel approach to improve sleep via the administration of an amino acid.…”

Section: Introductionmentioning

confidence: 99%

New Therapeutic Strategy for Amino Acid Medicine: Glycine Improves the Quality of Sleep

Bannai

Kawai

2012

J Pharmacol Sci

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Abstract. 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. Oral administration of glycine to rats was found to induce a significant increase in the plasma and cerebrospinal fluid glycine concentrations and a significant decrease in the core body temperature associated with an increase in cutaneous blood flow. 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.

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Subjective effects of glycine ingestion before bedtime on sleep quality

Cited by 27 publications

References 4 publications

The Sleep-Promoting and Hypothermic Effects of Glycine are Mediated by NMDA Receptors in the Suprachiasmatic Nucleus

The Sleep-Promoting and Hypothermic Effects of Glycine are Mediated by NMDA Receptors in the Suprachiasmatic Nucleus

Pharmacokinetics and cerebral distribution of glycine administered to rats

New Therapeutic Strategy for Amino Acid Medicine: Glycine Improves the Quality of Sleep

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