Glycine Abstracts 2

© 2012

New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep

            (Bannai and Kawai 2012) Download

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.

The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers

         (Bannai, Kawai et al. 2012) Download

Approximately 30% of the general population suffers from insomnia. Given that insomnia causes many problems, amelioration of the symptoms is crucial. Recently, we found that a non-essential amino acid, glycine subjectively and objectively improves sleep quality in humans who have difficulty sleeping. We evaluated the effects of glycine on daytime sleepiness, fatigue, and performances in sleep-restricted healthy subjects. Sleep was restricted to 25% less than the usual sleep time for three consecutive nights. Before bedtime, 3 g of glycine or placebo were ingested, sleepiness, and fatigue were evaluated using the visual analog scale (VAS) and a questionnaire, and performance were estimated by personal computer (PC) performance test program on the following day. In subjects given glycine, the VAS data showed a significant reduction in fatigue and a tendency toward reduced sleepiness. These observations were also found via the questionnaire, indicating that glycine improves daytime sleepiness and fatigue induced by acute sleep restriction. PC performance test revealed significant improvement in psychomotor vigilance test. We also measured plasma melatonin and the expression of circadian-modulated genes expression in the rat suprachiasmatic nucleus (SCN) to evaluate the effects of glycine on circadian rhythms. Glycine did not show significant effects on plasma melatonin concentrations during either the dark or light period. Moreover, the expression levels of clock genes such as Bmal1 and Per2 remained unchanged. However, we observed a glycine-induced increase in the neuropeptides arginine vasopressin and vasoactive intestinal polypeptide in the light period. Although no alterations in the circadian clock itself were observed, our results indicate that glycine modulated SCN function. Thus, glycine modulates certain neuropeptides in the SCN and this phenomenon may indirectly contribute to improving the occasional sleepiness and fatigue induced by sleep restriction.

Benign prostatic hypertrophy: amino acid therapy for symptomatic relief

            (Damrau 1962) Download

Glycine-extended gastrin potentiates gastrin-stimulated gastric acid secretion in rats

            (Higashide, Gomez et al. 1996) Download

The purpose of this study was to examine whether an intermediate form of amidated gastrin, glycine-extended gastrin (Gly-G), can stimulate gastric acid secretion in conscious rats prepared with gastric fistulas. Intravenous administration of Gly-G (20 nmol.kg-1.h-1) alone for 2 h did not stimulate gastric acid secretion; however, administration of Gly-G (20 nmol.kg-1.h-1) in combination with a bolus administration of gastrin (9.5 nmol/kg) potentiated acid secretion significantly. Gastric acid secretion in response to gastrin alone and gastrin plus Gly-G (2 nmol.kg-1.h-1) was 109.1 +/- 21.6 and 170.1 +/- 27.7 mueq.kg-1.h-1, respectively (P < 0.05). Gastric acid secretion in response to gastrin alone and gastrin plus Gly-G (20 nmol.kg-1.h-1) was 84.8 +/- 17.5 and 164.1 +/- 29.3 mueq.kg-1.h-1, respectively (P < 0.05). Intravenous administration of Gly-G (20 nmol.kg-1.h-1) failed to increase histamine (1 mg/kg)-stimulated acid output. These results demonstrate that Gly-G can selectively potentiate the stimulatory effect of gastrin on acid secretion in rats and that the unprocessed form of gastrin, Gly-G, can exert a biological effect in the stomach.

Subjective effects of glycine ingestion before bedtime on sleep quality

(Inagawa, Hiraoka et al. 2006) Download

The effects of glycine on sleep quality were examined in a randomized double-blinded cross-over trial. The volunteers, with complaints about the quality of their sleep, ingested either glycine (3 g) or placebo before bedtime, and their subjective feeling in the following morning was evaluated with the St. Mary's Hospital Sleep Questionnaire and Space-Aeromedicine Fatigue Checklist. The glycine ingestion 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.

Stimulation of gastric acid secreted by glycine and related oligopeptides in humans

            (Wald and Adibi 1982) Download

To investigate the effect of oligopeptides on gastric secretion in humans, we investigated acid secretion in healthy volunteers after the intragastric infusion of physiological saline, glycine (100 mM), diglycine (50 mM), triglycine (33 mM), and tetraglycine (25 mM). All test solutions were equivalent in glycine content, osmolality (300 mosmol), and pH (5.5). Although the rate of acid secretion was greater during glycine than saline infusion [5.6 +/- 0.8 vs. 3.3 +/- 1.1 mmol/h (means +/- SE); P less than 0.05], the rate of acid secretion during glycine infusion was not significantly different from that induced by its related peptides. There were increases in plasma glycine concentration during infusion of glycine and its related peptides but no detectable changes in serum gastrin levels. The increases in plasma glycine must have been due to absorption from the small intestine because there was no gastric absorption of glycine in free or dipeptide form nor diglycine hydrolysis in the stomach. Therefore, our results permit implicating only the increased plasma glycine concentrations as the stimulus for acid secretion by glycine and its homologous peptides.

Glycine ingestion improves subjective sleep quality in human volunteers

            (Yamadera, Inagawa et al. 2007) Download

In human volunteers who have been continuously experiencing unsatisfactory sleep, effects of glycine ingestion (3 g) before bedtime on subjective sleep quality were investigated, and changes in polysomnography (PSG) during sleep were analyzed. Effects on daytime sleepiness and daytime cognitive function were also evaluated. Glycine improved subjective sleep quality and sleep efficacy (sleep time/in-bed time), and shortened PSG latency both to sleep onset and to slow wave sleep without changes in the sleep architecture. Glycine lessened daytime sleepiness and improved performance of memory recognition tasks. Thus, a bolus ingestion of glycine before bedtime seems to produce subjective and objective improvement of the sleep quality in a different way than traditional hypnotic drugs such as benzodiazepines.


References

Bannai, M. and N. Kawai (2012). "New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep." J Pharmacol Sci 118(2): 145-8 PMID: 22293292

Bannai, M., N. Kawai, et al. (2012). "The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers." Front Neurol 3: 61 PMID: 22529837

Damrau, F. (1962). "Benign prostatic hypertrophy: amino acid therapy for symptomatic relief." J Am Geriatr Soc 10: 426-30 PMID: 13883328

Higashide, S., G. Gomez, et al. (1996). "Glycine-extended gastrin potentiates gastrin-stimulated gastric acid secretion in rats." Am J Physiol 270(1 Pt 1): G220-4 PMID: 8772521

Inagawa, K., T. Hiraoka, et al. (2006). "Subjective effects of glycine ingestion before bedtime on sleep quality." Sleep and Biological Rhythms 4(1): 75–77 PMID:

Wald, A. and S. A. Adibi (1982). "Stimulation of gastric acid secreted by glycine and related oligopeptides in humans." Am J Physiol 242(2): G85-8 PMID: 7065145

Yamadera, W., K. Inagawa, et al. (2007). "Glycine ingestion improves subjective sleep quality in human volunteers." Sleep and Biological Rhythms 5(2): 126–131 PMID: