Abstract
The effects of γ-aminobutyric acid (GABA) on sleep and its levels in blood after oral administration were investigated in humans. A randomized, single-blind, placebo-controlled crossover-designed study was conducted to evaluate the effect of GABA on sleep. Sleep was evaluated by electroencephalography (EEG) after oral GABA administration. GABA significantly shortened sleep latency and increased the total non-rapid eye movement (non-REM) sleep time. Questionnaires showed that subjects receiving GABA realized its effects on sleep. In addition, the blood level of GABA after administration was investigated, and the absorption and metabolism rates of GABA were determined. GABA was quickly absorbed, and the blood level of GABA was the highest 30 min after oral administration, with a subsequent decrease in concentration. As GABA strongly affected the early stage of sleep, the effect of GABA on sleep may be connected to its levels in blood.
Keywords: γ-Aminobutyric acid, sleep, electroencephalogram, absorption
References
- 1.Yoto A, Murao S, Motoki M, Yokoyama Y, Horie N, Takeshima K, Masuda K, Kim M, Yokogoshi H. Oral intake of aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks. Amino Acids. 2012;43:1331–1337. doi: 10.1007/s00726-011-1206-6. [DOI] [PubMed] [Google Scholar]
- 2.Petty F, Kramer G, Feldman M. Is plasma GABA of peripheral origin? Biol. Psychiat. 1987;22:725–732. doi: 10.1016/0006-3223(87)90204-6. [DOI] [PubMed] [Google Scholar]
- 3.Bjork JM, Moeller FG, Kramer GL, Kram M, Suris A, Rush AJ, Petty F. Plasma GABA levels correlate with aggressiveness in relatives of patients with unipolar depressive disorder. Psychiat. Res. 2001;101:131–136. doi: 10.1016/S0165-1781(01)00220-7. [DOI] [PubMed] [Google Scholar]
- 4.Lanctot KL, Herrmann N, Rothernburg L, Eryavec G. Behavioral correlates of GABAergic disruption in Alzheimer’s disease. Int. Psychogeriatr. 2007;19:151–158. doi: 10.1017/S1041610206003899. [DOI] [PubMed] [Google Scholar]
- 5.Abdou AM, Higashiguchi S, Horie K, Kim M, Hatta H, Yokogoshi H. Relaxation and immunity enhancement effects of aminobutyric acid (GABA) administration in humans. Biofactors. 2006;26:201–208. doi: 10.1002/biof.5520260305. [DOI] [PubMed] [Google Scholar]
- 6.Nakamura H, Takishima T, Kometani T, Yokogoshi H. Psychological stressreducing effect of chocolate enriched with γ-aminobutyric acid (GABA) in humans: Assessment of stress using heart rate variability and salivary chromogranin A. Int. J. Food Sci. Nutr. 2009;60:106–113. doi: 10.1080/09637480802558508. [DOI] [PubMed] [Google Scholar]
- 7.Fujibayashi M, Kamiya T, Takagaki K, Moritani T. Activation of autonomic nervous system activity by the oral ingestion of GABA. J. Jpn. Soc. Nutr. Food Sci. 2008;61:129–133. doi: 10.4327/jsnfs.61.129. [DOI] [Google Scholar]
- 8.Kim K, Uchiyama M, Okawa M, Liu X, Ogihara R. An epidemiological study of insomnia among the Japanese general population. Sleep. 2000;23:41–47. [PubMed] [Google Scholar]
- 9.Adam K, Oswald I. A comparison of the effects of chlormezanone and nitrazepam on sleep. Br. J. Clin. Pharmacol. 1982;14:57–65. doi: 10.1111/j.1365-2125.1982.tb04934.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Lemma S, Gelaye B, Berhane Y, Worku A, Williams MA. Sleep quality and its psychological correlates among university students in Ethiopia: A crosssectional study. BMC Psychiatry. 2012;12:237. doi: 10.1186/1471-244X-12-237. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Yamatsu A, Yamashita Y, Horie K, Takeshima K, Horie N, Masuda K, Yamane T, Kim M. Beneficial action of GABA on sleep and frequent night urination in the elderly. Jpn. Pharmacol. Ther. 2013;41:985–988. [Google Scholar]
- 12.Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh sleep quality index: A new instrument for psychiatric practice and research. Psychiat. Res. 1989;28:193–213. doi: 10.1016/0165-1781(89)90047-4. [DOI] [PubMed] [Google Scholar]
- 13.Velez JC, Souza A, Traslavina S, Barbosa C, Wosu A, Andrade A, Frye M, Fitzpatrick AL, Gelaye B, Williams MA. The epidemiology of sleep quality and consumption of stimulant beverages among Patagonian Chilean college students. 2013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Takahashi H, Masaki C, Makino M, Yoshida M, Mukaibo T, Kondo Y, Nakamoto T, Hosokawa R. Management of sleep-time masticatory muscle activity using stabilization splints affects psychological stress. J. Oral Rehabil. 2013;40:892–899. doi: 10.1111/joor.12110. [DOI] [PubMed] [Google Scholar]
- 15.Iber C, Ancoli-Israel S, Chesson A, Quan SF. The AASM manual for the scoring of sleep and associated events: Rules, terminology, and technical specification. 2007. [Google Scholar]
- 16.Greenblatt DJ, Shader RI, Divoll M, Harmatz JS. Benzodiazepines: A summary of pharmacokinetic properties. Br. J. Clin. Pharmaco. 1981;11:11S–16S. doi: 10.1111/j.1365-2125.1981.tb01833.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Markwald RR, Lee-Chiong TL, Burke TM, Snider JA, Wright KP. Effects of the melatonin MT-1/MT-2 agonist Ramelteon on daytime body temperature and sleep. Sleep. 2010;33:825–831. doi: 10.1093/sleep/33.6.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Roberts E. γ-Aminobutyric acid and nervous system function-A perspective. Biochem. Pharmacol. 1974;23:2637–2649. doi: 10.1016/0006-2952(74)90033-1. [DOI] [PubMed] [Google Scholar]