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. 2019 Dec;57(1):65-73.
doi: 10.1080/13880209.2018.1557698.

GABA and l-theanine mixture decreases sleep latency and improves NREM sleep

Suhyeon Kim  1 , Kyungae Jo  1 , Ki-Bae Hong  2 , Sung Hee Han  3 , Hyung Joo Suh  4
Affiliations

GABA and l-theanine mixture decreases sleep latency and improves NREM sleep

Suhyeon Kim et al. Pharm Biol. 2019 Dec.

Abstract

Context: γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter and it is well established that activation of GABAA receptors favours sleep. l-Theanine, a naturally occurring amino acid first discovered in green tea, is a well-known anti-anxiety supplement with proven relaxation benefits.

Objective: This study investigated the potential synergistic sleep enhancement effect of GABA/l-theanine mixture.

Materials and methods: Pentobarbital-induced sleep test was applied to find proper concentration for sleep-promoting effect in ICR mice. Electroencephalogram (EEG) analysis was performed to investigate total sleeping time and sleep quality in normal SD rats and caffeine-induced awareness model. Real-time polymerase chain reaction (RT-PCR) was applied to investigate whether the sleep-promoting mechanism of GABA/l-theanine mixture involved transcriptional processes.

Results: GABA/l-theanine mixture (100/20 mg/kg) showed a decrease in sleep latency (20.7 and 14.9%) and an increase in sleep duration (87.3 and 26.8%) compared to GABA or theanine alone. GABA/l-theanine mixture led to a significant increase in rapid eye movement (REM) (99.6%) and non-REM (NREM) (20.6%) compared to controls. The use of GABA/l-theanine mixture rather than GABA or l-theanine alone restored to normal levels sleep time and quality in the arousal animal model. The administration of GABA/l-theanine led to increased expression of GABA and the glutamate GluN1 receptor subunit.

Conclusions: GABA/l-theanine mixture has a positive synergistic effect on sleep quality and duration as compared to the GABA or l-theanine alone. The increase in GABA receptor and GluN1 expression is attributed to the potential neuromodulatory properties of GABA/l-theanine combination, which seems to affect sleep behaviour.

Keywords: electroencephalography; insomnia; pentobarbital-induced sleep test; γ-Aminobutyric acid.

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Figures

Figure 1.
Figure 1.
Effects of GABA or l-theanine on sleep latency (A, C) and sleep duration (B, D) in mice administered with a hypnotic dosage of pentobarbital (42 mg/kg, i.p.). Values are presented as the means ± standard error (SE) for each group, n = 8. Different letters indicate significant differences (p < 0.05) among samples by Tukey’s multiple range test. Symbols indicate significant differences by Bonferroni test, as **p < 0.01, *p < 0.05.
Figure 2.
Figure 2.
Effects of GABA/l-theanine mixture on sleep latency (A, C) and sleep duration (B, D) in mice administered with a hypnotic dosage of pentobarbital (42 mg/kg, i.p.). Values are presented as the means ± standard error (SE) for each group, n = 8. Different letters indicate significant differences (p < 0.05) among samples by Tukey’s multiple range test. Symbols indicate significant differences by Bonferroni test, as **p < 0.01, *p < 0.05.
Figure 3.
Figure 3.
Effects of the GABA, l-theanine, and GABA/l-theanine mixture on sleep quantity and quality. Values are presented as the means ± standard error (SE) for each group, n = 8. Different letters indicate significant differences (p < 0.05) among samples by Tukey’s multiple range test. Symbols indicate significant differences at ***p < 0.001, **p < 0.01, *p < 0.05 by Bonferroni test. NS: not significant.
Figure 4.
Figure 4.
Effects of GABA, l-theanine, and GABA/l-theanine mixture on sleep quantity and quality during administration periods. Values are presented as the means ± standard error (SE) for each group, n = 8. Symbols indicate significant differences by Bonferroni test, as ***p < 0.001, **p < 0.01, *p < 0.05.
Figure 5.
Figure 5.
Effects of the GABA, l-theanine, and GABA/l-theanine mixture on caffeine-induced wakefulness in rats at a dosage of caffeine (10 mg/kg). Values are presented as the means ± standard error (SE) for each group, n = 8. Different letters indicate significant differences (p < 0.05) among samples by Tukey’s multiple range test. Symbols indicate significant differences by Bonferroni test, as ***p < 0.001, **p < 0.01 compared with arousal group.
Figure 6.
Figure 6.
Effects of the GABA/l-theanine mixture on GABA and glutamate receptors mRNA expression in the mouse brain. Values are presented as mean ± standard error of the mean (SEM) for the brain regions of 8 mice and for each group, n = 8. Different letters indicate significant differences (p < 0.05) among samples by Tukey’s multiple range test. Symbols indicate significant differences by Bonferroni test, as ***p < 0.001, **p < 0.01, *p < 0.05. NS: not significant.
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Grants and funding

This research was supported by the Ministry of Trade, Industry & Energy (MOTIE), Korea Institute for Advancement of Technology (KIAT) through the Encouragement Program for The Industries of Economic Cooperation Region (R0004012).

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