GABA and L-theanine mixture effect on sleep

Tea contains a variety of healthy ingredients, each of which has its own specific health benefits. On tea, on the one hand, tea can refresh the mind and relieve fatigue; on the other hand, it can be said that tea can calm down and relieve stress; the former is mainly attributed to the action of polyphenols and alkaloids in tea, while the latter Mainly due to the action of the components such as theanine and γ-aminobutyric acid (GABA). Today, I will share a study on the synergy between GABA and L-theanine to improve sleep, and see how GABA and L-theanine work together to improve sleep.

1. Abstract

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

Studies have shown that 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 neuromodulator properties of GABA & L-Theanine combination, which seems to affect sleep behavior.

2. Introduction

Sleep loss and other related disturbances pose an important health problem, as they can lead to significant functional impairments. Sleep disturbances can affect daily life considerably and reduce the quality of life. The importance of a good night’s sleep is well-established, nevertheless many people suffering from sleep disorders prefer not to use hypnotic drugs, despite providing effective symptomatic relief. Therefore, it is necessary to develop new bioactive substances derived from natural sources that present with similar efficacy but fewer side effects than hypnotic drugs, for the successful treatment of sleep-related disturbances.

γ-Glutamylethylamine, also known as l-theanine, and γ-aminobutyric acid (GABA) are known agents for improving sleep disturbances. GABA is a non-proteinogenic amino acid and is the main inhibitory neurotransmitter in the mammalian brain. Hence GABAA receptors are a primary target in the search for natural anxiolytic compounds or sedatives. There is an increasing interest in investigating the effect of GABA-mediated inhibitory neurotransmission, in respect to its potential benefit on counteracting sleep disruption caused by various conditions, such as stress, diseases and caffeine intake, etc.

L-theanine is an amino acid present in tea leaves, accounting for 1-2% (w/w) of the dry weight of tea, and is an active ingredient that induces sedation. Studies have shown that L-theanine can play a neuroprotective role, regulate neurotransmitter activity, reduce psychological stress and sleep disorders; Nathan et al also reported that L-theanine intake increases serotonin in the brain, Dopamine and GABA levels.

3. Results

3.1 Effects of GABA and l-theanine on sleep latency and duration in the pentobarbital-induced sleep model

Figure 1The sleep latency decreased with increasing GABA concentration, and sleep time increased with increasing GABA concentration. In terms of sleep latency, compared with the control group, there was a significant difference after taking 100 mg/kg GABA, but there was no significant difference with other GABA concentrations; in terms of sleep duration, compared with the control group, 100 mg/kg GABA group There was also a significant difference in sleep time (p < 0.05); no significant differences in sleep duration were observed after taking any other GABA concentrations.

After taking 20 or 30 mg/kg L-theanine, the sleep latency was significantly lower than that of the control group; while taking 40 mg/kg of L-theanine did not reduce the sleep latency; in short, taking 20 mg/kg of L- Theanine causes a decrease in sleep latency and an increase in sleep duration.

3.2 Effects of GABA/l-theanine combination on sleep latency and duration in the pentobarbital-induced sleep model

Figure 2The sleep latency of the GABA/L-theanine dose combination (80/30 and 100/20 mg/kg) was slightly lower than that of the control group; for sleep duration, the sleep time of all combinations showed an increasing trend; especially 100/ A 20 mg/kg dose combination of GABA/L-theanine mixture increased sleep duration most.

GABA/L-theanine (100/20 mg/kg) combination decreased sleep latency and sleep duration compared with GABA (100 mg/kg) or theanine (20 mg/kg) alone; GABA/L-tea the combined use of the amino acids shows a synergistic effect on sleep latency and sleep duration.

3.3 Effects of GABA and l-theanine mixture on sleep architecture

Figure 3Compared with the control group, GABA alone (100 mg/kg) significantly increased REM sleep time, but there was no significant difference in non-rapid eye movement (NREM); L-theanine (20 mg/kg) was administered alone. Significantly increased REM time, but there was no significant difference in NREM sleep time. Both NREM and REM were significantly increased after taking the GABA/L-theanine mixture; taking the GABA/L-theanine mixture improved sleep time and quality compared to GABA or L-theanine alone.

After taking GABA or L-theanine and taking GABA/L-theanine mixture, the θ wave increased significantly; after taking GABA or L-theanine or GABA/L-theanine mixture, respectively, the δ wave showed a decrease. The trend, but there is no significant difference between the groups.

3.4 Effects of GABA and l-theanine combination on sleep architecture during three sleep periods

Figure 4In all three periods, the NREM sleep was significantly increased in the GABA/L-theanine mixture group compared with the control group; after taking the GABA or L-theanine or GABA/L-theanine mixture, respectively, and the control Compared with the group, REM sleep always increased significantly.

Taking a mixture of GABA and L-theanine can significantly prolong sleep time, especially NREM time during long-term use. In addition, administration of the GABA/L-theanine mixture increased the θ wave in NREM sleep compared to the control group, which reduced the delta wave oscillation; the δ wave gradually increased with long-term administration. Therefore, the longer the GABA/L-theanine mixture is taken, the better the sleep quality and the longer the induced sleep duration.

3.5 EEG acquisition and analysis in a caffeine-induced wakefulness model

Figure 5Administration of GABA, L-theanine, or a combination of both in a caffeine-induced arousal model resulted in significant differences in sleep and wakefulness times compared to the awakened group. In the arousal model, the L-theanine or GABA/L-theanine mixture was used to restore the NREM sleep time to the control level. However, taking the GABA/L-theanine mixture in the arousal model tended to restore REM sleep time, but there was no significant difference from the arousal group.

Administration of a GABA/L-theanine mixture increased the theta and delta wave oscillations in NREM sleep compared to the awakened group. These results indicate that in the awakening animal model, GABA and L-theanine mixture can restore sleep time and quality to normal levels.

3.6 Effects of GABA and l-theanine combination on the mRNA levels of neurotransmitter receptors

Figure 6After taking the GABA/L-theanine mixture, the transcription level of the GABA A receptor was 1.53 times higher than that of the control group. Furthermore, administration of the GABA/L-theanine mixture resulted in a significant change in the mRNA level of GABAB-R2 compared to the control; whereas the mRNA level of GABAB-R1 was not significantly different.

The GABA/L-theanine mixture significantly increased the mRNA level of the GluN1 glutamate receptor subunit compared to the control; whereas the L-theanine alone changed the GluR1 glutamate receptor and the GluN1 glutamate subunit. Base expression. These results indicate that administration of a GABA/L-theanine mixture results in increased expression of GABA receptor GABA A, GABAB-R1 and GABAB-R2, and GluN1 glutamate receptor subunits, possibly improving sleep behavior and neuromodulation.

4. Discussion

The combination of GABA and L-theanine (100/20 mg/kg) not only reduced sleep latency, but also prolonged sleep time; it was confirmed that GABA and L-theanine have synergistic effects on sleep behavior, significantly reducing sleep latency. Prolong sleep time; its mechanism may be mediated by altering the expression of GABA and/or glutamate receptors in the brain.