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Relaxation and immunity enhancement effects of γ-Aminobutyric acid (GABA) administration in humans

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The effect of orally administrated gamma-aminobutyric acid (GABA) on relaxation and immunity during stress has been investigated in humans. Two studies were conducted. The first evaluated the effect of GABA intake by 13 subjects on their brain waves. Electroencephalograms (EEG) were obtained after 3 tests on each volunteer as follows: intake only water, GABA, or L-theanine. After 60 minutes of administration, GABA significantly increases alpha waves and decreases beta waves compared to water or L-theanine. These findings denote that GABA not only induces relaxation but also reduces anxiety. The second study was conducted to see the role of relaxant and anxiolytic effects of GABA intake on immunity in stressed volunteers. Eight acrophobic subjects were divided into 2 groups (placebo and GABA). All subjects were crossing a suspended bridge as a stressful stimulus. Immunoglobulin A (IgA) levels in their saliva were monitored during bridge crossing. Placebo group showed marked decrease of their IgA levels, while GABA group showed significantly higher levels. In conclusion, GABA could work effectively as a natural relaxant and its effects could be seen within 1 hour of its administration to induce relaxation and diminish anxiety. Moreover, GABA administration could enhance immunity under stress conditions.
... He et al. [36] reported that oral administration of GABA could increase the distance and time in OFT of an emotional stress rat model. In human studies, Abdou et al. [37] found that oral intake of GABA markedly increased alpha waves and decreased beta waves in the brain. Finally, they concluded that GABA could induce a calming effect and diminish anxiety. ...
... Adverse events and concern for misuse highlight the need for safe and effective alternatives for sleep management. Rest-ZZZ (LifeSeasons, Inc.) is a natural sleep supplement containing active ingredients independently shown to improve various sleep quality (SQ) parameters [8][9][10][11][12][13][14]. Making up the largest quantity of active ingredients in Rest-ZZZ, melatonin promotes sleep as a result of the activation of high-affinity, G protein coupled receptors, MT1 and MT2 [15]. ...
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The purpose of this study was to investigate the safety and efficacy of Rest-ZZZ, a natural sleep supplement, in healthy adults without a diagnosed sleep disorder. This randomized, double-blind, placebo-controlled, cross-over study consisted of three 7-day supplementation periods with either Rest-ZZZ, Diphenhydramine (DPH), or Placebo, with a 7-day washout. Twenty-seven participants were randomized to one of three intervention sequences and the Healthy People Sleep Quality Index (HPSQI), Quality of Life (QoL), and Profile of Mood States (POMS) questionnaires were assessed at the beginning and end of each supplementation period. Rest-ZZZ and Placebo showed improvements in sleep-related QoL ( p ≤ 0.044) and total mood disturbance (TMD) ( p = ≤ 0.028). Fatigue–Inertia was reduced by all study products ( p ≤ 0.031). DPH did not result in any significant improvements on sleep quality parameters. A subgroup analysis of participants ≤ 45 years found enhanced efficacy of Rest-ZZZ and improvement in sleep-related QoL vs. Placebo ( p = 0.007), as well as improvements in sleep duration ( p = 0.007), sleep debt ( p = 0.011), and sleep-related QoL ( p = 0.033). DPH supplementation resulted in significant improvement in only sleep debt ( p = 0.038). Rest-ZZZ had a safe hematology and chemistry profile. Rest-ZZZ resulted in restful sleep that generated corresponding improvements in sleep-related QoL and overall mood. Rest-ZZZ is an efficacious sleep supplement with a favorable safety profile, particularly in those aged 25–45 years.
... [7][8][9][10][11] Clinical trials studying oral supplementation of GABA in humans are still scarce and focus mainly on the effects on mental processes. 12,13 GABA is primarily known as a neurotransmitter that is endogenously formed. Endogenous GABA is synthesized from glutamate via the enzymatic activity of glutamic acid decarboxylase in the brain, pancreas, liver, and it is produced by the gut microbiota. ...
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Gamma-aminobutyric acid (GABA) and its precursor glutamate play signaling roles in a range of tissues. Both function as neurotransmitters in the central nervous system, but they also modulate pancreatic and...
... Studies in mice have shown that GABA at dose levels of 100 and 150 µg improved improve discrimination learning ability (Ishikawa and Saito, 1978). Exposure to a high altitude environment and ingestion of 100 mg GABA in subjects with acrophobia has been shown to increase alpha brain waves and decrease immunoglobulin A levels, thereby promoting relaxation and reducing anxiety (Abdou et al., 2006). Daily intake of fermented milk containing 10 mg of GABA for 12 weeks can also help control blood pressure levels in patients with mild hypertension (Inoue et al., 2003). ...
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Kazakh cheese is a traditional dairy product in Xinjiang, China. The function and potential probiotic characteristics of Saccharomyces cerevisiae DL6–20 and Kluyveromyces marxianus B13–5 in Kazakh cheese and its contribution to cheese fermentation was studied. In this study, the effect of the addition ratio of gamma aminobutyric acid (GABA)-producing S. cerevisiae DL6–20 and K. marxianus B13–5 on cheese quality was investigated. Cheeses were prepared by fermentations with a total of six treatments: comercial culture alone as control (CS), a combination with one yeast, either; K. marxianus B13–5 (CSM); S. cerevisiae DL6–20 (CSS); and three different proportions of this two yeasts (CSM:CSS 1:1, 1:2, 2:1). We measured the GABA content of cheese, as well as basic physical and chemical indicators, microbial content, free amino acid (FAA) content, texture, and flavor compound content. The total FAA content of mixed bacteria fermentation was higher than that of the single bacteria alone. The GABA content CSM:CSS 1:2 GABA content was 0.114 g/100 g, CSM:CSS 2:1 GABA content was 0.12 g/100 g, CSM:CSS1:1 content of GABA produced in the late ripening period of cheese was the highest, reaching 0.189 g/100 g and the number of LAB and yeasts in CSM:CSS 1:1 was higher than that of other cheeses. The mixed-strain fermentation generally produced cheeses with a higher protein content than that of the single-strain fermentation in the late stage of the maturation process, especially the protein content of CSM:CSS 1:1 during the ripening period, when the protein content was highest at day 50. CSM:CSS 1:1 had a low moisture content, making it easy to store. With the exception of water and protein content, there is no significant difference in other physical and chemical indicators. CSM:CSS 1:1 contributed to the formation of cheese texture. In addition, multivariate statistical analysis indicated that mixed-strain fermentation was beneficial to the production of cheese aroma, with the aroma production performance of CSM:CSS 1:2 and CSM:CSS 2:1 found to be better than that of CSM: CSS 1:1.
... Recently, it has been manufactured and widely used as a dietary supplement. Previous studies in human trials demonstrated that dietary GABA induces antihypertensive effects [6], alleviates anxiety [7], and improves sleep quality [8] and cognitive functions [9,10]. As a result, GABA is blended into many functional foods and is sold worldwide including in Europe, the United States, and Asia. ...
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Gamma-aminobutyric acid (GABA) is present in the mammalian brain as the main inhibitory neurotransmitter and in foods. It is widely used as a supplement that regulates brain function through stress-reducing and sleep-enhancing effects. However, its underlying mechanisms remain poorly understood, as it is reportedly unable to cross the blood–brain barrier. Here, we explored whether a single peroral administration of GABA affects feeding behavior as an evaluation of brain function and the involvement of vagal afferent nerves. Peroral GABA at 20 and 200 mg/kg immediately before refeeding suppressed short-term food intake without aversive behaviors in mice. However, GABA administration 30 min before refeeding demonstrated no effects. A rise in circulating GABA concentrations by the peroral administration of 200 mg/kg GABA was similar to that by the intraperitoneal injection of 20 mg/kg GABA, which did not alter feeding. The feeding suppression by peroral GABA was blunted by the denervation of vagal afferents. Unexpectedly, peroral GABA alone did not alter vagal afferent activities histologically. The coadministration of a liquid diet and GABA potentiated the postprandial activation of vagal afferents, thereby enhancing postprandial satiation. In conclusion, dietary GABA activates vagal afferents in collaboration with meals or meal-evoked factors and regulates brain function including feeding behavior.
... A systematic review and meta-analysis showed that the global prevalence estimate was 28.0% for depression, 26.9% for anxiety, 24.1% for post-traumatic stress Growing evidence suggests that certain food ingredients affect fatigue recovery, mood improvement, and stress reduction. For example, the daily intake of chicken essence has been reported to aid the recovery from mental fatigue in healthy men [10], and the oral administration of GABA has been known to help reduce stress and fatigue [11][12][13][14]. Recent studies on the gut microbiome suggest that probiotic materials are important solutions for not only the intestinal environment but, also, mood conditions [15,16]. ...
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Background: The importance of maintaining good mental health with overall well-being has recently drawn attention from various spheres of academics and the working population. Amino acid intake has been reported to reduce depression symptoms and other mental health problems. However, the effectiveness of amino acid intake (i.e., single or combined) remains unknown. In this study, we assessed a combination of five amino acids (serine, alanine, glutamate, aspartate, and tyrosine; SAGAT) reported to regulate mental health. Methods: A randomized, double-blind, placebo-controlled exploratory trial was conducted. Participants, aged between 20 and 65 years with fatigue sensation, were randomized to receive either SAGAT or the placebo and ingested them for four weeks. A transient mental work was loaded at day 0 and after four weeks of intervention. As the primary outcomes, the fatigue sensation was assessed. The mood status, cognitive function, work efficiency, and blood marker were also measured as secondary outcomes. Results: The number of participants analyzed for the efficacy evaluation were 20 in SAGAT and 22 in the placebo. There were no significant differences in the primary outcomes. However, as the secondary outcomes, the SAGAT group showed a significant improvement in motivation and cognitive function in the recovery period after mental work loaded in a four-week intervention compared to the placebo. Conclusion: The current findings suggest that SAGAT contributes to maintaining proper motivation and cognitive function. Clinical trial registration: University Hospital Medical Information Network Clinical Trial Registry (ID: UMIN 000041221).
... Gamma-aminobutyric acid (GABA), a nonproteinogenic amino acid, is used as a bioactive component of drugs in the pharmaceuticals and a major precursor for the synthesis of butyrolactam and polyamide 4 (nylon 4) [17][18][19][20]. GABA can be synthesized from Lglutamic acid in a one-step decarboxylation reaction catalyzed by glutamate decarboxylase (GAD, EC 4.1.1.15). ...
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Gamma-aminobutyric acid (GABA) can be used as a bioactive component in the pharmaceutical industry and a precursor for the synthesis of butyrolactam, which functions as a monomer for the synthesis of polyamide 4 (nylon 4) with improved thermal stability and high biodegradability. The bio-based fermentation production of chemicals using microbes as a cell factory provides an alternative to replace petrochemical-based processes. Here, we performed model-guided metabolic engineering of Corynebacterium glutamicum for GABA and butyrolactam fermentation. A GABA biosynthetic pathway was constructed using a bi-cistronic expression cassette containing mutant glutamate decarboxylase. An in silico simulation showed that the increase in the flux from acetyl-CoA to α-ketoglutarate and the decrease in the flux from α-ketoglutarate to succinate drove more flux toward GABA biosynthesis. The TCA cycle was reconstructed by increasing the expression of acn and icd genes and deleting the sucCD gene. Blocking GABA catabolism and rewiring the transport system of GABA further improved GABA production. An acetyl-CoA-dependent pathway for in vivo butyrolactam biosynthesis was constructed by overexpressing act-encoding ß-alanine CoA transferase. In fed-batch fermentation, the engineered strains produced 23.07 g/L of GABA with a yield of 0.52 mol/mol from glucose and 4.58 g/L of butyrolactam. The metabolic engineering strategies can be used for genetic modification of industrial strains to produce target chemicals from α-ketoglutarate as a precursor, and the engineered strains will be useful to synthesize the bio-based monomer of polyamide 4 from renewable resources.
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Bushukan is one of the citrus cultivars predominantly cultivated in Shimanto City, Kochi, Japan. Bushukan has a unique flavor, and typically both the juice and peels are utilized. However, the peel remaining after juice has been extracted during commercial processes typically becomes waste. To reduce this waste, the peel residue was put through lactic fermentation. A new strain of Latilactobacillus sakei, isolated from Bushukan flowers, and Lactoplantibacillus plantalum and Levilactobacillus brevis isolated from post-fermented tea were used to initiate this process. In this study, paste from Bushukan peel was mixed with the lactic acid bacteria and sucrose and incubated at 37℃ for 4 days. Following incubation, acidity increased (pH decreased) as the lactic acid concentration increased. d-amino acid was detected in the fermented Bushukan peel. Lactate fermentation provides additional physiological activities to Bushukan peel and gives new application potency.
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γ-Aminobutyrate (GABA) is an important chemical by itself and can be further used for the production of monomer used for the synthesis of biodegradable polyamides. Until now, GABA production usingCorynebacterium glutamicum harboring glutamate decarboxylases (GADs) has been limited due to the discrepancy between optimal pH for GAD activity (pH 4.0) and cell growth (pH 7.0). In this study, we developed recombinant C. glutamicum strains expressing mutated GAD from Escherichia coli (EcGADmut) and GADs from Lactococcus lactis CICC20209 (LlGAD) and Lactobacillus senmaizukei (LsGAD), all of which showed enhanced pH stability and adaptability at a pH of approximately 7.0. In shake flask cultivations, the GABA productions of C. glutamicum H36EcGADmut, C. glutamicum H36LsGAD, and C. glutamicum H36LlGAD were examined at pH 5.0, 6.0, and 7.0, respectively. Finally, C. glutamicum H36EcGADmut (40.3 and 39.3 g L-1), H36LlGAD (42.5 and 41.1 g L-1), and H36LsGAD (41.6 and 40.2 g L-1) produced improved GABA titers and yields in batch fermentation at pH 6.0 and pH 7.0, respectively, from 100 g L-1 glucose. The recombinant strains developed in this study could be used for the establishment of sustainable direct fermentative GABA production from renewable resources under mild culture conditions, thus increasing the availability of various GADs.
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The effect of γ-amino butyric acid (GABA)-enriched soybean on blood pressure was investigated in male spontaneously hypertensive rats. Ten-week-old rats were given diets containing graded levels of GABA-enriched soybean powder for 8 weeks. The systolic blood pressure in rats fed 0.15% GABA diet was significantly lower at 1st week and maintained lower values for 4 weeks as compared with 0% GABA controls. No effect on blood pressure was found in those of 0.03 and 0.3% GABA. The results suggest that there exist appropriate dietary GABA level to get the blood pressure lowering effect.
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The effects of anxiety, depression and psychological stress on the secretion rate of salivary immunoglobulin (Ig)A were examined in a cross-sectional study of 114 registered nurses. A single, timed (five minutes) sample of whole unstimulated saliva was collected from each nurse; at the time of collection, psychosocial data for each nurse were collected by questionnaire. Nurses who reported more frequent episodes of anxiety had significantly lower mean secretion rates of salivary IgA than did nurses who reported only occasional episodes of anxiety. The concentration of secretory IgA in saliva decreased as the salivary volume increased. It was not possible to demonstrate whether anxiety influenced IgA secretion in saliva independently of its effects on salivary flow.