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In the GABA shunt, GABA is synthesized from glutamate in a process catalyzed by GAD. GABA is metabolized by GABA-T into succinate semi-aldehyde, which is then reduced to gamma-hydroxybutyrate or oxidized to succinate and eventually converted to CO2 and water via the TCA cycle. GAD, glutamatic acid decarboxylase; GABA-T, GABA transaminase; SSA, succinic semialdehyde; SSA-DH, succinic semialdehyde dehydrogenase; TCA cycle, tricarboxylic acid cycle. Green, enzymes; Orange, cofactor.
Source publication
Gamma-amino butyric acid (GABA) is marketed in the U.S. as a dietary supplement. USP conducted a comprehensive safety evaluation of GABA by assessing clinical studies, adverse event information, and toxicology data. Clinical studies investigated the effect of pure GABA as a dietary supplement or as a natural constituent of fermented milk or soy mat...
Citations
... Butyric acid is also used as a histone deacetylase inhibitor for treating intestinal inflammation, cardiovascular disease, and cancer. Butyric acid can further serve as a substrate to produce biofuel butanol through hydrogen-catalyzed reduction (EFSA Panel on Dietetic Products, Nutrition and Allergies, 2009;Alimentarius, 2015;Sarasa et al., 2020;Oketch-Rabah et al., 2021). Microbially synthesized bio-butyric acid is gaining traction due to consumer preferences for natural products and the global emphasis on environmental sustainability, particularly the concept of carbon neutrality. ...
Introduction
Sweet sorghum juice is a typical production feedstock for natural, eco-friendly sweeteners and beverages. Clostridium tyrobutyricum is one of the widely used microorganisms in the food industry, and its principal product, bio-butyric acid is an important food additive. There are no published reports of Clostridium tyrobutyricum producing butyric acid using SSJ as the sole substrate without adding exogenous substances, which could reach a food-additive grade. This study focuses on tailoring a cost-effective, safe, and sustainable process and strategy for their production and application.
Methods
This study modeled the enzymolysis of non-reducing sugars via the first/second-order kinetics and added food-grade diatomite to the hydrolysate. Qualitative and quantitative analysis were performed using high-performance liquid chromatography, gas chromatography-mass spectrometer, full-scale laser diffraction method, ultra-performance liquid chromatography–tandem mass spectrometry, the cell double-staining assay, transmission electron microscopy, and Oxford nanopore technology sequencing. Quantitative real-time polymerase chain reaction, pathway and process enrichment analysis, and homology modeling were conducted for mutant genes.
Results
The treated sweet sorghum juice showed promising results, containing 70.60 g/L glucose and 63.09 g/L fructose, with a sucrose hydrolysis rate of 98.29% and a minimal sucrose loss rate of 0.87%. Furthermore, 99.62% of the colloidal particles and 82.13% of the starch particles were removed, and the concentrations of hazardous substances were effectively reduced. A food microorganism Clostridium tyrobutyricum TGL-A236 with deep utilization value was developed, which showed superior performance by converting 30.65% glucose and 37.22% fructose to 24.1364 g/L bio-butyric acid in a treated sweet sorghum juice (1:1 dilution) fermentation broth. This titer was 2.12 times higher than that of the original strain, with a butyric acid selectivity of 86.36%. Finally, the Genome atlas view, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and evolutionary genealogy of genes: Non-supervised Orthologous (eggNOG) functional annotations, three-dimensional structure and protein cavity prediction of five non-synonymous variant genes were obtained.
Conclusion
This study not only includes a systematic process flow and in-depth elucidation of relevant mechanisms but also provides a new strategy for green processing of food raw materials, improving food microbial performance, and ensuring the safe production of food additives.
... In recent times, interest has surged in GABA-containing food supplements and their hypothetical impact on brain activity and functions. A study found that consistent administration of GABA to rats and dogs, even at doses up to 1 g/kg/day, did not exhibit any indications of toxicity [24]. Notably, some research has linked GABA to reductions in blood pressure, implying a potential risk of hypotension when used alongside antihypertensive drugs [24]. ...
... A study found that consistent administration of GABA to rats and dogs, even at doses up to 1 g/kg/day, did not exhibit any indications of toxicity [24]. Notably, some research has linked GABA to reductions in blood pressure, implying a potential risk of hypotension when used alongside antihypertensive drugs [24]. Oral GABA's potential to affect stress and sleep was examined through various studies. ...
Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system (CNS), plays a pivotal role in maintaining the delicate balance between inhibitory and excitatory neurotransmission. Dysregulation of the excitatory/inhibitory balance is implicated in various neurological and psychiatric disorders, emphasizing the critical role of GABA in disease-free brain function. The review examines the intricate interplay between the gut–brain axis and CNS function. The potential impact of dietary GABA on the brain, either by traversing the blood–brain barrier (BBB) or indirectly through the gut–brain axis, is explored. While traditional beliefs questioned GABA’s ability to cross the BBB, recent research challenges this notion, proposing specific transporter systems facilitating GABA passage. Animal studies provide some evidence that small amounts of GABA can cross the BBB but there is a lack of human data to support the role of transporter-mediated GABA entry into the brain. This review also explores GABA-containing food supplements, investigating their impact on brain activity and functions. The potential benefits of GABA supplementation on pain management and sleep quality are highlighted, supported by alterations in electroencephalography (EEG) brain responses following oral GABA intake. The comprehensive overview encompasses GABA’s sources in the diet, including brown rice, soy, adzuki beans, and fermented foods. GABA’s presence in various foods and supplements, its association with gut microbiota, and its potential as a therapeutic strategy for neurological disorders are thoroughly examined. The articles were retrieved through a systematic review of the databases: OVID, SCOPUS, and PubMed (keywords “GABA”, “oral GABA“, “sleep”, “cognition”, “neurodegenerative”, “blood-brain barrier”, “gut microbiota”, “supplements” and “therapeutic”, and by searching reference sections from identified studies and review articles). This review presents the relevant literature available on the topic and discusses the mechanisms, effects, and hypotheses that suggest oral GABA benefits range from neuroprotection to blood pressure control. The literature suggests that oral intake of GABA affects the brain illustrated by changes in EEG scans and cognitive performance, with evidence showing that GABA can have beneficial effects for multiple age groups and conditions. The potential clinical and research implications of utilizing GABA supplementation are vast, spanning a spectrum of diseases ranging from neurodegeneration to blood pressure regulation. Importantly, recommendations for the use of oral GABA should consider the dosage, formulation, and duration of treatment as well as potential side effects. Effects of GABA need to be more thoroughly investigated in robust clinical trials to validate efficacy to progress the development of alternative treatments for a variety of disorders.
... A safety assessment of GABA was conducted by the United States Pharmacopeia, and the data were collected from clinical studies, adverse event information, and toxicology trials. The results showed that there were no serious adverse events in the human body with an intake of 18 g/day GABA for 4 days or 120 mg/day GABA for 12 weeks [7]. ...
A γ–aminobutyric acid (GABA)–producing strain JC30 was isolated from traditional kimchi, which was identified as Pediococcus pentosaceus by 16S rDNA sequencing. P. pentosaceus JC30 was highly tolerant to acid, bile salt, and high temperatures. The survival rate of JC30 in MRS medium (pH 2.5) for 3 h was 60.96 %. Furthermore, the survival rate of JC30 in MRS medium with 3 mg/mL bile salt for 24 h was 86.62 %. The survival rate of JC30 in MRS medium at 56 °C and 58 °C for 10 min was 97.17 % and 78.20 %, respectively. When 2 % v/v JC30 (8.0 log10 CFU/mL) was added to prepare sourdough and the sourdough was then used to make bread, the bread had a higher specific volume (5.13 ± 0.12 mL/g) and GABA content (3.32 ± 0.04 mg/g DW) than the control.
... GABA activates vagal afferents and modulates brain function [9]. GABA is metabolized to succinic semialdehyde by GABA transaminase, and it is then either reduced to gamma-hydroxybutyrate or oxidized to succinate and finally converted to CO2 and water via the citric acid cycle [10]. Various physiological effects of GABA have been reported, including improvement of sleep quality [11], anti-stress [12], and suppression of blood pressure elevation [13]. ...
Background: Aging-related declines in skeletal muscle mass, muscle strength, and physical function are related to instability, falls, and frailty in older people, resulting in the need for nursing care. Objective: To investigate the effect of oral γ-aminobutyric acid (GABA) intake and exercise on muscle parameters in healthy subjects whose muscle strength is beginning to decline with age. Methods: A randomized, double-blind, placebo-controlled, parallel-group comparative study was conducted. Fifty subjects (over 40 years old) were randomly divided into the GABA (100 mg/day) or placebo food intake group. Subjects orally consumed the respective study substance every day for 12 weeks. They performed daily “locomotion training” as devised by the Japanese Orthopedic Society. Muscle mass, fat mass, and knee extension muscle strength were measured. Results: The two groups had no significant differences in muscle and fat mass. Compared with the placebo food group, the GABA group showed a significant improvement in knee extension muscle strength in the left and right legs at pre-dose Week 0 (at Week 6, p = 0.02). In post hoc subgroup analysis by sex, when compared with the placebo food intake group, the GABA food intake group showed significant improvement in knee extension muscle strength of the right leg at Weeks 6 (p = 0.001) and 12 (p = 0.007), the left leg at Week 6 (p = 0.02), the stronger of the left and right legs at pre-dose Week 0 (at Week 6, p = 0.001), and the weaker of the left and right legs at pre-dose Week 0 (at Week 12, p = 0.013) in males. Conclusions: These results suggest that GABA intake combined with daily exercise is effective for maintaining knee extension muscle strength, which decreases with age. Furthermore, there were no safety issues with the intake of GABA-containing food during this study. Trial registration: UMIN-CTR: UMIN000050152. Keywords: γ-Aminobutyric acid, GABA, Muscle mass, Knee extension muscle strength, Aging
... Gamma-amino butyric acid (GABA) is a non-protein amino acid with four carbon atoms, known for its potential health benefits, including stress reduction and improved sleep, as indicated in human studies [37] . The effects of soaking conditions and germination duration on white waxy corn can be observed in Figure 6. ...
White waxy corn enjoys global popularity because of its appealing taste and distinctive texture. Although it serves as a dietary cornerstone in numerous regions, it is characterized by relatively modest nutritional content. The objective of this research is to investigate various soaking solutions (including citrate buffer pH 3.0, citrate buffer pH 3.0 with 0,5% vitamin B6, citrate buffer pH 3.0 with 0,5% vitamin B6 and 0,5% glutamic acid) and different germination periods (ranging from 0 to 96 hours) on the level of antioxidant activity, ɣ-aminobutyric acid (GABA), polyphenols, and protein in white waxy corn. The highest ABTS inhibition (66.8%) was achieved through the soaking process involving citrate buffer pH 3.0 combined with L-glutamic acid and vitamin B6 solution during 96-hour germination. In contrast, the highest GABA concentration (213.9 ppm) was attained using citrate buffer pH 3.0 for 96-hour germination. The highest protein content (3110.9 ppm) was observed after 72 hours of germination using a soaking solution of citrate buffer pH three combined with L-glutamic acid and vitamin B6. However, the highest polyphenol (5603.3 ppm) was obtained using citrate buffer pH three for 72 hours. Soaking and germination can improve the chemical composition and antioxidant activity of white waxy corn.
... If so, a brand-new reaction mode for hydrazones would be revealed by radical deconstruction of hydrazonyl NÀ N bond in the form of using imino-N atom in olefin carboamination and amidyl N-atom in HLF reaction. [23] Herein, we demonstrate realization of this goal by merging radical olefin carboamination [22] with HLF reaction [12] by the reaction of N-homoallyl mesitylenesulfonyl (Mts)-hydrazones with ethyl iododifluoroacetate under photocatalytic redox neutral conditions. Olefin difunctionalization and HLF reaction are two kind of important conversion strategies which have been extensively studied since they have the ability to equip two new bonds onto alkenes and functionalize the remote inert Csp 3 À H bond, respectively. ...
... For example, γaminobutyric acid (GABA) is a neurotransmitter widely found in the central nervous system and peripheral nervous system of the human body. [23] α,α-Difluoro methotrexate (MTX) as a dihydrofolate reductase inhibitor shows significantly enhanced cancer therapeutic effect than its matrix (Scheme 1D). [24] On the other hand, sulphonamide is a critical pharmacophore that serves as an antibiotic drug. ...
As a type of elementary organic compounds containing N−N single bond, hydrazone involved chemical conversions are extremely extensive, but they are mainly limited to N2‐retention and N2‐removal modes. We report herein an unprecedented protocol for the realization of division utilization of the N2‐moiety of hydrazone by a radical facilitated N−N bond deconstruction strategy. This new conversion mode enables the successful combination of alkene carboamination and Hofmann‐Löffler‐Freytag reaction by the reaction of N‐homoallyl mesitylenesulfonyl hydrazones with ethyl difluoroiodoacetate under photocatalytic redox neutral conditions. Mechanism studies reveal that the reaction undergoes a radical relay involving addition, crucial remote imino‐N migration and H‐atom transfer. Consequently, a series of structurally significant ϵ‐N‐sulphonamide‐α,α‐difluoro‐γ‐amino acid esters are efficiently produced via continuous C−C bond and dual C−N bonds forging.
... Gamma-amino butyric acid (GABA) is another substance extensively used in the U.S. as an ingredient in dietary supplements marketed for the relief of anxiety and to elevate mood [40]. While it is allowed in the U.S. and several EU countries, two notifications were issued: one due to unauthorized claims and another because GABA is classified as a medicinal substance in Finland by the Finnish Medicines Agency. ...
In recent years, the consumption of dietary supplements has grown worldwide, particularly in developed regions. However, this growing market has also become a prime target for adulteration practices, with some manufacturers illegally adding pharmaceuticals into plant-based food supplements (PFS) to enhance their effects. While extensive research has focused on detecting adulterant drugs in PFS tailored for improving sexual performance, weight loss, and muscle building, less attention has been given to supplements intended for mood enhancement, sleep aid, and cognitive function (nootropics). Nonetheless, recent reports indicate an increasing level of adulteration within this group of PFS. Therefore, this review aims at providing a comprehensive overview on the adulteration of PFS tailored for brain health, with a focus on the analytical techniques utilized for detection while also presenting data on consumption patterns and the prevalence of reported adulterants. Considering that the detection of such fraudulent practices primarily relies on chromatographic techniques coupled with mass spectrometry (MS), the developments in this field comprising either targeted or untargeted analysis of pharmaceutical adulterants are discussed.
... 9. Individuals who engage in strenuous sports or diet. 10. Individuals with extremely irregular diet. ...
Fermented barley GABA 90 % (FB-GABA, Sanwa Shurui Co., Ltd., Oita, Japan) is a product that is prepared by concentrating and powdering γ-aminobutyric acid (GABA) produced by Enterococcus malodoratus FC 301. FC 301 is isolated from food and cultured in a medium of fermented barley extract generated in the manufacturing process of Shochu, a Japanese distilled liquor (Furuta et al., 2010). Abbreviations BP: Blood pressure; SCR: Screening; BMI: Body mass index; MCV: Mean corpuscular volume; MCHC: Mean corpuscular hemoglobin concentration; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; LDH: Lactate dehydrogenase; CK: Creatine kinase; HbA1c: Hemoglobin A1c Fermented barley GABA 90 % (FB-GABA, Sanwa Shurui Co., Ltd., Japan) is a powdered product of γ-aminobutyric acid (GABA) produced by Enterococcus malodoratus FC 301, which is cultured in a medium of fermented barley extract generated in the manufacture of Shochu, a Japanese distilled liquor. GABA accounts for more than 90 % of FB-GABA. The approximately 10 % remaining contains components produced by FC 301 and those derived from fermented barley extract used as a medium. Consuming 200 mg of GABA per day improves cognitive function without any health risks. In order to intake 200 mg/day of GABA, it is necessary to intake 223 mg/day of FB-GABA. Japanese Consumer Affairs Agency is requesting confirmation of the safety of overdosing (5 times the normal amount) for health foods such as tablets. We investigated the safety of intake of 1341.9 mg/day of FB-GABA for 4 weeks. Forty-eight participants were randomly divided into two groups. Each group ingested the test tablets containing 1341.9 mg of FB-GABA or the placebo tablets containing 1341.9 mg of dextrin for 4 weeks. Evaluation parameters included body measurements, physical examinations, and blood and urine tests. The principal investigator performed the medical interviews. The principal investigator judged that there were no safety issues with overdose intake of the trial food for 4 weeks based on the primary endpoints of body measurements, physical examinations, laboratory tests, and adverse events. We concluded that there were no safety issues with intake of 1341.9 mg/day of FB-GABA for 4 weeks.
... 9. Individuals who engage in strenuous sports or diet. 10. Individuals with extremely irregular diet. ...
Fermented barley GABA 90% (FB-GABA, Sanwa Shurui Co., Ltd., Japan) is a powdered product of γ-aminobutyric acid (GABA) produced by Enterococcus malodoratus FC 301, which is cultured in a medium of fermented barley extract generated in the manufacture of Shochu, a Japanese distilled liquor. GABA accounts for more than 90% of FB-GABA. The approximately 10% remaining contains components produced by FC 301 and those derived from fermented barley extract used as a medium. Consuming 200 mg of GABA per day improves cognitive function without any health risks. In order to intake 200 mg/day of GABA, it is necessary to intake 223 mg/day of FB-GABA. Japanese Consumer Affairs Agency is requesting confirmation of the safety of overdosing (5 times the normal amount) for health foods such as tablets. We investigated the safety of intake of 1341.9 mg/day of FB-GABA for 4 weeks. Forty-eight participants were randomly divided into two groups. Each group ingested the test tablets containing 1341.9 mg of FB-GABA or the placebo tablets containing 1341.9 mg of dextrin for 4 weeks. Evaluation parameters
included body measurements, physical examinations, and blood and urine tests. The principal investigator performed the medical interviews. The principal investigator judged that there were no safety issues with overdose intake of the trial food for 4 weeks based on the primary endpoints of body measurements, physical examinations, laboratory tests, and adverse events. We concluded that there were no safety issues with intake of 1341.9 mg/day of FB-GABA for 4 weeks.
... Conversely, certain hypotheses propose that SHS exposure might elevate the levels of neurotransmitters such as dopamine, serotonin, or GABA (Hammad et al., 2023). Furthermore, increasing GABA levels could potentially aid in treating conditions like high blood pressure, diabetes, and insomnia (de Bie et al., 2023;Oketch-Rabah et al., 2021). ...
