Gamma-aminobutyric acid

evidence_span

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experimental_model

Islet cell electrophysiology and signalling with GABA therapy in diabetes-prone and severely diabetic mice

exposure

GABA given therapeutically, with membrane potential, calcium influx and survival pathway readouts in beta cells

limitations

A mouse therapy study. Its electrophysiological claim about beta cells is stated as a contrast with alpha cells and brain rather than shown alongside a measured chloride gradient.

nutrient_topic

GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

organism

Mouse

plain_language

In the insulin-producing cell the same molecule does the opposite of what it does in the brain, and the cells survive better for it.

primary_references

[gb-p21709230] GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes. (2011). https://pubmed.ncbi.nlm.nih.gov/21709230/ DOI: 10.1073/pnas.1102715108

tissue_or_cell_type

Pancreatic islet and immune system

GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 430–441

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Islet cell electrophysiology and signalling with GABA therapy in diabetes-prone and severely diabetic mice · source_derived_draft · unverified_draft

### gb-gaba-depolarises-the-beta-cell Unlike in adult brain or islet alpha-cells in which GABA exerts hyperpolarizing effects, in islet beta-cells GABA produces membrane depolarization and calcium influx leading to the activation of PI3-kinase and Akt-dependent growth and survival pathways, this provides a potential mechanism underlying findings that GABA therapy preserves beta-cell mass and prevents the development of type 1 diabetes, remarkably in severely diabetic mice GABA restores beta-cell mass and reverses the disease, and GABA suppresses insulitis and systemic inflammatory cytokine production. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: In the insulin-producing cell the same molecule does the opposite of what it does in the brain, and the cells survive better for it. organism: Mouse tissue_or_cell_type: Pancreatic islet and immune system experimental_model: Islet cell electrophysiology and signalling with GABA therapy in diabetes-prone and severely diabetic mice limitations: A mouse therapy study. Its electrophysiological claim about beta cells is stated as a contrast with alpha cells and brain rather than shown alongside a measured chloride gradient. exposure: GABA given therapeutically, with membrane potential, calcium influx and survival pathway readouts in beta cells evidence_span: {"source_cache": "artifacts/gaba-research/21709230.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "926bc916592c55cf6089bcb240ec5545e0ff3850e6d927bb82efacfc61841175", "start_char": 0, "end_char": 1117, "text_sha256": "926bc916592c55cf6089bcb240ec5545e0ff3850e6d927bb82efacfc61841175"} [gb-p21709230] GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes. (2011). https://pubmed.ncbi.nlm.nih.gov/21709230/ DOI: 10.1073/pnas.1102715108

evidence_span

{"source_cache": "artifacts/gaba-research/30305619.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4d53b15743f61b910fb1db4781905673c81a070c12245068a369548544e3bc6e", "start_char": 0, "end_char": 1146, "text_sha256": "4d53b15743f61b910fb1db4781905673c81a070c12245068a369548544e3bc6e"}

experimental_model

Autophagy and phagosome assays in macrophages with receptor and protein dependency, and infection burden in two whole animals

exposure

GABA and GABAergic drugs during intracellular mycobacterial infection, with GABAergic inhibition in vivo

limitations

The dependency on the receptor and on a specific autophagy protein is tested, and the outcome is measured in two species. The direction is the opposite of the autoimmunity records.

nutrient_topic

GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

organism

Mouse and zebrafish

plain_language

Here the same molecule helps rather than suppresses: it drives the cell to digest the bacteria inside it, and blocking it lets the infection grow.

primary_references

[gb-p30305619] GABAergic signaling linked to autophagy enhances host protection against intracellular bacterial infections. (2018). https://pubmed.ncbi.nlm.nih.gov/30305619/ DOI: 10.1038/s41467-018-06487-5

tissue_or_cell_type

Macrophage

GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 586–597

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Autophagy and phagosome assays in macrophages with receptor and protein dependency, and infection burden in two whole animals · source_derived_draft · unverified_draft

### gb-gaba-helps-the-host-kill-bacteria Intracellular bacterial infection decreases GABA levels in vitro in macrophages and in vivo in sera, treatment of macrophages with GABA or GABAergic drugs promotes autophagy activation, enhances phagosomal maturation and antimicrobial responses against mycobacterial infection, in macrophages the GABAergic defense is mediated via macrophage type A GABA receptor, intracellular calcium release and the GABA type A receptor-associated protein-like 1, and GABAergic inhibition increases bacterial loads in mice and zebrafish in vivo suggesting that the GABAergic defense plays an essential function in metazoan host defenses. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: Here the same molecule helps rather than suppresses: it drives the cell to digest the bacteria inside it, and blocking it lets the infection grow. organism: Mouse and zebrafish tissue_or_cell_type: Macrophage experimental_model: Autophagy and phagosome assays in macrophages with receptor and protein dependency, and infection burden in two whole animals limitations: The dependency on the receptor and on a specific autophagy protein is tested, and the outcome is measured in two species. The direction is the opposite of the autoimmunity records. exposure: GABA and GABAergic drugs during intracellular mycobacterial infection, with GABAergic inhibition in vivo evidence_span: {"source_cache": "artifacts/gaba-research/30305619.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4d53b15743f61b910fb1db4781905673c81a070c12245068a369548544e3bc6e", "start_char": 0, "end_char": 1146, "text_sha256": "4d53b15743f61b910fb1db4781905673c81a070c12245068a369548544e3bc6e"} [gb-p30305619] GABAergic signaling linked to autophagy enhances host protection against intracellular bacterial infections. (2018). https://pubmed.ncbi.nlm.nih.gov/30305619/ DOI: 10.1038/s41467-018-06487-5

evidence_span

{"source_cache": "artifacts/gaba-research/15470076.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e5523c02fc4571d5ab6c23776794b4b5cf025fb86cdba9acdc12011f3a6b2e09", "start_char": 0, "end_char": 1443, "text_sha256": "e5523c02fc4571d5ab6c23776794b4b5cf025fb86cdba9acdc12011f3a6b2e09"}

experimental_model

Subunit analysis with ex vivo antigen responses, adoptive transfer and treatment of disease-prone mice

exposure

GABA at low concentrations ex vivo, and 600 micrograms daily in mice with established autoimmunity

limitations

A mouse type 1 diabetes model. The cell cycle result offers a mechanism for the disease effect but is measured separately from it.

nutrient_topic

GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

organism

Mouse

plain_language

Low doses slowed the immune attack on the insulin-producing cells even after that attack had already started.

primary_references

[gb-p15470076] Gamma-aminobutyric acid inhibits T cell autoimmunity and the development of inflammatory responses in a mouse type 1 diabetes model. (2004). https://pubmed.ncbi.nlm.nih.gov/15470076/ DOI: 10.4049/jimmunol.173.8.5298

tissue_or_cell_type

CD4 T cell and pancreatic islet

GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 534–545

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Subunit analysis with ex vivo antigen responses, adoptive transfer and treatment of disease-prone mice · source_derived_draft · unverified_draft

### gb-gaba-slows-the-autoimmune-t-cell A subset of GABA-A receptor subunits are expressed by CD4-positive T cells including the delta subunit that confers high affinity for GABA and sensitivity to alcohol, GABA at relatively low concentrations down-regulated effector T cell responses to beta cell antigens ex vivo and administration of GABA retarded the adoptive transfer of type 1 diabetes in NOD/scid mice, treatment with a low dose of GABA at 600 micrograms daily dramatically inhibited the development of proinflammatory T cell responses and disease progression in disease-prone mice that already had established autoimmunity, and GABA inhibited T cell receptor-mediated T cell cycle progression in vitro which may underlie the therapeutic effects. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: Low doses slowed the immune attack on the insulin-producing cells even after that attack had already started. organism: Mouse tissue_or_cell_type: CD4 T cell and pancreatic islet experimental_model: Subunit analysis with ex vivo antigen responses, adoptive transfer and treatment of disease-prone mice limitations: A mouse type 1 diabetes model. The cell cycle result offers a mechanism for the disease effect but is measured separately from it. exposure: GABA at low concentrations ex vivo, and 600 micrograms daily in mice with established autoimmunity evidence_span: {"source_cache": "artifacts/gaba-research/15470076.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e5523c02fc4571d5ab6c23776794b4b5cf025fb86cdba9acdc12011f3a6b2e09", "start_char": 0, "end_char": 1443, "text_sha256": "e5523c02fc4571d5ab6c23776794b4b5cf025fb86cdba9acdc12011f3a6b2e09"} [gb-p15470076] Gamma-aminobutyric acid inhibits T cell autoimmunity and the development of inflammatory responses in a mouse type 1 diabetes model. (2004). https://pubmed.ncbi.nlm.nih.gov/15470076/ DOI: 10.4049/jimmunol.173.8.5298

evidence_span

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experimental_model

Two small studies: electroencephalography after a single intake, and salivary immunoglobulin during a stressor

exposure

Orally administered GABA against water and against L-theanine, and GABA against placebo in acrophobic subjects crossing a suspended bridge

limitations

Thirteen subjects in the first study and eight in the second, with no correction for multiple comparisons reported. The immunity claim rests on salivary immunoglobulin A in eight people.

nutrient_topic

GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

organism

Human

plain_language

A gram taken by mouth changed the pattern of brain waves within an hour in thirteen people.

primary_references

[gb-p16971751] Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. (2006). https://pubmed.ncbi.nlm.nih.gov/16971751/ DOI: 10.1002/biof.5520260305

tissue_or_cell_type

Brain electrical activity and saliva

GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 352–363

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two small studies: electroencephalography after a single intake, and salivary immunoglobulin during a stressor · source_derived_draft · unverified_draft

### gb-oral-gaba-shifts-the-eeg The first study evaluated the effect of GABA intake by 13 subjects on their brain waves, with electroencephalograms obtained after three tests on each volunteer taking only water, GABA, or L-theanine, and after 60 minutes of administration GABA significantly increased alpha waves and decreased beta waves compared to water or L-theanine, while in a second study eight acrophobic subjects crossing a suspended bridge as a stressful stimulus showed a marked decrease of salivary immunoglobulin A in the placebo group while the GABA group showed significantly higher levels. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: A gram taken by mouth changed the pattern of brain waves within an hour in thirteen people. organism: Human tissue_or_cell_type: Brain electrical activity and saliva experimental_model: Two small studies: electroencephalography after a single intake, and salivary immunoglobulin during a stressor limitations: Thirteen subjects in the first study and eight in the second, with no correction for multiple comparisons reported. The immunity claim rests on salivary immunoglobulin A in eight people. exposure: Orally administered GABA against water and against L-theanine, and GABA against placebo in acrophobic subjects crossing a suspended bridge evidence_span: {"source_cache": "artifacts/gaba-research/16971751.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f0958495814a3c685efcafef73349d34248a2648872afa7e4a92c93132d9b631", "start_char": 0, "end_char": 1322, "text_sha256": "f0958495814a3c685efcafef73349d34248a2648872afa7e4a92c93132d9b631"} [gb-p16971751] Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. (2006). https://pubmed.ncbi.nlm.nih.gov/16971751/ DOI: 10.1002/biof.5520260305

evidence_span

{"source_cache": "artifacts/gaba-research/27916274.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4be6f165f91fed2e5ce13c111ae778fef006821e139b2702a3833f5924a4fffd", "start_char": 0, "end_char": 1087, "text_sha256": "4be6f165f91fed2e5ce13c111ae778fef006821e139b2702a3833f5924a4fffd"}

experimental_model

Lineage tracing and functional testing in mice with sustained GABA exposure, and treatment of transplanted human islets

exposure

Sustained long-term GABA administration in vivo, and GABA treatment of transplanted human islets

limitations

The human component is transplanted islets rather than people, and the cell counts are suggestive of conversion rather than a lineage trace in human tissue.

nutrient_topic

GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

organism

Mouse

plain_language

Given long enough, the molecule appeared to turn one islet cell type into the other, repeatedly reversing diabetes in mice.

primary_references

[gb-p27916274] Long-Term GABA Administration Induces Alpha Cell-Mediated Beta-like Cell Neogenesis. (2017). https://pubmed.ncbi.nlm.nih.gov/27916274/ DOI: 10.1016/j.cell.2016.11.002

tissue_or_cell_type

Pancreatic islet and duct

GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 443–454

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lineage tracing and functional testing in mice with sustained GABA exposure, and treatment of transplanted human islets · source_derived_draft · unverified_draft

### gb-sustained-gaba-makes-new-beta-like-cells GABA was identified as an inducer of alpha-to-beta-like cell conversion in vivo, this conversion induces alpha cell replacement mechanisms through the mobilization of duct-lining precursor cells that adopt an alpha cell identity prior to being converted into beta-like cells solely upon sustained GABA exposure, these neo-generated beta-like cells are functional and can repeatedly reverse chemically induced diabetes in vivo, and similarly the treatment of transplanted human islets with GABA results in a loss of alpha cells and a concomitant increase in beta-like cell counts suggestive of alpha-to-beta-like cell conversion processes also in humans. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: Given long enough, the molecule appeared to turn one islet cell type into the other, repeatedly reversing diabetes in mice. organism: Mouse tissue_or_cell_type: Pancreatic islet and duct experimental_model: Lineage tracing and functional testing in mice with sustained GABA exposure, and treatment of transplanted human islets limitations: The human component is transplanted islets rather than people, and the cell counts are suggestive of conversion rather than a lineage trace in human tissue. exposure: Sustained long-term GABA administration in vivo, and GABA treatment of transplanted human islets evidence_span: {"source_cache": "artifacts/gaba-research/27916274.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4be6f165f91fed2e5ce13c111ae778fef006821e139b2702a3833f5924a4fffd", "start_char": 0, "end_char": 1087, "text_sha256": "4be6f165f91fed2e5ce13c111ae778fef006821e139b2702a3833f5924a4fffd"} [gb-p27916274] Long-Term GABA Administration Induces Alpha Cell-Mediated Beta-like Cell Neogenesis. (2017). https://pubmed.ncbi.nlm.nih.gov/27916274/ DOI: 10.1016/j.cell.2016.11.002

evidence_span

{"source_cache": "artifacts/gaba-research/18954912.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3723b5b4b643817af252230d67dafbc0b5ca2deadb17cdbdbc9f340ddfc6a472", "start_char": 0, "end_char": 728, "text_sha256": "3723b5b4b643817af252230d67dafbc0b5ca2deadb17cdbdbc9f340ddfc6a472"}

experimental_model

Patch clamp and proliferation assays on encephalitogenic T cells at physiological GABA concentrations

exposure

GABA at nanomolar to micromolar concentrations, the range present around neurons

limitations

A small subunit and function study in one T cell type. It measures the concentration range that matters rather than assuming it.

nutrient_topic

GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

organism

Rat

plain_language

These cells carry the kind of channel built for a steady background level rather than a synaptic pulse, and that background level slows them down.

primary_references

[gb-p18954912] GABA, a natural immunomodulator of T lymphocytes. (2008). https://pubmed.ncbi.nlm.nih.gov/18954912/ DOI: 10.1016/j.jneuroim.2008.08.017

tissue_or_cell_type

Encephalitogenic T cell

GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 508–519

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patch clamp and proliferation assays on encephalitogenic T cells at physiological GABA concentrations · source_derived_draft · unverified_draft

### gb-t-cells-read-ambient-gaba We examined in encephalitogenic T cells if they expressed functional GABA channels that could be activated by the low nanomolar to 1 micromolar physiological concentrations of GABA present around neurons in the brain, the cells expressed the alpha1, alpha4, beta2, beta3, gamma1 and delta GABA-A channel subunits and formed functional extrasynaptic-like GABA channels that were activated by 1 micromolar GABA, and 100 nanomolar and higher GABA concentrations decreased T cell proliferation. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: These cells carry the kind of channel built for a steady background level rather than a synaptic pulse, and that background level slows them down. organism: Rat tissue_or_cell_type: Encephalitogenic T cell experimental_model: Patch clamp and proliferation assays on encephalitogenic T cells at physiological GABA concentrations limitations: A small subunit and function study in one T cell type. It measures the concentration range that matters rather than assuming it. exposure: GABA at nanomolar to micromolar concentrations, the range present around neurons evidence_span: {"source_cache": "artifacts/gaba-research/18954912.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3723b5b4b643817af252230d67dafbc0b5ca2deadb17cdbdbc9f340ddfc6a472", "start_char": 0, "end_char": 728, "text_sha256": "3723b5b4b643817af252230d67dafbc0b5ca2deadb17cdbdbc9f340ddfc6a472"} [gb-p18954912] GABA, a natural immunomodulator of T lymphocytes. (2008). https://pubmed.ncbi.nlm.nih.gov/18954912/ DOI: 10.1016/j.jneuroim.2008.08.017

evidence_span

{"source_cache": "artifacts/gaba-research/2550826.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9062539804213a1ccf427b75c8f6d262b151e22464cd6b7c84640f222f7dea94", "start_char": 0, "end_char": 1225, "text_sha256": "9062539804213a1ccf427b75c8f6d262b151e22464cd6b7c84640f222f7dea94"}

experimental_model

Electrophysiology of pancreatic alpha 2 cells with glucose and GABA

exposure

GABA co-secreted with insulin from beta cells, acting on GABA-A receptor chloride channels in alpha 2 cells

limitations

An early electrophysiological model. It proposes that GABA mediates part of the effect of glucose rather than demonstrating the whole of it.

nutrient_topic

GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

organism

Guinea pig and rat

plain_language

The cells that release insulin release GABA with it, and that is part of how a meal switches off the opposing hormone.

primary_references

[gb-p2550826] Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels. (1989). https://pubmed.ncbi.nlm.nih.gov/2550826/ DOI: 10.1038/341233a0

tissue_or_cell_type

Pancreatic islet

GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 404–415

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Electrophysiology of pancreatic alpha 2 cells with glucose and GABA · source_derived_draft · unverified_draft

### gb-the-islet-signals-with-gaba The inhibitory neurotransmitter GABA is present in the endocrine part of the pancreas at concentrations comparable to those encountered in the central nervous system and co-localizes with insulin in pancreatic beta cells, and we describe a mechanism whereby GABA co-secreted with insulin from beta cells may mediate part of the inhibitory action of glucose on glucagon secretion by activating GABA-A receptor chloride channels in alpha 2 cells, providing a model for feedback regulation of glucagon release which may be of significance for understanding the hypersecretion of glucagon frequently associated with diabetes. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: The cells that release insulin release GABA with it, and that is part of how a meal switches off the opposing hormone. organism: Guinea pig and rat tissue_or_cell_type: Pancreatic islet experimental_model: Electrophysiology of pancreatic alpha 2 cells with glucose and GABA limitations: An early electrophysiological model. It proposes that GABA mediates part of the effect of glucose rather than demonstrating the whole of it. exposure: GABA co-secreted with insulin from beta cells, acting on GABA-A receptor chloride channels in alpha 2 cells evidence_span: {"source_cache": "artifacts/gaba-research/2550826.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9062539804213a1ccf427b75c8f6d262b151e22464cd6b7c84640f222f7dea94", "start_char": 0, "end_char": 1225, "text_sha256": "9062539804213a1ccf427b75c8f6d262b151e22464cd6b7c84640f222f7dea94"} [gb-p2550826] Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels. (1989). https://pubmed.ncbi.nlm.nih.gov/2550826/ DOI: 10.1038/341233a0

evidence_access

Primary abstract

experimental_model

Mouse and human enteroendocrine signaling study; direction and cell-specific exposure unresolved in the accessed abstract.

limitations

This is recorded only as context-dependent modulation; no direction, effective dietary dose or supplement synergy is inferred.

nutrient_topic

Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia

plain_language

Other dietary compounds may change a response at a shared signaling system.

primary_references

Rebaudioside A from Stevia rebaudiana stimulates GLP-1 release by enteroendocrine cells via bitter taste signalling pathways. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37431625/ · DOI 10.1039/d3fo00818e

Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 282–288

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse and human enteroendocrine signaling study; direction and cell-specific exposure unresolved in the accessed abstract. · source_derived_draft · unverified_draft

## stevia-gut-gaba Other dietary compounds may change a response at a shared signaling system. The study reported that GABA and 6-methoxyflavanone can modulate rebaudioside-A-dependent GLP-1 release. Model: Mouse and human enteroendocrine signaling study; direction and cell-specific exposure unresolved in the accessed abstract. Limitations: This is recorded only as context-dependent modulation; no direction, effective dietary dose or supplement synergy is inferred. Evidence access: Primary abstract Rebaudioside A from Stevia rebaudiana stimulates GLP-1 release by enteroendocrine cells via bitter taste signalling pathways. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37431625/ · DOI 10.1039/d3fo00818e

experimental_model

Purified pig GABA aminotransferase; crystallography

exposure

Purified native pig GABA aminotransferase structure.

limitations

Pig enzyme evidence cannot alone predict human brain GABA responses to B6.

nutrient_topic

Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6

organism

Sus scrofa

plain_language

B6 participates in GABA breakdown as well as synthesis.

primary_references

[storici-1999-gaba-at] Crystal structure of GABA-aminotransferase, a target for antiepileptic drug therapy (1999). https://iris.uniroma1.it/handle/11573/393739 DOI: 10.1021/bi990478j

tissue_or_cell_type

Purified pig enzyme

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1071–1081

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified pig GABA aminotransferase; crystallography · source_derived_draft · unverified_draft

### b6-neuro-gaba-degradation Pig GABA aminotransferase contains a PLP-dependent active site for GABA degradation. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6 participates in GABA breakdown as well as synthesis. organism: Sus scrofa tissue_or_cell_type: Purified pig enzyme experimental_model: Purified pig GABA aminotransferase; crystallography limitations: Pig enzyme evidence cannot alone predict human brain GABA responses to B6. exposure: Purified native pig GABA aminotransferase structure. [storici-1999-gaba-at] Crystal structure of GABA-aminotransferase, a target for antiepileptic drug therapy (1999). https://iris.uniroma1.it/handle/11573/393739 DOI: 10.1021/bi990478j

experimental_model

Recombinant human GAD isoforms; crystallography and enzyme kinetics

exposure

Glutamate turnover in recombinant enzyme assays.

limitations

Recombinant chemistry does not establish a human supplementation response.

nutrient_topic

Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6

organism

Homo sapiens

plain_language

Activated B6 helps this enzyme make GABA.

primary_references

[fenalti-2007-gad] GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop (2007). https://doi.org/10.1038/nsmb1228 DOI: 10.1038/nsmb1228

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 949–959

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human GAD isoforms; crystallography and enzyme kinetics · source_derived_draft · unverified_draft

### b6-neuro-gad1-gaba PLP-bound human GAD67 catalyzes glutamate decarboxylation to GABA. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Activated B6 helps this enzyme make GABA. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human GAD isoforms; crystallography and enzyme kinetics limitations: Recombinant chemistry does not establish a human supplementation response. exposure: Glutamate turnover in recombinant enzyme assays. [fenalti-2007-gad] GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop (2007). https://doi.org/10.1038/nsmb1228 DOI: 10.1038/nsmb1228

experimental_model

Recombinant human GAD isoforms; crystallography and enzyme kinetics

exposure

Glutamate turnover in recombinant enzyme assays.

limitations

Recombinant chemistry does not establish a human supplementation response.

nutrient_topic

Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6

organism

Homo sapiens

plain_language

Activated B6 helps this enzyme make GABA.

primary_references

[fenalti-2007-gad] GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop (2007). https://doi.org/10.1038/nsmb1228 DOI: 10.1038/nsmb1228

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 961–971

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human GAD isoforms; crystallography and enzyme kinetics · source_derived_draft · unverified_draft

### b6-neuro-gad2-gaba PLP-bound human GAD65 catalyzes glutamate decarboxylation to GABA. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Activated B6 helps this enzyme make GABA. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human GAD isoforms; crystallography and enzyme kinetics limitations: Recombinant chemistry does not establish a human supplementation response. exposure: Glutamate turnover in recombinant enzyme assays. [fenalti-2007-gad] GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop (2007). https://doi.org/10.1038/nsmb1228 DOI: 10.1038/nsmb1228

evidence_span

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experimental_model

Reverse transcription PCR, Western blot and confocal immunostaining with uptake kinetics in an immortalised brain capillary endothelial line

exposure

Tritiated GABA uptake by a conditionally immortalised mouse brain capillary endothelial cell line used as an in vitro barrier model

limitations

An in vitro barrier model. It identifies the transporter and its kinetics; it does not establish the direction of net flux across an intact barrier.

nutrient_topic

GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

organism

Mouse

plain_language

The barrier has a dedicated carrier for this molecule, and its affinity is low enough that it only moves appreciable amounts at high concentrations.

primary_references

[gb-p11598501] GAT2/BGT-1 as a system responsible for the transport of gamma-aminobutyric acid at the mouse blood-brain barrier. (2001). https://pubmed.ncbi.nlm.nih.gov/11598501/ DOI: 10.1097/00004647-200110000-00012

tissue_or_cell_type

Brain capillary endothelium

transport_effect

raises Measured as cellular uptake of tritiated GABA, sodium- and chloride-dependent.

transport_pool

the expressing cell Measured as cellular uptake of tritiated GABA, sodium- and chloride-dependent.

GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 326–337

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reverse transcription PCR, Western blot and confocal immunostaining with uptake kinetics in an immortalised brain capillary endothelial line · source_derived_draft · unverified_draft

### gb-a-transporter-handles-gaba-at-the-barrier GABA transport was studied by cellular uptake of tritiated GABA which was sodium-, chloride- and concentration-dependent with a Michaelis-Menten constant of 679 plus or minus 80 micromol per litre and a maximal uptake rate of 4,790 pmol per milligram protein per 5 minutes, uptake was significantly inhibited by betaine, beta-alanine, nipecotic acid, taurine and quinidine whereas probenecid, L-proline, creatine and glycine had no effect, and confocal immunofluorescent microscopy demonstrated colocalization of GAT2/BGT-1 with P-glycoprotein, a barrier-specific marker, on brain capillaries. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: The barrier has a dedicated carrier for this molecule, and its affinity is low enough that it only moves appreciable amounts at high concentrations. organism: Mouse tissue_or_cell_type: Brain capillary endothelium experimental_model: Reverse transcription PCR, Western blot and confocal immunostaining with uptake kinetics in an immortalised brain capillary endothelial line limitations: An in vitro barrier model. It identifies the transporter and its kinetics; it does not establish the direction of net flux across an intact barrier. exposure: Tritiated GABA uptake by a conditionally immortalised mouse brain capillary endothelial cell line used as an in vitro barrier model evidence_span: {"source_cache": "artifacts/gaba-research/11598501.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "97e62b677991c2535e9cd91c1283edc6415a64f66def965c17e478f7b676f708", "start_char": 0, "end_char": 1589, "text_sha256": "97e62b677991c2535e9cd91c1283edc6415a64f66def965c17e478f7b676f708"} [gb-p11598501] GAT2/BGT-1 as a system responsible for the transport of gamma-aminobutyric acid at the mouse blood-brain barrier. (2001). https://pubmed.ncbi.nlm.nih.gov/11598501/ DOI: 10.1097/00004647-200110000-00012

evidence_span

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experimental_model

Identification of a metabolite secreted by activated B cells, with monocyte differentiation and two genetic tests in mice

exposure

B cell-derived GABA, with B cell deficiency and B cell-specific inactivation of the GABA-generating enzyme GAD67

limitations

The B cell-specific enzyme deletion is what makes the source assignment strong. The enzyme deleted is GAD67, not the GAD65 that is the diabetes autoantigen.

nutrient_topic

GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

organism

Mouse

plain_language

B cells release this molecule into a tumour, where it turns arriving monocytes into cells that shut down the killers.

primary_references

[gb-p34732892] B cell-derived GABA elicits IL-10+ macrophages to limit anti-tumour immunity. (2021). https://pubmed.ncbi.nlm.nih.gov/34732892/ DOI: 10.1038/s41586-021-04082-1

tissue_or_cell_type

B cell, monocyte and tumour

GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 599–610

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Identification of a metabolite secreted by activated B cells, with monocyte differentiation and two genetic tests in mice · source_derived_draft · unverified_draft

### gb-b-cells-secrete-gaba-that-shields-tumours We identify the metabolite and neurotransmitter GABA as a candidate signalling molecule synthesized and secreted by activated B cells and plasma cells, B cell-derived GABA promotes monocyte differentiation into anti-inflammatory macrophages that secrete interleukin-10 and inhibit CD8-positive T cell killer function, and in mice B cell deficiency or B cell-specific inactivation of the GABA-generating enzyme GAD67 enhances anti-tumour responses. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: B cells release this molecule into a tumour, where it turns arriving monocytes into cells that shut down the killers. organism: Mouse tissue_or_cell_type: B cell, monocyte and tumour experimental_model: Identification of a metabolite secreted by activated B cells, with monocyte differentiation and two genetic tests in mice limitations: The B cell-specific enzyme deletion is what makes the source assignment strong. The enzyme deleted is GAD67, not the GAD65 that is the diabetes autoantigen. exposure: B cell-derived GABA, with B cell deficiency and B cell-specific inactivation of the GABA-generating enzyme GAD67 evidence_span: {"source_cache": "artifacts/gaba-research/34732892.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "907d2a95afcac30a55ebfa4a6056c31ca53c452caff350ded70a60c9fc2eb17b", "start_char": 0, "end_char": 878, "text_sha256": "907d2a95afcac30a55ebfa4a6056c31ca53c452caff350ded70a60c9fc2eb17b"} [gb-p34732892] B cell-derived GABA elicits IL-10+ macrophages to limit anti-tumour immunity. (2021). https://pubmed.ncbi.nlm.nih.gov/34732892/ DOI: 10.1038/s41586-021-04082-1

evidence_span

{"source_cache": "artifacts/gaba-research/30531975.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c5ec17a6d5ab61a71d407f753583383c556fb07e10434eb3a3c7b42e4d0953f9", "start_char": 0, "end_char": 1773, "text_sha256": "c5ec17a6d5ab61a71d407f753583383c556fb07e10434eb3a3c7b42e4d0953f9"}

experimental_model

Co-culture isolation with bioassay-driven purification, genome-based metabolic modelling, stool transcriptomics and brain imaging

exposure

A gut isolate that grows only in the presence of another species, and the growth factor it requires

limitations

The correlation with depression imaging is observational and the causal direction is not established. The bacteriology is direct.

nutrient_topic

GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

organism

Human

plain_language

One gut bacterium cannot grow without this molecule and another makes it in quantity, and the human gut expresses both halves.

primary_references

[gb-p30531975] GABA-modulating bacteria of the human gut microbiota. (2019). https://pubmed.ncbi.nlm.nih.gov/30531975/ DOI: 10.1038/s41564-018-0307-3

tissue_or_cell_type

Gut microbiota and brain

GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 495–506

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Co-culture isolation with bioassay-driven purification, genome-based metabolic modelling, stool transcriptomics and brain imaging · source_derived_draft · unverified_draft

### gb-gut-bacteria-make-and-consume-gaba Co-culture was used to isolate KLE1738 which required the presence of Bacteroides fragilis to grow, bioassay-driven purification of the supernatant led to isolation of the growth factor which surprisingly is the major inhibitory neurotransmitter GABA, GABA was the only tested nutrient that supported the growth of KLE1738, a variety of GABA-producing bacteria were isolated and Bacteroides species produced large quantities of GABA, transcriptome analysis of human stool from healthy individuals showed that GABA-producing pathways are actively expressed by Bacteroides, Parabacteroides and Escherichia species, and relative abundance levels of faecal Bacteroides are negatively correlated with brain signatures associated with depression. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: One gut bacterium cannot grow without this molecule and another makes it in quantity, and the human gut expresses both halves. organism: Human tissue_or_cell_type: Gut microbiota and brain experimental_model: Co-culture isolation with bioassay-driven purification, genome-based metabolic modelling, stool transcriptomics and brain imaging limitations: The correlation with depression imaging is observational and the causal direction is not established. The bacteriology is direct. exposure: A gut isolate that grows only in the presence of another species, and the growth factor it requires evidence_span: {"source_cache": "artifacts/gaba-research/30531975.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c5ec17a6d5ab61a71d407f753583383c556fb07e10434eb3a3c7b42e4d0953f9", "start_char": 0, "end_char": 1773, "text_sha256": "c5ec17a6d5ab61a71d407f753583383c556fb07e10434eb3a3c7b42e4d0953f9"} [gb-p30531975] GABA-modulating bacteria of the human gut microbiota. (2019). https://pubmed.ncbi.nlm.nih.gov/30531975/ DOI: 10.1038/s41564-018-0307-3

evidence_span

{"source_cache": "artifacts/gaba-research/20133656.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "15fc62882eb9a9c1f5daad1bd2845bc99c94f1cf076620badc55b6be390e35fd", "start_char": 0, "end_char": 896, "text_sha256": "15fc62882eb9a9c1f5daad1bd2845bc99c94f1cf076620badc55b6be390e35fd"}

experimental_model

Demonstration of GABA synthesis and catabolism machinery in immune cells with electrophysiology and an autoimmune disease model

exposure

Increasing GABAergic activity in established experimental autoimmune encephalomyelitis

limitations

The disease effect is on ongoing paralysis rather than prevention. The assignment to antigen-presenting cells rests on direct effects measured on those cells.

nutrient_topic

GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

organism

Mouse

plain_language

The immune system has the whole apparatus to make and break down this transmitter, and uses it on itself.

primary_references

[gb-p20133656] Inhibitory role for GABA in autoimmune inflammation. (2010). https://pubmed.ncbi.nlm.nih.gov/20133656/ DOI: 10.1073/pnas.0915139107

tissue_or_cell_type

Antigen-presenting cell and central nervous system

GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 547–558

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Demonstration of GABA synthesis and catabolism machinery in immune cells with electrophysiology and an autoimmune disease model · source_derived_draft · unverified_draft

### gb-immune-cells-make-their-own-gaba Immune cells synthesize GABA and have the machinery for GABA catabolism, antigen-presenting cells express functional GABA receptors and respond electrophysiologically to GABA, thus the immune system harbors all of the necessary constituents for GABA signaling and GABA itself may function as a paracrine or autocrine factor, increasing GABAergic activity ameliorates ongoing paralysis in experimental autoimmune encephalomyelitis via inhibition of inflammation, and GABAergic agents act directly on antigen-presenting cells decreasing MAPK signals and diminishing subsequent adaptive inflammatory responses to myelin proteins. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: The immune system has the whole apparatus to make and break down this transmitter, and uses it on itself. organism: Mouse tissue_or_cell_type: Antigen-presenting cell and central nervous system experimental_model: Demonstration of GABA synthesis and catabolism machinery in immune cells with electrophysiology and an autoimmune disease model limitations: The disease effect is on ongoing paralysis rather than prevention. The assignment to antigen-presenting cells rests on direct effects measured on those cells. exposure: Increasing GABAergic activity in established experimental autoimmune encephalomyelitis evidence_span: {"source_cache": "artifacts/gaba-research/20133656.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "15fc62882eb9a9c1f5daad1bd2845bc99c94f1cf076620badc55b6be390e35fd", "start_char": 0, "end_char": 896, "text_sha256": "15fc62882eb9a9c1f5daad1bd2845bc99c94f1cf076620badc55b6be390e35fd"} [gb-p20133656] Inhibitory role for GABA in autoimmune inflammation. (2010). https://pubmed.ncbi.nlm.nih.gov/20133656/ DOI: 10.1073/pnas.0915139107

evidence_span

{"source_cache": "artifacts/gaba-research/19811362.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f372e3ce2c34cf5dcbac79af1c003b562d14665f547fab69748c5ee625c34886", "start_char": 0, "end_char": 1307, "text_sha256": "f372e3ce2c34cf5dcbac79af1c003b562d14665f547fab69748c5ee625c34886"}

experimental_model

Placebo-controlled double-blind study over twelve weeks with four weeks of follow-up

exposure

GABA-rich Chlorella supplying 20 milligrams of GABA twice daily against placebo

limitations

Eighty subjects with high-normal or borderline blood pressure. The intervention is a whole algal preparation, so the effect is not attributable to GABA alone.

nutrient_topic

GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

organism

Human

plain_language

Twelve weeks of a GABA-rich algal supplement lowered the upper blood pressure reading.

primary_references

[gb-p19811362] Anti-hypertensive effect of gamma-aminobutyric acid (GABA)-rich Chlorella on high-normal blood pressure and borderline hypertension in placebo-controlled double blind study. (2009). https://pubmed.ncbi.nlm.nih.gov/19811362/ DOI: 10.1080/10641960902977908

tissue_or_cell_type

Systemic circulation

GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 378–389

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Placebo-controlled double-blind study over twelve weeks with four weeks of follow-up · source_derived_draft · unverified_draft

### gb-an-algal-preparation-lowered-pressure Eighty subjects with systolic blood pressure 130 to 159 millimetres of mercury or diastolic 85 to 99 took GABA-rich Chlorella supplying 20 milligrams as gamma-aminobutyric acid or placebo twice daily for 12 weeks with follow-up for an additional 4 weeks, systolic blood pressure in the subjects given GABA-rich Chlorella significantly decreased compared with placebo, diastolic blood pressure had the tendency to decrease, neither adverse events nor abnormal laboratory findings were reported, and reduction of systolic pressure in the subjects with borderline hypertension was higher than in those with high-normal blood pressure. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: Twelve weeks of a GABA-rich algal supplement lowered the upper blood pressure reading. organism: Human tissue_or_cell_type: Systemic circulation experimental_model: Placebo-controlled double-blind study over twelve weeks with four weeks of follow-up limitations: Eighty subjects with high-normal or borderline blood pressure. The intervention is a whole algal preparation, so the effect is not attributable to GABA alone. exposure: GABA-rich Chlorella supplying 20 milligrams of GABA twice daily against placebo evidence_span: {"source_cache": "artifacts/gaba-research/19811362.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f372e3ce2c34cf5dcbac79af1c003b562d14665f547fab69748c5ee625c34886", "start_char": 0, "end_char": 1307, "text_sha256": "f372e3ce2c34cf5dcbac79af1c003b562d14665f547fab69748c5ee625c34886"} [gb-p19811362] Anti-hypertensive effect of gamma-aminobutyric acid (GABA)-rich Chlorella on high-normal blood pressure and borderline hypertension in placebo-controlled double blind study. (2009). https://pubmed.ncbi.nlm.nih.gov/19811362/ DOI: 10.1080/10641960902977908

evidence_span

{"source_cache": "artifacts/gaba-research/8621444.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1723620d459b4f48ad397d59284df3f0619894ba82c6d066a42a47a0edb22216", "start_char": 0, "end_char": 1531, "text_sha256": "1723620d459b4f48ad397d59284df3f0619894ba82c6d066a42a47a0edb22216"}

experimental_model

Purification of a radioligand binding protein from pig cerebral cortex with N-terminal sequencing and expression in transfected cells

exposure

Tritiated gabapentin binding, followed through a six-step purification to protein identity

limitations

A binding and purification study. It identifies what the drug binds; it does not test the GABA receptors, so the absence of GABA-receptor binding is not measured here.

nutrient_topic

GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

organism

Pig and rat

plain_language

The anticonvulsant designed as a GABA analogue turned out to bind a calcium channel subunit instead.

primary_references

[gb-p8621444] The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel. (1996). https://pubmed.ncbi.nlm.nih.gov/8621444/ DOI: 10.1074/jbc.271.10.5768

tissue_or_cell_type

Cerebral cortex, heart and skeletal muscle

GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 300–311

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purification of a radioligand binding protein from pig cerebral cortex with N-terminal sequencing and expression in transfected cells · source_derived_draft · unverified_draft

### gb-the-drug-named-for-gaba-binds-a-calcium-channel Gabapentin is a novel anticonvulsant drug with a mechanism of action apparently dissimilar to that of other antiepileptic agents, the detergent-solubilized binding protein from pig cerebral cortex membranes was purified 1022-fold, the purified protein had an apparent subunit molecular weight of 130,000 and was heavily glycosylated, its partial N-terminal amino acid sequence EPFPSAVTIK was identical to that reported for the alpha2delta subunit of the L-type calcium channel, binding to cells transfected with alpha2delta complementary DNA was elevated more than 10-fold over controls, and tritiated gabapentin is the first pharmacological agent described that interacts with an alpha2delta subunit of a voltage-dependent calcium channel. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: The anticonvulsant designed as a GABA analogue turned out to bind a calcium channel subunit instead. organism: Pig and rat tissue_or_cell_type: Cerebral cortex, heart and skeletal muscle experimental_model: Purification of a radioligand binding protein from pig cerebral cortex with N-terminal sequencing and expression in transfected cells limitations: A binding and purification study. It identifies what the drug binds; it does not test the GABA receptors, so the absence of GABA-receptor binding is not measured here. exposure: Tritiated gabapentin binding, followed through a six-step purification to protein identity evidence_span: {"source_cache": "artifacts/gaba-research/8621444.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1723620d459b4f48ad397d59284df3f0619894ba82c6d066a42a47a0edb22216", "start_char": 0, "end_char": 1531, "text_sha256": "1723620d459b4f48ad397d59284df3f0619894ba82c6d066a42a47a0edb22216"} [gb-p8621444] The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel. (1996). https://pubmed.ncbi.nlm.nih.gov/8621444/ DOI: 10.1074/jbc.271.10.5768

evidence_access

Primary full text; Figures 2 and 3

experimental_model

Purified recombinant human R105 and G105 variants.

limitations

Measured Km values for the tested guanidino acids exceeded 50 mM; physiological substrate flux remains unresolved.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

The same protein was active when supplied a different substrate.

primary_references

Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 124–130

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified recombinant human R105 and G105 variants. · source_derived_draft · unverified_draft

## agmatine-sulfate-agmat-gba The same protein was active when supplied a different substrate. Both purified human AGMAT variants hydrolyzed guanidinobutyrate, supporting a guanidino-acid hydrolase function. Model: Purified recombinant human R105 and G105 variants. Limitations: Measured Km values for the tested guanidino acids exceeded 50 mM; physiological substrate flux remains unresolved. Evidence access: Primary full text; Figures 2 and 3 Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

evidence_access

Primary full text; Figure 4B

experimental_model

Purified human GATM.

limitations

Presence of this route does not prove a change in brain inhibitory neurotransmission after agmatine supplementation.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

The same guanidino metabolite has another possible source besides agmatine oxidation.

primary_references

Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 196–202

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human GATM. · source_derived_draft · unverified_draft

## agmatine-sulfate-gatm-gaba The same guanidino metabolite has another possible source besides agmatine oxidation. Human GATM used GABA as an amidino acceptor to form guanidinobutyrate in vitro. Model: Purified human GATM. Limitations: Presence of this route does not prove a change in brain inhibitory neurotransmission after agmatine supplementation. Evidence access: Primary full text; Figure 4B Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Developmental expression and antisense suppression

exposure

KCC2 expression during maturation; antisense inhibition

limitations

Neuronal gradient mechanism; dietary chloride restriction is not the intervention.

nutrient_topic

Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride

organism

Rat

plain_language

GABA’s electrical effect depends on the chloride gradient maintained by the cell.

primary_references

[chloride-p9930699] The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. (1999). https://pubmed.ncbi.nlm.nih.gov/9930699/ DOI: 10.1038/16697

tissue_or_cell_type

Hippocampal pyramidal neurons

trigger_kind

machinery_impairment Imported condition classification; unverified.

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 406–417

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Developmental expression and antisense suppression · source_derived_draft · unverified_draft

### chloride-kcc2-gaba-loss Suppressing KCC2 shifted the GABA-A reversal potential in a positive direction in mature neurons. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: GABA’s electrical effect depends on the chloride gradient maintained by the cell. organism: Rat tissue_or_cell_type: Hippocampal pyramidal neurons experimental_model: Developmental expression and antisense suppression limitations: Neuronal gradient mechanism; dietary chloride restriction is not the intervention. exposure: KCC2 expression during maturation; antisense inhibition evidence_span: {"source_cache": "artifacts/chloride-research/9930699.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6", "start_char": 0, "end_char": 1181, "text_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6"} [chloride-p9930699] The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. (1999). https://pubmed.ncbi.nlm.nih.gov/9930699/ DOI: 10.1038/16697

evidence_span

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experimental_model

Nkcc1 knockout and neuronal activity measurements

exposure

Nkcc1 deletion

limitations

Developmental hippocampal model; does not generalize to every immature neuron.

nutrient_topic

Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride

organism

Mouse

plain_language

Chloride loading can help GABA excite developing neurons in this specific circuit.

primary_references

[chloride-p19295148] NKCC1-dependent GABAergic excitation drives synaptic network maturation during early hippocampal development. (2009). https://pubmed.ncbi.nlm.nih.gov/19295148/ DOI: 10.1523/jneurosci.1377-08.2009

tissue_or_cell_type

Early postnatal hippocampal CA1 network

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 419–430

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nkcc1 knockout and neuronal activity measurements · source_derived_draft · unverified_draft

### chloride-nkcc1-gaba Nkcc1 deletion attenuated GABA-triggered depolarization and calcium transients during early hippocampal development. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chloride loading can help GABA excite developing neurons in this specific circuit. organism: Mouse tissue_or_cell_type: Early postnatal hippocampal CA1 network experimental_model: Nkcc1 knockout and neuronal activity measurements limitations: Developmental hippocampal model; does not generalize to every immature neuron. exposure: Nkcc1 deletion evidence_span: {"source_cache": "artifacts/chloride-research/19295148.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "55bc6d4f9cf1d9a44f4d6c851dabd587bb2ffb7a337f67c5f9e7bfe8aefa870f", "start_char": 0, "end_char": 982, "text_sha256": "55bc6d4f9cf1d9a44f4d6c851dabd587bb2ffb7a337f67c5f9e7bfe8aefa870f"} [chloride-p19295148] NKCC1-dependent GABAergic excitation drives synaptic network maturation during early hippocampal development. (2009). https://pubmed.ncbi.nlm.nih.gov/19295148/ DOI: 10.1523/jneurosci.1377-08.2009

evidence_access

Primary abstract

experimental_model

Recombinant human enzyme substrate comparison.

limitations

Shared synthesis does not mean the two peptides have identical functions.

nutrient_topic

Carnosine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnosine / beta-alanyl-L-histidine

plain_language

The same enzyme can assemble a related GABA-containing peptide.

primary_references

Molecular identification of carnosine synthase as ATP-grasp domain-containing protein 1 (ATPGD1). · 2010 · https://pubmed.ncbi.nlm.nih.gov/20097752/ · DOI 10.1074/jbc.M109.095505

Carnosine: synthesis, transport, carbonyl chemistry and nutrient interactions (2026-09-19) · lines 36–42

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human enzyme substrate comparison. · source_derived_draft · unverified_draft

## carnosine-homocarnosine The same enzyme can assemble a related GABA-containing peptide. Purified human CARNS1 also synthesized homocarnosine using GABA, with lower catalytic efficiency than the beta-alanine reaction. Model: Recombinant human enzyme substrate comparison. Limitations: Shared synthesis does not mean the two peptides have identical functions. Evidence access: Primary abstract Molecular identification of carnosine synthase as ATP-grasp domain-containing protein 1 (ATPGD1). · 2010 · https://pubmed.ncbi.nlm.nih.gov/20097752/ · DOI 10.1074/jbc.M109.095505