Gaba - NutraPedia

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GABA (Gamma-Aminobutyric Acid)

1) Conditions Studied for GABA

GABA has been studied for a variety of conditions, including:

Anxiety disorders
Depression
Epilepsy and seizures
Insomnia and sleep disorders
Chronic pain
Attention deficit hyperactivity disorder (ADHD)

2) Efficacy in Treating Conditions

Research on the efficacy of GABA for treating these conditions is mixed and sometimes inconclusive. For example:

Some studies suggest that GABA supplementation may help with anxiety and sleep disorders, but more research is needed for definitive conclusions.
In the case of epilepsy, GABAergic drugs are used, but directly supplementing with GABA may not effectively cross the blood-brain barrier.

3) Health Benefits of GABA

Potential health benefits associated with GABA include:

Reducing symptoms of anxiety
Promoting relaxation and reducing stress
Improving sleep quality
Possibly aiding in the management of premenstrual syndrome (PMS)
May have a role in regulating blood pressure

4) Downsides of GABA

While GABA is generally considered safe, there can be downsides, such as:

Mild side effects like stomach upset, headache, and sleepiness
Uncertainty about the effective dosage and long-term impact
Potential interaction with medications, such as those for high blood pressure and sedatives

5) GABA and Genetic Variations

Some genetic variations may affect how individuals respond to GABA. For instance:

People with variations in the GABRA6 gene may experience different effects from GABA-related drugs.
Individuals with certain polymorphisms in GABA receptor genes could have a higher risk of developing conditions like epilepsy, which influences how they might respond to GABA supplementation.

However, more research is required to fully understand the impact of genetic variations on the effectiveness and safety of GABA supplementation.

GABA and GABA(A) Receptor Subtypes in Neuroscience Research

Introduction to GABA(A) Receptors

GABA(A) receptors are chloride channels essential for fast inhibitory neurotransmission in the central nervous system. They are part of the Cys-loop pentameric ligand-gated ion channel superfamily and are made up of 19 homologous subunit gene products. The subunit composition of these receptors results in a variety of receptor subtypes, each with distinct properties such as distribution, timing, roles in neural circuits and behaviors, regulatory mechanisms, and pharmacological profiles.

Classification of GABA(A) Receptor Subtypes

The updated classification of GABA(A) receptor subtypes includes 26 members, categorized into groups: "identified," "existence with high probability," and "tentative." This classification is expected to evolve with new experimental evidence.

Pharmacology of GABA(A) Receptors

Researchers have found compounds that target individual GABA(A) receptor subtypes, which may lead to reduced side effects in animal behavioral experiments. However, the specificity of these compounds and their effects in humans require further research to develop ligands with improved selectivity, particularly those that can effectively reduce anxiety (anxioselectivity).

Pharmaceutical Properties of GABA

GABA is a significant inhibitory neurotransmitter with various pharmaceutical effects on peripheral tissues and organs, including anti-hypertensive, anti-diabetic, anti-cancer, and more. It plays a critical role in modulating synaptic transmission and could be considered a potential alternative therapeutic agent.

GABA, Glutamate, and Cortical Excitability

GABA and glutamate are key neurotransmitters that regulate cortical excitability through a balance of inhibitory and excitatory signals. GABA is produced from glutamate and influences cortical excitability, with metabolites that possess anticonvulsant properties.

GABA and Brain Neurochemistry

A systematic review combining measures of GABA and glutamate levels with brain activity via fMRI found negative associations between local GABA levels and fMRI activation during certain tasks. This suggests the need for further research to uncover aspects of mental health disorders characterized by abnormal interactions between neurochemistry and neurophysiology.

Oral GABA Intake and Its Effects

Studies provide limited evidence supporting the effectiveness of oral GABA intake in reducing stress and very limited evidence for its benefits on sleep, indicating the need for more research. GABA supplementation showed some improvement in temporal attention in young adults, and oral intake might alleviate stress by affecting brain wave activities during mental tasks.

GABA in Psychiatric and Neurological Disorders

Research suggests a hypo-GABAergic state in the frontal cortex of schizophrenia patients. Systematic gene expression analysis revealed down-regulation of GABA receptor subunits in both elderly and younger schizophrenia patients. GABA levels may serve as a biomarker for depressive states in unipolar disorder and normalize with treatment in bipolar disorder.

GABA and Brain GABA Levels

A systematic literature review examining brain GABA levels in various psychiatric disorders using (1) H-MRS found evidence of reduced brain GABA levels in individuals with ASD and those suffering from MDD.

GABA and Body Temperature Regulation

Oral GABA intake can lower body temperature and decrease heat production in humans resting in a hot environment. GABA may reduce esophageal temperature by affecting cold-sensitive neurons at rest and by diminishing sympathetic nervous system activity during exercise.

GABA Supplementation and Muscle Hypertrophy

GABA combined with whey protein may enhance muscle hypertrophy and increase whole-body fat-free mass when paired with exercise. GABA supplementation raises growth hormone levels both at rest and after exercise.

GABA and Hormonal Regulation

GABA can influence the secretion of growth hormone and prolactin in humans, and the GABAergic control of GH secretion is impaired in heroin addicts. Furthermore, activating GABA A receptors with alprazolam can significantly dampen physiological responses during exercise in both healthy individuals and those with type 1 diabetes.

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