GABA
What is GABA?
GABA stands for gamma-aminobutyric acid. It is an amino acid produced in the brain and spinal cord. Amino acids are the building blocks of proteins.
GABA’s main role is to calm neurons down and reduce their activity. It can help alleviate pain, lower blood pressure, stabilize our mood, help us sleep and allow us to feel calm and relaxed.
GABA functions as a neurotransmitter, chemical messenger for brain cells (aka neurons).[3]
In utero and the early weeks of life, GABA is actually excitatory and causes the neurons (brain cells) to fire. However, as the infant grows and develops, there is a shift and GABA becomes inhibitory. Thus GABA’s main role in mature brains is to calm neurons down and reduce their activity.
Defects in the GABA shift (from excitatory to inhibitory) are associated with neurodevelopmental disorders, including autism. [7]
In contrast, glutamate is the main excitatory neurotransmitter in mature brains. Think of glutamate as the green light, telling the neurons to be active and fire and GABA is the red light, telling the neurons to slow down and stop firing.
When GABA is low, the nerve cells fire too often and a person may experience insomnia, depression, anxiety, panic attacks, headaches, seizures and impaired memory and cognition.
Our bodies make GABA from glutamate via an enzyme that requires Vitamin B6. If the activity of this enzyme is reduced, glutamate increases and GABA synthesis decreases. [18]
Vitamin B6 deficiency is rare but can manifest as seizures in infancy that do not respond to anti-convulsant medications.[3]
Research has shown that people with autism may have low GABA. They are also prone to epilepsy, often have anxiety, difficulty sleeping, and may have trouble converting glutamine to GABA, possibly due to a deficiency in vitamin B6. It is easy to see how many symptoms of low GABA also overlap with common autism symptoms.
Is GABA Beneficial for Autism?
The main effects of GABA are in helping alleviate pain, lowering blood pressure, stabilizing our mood, helping us sleep and allowing us to feel calm and relaxed. GABA is also involved in:
Muscle tone [19]
Immune system
Endocrine system
Metabolism
Gastrointestinal health
GABA & Medications
Many drugs modulate GABA signalling, including [3]:
Benzodiazepines (often prescribed for anxiety, insomnia, seizures or alcohol withdrawal)
Valproic acid (mood stabilizer, anti-seizure medication)
Vigabatrin (anti-seizure medication)
Propofol (a sedative)
Gabapentin is a prescription anticonvulsant medication that mimics the effects of GABA. It is used to control seizures and relieve pain.
Sources of GABA
Our bodies can make GABA well from the following foods [1]:
Raw spinach
Potato
Cruciferous veggies like kale and broccoli
Mushrooms (especially shiitake)
Nuts (especially chestnuts)
Sprouted beans
Peas
Tomatoes
Rice and oats
Supplementation
There is debate regarding whether or not GABA can cross the blood brain barrier (BBB) when taken as a supplement or, how much crosses the BBB, what dose is required to elicit an effect, what method of administration is required and the effect of the age on dosing requirements. [2]
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Powder
Also contains magnesium, myo-inositol, taurine, and L-theanine
Avoid using if your child is sensitive to any of the above supplements or are already using in other supplements
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Capsules
Designs for Health Insomnitol Capsules (also available in chewable linked below)
Liquid
Chewable
Designs for Health Insomnitol Chewable (also available in capsule linked above)
Also contains vitamin B6, Valerian, Passion Flower, Lemon Balm, Chamomile, 5-HTP, and melatonin
Avoid using if your child is sensitive to any of the above supplements or are already using in other supplements
DISCLAIMER: Before starting any supplement or medication, always consult with your healthcare provider to ensure it is a good fit for your child. Dosage can vary based on age, weight, gender, and current diet.
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Authors
Reviewed & Edited by: Brittyn Coleman, MS, RDN/LD, CLT
GABA & Autism in the Research
GABA & and Glutamate Levels
Brain GABA levels were lower in ASD and in depressed patients compared with controls. This fits a growing body of evidence of increased excitatory (glutamate) and reduced inhibitory (GABA) neurotransmission in ASD. However, evidence supporting the benefit of GABAergic drugs in ASD is limited and inconclusive. [4]
Analysis revealed associations between reduced GABA level, neuroinflammation, and glutamate excitotoxicity. This study indicates that autism is a developmental synaptic disorder showing an imbalance in GABAergic and glutamatergic synapses as a consequence of neuroinflammation.[6]
The plasma GABA and glutamate levels are altered in children with ASD. In particular, there is a significant elevation of plasma GABA, while levels of plasma glutamine are significantly lower as compared with the controls. [9]
In contradiction to the common hypothesis of reduced GABA in autism, we demonstrate that concentrations of both GABA and glutamate, in all the brain regions examined, are comparable in individuals with autism and in neurotypical adults.[11]
GABA & the Immature Brain
In early development, GABA signaling causes negative chloride ions to flow out of the neuron. This is depolarizing, which means the neuron becomes more positive at rest. The postnatal shift from GABA being depolarizing/excitatory to hyperpolarizing (more negative) and inhibitory is a pivotal event in brain development and its timing affects brain function throughout life. While being depolarizing, GABA’s role shifts in each step of early brain development and it governs the development of young neurons, from proliferation to migration, from migration to differentiation, and finally from differentiation to synapse formation. [7]
The shift for GABA from excitatory to inhibitory is not a single event. Rather it is gradual and the timing of the GABA shift appears strongly dependent on cell type, sex and brain region. The timing of the postnatal GABA shift needs to be coordinated with brain activity and sensory input to assure proper network development and life-long function. [7]
Findings suggest that the GABA shift is delayed or perhaps even entirely absent in patients with various neurodevelopmental disorders. It’s possible that subtle changes in the perinatal network may fail to activate the signals needed for the GABA shift. [7]
Excessive leptin, inadequate thyroid hormone and oxytocin signaling, which may also delay the GABA shift, have been implicated in the development of ASD. [7]
GABA & Mitochondrial Function
Mitochondrial hyperactivity causes GABA build-up in the mitochondria, reducing GABA signaling and resulting in social deficits. Manipulation of GABA signaling or mitochondria activity with medications and genetics can correct these observed abnormalities. [8]
GABA-altering Medications
Our study confirmed the clinical efficacy of Bumetanide on alleviating the core symptoms of ASD in young children and it is the first demonstration that the improvement is associated with reduction in GABA/Glutamate ratios.[10]
GABA & Epilepsy
ASD and epilepsy are associated with GABA abnormalities which can elevate the excitation-to-inhibition balance, resulting in hyperexcitability of the cortex and, in turn, increase the risk of seizures. [18]
Of children with mitochondrial disease and ASD, 41% have seizures. An energy deficiency can result in seizure and inhibitory GABA interneurons are highly affected by an energy deficit. In addition, processes critically involved in the release and reuptake of neurotransmitters and maintenance of the neuronal resting potential, such as calcium homeostasis, are critically dependent on mitochondrial function. [18]
Children with ASD have been shown to have abnormalities in vitamin B12 (cobalamin) dependent pathways, and supplementation improves metabolites in these pathways and behavior. Cobalamin is essential for myelin synthesis and methylation. Neurons with damaged myelin sheaths are more susceptible to the excitatory effects of glutamate.[18]
GABA & the Microbiome
Recent studies have shown that those with ASD displayed altered GABA metabolite profiles in feces when compared with neurotypical children, which is probably related to gut dysbiosis. Precursors of GABA were elevated in ASD children, which may mean that the conversion to GABA is lacking. [12]
Bifidobacterium spp. has been reported to produce GABA. In agreement with this finding, Bifidobacterium spp. in the present study was found significantly increased, which implies the elevated level of precursor of GABA may be induced by the increased Bifidobacterium spp. [12]
Bacteroides produce large quantities of GABA. An analysis of human stool samples from healthy individuals showed that GABA-producing pathways are actively expressed by Bacteroides, Parabacteroides and Escherichia species. Relative abundance levels of faecal Bacteroides are negatively correlated with brain signatures associated with depression.[17]
GABA & Touch/Movement
Self-reported hypersensitivity correlates with reduced GABA levels in brain areas processing touch. Our study suggests that this neurotransmitter may play a key role in tactile hypersensitivity in autism.[13]
Sensorimotor GABA levels were significantly reduced in children with autism compared to healthy controls. GABA levels correlate with behavioral measures of inhibition. Children with autism have reduced GABA, associated with abnormalities in tactile performance. [14]
Previous studies have suggested that the GABA+ concentration in M1 modulates the neural activity and muscle strength. These findings suggest that increased GABA in M1 reduces neural activity and results in motor dysfunction that is observed as reduced muscle strength. [16]
GABA & Genetics
This evidence suggests an association between mutations affecting the function of GABA and ASD. Furthermore, reduced expression of GABAergic genes and lower density of GABA related proteins have been found in the brains of ASD patients. [15]
GABA & Sleep
GABA is an inhibitory neurotransmitter, which through the activation of the GABA-A receptor, causes the muscle inhibition described in REM sleep. GABA is found in the suprachiasmatic nuclei (SCN) and VLPO circuits, which are responsible for modulating sleep and circadian rhythmicity.[20]
Melatonin and benzodiazepines can bind to GABA-A receptors with some GABA projections stimulating melatonin production. There is also an increase of GABA in the hypothalamus and pineal gland seen after the administration of exogenous melatonin, which may indicate a feedback loop between melatonin and GABA. [20]
Read more about sleep in the Sleep Issues note.
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[1] Briguglio M, Dell'Osso B, Panzica G, et al. Dietary Neurotransmitters: A Narrative Review on Current Knowledge. Nutrients. 2018;10(5):E591.
[2] Boonstra E, de Kleijn R, Colzato LS, Alkemade A, Forstmann BU, Nieuwenhuis S. Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Front Psychol. 2015;6:1520.
[3] Jewett BE, Sharma S. Physiology, GABA. [Updated 2021 Jul 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513311/
[4] Schür RR, Draisma LW, Wijnen JP, et al. Brain GABA levels across psychiatric disorders: A systematic literature review and meta-analysis of (1) H-MRS studies. Hum Brain Mapp. 2016;37(9):3337-52.
[5] Horder J, Petrinovic MM, Mendez MA, et al. Glutamate and GABA in autism spectrum disorder-a translational magnetic resonance spectroscopy study in man and rodent models. Transl Psychiatry. 2018;8(1):106.
[6] El-Ansary A, Al-Ayadhi L. GABAergic/glutamatergic imbalance relative to excessive neuroinflammation in autism spectrum disorders. J Neuroinflammation. 2014;11:189.
[7] Peerboom C, Wierenga CJ. The postnatal GABA shift: A developmental perspective. Neurosci Biobehav Rev. 2021;124:179-92.
[8] Kanellopoulos AK, Mariano V, Spinazzi M, et al. Aralar Sequesters GABA into Hyperactive Mitochondria, Causing Social Behavior Deficits. Cell. 2020;180(6):1178-1197.e20.
[9] Marotta R, Risoleo MC, Messina G, et al. The Neurochemistry of Autism. Brain Sci. 2020;10(3):E163.
[10] Zhang L, Huang CC, Dai Y, et al. Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios. Transl Psychiatry. 2020;10(1):9.
[11] Kolodny T, Schallmo MP, Gerdts J, Edden RAE, Bernier RA, Murray SO. Concentrations of Cortical GABA and Glutamate in Young Adults With Autism Spectrum Disorder. Autism Res. 2020;13(7):1111-29.
[12] Dan Z, Mao X, Liu Q, et al. Altered gut microbial profile is associated with abnormal metabolism activity of Autism Spectrum Disorder. Gut Microbes. 2020;11(5):1246-67.
[13] Sapey-Triomphe LA, Lamberton F, Sonié S, Mattout J, Schmitz C. Tactile hypersensitivity and GABA concentration in the sensorimotor cortex of adults with autism. Autism Res. 2019;12(4):562-75.
[14] Puts NAJ, Wodka EL, Harris AD, et al. Reduced GABA and altered somatosensory function in children with autism spectrum disorder. Autism Res. 2017;10(4):608-19.
[15] Eissa N, Al-Houqani M, Sadeq A, Ojha SK, Sasse A, Sadek B. Current Enlightenment About Etiology and Pharmacological Treatment of Autism Spectrum Disorder. Front Neurosci. 2018;12:304.
[16] Umesawa Y, Matsushima K, Atsumi T, et al. Altered GABA Concentration in Brain Motor Area Is Associated with the Severity of Motor Disabilities in Individuals with Autism Spectrum Disorder. J Autism Dev Disord. 2020;50(8):2710-22.
[17] Strandwitz P, Kim KH, Terekhova D, et al. GABA-modulating bacteria of the human gut microbiota. Nat Microbiol. 2019;4(3):396-403.
[18] Frye RE, Casanova MF, Fatemi SH, et al. Neuropathological Mechanisms of Seizures in Autism Spectrum Disorder. Front Neurosci. 2016;10:192.
[19] Termsarasab P, Thammongkolchai T, Frucht SJ. Medical treatment of dystonia. J Clin Mov Disord. 2016;3:19.
[20] Ballester P, Richdale AL, Baker EK, Peiró AM. Sleep in autism: A biomolecular approach to aetiology and treatment. Sleep Med Rev. 2020;54:101357.
[21] Depolarization, hyperpolarization & neuron action potentials (article). Khanacademy.org. https://www.khanacademy.org/science/biology/human-biology/neuron-nervous-system/a/depolarization-hyperpolarization-and-action-potentials. Accessed October 27, 2021.
