GABA

Synonym: 

Gamma-aminobutyric acid

Acide Gamma-Aminobutyrique

Ácido Gama-Aminobutríco

Beta-Phenyl-Gamma-Aminobutyric Acid

Gamma Amino Butyric Acid

Description

GABA, or Gamma-aminobutyric acid is an important neurotransmitter with an inhibitory (inhibitory) function in the central nervous system. Neurotransmitters enable communication between neurons via messenger substances. GABA is also a nonessential amino acid. There are stimulatory (exit) and inhibitory (inhibitory) neurotransmitters, and the two keep each other in balance. When overactivity occurs in neurons, GABA that has inhibitory activity will inhibit this overactivity. As a result, GABA acts as a natural tranquilizer, inhibits nerve impulses and has stress-regulating activity.

Certain factors such as stress, improper diet or nutritional deficiencies or use of medications, alcohol and drugs affect the amount of neurotransmitters. GABA is found in natural food sources such as (leafy) vegetables, soy and broad beans, nuts, seeds, tomatoes and eggs, among others.

Operation

GABA is commonly used for reducing anxiety, improving mood, reducing Pre Menstrual Syndrome (PMS) and in treating ADHD. GABA is also used for other neuropsychiatric conditions such as stress, epilepsy and sleep disorders. It is also used for muscle building, fat burning, stabilizing blood pressure and reducing pain.

Taking GABA through the buccal mucosa has a direct effect on increasing well-being, reduction in pain from injury, increasing fitness from exercise, lowering body fat and reducing body weight.

Features

GABA is the major inhibitory neurotransmitter in the Central Nervous System. It is synthesized in the brain by the decarboxylation of glutamate (1, 2). In healthy humans, a dose of 5 to 10 grams of GABA caused an increase in C-peptide, insulin and glucagon, while blood glucose levels remained the same (3). GABA is synthesized from glutamic acid under the influence of the enzyme glutamate decarboxylase (GAD), co-factor pyridoxal-5-phosphate (active vitamin B6). It is found in relatively high concentrations in the CNS ( Central nervous system) distributed throughout much of the brain. GABA has anticonvulsant, sedative and anxiety-reducing effects at the cellular level (1, 2). Most effects are generated via the GABA a and GABA b receptors. GABA, as an inhibitory neurotransmitter, inhibits the excitatory activity of the neurotransmitter glutamate. This may prevent neurological and psychiatric disorders. In a study of healthy volunteers, a dose of 5 grams of GABA was seen to increase HGH ( Human Growth Hormone), while long-term use of 18 grams of GABA per day showed a decrease (4).

Brain-blood barrier

GABA can hardly cross the brain-blood barrier yet GABA is very often used with positive results. Especially in stress-related complaints including sleep and anxiety disorders. One explanation could be that when sufficient GABA is present peripherally, this positively influences the action and effectiveness of GABA in the CNS. Another possibility is that GABA does cross the blood-brain barrier. Sublingual intake is preferred.

Indications:

Stress

There is clinical evidence that taking 250 mg of GABA sublingually (letting it melt under the tongue) decreases tension, anxiety, confusion and depression in stressed people (5, 6). Stress-related symptoms such as headaches, difficulty concentrating, irritability, fretting, inability to get to sleep due to busy thoughts, hyperactivity, and the like may arise due to insufficient functioning of GABA in the brain. This causes an overactivity of glutamate. When taken sublingually, this overactivity is inhibited, resulting in a calming and relaxing effect. In several studies, this has also been demonstrated on the basis of specific brain waves. Stress resistance increases in stress sensitive people.

Fear

Description: 

Anxiety is a physiological state characterized by emotions, tension and restlessness. Anxiety has different degrees. Examples of milder forms are: "not feeling comfortable," fear of failure and exam anxiety. The more severe forms are panic disorders, phobias, obsessions and post-traumatic stress syndrome. Anxiety can also result from other conditions such as chronic fatigue syndrome, cardiovascular disease. There are various forms of anxiety. Anxiety for a short time such as thunderstorms, anxiety as a panic attack, anxiety in the form of obsessive-compulsive disorder but also anxiety in the form of a phobia. Often there is a deficiency of GABA (Gamma Amino Butyric Acid).

Symptoms: 

Severe anxiety is often accompanied by physical symptoms such as increased heart rate and blood pressure, palpitations, dizziness, dry mouth, chest pain, sweating, nausea, shortness of breath and headache. Often there is an increased production of adrenaline in the blood. Sometimes anxiety can be a symptom of stress.

Nutrition recommendations: 

Consume foods rich in omega 3 fatty acids or oily fish. Avoid foods containing refined sugar and moderate meat consumption.

Notes: 

Neurotransmitters are substances that can transmit messages in the brain by acting on a receptor. Three neurotransmitter systems, namely those for GABA (gamma-aminobutyric acid), serotonin and glutamate play an important role in anxiety. These systems are complex; they have a "direct" effect, they affect each other, as well as other neurotransmitter systems. Benzodiazepines, the most commonly used antianxiety drugs, enhance the action of naturally occurring GABA by acting on the GABA-A receptor.

Depression

Description: 

Depression is a mental disorder in which the person experiences a dejected mood and/or a loss of interest and pleasure in daily activities for a period of time. In addition to these two main symptoms, the following symptoms may occur; weight loss or gain, inability to sleep or just sleeping too much, a tense and restless attitude or just an inhibited attitude, fatigue and loss of energy, feelings of worthlessness and guilt, difficulty concentrating and inability to make decisions and thoughts of death and suicide. In normal parlance, the term "depressed" is used fairly readily to describe a state in which a person is in a slump. When symptoms are not as strong, but a person experiences these symptoms for two years, dysthymic disorder may be present. If, in addition to these depressive symptoms, a person experiences periods in which the mood is actually extremely positive and/or irritable, sleeps little and experiences a sharp increase in energy, there may be bipolar disorder (formerly known as manic depression). However, one speaks of clinical depression only when an extensive number of criteria are met. These are established diagnostic manuals. 

There are different types of depression:

  • Unipolar depression. A long period in which the mood is constantly gloomy and dejected.
  • Bipolar depression. Manic depressive means periodically alternating from gloomy to manic.
  • Postpartum depression. The depression occurs after childbirth and is similar to unipolar depression.
  • Winter depression. Complaints such as gloom, irritability and fatigue occur during the winter months.
  • Chronic depression. Mild form that lasts longer than 2 years. Periods alternate with sometimes complaints about eating behavior, fatigue, sleep problem, concentration disorder. The cause of this form is not clear.

Fibromyalgia

  • Description: 
  • Fibromyalgia is a syndrome related to fiber, muscle fiber, nerve fiber (fibro) and muscle disease (myalgia). It is characterized by muscle pain and pressure sores scattered throughout the body. The syndrome is often accompanied by several general complaints such as sleep disturbances, fatigue, muscle stiffness and sometimes headaches. A combination with chronic fatigue syndrome occurs frequently. Practical experience shows that in patients with fibromyalgia, osteoporosis is also a serious problem. Anti-depressants or other medications are often prescribed. Fibromyalgia occurs mainly in women between the ages of 30 and 50. Frustration stress can be a major factor in the development of fibromyalgia. Long periods of stress weaken our immune system and autonomic nervous system. Pain often causes a person to become less active, and that in itself can lead to increased stress and anxiety and even depression. That stress contributes to the depletion of serotonin in the brain. This in turn makes the pain one feels more intense. Then the cycle begins again. About ninety percent of fibromyalgia patients have a sleep problem. The pursuit of a good night's sleep is a priority in the treatment of fibromyalgia since in deep REM sleep, the recovery phase takes place under the guidance of the HGH hormone.( Human Growth Hormone )
  •  
  • Treatment principles
  • The treatment principle should focus on achieving a good night's sleep, identifying allergies and adjusting the diet accordingly, restoring healthy digestion, balancing the acid/base ratio and improving the immune system.
  •  
  • Symptoms: 
  • Pain in muscles and joints, sleep problems, sometimes fluctuating moods.

Cushing's disease

There is clinical evidence that taking GABA at a dosage of 1 to 3 grams daily for one month reduces Adrenocorticotropic Hormone.(ACTH) hormone in blood plasma 60 minutes after ingestion, as do cortisol and ACTH levels up to 2 days after stopping GABA administration (7).

Pre Menstrual Syndrome

Synonym: 

PMS

Description: 

Premenstrual syndrome (PMS) is a group of complaints or symptoms that can occur just before menstruation. The main PMS symptoms are crying spells (without depressive feelings), palpitations, dizziness, swollen breasts or abdomen, headaches, tight skin, constipation, fatigue and sometimes abdominal pain and cramps. Women may also suffer psychologically from feelings of anxiety and/or depression, nervousness, irritability or a short fuse. About 4% of women between the ages of 16 and 40 regularly suffer from P.M.S. The syndrome does not have to exist throughout the fertile period: it is also possible that it arises after the age of 30 or after having children.

Notes: 

It is hypothesized that the cause of PMS may be related to progesterone levels in the second week after menstruation. A deficiency of B6 and magnesium gives rise to PMS symptoms. Recently, the neurotransmitter serotonin-one of the substances that transmit signals between certain brain cells-was added to the list.

Sleep disorders

Synonym: 

Insommnia

Description: 

The inability to fall asleep or continue sleeping is called insomnia. There are many different causes. A disturbance in hormonal balance can cause a disturbance in circadian rhythm. And vice versa a disturbance in the hormone balance can cause a disturbance in the circadian rhythm. The circadian rhythm is the day and night rhythm of humans and animals. But restless legs, sleep apnea, pain, itching or depression can also cause a disturbance in sleep. Good sleep is enormously important for the repair of muscle, nerve and brain tissue.

Symptoms: 

Problems falling asleep, falling through, or coming into deep (REM) sleep

Car sick

Clinical research has shown that GABA at a dose of 500 mg can prevent car sickness and at the same dose 3 times daily reduces car sickness compared to a placebo. GABA also reduces symptoms present in carsickness such as chills, cold sweats and pallor compared to a placebo (8).

High Blood Pressure

Clinical research shows that use of GABA in combination with Chlorella 250 mg twice daily for 12 weeks lowers both systolic pressure and diastolic pressure (9). Another clinical study shows the same results with intake of a combination GABA with fermented milk 100 ml (FMG) also for 12 weeks (10).

Epilepsy

Studies show that combining phosphatidylserine at a dose of 500 mg with GABA at a dose of 2500-3000 mg for 3-8 months reduces seizure frequency in patients with absence and partial seizures compared to baseline (11). The GABA system plays a key role in whether or not seizures occur. Impaired function of the GABA system results in overactivity of the excitatory neurotransmitter, which can cause seizures. In a large proportion of epilepsy patients, antibodies are formed against the enzyme GAD. With insufficient production of GAD, GABA concentration becomes too low and the vicious cycle is complete. Antiepileptic drugs are based on improving GABA action on the brain. Supplementation with GABA (sublingual) can reduce the number of epileptic seizures. Dosage must be taken into account here because there are also conflicting research results and the mechanism of action of GABA in relation to epilepsy is not yet fully known (12).

Chronic bronchitis

Clinical research shows that intake of GABA at a daily dose of 1500 mg for 18 to 20 days in combination with usual bronchitis treatment in acute shortness of breath there was a prolongation of recovery with an extension of bronchitis free period compared with usual treatment alone (13).

ADHD

Clinical research shows that in children with ADHD between 7 and 10 years of age with the use of GABA for 2 months improves learning, attention, memory and mental and social skills (14, 15, 16).

Sports

The release of the growth hormone HGH can be stimulated by the intake of GABA. Especially among athletes, this has positive effects with muscle mass for strength sports. Just before a workout, GABA can be used to stimulate the concentration of the growth hormone HGH for increasing muscle mass.

Contraindications

GABA deficiency may occur in disorders of the gastrointestinal system. First recovery from this intestinal disorder is recommended before using GABA. If one is hypersensitive to GABA, it is also discouraged. When using all drugs that act on the GABA agonists such as benzodiazepines, barbiturates, antidepressants, alcohol and food enriched with GABA, it is advisable to be careful with GABA and not to use it simultaneously. Caution is also advised with agents that may increase the risk of bleeding, such as anticoagulants and Ginkgo biloba. For any other possible interactions, contact an expert such as pharmacists or orthomolecular physician/therapist.

Side effects

No significant side effects are known from GABA. Occasionally, tingling may occur briefly. No scientific information is known about side effects after long-term use in high doses. The application of high concentrations (5 -10 grams), such as possibly in strength sports, may affect endogenous pancreatic function.

Interactions with herbs

GABA can lower blood pressure in people with hypertension. This could theoretically interact with herbs that lower blood pressure with a danger of low blood pressure (10). Some caution with cocoa, alpha-linolenic acid, psyllium and cod liver oil.

Drug interactions

GABA can lower blood pressure and may increase the risk of hypotension if taken together with drugs that lower blood pressure such as captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), amlodipine (Norvasc), hydrochlorothiazide (HydroDiuril), furosemide (Lasix) (10).

Safety

GABA can be taken safely provided the dosage is right and not used for too long. Many studies lasted 12 weeks and demonstrated safety (5, 6, 7, 8, 9, 11, 12, 13, 15, 16, 17, 18, 19). There are insufficient studies in pregnant and breastfeeding women to establish safety: avoid use.

Dosage

The recommended daily dosage for adults is:

  • For general use: up to 500 mg (sublingual)
  • For stress and anxiety disorders: melt a maximum of 750 mg spread under the tongue 3 times daily
  • For sleep disorders: 100 - 1000 mg before sleeping.
  • For growth hormone stimulation: 500 mg (sublingual), or 3 grams (in chewable tablets) just before exercise.

GABA is essential in calming and regulating the HPA axis (pituitary-epithelial-adrenal axis). In addition to supplementation, which can be a quick win, solving the ultimate cause of the GABA deficiency is necessary to restore proper functioning of the HPA axis. In doing so, attention to resolving any existing neuro-inflammation through lifestyle interventions, regulating the citric acid cycle through exercise and targeted diet and supplementation, and restoring the microbiome with nutrition and pre- and probiotics, is indispensable.

References:

1. Crowley, Tadhg, et.al. , 2016, Inhibiting Neuroinflammation: The Role and Therapeutic Potential of GABA in Neuro-Immune Interactions; Brain, Behavior, and Immunity 54 (May 2016): 260–77. https://doi.org/10.1016/j.bbi.2016.02.001.

2. Guerriero, Réjean M. et.al, 2015, Glutamate and GABA Imbalance Following Traumatic Brain Injury; Current Neurology and Neuroscience Reports 15, no. 5 (May 2015): 27. https://doi.org/10.1007/s11910-015-0545-1.

3. Heberden, C. (2016). Modulating adult neurogenesis through dietary interventions. Nutrition Research Reviews, 29(2), 163-171. doi:10.1017/S0954422416000081

4. Liddelow, Shane et.al, 2017, Neurotoxic Reactive Astrocytes Are Induced by Activated Microglia; Nature 541, no. 7638 (January 2017): 481–87. https://doi.org/10.1038/nature21029.

5. May, Xin, et.al, 2016, Dual Mechanisms Regulating Glutamate Decarboxylases and Accumulation of Gamma-Aminobutyric Acid in Tea (Camellia Sinensis) Leaves Exposed to Multiple Stresses; Scientific Reports 6, no. 1 (July 2016): 23685. https://doi.org/10.1038/srep23685.

6. Mendelev, Natalia, et.al, 2012, Selenite Stimulates Mitochondrial Biogenesis Signaling and Enhances Mitochondrial Functional Performance in Murine Hippocampal Neuronal Cells; Edited by Paul A. Cobine. PLoS ONE 7, no. 10 (Oct. 22, 2012): e47910. https://doi.org/10.1371/journal.pone.0047910.

7. Neal, Matthew&Jason R. Richardson, 2018, Epigenetic Regulation of Astrocyte Function in Neuroinflammation and Neurodegeneration; Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1864, no. 2 (February 2018): 432–43. https://doi.org/10.1016/j.bbadis.2017.11.004.

8. Ngo, Dai-Hung&Thanh Sang Vo, 2019, An Updated Review on Pharmaceutical Properties of Gamma-Aminobutyric Acid; Molecules 24, no. 15 (July 24, 2019): 2678. https://doi.org/10.3390/molecules24152678.

9. Sherwin, Eoin et.al, 2018, Recent Developments in Understanding the Role of the Gut Microbiota in Brain Health and Disease: The Gut Microbiota in Brain Health and Disease; Annals of the New York Academy of Sciences 1420, no. 1 (May 2018): 5-25. https://doi.org/10.1111/nyas.13416.

10. Shi, Z., Ren, H., Huang, Z. et al. Fish Oil Prevents Lipopolysaccharide-Induced Depressive-Like Behavior by Inhibiting Neuroinflammation. Mol Neurobiol 54, 7327-7334 (2017). https://doi.org/10.1007/s12035-016-0212-9

11. Stanhope Kimber L, Valentina Medici, Andrew A Bremer, Vivien Lee, Hazel D Lam, Marinelle V Nunez, Guoxia X Chen, Nancy L Keim, Peter J Havel, A dose-response study of consuming high-fructose corn syrup-sweetened beverages on lipid/lipoprotein risk factors for cardiovascular disease in young adults, The American Journal of Clinical Nutrition, Volume 101, Issue 6, June 2015, Pages 1144-1154, https://doi.org/10.3945/ajcn.114.100461

12. Teng Kim-Tiu, Chee-Yan Chang, M.S. Kanthimathi, Alexander Tong Boon Tan, Kalanithi Nesaretnam, Effects of amount and type of dietary fats on postprandial lipemia and thrombogenic markers in individuals with metabolic syndrome, Atherosclerosis, Volume 242, Issue 1, 2015, Pages 281-287

13. Vors Cécile, Gaëlle Pineau, Jocelyne Drai, Emmanuelle Meugnier, Sandra Pesenti, Martine Laville, Fabienne Laugerette, Corinne Malpuech-Brugère, Hubert Vidal, Marie-Caroline Michalski, Postprandial Endotoxemia Linked With Chylomicrons and Lipopolysaccharides Handling in Obese Versus Lean Men: A Lipid Dose-Effect Trial, The Journal of Clinical Endocrinology & Metabolism, Volume 100, Issue 9, September 1, 2015, Pages 3427-3435, https://doi.org/10.1210/jc.2015-2518