Mechanism of action:

GABA produced within the brain acts as a neurotransmitter, carrying signals from neuron to neuron.

Although many of the known neurotransmitters function as both excitatory and inhibitory, GABA is unique in that it functions in the adult human brain as the primary inhibitor and calming agent for excitatory neurotransmitters which are firing too rapidly.

It has been referred to as “nature’s valium” because of the calming effect it can exert.

When GABA levels are low, an excitatory neurotransmitter can fire too often in the brain without any inhibition. When the brain is functioning optimally, a balance is maintained.

When needed, GABA is synthesized from Glutamate and is sent out in an attempt to balance the over-firing, or excitation.

Pharmacodynamics:

A Shimadzu High-Performance Liquid Chromatography system LC-20AD (Shimadzu Corp., Japan) was used to perform the separation of GABA and internal standard (d -GABA). The separation was achieved on a Phenomenex Luna HILIC column (100 mm×3.0 mm, 3 µm; Phenomenex Corp., USA) maintained at 402◦C. The mobile phase consisted of water–acetonitrile (20:80, v/v) at a flow rate of 0.5 mL/min. The injection volume was 5 µL. A triple quadruple mass spectrometer (ABI 4000 II, Applied Biosystems Corp, USA) was equipped with an electrospray ionization (ESI) for analytical detection. The ESI source was set in positive ionization mode. Multiple reactions monitoring (MRM) was used to monitor precursor to product ion transition of m/z 104→69 for GABA, and m/z 106→71 for d -GABA with scan time of 0.10 s per transition. The data acquisition and sample quantification were operated using Analyst 1.6 software (Applied Biosystems Corp, USA). An aliquot of the plasma sample (100 µL) was transferred to an Eppendorf micro tube for processing. 25 µL internal standard (500 ng/mL d -GABA) 100 µL, methanol:water (1:1, v/v) and 500 µL acetonitrile were added and vortex mixed for 1 min. After centrifugation for 10 min at 13,000 rpm, a 5 µL aliquot of the supernatant was injected onto the LC–MS/MS system for analysis. The calibration range was 5.0–1000 ng/mL in plasma. The extraction recovery of GABA at the low, middle and high level of quality control was 92.7, 91.5, and 98.2%, respectively. The precision (RSD) and accuracy (relative bias) of the method were evaluated to be within 9.9% and from −0.9 to 4.3%. The PK parameters for GABA were calculated after substratction of baseline GABA concentration and estimated from plasma samples, by means of standard non compartmental methods using the WinNonlin software (Version 4.1, Pharsight Corp, USA). The maximum plasma concentration (C) and the corresponding time (T ) were determined directly from the concentration-time profiles during the three periods. The areas under the concentration-time curves from zero to 24 h (AUC0–24h ) and to 4 h (AUCmax 0–4h ) were calculated using the linear trapezoidal rule. Other PK parameters assessed included oral clearance (CL/F), apparent volume of distribution (V/F), ratio of accumulation (RA), area under the curve from the time zero extrapolated to infinity (AUCinf ).

Pharmacodynamics:

One milliliter blood sample for GLP-1 (active form) and glucagon detection was collected into a precooled Vacutainer EDTAplasma tube that contained Sitagliptin (Sigma S8576, final blood concentration was 100 µmol/L) and Aprotinin (Sigma A1153, final blood concentration was 250 KIU/ml) at pre dose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 h post-dose from subjects during the three periods as PK analysis. Immediately, tubes were inverted to mix followed by immediate centrifugation (3000 g at 4 degree C for 10 min) and storage at −80◦C until analysis. Plasma glucagon concentrations were measured by ELISA (Mercodia, Catalog No. 10-1271-01). Plasma GLP-1 (active form) concentrations were also measured by ELISA (Millipore, Catalog No. EGLP-35K).

Precautions:

As a nutritional supplement, GABA has been used for anxiety, panic attacks, ADHD, depression, insomnia, alcoholism, and nervousness.

But before you decide to take this natural compound to help you relax and sleep better, you might be wondering whether or not it is safe.

Side effects:

GABA is likely safe when taken correctly by mouth for short periods of time, up to 12 weeks.

Some commonly reported GABA Supplements Side Effects include:

Sleepiness
Somnolence
Upset stomach
Pain in the Head
Muscle Weakness
Breathing patterns
Tingling sensations
Shortness of breath
Decreased Alertness
Alteration in heart rate
Upset stomach and indigestion

Dosage:

To reduce high blood pressure, health professionals with the University of Pittsburgh Medical Center recommend adults take 10 mg of GABA daily. Higher doses of GABA of up to 1,000 mg daily may be necessary to alleviate symptoms associated with insomnia or anxiety. For more personalized dosing recommendations, seek guidance from your medical provider.

The appropriate dose of GABA (gamma-aminobutyric acid) depends on several factors such as the user’s age, health, and several other conditions. At this time there is not enough scientific information to determine an appropriate range of doses for GABA. Keep in mind that natural products are not always necessarily safe and dosages can be important. Be sure to follow relevant directions on product labels and consult your pharmacist or physician or other healthcare professional before using. There is no standard recommended dosage for GABA supplementation, however, there are studies utilizing specific doses which offer us some guidelines, as well as thousands of anecdotal reports sharing their standard dosage.

Most users find that taking between 250mg-750mg, two or three times each day is beneficial. Those taking GABA for insomnia usually take between 500mg-750mg once, right before bedtime.

Over dosage:

Symptoms of overdose include double vision, slurred speech, drowsiness, laziness or sometimes diarrhoea. Consult your doctor if you experience any such symptoms or reach out to your nearest hospital

Warning:

Talk to your doctor if
• If you experience behavioral change and have suicidal thoughts after taking this medicine
• If you have a heart, kidney, liver, brain or breathing disorder

Duration of action:

This indicates that GABA was rapidly absorbed, with maximum plasma concentrations achieved approximately 1–1.5 h after an oral dose, and subsequent mean elimination half-life in a range of 5–5.2 h. No serious adverse effects have been associated with the use of GABA. Nonetheless, comprehensive safety studies have not been performed. Maximum safe doses in young children, pregnant or nursing women, or people with severe liver or kidney disease have not been established.

Drug- drug interactions:

We currently have no information for GAMMA-AMINOBUTYRIC ACID (GABA) Interactions. Not enough is known about how GABA may interact with drugs, foods, or other herbs and supplements, but use with caution if taking with blood pressure medications.

Be sure to tell your doctor about any supplements you’re taking, even if they’re natural. That way, your doctor can check on any potential side effects or interactions with medications, foods, or other herbs and supplements. They can let you know if the supplement might raise your risks.

The U.S. Food and Drug Administration (FDA) does regulate dietary supplements; however, it treats them like foods rather than medications. Unlike drug manufacturers, the makers of supplements don’t have to show their products are safe or effective before selling them on the market. Anti-Hypertensive Drugs and supplements that have been shown to lower blood pressure, including cocoa, alpha-linolenic acid, blond psyllium, cod liver oil and more.

To date, there are no knowing medication interactions associated with taking GABA supplements. Before taking this supplement, however, discuss all medications you’re taking with your physician.

Adverse reactions:

Nearly all antibiotic agents have been associated with CNS effects. Although uncommon, these events can be severe. Once the antibiotic is discontinued, effects are usually reversible. It is important for mental health care providers to recognize antibiotics as a potential cause of neuropsychiatric adverse effects, as discontinuation often leads to rapid recovery.

Pregnancy:

Pregnancy and breast-feeding: Not enough is known about the use of GABA during pregnancy and breast-feeding. Stay on the safe side and avoid use.

Fertility:

In conclusion, GABA modulated sperm kinematic parameters and increased hyperactivation. These effects have the same magnitude of those produced by progesterone and seem to be mediated mainly by the GABA receptor. We speculate that GABA may be a physiological regulator of sperm function.

Contraindications:

The safety and effectiveness of GABA supplements have not been evaluating during pregnancy or related side effects. For this reason, women who are pregnant or lactating should avoid taking GABA supplements. Besides, people with liver or kidney disease shouldn’t take GABA supplements without first consulting a doctor.

Storage:

• Store this medicine below 30°C protected from light
• Keep it out of the reach of children

Breastfeeding:

Pregnancy and breast-feeding: Not enough is known about the use of GABA during pregnancy and breast-feeding. Stay on the safe side and avoid use.