Side Effects of GABA

GABA is usually described as a well-tolerated supplement, and safety-review data generally confirm this. But "well tolerated" does not mean "has no side effects." The editorial team has gathered which adverse reactions are described in studies, what they depend on, and in which situations the risks increase.

What safety reviews say

The most thorough document on the safety of GABA supplements is the review by the United States Pharmacopeia (USP), published by Oketch-Rabah et al. in 2021. The experts analyzed clinical studies, adverse-reaction data, and preclinical work and concluded that when used at the doses usually found in supplements, no serious safety problems were identified.

At the same time, the authors drew attention to several points: a transient decrease in blood pressure, certain subjective sensations when taking high doses, and a lack of data on pregnancy, breastfeeding, and long-term use. It is precisely these aspects that we will examine in more detail.

It is important to understand the limitations of such an assessment. Most clinical studies of GABA were short — from a single dose to a few weeks — and included healthy adults. Rare side effects under such conditions may simply not have time to appear.

Another review — by Hepsomali et al. (2020), devoted to stress and sleep — also did not record serious adverse events in the included studies, but emphasized that the reporting of side effects in many works was incomplete.

The most common side effects

Drowsiness and a feeling of relaxation are essentially a continuation of GABA's expected action. If the supplement is taken during the day, especially before driving, heavy-weight training, or work requiring concentration, this effect can become a problem.

Gastrointestinal symptoms — nausea, abdominal discomfort, changes in stool — are described in some people, as with many other supplements. They are usually mild and pass after reducing the dose or taking it with food.

Reactions specific to GABA are described mainly at high, gram-level doses used in some early studies: a tingling sensation in the skin of the face and body, burning in the throat, a short-lived sensation of shortness of breath. The USP review mentions these effects as transient, that is, ones that resolved on their own.

Also, some people report headache or, conversely, paradoxical agitation instead of calming. The mechanism of such reactions is unclear, and they occur rarely, but they are worth taking into account: if the supplement causes unpleasant sensations, it should be discontinued.

Effect on blood pressure

GABA is able to lower blood pressure. This effect has been studied separately, in particular in Japanese studies of fermented dairy products enriched with GABA. For example, in the work by Inoue et al. (2003) in people with mild hypertension, such a product was accompanied by a moderate decrease in pressure compared with placebo.

For a person with elevated pressure this may seem like an advantage, but this is precisely where the risk lies. If a person is already taking antihypertensive drugs, an additional hypotensive effect can cause dizziness and weakness, especially when standing up abruptly.

Athletes with naturally low pressure should also be careful. The combination of GABA, dehydration after a long workout, a hot shower, or a sauna theoretically increases the risk of orthostatic hypotension — a short-term drop in pressure with weakness and darkening in the eyes.

That is precisely why the USP review mentions hypotension as an effect worth warning about. The practical conclusion: people with hypotension and those being treated for hypertension should discuss taking GABA with a doctor and monitor pressure in the first days.

Interactions that intensify adverse effects

The most predictable problems arise when GABA is combined with substances that also depress the central nervous system. Even if GABA itself enters the brain to a limited extent, the total sedative effect of such combinations cannot be ruled out.

• benzodiazepines, Z-hypnotics, and barbiturates;
• antiepileptic drugs, in particular gabapentinoids;
• baclofen and other muscle relaxants;
• first-generation antihistamines;
• alcohol;
• antihypertensive drugs (due to the effect on pressure).

In people with epilepsy who receive anticonvulsant therapy, independent changes in the "GABAergic" background are undesirable: any supplements claiming to affect the nervous system should be coordinated with a neurologist.

Separately about combining with stimulants. Some athletes take GABA in the evening to "remove" the effect of caffeine or a pre-workout complex after an evening workout. Such a "seesaw" of stimulation and inhibition is not physiological, and it is simpler to change the timing of stimulant intake.

There are no data on the interaction of GABA with dietary supplements like protein, creatine, or vitamins, and the editorial team sees no pharmacological grounds to expect problems here.

Product quality and confusion with GABA derivatives

Some of the "side effects of GABA" are actually not related to it. Products appear on the market in which, under names like "GABA complex," phenibut or other GABA derivatives are contained. Phenibut penetrates the brain better and can cause tolerance, dependence, and severe withdrawal syndrome.

In 2015 the FDA sent warnings to manufacturers of supplements containing picamilon — a compound of GABA with nicotinic acid, which, in the regulator's opinion, does not meet the definition of a dietary ingredient. Such products have a completely different action profile than pure GABA.

Another risk is contamination and dose mismatch. Independent checks of the supplement market in various countries regularly reveal products whose composition does not match the label. Therefore the editorial team advises choosing brands with independent laboratory control.

Finally, the groups for which there is simply no data: pregnant and breastfeeding women, children and adolescents, people with severe liver and kidney disease. For them, the absence of described side effects means not safety but a lack of research.

Editorial conclusions

According to safety reviews, GABA at typical supplement doses is well tolerated, and no serious adverse events have been recorded in clinical studies.

The most common side effects are drowsiness, gastrointestinal discomfort, and, at high doses, tingling and burning in the throat. Special attention should be paid to lowered pressure and to combining with sedatives and alcohol.

Many problems attributed to GABA are actually caused by its derivatives like phenibut or by low-quality products. Carefully reading the composition is the simplest way to avoid them.

Also read our materials "Who Should Not Take GABA," "How to Take GABA: Dosage, Timing, Duration," and "GABA: Dosage Forms and Which to Choose."

References

1. Oketch-Rabah HA, Madden EF, Roe AL, Betz JM. United States Pharmacopeia (USP) safety review of gamma-aminobutyric acid (GABA). Nutrients. 2021;13(8):2742.
2. Hepsomali P, Groeger JA, Nishihira J, Scholey A. Effects of oral gamma-aminobutyric acid (GABA) administration on stress and sleep in humans: a systematic review. Front Neurosci. 2020;14:923.
3. Inoue K, Shirai T, Ochiai H, et al. Blood-pressure-lowering effect of a novel fermented milk containing gamma-aminobutyric acid (GABA) in mild hypertensives. Eur J Clin Nutr. 2003;57(3):490–495.
4. Li J, Zhang Z, Liu X, et al. Study of GABA in healthy volunteers: pharmacokinetics and pharmacodynamics. Front Pharmacol. 2015;6:260.
5. Boonstra E, de Kleijn R, Colzato LS, et al. Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Front Psychol. 2015;6:1520.
6. Cavagnini F, Invitti C, Pinto M, et al. Effect of acute and repeated administration of gamma aminobutyric acid (GABA) on growth hormone and prolactin secretion in man. Acta Endocrinol (Copenh). 1980;93(2):149–154.