Gaba for better focus and less stress

Geschatte leestijd: 15 minutenGamma-Aminobutyric acid, or GABA (Dutch: gamma-aminoboterzuur), is an amino acid that reduces stress and promotes relaxation and better focus. As such, it could possibly be an alternative to cannabis and alcohol for people who use these to relax. In this article, I describe what GABA exactly is and discuss research that has been done on its presumed positive effects on mental well-being.

In the following sections on GABA, I will delve into its effects on growth hormone, the immune system, and fat burning.

Table of Contents

• What is GABA
• GABA and relaxation
• Brainwaves
• Research on the effect of GABA
• Importance of GABA for athletic performance
• Warning: Drowsiness caused by GABA
• GABA & Growth hormone
• GABA and increased release of growth hormone at rest
• GABA and increased release of growth hormone after training
• GABA lowers dopamine, increases prolactin, and thereby lowers testosterone
• GABA-A receptor and GABA-B receptor
• Conclusion: Is GABA positive for muscle growth or not?
• “Can you lose weight with GABA?”
• More eating due to glutamate, less eating due to GABA
• GABA for reduced appetite
• Conclusion

What is GABA

Although GABA is a (γ-)amino acid, it does not occur in the chains of (α-)amino acids found in proteins. In your body, it functions as a neurotransmitter, a signaling molecule that facilitates the transmission of nerve impulses. Neurotransmitters can either stimulate nerve activity (“excitatory” neurotransmitters) or inhibit it (“inhibitory” neurotransmitters). GABA is the main inhibitory neurotransmitter.

GABA was discovered in the fifties and sixties of the last century. Before that, only the existence of excitatory neurotransmitters, of which glutamate is the most important, was known (1,2). GABA and glutamate together account for 80% of brain activity.

GABA and relaxation

As an inhibitory neurotransmitter, GABA reduces nervous system activity, leading to a sense of calmness while reducing feelings of anxiety and stress. GABA maintains balance with excitatory neurotransmitters, especially glutamate. For example, epilepsy is suspected to be caused by an imbalance between GABA and glutamate, both of which are produced in the body from glutamic acid (3 to 6).

GABA may also play a role in stabilizing mood swings (7). It is also being investigated as a treatment for ADHD (8,9).

Brainwaves

What is GABA

Without going too deep into this, it’s handy to know that there are four types of brainwaves which are measured with EEG: delta, theta, alpha, and beta (10). Alpha waves are mainly measured when you are alert in a relaxed way, or in other words: Clear-minded. Beta waves are measured when you are in a stressful situation and it takes more effort to mentally concentrate. Alpha and beta waves are therefore a good indication of your mood and ability to concentrate (11,12) and thus a good indication of the effect of GABA (10).

Research on the effect of GABA

Researchers in Japan therefore measured the alpha and beta waves after giving three different solutions of 200ml to 13 participants in the study (men and women, aged 21 to 35) (10):

1. Distilled water only (placebo)
2. With 100mg GABA (obtained from fermentation of lactic acid bacteria)
3. With 200mg L-theanine

L-theanine is an amino acid that acts as an “agonist” for GABA. This means that it increases (the activity of) GABA (but also serotonin and dopamine) (14,15). The research was conducted on behalf of a Japanese food producer that claimed to have health benefits. They wanted to find out if GABA and theanine would be suitable as ingredients for calming drinks and/or drinks that improve concentration (13). To give the research some legitimacy, it was carried out by Shizuoka University in collaboration with Kyoto Women’s University.

We see that GABA causes the greatest increase in alpha waves, while theanine has a smaller effect on them (despite the twice as large dosage). Conversely, we also see that GABA has the greatest inhibitory effect on beta waves. The researchers therefore conclude:

GABA could work effectively as a natural relaxant and its effects could be seen within 1 hour of its administration to induce relaxation and diminish anxiety.

A.M. Abdou, Pharma Foods International Co

Despite the (non-objective) sponsor, I chose this research because it clearly demonstrates the effect of GABA. However, the effects of GABA on relaxation, focus, and stress have been demonstrated in several studies (16 to 23).

Low GABA levels in the brain are associated with depression, restlessness, anxiety, insomnia, and a poor mood state.

B.S. Weeks, Department of Biology, Adelphi University

Importance of GABA for athletic performance

The words muscle mass, muscle strength, or body fat have not yet been mentioned in this entire article, and this is not a website about psychiatric conditions such as anxiety disorders and depressions. So why is GABA interesting for people who want to improve their bodies?

For various reasons. Rest, in physical and mental terms, has many effects on our bodies. Good physical rest through sleep results, among other things, in increased production of (the “good hormones”) growth hormone and testosterone, while stress increases the catabolic (muscle-breaking) hormone cortisol. Too much stress for too long also deteriorates your immune system. In addition, sleep promotes oxygen uptake and fat burning (24).

Mental rest makes it easier to get physical rest. GABA, for example, is also used against insomnia. Anxiety that keeps people awake at night can also be reduced in many cases with GABA. Finally, it can be a healthier alternative to drugs that people use to relax such as cannabis and alcohol. For instance, I know many bodybuilders (and others) who smoke weed to relax. Although I once wrote an article that showed the negative effect of marijuana on athletic performance was limited (25), it has other harmful effects on health, making alternatives desirable.

Warning: Drowsiness caused by GABA

GABA can also make you sleepy. It is good to keep this in mind and not to try it for the first time when you are about to drive a long distance. You may also want to use GABA for mental focus, for example, during an exam, but even then it is wise to first know what effect it has on you. If drowsiness outweighs mental focus and clarity, your exam will not improve. This depends, of course, on the personal balance between glutamate and GABA, which can vary in everyone.

GABA & Growth hormone

Growth hormone plays an important role in the growth and maintenance of muscle mass. It ensures, among other things, that muscles and cartilage produce more proteins and that muscles use more fatty acids for energy (1). Growth hormone (or somatotropin, or HGH from Human Growth Hormone) exists in various molecular forms (irGH, ifGH), but to keep it simple in this article, I will simply refer to it as growth hormone.

Growth hormone is produced in the anterior pituitary gland and is mainly released at night during sleep, while levels are relatively low during the day (2). However, there are ways to stimulate release during the day including exercise (3), both cardio (4,5) and strength training (6,7,8). The intake of (certain) amino acids is also said to stimulate the release of growth hormone (9).

GABA and increased release of growth hormone at rest

GABA is one of those (γ-)amino acids that is said to increase the release of growth hormone at rest (10,11).

Researchers at the University of Milan gave 5 grams of GABA to nineteen participants in 1980 (10). Eighteen other participants received a placebo. Blood was taken before and three hours after ingestion to determine the amount of growth hormone. They observed a significant increase in growth hormone after the intake of GABA. However, they also observed that administration of 18 grams of GABA for 4 days ultimately resulted in a much smaller effect on growth hormone. This raises the question of whether this effect lasts only a few days.

In 2007, American researchers also tested the response of growth hormone to oral intake of GABA (12). They gave 11 trained men (18-30 years old) 3 grams of GABA or a placebo (sucrose). 15, 30, 45, 60, 75, and 90 minutes after ingestion, their blood values ​​of growth hormone (irGH and ifGH) were measured. They found that GABA increased growth hormone more than the placebo. The peak concentration even increased by 400%!

At rest, GABA ingestion elevated both irGH and ifGH compared with placebo. Specifically, peak concentrations of both hormones were elevated by about 400%, and the area under the curve (AUC) was elevated by about 375%

Michael E. Powers, Division of Athletic Training, Shenendoah University, Winchester

GABA and increased release of growth hormone after training

The Americans also looked at the influence of GABA on the increase in growth hormone due to training. First, they looked at the effect of training on growth hormone without the influence of GABA to later compare this. As expected, training resulted in an increase in growth hormone compared to rest. However, if they took GABA before training, the increase in growth hormone was 175% (ifGH) to 200% (irGH) greater.

Additionally, 200% greater irGH (P < 0.01) and 175% greater ifGH (P < 0.05) concentrations were observed in the EX-GABA than in the EX-P condition, 30 min after ingestion…

…Conclusions: Our data indicate that ingested GABA elevates resting and postexercise irGH and ifGH concentrations. The extent to which irGH/ifGH secretion contributes to skeletal muscle hypertrophy is unknown, although augmenting the postexercise irGH/ifGH response may improve resistance training-induced muscular adaptations.

Michael E. Powers, Division of Athletic Training, Shenendoah University, Winchester

In the graph below, you can see the influence of GABA on growth hormone in both rest and after training as determined by the American researchers:

FIGURE 2-Immunoreactive growth hormone (irGH) (A) and immunofunctional GH (ifGH) (B) time-point concentrations for the rest-placebo (P), rest-GABA, exercise (EX)-P, and EX-GABA conditions. Data are means ± SE. * EX-GABA different from rest-P and rest-GABA (P < 0.01); † EX-P different from rest-P and rest-GABA (P < 0.05); # EX-GABA different from EX-P (P < 0.05); ** EX-GABA different from rest-P (P < 0.01); § EX-P different from rest-P (P < 0.05).

GABA lowers dopamine, increases prolactin, thus lowering testosterone

Now you may already be ordering GABA from Bodyenfitshop or Bodylab, but maybe you should wait a bit. It seems that it’s not all sunshine and roses when it comes to GABA. Unfortunately, it’s not that simple.

• GABA –> Negative influence on dopamine (13) + Positive influence on prolactin (11)
• Dopamine –> Negative influence on prolactin (15)
• Prolactin –> Negative influence on testosterone (via LH) (14)

In the study from the University of Milan that I showed above, more came up than just the increase in growth hormone:

(5g) GABA caused a significant elevation of plasma growth hormone levels (P less than 0.001), but did not consistently alter plasma prolactin concentration since only 5 out of 15 subjects showed an increase of the hormone. Eight additional subjects were submitted to an insulin tolerance test before and after per os administration of 18 g GABA daily for 4 days. Protracted GABA treatment significantly blunted the response of growth hormone and enhanced that of prolactin to insulin hypoglycaemia.

F. Cavagnini, University of Milan

The single intake of 5 grams of GABA thus resulted in an increase in growth hormone while in 1/3 of the participants, an increase in prolactin also occurred. If they took as much as 18 grams of GABA for four consecutive days, the effect on growth hormone was lower, but prolactin increased even more. This has a negative effect on testosterone.

Furthermore, GABA suppresses the release of dopamine, another neurotransmitter that contributes to feelings of happiness, pleasure, and prosperity (13).

So, the increase in prolactin as seen in Milan may be caused by the decrease in dopamine, as it is known that dopamine has an inhibitory effect on prolactin.

Why is this important? Because both effects of GABA, both the decrease in dopamine and the increase in prolactin, are likely to result in a decrease in testosterone. Prolactin has already been shown to have a negative effect on testosterone (14). The production of testosterone depends on the activity of luteinizing hormone (LH) and Gonadotropin-releasing hormone (GnRH), and these are lowered by prolactin (14).

Are you still following? So, GABA lowers dopamine and increases (thus) prolactin. Because prolactin has increased, (the activity of) LH and GnRH decreases, which in turn leads to a decrease in the release of testosterone. It should be noted that this is a logical deduction from independently known relationships, but directly this negative relationship between GABA and testosterone has not yet been proven.

GABA-A receptor and GABA-B receptor

As if it wasn’t complicated enough, a distinction must also be made between various types of receptors for GABA. Receptors are those parts of cells that react to certain substances and thus ensure that that substance can do its work in the cell. For GABA, a distinction is made between GABA-A and GABA-B (B1&B2) receptors, both of which react to GABA in different ways. In the studies above, no distinction was made, so we see the results of the effect on both the A and B receptors lumped together. However, if we separately look at the influence on GABA-B receptors, the picture looks very different.

Baclofen is a medication that selectively works on the GABA-B receptor instead of on both receptors like GABA itself does. In practice, it is mainly used as a muscle relaxant for muscle cramps caused by nerve irritation (such as ALS, spasticity, and MS). Researchers at the University of Illinois gave Baclofen to castrated and normal rams (16). They found that administration of Baclofen led to an increase in GnRH which led to an increase in LH, and thus would result in an increase in testosterone if the rams were not castrated.

In the case of the non-castrated rams, testosterone was administered first. Normally, this would lower their own production, as happens with anabolic steroid users. Testosterone works through negative feedback. The more testosterone there already is, the less GnRH is produced by the hypothalamus, the less LH and FSH (follicle-stimulating hormone) are produced by the pituitary gland, and thus the less testosterone is produced by the testes. Administration of Baclofen changed this. For example, FSH no longer decreased, and the researchers therefore suspected that Baclofen has a regulatory effect on GnRH and LH and reduces the inhibitory effect of externally administered testosterone on its own production. There are therefore users of anabolic steroids who report feeling like they have used twice as many steroids when using Baclofen during their cycle.

Selective agonists of GABA-B receptors, therefore products like Baclofen that only activate the GABA-B receptors, may be more interesting than GABA itself, which activates both receptors and ultimately has a negative influence on testosterone. This is also evident from research in Germany, which showed that Baclofen, like GABA, also leads to an increase in growth hormone (17). This would allow you to have the benefits of GABA without the drawbacks.

After inhibition of endogenous GABA synthesis, GH production was stimulated by baclofen, a GABA-B receptor agonist. By contrast, blocking GABA-B receptors by an antagonist, phaclofen, decreased GH levels. We conclude that in GH-producing cells, GABA acts as an autocrine factor via GABA-B receptors to control GH levels.

K. Gamel-Didelon, Anatomical Institute of the University of Munich

However, Baclofen is a medication and as such can have side effects. So you can’t just switch from GABA to Baclofen, which is formally only available on prescription. Moreover, more research needs to be done on the effect on the different receptors and how to benefit from this in practice.

Conclusion: Is GABA positive for muscle growth or not?

Looking at GABA itself and its effects on both GABA-A and GABA-B receptors (increase in growth hormone, decrease in testosterone), it remains questionable whether we benefit from this. Ultimately, it’s not about growth hormone or testosterone, but about the increase in muscle mass and strength we want to achieve. However, there have been no studies that simply look at the influence of GABA on lean mass and strength. So it is not known whether the increase in growth hormone outweighs the (presumed) decrease in testosterone.

It’s only a question whether that’s coincidental. Personally, I find it much easier to set up a study that looks at the effect on muscle mass than to measure growth hormone. You would think that the supplement industry, eager to sell you GABA, would benefit from funding such research. It is possible that they prefer to refer to studies from which you could deduce that GABA works positively than to actually conduct research into the results on muscle mass only to find out that these results do not exist. The studies that have been conducted have been done by researchers who are not at all interested in muscle mass but mainly look at possible applications for muscle diseases or mental illnesses or simply want to know in what different ways GABA exerts influence and where.

Where the evidence for the calming effect of GABA has been well established, this is much less the case or not at all for the positive effect on muscle mass.

“Can you lose weight with GABA?”

GABA can help with weight loss by reducing appetite. This reduced feeling of hunger can make it easier to stick to your diet.

A reader recently sent me a list of supposed fat burners with the question of what I thought of these various fat burners. Coincidentally, I had just written an article on studies on various supposed fat burners. GABA was not included here because I had hardly found anything about it regarding weight loss. However, the name GABA comes up more often when it comes to losing weight. So I decided to dedicate a separate article to it, but first had to spend two parts on the background of GABA and the effects for which it is primarily known (mental clarity and influence on hormone balance). Now finally the article with the answer to the question that led to this series.

In short: GABA is not a fat burner. There are no studies that have shown (or refuted) that GABA leads to faster fat burning. That doesn’t mean that GABA can’t help with weight loss. GABA has been shown to reduce appetite, especially when hunger is caused by a dietary deficiency such as during a diet.

Eating more due to glutamate, eating less due to GABA

(The need for) eating is a complex type of behavior regulated by various areas in the forebrain (“prosencephalon”) and brainstem (“truncus cerebri”) (1). These transmit signals to initiate, sustain, and terminate the action of eating (2,3,4). Especially the lateral part of the hypothalamus (and the neurotransmitters in it) play a major role in the amount of food we eat (5 through 9).

In part I of the GABA series, I discussed the difference between the neurotransmitters glutamate (the “accelerator” for brain activity) and GABA (the “brake”). Glutamate and GABA both also play a role in determining appetite.

In 1993, researchers at the University of California looked at what happened when glutamate was directly injected into the lateral hypothalamus of rats that were already satiated at that time (10,11). Within two to three minutes after the injection, the rats started eating again. The amount depended on the dosage of the glutamate injection (positive correlation) and the effects lasted for about an hour.

Finally, analysis of meal and behavioral patterns produced by LH injection of glutamate (600 nmol) and KA (1.0 nmol) revealed that the elicited eating usually began 2-3 min postinjection and consisted of a single normal to large size meal. There were no other behavioral effects during this initial postinjection period and no effects on other oral behaviors, like drinking or gnawing, at any time. Collectively, these findings suggest that glutamate may act through several subtypes of its receptors on some LH neurons to elicit eating.

B.G. Stanley, University of California

Conversely, administering an antagonist of glutamate (a substance that inhibits the action of glutamate) was found to reduce appetite (12). Rats that received an antagonist of glutamate injected into the lateral hypothalamus twice a day for 8 days ate 65% less during that period and lost 13 grams per day. It is important to realize that the average male rat of the Sprague Dawley strain used weighs between 450 and 520 grams (13). Translated, that would mean a weight loss of between 2 and 2.3 kilos per day for someone weighing 80 kilos!

If glutamate can have this effect, it is not surprising that GABA, as an inhibitor of glutamate, plays an important role. So you would expect GABA to reduce your appetite. This has already been demonstrated in research from 1975 and ’78 (14,15). These studies not only showed that the largest amount of GABA was found in the lateral part of the hypothalamus (15) and followed a day-and-night rhythm (14), but also that this rhythm corresponded with feeding patterns in rats (16).

In 1977, researchers injected a GABA antagonist into the lateral part of the hypothalamus of rats, a substance that inhibits the action of GABA (17). As you might expect, the rats ate more. This did not happen, however, when it was injected into another part of the hypothalamus such as the “periventricular” part, confirming the specific local action in the lateral part (18).

GABA would especially limit nocturnal binge eating and hunger due to a dietary deficiency (1). Glutamate levels rise at the beginning of a meal (first 1/3 part of the meal) to make you eat, but then decrease to below basal levels towards the end of the meal. GABA also rises from the beginning of the meal, but continues to rise and reaches its peak in the last (1/3) part of the meal (19). Simply put, you could say that glutamate makes you start eating and GABA makes you stop.

GABA for reduced appetite

An important caveat here is that for all the studies mentioned here, no GABA was used. Instead, agonists and antagonists of glutamate and GABA receptors were used. These are substances that cause the body to show an enhanced (agonist) or reduced (antagonist) response to the action of glutamate and GABA. Thus, GABA itself was not used to demonstrate an enhanced effect of GABA, but rather drugs that achieve this effect.

Although GABA has such a function in the body, this does not automatically mean that oral intake of GABA enhances the effect. It has therefore not been demonstrated that intake of GABA can lead to the same appetite-reducing effect.

Conclusion

Having less hunger while dieting naturally makes it easier to stick to the diet. So it’s simply easier to eat less. In this regard, GABA can help with weight loss. However, this works very differently from fat burners like green tea and caffeine which increase post-meal calorie burning and prevent you from gaining (or help you lose) weight from the same amount of food. Moreover, it is therefore questionable whether you can enhance this effect of GABA in the body by taking GABA.

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