Gamma-aminobutyric acid (GABA) is a widely distributed non-proteinogenic amino acid that occurs in microorganisms, plants, and vertebrates [1]. It is recognized as the main inhibitory neurotransmitter in the central nervous system and has physiological roles related to synaptic transmission, neuronal development and relaxation, and the prevention of sleep disruption and depression [2,3].
GABA is found in foods consumed in the diet, such as vegetables, fruits, and fermented foods [4]. Oral supplementation with GABA has been shown to improve anxiety [5], reduce psychological stress [6], bring about relaxation [7], and improve sleep [8]. It also controls the secretion of growth hormone from the pituitary gland, a hormone involved in the growth and maintenance of skeletal muscle [9,10]. GABA itself has also been implicated as a potential myokine, a term used to describe cellular signaling molecules that are secreted from muscle and impact various other organs [11]. Signaling through GABA receptors has also been associated with the growth and maintenance of skeletal muscle tissue [12].
Skeletal muscle is an essential tissue that constitutes approximately 40% of total body mass. It plays important roles in regulating resting metabolism, lipid oxidation, glucose disposal after feeding, and supporting posture and locomotion [13,14]. Losses in muscle mass and function, particularly those that occur with advancing age [15], can contribute to the onset of metabolic disease. The major stimuli that drive muscle protein accretion (i.e., hypertrophy or growth) are resistance exercise training and the provision of dietary protein or nutrients [16,17].
The goals of this article are to explore the effect of GABA on muscle protein synthesis and evaluate its use as an ergogenic aid for the maintenance or enhancement of skeletal muscle mass to support optimal health.
GABA, growth hormone, and resistance exercise training
GABA is commercially available as an oral amino acid supplement and is alleged to directly stimulate the secretion of growth hormone through centrally mediated mechanisms [18,19].
In male rats, GABA administration and casein protein for 10 days elevated resting growth hormone concentrations in the blood plasma and promoted baseline protein synthesis in the gastrocnemius muscle, brain, and liver [20].
Research in young resistance-trained human males has shown that ingesting GABA elevates resting and post-exercise growth hormone concentrations in the blood serum [18]. However, the authors of the study emphasized that the extent to which growth hormone secretion is associated with muscle growth/hypertrophy is unknown. What is clear is that growth hormone has acute stimulatory effects on amino acid transport, and insulin-like growth factor-1, that contribute toward muscle protein synthesis [21-24].
An important aspect of this study is that GABA increased the peak values of both forms of growth hormone (immunoreactive and immunofunctional) by around 400% compared with placebo. However, this study was limited in that it only measured the acute effects of GABA supplementation, and the direct effects on skeletal muscle metabolism were not explored.
GABA, whey protein, and skeletal muscle mass in humans
In healthy males, when oral GABA plus whey protein was provided daily for 12 weeks, alongside resistance training twice per week, resting plasma growth hormone concentrations were increased at 4 and 8 weeks compared with baseline [4]. In a group that only consumed whey protein alone, growth hormone concentrations were only elevated at 8 weeks. Nonetheless, the group that received GABA and whey protein group had significantly enhanced whole body fat-free mass after 12 weeks, albeit in untrained middle-aged men with suboptimal protein intake. It must be noted however that fat-free mass includes the body composition of water, organs, bone, connective tissue, as well as muscle.
GABA and muscle tone
During sleep, GABA serves as a muscle relaxant and it is also the primary amino acid that sets overall muscle tone [25]. Muscle tone is regulated across sleep-wake states, being maximal in waking, reduced in slow-wave sleep, and absent in rapid eye movement or REM sleep [26].
Chronic sleep deprivation is a major catabolic stressor that can fuel the loss of muscle mass and function [27]. In an acute study in humans, sleep deprivation reduced muscle protein synthesis by 18% and induced a catabolic environment [27]. Oral supplementation with GABA has been shown to increase overall autonomic and parasympathetic nervous system activities, bringing about relaxation effects [28]. Theoretically, this restoration of parasympathetic tone by GABA and its effects on stress and sleep [8] might promote enhanced exercise recovery and increase muscle protein synthesis [27].
Summary
Although limited, the evidence presented here indicates that GABA supplementation might help promote the acute release of growth hormone, which could have indirect effects on skeletal muscle protein synthesis and therefore muscle mass. When consumed over 12 weeks alongside regular resistance training, GABA and whey protein supplementation can support the accumulation of whole body fat-free mass even in the presence of suboptimal dietary protein intake, and in people with no previous training history. What is abundantly clear is that further research needs to be conducted on the potential benefits of GABA supplementation for skeletal muscle health.
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References
[1] D.-H. Ngo, T.S. Vo, An Updated Review on Pharmaceutical Properties of Gamma-Aminobutyric Acid, Molecules 24 (2019) 2678. https://doi.org/10.3390/molecules24152678.
[2] D.T. Plante, J.E. Jensen, J.W. Winkelman, The role of GABA in primary insomnia, Sleep 35 (2012) 741–742. https://doi.org/10.5665/sleep.1854.
[3] F. Petty, GABA and mood disorders: a brief review and hypothesis, J Affect Disord 34 (1995) 275–281. https://doi.org/10.1016/0165-0327(95)00025-i.
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