β-alanine is one of the most popular sports supplements used by strength/power athletes today. The popularity of β-alanine derives from its ability to buffer intracellular pH in skeletal muscle, with the consequent delay of fatigue during high-intensity exercise.
This supplement is a non-protein amino acid that does not appear to have any ergogenic potential on its own. Once ingested, it combines with histidine in a reaction catalyzed by the enzyme carnosine synthase, where the pKa of the imidazole ring of the histidine residue allows it to act as a highly effective intracellular pH buffer within skeletal muscle and other organs.
It is found abundantly in excitable tissues, such as skeletal muscle, the heart and in some regions of the brain, although the highest concentrations in humans are found in muscle (with higher concentrations in type II fibers).
Bagchi, D., Nair, S., & Sen, C. K. (Eds.). (2018). Nutrition and enhanced sports performance: muscle building, endurance, and strength. Academic Press.
Beta-alanine is produced endogenously in the liver from the degradation of uracil along with an alternative synthesis in the intestine and kidney. Although the researchers suggest that total availability from endogenous synthesis and dietary intake is quite low (higher prevalence in foods of animal origin, needing impractical amounts for day-to-day use).
So if we are looking for certain benefits, perhaps supplementation with beta alanine is the only way or the easiest way to raise carnosine levels. Beta-alanine is considered the rate-limiting substrate for carnosine synthesis. Thus, the objective of its supplementation is to increase the carnosine content in skeletal muscle, which improves the intracellular buffering capacity and other functions that we will talk about from a clinical perspective where there is much to be investigated...
Several physiological functions have been attributed to carnosine in skeletal muscle, including antioxidant activity and protection against protein glycosylation and carbonylation. Carnosine's antioxidant properties have been demonstrated through its ability to remove reactive oxygen species (ROS). This ability as an antioxidant is mainly due to its histidine component, while β-alanine has been shown to be ineffective as an antioxidant in itself.
High-intensity exercise causes a significant response to oxidative stress, causing inflammation and muscle damage. The attenuation of oxidative stress is beneficial for subsequent recovery. However, carnosine as an antioxidant in vivo has been limited to animal models, where it has been shown to have different physiological functions, therefore, the efficacy of carnosine as an antioxidant in humans remains quite a bit to be explored and investigated.
In vitro studies with human and animal muscle fibers have also attributed other functions to carnosine, including calcium sensitization, transient calcium regulation (i.e., increased calcium release and reuptake by the sarcoplasmic reticulum), and improved muscle excitation-contraction.
However, a recent human study did not support the hypothesis of increasing carnosine to increase calcium, its sensitivity, and release, but it did support the finding that carnosine may enhance calcium reuptake. Clearly, more studies investigating these issues are still required to clarify the physiological roles of carnosine. Despite some controversies, an indisputable function of carnosine is regulation as an intracellular buffer since its side chain (i.e., that of the imidazole ring) has a pKa of 6.83, making carnosine an effective physicochemical buffer.
Also of interest, carnosine has been shown to act as a chelating agent for ions such as copper and zinc, whose excessive accumulation that can lead to lipid peroxidation and cell damage. In addition, it has been shown to act as a protective agent against the formation of advanced lipoxidation and glycation end products, delaying the aging process and possible prevention of various diseases.
Another emerging area of research is beta-alanine supplementation and its potential antioxidant role in the brain. One of the initial studies examining β-alanine supplementation and brain function was conducted by Murakami and Furuse (2010) where they fed mice a β-alanine-enriched diet for about 5 weeks and observed a significant increase in carnosine content in the cerebral cortex and hypothalamus. These increases were associated with an increase in brain-derived neurotrophic factor (BDNF) exerting a neuroprotective effect and a decrease in the concentration of 5-hydroxyindoleacetic acid, a metabolite of serotonin, despite the rodents' exposure to stressful conditions (anxiolytic compounds).
The mechanism associated with elevated brain carnosine and maintenance of BDNF expression in the hippocampus is not well understood, but is likely related to carnosine's role as a neural protector through its action as an antioxidant. It has been suggested that oxidative stress and inflammation in the brain are part of the aftermath of physiological events that contribute to post-traumatic stress disorder, but may also contribute to cognitive and mild traumatic brain injury-associated (mTBI)-associated neurodegeneration.
A recent study by Hoffman et al. (2017) investigated the benefit of β-alanine supplementation on mTBI-related cognitive and behavioral responses. In addition, the effects of β-alanine ingestion on the expression of the inflammatory protein, neurotrophin and tau in the hippocampus were also examined.
The results of the study indicated that 30 days of β-alanine intake in rats were effective in reducing the incidence of mTBI-like phenotype, where they also appeared to have a reduced inflammatory response (an attenuation of glial fibrillary acidic protein) and increased BDNF expression in specific regions of the hippocampus compared to rats exposed to trauma and fed a normal diet. The results of this study provided initial evidence that 30 days of β-alanine supplementation may increase resistance to mTBI-like responses in exposed animals and may provide additional support for a possible antioxidant role of elevated carnosine levels.
BIBLIOGRAPHY
- Bagchi, D., Nair, S., & Sen, C. K. (Eds.). (2018). Nutrition and enhanced sports performance: muscle building, endurance, and strength. Academic Press.
- Hoffman, J. R., Zuckerman, A., Ram, O., Sadot, O., Stout, J. R., Ostfeld, I., et al. (2017). Behavioral and inflammatory response in animals exposed to a low-pressure blast wave and supplemented with β-alanine. Amino Acids, 49, 871–886.
- Hoffman, J. R., Varanoske, A., & Stout, J. R. (2018). Effects of β-alanine supplementation on carnosine elevation and physiological performance. In Advances in food and nutrition research (Vol. 84, pp. 183-206). Academic Press.
- Trexler, E. T., Smith-Ryan, A. E., Stout, J. R., Hoffman, J. R., Wilborn, C. D., Sale, C., et al. (2015). International society of sports nutrition position stand: Beta-alanine. Journal of the International Society of Sports Nutrition, 12, 30.
- Murakami, T., & Furuse, M. (2010). The impact of taurine-and beta-alanine-supplemented diets on behavioral and neurochemical parameters in mice: Antidepressant versus anxiolytic-like effects. Amino Acids, 39, 427–434.
AUTHOR
Marcos Rueda Córdoba
- Graduate in Human Nutrition and Dietetics (UGR) and Official Master's Degree in Nutrition in Physical Activity and Sport (UCAM). Anthropometrist ISAK I, Creator of content and specialized courses in sports nutrition through online and face-to-face platforms. Lecturer at Grupo San Valero (Universidad San Jorge, Zaragoza)
- Nutrition consultation in person in Granada and online
