Carnosine (beta-alanyl-L-histidine) is the dipeptide that is one of the most important intracellular buffers in the muscle — it is synthesised in the muscle and the brain from the beta-alanine and the histidine by the carnosine synthase enzyme, and it is the most abundant intracellular buffer in the skeletal muscle (at concentrations of 10-50 mM), where it accounts for approximately 10-20% of the total buffering capacity of the muscle. The carnosine is a potent buffer — it accepts the hydrogen ions (H+) that are generated during the high-intensity exercise (when the ATP is hydrolysed and the lactic acid is produced), and it thereby prevents the metabolic acidosis, the muscle fatigue, and the performance decline that are associated with the high-intensity exercise. The carnosine also has additional important functions in the muscle — it is an antioxidant, it chelates the heavy metals (copper, zinc), it protects the muscle proteins from the glycation, and it acts as a neurotransmitter or a neuromodulator in the brain. Without adequate carnosine and intracellular buffering, the muscle acids accumulate during the exercise, the pH drops, the muscle fatigue develops, and the exercise performance is impaired — the hallmark of the carnosine deficiency and of the low buffering capacity states that are associated with the high-intensity exercise, the metabolic syndrome, and the sarcopenia. The typical dietary carnosine intake from the red meat, the poultry, and the fish is approximately 50-200mg daily, and the endogenous synthesis from the beta-alanine and the histidine is the primary source of the carnosine in the muscles — making the beta-alanine (the rate-limiting precursor of the carnosine synthesis) one of the most important and most effective ergogenic aids for the improvement of the exercise performance and for the delay of the muscle fatigue.
Carnosine and the High-Intensity Exercise Performance
Carnosine supports the high-intensity exercise performance primarily through its role as an intracellular buffer — it accepts the H+ ions that are generated during the intense muscle contraction, and it thereby prevents the drop in the intracellular pH (from approximately 7.0 at rest to approximately 6.5 during the intense exercise) that is the primary cause of the muscle fatigue and the force reduction during the high-intensity exercise. The carnosine is particularly effective as a buffer because it has a pKa of approximately 6.9 (which is close to the physiological pH and to the pH range that is achieved during the intense exercise), and it is therefore one of the most effective and most appropriate buffers for the muscle intracellular environment. The carnosine also enhances the calcium sensitivity of the muscle fibres (through its action on the troponin C), and this effect further contributes to the improved muscle contractility and the reduced fatigue during the high-intensity exercise. The combination of the intracellular buffering and the calcium sensitisation makes the carnosine one of the most effective and most specific ergogenic aids for the high-intensity exercise performance (such as the 100-400m sprints, the jumping, the high-intensity resistance training), and it explains why the beta-alanine supplementation (which increases the carnosine levels in the muscle by 30-80%) has been consistently shown to improve the exercise performance in multiple sports and in multiple exercise modalities.
The clinical importance of the carnosine for the exercise performance is underscored by the observation that the beta-alanine supplementation significantly improves the high-intensity exercise performance. A meta-analysis of 15 RCTs in over 500 athletes found that the beta-alanine supplementation at 3-6g daily for 4-12 weeks significantly improved the exercise capacity (by 5-10%, as measured by the time to exhaustion tests) and the exercise performance (by 3-7%, as measured by the 400m sprint time and the multiple set resistance training volume) — demonstrating the potent and clinically meaningful ergogenic effect of the beta-alanine (through the carnosine elevation) in athletes.
Practical Application
For general carnosine support for the exercise performance and for the muscle buffering capacity, the evidence-based approach is to supplement with the beta-alanine at 3-6g daily (as the pure beta-alanine powder or as the beta-alanine combined with the other amino acids in the carnosine or the sarcosine, taken in divided doses of 1-2g to minimise the paraesthesia side effect). The beta-alanine should be taken consistently for at least 4-8 weeks before the full carnosine-elevating effect is observed (because the carnosine synthesis in the muscle is a slow process, and the carnosine levels increase gradually over the 4-8 weeks of the beta-alanine supplementation). The beta-alanine is generally well-tolerated with no significant adverse effects at the doses that are used for the exercise performance (up to 8g daily), though the high doses may cause the paraesthesia (a tingling sensation in the skin) in some individuals — this side effect is harmless and can be minimised by taking the beta-alanine in smaller divided doses throughout the day. For comprehensive carnosine support and exercise performance, beta-alanine pairs well with the creatine (which is the most effective and most widely used ergogenic aid for the strength and the power, and which works synergistically with the beta-alanine for the improvement of the high-intensity exercise performance and for the muscle gain — the combination of the beta-alanine and the creatine is one of the most effective and most evidence-based ergogenic aid combinations, and it is significantly more effective than either compound alone for the improvement of the exercise performance and for the increase of the muscle mass), with the caffeine (which is the most effective and most widely used stimulant for the exercise performance and which works synergistically with the beta-alanine for the improvement of the exercise capacity and for the reduction of the perceived exertion — the combination of the beta-alanine and the caffeine is one of the most effective combinations for the enhancement of the high-intensity exercise performance and for the delay of the muscle fatigue), with the sodium bicarbonate (which is another buffering compound that works synergistically with the beta-alanine for the enhancement of the buffering capacity and for the improvement of the high-intensity exercise performance — the combination of the beta-alanine and the sodium bicarbonate is one of the most effective combinations for the high-intensity exercise performance, particularly for the events that last 1-10 minutes), and with the L-histidine (which is the other precursor of the carnosine and which works synergistically with the beta-alanine for the carnosine synthesis — the combined supplementation of the beta-alanine and the L-histidine is more effective than the beta-alanine alone for the carnosine elevation and for the improvement of the muscle buffering capacity).
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