Creatine is an amino acid derivative (from arginine, glycine, and methionine) that is available in meats and fish and is synthesized in the liver, pancreas, and kidneys. Because creatine plays a critical role in ATP metabolism, creatine supplementation theoretically increases the bioavailability of phosphocreatine (PCr) in skeletal muscle cells, enhancing muscle performance. Having more available PCr facilitates the resynthesis of ATP to provide energy for brief, high-intensity exercise (e.g., resistance training). This results in a better match between ATP supply and demand. PCr may also increase the force of muscular contraction and delay fatigue during anaerobic exercise by buffering the intracellular hydrogen ions formed with lactate production.
The amount of creatine in human skeletal muscle normally ranges between 90 and 160 mmoles per kilogram of muscle in dry muscle. The effectiveness of creatine supplementation appears to vary with these baseline levels; the greatest advantage is observed in those with the lowest baseline levels. Although anecdotal evidence suggests that increased muscle cramping occurs with creatine supplementation, no serious side effects have been scientifically verified.
More than two dozen studies have reported that creatine supplementation enhances the development of lean body mass and muscle strength in response to resistance training. This increased muscle strength and mass could be attributable to several mechanisms, including an effect on protein metabolism, synthesis, and transcriptional expression at the genetic level. Research supports this theory: Five-day oral dosages of 20 grams per day have been shown to increase muscle creatine availability by 20 percent and significantly accelerate PCr regeneration after intense muscle contraction. Significant enhancement of performance – both brief, high-intensity work and total time to exhaustion – has been observed in male athletes using creatine supplementation of 20 to 30 grams per day.
Long-term creatine supplementation has been shown to enhance the progress of muscle strength during resistance training in sedentary males and females. Twelve weeks of creatine supplementation enhances fat-free mass, physical performance, and muscle morphology in healthy men in response to heavy resistance training. This likely is attributable to higher-quality training sessions. Short-term creatine loading results in enhancement of both maximal strength and weightlifting performance. Therefore, part of the ergogenic (performance enhancing) effect of creatine shown in studies is likely attributable to this acute effect and part likely is attributable to the ability to train with higher workloads (although the relative contributions of these mechanisms remain unclear).
Branched-Chain Amino Acids
Branched-chain amino acids include three essential amino acids (leucine, isoleucine, and valine) that are needed to maintain muscle and preserve glycogen. Branched-chain amino acids are found naturally in foods such as dairy products, meat, whey, and eggs. Because of their role in muscle metabolism, branched-chain amino acids sometimes are isolated and consumed as a dietary supplement. In a study of branched-chain amino acid supplementation during four weeks of resistance training overreaching (defined earlier), initial reductions in strength and power were attenuated.
Carnitine is synthesized in the human liver and kidneys and is found in meats and dairy products. L-carnitine (the supplement form of carnitine) is thought to benefit exercise performance because it spares muscle glycogen by increasing free fatty acid transport across mitochondrial membranes, thus increasing fatty acid oxidation and use for energy. L-carnitine also appears to delay fatigue by reducing muscle lactate accumulation associated with exercise.
Some studies have shown a decreased respiratory exchange ratio – the ratio of carbon dioxide expired to oxygen consumed at the level of the lungs – with L-carnitine supplementation (2-6 grams per day) during exercise, suggesting that fatty acids rather than carbohydrate were used for energy. However, another study measuring muscle glycogen and lactate concentrations directly through biopsy and serum analysis failed to demonstrate any glycogen-sparing effect or reductions in lactate concentrations while supplementing with 6 grams per day of L-carnitine. Supplementation of L-carnitine L-tartrate (a source of L-carnitine when split into L-carnitine and L-tartaric acid in the body) in healthy men for three weeks has been shown to reduce the amount of exercise-induced muscle tissue damage, leave a greater number of receptors intact for hormonal interactions, reduce the level of muscle soreness, and result in less of an increase in markers of muscle damage and free radicals (atoms or compounds with unpaired electrons, which are thought to cause cellular damage).
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