Where is this standard recommendation posted at strategic?
Sorry, I was off from AM for about a week!
Here is an abridged source:
Citrulline Malate
By Elzi Volk
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What causes fatigue?
Many factors can contribute to fatigue in varying degrees during endurance running: decreases in blood glucose, dehydration, increased body temperature, and depletion of muscle glycogen. When high intensity exercise demands more energy than the individual’s maximal aerobic power, anaerobic metabolism compensates by converting muscle glycogen to glucose and providing ATP. As intensity and distance increase, muscle high energy phosphates (ATP and phosphocreatine) decrease, and lactate and hydrogen ions increase. Fatigue develops as a consequence. To avoid fatigue, adequate tissue levels of ATP and phosphocreatine must be maintained, and lactic acid and hydrogen ions must be continually removed.
Creatine in muscle cells provides the basic substrate for phosphocreatine, which buffers rapid fluctuations of ATP. However, other substances are required to not only propel forward the reactions that synthesize ATP, but also to clean up the by products. During intense muscular activity lactic acid is produced, which dissociates into lactate and hydrogen ions. Elevated levels of these by-products can depress the force output of muscle.
During intense exercise, the breakdown of proteins produces ammonia in muscle that can accumulate in the cells or is released into the circulation where it travels to the liver. When ammonia accumulates locally it becomes toxic, interfering with the activity of important enzymes and increasing the permeability of the cell to damaging ions. Human adults excrete approximately 20 grams of urea per day. If this rate decreases, ammonia accumulates in the blood to toxic levels. Normally, blood ammonia is very low (0.5 mg/l). Only two to three times this level is required to produce toxic symptoms, including memory loss, psychosis, tremors, and ability to concentrate.
To avoid accumulation in muscle and liver cells a series of reactions known collectively as the ‘urea cycle’ converts ammonia into a waste product. The metabolism of nitrogen and carbon dioxide produces urea that is then transported to the kidneys for excretion in urine.
In the mitochondria, the ‘power house’ of cells, ammonia combines with carbon dioxide and ornithine to form an amino acid called citrulline. Citrulline is then transported out of the mitochondria into the cytoplasm where it is then converted to yet another amino acid called arginine. Thus citrulline is essential to detoxify and remove ammonia from muscle and liver cells.
Arginine serves as a precursor for creatine, but is mostly known as the precursor for nitric oxide (NO2), a key signaling molecule. The mechanism of action by Viagra, the popular drug for treating impotence in men, is increased NO2 levels mediating relaxation of smooth muscle in blood vessels. Additionally, NO2 acts as an anti-oxidant alleviating oxidative stress.
Supplementing the diet with arginine has had limited success in increasing its levels and NO2 in tissues. Studies have shown that the rate of synthesis of arginine in the body is unaffected by intake of dietary arginine. One reason may be the short half-life (one hour) of dietary arginine. Also, dietary arginine is used mostly in the liver, where uptake of arginine is rapid after eating a meal containing about 30-50 grams of protein (about 1-2 grams of arginine). Instead, dietary supplementation with arginine’s precursor, citrulline, has been shown to be more efficient in increasing tissue arginine and NO2 levels. Therefore, citrulline serves as a substrate for energy precursors.
What is citrulline malate and what does it do?
Citrulline is a non-essential amino acid and plays a role in nitrogen balance and metabolic processes. Although not a component of most proteins in the body, citrulline is found in some specialized proteins in the hair, skin and neural cells. It is primarily synthesized from glutamine in the intestines but is also found naturally in trace amounts in some foods.
Citrulline supplied by the diet is efficiently absorbed from the stomach and enters the blood via the major vein draining the digestive system that empties into the liver. Much of it bypasses uptake in the liver and is then circulated for distribution to the kidneys, brain, muscle and other tissues for conversion to arginine.
Supplemental citrulline malate is a salt form of the amino acid. The malate, or malic acid, is found in fruits such as apples and enhances the effects of citrulline. Malic acid takes part in aerobic cellular respiration where oxygen and a carbon compound (acetyl Co-A) are used to produce immediate energy and CO2 in the mitochondria of the cell. This is called the Kreb’s cycle. Malate conditions the recycling of lactate and pyruvate promoting efficient energy production and protecting muscles from fatigue.
How does citrulline malate benefit the athlete?
Citrulline malate improves aerobic performance and capacity by influencing lactic acid metabolism and reducing fatigue. Studies in Europe, where citrulline malate has been used for over 20 years, demonstrate reduction in mental and physical fatigue and exhaustion in geriatric and post-surgery patients. Laboratory studies with rats and microbes support the results seen in humans. Administration of citrulline malate to animals protected against acidosis and ammonia poisoning. In a microbial model, malate accelerated the clearance of ammonium and citrulline facilitated lactate metabolism. The results suggest a synergistic action of the complex.
Supplementation of citrulline malate to humans has shown promising results. French researchers reported in several human studies that blood lactate concentrations were reduced and ammonia elimination was increased after physical exertion. Rapid recovery from physical effort correlated to the disappearance of lactate from blood after performance at a high level of acidosis suggesting an essential role in acid-base balance.
Effects on metabolism in the finger flexor muscles after 15 days of citrulline malate supplementation were determined during exercise. Subject reports of significant reduction in fatigue were supported by an increase in the rate of oxidative ATP and energy production.
Two groups of basketball players were supplemented with citrulline malate for over 13 days with two different dosages. The group with the higher dosage had significant improvements in maximal workload during an exercise test on a cycle ergometer. Although fewer improved on the second maximal cycling test, the authors concluded that citrulline malate may improve aerobic performance.
What dosages are recommended?
The effective dosages commonly seen in the literature is three to four grams twice daily. Citrulline malate is reported as well tolerated and rapidly acting. Clinical results have been detected by the third to fifth day after start of administration.
Overall, studies suggest that citrulline malate supplementation can boost athletic performance and enhance recovery by eliminating the amino acid breakdown products of protein metabolism and augmenting the detoxifying capacity of liver cells in removal of ammonium and lactate from the blood.
References
Bendahan D, Mattei JP, Ghattas B, et al. 2002. Citrulline/malate promotes aerobic energy production in human exercising muscle. Br J Sports Med; 36(4):282-9.
Briand J, Blehaut H, Calvayrac R, Laval-Martin D. 1992. Use of a microbial model for the determination of drug effects on cell metabolism and energetics: study of citrulline-malate. Biopharm Drug Dispos; 13(1):1-22.
Callis A, Magnan de Bornier B, Serrano JJ, et al. 1991.Activity of citrulline malate on acid-base balance and blood ammonia and amino acid levels. Study in the animal and in man. Arzneimittelforschung; 41(6):660-3.
Fornaris E, Vanuxem J, Duflot P, et al. 1984. [Pharmacological/clinical approach of citrulline malate activity: study of blood lactate levels during standardized muscular exercise]. Gazette Medicale, 91(11):125-128.
Goubel F, Vanhoutte C, Allaf O, et al. 1997. Citrulline malate limits increase in muscle fatigue induced by bacterial endotoxins. Can J Physiol Pharmacol; 75(3):205-7.
Hartman WJ, Torre PM, Prior RL. 1994. Dietary citrulline but not ornithine counteracts dietary arginine deficiency in rats by increasing splanchnic release of citrulline. J Nutr; 124(10):.
Janeira MA, Santos PJ. 1998. Citrulline malate effects on the aerobic-anaerobic threshold and in post-exercise blood lactate recovery. Med Sci Sports Exerc; 30(5 supp): abstract 881.
Vanuxem D, Duflot JC, Prevot H, et al. 1990. [Influence of an anti-astenia agent, citrulline malate, on serum lactate and ammonia kinetics during a maximum exercise test in sedentary subjects]. Sem Hop Paris; 66(9):477-481.
Waugh WH, Daeschner CW, Files BA, et al. 2001. Oral citrulline as arginine precursor may be beneficial in sickle cell disease: early phase, two results. J Natl Med Assoc; 93(10):363-71.
