<body><h1>Citrulline Malate</h1><p><br></p><p> syn. citrulline malic acid salt syn. L-citrulline-DL-malate </p><p> </p><p> image </p><h2> Description: </h2><p> Citrulline malate (CtM) is the malic acid salt of citrulline, a naturally occurring nonessential alpha amino acid. Citrulline is not used directly in the assembly of tissue proteins like the 20 common amino acids, but instead is involved with other important functions including metabolic byproduct removal and cellular energy metabolism. Citrulline is found in many fruits, though its levels are particularly high in watermelon. In Europe, citrulline malate is sold as a medicinal product under the Stimol brand name (Gentilly, France). It is widely used to treat fatigue, and as a general energy tonic. In the United States and other regions with strong sports nutrition markets, citrulline malate is commonly sold to improve muscle endurance and aerobic exercise performance.</p><p> image</p><p> To understand the mode of action for citrulline malate, we can examine its two constituents. Citrulline serves as an intermediary in the urea cycle, which is necessary for the excretion of ammonia, a toxic byproduct of anaerobic metabolism. Citrulline is also a precursor to arginine, and may have some role in vasodilation.224 This action may help increase blood flow to the muscles, facilitating oxygen and nutrient delivery. Malic acid may also provide an additional active component, as an intermediary in the citric acid (Krebs) cycle. This system is vital to aerobic metabolism, and facilitates the conversion of proteins, fats, and carbohydrates into useable cellular energy (ATP). The full spectrum of activity for citrulline malate likely involves the interaction of both of these components. </p><p> Many of the beneficial properties of citrulline malate are well supported. For example, CtM has been clearly documented to help combat general fatigue in humans.225 It may also help stabilize the acid/base balance,226 which could help the muscles maintain an optimal pH range for performance. The exercise-induced buildup of ammonia and lactate are also significantly reduced with the supplementation of citrulline malate 227 (both ammonia and lactate are implicated in exercise fatigue). CtM supplementation may also increase cellular ATP levels, the main form of stored cellular energy. Again, this could allow citrulline malate supplementation to improve exercise performance by helping to maintain optimal energy production. Citrulline malate appears to be a promising ergogenic supplement in both aerobic and anaerobic conditions.</p><h2> Promoted Benefits:</h2><p> Citrulline malate is promoted to increase energy, improve aerobic and anaerobic exercise endurance, and support vasodilation. </p><p> </p><h2> Clinical Studies: </h2><p> Citrulline malate has been shown in human placebo-controlled studies to improve metabolic markers (ammonia, lactate) often linked to positive changes in body composition or performance. It has a Clinical Support Rating of 3 (3/5).</p><p> The most widely referenced study of citrulline malate and exercise involved its supplementation by a group of inactive (sedentary) male subjects complaining of fatigue.228 Subjects consumed 6 g of citrulline malate per day for a period of 15 days. Exercise was conducted for evaluations of metabolic response at various points in the experiment, which involved finger flexions for 1.5-second intervals while lifting a 6 kg weight. Subjects taking CtM noticed a significant reduction in perceived fatigue, an increase in oxidative ATP production during exercise (+34%), and an increase in the rate of phosphocreatine replenishment (+20%) after exercise compared to their unsupplemented measurements. These results suggest citrulline malate can increase energy production during exercise. This study was not placebo-controlled. These studies suggest that citrulline malate may improve exercise performance, especially with regard to anaerobic endurance-type activities. Further research is needed to confirm significant ergogenic value with regular supplementation by experienced exercising individuals.</p><p> The above study adds support to two prior placebo-controlled investigations involving the use of citrulline malate by sedentary individuals. These studies demonstrated significant reductions in serum lactate and ammonia levels when citrulline malate was supplemented prior to exercise.229,230 Although performance measures were not taken as part of these investigations, the results would likely cause some attenuation of normal exercise fatigue.</p><h2> Empirical Evidence: </h2><p> Citrulline malate is widely available as a stand-alone nutritional supplement. The feedback on its use as a sport supplement tends to be positive. A majority of users seem to report noticeable benefits with regard to energy and muscle endurance. In aerobic/endurancetype activities, it seems to allow for high-level performance for longer periods. Although less consistent, many involved in resistance training programs also find CtM to be of value, reporting an increase in anaerobic muscle endurance (generally equating to more sets and/or reps during training). A minority of users do fail to notice even minor benefits to using citrulline malate. It is unknown if this is due to the influence of training or dietary factors, or individual insensitivity to CtM. Citrulline malate has an Empirical Evidence Rating of 4 (4/5).</p><p><br></p><h2> Effective Dosage: </h2><p> Based on clinical studies, a dosage of 6 g per day is recommended. </p><h2> Side Effects / Safety: </h2><p> Citrulline malate was well tolerated during clinical studies, with no significant side effects.</p><p> </p><p> </p><p> </p></body>
