Metabolic Precursors of l-Arginine Supplementation in Sports: A Focus on l-Citrulline and l-Ornithine

Abstract

Exercise induces rapid adenosine triphosphate (ATP) consumption in muscles, resulting in energy deficiency, an important factor in fatigue (Sahlin et al., Acta Physiol Scand 162:261–266, 1998). Moreover, during intense exercise, there is an augmented production of ammonia and inosine monophosphate (IMP) in exercised muscle. The accumulation of ammonia is very toxic for the organism and has to be eliminated in the form of urea through the urea cycle (Meneguello et al., Cell Biochem Funct 21:85–91, 2003). Thus, the effect of supplementation by l-citrulline and l-ornithine, which are intermediates of the urea cycle and metabolic precursors of l-arginine, on l-arginine availability, ammonia detoxification and nitric oxide (NO) synthesis from l-arginine, a substrate for nitric oxide synthases (NOS), has been investigated (Fig. 24.1). l-Arg is a conditionally essential amino acid during periods of rapid growth, in response to a traumatic or pathologic insult (Paddon-Jones et al., J Nutr 134:2888S–2894S, 2004; Witte and Barbul, Wound Repair Regen 11:419–423, 2003), or during exercise (Alvares et al., Nutr Res 34:31–39, 2014; Linden et al., Med Sci Sports Exerc 43:1626–1634, 2011), and the demand for l-arginine may not be fully met by de novo synthesis and normal dietary intake alone. The demands for l-arginine in physically active subjects are increased with respect to healthy individuals in order to satisfy the increased protein and creatine turnover and urea as well as NO production associated to acute exercise, but the dietary and de novo synthesis of l-arginine also increases l-arginine availability to meet l-arginine demands in active people (Fig. 24.2). The balance of these processes could be modified in function of the intensity, duration, frequency and type of exercise. Plasma levels of l-arginine are used as a marker of the balance between availability and demand of l-arginine in different pathological and physiological situations (Luiking et al., Am J Physiol Endocrinol Metab 303:E1177–E1189, 2012). There is evidence that acute exercise decreases the plasma levels of l-arginine (Reid et al., J Int Soc Sports Nut 7:P22, 2010), but there is also evidence that the plasma levels of l-arginine are maintained after acute exercise (Luiking et al., Am J Physiol Endocrinol Metab 303:E1177–E1189, 2012; Tang et al., J Nutr 141:195–200, 2011). Diet supplementation with l-arginine or its metabolic precursors such as l-ornithine and l-citrulline has recently received much interest in sports science.