Metabolically, L-arginine is integral in transporting, processing, and excreting nitrogen. Furthermore it serves as a much needed substrate for the synthesis of creatine and the potent vasodilator nitric oxide. The formation of nitric oxide (NO) from L-arginine requires an enzyme called nitric oxide synthase (NOS). Vascular endothelial cells (located on the inside of blood vessels) contain the eNOS isoform, which is a key player in vasodilation. Human skeletal muscle fibers contain eNOS and (neuronal) nNOS, with nNOS being expressed more so than eNOS. It has been suggested that nNOS is the form of nitric oxide synthase responsible for regulating exercise metabolism (McConell, 2007).
Benefits of L-arginine with acute supplementation
When L-arginine is supplemented in resting humans, it decreases total peripheral resistance through a substantial positive and dose-dependent impact on NO release. This decrease in vascular resistance is due to robust vasodilation that increases blood flow to peripheral tissues (e.g., skeletal muscle). Supplementation of L-arginine has been associated with health benefits such as, decreased resting mean arterial blood pressure, inhibited platelet aggregation, improvement of endothelium mediated vasodilation, and prevention of atherosclerosis (i.e., hardening arteries) (Bode-Boger et al., 1998). In addition, from a performance perspective, L-arginine supplementation at rest increases plasma growth hormone levels, norepinephrine and epinephrine concentrations, as well as insulin, glucagon, and prolactin levels (Bode-Boger et al., 1999;Maccario et al., 1997;Paolisso et al., 1997). In a recent investigation, McConell et al. observed that L-arginine infusion greatly increased glucose clearance during prolonged exercise in healthy, young, endurance trained men (McConell et al., 2006); they hypothesized that this metabolic effect was due to a L-arginine-induced increase in skeletal muscle NOS. In the same study, the researchers noted increased glucose release from the liver during exercise with L-arginine supplementation. The authors speculated that since L-arginine results in greater plasma glucose uptake (by skeletal muscle), this may be the signal for greater hepatic glucose release.
What does this mean to the athlete on a day-to-day basis?
- Increased blood flow to resting skeletal muscle, resulting in substantially greater post-workout clearance of metabolites and delivery of nutrients. This effect helps to speed recovery and increase in bioavailability of nutrients to trained tissues.
- Increased uptake of plasma glucose to skeletal muscle during exercise with L-arginine supplementation = greater energy utilization.
- Maintenance of healthy cardiovascular system
Significant support comes from a recent placebo controlled investigation where twenty resistance-trained men ingested L-arginine a-ketoglutarate (4 g, 3 times per day) for 8 weeks, while15 others were given a placebo. The researchers observed greater gains in bench-press strength and greater power during anaerobic (Wingate) peak power testing with L-arginine a-ketoglutarate supplementation (Campbell et al., 2006). In addition, it has been suggested that long-term supplementation of L-arginine improves insulin sensitivity by increasing skeletal muscle mitochondrial biogenesis (McConell, 2007); such an effect supports a mechanism for increased skeletal muscle glucose uptake and force generative capacity. Finally, researchers recently observed significantly augmented angiogenesis (new blood vessel growth) in the heart and skeletal muscle in rats that underwent 6 weeks of exercise training with L-arginine supplementation. Furthermore, the authors noted an increase in skeletal muscle and heart NOS expression (Suzuki, 2006).
What does this mean to the athlete on a month-to-month basis?
- L-arginine supplementation over the long-term conclusively increases strength and anaerobic power.
- Chronic L-arginine ingestion has the capacity to upregulate mitochondria (the energy "power-houses") in skeletal muscle, resulting in greater substrate utilization.
- L-arginine has been shown to increase the growth of blood vessels in skeletal muscle and the heart, resulting in greater capacity to deliver nutrients and remove metabolites during and after your workout.
- Over the long-term L-arginine supplementation seems to increase NOS expression which has the ability to increase energy utilization and NO dilatory capacity in skeletal muscle.
Bode-Boger SM, Boger RH, Galland A, Tsikas D, & Frolich JC (1998). L-arginine-induced vasodilation in healthy humans: pharmacokinetic-pharmacodynamic relationship. Br J Clin Pharmacol 46, 489-497.
Bode-Boger SM, Boger RH, Loffler M, Tsikas D, Brabant G, & Frolich JC (1999). L-arginine stimulates NO-dependent vasodilation in healthy humans--effect of somatostatin pretreatment. J Investig Med 47, 43-50.
Campbell B, Roberts M, Kerksick C, Wilborn C, Marcello B, Taylor L, Nassar E, Leutholtz B, Bowden R, Rasmussen C, Greenwood M, & Kreider R (2006). Pharmacokinetics, safety, and effects on exercise performance of l-arginine alpha-ketoglutarate in trained adult men. Nutrition 22, 872-881.
Maccario M, Oleandri SE, Procopio M, Grottoli S, Avogadri E, Camanni F, & Ghigo E (1997). Comparison among the effects of arginine, a nitric oxide precursor, isosorbide dinitrate and molsidomine, two nitric oxide donors, on hormonal secretions and blood pressure in man. J Endocrinol Invest 20, 488-492.
McConell GK (2007). Effects of L-arginine supplementation on exercise metabolism. Curr Opin Clin Nutr Metab Care 10, 46-51.
McConell GK, Huynh NN, Lee-Young RS, Canny BJ, & Wadley GD (2006). L-Arginine infusion increases glucose clearance during prolonged exercise in humans. Am J Physiol Endocrinol Metab 290, E60-E66.
Paolisso G, Tagliamonte MR, Marfella R, Verrazzo G, D'Onofrio F, & Giugliano D (1997). L-arginine but not D-arginine stimulates insulin-mediated glucose uptake. Metabolism 46, 1068-1073.
Suzuki J (2006). L-arginine supplementation causes additional effects on exercise-induced angiogenesis and VEGF expression in the heart and hind-leg muscles of middle-aged rats. J Physiol Sci 56, 39-44.