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L-Arginine

Click on the link below for a downloadable [PDF] of this information:
HPRC Dietary Supplement Classification System: L-Arginine

Background

L-Arginine

L-arginine is an amino acid that is necessary for the body to make protein and is found in red meat, poultry, fish, and dairy foods. It was studied in the early- and mid-1990s for its potential effects on wound healing, post-operative recovery, AIDS-related wasting, and angina pectoris, among other conditions. In the last decade, L-arginine has been marketed as an ergogenic (i.e., performance-enhancing) supplement, most notably in the “nitric oxide” class of supplements.

The ostensible ergogenic potential is through three mechanisms. First, the substrate L-arginine along with O2 is converted to citrulline and NO (nitric oxide). Nitric oxide causes vasodilation (widening of blood vessels), which can increase blood flow to tissues such as myocardial and skeletal muscle. The primary theory behind its use as an ergogenic aid is this vasodilation, which is thought to increase blood and nutrient flow to skeletal muscle.1,2 Second, L-arginine is a substrate in the pathway for the production of creatine, which is produced in the liver.1,2 (Creatine is covered in a separate monograph.) Third, under certain conditions, L-arginine is known to increase the release of endogenous growth hormone.1,3-8

Dose Range and Upper Limit

L-Arginine

Food and Nutrition Board DRI:

RDA/AI: Not relevant for this substance.

Upper Limit: Not relevant for this substance. Normal dietary intake approximates 5.4 g/100 g of mixed dietary proteins.9 The Observed Safe Level (OSL) for L-arginine is considered to be 20 grams per day in healthy adults.10

Doses Used In Randomized Clinical Trials: Most human studies on L-arginine have used doses of five to nine grams per day, or alternatively, 0.1 g/kg/day.6,11-17

Toxicology Data: No NOAEL (no observed adverse effect level) or LOAEL (lowest observed adverse effect level) could be determined9 for L-arginine.10

Benefits and Risks

L-Arginine

Evaluation of Potential Benefits

The primary putative ergogenic benefits of L-arginine are related to the performance of military tasks that call for increases in peak power, improvement in VO2max (a measure of aerobic fitness), and muscle endurance. Studies on L-arginine have been small and show mixed results for the ergogenic benefit of supplementation at the doses discussed above (see Dose Range and Upper Limit).3,11-13,16,18-20 Although there are some studies showing benefits of L-arginine supplementation vis-à-vis peak power and VO2max, other studies show none.14,17,18

Some studies have looked at the purported ergogenic mechanisms, including the release of endogenous growth hormone. Although L-arginine supplementation likely increases growth hormone secretion while a person is at rest, supplementation in conjunction with exercise does not appear to increase endogenous growth hormone more than exercise alone.4-8,19

There is little evidence to support the claim that L-arginine taken in conjunction with creatine increases the creatine found in skeletal muscle.15

Potential Detrimental Effects on…

Military Performance: Although L-arginine is a naturally occurring amino acid, it is known to cause abdominal bloating and diarrhea when taken as a supplement.21 In small studies, it has been shown to increase airway reactivity in asthmatic patients.22 As a potential vasodilator, it has the potential to affect mechanisms leading to vascular headaches.23

Military Survivability: L-arginine has been linked to several anecdotal reports of adverse events requiring medical attention. Such events have included palpitations, headache, and elevated blood pressure.23 Many of these adverse events were associated with multiple-ingredient products (i.e., “nitric oxide” products) in which L-arginine was one component, and it is uncertain as to which product or combination of products led to the adverse events.

Other Health Risks

L-arginine is often included in multiple-ingredient “nitric oxide” products, making it difficult to attribute adverse events and health risks to any one ingredient or combination of ingredients. Any combination product should be used with caution.

Interactions with Medications or Other Bioactive Substances

All interactions with L-arginine are theoretical and are related to L-arginine’s vasodilatory effects. L-arginine supplementation should be used with caution in patients taking:

Antihypertensive medications and nitrates. Vasodilation caused by L-arginine could have an additive effect with antihypertensives and could cause hypotension.22
Phosphodiesterase type 5 (PDE-5) inhibitors (e.g., sildenafil, vardenafil, tadalafil). Vasodilatory effects of PDE-5 inhibitors could in theory have additive effects with those of L-arginine.22
Triptan medications. Vasoconstrictor mechanisms of triptans could compete with the vasodilatory effects of L-arginine.24

Similar effects can occur when L-arginine is used in combination with supplements such as coenzyme Q-10 and fish oil.22

For details of these and other potential interactions, visit the Natural Medicines Comprehensive Database.22

Withdrawal Effects

None noted.

Concern and Benefit Estimate (see Dietary Supplement Risk Matrix)

Benefit potential: Low to Moderate
Risk (safety concern): Moderate
Classification score: 8

L-arginine supplements exceeding normal dietary intakes—used either singly or in combination dietary supplement products—have little proof of benefit with significant safety concerns.

References

L-Arginine

  1. Campbell BI, Bounty PML, Roberts M. The Ergogenic Potential of Arginine. Journal of the International Society of Sports Nutrition. 2004;1(2):35-8.
  2. Morris S. Enzymes of Arginine Metabolism. J. Nutr. 2004;134(10):2743S-7S.
  3. Campbell B, Roberts M, Kerksick C, Wilborn C, et al. Pharmacokinetics, safety, and effects on exercise performance of L-arginine alpha-ketoglutarate in trained adult men. Nutrition. 2006;22(9):872-81.
  4. Chromiak JA, Antonio J. Use of amino acids as growth hormone-releasing agents by athletes. Nutrition. 2002;18(7-8):657-61.
  5. Collier SR, Collins E, Kanaley JA. Oral arginine attenuates the growth hormone response to resistance exercise. J. Appl. Physiol. 2006;101(3):848-52.
  6. Fayh APT, Friedman R, Sapata KB, de Oliveira AR. Effect of L-arginine supplementation on secretion of human growth hormone and insulline-like growth factor in adults. Arq. Bras. Endocrinol. Metabol. 2007;51(4):587-92.
  7. Kanaley JA. Growth hormone, arginine and exercise. Curr. Opin. Clin. Nutr. Metab. Care. 2008;11(1):50-4.
  8. McConell GK. Effects of L-arginine supplementation on exercise metabolism. Curr. Opin. Clin. Nutr. Metab. Care. 2007;10(1):46-51.
  9. Panel on Micronutrients, Panel on the Definition of Dietary Fiber, Subcommittees on Upper Reference Levels of Nutrients, Subcommittee on Interpretation and Uses of Dietary Reference Intakes, et al. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). Washington, DC: Food and Nutrition Board, Institute of Medicine, National Academy of Sciences; 2005.
  10. Shao A, Hathcock JN. Risk assessment for the amino acids taurine, L-glutamine and L-arginine. Regul. Toxicol. Pharmacol. 2008;50(3):376-99.
  11. Bescos R, Gonzalez-Haro C, Pujol P, Drobnic F, et al. Effects of Dietary L-Arginine Intake on Cardiorespiratory and Metabolic Adaptation in Athletes. Int. J. Sport Nutr. Exerc. Metab. 2009;19(4):355-65.
  12. Fahs CA, Heffernan KS, Fernhall B. Hemodynamic and Vascular Response to Resistance Exercise with L-Arginine. Med. Sci. Sports Exerc. 2009;41(4):773-9.
  13. Jahangir E, Vita JA, Handy D, Holbrook M, et al. The effect of L-arginine and creatine on vascular function and homocysteine metabolism. Vascular Medicine. 2009;14(3):239-48.
  14. Koppo K, Taes YE, Pottier A, Boone J, et al. Dietary Arginine Supplementation Speeds Pulmonary VO2 Kinetics during Cycle Exercise. Med. Sci. Sports Exerc. 2009;41(8):1626-32.
  15. Little JP, Forbes SC, Candow DG, Cornish SM, et al. Creatine, Arginine alpha-Ketoglutarate, Amino Acids, and Medium-Chain Triglycerides and Endurance and Performance. Int. J. Sport Nutr. Exerc. Metab. 2008;18(5):493-508.
  16. Liu TH, Wu CL, Chiang CW, Lo YW, et al. No effect of short-term arginine supplementation on nitric oxide production, metabolism and performance in intermittent exercise in athletes. J. Nutr. Biochem. 2009;20(6):462-8.
  17. Tsai PH, Tang TK, Juang CL, Chen KWC, et al. Effects of Arginine Supplementation on Post-Exercise Metabolic Responses. Chin. J. Physiol. 2009;52(3):136-42.
  18. Abel T, Knechtle B, Perret C, Eser P, et al. Influence of chronic supplementation of arginine aspartate in endurance athletes on performance and substrate metabolism - A randomized, double-blind, placebo-controlled study. Int. J. Sports Med. 2005;26(5):344-9.
  19. Buford BN, Koch AJ. Glycine-arginine-alpha-ketoisocaproic acid improves performance of repeated cycling sprints. Med. Sci. Sports Exerc. 2004;36(4):583-7.
  20. Stevens BR, Godfrey MD, Kaminski TW, Braith RW. High-intensity dynamic human muscle performance enhanced by a metabolic intervention. Med. Sci. Sports Exerc. 2000;32(12):2102-8.
  21. Grimble GK. Adverse gastrointestinal effects of arginine and related amino acids. J. Nutr. 2007;137(6):1693S-701S.
  22. Jellin J, Gregory, PJ, eds. L-Arginine. Natural Medicines Comprehensive Database 2011; http://www.naturaldatabase.com.
  23. Prosser JM, Majlesi N, Chan GM, Olsen D, et al. Adverse effects associated with arginine alpha-ketoglutarate containing supplements. Hum. Exp. Toxicol. 2009;28(5):259-62.
  24. Tepper SJ. Drug Interactions in Headache: What to Watch for and Why. Information for Patients [web page]. 2008; http://www.achenet.org/resources/drug_interactions_in_headache_what_to_watch_for_and_why/. Accessed Oct 11, 2011.