Arginine

Summary (The Good, The Bad, and all other Essential Benefits/Effects/Facts Information)

L-Arginine is a conditionally essential amino acid in which its need for is increased during periods of disease/sickness and relative deficiency such as diabetes.

It is generally touted as a vasodilator (increases blood vessel circumference) and thus a Muscle Builder, and is thought to do so via increasing Nitric Oxide (NO) synthesis. However, due to a poor uptake rate in the intestines and excessive metabolism in the liver, very little L-arginine makes it to the muscles and peripheral tissue. Increasing the dose does not work in this scenario as high doses of L-arginine cause gastric distress and diarrhea. For muscle building, the similar compound L-Citrulline is a better alternative.

L-Arginine does have benefit for health though, as it can increase the production of urea (ammonia waste product from protein) and the filtration rate in the kidneys, leading it to be a good diabetic health compound as it aids kidney function and may prevent against excessive acidity which could contribute to ketoacidosis.

Also Known As

L-Arginine

Is a Form of

• Health Support
• Amino Acid Supplement

Goes Well With

Anionic salts such as Alpha-ketoglutarate

How to Take (recommended dosage, active amounts, other details)

Benefits have been seen in regards to an oral dose between 5 and 10g of L-arginine for increasing growth hormone levels. Doses up to 20g are well tolerated, but higher doses may cause diarrhea.

Things to Note

Arginine is non-stimulatory.

Caution Notice (just some FYI - if needed)

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Detailed Summary

1. Roles of Arginine In Vivo
2. Regulation of Arginine Metabolism
3. Arginine and Physical Performance
4. Arginine and Nitric Oxide
5. Pairing with Alpha-ketoglutarate and Other Salts
6. Gastrointestinal Complications
7. Arginine and Fat-Loss
8. Arginine as an Anxiolytic
9. Arginine and Wound Healing
10. Arginine Safety Profile

Edit1. Roles of Arginine In Vivo

Arginine has many wide reaching roles in the body, including:

• Acting as a precursor for Glutamine and proline synthesis
• Acting as a potent secretagogue
• Stimulating production of NO (Nitric Oxide) and Agmatine
• Stimulating Ureagenesis and Gluconeogenesis

Edit2. Regulation of Arginine Metabolism

Arginine is a highly regulated amino acid, and as such supplemental arginine may not always result in changes in the areas of the body arginine mediates.

Arginine is first met with intestinal and splanchic metabolism, in which a degree of arginine is consumed by enterocytes or interconverted into L-citrulline or L-ornithine. Aside from the liver utilizing arginine to a high degree, intestinal uptake of arginine is also poor under normal conditions and increased during conditions of disease^[1] It seems that a minimal amount of L-Arginine gets to systemic tissue in relation to other amino acids in the Urea cycle, as supplemental L-Ornithine achieves twice the serum concentration relative to L-Arginine and L-Citrulline 9.3 times the amount. This seems directly related to the degree of hepatic and intestinal metabolism.^[2][3][4]

Despite complications with splanchic metabolism, arginine does enter peripheral tissue. A 10g load in a fasted state has been noted to increase blood arginine levels 3-fold.^[5]

After first pass metabolism, arginine is taken up by a wide range of tissues such as endothelial cells, fibroblasts, and immune cells. Transport to periphery tissues typically occurs as the liver converts L-arginine into L-citrulline, and then the kidney uptakes serum L-citrulline and converts it back into L-arginine.^[6] This avoids hepatic build-up of L-arginine. The vast majority of arginine for peripheral tissues comes vicariously through intrinsic L-citrulline conversion to Argininosuccinic Acid via the enzyme Argininosuccinate synthetase and then to L-Arginine via Argininosuccinate lysase in the proximal convoluted tubules.^[7]

Dietary arginine accounts for 40-60% of serum arginine, as evidenced by an equivalent drop during arginine free periods. The rate of conversion of L-citrulline into L-arginine seems unaffected by dietary intake.^[8]

Edit3. Arginine and Physical Performance

Supplemental Arginine in vivo seems to have mixed results.^[9] Numerous studies show no results with arginine supplementation^{[10][11][12][13]} whereas some have shown either direct benefits.^[14][15][16]

The benefits of Arginine metabolism appear to be more related to insulin sensitivity and increasing serum growth hormone levels, rather than a Nitric Oxide dependent increasing of exercise performance.

Edit4. Arginine and Nitric Oxide

Arginine is the main precursor for Nitric Oxide, of which is a potent vasodilator.

Supplementing with L-arginine only seems to aid in nitric oxide synthesis during scenarios or disease states in which the body is deficient in L-arginine such as diabetes or some forms of hypertension. In healthy subjects increased plasma L-arginine does not result in increased NO synthesis rates by itself.^{[17][18][19][20]}

Edit5. Pairing with Alpha-ketoglutarate and Other Salts

Arginine seems to have increased intestinal uptake when paired with a salt such as alpha-ketoglutarate.^[21]

The mechanism by which it works should extend to the chloride salt (Arginine hydrochloride) as well as the salts aspartate, pyroglutamate, and malate as evidenced by experiments with L-ornithine.^[22]

Edit6. Gastrointestinal Complications

L-arginine has a fairly poor gastrointestinal uptake rate. It also may act as an absorbagogue, releasing water and electrolytes into the gut lumen via NO stimulation and inducing gastric upset and diarrhea.^[1]

Most gastrointestinal side effects occurred with acute doses over 9g in healthy subjects, with a higher number for those with diabetes or other disease states due to higher intestinal uptake rates of L-arginine in these states.

Edit7. Arginine and Fat-Loss

L-Arginine is recently being reviewed for its effects in fat loss. Although not overly significant acutely it holds promise in altering fat homeostasis markers by various pathways, especially in diabetic patients.^[23]

Edit8. Arginine as an Anxiolytic

L-Arginine, when paired with L-Lysine, shows promise in reducing anxiety^[24] when both amino acids are administered in doses of 2.5-3g per day. There is limited but promising evidence for this compound in this regard.^[25][26]

Edit9. Arginine and Wound Healing

Arginine has been observed to accelerate lympocyte (immune cell) proliferation and wound healing rates.^[27][28] This mechanism appears to be mediated via activation of NO-synthase^[29][30] and has been seen with another intermediate of Arginine metabolism, Ornithine.^[31]

Edit10. Arginine Safety Profile

The observed safety limit, the highest dose in which one can be relatively assured that no side effects will occur over a lifetime, has been suggested at being 20g of arginine a day in supplemental form (above food intake).^[32] Higher doses have been tested and well tolerated, but no evidence exists to suggest their safety in all populations across a lifetime.

Scientific Support & Reference Citations

Pharmacokinetics of arginine and related amino acids

References

1. Adverse Gastrointestinal Effects of Arginine and Related Amino Acids
2. Morris SM Jr. Recent advances in arginine metabolism. Curr Opin Clin Nutr Metab Care. (2004)
3. De Bandt JP, et al. Metabolism of ornithine, alpha-ketoglutarate and arginine in isolated perfused rat liver. Br J Nutr. (1995)
4. Curis E, et al. Almost all about citrulline in mammals. Amino Acids. (2005)
5. Tangphao O, et al. Pharmacokinetics of intravenous and oral L-arginine in normal volunteers. Br J Clin Pharmacol. (1999)
6. Mathematical modeling of citrulline/arginine renal conversion
7. Crenn P, Cynober L. Effect of intestinal resections on arginine metabolism: practical implications for nutrition support. Curr Opin Clin Nutr Metab Care. (2010)
8. Plasma arginine and citrulline kinetics in adults given adequate and arginine-free diets
9. Álvares TS, et al. L-Arginine as a potential ergogenic aid in healthy subjects. Sports Med. (2011)
10. Abel T, 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)
11. Colombani PC, et al. Chronic arginine aspartate supplementation in runners reduces total plasma amino acid level at rest and during a marathon run. Eur J Nutr. (1999)
12. Liu TH, 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)
13. Fahs CA, Heffernan KS, Fernhall B. Hemodynamic and vascular response to resistance exercise with L-arginine. Med Sci Sports Exerc. (2009)
14. Schaefer A, et al. L-arginine reduces exercise-induced increase in plasma lactate and ammonia. Int J Sports Med. (2002)
15. Lucotti P, et al. Beneficial effects of a long-term oral L-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients. Am J Physiol Endocrinol Metab. (2006)
16. McConell GK. Effects of L-arginine supplementation on exercise metabolism. Curr Opin Clin Nutr Metab Care. (2007)
17. Lekakis JP, et al. Oral L-arginine improves endothelial dysfunction in patients with essential hypertension. Int J Cardiol. (2002)
18. Nitric oxide precursors and congenital heart surgery: A randomized controlled trial of oral citrulline
19. L-Arginine and Atherothrombosis
20. Preli RB, Klein KP, Herrington DM. Vascular effects of dietary L-arginine supplementation. Atherosclerosis. (2002)
21. Campbell B, et al. Pharmacokinetics, safety, and effects on exercise performance of L-arginine alpha-ketoglutarate in trained adult men. Nutrition. (2006)
22. Cynober L, et al. Action of ornithine alpha-ketoglutarate, ornithine hydrochloride, and calcium alpha-ketoglutarate on plasma amino acid and hormonal patterns in healthy subjects. J Am Coll Nutr. (1990)
23. McKnight JR, et al. Beneficial effects of L-arginine on reducing obesity: potential mechanisms and important implications for human health. Amino Acids. (2010)
24. Lakhan SE, Vieira KF. Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review. Nutr J. (2010)
25. Jezova D, et al. Subchronic treatment with amino acid mixture of L-lysine and L-arginine modifies neuroendocrine activation during psychosocial stress in subjects with high trait anxiety. Nutr Neurosci. (2005)
26. Smriga M, et al. Oral treatment with L-lysine and L-arginine reduces anxiety and basal cortisol levels in healthy humans. Biomed Res. (2007)
27. Barbul A, et al. Arginine enhances wound healing and lymphocyte immune responses in humans. Surgery. (1990)
28. Shi HP, et al. Supplemental L-arginine enhances wound healing in diabetic rats. Wound Repair Regen. (2003)
29. Debats IB, et al. Role of arginine in superficial wound healing in man. Nitric Oxide. (2009)
30. Shi HP, et al. Supplemental dietary arginine enhances wound healing in normal but not inducible nitric oxide synthase knockout mice. Surgery. (2000)
31. Shi HP, et al. Effect of supplemental ornithine on wound healing. J Surg Res. (2002)
32. Shao A, Hathcock JN. Risk assessment for the amino acids taurine, L-glutamine and L-arginine. Regul Toxicol Pharmacol. (2008)

Last Updated: Mar 5, 2012 18:36:09