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Arginine is an amino acid found in many foods, including dairy products, meat, poultry, and fish. It plays a role in several important mechanisms in the body, including cell division, wound healing, removal of ammonia from the body, immunity to illness, and the secretion of important hormones.
The body also uses arginine to make nitric oxide, a substance that relaxes the blood vessels. Based on this, arginine has been proposed as a treatment for various cardiovascular diseases, including congestive heart failure and intermittent claudication, as well as impotence, female sexual dysfunction, and an unpleasant urinary condition called interstitial cystitis. Arginine's effects on immunity have made it useful as part of an "immune cocktail" given to severely ill hospitalized patients and also, possibly, for preventing colds.
-------------------------------------------------------------------------------- Requirements/Sources Normally, the body either gets enough arginine from food, or manufactures all it needs from other widely available nutrients. Certain stresses, such as severe burns, infections, and injuries, can deplete your body's supply of arginine. For this reason, arginine (combined with other nutrients) is used in a hospital setting to help enhance recovery from severe injury or illness. Arginine is found in dairy products, meat, poultry, fish, nuts, and chocolate. -------------------------------------------------------------------------------- Therapeutic Dosages A typical supplemental dosage of arginine is 2 to 3 g per day. For congestive heart failure, higher dosages ranging from 5 to 15 g have been used in trials. Warning: Do not try to self-treat congestive heart failure. If you have this condition, be sure to consult your physician before taking any supplements. -------------------------------------------------------------------------------- Therapeutic Uses Small double-blind studies suggest that arginine might be helpful for the treatment of several seemingly unrelated conditions that are, in fact, all linked by arginine's effects on nitric oxide: congestive heart failure, intermittent claudication, angina, impotence and sexual dysfunction in women. 1-6,8,9,40 NOTE: The first three conditions in this list are life-threatening. If you have angina, congestive heart failure or intermittent claudication, do not attempt to treat yourself with arginine except under physician's supervision. One preliminary, double-blind study suggests that arginine supplementation might help prevent colds.10 A small, double-blind, placebo-controlled study suggests that use of arginine (700 mg four times daily) may support transdermal nitroglycerin therapy for angina.44 Ordinarily, the drug nitroglycerin becomes less effective over time as the body develops a tolerance to it. However, arginine supplements appear to help prevent the development of tolerance. NOTE: Angina is too serious a disease for self-treatment. If you have angina, do not take arginine (or any other supplement) except on physicians advice. The results of one controlled (but not blinded) study in women suggest that arginine might help standard fertility therapy (in vitro fertilization) work better.17 However, studies in men have found no benefit.1116 A double-blind, placebo-controlled crossover trial of 10 individuals with Raynauds phenomenon failed to find arginine at 8 g daily effective for reducing symptoms.42 Weak evidence suggests that arginine might improve insulin action in people with type 2 (adult-onset) diabetes.18 Arginine has been tested as a treatment for interstitial cystitis, but thus far it has not been shown effective.7Preliminary double-blind studies have also failed to find arginine helpful for kidney failure,19asthma,45 or male infertility.46 There is some evidence that nutritional mixtures containing arginine may enhance recovery from major surgery, injury, or illness.20 -------------------------------------------------------------------------------- What Is the Scientific Evidence for Arginine? NOTE: The first three conditions in this list are life-threatening. If you have angina, congestive heart failure of intermittent claudication, do not attempt to treat yourself with arginine except under physician's supervision. Congestive Heart Failure Three small double-blind studies enrolling a total of about 70 individuals with congestive heart failure found that oral arginine at a dose of 5 to 15 g daily could significantly improve symptoms as well as objective measurements of heart function.21,22,23 Intermittent Claudication People with advanced hardening of the arteries, or atherosclerosis, often have difficulty walking due to lack of blood flow to the legs, a condition known as intermittent claudication. Pain may develop after walking less than half a block. In a double-blind study of 41 individuals, 2 weeks of treatment with a high dose of arginine improved walking distance by 66%; no benefits were seen in the placebo group or a low-dose arginine group.43 Good results were also seen in another study, although its convoluted design makes interpreting the results somewhat difficult.25 Angina A double-blind study of 25 individuals with angina pectoris found that treatment with arginine at a dose of 6 g per day improved exercise tolerance, but not objective measurements of heart function.26 A double-blind placebo-controlled crossover trial of 36 individuals with heart disease found that use of arginine (along with antioxidant vitamins and minerals) at a daily dose of 6.6 grams reduced symptoms of angina.40 Impotence In a double-blind trial, 50 men with problems developing an erection received either 5 g of arginine per day or placebo for 6 weeks.27 More men in the treated group experienced improvement in sexual performance than in the placebo group. A double-blind crossover study of 32 men found no benefit with 1500mg of arginine daily for 17 days.39 However, the lower dose of arginine as well as the shorter course of treatment may explain the discrepancy between these two studies. Arginine has also been evaluated in combination with the drug yohimbine (as opposed to the herb yohimbe).47 A double-blind, placebo-controlled trial of 45 men found that one-time use of this combination therapy an hour or two prior to intercourse improved erectile function, especially in those with only moderate erectile dysfunction scores. Arginine and yohimbine were both taken at a dose of 6 grams. NOTE: do not use the drug yohimbine (or the herb yohimbe) except under physician supervision, as it presents a number of safety risks. Sexual Dysfunction in Women Some postmenopausal women have difficulty experiencing sexual arousal. One small double-blind study of yohimbine combined with arginine found an increase in measured physical arousal among 23 women with this condition.28 However, the women themselves did not report any noticeable subjective effects, suggesting that the effect was slight. In addition, only the combination of yohimbine and arginine produced results; neither substance was effective when taken on its own. Interstitial Cystitis Interstitial cystitis is a condition in which an individual feels like he or she has symptoms of a bladder infection, but no infection is present. Medical treatment for this condition is less than satisfactory. A 3-month double-blind trial of 53 individuals with interstitial cystitis found only weak indications that arginine might improve symptoms of interstitial cystitis.29 Several participants dropped out of the study; when this was properly taken into account using a statistical method called "ITT analysis," no benefit at all could be proven. A very small double-blind trial also failed to find evidence of benefit.30 Colds A 2-month double-blind study involving 40 children with a history of frequent colds concluded that arginine seemed to provide some protection against respiratory infections.31 Of the children who were given arginine, 15 stayed well during the 60 days of the study. By contrast, only 5 of the children who took placebo stayed well, a significant difference. Nutritional Support in Hospitalized Patients Several nutritional products that contain arginine as well as other substances have been tried in hospital settings to enhance recovery following major surgery, illness, or injury. These mixtures are delivered "enterally," which means through a tube into the stomach. A review of 15 studies, about half of them double-blind and involving a total of 1,557 individuals, found that such products can reduce episodes of infection, time on ventilator machines, and length of stay in the hospital.32,33 However, because of the many nutrients contained in these so-called "immunonutrient" mixtures, it is not clear whether arginine deserves the credit. -------------------------------------------------------------------------------- Safety Issues At moderate doses (2 to 3 g per day), oral arginine appears to be safe and essentially side-effect free, although minor gastrointestinal upset can occur. However, there are some potential safety issues regarding high-dose arginine. These cautions are based on findings from animal studies and hospital experiences of intravenous administration. For example, arginine may stimulate the body's production of gastrin, a hormone that increases stomach acid.34 For this reason, there are concerns that arginine could be harmful for individuals with ulcers and people taking drugs that are hard on the stomach. In addition, a double blind trial found that arginine (30 g/day) may increase the risk of esophageal reflux (heartburn) by relaxing the sphincter at the bottom of the esophagus.41 Arginine might also alter potassium levels in the body, especially in people with severe liver disease.35 This is a potential concern for individuals who take drugs that also alter potassium balance (such as potassium-sparing diuretics and ACE inhibitors), as well as those with severe kidney disease. If you fall into any of these categories, do not use high-dose arginine except under physician supervision. Evidence that arginine can improve insulin sensitivity36 raises theoretical concerns that, if you have diabetes and take arginine, your blood sugar could fall too low. However, one study suggests that arginine is safe for use by people with stable type 2 (adult-onset) diabetes.37 Maximum safe doses in pregnant or nursing women, young children, and those with severe liver or kidney disease have not been established. -------------------------------------------------------------------------------- Interactions You Should Know About If you are taking Lysine to treat herpes: Arginine might counteract the potential benefit.38 Drugs that are hard on the stomach (such as nonsteroidal anti-inflammatory medications): Taking high doses of arginine might stress your stomach further. Medications that can alter the balance of potassium in your body (such as potassium-sparing diuretics or ACE inhibitors): High doses of arginine should be used only under physician supervision. Transdermal nitroglycerin: Arginine may help prevent the development of tolerance. (NOTE: Doctors supervision is essential.) References 1. Hambrecht R, Hilbrich L, Erbs S, et al. Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation. J Am Coll Cardiol. 2000;35:706713. 2. Rector TS, Bank AJ, Mullen KA, et al. Randomized, double-blind, placebo-controlled study of supplemental oral L-arginine in patients with heart failure. Circulation. 1996;93:21352141. 3. Watanabe G, Tomiyama H, Doba N. Effects of oral administration of L-arginine on renal function in patients with heart failure. J Hypertens. 2000;18:229234. 4. Chen J, Wollman Y, Chernichovsky T, et al. Effect of oral administration of high-dose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double-blind, randomized placebo-controlled study. BJU Int. 1999;83:269273. 5. Maxwell A. Annual meeting of American College of Cardiology, 1999. 6. Boger RH, Bode-Boger SM, Thiele W, et al. Restoring vascular nitric oxide formation by L-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease. J Am Coll Cardiol. 1998;32:13361344. 7. Korting GE, Smith SD, Wheeler MA, et al. A randomized double-blind trial of oral L-arginine for treatment of interstitial cystitis. J Urol. 1999;161:558565. 8. Meston CM, Worcel M. The effects of yohimbine plus L-arginine glutamate on sexual arousal in postmenopausal women with sexual arousal disorder. Arch Sex Behav. 2002;31:323-332. 9. Bednarz B, Wolk R, Chamiec T, et al. Effects of oral L-arginine supplementation on exercise-induced QT dispersion and exercise tolerance in stable angina pectoris. Int J Cardiol. 2000;75:205210. 10. Baligan M, Giardina A, Giovannini G, et al. L-arginine and immunity. Study of pediatric subjects [translated from Italian]. Minerva Pediatr. 1997;49:537542. 11. De Aloysio D, Mantuano R, Mauloni M, et al. The clinical use of arginine aspartate in male infertility. Acta Eur Fertil. 1982;13:133167. 12. Tanimura J. Studies on arginine in human semen. II. The effects of medication with L-arginine-HCl on male infertility. Bull Osaka Med Sch. 1967;13:8489. 13. Schachter A, Goldman JA, Zukerman Z. Treatment of oligospermia with the amino acid arginine. J Urol. 1973;110:311313. 14. Schachter A, Friedman S, Goldman JA, et al. Treatment of oligospermia with the amino acid arginine. Int J Gynaecol Obstet. 1973;11:206209. 15. Mroueh A. Effect of arginine on oligospermia. Fertil Steril. 1970;21:217219. 16. Pryor JP, Blandy JP, Evans P, et al. Controlled clinical trial of arginine for infertile men with oligozoospermia. Brit J Urol. 1978;50:4750. 17. Battaglia C, Salvatori M, Maxia N, et al. Adjuvant L-arginine treatment for in-vitro fertilization in poor responder patients. Hum Reprod. 1999;14:16901697. 18. Piatti PM, Monti LD, Valsecchi G, et al. Long-term oral L-arginine administration improves peripheral and hepatic insulin sensitivity in type 2 diabetic patients. Diabetes Care. 2001;24:875880. 19. De Nicola L, Bellizzi V, Minutolo R, et al. Randomized, double-blind, placebo controlled study of arginine supplementation in chronic renal failure. Kidney Int. 1999;56:674684. 20. Beale R, Bryg D, Bihari D. Immunonutrition in the critically ill: A systematic review of clinical outcome. Crit Care Med. 1999;27:27992805. 21. Hambrecht R, Hilbrich, L, Erbs S, et al. Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation. J Am Coll Cardiol. 2000;35:706713. 22. Rector TS, Bank AJ, Mullen KA, et al. Randomized, double-blind, placebo-controlled study of supplemental oral L-arginine in patients with heart failure. Circulation. 1996;93:21352141. 23. Watanabe G, Tomiyama H, Doba N. Effects of oral administration of L-arginine on renal function in patients with heart failure. J Hypertens. 2000;18:229234. 24. Maxwell A. Annual meeting of American College of Cardiology, 1999. 25. Boger RH, Bode-Boger SM, Thiele W, et al. Restoring vascular nitric oxide formation by L-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease. J Am Coll Cardiol. 1998;32:13361344. 26. Bednarz B, Wolk R, Chamiec T, et al. Effects of oral L-arginine supplementation on exercise-induced QT dispersion and exercise tolerance in stable angina pectoris. Int J Cardiol. 2000;75:205210. 27. Chen J, Wollman Y, Chernichovsky T, et al. Effect of oral administration of high-dose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double-blind, randomized placebo-controlled study. BJU Int. 1999;83:269273. 28. Meston CM, Worcel M. The effects of yohimbine plus L-arginine glutamate on sexual arousal in postmenopausal women with sexual arousal disorder. Arch Sex Behav. 2002;31:323-332. 29. Korting GE, Smith SD, Wheeler MA, et al. A randomized double-blind trial of oral L-arginine for treatment of interstitial cystitis. J Urol. 1999;161:558565. 30. Cartledge JJ, Davies A, Eardley I. A randomized double-blind placebo-controlled crossover trial of the efficacy of L-arginine in the treatment of interstitial cystitis. BJU Int. 2000;85:421426. 31. Baligan M, Giardina A, Giovannini G, et al. L-arginine and immunity. Study of pediatric subjects [translated from Italian]. Minerva Pediatr. 1997;49:537542. 32. Beale R, Bryg D, Bihari D. Immunonutrition in the critically ill: A systematic review of clinical outcome. Crit Care Med. 1999;27:27992805. 33. Piatti PM, Monti LD, Valsecchi G, et al. Long-term oral L-arginine administration improves peripheral and hepatic insulin sensitivity in type 2 diabetic patients. Diabetes Care. 2001;24:875880. 34. AHFS Drug Information. Bethesda, Md: American Society of Hospital Pharmacists. 2000:23062307. 35. AHFS Drug Information. Bethesda, Md: American Society of Hospital Pharmacists. 2000:23062307. 36. Piatti PM, Monti LD, Valsecchi G, et al. Long-term oral L-arginine administration improves peripheral and hepatic insulin sensitivity in type 2 diabetic patients. Diabetes Care. 2001;24:875880. 37. Bruinsma KA, Anderson BE, Prendergast JJ, et al. Effects of an L-arginine-enriched medical food in patients with type II diabetes [abstract]. Diabetes. 2001;50(suppl 2):Abst #1796-PO. 38. Griffith RS, DeLong DC, Nelson J. Relation of arginine-lysine antagonism to herpes simplex growth in tissue culture. Chemotherapy. 1981;27:209213. 39. Klotz T, Mathers MJ, Braun M, et al. Effectiveness of oral L-arginine in first-line treatment of erectile dysfunction in a controlled crossover study. Urol Int. 1999;63(4):220-223. 40. Maxwell AJ, Zapien MP, Pearce GL, et al. Randomized trial of a medical food for the dietary management of chronic, stable angina. J Am Coll Cardiol. 2002;39:3745. 41. Luiking YC, Weusten BL, Portincasa P, et al. Effects of long-term oral L-arginine on esophageal motility and gallbladder dynamics in healthy humans. Am J Physiol. 1998;274(6 pt 1):G984G991. 42. Khan F, Litchfield SJ, McLaren M, et al. Oral L-arginine supplementation and cutaneous vascular responses in patients with primary Raynaud's phenomenon. Arthritis Rheum. 1997;40:352357. 43. Maxwell AJ, Anderson BE, Cooke JP. Nutritional therapy for peripheral arterial disease: a double-blind, placebo-controlled, randomized trial of HeartBar. Vasc Med. 2000;5(1):11-9. 44. Parker JO, Parker JD, Caldwell RW, et al. The effect of supplemental L-arginine on tolerance development during continuous transdermal nitroglycerin therapy. J Am Coll Cardiol. 2002;39:1199-1203. 45. de Gouw HW, Verbruggen MB, Twiss IM, et al. Effect of oral L-arginine on airway hyperresponsiveness to histamine in asthma. Thorax. 1999;54:1033-1035. 46. Pryor JP, Blandy JP, Evans P, et al. Controlled clinical trial of arginine for infertile men with oligozoospermia. Br J Urol. 1978;50:47-50. 47. Lebret T, Herve JM, Gorny P, et al. Efficacy and safety of a novel combination of L-arginine glutamate and yohimbine hydrochloride: a new oral therapy for erectile dysfunction. Eur Urol. 2002;41:608-613. |
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