Arginine

Overview

L-Arginine is a substance that is produced in the body that plays an essential role in the nitric oxide pathway, a pathway involved in the cascade reactions that are responsible for vasodilation. Due to this function, arginine supplements are associated with cardiovascular health, especially in conditions where the nitric oxide pathway may be working insufficiently. For example, there is evidence that in the development of arteriosclerosis, people with high cholesterol have an endothelium that has the reduced ability to produce nitric oxide, and therefore the arteries can not dilate effectively. This leads to the consequence of blood cells having the ability to attach to the inner vessels and cause blockages. L-Arginine has also been shown to stimulate lymphocyte production, and it has therefore been studied in diets of surgery patients.

During the nitric oxide pathway, the nitric oxide synthase enzyme catalyzes the oxidation of arginine to citrulline and nitric oxide (NO). NO production in turn causes vasodilation, and is involved in the overall regulation of overall vasoresistance. Since arginine is produced by our bodies it has been classified as a nonessential nutrient for supplementation, however, recently the amount of arginine produced by the body has been found to be insufficient for maintaining health.

Comments

Due to the popularity of dietary supplements for sexual function improvement and the known action of arginine on the NO pathway, numerous supplements now include arginine in combination with other herbs for sexual dysfunction and performance. However, few studies have confirmed the benefits of these combinations nor the action of the single components.

Scientific Support

Cardiovascular Health

A meta-analysis of the use of L-arginine in the enteral/oral diets of stressed patients was conducted to reduce the confusion of whether or not the diets were immune enhancing and beneficial. Although the review found these L-arginine “immune-enhancing” diets to be beneficial, the author contended that nothing proved that this effect was not confounded by other bioactive components, including omega-3 fatty acids, RNAs, and antioxidant vitamins. The author also pointed out that the L-arginine supplemented enteral/oral diets could have a harmful effect in hemodynamically unstable patients, and in patients with multiple organ failure (Cynober, 2003).

A medical food called the Heart Bar is now sold that looks just like the numerous other sports and protein bars. The heart bar is intended to act as a food that nutritionally supports cardiovascular health with its major active constituent being arginine. Its use is substantiated by numerous peer reviewed clinical studies, and it is regulated specially as a “medical food” by the FDA. In one study (a randomized, double-blind, placebo-controlled, crossover trial), thirty-six stable angina outpatients were tested for the electrocardiographic, vascular and clinical effects of the Heart Bar. This medical food was found to improve vascular function, exercise capacity and aspects of quality of life in patients with stable angine (Maxwell et al., 2002).

L-Arginine was clinically studied in a single-blind, controlled, crossover dietary intervention study for its effect on certain cardiovascular parameters, especially blood pressure. Six subjects were given isocaloric diets for one week, with constant measures of sodium in each diet (approx. 180 mmol/day). Three diets were given in random order to each participant: a) control, b) L-arginine enriched by natural foods, and c) L-arginine supplemented orally (same as control diet otherwise). Both arginine-rich diets (b and c) resulted in a blood pressure decrease. The diet b ( but not diet c) resulted in lower total serum cholesterol and triglyceride levels and higher HDL cholesterol. The diet c, and to a lesser extent diet b, resulted in higher creatine clearance (slight) and a fall in fasting glucose. The authors concluded an increase of L-arginine in the diet to lower blood pressure and affect kidney function and carbohydrate metabolism (Siani et al, 2000).

Fujita et al. (2000) clinically tested the ability of L-arginine to affect coronary perfusion abnormality during exercise. Twelve patients with angina pectoris and normal coronary arteries underwent exercise thallium-201 scintigraphy both with intravenous L-arginine or without (control). The administration of L-arginine was found to prolong exercise time and improve the severity score. In 7 of the 12 patients, the TI-201 redistribution disappeared after L-arginine administration, and the percentage of serum L-citrulline increased, and percentage of epicardial coronary diameter in response to acetylcholine compared to the other patients who did not show a change in TI-201 redistribution. The authors concluded that exogenous L-arginine was able to improve myocardial perfusion during exercise in this subset of patients.

High Blood Pressure

In order to determine whether or not a deficient L-arginine-nitric oxide system is active in cortisol-induced hypertension, the effect of L-arginine uptake was studied. Eight healty men were included in the study, and hydrocortisone acetate (50 mg) was given orally every six hours for 24 hous after a 5-day fixed salt diet. L-Arginine levels were not found to be affected by cortisol treatment, and therefore, there was no correlation between cortisol induced hypertension and the L-arginine transport system (Chin-Dusting et al., 2003).

Immune Function

L-Arginine was clinically tested in patients with far advanced gastric cancer for its ability to stimulate lymphocyte production, since it had been previously shown to stimulate lymphocyte production in healthy individuals. The patients received a dietary supplement of L-arginine (30 g daily for 7 days), and the lymphocyte counts and T/B cell ratio in the peripheral blood was tested. Although L-arginine did not show any significant side effects (except transient nausea in 1 patient) or impair liver function, it also did not stimulate lymphocyte function. The authors suggested the possibility that the cancer patients had immune systems that were intrinsically defected, and therefore could not be stimulated (Wu et al., 1993).

Li et al. (1993) tested the ability of L-arginine to decrease incidence of sepsis after surgery in patients with obstructive jauntice. Since arginine had been known as a T lymphocyte stimulator, the use of supplementation and the immunological status of patients with obstructive jauntice after surgery was studied. Arginine was found to significantly enhance immune function of patients with obstructive jauntice.

In order to study the immunomodulatory effect of arginine in surgery patients, 30 cancer patients were randomized, and sixteen were given L-arginine (25 g/day) while the other 14 were given isonitrogenous L-glycine (43 g/day) for 7 days after major surgery. Parameters measured were nitrogen balance (daily), and immune parameters before and after surgery on days 1,4 and 7. T-Lymphocyte response was significantly enhanced to concanavalin A in the L-arginine group compared to the glycine group. L-arginine was also found to increase the CD4 phenotype. L-Arginine was found to be beneficial in modulating the immune system in surgery patients. This immune modulating effect was found to be nontoxic and distinct in its mechanism from its moderate effect on nitrogen metabolism (Daly et al., 1988).

Safety / Dosage

The daily requirement of arginine supplementation has been calculated to be approximately 8 grams daily (for a 70-kg person). Supplements in the range of 8-21 grams daily have been used clinically in people with high cholesterol in order to restore the proper functioning of the vasodilatory pathways. Supplements in the range of 9-14 grams daily have been used clinically to increase blood flow to the peripheries and improve conditions of myocardial ischemia and walking pain due to claudication.

The average daily intake of arginine in the American diet has been calculated to be approximately 5 grams daily. In order to increase arginine in the diet, the primary dietary sources of this amino acid are meats and other high protein foods (nuts, eggs).

References

1.Chin-Dusting JP, Ahlers BA, Kaye DM, Kelly JJ, Whitworth JA. L-arginine transport in humans with cortisol-induced hypertension. Hypertension. 2003 Jun;41(6):1336-40. Epub 2003 Apr 21.

2.Cynober L. Immune-enhancing diets for stressed patients with a special emphasis on arginine content: analysis of the analysis. Curr Opin Clin Nutr Metab Care. 2003 Mar;6(2):189-93.

3.Daly JM, Reynolds J, Thom A, Kinsley L, Dietrick-Gallagher M, Shou J, Ruggieri B. Immune and metabolic effects of arginine in the surgical patient. Ann Surg. 1988 Oct;208(4):512-23.

4.Fujita H, Yamabe H, Yokoyama M. Effect of L-arginine administration on myocardial thallium-201 perfusion during exercise in patients with angina pectoris and normal coronary angiograms. J Nucl Cardiol. 2000 Mar-Apr;7(2):97-102.

5.Li H, Xiong ST, Zhang SX, Liu SB, Luo Y. Immunological status of patients with obstructive jaundice and immunostimulatory effect of arginine. J Tongji Med Univ. 1993;13(2):111-5.

6.Maxwell AJ, Zapien MP, Pearce GL, MacCallum G, Stone PH. Randomized trial of a medical food for the dietary management of chronic, stable angina. J Am Coll Cardiol. 2002 Jan 2;39(1):37-45.

7.Siani A, Pagano E, Iacone R, Iacoviello L, Scopacasa F, Strazzullo P.Blood pressure and metabolic changes during dietary L-arginine supplementation in humans. Am J Hypertens. 2000 May;13(5 Pt 1):547-51.

8.Wu CW, Chi CW, Chiu CC, Wu HS, Liu WY, P'eng FK, Wang SR. Can daily dietary arginine supplement affect the function and subpopulation of lymphocytes in patients with advanced gastric cancer? Digestion. 1993;54(2):118-24.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.