L-arginine improves vascular function by overcoming the deleterious effects of ADMA, a novel cardiovascular risk factor

Alternative Medicine Review, March, 2005 by Rainer H. Boger, Eyal S. Ron

In a preliminary study of five patients with coronary artery disease in whose myocardial perfusion had been maximized and stabilized on conventional cardiovascular medications, 3 g sustained-release L-arginine was given twice daily for 12 weeks. Significant improvements in heart function and myocardial perfusion were seen via PET imaging. (68)

Conclusions

ADMA is an endogenous and competitive inhibitor of NO synthase. Plasma levels of this inhibitor are elevated in patients with atherosclerosis and in those with risk factors for atherosclerosis. (34,36) In these patients, plasma ADMA levels are correlated with the severity of endothelial dysfunction and atherosclerosis. By inhibiting the production of NO, ADMA can impair blood flow, accelerate atherogenesis, and interfere with angiogenesis.

Supplemental L-arginine improves endothelial function, myocardial perfusion, angina, erectile dysfunction, and exercise tolerance, regardless of ADMA status. However, many patients exhibiting one of these impairments demonstrate elevated blood ADMA. Therefore, testing for plasma ADMA levels may give the physician a better idea of those patients who may respond best to prolonged L-arginine supplementation, as data are accumulating to show that patients with elevated ADMA are the most likely to benefit. The ratio of L-arginine to ADMA is considered to be the most accurate measure of eNOS substrate availability. This ratio will increase during L-arginine supplementation, regardless of initial ADMA concentration. Due to the pharmacokinetics of oral L-arginine and the positive results from preliminary studies, it appears supplementation with a sustained-release L-arginine preparation will achieve positive therapeutic results at lower dosing levels.

Table 1. Clinical Conditions with Elevated ADMA

Condition                       Fold increase       Ref
                                vs. controls

Hypercholesterolemia                 2-3             [1]
Hypertriglyceridemia                  2             [19]
Hypertension                          2             [20]
Pulmonary Hypertension               2-3            [21]
Peripheral Arterial Disease          2-4          [22, 23]
Chronic Renal Failure               2-12          [24, 25]
Congestive Heart Failure             2-3            [26]
Type 2 Diabetes                       2             [27]
Preeclampsia                          2             [28]

References

(1.) Boger RH, Bode-Boger SM, Szuba A, et al. Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation 1998;98:1842-1847.

(2.) Panza JA, Quyyumi AA, Brush JE Jr, Epstein SE. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 1990;323:22-27.

(3.) Celermajer DS, Sorensen KE, Georgakopoulos D, et al. Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation 1993;88:2149-2155.