The nitric oxide pathway: Is L-arginine a gate to the new millennium medicine? A meta-analysis of L-arginine effects

Background: During the past ten years, there has been a growing interest in L-arginine (LA), a semi-essential amino acid, which has recently been shown as a physiological precursor of nitric oxide (NO). Aim: The aim of this study is to determine the current role of LA in both cardiovascular and general medicine. Methods: We performed MEDLINE searches covering a period of 33.5 years (January 1966 to July 1999) for 'L-arginine' (unlimited search). Since we focused on the potential importance of LA for clinical medicine, we added the term 'disease' to limit the search (limited search). Results: During the period of interest 25883 articles devoted to the issue were found on unlimited search, whereas only 1656 on the limited one (mean annual rate 772 and 49 articles per year, respectively). Drastic elevation in annual rate both for unlimited and limited searches were found during the last 5 years - 2055 and 194 articles per year, respectively. The effects of LA dietary supplementation at relatively high doses have been studied extensively in several populations. LA exerts favorable effects in the prevention and treatment of cardiovascular disorders associated with endothelial dysfunction, atherogenesis and thrombosis. On the basis of the data from experimental and clinical studies, the long term oral LA supplementation has proven to be useful in avoiding endothelial damage and restoring injured endothelial function in patients with cardiovascular risk factors (hypercholesterolemia, smoking, diabetes, advanced age) or with several chronic cardiovascular disorders, such as coronary disease, peripheral and cerebral vascular disease, mild and moderate heart failure. Intravenous LA administration is likely to represent a potentially novel therapeutic strategy in hospitalized patients with critical limb ischemia, during angioplasty, coronary bypass grafting and cardiac transplantation. In addition, LA led to an improvement in interstitial cystitis symptoms, male reproductive activity, recovery from trauma and prognosis of chemotherapy in breast cancer. Conclusion: Our data clearly demonstrate a significant growth of interest in LA in clinical medicine. Arginine is gaining a prominent position as a part of the therapeutic arsenal in the management of LA-NO pathway-related disorders.