There were two separate studies of oral L-arginine. The first was a dose ranging study involving 80 patients receiving four different doses of L-arginine (9 grams, 6 grams, 3 grams, or 0 grams). The dosing of L-arginine was performed in a randomized placebo-controlled fashion. Patients receive six weeks of therapy. Patients with diabetic retinopathy, active malignancy or previous malignancy in a state of remission, or autoimmune disorders were excluded. Ophthalmological exams were performed to screen for pathological angiogenesis in the retina. After the completion of the dose response study, the investigators studied the safety and efficacy of prolonged (12 months) L-arginine therapy. The primary end point was absolute claudication distance (ACD) and a statistical analysis was performed of the logarithm ACDT / ACDB. A treadmill was performed at one month after cessation of therapy to determine if there was a structural alteration of the indices of limb hemodynamics including the ankle brachial index (ABI) and plethysmography was performed at 6 and 12 months of therapy and at 1 month after sensation of therapy. The study correlated measures of limb blood flow with evidence of increased nitric oxide synthesis by measuring urinary nitrogen oxide. Flow mediated vasodilation (FMVD) of the brachial artery was measured. The choice of monitoring flow mediated vasodilation of the brachial artery, while appropriate for showing a systemic enhancement of nitric oxide synthesis, would not directly support an improvement of endothelial function in the vascular bed of interest.