Increases in walking distance in patients with peripheral vascular disease treated with L-carnitine: A double-blind, cross-over study

A double-blind, cross-over study was designed to evaluate the effects of L-carnitine in patients with peripheral vascular disease. After drug washout, 20 patients were randomly assigned to receive placebo or L-carnitine (2 g bid, orally) for a period of 3 weeks and were then crossed over to the other treatment for an additional 3 weeks. The effect on walking distance at the end of each treatment period was measured by treadmill test. Absolute walking distance rose from 174 ± 63 m with placebo to 306 ± 122 m (p <.01) with carnitine. Biopsy of the ischemic muscle, carried out before and after 15 days of L-carnitine administration in four additional patients, showed that treatment significantly increased total carnitine levels. An additional goal of this study was to ascertain the effects of L-carnitine on the metabolic changes induced by exercise in the affected limb. In six patients under control conditions, arterial and popliteal venous lactate and pyruvate concentrations were determined at rest, when the maximal walking distance was reached, and 5 min after the walking test. Twenty-four hours later, L-carnitine was administered intravenously (3 g as a bolus followed by an infusion of 2 mg/kg/min for 30 min) and metabolic assessments were repeated. Five minutes after the walking test, popliteal venous lactate concentration increased by 107 ± 16% before treatment and by only 54 ± 32% (p <.01) after carnitine. Furthermore, carnitine induced a more rapid recovery to the resting value of the lactate/pyruvate ratio. These data suggest that carnitine improves pyruvate utilization and oxidative phosphorylation efficiency in the skeletal muscle of the ischemic leg. L-Carnitine, administered intravenously to 18 patients at the same dosage as above, did not modify blood flow or the ankle/arm systolic blood pressure ratio. In an additional eight patients, this intravenous dose produced an increase in walking distance similar to that observed with oral treatment. In conclusion, this study demonstrates that L-carnitine, although not affecting the general or regional hemodynamics, improves the walking capacity of patients with intermittent claudication, probably through a metabolic mechanism.