Effect of carnitine supplementation on progression of carotid plaque in the metabolic syndrome: the ECoM study

Abstract Background/Introduction L-carnitine (L-C) has been investigated as a potential therapy for cardiovascular (CV) disease, but its direct effects on human atherosclerosis are unknown. Epidemiological studies suggest a possible reduction of CV risk factors following treatment, whereas animal studies have shown that L-C may increase pro-atherogenic metabolites. Purpose The purpose of this study was to determine whether L-C therapy led to atherosclerosis progression or regression by direct quantification of carotid atherosclerotic lesions in patients with metabolic syndrome (MetS). Methods This study was a Phase 2, prospective, parallel, double blinded, randomized, placebo-controlled, two-center trial. MetS was defined according to the International Diabetes Federation harmonized definition, where presence of any 3 of the 5 following risk factors constituted a diagnosis: elevated waist circumference; elevated triglycerides; reduced HDL or treated; elevated blood pressure or treated; elevated glucose or HbA1c or treated. Participants with a baseline carotid total plaque volume (TPV) ≥50 mm3 were randomized to placebo or 2 g L-C daily for 6 months. Plaque progression was quantified by 3D carotid ultrasound for change in TPV and reduction in vessel lumen area (% area stenosis, Fig. 1). Absolute differences were assessed on the raw scale, while percent change on the log scale. Analysis of covariance (ANCOVA) was used to assess within- and between-arm differences. Results Of the 177 participants randomized, 157 completed the study (L-C n=76, placebo n=81). No statistically significant difference between arms was found in the primary outcome (TPV). However, there was progression of plaque stenosis in the treatment arm: the L-C group had an increase in stenosis of 9.8% (p=0.01) higher than the placebo arm, and a 2.7% (p=0.03) greater absolute change. Total cholesterol and LDL levels (0.10 mmol/L and 0.05 mmol/L, respectively) were higher in the intervention arm compared to the placebo arm (−0.06 mmol/L and −0.07 mmol/L). Figure 1 Conclusions We observed progression of atherosclerosis with L-C therapy compared to placebo in patients with MetS. The clear lack of benefit of L-C therapy in this population raises serious concerns for its further use as a potential therapy. Given its association with pro-atherogenic metabolites our study offers further understanding of the atherosclerotic process. Acknowledgement/Funding Heart and Stroke Foundation of Canada