Effectiveness of l-carnitine supplementation in patients with erythropoietin-resistant anemia

Abstract

Whilst L-carnitine (LC) supplementation is recommended for the treatment of EPO-resistant anemia, the extent of effectiveness has been shown to vary considerably. Previous work by Reuter et al (2008) demonstrated a significant association between EPO-resistance and carnitine pool composition; based on these findings, it is hypothesized that patients who have a high EPO resistance index (ERI) are more likely to respond to LC supplementation. Preliminary assessment of this hypothesis was conducted as retrospective analysis, using prospectively-defined criteria, of data from 2 randomized, double-blind, placebo-controlled trials. HD patients were administered LC (20 mg/kg/wk/dialysis i.v.) or placebo for 24 weeks, with EPO dose and hemoglobin data assessed at Weeks 0, 12 & 24. Patients were classified as High (>0.02 μg/kg/wk/gHb) or Low ERI based on baseline data. Treatment effectiveness was analyzed using %baseline ERI for all patients (Low ERI & High ERI) and for High ERI patients only. 77 patients (38 LC/39 placebo) were included in the analysis, of which 22 (14 LC/8 placebo) were classified as High ERI. Analysis of all patient data indicated no significant differences between Week 0, 12 & 24 %baseline ERI for neither the LC nor placebo groups, whereas analysis of High ERI patient data indicated a significant reduction in %baseline ERI at Week 12 & 24 compared to Week 0 ( p =0.004) for the LC treatment group, with no significant placebo treatment effect. Similarly, analysis of %baseline ERI area-under-the-curve from 0–24°weeks indicated no significant treatment effects when all patients were included in the analysis, whereas for High ERI patients, significantly lower values were demonstrated for LC vs placebo ( p =0.016). These findings suggest that High ERI patients may receive the most benefit from LC supplementation. It is proposed that LC treatment results in an improvement in CPT activity via normalization of the LC/acylcarnitine ratio, thereby resulting in stabilization of the RBC membrane and improvement in anemia. A randomized, double-blind, placebo-controlled study is being conducted to investigate this further.