Effects of Reducing L-Carnitine Supplementation on Carnitine Kinetics and Cardiac Function in Hemodialysis Patients: A Multicenter, Single-Blind, Placebo-Controlled, Randomized Clinical Trial

Abstract

L-carnitine (LC) supplementation improves cardiac function in hemodialysis (HD) patients. However, whether reducing LC supplementation affects carnitine kinetics and cardiac function in HD patients treated with LC remains unclear. Fifty-nine HD patients previously treated with intravenous LC 1000 mg per HD session (three times weekly) were allocated to three groups: LC injection three times weekly, once weekly, and placebo, and prospectively followed up for six months. Carnitine fractions were assessed by enzyme cycling methods. Plasma and red blood cell (RBC) acylcarnitines were profiled using tandem mass spectrometry. Cardiac function was evaluated using echocardiography and plasma B-type natriuretic peptide (BNP) levels. Reducing LC administration to once weekly significantly decreased plasma carnitine fractions and RBC-free carnitine levels during the study period, which were further decreased in the placebo group (p < 0.001). Plasma BNP levels were significantly elevated in the placebo group (p = 0.03). Furthermore, changes in RBC (C16 + C18:1)/C2 acylcarnitine ratio were positively correlated with changes in plasma BNP levels (β = 0.389, p = 0.005). Reducing LC administration for six months significantly decreased both plasma and RBC carnitine levels, while the full termination of LC increased plasma BNP levels; however, it did not influence cardiac function in HD patients.

Keywords: CPT2; acylcarnitine; brain natriuretic peptide; cardiac function; cardiomyopathy; carnitine deficiency; end-stage kidney disease; free fatty acid; heart failure; hemodialysis.

Figure 1

CONSORT flow diagram of this trial. Sixty-four hemodialysis patients were assessed for eligibility, and 57 were randomized and allocated to LC 3/week, LC 1/week + placebo 2/week, and placebo 3/week groups and followed up for six months. Hb: hemoglobin; LC: L-carnitine.

Figure 2

Trial design. Patients were randomized to LC 1000 mg 3/week, LC 1000 mg 1/week + placebo 2/week, and placebo 3/week groups and followed up for six months. Blood samples, including carnitine fractions and profiling, were examined before the study period, day 30, day 60, and day 176 of the study period. Echocardiography was evaluated before and on day 176 of the study period. LC: L-carnitine.

Figure 3

Kinetics of plasma total carnitine, free carnitine, acylcarnitine levels, and acyl/free carnitine ratio during the study. (A) plasma total carnitine levels; (B) plasma free carnitine levels; (C) plasma acylcarnitine levels; (D) acyl/free carnitine ratio. LC-3: LC 1000 mg three times weekly; LC-1: LC 1000 mg once and placebo (saline 5 mL) twice weekly; LC-0: placebo three times weekly (LC-0). **** p < 0.0001 vs. LC-3; ^## p < 0.01; ^### p < 0.001; ^#### p < 0.0001 vs. LC-0.

Figure 4

Kinetics of RBC-free carnitine level during the study. LC-3: LC 1000 mg three times weekly; LC-1: LC 1000 mg once and placebo (saline 5 mL) twice weekly; LC-0: placebo three times weekly (LC-0). **** p < 0.0001 vs. LC-3; ^# p < 0.05; ^### p < 0.001; ^#### p < 0.0001 vs. LC-0.

Figure 5

Correlation between changes in BNP with (C16 + C18:1)/C2 in (A) plasma; and (B) RBCs. BNP: B-type natriuretic peptide; RBC: red blood cell.