Potential Inhibitory Effects of L-Carnitine Supplementation on Tissue Advanced Glycation End Products in Patients with Hemodialysis

Background and Aims: Advanced glycation end products (AGEs) contribute to cardiovascular disease in patients with hemodialysis (HD). We have recently found that carnitine levels are inversely associated with skin AGE levels in HD patients. We examined whether l-carnitine supplementation reduced skin AGE levels in HD patients with carnitine deficiency. Methods: This was a single-center study. One hundred and two HD patients (total carnitine levels <50mol/L) were enrolled and randomized to either oral administration of l-carnitine (900mg/day) (n=51) or control (n=51). After 6 months, metabolic and inflammatory variables, including serum levels of carnitine, were measured. Skin AGE levels were determined by evaluating skin auto-fluorescence with an AGE-reader. Results: There were no significant differences of clinical variables at baseline between the control and l-carnitine therapy group. Thirty-two patients did not complete the assessment or treatment of the study. Oral l-carnitine supplementation for 6 months significantly increased low-density lipoprotein cholesterol (LDL-C), triglycerides, total, free, and acyl carnitine levels, while it decreased alanine transaminase, acyl/free carnitine ratio, (2)-microglobulin, and skin AGE values. Change in total carnitine values from baseline (total carnitine) and free carnitine were inversely associated with skin AGE levels in l-carnitine-treated patients (p=0.036 and p=0.016, respectively). In multiple regression analysis, free carnitine was a sole independent determinant of skin AGEs (R-2=0.178). Conclusions: The present study demonstrated that oral l-carnitine supplementation significantly decreased skin AGE levels in HD patients with carnitine deficiency. These observations suggest that supplementation of l-carnitine might be a novel therapeutic strategy for preventing the accumulation of tissue AGEs in carnitine-deficient patients with HD.