Dyslipidemia, Oxidative Stress and Cardiac Dysfunction in Children with Chronic Renal Failure: Effects of L-Carnitine Supplementation

Abstract

Background: Secondary carnitine deficiency may develop in chronic renal failure (CRF) patients undergoing longterm hemodialysis (HD), with a resulting higher incidence of cardiovascular diseases, dyslipidemia and oxidative stress. We studied the efficacy of 12 months of L-carnitine supplementation on the amelioration of dyslipidemia, oxidative stress and cardiac dysfunction in 24 CRF children undergoing long-term HD compared with 24 age-and sex-matched controls. Methods: Plasma samples were analyzed spectrophotometerically before and after dialysis sessions and after 2-month supplementation with oral L-carnitine (50 mg/kg/day) for free carnitine (FC), the lipid profile, and oxidative stress markers. Echocardiography the day following dialysis measured cardiac diameters, wall thicknesses, left ventricular mass index (Ml), end diastole and systole volume indices and functions. Results: The pre-dialysis FC concentration was substantially lower than controls and decreased significantly at the end of the dialysis session. Pre-and post-dialysis plasma levels of free fatty acids (FFAs), trigyleride (TG), total cholesterol (TC) and oxidative stress markers significantly increased while high-density lipoprotein cholesterol (HDL-C) and phospholipids significantly decreased compared to controls. Echocardiography detected a significant increase in cardiac diameters and thickness, and systolic and diastolic cardiac dysfunction. After L-carnitine supplementation, plasma levels of FC increased to normal levels. FFAs, TC and HDL-C returned to control levels while TG, phospholipids, and the oxidative stress markers decreased but remained significantly higher than controls. There was a significant decrease in cardiac diameters and an increase in left ventricular diastolic function (E/A ratio), but no correlation between FC levels and echocardiographic parameters. Pre-dialysis, post-dialysis and after treatment, plasma FC level showed a significant positive correlation with HDL-C and phospholipids and a significant negative correlation with each of oxidative stress markers, FFAs, TG and TC. On the other hand, FFAs showed a significant positive correlation with TG, TC, DC, NO and a significant negative correlation with HDL-C and phospholipids. Conclusion: This study demonstrates that CRF children under regular HD suffer from a decrease in the level of plasma FC, dyslipidemia, oxidative stress, and an increase in cardiac diameters and thickness with impairment of cardiac functions. Oral L-carnitine supplementation at a dose of 50 mg/kg for 2 months can increase plasma FC level, improve dyslipidemia, decrease oxidative stress with reduction of cardiac diameters and increase in diastolic function.

Effect of Carnitine and herbal mixture extract on obesity induced by high fat diet in rats

“…L-carnitine supplementation produced significant decreases in serum TG, VLDL, and T-cholesterol, LDL-C while there were significant increases in HDL cholesterol in obese rats. These results are in agreement with those of González-Ortiz et al [ 53 ] and El-Metwally et al ., [ 54 ] who reported that oral L-carnitine increases plasma free carnitine levels, improves dyslipidemia and decreases oxidative stress, with reduction of cardiac parameters.…”

Multiple Antioxidants and L-Arginine Modulate Inflammation and Dyslipidemia in Chronic Renal Failure Rats

“…Similar findings are recently reported in hemodialysis patients receiving oral L-arginine supplementation. [81] Multiple recent studies reported the ability of each of the antioxidants used in the current study to decrease blood lipids in different diseases. [94][95][96][97][98] Thus, the combined hypolipidemic effect of catechin, L-carnitine, and vitamins E and C may underlie the reduction of cholesterol and triglyceride levels in the antioxidant-treated group.…”

“…[76] Regarding vitamin C, it functions as a cofactor for biosynthesis of carnitine, [77,78] and it exerts a protective role against the peroxidative damage through its lipid-lowering effect. [79] Carnitine itself has antioxidant action and a strong inhibitory effect on free radical production, [80,81] and it exerts thiol and methionine-sparing activity. [82] Furthermore, recent data showed that L-carnitine treatment is able to modify some particular aspects of the inflammatory status characterizing CRF patients.…”

Carnitine supplementation improves cardiac strain rate in children on chronic hemodialysis

“…The mean dialysis vintage of the children in our study was shorter (9.3±2.2 months) than that of the children studied by El-Metwally [32] (19.1± 2.5 months) and Topaloglu et al [20] (all patients on HD for at least 1 year), all of whom had evidence of cardiac abnormalities by standard ECHO. However, usage of more sensitive speckle-tracking ECHO in our study population revealed a significant improvement in the longitudinal strain rate in response to levocarnitine supplementation, which was not observed in our control group or in children on chronic HD who did not receive levocarnitine supplementation.…”

“…They found that children on chronic HD had increased cardiac diameters and thickness as well as decreased systolic and diastolic function (SF, EF, and E/A ratio) compared with the controls at baseline. Two months of oral levocarnitine supplementation reduced the cardiac diameters and increased diastolic function in these children, but did not improve LV systolic function, mass, and volume indices, or reduce cardiac wall thickness [32]. The authors similarly concluded that a longer duration of carnitine supplementation may be needed to replete carnitine muscle tissue stores, reduce the accumulation of acyl groups, and increase the activity of carnitine palmitoyltransferase in order to achieve improvement in cardiac function.…”