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      Effect of L-Carnitine on the Serum Lipoproteins and HDL-C Subclasses in Hemodialysis Patients

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          Abstract

          Aims: Following carnitine administration a decrease in plasma levels of triglyceride (TG) and increase in total high-density lipoprotein cholesterol (HDL-C) has been reported. Our hypothesis was that it also improves the HDL<sub>2</sub>/HDL<sub>3</sub> ratio, symptomatic intradialytic hypotension, and anemia in hemodialysis (HD) patients. Methods: Forty HD patients with a mean (± SD) age of 53 ± 13 years were treated with 500 mg/day carnitine taken orally for 2 months. Patients were used as their own controls (before treatment). Lipid and lipoproteins were determined by Alcyon Abbott autoanalyzer. HDL subclasses were measured by magnesium precipitation after fractionation with dextran sulfate. Hemoglobin, hematocrit and serum albumin were measured by standard methods. The results were analyzed by SPSS 11.05. Results: We found a significant decrease in serum TG (2.22 ± 0.99 vs. 1.93 ± 1.07 mmol/l, p < 0.01) and VLDL-C (0.93 ± 0.36 vs. 0.81 ± 0.34 mmol/l, p = 0.01) and a marked increase in HDL-C (0.9 ± 0.16 vs. 1.06 ± 0.24 mmol/l, p < 0.05), HDL<sub>2</sub>-C (0.17 ± 0.06 vs. 0.27 ± 0.14 mmol/l, p < 0.05) and albumin (37 ± 4 vs. 42 ± 5 g/l, p = 0.01) levels. The serum levels of total cholesterol (4.61 ± 0.89 vs. 4.5 ± 0.95 mmol/l, p = 0.1), LDL-C (2.78 ± 0.85 vs. 2.6 ± 0.89 mmol/l, p > 0.05), HDL<sub>3</sub>-C (0.73 ± 0.1 vs. 0.79 ± 0.17 mmol/l, p > 0.05), hemoglobin, hematocrit, and intradialytic blood pressure did not change after the treatment. Conclusion: Treatment with 500 mg/day carnitine taken orally for 2 months reduces serum levels of TG and VLDL-C, and increases HDL-C, HDL<sub>2</sub>-C and albumin in HD patients.

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          Most cited references 27

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          Lipids and risk of coronary heart disease The Framingham Study

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            Dialysis-related carnitine disorder and levocarnitine pharmacology.

             Allan Evans (2003)
            Among the homeostatic processes controlling the endogenous L-carnitine pool in humans, the kidney has a vital role through extensive and adaptive tubular reabsorption. Kidney disease can lead to disturbances in L-carnitine homeostasis, and long-term hemodialysis therapy can lead to a significant reduction in plasma and tissue L-carnitine levels and an increase in the ratio of acyl-L-carnitine to free L-carnitine. These alterations may interfere with the oxidation of fatty acids and removal from tissues of unwanted short-chain acyl groups. A dialysis-related carnitine disorder (DCD) arises when these biochemical abnormalities exist in association with such clinical symptoms as muscle weakness, cardiomyopathy, intradialytic hypotension, or anemia that is resistant to erythropoietin therapy. Exogenous L-carnitine, administered intravenously, is approved for the treatment of secondary carnitine deficiency caused by long-term hemodialysis. Although intravenous administration of 20-mg/kg doses at the end of each hemodialysis session leads to supraphysiological levels of the compound in plasma, these levels do not appear to be associated with adverse effects. Because more than 99% of the body's carnitine pool is located outside of plasma, supraphysiological plasma levels appear to be required to ensure that depleted muscle stores can be replenished. Although oral L-carnitine has been used for the treatment of DCD, the bioavailability of oral L-carnitine is low (<15%) in healthy subjects and unknown in patients with end-stage renal disease. Moreover, gastrointestinal degradation of L-carnitine to trimethylamine and other compounds might limit the usefulness of long-term oral L-carnitine administration in this patient group.
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              Multicenter trial of L-carnitine in maintenance hemodialysis patients. II. Clinical and biochemical effects.

              Since carnitine deficiency has been reported in some patients undergoing maintenance hemodialysis, we studied the effects of intravenous infusion of L-carnitine or placebo at the end of each dialysis treatment. The trial, which lasted seven months (one month baseline, 6 months treatment) was multicenter, double blind, placebo controlled, and randomized. Eighty-two long-term hemodialysis patients, who were given either carnitine (N = 38) or placebo (N = 44), completed this study. In each group, clinical and biochemical parameters during treatment were compared with baseline values. Intra-dialytic hypotension and muscle cramps were reduced only in the carnitine treated group, while improvement in post-dialysis asthenia was noticed in both carnitine and placebo groups. Maximal oxygen consumption, measured during a progressive work exercise test, improved significantly in the carnitine group (111 +/- 50 ml/min. P less than 0.03) and was unchanged in the placebo group. L-carnitine treatment was associated with a significant drop in pre-dialysis concentrations of serum urea nitrogen, creatinine and phosphorus (means +/- SEM, 101 +/- 4.5 to 84 +/- 3.9, 16.7 +/- 0.67 to 14.7 +/- 0.64, and 6.4 +/- 0.3 to 5.5 +/- 0.4 mg/dl, respectively, P less than 0.004). No significant changes in any of these variables were noticed in the placebo group. Mid-arm circumference and triceps skinfold thickness were measured in 11 carnitine and 13 placebo treated patients. Calculated mid-arm muscle area increased in the carnitine patients (41.37 +/- 2.68 to 45.6 +/- 2.82 cm2, P = 0.05) and remained unchanged in the placebo patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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                Author and article information

                Journal
                NEC
                Nephron Clin Pract
                10.1159/issn.1660-2110
                Nephron Clinical Practice
                S. Karger AG
                1660-2110
                2005
                December 2005
                10 August 2005
                : 101
                : 4
                : c174-c179
                Affiliations
                Division of Nephrology, Laboratory of Clinical Pharmacy, Faculty of Medicine and Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
                Article
                87411 Nephron Clin Pract 2005;101:c174–c179
                10.1159/000087411
                16103722
                © 2005 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Tables: 3, References: 51, Pages: 1
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/87411
                Categories
                Original Paper

                Cardiovascular Medicine, Nephrology

                Hemodialysis, Carnitine, HDL subclasses

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