Home About us Current issue Back issues Submission Instructions Advertise Contact Login   

Search Article 
  
Advanced search 
 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 1258 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 
 

Table of Contents   
ORIGINAL ARTICLE  
Year : 2011  |  Volume : 22  |  Issue : 6  |  Page : 1155-1159
The effect of L-Carnitine supplementation on lipid parameters, inflammatory and nutritional markers in maintenance hemodialysis patients


1 Department of Biochemistry, Sri Venkateswara Institute of Medical Sciences (SVIMS), Tirupati, Chittoor District, Andhra Pradesh, India
2 Department of Nephrology, Sri Venkateswara Institute of Medical Sciences (SVIMS), Tirupati, Chittoor District, Andhra Pradesh, India

Click here for correspondence address and email

Date of Web Publication8-Nov-2011
 

   Abstract 

Protein energy malnutrition and inflammation are common and usually concurrent in maintenance hemodialysis (MHD) patients. Carnitine, a small molecule involved in fatty acid metabolism, is significantly decreased in long-term HD patients. L-Carnitine supplementation may have potential benefits in improving dialysis-related disorders. However, there are conflicting reports with regard to the beneficial effects of L-Carnitine supplementation. Hence, the present study was carried out to evaluate the effect of L-Carnitine supplementation on lipid parameters, apoproteins and inflammatory and nutritional markers in HD patients. A total of 35 patients with end-stage renal disease, on MHD for a period of 2 to 5 years were recruited into the study. The study group consisted of 20 patients who received Carnitine supplementation intravenously three times a week after each HD session, at 1 g/dose, while the control group consisted of 15 patients without supplementation with L-Carnitine. Highly sensitive C-reactive protein (hsCRP), total protein, albumin, lipid profile and apoprotein AI and B were determined at baseline and at the end of the study. A significant decrease in the hsCRP levels was observed in the Carnitine-supplemented group (P < 0.05). However, no significant change was observed in the lipid parameters and nutritional markers in the Carnitine-supplemented group. In conclusion, the present study demonstrates the significant benefit of L-Carnitine supplementation on inflammatory status in MHD patients as noted by marked decrease in hsCRP levels in comparison with the control group.

How to cite this article:
Suchitra M M, Ashalatha V L, Sailaja E, Rao A M, Reddy V S, Bitla AR, Sivakumar V, Rao PS. The effect of L-Carnitine supplementation on lipid parameters, inflammatory and nutritional markers in maintenance hemodialysis patients. Saudi J Kidney Dis Transpl 2011;22:1155-9

How to cite this URL:
Suchitra M M, Ashalatha V L, Sailaja E, Rao A M, Reddy V S, Bitla AR, Sivakumar V, Rao PS. The effect of L-Carnitine supplementation on lipid parameters, inflammatory and nutritional markers in maintenance hemodialysis patients. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2019 Nov 22];22:1155-9. Available from: http://www.sjkdt.org/text.asp?2011/22/6/1155/87221

   Introduction Top


Cardiovascular disease (CVD) is the leading cause of mortality in hemodialysis (HD) patients. A number of factors and co-morbid conditions common in dialysis are implicated as risk factors, including diabetes, hypertension, hyperlipidemia, inflammation, anemia and imbalances in mineral metabolism. [1] An inflammatory process is common in HD, and is associated with an increased risk for CVD. [2]

Several treatment protocols are in practice for this purpose, and Carnitine supplementation is one of them. L-Carnitine is a small compound (molecular weight, 162 D) and represents one of the main sources of endogenous Carnitine synthesis from lysine, methionine, ascorbate, niacin, pyridoxine and iron. [3] Carnitine depletion in dialysis patients is due to various causes, in particular due to a marked decrease in the production of Carnitine. [4],[5] It has been known that plasma and tissue Carnitine levels are significantly decreased in patients on long-term HD due to loss through the dialyzer membrane. [6]

L-Carnitine administration has been proven to be clinically beneficial in diseases characterized by Carnitine deficiency, which include ischemic car-diomyopathy and peripheral atherosclerosis. L-Carnitine supplementation was found to improve the quality of life in terms of improvement in physical performance and various comorbid conditions, like weakness, poor exercise tolerance and easy fatigability. [7] However, reports on the effects of L-Carnitine supplementation in HD patients are not consistent and quite contradictory. Scattered reports indicate that supplementation of L-Carnitine will improve patient status and symptoms, with significant improvement in laboratory parameters, especially on lipid levels [8] and inflammatory and nutritional parameters [9],[10] among HD patients. On the contrary, there are studies indicating no significant benefit with L-Carnitine supplementation. [11],[12]

Hence, the present study was undertaken to evaluate the effect of L-Carnitine supplementation on nutritional and inflammatory markers and lipid, lipoprotein and apoprotein AI and B levels, as these factors may contribute to the excessive atherosclerotic cardiovascular mortality in dialysis patients.


   Materials and Methods Top


Subjects

We studied 35 patients with end-stage renal disease (ESRD) undergoing maintenance HD (for a period of 2 to 5 years) who consented to be a part of the study and were randomized in a single blinded manner to receive L-Carnitine or placebo at the SVIMS Hospital, Tirupati, Andhra Pradesh, for a period of six months between November 2007 and March 2008. A total of 20 patients were supplemented with L-Carnitine (study group) and the remaining 15 patients served as the control group. L-Carnitine was administered intravenously three times a week after each HD session, at a dose of 1 g/dose. The tests were performed at baseline and every month until the end of the study. The dialysis schedule of the patients was four hours dialysis sessions (three times in a week) using bicarbonate dialysate and polysulfone F5 membrane with a flow rate of 55 mL/min and a blood flow rate of 200 to 250 mL/min. The underlying causes of ESRD were diabetic nephropathy, hypertensive nephropathy, chronic glomerulonephritis, ischemic nephropathy and chronic interstitial nephritis. Patients with active infection and smokers were excluded from the study.

Sample Collection and Laboratory Analysis

Five milliliters of venous blood was collected in heparinzed tubes prior to the dialysis session, after an overnight fast. The samples were centrifuged at 3000 rpm for 15 min and the plasma was separated and stored at -80 o C until analysis. Highly sensitive C-reactive protein (hsCRP) and apo-protein AI and B (Apo AI and Apo B) were estimated by immuno-turbidimetric methods using APTEC Diagnostics kits on a Beckman Synchron CX9 auto-analyzer. Total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), total proteins and albumin were measured using commercially available kits on a Beckman Synchron CX9 auto-analyzer. Low-density lipo-protein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) were calculated using Friedewalds Formula. [13]


   Statistical Analysis Top


All the values obtained were expressed as mean and standard error of mean (SEM). Non-parametric Mann Whitney U test was applied to compare the difference in the means of the various biochemical parameters and differences were considered as significant at a P-value <0.05. Statistical analysis was carried out using SPSS version 11.5.


   Results Top


Demographic data of controls and study group are given in [Table 1]. Mean and standard error of mean, P-value of inflammatory and nutritional status represented by parameters such as hsCRP, total protein and albumin, and lipid parameters such as total cholesterol, triglycerides, HDL-C, LDL-C, VLDL-C, Apo AI and Apo B, of controls and study group are shown in [Table 2].
Table 1: Demographic data of control and study groups.

Click here to view
Table 2: Inflammatory and nutritional markers, lipids, lipoprotein and apoprotein levels in control and study groups.

Click here to view


There was no significant change in total pro­tein and albumin levels; the hsCRP levels were significantly lower in the Carnitine supplemented group (P < 0.05). According to the statistical analysis, we were unable to show improvement in total protein and albumin in the study group and, thus, the improvement can be attributed to Carnitine supplementation. No significant improvement was observed in lipid, lipoprotein and apoprotein levels in the Carnitine supplemented group, while a significant decrease in triglycerides and increase in HDL-C levels was observed in the control group.


   Discussion Top


Hemodialysis patients are at increased risk for CVD compared with the general population. Inflammation has been commonly observed in maintenance HD patients; inflammatory processes may be the possible cause of accelerated atherosclerosis as well as protein energy malnutrition (PEM), which lead to poor outcome in patients with underlying kidney disease. [14] Epidemiological studies have consistently shown a strong association between clinical outcomes and measures of both malnutrition and inflammation in dialysis patients. Both these conditions have been observed to co-exist in ESRD patients, and have been termed as malnutrition inflammation complex syndrome. [2] Carnitine deficiency is believed to be responsible for various co-morbid conditions in HD patients, and restoring serum or tissue Carnitine levels has been associated with improvement in some abnormalities.

Hence, L-Carnitine supplementation should carry beneficial effects on inflammatory, nutritional and lipid parameters, which are associated with a higher risk for CVD in HD patients.

Inflammation is a fundamental protective response in acute situations. However, a sustained chronic inflammatory process with an elevated level of inflammatory proteins may be a major determinant of the low quality of life and adverse effects in HD patients. [15] The gold standard among the inflammatory markers in HD is hsCRP, and it has been reported that elevated levels are positively correlated with cardiovascular events in dialysis patients. Inflammatory stimuli cause an increase in production of cytokines, such as IL-1, IL-6 and TNFα, which in turn lead to increased CRP levels. [16] L-Carnitine may suppress pro-inflammatory cytokines, and thereby decrease CRP levels. In this study, we found a significant decrease in hsCRP levels in the Carnitine-supplemented group, which signifies the beneficial effect of L-Carnitine supplementation on inflammatory status in HD patients. There are only few studies reporting the effect of L-Carnitine on hsCRP levels in HD patients, and this controlled study supports the findings.

Biochemical markers suggestive of undernutrition are directly correlated with mortality in HD; in particular, serum albumin is a significant predictor of mortality in HD patients. [17] Many studies have shown that supplementation of L-Carnitine leads to improvement in nutritional parameters in dialysis patients, [2] while other studies have indicated no significant benefit. [18] The present study revealed no significant effect of Carnitine on total protein and albumin levels, which is in agreement with the study of Fernandez-Reyes MJ et al. [17]

There are studies reporting the positive effects of L-Carnitine in terms of lipid parameters, [19],[20] despite other studies indicating no significant benefit. [21] However, we were not able to find any significant effect of L-Carnitine supplementation on serum lipid profile and Apo AI and Apo B levels. Our study is in accordance with that of Hurot JM et al, [21] who suggested that L-Carnitine supplementation cannot be recommended for treating dyslipidemia, particularly when compared with other currently approved medications.

In conclusion, our study shows that supplementation of L-Carnitine in HD patients may not have significant beneficial effects on nutritional status and lipid parameters, including apoproteins, but may be beneficial in reducing inflammatory status. This may be due to regional variations and dietary habits compared with other ethnic populations who consume a high-fat content diet. Supplementation of L-Carnitine is not recommended routinely to all the dialysis patients; nevertheless, a therapeutic trial can be beneficial in patients with certain clinical features unresponsive to usual measures of treatment. However, the findings of our study point toward the need to probe the effects of L-Carnitine supplementation further in a larger patient population.

 
   References Top

1.Josef K, Walter HH. Iron overload and cardiovascular complications in dialysis patients. Nephrol Dial Transplant 2002;17:S25-9.  Back to cited text no. 1
    
2.Kalantar-Zadeh K, Ikizler TA, Block G, Avram MM, Kopple JD. Malnutrition-inflammation complex syndrome in dialysis patients: Causes and consequences. Am J Kidney Dis 2003;42:864-81.  Back to cited text no. 2
    
3.Steiber A, Kerner J, Hoppel C. Carnitine: A nutritional, biosynthetic, and functional perspective. Mol Aspects Med 2004;25:455-73.  Back to cited text no. 3
    
4.Labonia W. L-carnitine effects on anemia in hemodialysis patients treated with erythropoietin. Am J Kidney Dis 1995;25:757-64.  Back to cited text no. 4
    
5.Giovenali P, Fenocchio D, Montanari G, et al. Selective tropic effect of L-carnitine in type I and type II skeletal muscle fibers. Kidney Int 1994;46:1616-9.  Back to cited text no. 5
    
6.Golper TA, Wolfson M, Ahmad S, et al. Multi center trial of L-carnitine in maintenance hemodialysis patients. I. Carnitine concentrations and lipid effects. Kidney Int 1990;38:904-11.  Back to cited text no. 6
    
7.Rahul R, Siraz BM, Khandelwal PN, Kulkarni SG, Gade PR, Samra S. Results of a single blind, randomized, placebo-controlled clinical trial to study the effect of intravenous L-Carnitine supplementation on health-related quality of life in Indian patients on maintenance hemodialysis. Indian J Med Sci 2006;143-52.  Back to cited text no. 7
    
8.Attman P, Samuelsson O, Johansson A, Moberly JB, Alaupovie P. Dialysis modalities and Dyslipidemia. Kidney Int 2003;63:S110-2.  Back to cited text no. 8
    
9.Savica V, Santoro D, Mazzaglia G, et al. L-carnitine infusions may suppress serum C-reactive protein and improve nutritional status in maintenance hemodialysis patients. J Ren Nutr 2005;15:225-30.  Back to cited text no. 9
    
10.Duranay M, Akay H, Yilmaz FM, Senes M, Tekeli N, Yucel D. Effects of L-carnitine infusions on inflammatory and nutritional markers in hemodialysis patients. Nephrol Dial Transplant 2006;21:3211-4.  Back to cited text no. 10
    
11.Chazot C, Blanc C, Hurot JM, et al. Nutritional effects of carnitine supplementation in hemodialysis patients. Clin Nephrol 2003;59:24-30.  Back to cited text no. 11
    
12.Hurot JM, Cucherat M, Haugh M, Fouque D. Effects of L-carnitine supplementation in maintenance hemodialysis patients: a systemic review. J Am Soc Nephrol 2002;13:708-14.  Back to cited text no. 12
    
13.Friedwald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma without the use of the preparative ultracentrifuge. Clin Chem 1992;18:499-502.  Back to cited text no. 13
    
14.Kalantar-Zadeh K, Rodriguez RA, Humphreys MH. Association between serum ferritin and measures of inflammation, nutrition and iron in haemodialysis patients. Nephrol Dial Transplant 2004;19:141-9.  Back to cited text no. 14
    
15.Kalantar-Zadeh K, Kopple JD. Relative Contributions of Nutrition and inflammation to clinical outcome in Dialysis patients. Am J Kidney Dis 2001;38:1343-50.  Back to cited text no. 15
    
16.Yeun JY, Levine RA, Mantadilok V, Kaysen GA. C-reactive protein predicts all-cause and cardiovascular mortality in hemodialysis patients. Am J Kidney Dis 2000;32:469-76.  Back to cited text no. 16
    
17.Fernandez-Reyes MJ, Alvarez-Ude F, Sanchez R, Mon C, Iglesias P, Vazquez A. Nutritional status, comorbidity, and inflammation in haemodialysis. Nefrologia 2000;20:540-9.  Back to cited text no. 17
    
18.Vesela E, Racek J, Trefil L, Jankovych V, Pojer M. Effect of L-carnitine supplementation in hemodialysis patients. Nephron 2001;88:218-23.  Back to cited text no. 18
    
19.Elisaf M, Bairaktari E, Katopodis K, et al. Effects of L-carnitine supplementation on lipid parameters in hemodialysis patients. Am J Nephrol 1998;18:416-21.  Back to cited text no. 19
    
20.Argani H, Rahbaninoubar M, Ghorbanihagjo A, Golmohammadi Z, Rashtchizadeh N. Effects of L-carnitine on serum lipoproteins and HDL-C subclasses in hemodialysis patients. Nephron Clin Pract 2005;101:174-9.  Back to cited text no. 20
    
21.Hurot JM, Cucherat M, Haugh M, Fouque D. Effects of L-carnitine supplementation in maintenance Hemodialysis patients: A Systemic Review. J Am Soc Nephrol 2002;13:708-14.  Back to cited text no. 21
    

Top
Correspondence Address:
P.V.L.N. Srinivasa Rao
Department of Biochemistry, Sri Venkateswara Institute of Medical Sciences, Tirupati - 517 507, Chittoor District, Andhra Pradesh
India
Login to access the Email id


PMID: 22089773

Rights and Permissions



 
 
    Tables

  [Table 1], [Table 2]

This article has been cited by
1 Mechanisms underlying the anti-wasting effect of l-carnitine supplementation under pathologic conditions: Evidence from experimental and clinical studies
Ringseis, R. and Keller, J. and Eder, K.
European Journal of Nutrition. 2013; 52(5): 1421-1442
[Pubmed]
2 Effect of L-carnitine supplementation with or without moderate aerobic training on serum lipid profile and body fat percentage in obese women
Karimi, M. and Rafraf, M. and Rashidi, M. and Jafari, A.
Iranian Journal of Endocrinology and Metabolism. 2013; 14(5)
[Pubmed]



 

Top
   
 
 
    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  
 


 
    Abstract
   Introduction
    Materials and Me...
   Statistical Analysis
   Results
   Discussion
    References
    Article Tables
 

 Article Access Statistics
    Viewed4392    
    Printed123    
    Emailed0    
    PDF Downloaded1220    
    Comments [Add]    
    Cited by others 2    

Recommend this journal