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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2007  |  Volume : 18  |  Issue : 4  |  Page : 571-576
The Effect of Low Dose Omega-3 on Plasma Lipids in Hemodialysis Patients


1 Mazandaran University of Medical Science, Iran
2 Tehran University of Medical Science, Iran

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   Abstract 

Hemodialysis (HD) patients have a high incidence of cardiovascular disease and increased premature mortality. N-3 polyunsaturated fatty acids (PUFAs) are known to decrease plasma triglyceride (TG) levels and have a cardio-protective effect in subjects with normal renal function. The aim of this study was to investigate the effect of Omega-3 on plasma lipid levels in patients on HD. We included 33 patients on HD with serum TG higher than 200 mg/dl and total cholesterol higher than 220 mg/dl, in the study and randomly assigned them to treatment with 2 gm pearls of Omega-3 per day, given in two equal doses or a control group who did not receive this drug. The study was conducted for a period of 12 weeks. Patients were evaluated by measurement of fasting plasma lipid levels before and after the use of Omega-3. There was a significant (28%) increase in high-density lipoprotein levels (P < 0.01) and a significant (23 %) decrease in serum TG levels (P < 0.02) in the group that received Omega-3 supplement. There were no changes in total cholesterol or low-density lipoprotein levels in either group. Our study suggests that supplementation with low-dose Omega-3 has a favorable effect on plasma lipid levels in patients on HD.

Keywords: Hemodialysis, hyperlipidemia, Omega-3

How to cite this article:
Taziki O, Lessan-Pezeshki M, Akha O, Vasheghani F. The Effect of Low Dose Omega-3 on Plasma Lipids in Hemodialysis Patients. Saudi J Kidney Dis Transpl 2007;18:571-6

How to cite this URL:
Taziki O, Lessan-Pezeshki M, Akha O, Vasheghani F. The Effect of Low Dose Omega-3 on Plasma Lipids in Hemodialysis Patients. Saudi J Kidney Dis Transpl [serial online] 2007 [cited 2019 Oct 14];18:571-6. Available from: http://www.sjkdt.org/text.asp?2007/18/4/571/36514

   Introduction Top


Cardiovascular disease is the major cause of morbidity and mortality in patients with chronic renal failure.[1],[2] The pathogenesis is not fully understood, but a high prevalence of traditional risk factors for cardiovascular disease,[3],[4] a chronic inflammatory state,[5] an atherogenic lipid profile with low high-density lipoprotein (HDL) levels,[6] elevated triglyceride (TG) levels and high prevalence of elevated levels of low-density lipoprotein (LDL)[7],[8] could all have a role. At least 40% of patients with end-stage renal disease have known cardiovascular disease when treatment with dialysis is initiated.[2] Accumulating evidence suggests that the fish oil-derived bioactive eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids mediate cell membrane function, signal transduction and eicosanoid production in a clinically beneficial manner. Fish oil has been shown in different subsets of population to ameliorate cardiovascular mor­tality, [9] dampen the inflamematory and athero­sclerotic processes, [10] and improve blood pressure and lipid status. [11],[12] Blood and tissue EPA and DHA levels are determined primarily by dietary consumption, for which fresh-water fish and to a lesser extent, other sea food products are the major dietary sources. [13] Consequently, inadequate fish consumption may lead to low blood Omega-3 levels which, in turn could detrimentally affect clinical out comes, particularly in such a vulnerable group as patients on HD. There are a number of reasons to believe that patients on long-term HD consume inadequate amounts of fish­derived Omega-3 fatty acids. Unfortunately, available data on fish consumption and Omega-3 fatty acid status in patients on HD are sparse, incomplete and often conflicting.

The aim of this study was to investigate the effect of low dose Omega-3 on lipid profile among patients on maintenance HD at the dialysis center of the Imam Khomeini Hospital in Tehran, Iran.


   Patients and Methods Top


Study population

Thirty-three non-diabetic patients on mainte­nance HD at the Imam Khomeini general hospital, Tehran were recruited for this rando­mized clinical trial. Criteria for enrollment was the presence of hyperlipidemia as indicated by fasting serum total cholesterol concentration greater than 220 mg/dl and fasting serum TG concentration greater than 200 mg/dl during the month prior to the commencement of the study. Also, the study subjects should not have received any specific treatment with lipid lowering drugs within the past month.

All subjects had been on regular thrice­weekly maintenance HD for at least six months and had no co-morbid illnesses; all had a normal fasting plasma glucose concentration. Exclusion criteria were the presence of liver disease, thyroid disease, severe hypertension or cancer and use of any medication known to affect lipid concentration.

All subjects were informed about the study and written informed consent was obtained before the beginning of the study. Subject who failed to comply with the diet or had a weight change of three Kg or greater during the study period were excluded from the final analysis. The study patients were randomly assigned to treatment with pearls of Omega-3, administered in a dose of one gram twice daily or, the control group who did not receive this drug. Omega-3 (Zahravy-Iran) was adminis­tered for a total of 12 weeks (each pearl of Omega-3 contains 60% N-3 PUFA content (EPA/DHA = 3/2).

During four weeks run-in phase, all subjects followed the usual HD diet. A registered dietitian instructed subjects on this diet and counseled them about their individual need for protein, fat and energy. After the run-in phase, baseline blood samples were drawn and patients were divided into two groups: one group that received treatment with Omega-3 and the other, to whom Omega-3 was not given.

Individual dietary counseling was provided in order to incorporate adequate protein in the diet without causing weight gain or change in protein or energy intake. This requirement was reinforced at visits to the clinic and moni­tored during the study by reviewing dietary recalls. Clinic visits were conducted during each dialysis session. At each clinic visit, empty packets from the previous visit were collected to determine compliance. A 24-hour dietary recall was performed for all subjects for three days every six weeks. All subjects were instructed to maintain their edema free body weight and not to take any nutritional supple­ments during the study period. No lipid­lowering drugs or medications known to affect lipid concentrations were used during the trial period. Laboratory technicians were blinded about the treatment and control groups.

Blood Sampling and Laboratory Methods

Blood samples were collected every six weeks after 10-12 hours of fasting. Labo­ratory assessments included fasting serum lipids (TC, TG, HDL, LDL), albumin and creatinine. Body weight was measured before and after each dialysis session; post-dialysis weight was used to calculate the body mass index (BMI). Daily intake of nutrients was estimated from 24-hour dietary recall and analyzed using standard food composition. Serum TC and TG were measured by the enzymatic method whereas HDL and LDL were quantified by means of the homogenous assay method using an automated analyzer (Olympus Au 2700). All serum nutritional parameters were determined by using an automated analyzer. Hemodialysis adequacy was monitored by measurement of a urea kinetic model (KT/V calculated from natural log formula). [14]

Statistics

Continuous data are reported as mean ± SD. P-value less than 0.05 was considered statis­tically significant. All P-values are two-tailed and all confidence interval levels were com­puted at the 95% level. All patients who completed the study were included in the statistical analysis. Changes from baseline within each group were evaluated by using paired T-Test. Comparison of groups was per­formed using students T-Test for continuous variables. The statistical software used for analysis was SPSS, Version 10.0.


   Results Top


Thirty-three patients completed the study. The two groups were well matched with respect to age, sex and BMI at baseline. The subject characteristics at baseline are listed in [Table - 1]. The body weight of the study subjects in each group remained stable throughout the study. No significant differ­rences were found between the two groups in intake of nutrients, serum nutritional para­meters and HD adequacy.

Plasma TC and TG concentration at baseline and six and 12 weeks after treatment are listed in [Table - 2]. After 12-weeks of treatment with Omega-3, the serum TG decreased by 23% and serum HDL increased by 28% in the treatment group; both were statistically signi­ficant (P <0.05). There was no change in total cholesterol or LDL levels in the treatment group. No significant changes were noted in the control group in any of the lipid para­meters studied.


   Discussion Top


This study shows that Omega-3 has a beneficial effect on serum lipid profile in hyperlipidemic HD patients. There was a significant reduction in serum levels of TG and increased the levels of HDL, when com­pared with the control group. The impor­tance of hypertriglyceridemia as a cardio­vascular risk factor has been a major issue of discussion. However, a recent meta-analysis showed a correlation between high plasma TG levels and cardiovascular events, with a 32% increase in cardiovascular events for men and 76% increase for women [15] and the significance of plasma TG level in cardiovas­cular disease is increasingly acknowledged. [16]

Prominent characteristics of uremic dys­lipidemia are an increase in TG-rich ApoB­containing lipoprotein levels and a decrease in HDL concentration. It is well documented that N-3 PUFA reduces serum TG concentration by 25 to 30% in healthy individuals as well as in patients with hypertriglyceridemia in a dose dependent manner. In the present study, we showed a similar 23% reduction in serum TG level in patients on HD with low-dose supplementation with Omega-3. No effect of Omega 3 was seen on serum LDL cholesterol levels. This is in accordance with other studies. However, a mild increase in LDL levels by N-3 PUFA has occasionally been reported in patients with hypertriglyceridemia.[17] Our study did not show such reduction in LDL levels. The cause of absence of this effect in our study may be due to administration of relatively low dose of Omega-3 (2 g/d). Three smaller studies showed similar pattern after supplementation with N-3 PUFA in HD patients. [8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20]

Khajedi et al, [19] showed a significant reduc­tion in serum TG level and an increase in HDL level after treatment with 1.5 gm of N-3 PUFA for three months compared with corn oil and placebo. Rolf et al, [20] and Azor et al, [18] showed similar reduction in serum TG con­centration after EpA administration. However, both these studies were small and uncon­trolled. Svenson et al, [21] showed similar reduction in serum TG and an increase in HDL levels after treatment with 2.4 gm N-3 PUFA in patients with CRF, which is in accordance with our results. Additionally, N-3 fatty acids have successfully been used in combination with stains in patients with combined hyperlipidemia. [22] The relationship of survival and serum cholesterol levels in patients undergoing treatment with HD has a u-shaped curve, in which mortality is increased in patients with low and high cho­lesterol levels. [23] It has been shown that mortality in patients on HD is related to low serum cholesterol levels only when they have associated low serum albumin levels. [24] For this reason, the importance of lipid levels as a risk factor in HD patients is somewhat complex and is dependant on other factors, such as nutritional status and inflammation. Biological effects of N-3 fatty acids have been showed in animal and human studies in which the anti-inflammatory and anti throm­botic effects, theoretically, could be of rele­vance in patients with renal disease. [25] Recently, an observational study with more than 200 patients treated with dialysis showed that dietary fish intake was inversely related to mortality, with a 50% reduction in total mor­tality among fish users. [26]

In the present study, we found that both regular fish intake and supplementation with Omega-3 have a favorable effect on serum lipids in patients on HD. Hence, N-3 PUFA administered as capsules or fatty fish intake should be part of a primary prevention strategy to reduce cardiovascular disease in this group of patients. However, further studies with hard end-points are needed to subs­tantiate this observation.

 
   References Top

1.Levin A. Foley R. Cardiovascular disease in Chronic renal insufficiency. Am J Kidney Dis 2000;36:524-30.  Back to cited text no. 1    
2.Levey AS, Beto JA, Coonado BE, et al. Controlling the epidemic of cardiovascular disease in Chronic renal disease: What do we Know? What do we need to learn? Where do we go from here? Am J Kidney Dis 1998;32:853-906,.  Back to cited text no. 2    
3.Garg AX, Clark WF, Haynes B, House AA. Moderate renal insufficiency and the risk of cardiovascular mortality: Results from the NHANES 1. Kidney Int 2002;61:1486-94.  Back to cited text no. 3    
4.Longenecker JC, Coresh J, Powe NR, et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE study. J Am Soc Neprol 2002;13:1918-27.  Back to cited text no. 4    
5.Koenig W. Update on C-reactive protein as a risk marker in cardiovascular disease. Kidney Int Suppl 2003;84:S58-61.  Back to cited text no. 5  [PUBMED]  
6.National kidney Foundation: K/DOQI Clinical Practice Guidelines for Managing Dyslipidemias in chronic kidney Disease. Am J Kidney Dis 2003;41:S8-58.  Back to cited text no. 6    
7.Deighan C, Casalake M, McConnell M, Bolton-Jones JM, Packard C. Atherogenic lipoprotein phenotype in end-stage renal failure: Origin and extent of small dense low-density lipoprotein formation. Am J Kidney Dis 2000;35:852-62.  Back to cited text no. 7    
8.Rajman,Harper L, McPake D, Kendall M. Where D: Low-density lipoprotein sub fraction profiles in chronic renal failure. Neohrol Dial Transplant 1998;13:2281-7.  Back to cited text no. 8    
9.Gruppo Italiano per lo Studio della Sopravvivenzanell' Infarto Miocardio: Dietary Supplementation with n-3 infarction: RESULTS of the GISSI-Preventions trial. Lancet 1999;354:447-55.  Back to cited text no. 9    
10.De Caterina R, Zampolli A. From asthma to atherosclerosis-5 Lipoxygenase, leukotriense and inflammation. N Engl J Med 2004; 350:4-7.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]
11.Appel LJ, Miller ER 3 rd , Seidler AJ, Whelton PK. Does supplementation of diet with fish oil reduce blood pressure? A meta- analysis of controlled clinical trials. Arch Intern Med 1993;153:1429-38..  Back to cited text no. 11    
12.Harris WS. n-3 Fatty acids and serum lipoproteins: Human studies Am J Clin Nutr 1997;65:S1645-54.  Back to cited text no. 12    
13.Kris - Etherton PM, Taylor DS, Yu-Poth S, et al. Polyunsaturated fatty acids in the food chain in the United states. Am J Clin Nutr 2000;71:S179-88.  Back to cited text no. 13    
14.National Kidney Foundation: K/DOQI Clinical Practice Guidelines for Nutrition in Chronic Renal Failure. Am J Kidney Dis 2000;35:S1-140.  Back to cited text no. 14    
15.Austin M, Hokanson I, Edwards K. Hyper­triglyceridemia as a cardiovascular risk factor. Am J Cordial 1998;81:7B-12.  Back to cited text no. 15    
16.Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection Evaluation and Treatment of High Cholesterol in adult. Circulation 2002; 106:3143-421.  Back to cited text no. 16    
17.Harris WS. N-3 Fatty acids and serum lipoproteins: human studies. Am J Clin Nutr 1997;65:S1645-54.  Back to cited text no. 17    
18.Azar R, Dquitedt F, Awada J, Dequitedt P, Taquet A. Effect of fish oil rich in polyunsaturated fatty acids on hyperlipedemia of hemodialysis patients. Kidney Int Suppl 1989;27:S239-42.  Back to cited text no. 18    
19.Khajehdehi P. lipid lowering effect of polyunsaturated fatty acids in hemodialysis patients. J Ren Nut 2000;10:191-5.  Back to cited text no. 19    
20.Rolf N, Tenschert W, Lesson AE. Result of long term administration of omega -3 fatty acids in hemodialysis patients with dyslipo­proteinemia. Nephrol Dial Transplant 1990;5: 797-801.  Back to cited text no. 20    
21.Svensson MY, Christensen JH, Solling J, Schmidt EB. The effect of n-3 Fatty acids on plasma lipids and lipoproteins and blood pressure in patients with CRF. Am J Kidney Dis 2004;44:77-83.  Back to cited text no. 21    
22.Norday A. Statins and omega-3 fatty acids in the treatment of dyslipidemia and coronary heart disease. Minerva Med 2002;93:357-­63.  Back to cited text no. 22    
23.Lowrie EG, Lew NL. Death risk in hemodialysis patients: The predictive rate of commonly measured variable and an evaluation of death rate differences between facilities. Am J Kidney Dis 1990;15:458-­82.  Back to cited text no. 23  [PUBMED]  
24.Iseki K, Yamazato M, Tozava M, Takashita S. Hypocholestrolemia is a significant predictor of death in a cohort of chronic hemodialysis patients. Kidney Int 2002;61: 1887-93.  Back to cited text no. 24    
25.De Catrina R, Endres S, Kristiansen SD, Schmidt EB. N-3 Fatty acids and renal disease. Am J Kidney Dis 1994;24:397-415  Back to cited text no. 25    
26.Kutner NG, Clow PW, Zhang R, Aviles X. Association of fish intake and survival in a cohort of incident dialysis patients. Am J Kidney Dis 2002;39:1018-24.  Back to cited text no. 26  [PUBMED]  [FULLTEXT]

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Correspondence Address:
O Taziki
Department of Nephrology, Mazandaran University of Medical Sciences, Imam Khomeini Hospital, Sari
Iran
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PMID: 17951945

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    Tables

  [Table - 1], [Table - 2]

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