|
Effect of omega-3 supplementation on inflammatory parameters in patients on chronic ambulatory peritoneal dialysis
Afsoon Emami Naini, Reza Ebrahimi Kord Asiabi, Noushin Keivandarian, Firouzeh Moeinzadeh
Department of Internal Medicine, Isfahan Kidney Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| Date of Submission | 09-Feb-2014 |
| Date of Acceptance | 30-Nov-2014 |
| Date of Web Publication | 10-Aug-2015 |
Correspondence Address:
Dr. Firouzeh Moeinzadeh
Department of Internal medicine, Isfahan Kidney Diseases Research Center, Isfahan University of Medical Sciences, Isfahan
Iran
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2277-9175.162544
Clinical trial registration IRCT201303052417N11
Background: End stage renal disease (ESRD) is a state of micro inflammation that attenuates patient's life span and quality of life. Inflammatory markers like interlukin 6 (IL-6) and C- reactive protein (CRP) can predict inflammatory state in ESRD patients. Dietary limitations are risk factors for omega-3 deficiency in these patients. Omega-3 supplementation is an attractive material that proposed in inflammation modulation. The aim of this study is evaluation of effect of omega-3 supplementation on IL-6 and CRP level in chronic ambulatory peritoneal dialysis (CAPD) patients.
Materials and Methods: This randomized controlled double-blind clinical trial is performed in 40 CAPD patients in two academic hospitals in Isfahan, Iran. One group received 1000 mg omega-3 capsule (each capsule contains 180 mg Eicosapentanoic and 120 mg Dosahexanoic acid) three times a day orally for 8 weeks (n = 20) and the other matched group by placebo (n = 20). Serum level of IL-6 and quantitative CRP (Q-CRP) were measured in beginning and the end of the study. Finally all data were analyzed by SPSS version 18.
Results: Mean age of patients was 53 years old in omega-3 group patients and 54 years old in placebo group. There were not any differences in CRP and IL-6 level in the beginning and the end of study between two groups (P: 0.81 and 0.10 for CRP and 0.26 and 0.23 for IL-6, respectively).
Conclusion: Omega-3 supplementation did not effect on inflammatory markers (Q-CRP and IL-6) in CAPD patients after 8 weeks. Keywords: C- reactive protein, chronic ambulatory peritoneal dialysis, interlukin 6, omega-3
How to cite this article:
Naini AE, Asiabi RE, Keivandarian N, Moeinzadeh F. Effect of omega-3 supplementation on inflammatory parameters in patients on chronic ambulatory peritoneal dialysis. Adv Biomed Res 2015;4:167 |
How to cite this URL:
Naini AE, Asiabi RE, Keivandarian N, Moeinzadeh F. Effect of omega-3 supplementation on inflammatory parameters in patients on chronic ambulatory peritoneal dialysis. Adv Biomed Res [serial online] 2015 [cited 2023 Jun 1];4:167. Available from: https://www.advbiores.net/text.asp?2015/4/1/167/162544 |
| Introduction | |  |
Mortality in end stage renal disease patients (ESRD) is correlated with traditional and nontraditional or "novel" risk factors. [1] In Framingham Heart study, some characteristics like sex, hypertension, age, diabetes mellitus, smoking regarded as traditional risk factors. In addition, in some researches, some other risk factors including hypoalbuminemia, increased fibrinogen level and inflammation had related to cardiovascular mortality and morbidity referred as non-traditional risk factors. [2] Susceptibility to increasing inflammatory process look multiple reasons, perhaps of dialysis or non-dialysis factors. [3] In uremic patients, cytotoxines can generate excess oxidative stress that ultimately produce reactive oxygen species (ROS). [4],[5] Therefore, advanced glycation endproducts (AGEs) are produced and convert short-lasting inflammatory responses to sustained pro-inflammatory reactions that induce atherosclerosis and calcifications. [6],[7] Some inflammatory biomarkers are recognized in these processes that C-reactive protein (CRP) is the attractive molecules between them. [8] ESRD patients have elevated level of CRP due to dialysis membranes, fluid overload or chronic persistent infections caused by grafts and catheters. [9] According to one study, serum CRP level is associated with higher mortality independent of serum albumin level. [10] Another biomarker that was proposed as an useful molecule is interlukin-6 (IL-6) that acts as pro- and anti-inflammatory cytokine. [11] Serum level of IL6 in ESRD patients increases and its level do not change pre and post hemodialysis. [12] Some materials including fish oil could reduce atherosclerosis and inflammation via inhibition of lipid peroxidation. [13] However, some investigations describe the benefits of omega-3 supplementation in prevention of inflammation progression in hemodialysis patients. [14],[15] But few studies are designed for effect of omega-3 in peritoneal dialysis patients, as a modality for renal replacement therapy. [16],[17] In this study, we decided to evaluate the effect of omega-3 on IL6 and CRP, as inflammatory parameters, on CAPD patients.
| Materials and Methods | | |
This randomized controlled double-blind clinical trial was carried out in two CAPD centers in two university hospitals in Isfahan, Iran. Patients with ESRD on continuous ambulatory peritoneal dialysis for at least 3 months and at least 18 years old enrolled in the study after agreement of consent form. If the patients had thrombocytopenia (PLT < 100,000/mm 3 ), steatorrhea, malignancy, abnormal coagulation profile or need for anticoagulation therapy, they exclude from the study.
All patients those were enrolled into the study were divided into two groups as shown in [Figure 1]. In case group (N = 40), they receive omega-3 capsule, three times a day for 2 months. Each 1 gram capsule (Omega-3, Zahravi co. Tabriz. Iran) contains Eicosapentanoic (180 mg) and Dosahexanoic (120 mg). In placebo group (N = 40) they receive placebo capsule, manufactured by the same as case group. All capsules have opaque enveloped and each patient receives the drugs for 2 months. After this, patient is admitted for evaluation of compliance, side effects and managing some possible problems. The next drugs enveloped were given them 1 month later. Serum levels of Interlukin-6 (IL-6) and C-reactive protein (CRP) were measured at beginning and the end of the study using auto analyzer, by standard kits.
Patients were notified of the possibility of adverse effects such as abdominal pain, bloating, diarrhea, nausea and bleeding during the study. Incidence of these symptoms was evaluated by a specific questionnaire.
Statistical analysis
This study has approved by Isfahan Kidney Diseases Research Center (project no. 391350) and ethical committee of Isfahan University of Medical Sciences. This study was registered in Iranian registry of clinical trials with ID number: IRCT201303052417N11.
All statistical analyses were performed with SPSS software (version 18.0 SPSS Inc, Chicago, IL, USA). Statistical analysis was done with χ2 test, paired t-test and analysis of variance (ANOVA). A 2-sided probability value of < 0.05 was considered statistically significant and a 95% confidence interval was used.
| Results | | |
A total of 40 patients allowed to participating in this study. All candidates were randomized into either Omega-3 therapy (n = 20) or placebo therapy (n = 20). During this study, any patient describes significant side effects leading to drug discontinuation in both groups.
Demographic and baseline characteristics of all patients included in the study are shown in [Table 1]. Our data showed no significant difference between two groups regarding age, sex, body mass index (BMI), medication usage and cause of renal failure. | Table 1: Demographic characteristics of CAPD Patients at the start of study
Click here to view |
After 2 months, mean serum level of CRP were not shown significant differences analytic (P = 0.047 and 0.054 respectively). This finding was similar about IL-6 after 2 months supplementation between omega-3 and placebo groups (P = 0.064 and 0.066). Details of data are demonstrated in [Table 2] and [Table 3]. | Table 2: Comparison of Interlukin-6 (IL-6) and quantitative C-reactive protein (Q-CRP) in baseline and at 8 weeks in two groups
Click here to view |
 | Table 3: Comparison of Delta Interlukin-6 (IL-6) and Delta quantitative C-reactive protein (Q-CRP) in baseline and at 8 weeks in two groups
Click here to view |
| Discussion | | |
Inflammation in ESRD patients is a destructive state that has an important role in atherosclerosis and cardiovascular diseases. This process is mediated by some mediators like Interleukins, CRP and tumor necrotizing factor. [15],[18],[19] Some studies suggest that CRP is not only a marker of inflammation.
Inflammation but also be a direct mediator of vascular disease. [20] On the other hand, inflammation is a common process in renal failure that could predict outcome in chronic kidney diseases, in all stages. [21] Therefore, we can suppress this process with using substances that can suppress inflammation. Between these, omega-3, [18] magnesium, [22] Zinc [23] and dietary antioxidants [24] have been studied till now. Omega-3 fatty acids act via modulation of cell membrane and synthesis of lipid mediators. Omega-3 fatty acid is derived from α-linolenic acid (ALA) then converts to eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) in endoplasmic reticulum and peroxisomes, respectively. [25] Ultimately, anti inflammatory effects of omega-3 derived from down regulation of proinflammatory cytokines and cell surface molecules areinvolved in cell adhesion and activation. [26] For this reason, fish oil is used for some inflammatory states like in rhomatoid arthritis, [27] crohn, [28] Ig A nephropathy, [29] sepsis, [30] too.
Some studies are performed in end stage renal disease patients in order to evaluation and benefit assessment of omega-3 on inflammatory processes. Madsen et al.,[31] demonstrate that there was no significant differences in serum level of CRP in ESRD patients on hemodialysis after daily supplementation with 2.4 g omega-3 for 8 weeks compared to placebo group. Tayyebi et al.,[32] describe similar findings in their study but reveal significant decreases in serum level of TNF-α after 3 g omega-3 per day. Although Sahinarslan described that serum level of IL-6, TNF-α and CRP had no differences in two types of dialysis (hemodialysis or peritoneal dialysis), the most studies did in hemodialysis patients. [32] In our study, we did not find any significant changes in serum level of IL-6 and CRP after supplementation with omega-3. This finding is against the Tayyebi study, although that study was done in hemodialysis patients. [33]
| Conclusion | | |
Omega-3 supplementation did not have effect on inflammatory markers (Q-CRP and IL-6) in CAPD patients after 8 weeks.
| References | | |
| 1. | Yao Q, Pecoits-Filho R, Lindholm B, Stenvinkel P. Traditional and non-traditional risk factors as contributors to atherosclerotic cardiovascular disease in end-stage renal disease. Scand J Urol Nephrol 2004;38:405-16.  |
| 2. | Shlipak MG, Fried LF, Cushman M, Manolio TA, Peterson D, Stehman-Breen C, et al. Cardiovascular mortality risk in chronic kidney disease: Comparison of traditional and novel risk factors. JAMA 2005;293:1737-45. |
| 3. | Stenvinkel P, Ketteler M, Johnson RJ, Lindholm B, Pecoits-Filho R, Riella M, et al. IL-10, IL-6, and TNF-alpha: Central factors in the altered cytokine network of uremia--the good, the bad, and the ugly. Kidney Int 2005;67:1216-33. |
| 4. | Betjes MG. Immune cell dysfunction and inflammation in end-stage renal disease. Nat Rev Nephrol 2013;9:255-65. |
| 5. | Locatelli F, Canaud B, Eckardt KU, Stenvinkel P, Wanner C, Zoccali C. Oxidative stress in end-stage renal disease: An emerging threat to patient outcome. Nephrol Dial Transplant 2003;18:1272-80. |
| 6. | Axelsson J, Qureshi AR, Suliman ME, Honda H, Pecoits-Filho R, Heimbu¨rger O, et al. Truncal fat mass as a contributor to inflammation in end-stage renal disease. Am J Clin Nutr 2004;80:1222-9. |
| 7. | Tavafi M. Diabetic nephropathy and antioxidants. J Nephropathol 2013;2:20-7. |
| 8. | Schwedler S, Filep J, Galle J, Wanner C, Potempa LA. C-Reactive Protein: A family of proteins to regulate cardiovascular function. Am J Kidney Dis 2006;47:212-22. |
| 9. | Pupim LB, Himmelfarb J, McMonagle E, Shyr Y, Ikizler TA. Influence of initiation of maintenance hemodialysis on biomarkers of inflammation and oxidative stress. Kidney Int 2004;65:2371-9. |
| 10. | Nasri H. Serum C reactive protein (CRP) in association with various nutritional parameters in maintenance hemodialysis patients. Bratisl Lek Listy 2005;106:390-5. |
| 11. | Jones S, Horiuchi S, Topley N, Yamamoto N, Fuller G. The soluble interleukin 6 receptor: Mechanisms of production and implications in disease. FASEB J 2001;15:43-58. |
| 12. | Memoli B, Romano G, D'Arcangelo R, Del Prete M, Esposito P, Procino A, et al. The Role of Interleukin-6 and of Its Soluble Receptors in the Biocompatibility of Dialysis Treatment. Semin Nephrol 2004;24:492-4. |
| 13. | Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: The Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383-9. |
| 14. | Tayyebi-Khosroshahi H, Houshyar J, Tabrizi A, Vatankhah AM, Razzagi Zonouz N, Dehghan-Hesari R. Effect of Omega-3 Fatty Acid on Oxidative Stress in Patients on Hemodialysis. Iran J Kidney Dis 2010;4:322-6. |
| 15. | Pekovic PG, Milutinovic RZ, Gluvic Z, Lackovic M, Medic DR, Glibetic M. Inflammation, nutritional status PUFA profile and outcome in hemodialysis patients. Arch Biol Sci 2012;64:1173-80. |
| 16. | Filiopoulos V, Hadjiyannakos D, Takouli L, Metaxaki P, Sideris P, Vlassopoulos D. Inflammation and oxidative stress in end-stage renal disease patients treated with hemodialysis or peritoneal dialysis. Int J Artif Organs 2009;32:872-82. |
| 17. | Taheri S, Keyvandarian N, Moeinzadeh F, Mortazavi M, Emami Naini AE. The effect of omega-3 fatty acid supplementation on oxidative stress in continuous ambulatory peritoneal dialysis patients. Adv Biomed Res 2014;3:143. [ PUBMED]  |
| 18. | Friedman A, Moe S. Review of the Effects of Omega-3 Supplementation in Dialysis Patients. Clin J Am Soc Nephrol 2006;1:182-92. |
| 19. | Stenvinkel P. Inflammatory and atherosclerosis interactions in the depleted uremic patients. Blood Purif 2001;19:53-61. |
| 20. | Li JJ, Fang CH. C-reactive protein is not only an inflammatory marker but also a direct cause of cardiovascular disease. Med Hypotheses 2004;62:499-506. |
| 21. | Stenvinkel P. Inflammation in end-stage renal disease: The hidden enemy. Nephrol 2006;11:36-41. |
| 22. | Mortazavi M, Moeinzadeh F, Saadatnia M, Shahidi SH, McGee JC, Minagar A. Effect of agnesium Supplementation on Carotid Intima-Media Thickness and Flow-Mediated Dilatation among Hemodialysis Patients: A Double-Blind, Randomized, Placebo-Controlled Trial. Eur Neurol 2013;69:309-16. |
| 23. | Guo CH, Wang CL. Effects of Zinc Supplementation on Plasma Copper/Zinc Ratios, Oxidative Stress, and Immunological Status in Hemodialysis Patients. Int J Med Sci 2013;10:79-89. |
| 24. | Sahni N, Gupta KL. Dietary antioxidants and oxidative stress in predialysis chronic kidney disease patients. J Nephropathology 2012;1:134-42. |
| 25. | Hussein N, Ah-Sing E, Wilkinson P, Leach C, Griffin BA, Millward DJ. Long-chain conversion of [13C] linoleic acid and alpha-linolenic acid in response to marked changes in their dietary intake in men. J Lipid Re 2005;46:269-80. |
| 26. | De Caterina R, Cybulsky MI, Clinton SK, Gimbrone MA Jr, Libby P. The omega-3 fatty acid docosahexaenoate reduces cytokine-induced expression of proatherogenic and proinflammatory proteins in human endothelial cells. Arterioscler Thromb 1994;14:1829-36. |
| 27. | Calder PC. Joint Nutrition Society and Irish Nutrition and Dietetic Institute Symposium on 'Nutrition and autoimmune disease' PUFA, inflammatory processes and rheumatoid arthritis. Proceedings of the Nutrition Society 2008;67:409-18. |
| 28. | Belluzzi A, Brignola C, Campieri M, Pera A, Boschi S, Miglioli M. Effect of an enteric- coated fish oil preparation on relapses in Crohn s disease. N Engl J Med 1996;334:1557-60. |
| 29. | Donadio JV Jr, Bergstralh EJ, Offord KP, Spencer DC, Holley KE. A controlled trial of fish oil in IgA nephropathy. Mayo Nephrology Collaborative Group. N Engl J Med 1994;331:1194-9. |
| 30. | Fetterman JW Jr, Zdanowicz MM. Therapeutic potential of n-3 polyunsaturated fatty acids in disease. Am J Health Syst Pharm 2009;66:1169-79. |
| 31. | Madsen T, Schmidt EB, Christensen JB. The effect of n-3 fatty acids on C- reactive protein levels in patients with chronic renal failure. J Ren Nutr 2007;17:258-63. |
| 32. | Tayyebi-Khosroshahi H, Houshyar J, Dehghan-Hesari R, Alikhah H, Vatankhah A, Safaeian AR, et al. Effect of treatment with Omega-3 Fatty Acid on C reactive protein and tumor necrosis factor-alfa in hemodialysis patients. Saudi J Kidney Dis Transpl 2012;23:500-6. [ PUBMED] |
| 33. | Şahinarslan A, Güz G, Mutluay R, Okyay K, Demirtaş C, Paşaoğlu H, et al. The impact of dialysis type on biomarkers for cardiovascular diseases. Arch Turk Soc Cardiol 2011;39:456-62. |
[Figure 1]
[Table 1], [Table 2], [Table 3]
| This article has been cited by | | 1 |
Effects of Omega-3 Fatty Acid Intake in Patients Undergoing Dialysis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials |
|
| Rui Liu,Jiawei Jiang,Zhangning Fu,Chao Liu,Linong Yao,Hong Quan | | Journal of the American College of Nutrition. 2021; : 1 | | [Pubmed] | [DOI] | | | 2 |
Could Antioxidant Supplementation Delay Progression of Cardiovascular Disease in End-Stage Renal Disease Patients? |
|
| Stefanos Roumeliotis,Athanasios Roumeliotis,Xenia Gorny,Peter R. Mertens | | Current Vascular Pharmacology. 2020; 19(1): 41 | | [Pubmed] | [DOI] | | | 3 |
Efficacy of Polyunsaturated Fatty Acids on Inflammatory Markers in Patients Undergoing Dialysis: A Systematic Review with Network Meta-Analysis of Randomized Clinical Trials |
|
| Po-Kuan Wu,Shu-Ching Yeh,Shan-Jen Li,Yi-No Kang | | International Journal of Molecular Sciences. 2019; 20(15): 3645 | | [Pubmed] | [DOI] | | | 4 |
Antioxidant Supplementation in Renal Replacement Therapy Patients: Is There Evidence? |
|
| Vassilios Liakopoulos,Stefanos Roumeliotis,Andreas Bozikas,Theodoros Eleftheriadis,Evangelia Dounousi | | Oxidative Medicine and Cellular Longevity. 2019; 2019: 1 | | [Pubmed] | [DOI] | | | 5 |
The impact of omega-3 fatty acid supplementation on glycemic control in patients with gestational diabetes: a systematic review and meta-analysis of randomized controlled studies |
|
| Li Gao,Liyuan Lin,Nan Shan,Chun-Yan Ren,Xin Long,Yu-Han Sun,Lan Wang | | The Journal of Maternal-Fetal & Neonatal Medicine. 2018; : 1 | | [Pubmed] | [DOI] | | | 6 |
A Randomized Double-Blinded, Placebo-Controlled Trial Investigating the Effect of Fish Oil Supplementation on Gene Expression Related to Insulin Action, Blood Lipids, and Inflammation in Gestational Diabetes Mellitus-Fish Oil Supplementation and Gestational Diabetes |
|
| Mehri Jamilian,Mansooreh Samimi,Naghmeh Mirhosseini,Faraneh Afshar Ebrahimi,Esmat Aghadavod,Mohsen Taghizadeh,Zatollah Asemi | | Nutrients. 2018; 10(2): 163 | | [Pubmed] | [DOI] | | | 7 |
Update on the Impact of Omega 3 Fatty Acids on Inflammation, Insulin Resistance and Sarcopenia: A Review |
|
| | | International Journal of Molecular Sciences. 2018; 19(1): 218 | | [Pubmed] | [DOI] | | | 8 |
CRP, IL-2 and TNF-a level in patients with uremia receiving hemodialysis |
|
| Guohui Li,Haijun Ma,Yaoyao Yin,Junxia Wang | | Molecular Medicine Reports. 2017; | | [Pubmed] | [DOI] | | | 9 |
Beneficial Effects of 6-Month Supplementation with Omega-3 Acids on Selected Inflammatory Markers in Patients with Chronic Kidney Disease Stages 1–3 |
|
| Agnieszka Pluta,Pawel Strózecki,Jacek Kesy,Kinga Lis,Beata Sulikowska,Grazyna Odrowaz-Sypniewska,Jacek Manitius | | BioMed Research International. 2017; 2017: 1 | | [Pubmed] | [DOI] | | | 10 |
A Randomized Controlled Clinical Trial Investigating the Effects of Omega-3 Fatty Acids and Vitamin E Co-Supplementation on Biomarkers of Oxidative Stress, Inflammation and Pregnancy Outcomes in Gestational Diabetes |
|
| Mehri Jamilian,Shahrzad Hashemi Dizaji,Fereshteh Bahmani,Mohsen Taghizadeh,Mohammad Reza Memarzadeh,Maryam Karamali,Maryam Akbari,Zatollah Asemi | | Canadian Journal of Diabetes. 2016; | | [Pubmed] | [DOI] | |
|
 |
|
|
|
Search Pubmed for