Anthocyanins-rich interventions on oxidative stress, inflammation and lipid profile in patients undergoing hemodialysis: meta-analysis and meta-regression.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8804070 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5640 (Electronic) Linking ISSN: 09543007 NLM ISO Abbreviation: Eur J Clin Nutr Subsets: MEDLINE

Publication: <2003->: London : Nature Publishing Group
Original Publication: London : J. Libbey, c1988-

Anthocyanins*/therapeutic use ; Dyslipidemias*/complications ; Dyslipidemias*/drug therapy ; Inflammation*/complications ; Inflammation*/drug therapy ; Oxidative Stress*/drug effects ; Renal Insufficiency, Chronic*/complications ; Renal Insufficiency, Chronic*/therapy; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Cholesterol, HDL/analysis ; Dietary Supplements ; Renal Dialysis

The aim of this systematic review and meta-analysis was to evaluate the effects of anthocyanins-interventions on oxidative stress, inflammation, and lipid profile in patients undergoing hemodialysis. This systematic review and meta-analysis were registered on the International Prospective Register of Systematic Reviews (PROSPERO CRD42020209742). The primary outcome was anthocyanins-rich intervention on OS parameters and secondary outcome was anthocyanins-rich intervention on inflammation and dyslipidemia. RevMan 5.4 software was used to analyze the effect size of anthocyanins-rich intervention on OS, inflammation and dyslipidemia. Meta-analysis effect size calculations incorporated random-effects model for both outcomes 1 and 2. Eight studies were included in the systematic review (trials enrolling 715 patients; 165 men and 195 women; age range between 30 and 79 years). Anthocyanin intervention in patients undergoing hemodialysis decrease the oxidant parameters (std. mean: -2.64, 95% CI: [-3.77, -1.50], P ≤ 0.0001, I ²  = 97%). Specially by reduction of malondialdehyde products in favor of anthocyanins-rich intervention (std. mean: -14.58 µmol.L, 95% CI: [-26.20, -2.96], P ≤ 0.0001, I ²  = 99%) and myeloperoxidase (std. mean: -1.28 ηg.mL, 95% CI: [-2.11, -0.45], P = 0.003, I ²  = 77%) against placebo group. Decrease inflammatory parameters (std. mean: -0.57, 95% CI: [-0.98, -0.16], P = 0.007, I ²  = 79%), increase HDL cholesterol levels (std. mean: 0.58 mg.dL, 95% CI: [0.23, 0.94], P = 0.001, I ²  = 12%) against placebo group. Anthocyanins-rich intervention seems to reduce oxidative stress, inflammatory parameters and improve lipid profile by increasing HDL cholesterol levels in patients with chronic kidney disease undergoing hemodialysis.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Bikbov B, Purcell CA, Levey AS, Smith M, Abobli A, Abebe M, et al. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020;395:709–33. (PMID: 10.1016/S0140-6736(20)30045-3)
Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, et al. Chronic kidney disease: global dimension and perspectives. Lancet 2013;382:260–72. (PMID: 2372716910.1016/S0140-6736(13)60687-X)
Stevens PE, Levin A. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013;158:825–30. (PMID: 2373271510.7326/0003-4819-158-11-201306040-00007)
Hill NR, Fatoba ST, Oke JL, Hirst JA, O’Callaghan CA, Lasserson DS, et al. Global Prevalence of Chronic Kidney Disease - A Systematic Review and Meta-Analysis. PLoS ONE. 2016;11:e0158765. (PMID: 27383068493490510.1371/journal.pone.0158765)
Lv JC, Zhang LX. Prevalence and Disease Burden of Chronic Kidney Disease. Adv Exp Med Biol. 2019;1165:3–15. (PMID: 3139995810.1007/978-981-13-8871-2_1)
Liu B, Lan H, Lv L. Renal Fibrosis: Mechanisms and Therapies. Advances in Experimental Medicine and Biology. Singapure: Springer; 1st ed. 2019.
Himmelfarb J, Ikizler TA. Hemodialysis. N Engl J Med. 2010;363:1833–45. (PMID: 2104722710.1056/NEJMra0902710)
Liyanage T, Ninomiya T, Jha V, Neal B, Patrice HM, Okpechi I, et al. Worldwide access to treatment for end-stage kidney disease: a systematic review. Lancet 2015;385:1975–82. (PMID: 2577766510.1016/S0140-6736(14)61601-9)
Wang V, Vilme H, Maciejewski ML, Boulware LE. The Economic Burden of Chronic Kidney Disease and End-Stage Renal Disease. Semin Nephrol. 2016;36:319–30. (PMID: 2747566210.1016/j.semnephrol.2016.05.008)
Silva Junior GBD, Oliveira JGR, Oliveira MRB, Vieira LJES, Dias ER. Global costs attributed to chronic kidney disease: a systematic review. Rev Assoc Med Bras (1992). 2018;64:1108–16. (PMID: 3056998710.1590/1806-9282.64.12.1108)
Neovius M, Jacobson SH, Eriksson JK, Elinder CG, Hylander B. Mortality in chronic kidney disease and renal replacement therapy: a population-based cohort study. BMJ Open. 2014;4:e004251. (PMID: 24549162393198810.1136/bmjopen-2013-004251)
Lowe F. Biomakers of oxidative stress. In: Laher I, editor. Systems of Biology of Free Radical and Antioxidants. 2. Berlin, Heidelberg:Springer; 2014. p. 65–87.
Liakopoulos V, Roumeliotis S, Gorny X, Dounousi E, Mertens PR. Oxidative stress in hemodialysis patients: a review of the literature. Oxid Med Cell Longev. 2017;2017:3081856. (PMID: 291386775613374)
Liakopoulos V, Roumeliotis S, Zarogiannis S, Eleftheriadis T, Mertens PR. Oxidative stress in hemodialysis: Causative mechanisms, clinical implications, and possible therapeutic interventions. Semin Dial. 2019;32:58–71. (PMID: 3028878610.1111/sdi.12745)
Mafra D, Borges NA, Lindholm B, Shiels PG, Evenepoel P, Stenvinkel P. Food as medicine: targeting the uraemic phenotype in chronic kidney disease. Nat Rev Nephrol. 2020;3:153–171.
Sebastian RS, Enns CW, Goldman JD, Martin CL, Steinfeldt LC, Murayi T, et al. A new database facilitates characterization of flavonoid intake, sources, and positive associations with diet quality among US adults. J Nutr. 2015;145:1239–48. (PMID: 25948787444212010.3945/jn.115.213025)
Abdal Dayem A, Choi HY, Yang GM, Kim K, Saha SK, Cho SG. The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms. Nutrients. 2016;9:581. (PMID: 10.3390/nu8090581)
Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA. Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr. 2001;74:418–25. (PMID: 1156663810.1093/ajcn/74.4.418)
Smeriglio A, Barreca D, Bellocco E, Trombetta D. Chemistry, Pharmacology and Health Benefits of Anthocyanins. Phytother Res. 2016;30:1265–86. (PMID: 2722103310.1002/ptr.5642)
Khoo HE, Azlan A, Tang ST, Lim SM. Anthocyanidins and anthocyanins: colored pigments as food, pharmaceutical ingredients, and the potential health benefits. Food Nutr Res. 2017;61:1361779. (PMID: 28970777561390210.1080/16546628.2017.1361779)
Ali T, Kim T, Rehman SU, Khan MS, Amin FU, Khan M, et al. Natural Dietary Supplementation of Anthocyanins via PI3K/Akt/Nrf2/HO-1 Pathways Mitigate Oxidative Stress, Neurodegeneration, and Memory Impairment in a Mouse Model of Alzheimer’s Disease. Mol Neurobiol. 2018;55:6076–93. (PMID: 2917098110.1007/s12035-017-0798-6)
Aboonabi A, Singh I, Rose’ Meyer R. Cytoprotective effects of berry anthocyanins against induced oxidative stress and inflammation in primary human diabetic aortic endothelial cells. Chem Biol Interact. 2020;317:108940. (PMID: 3193536510.1016/j.cbi.2020.108940)
Asgary S, Sahebkar A, Afshani MR, Keshvari M, Haghjooyjavanmard S, Rafieian-Kopaei M. Clinical evaluation of blood pressure lowering, endothelial function improving, hypolipidemic and anti-inflammatory effects of pomegranate juice in hypertensive subjects. Phytother Res. 2014;28:193–9. (PMID: 2351991010.1002/ptr.4977)
Spormann TM, Albert FW, Rath T, Dietrich H, Will F, Stockis JP, et al. Anthocyanin/polyphenolic-rich fruit juice reduces oxidative cell damage in an intervention study with patients on hemodialysis. Cancer Epidemiol Biomark Prev. 2008;17:3372–80. (PMID: 10.1158/1055-9965.EPI-08-0364)
Shema-Didi L, Kristal B, Ore L, Shapiro G, Geron R, Sela S. Pomegranate juice intake attenuates the increase in oxidative stress induced by intravenous iron during hemodialysis. Nutr Res. 2013;33:442–6. (PMID: 2374655910.1016/j.nutres.2013.04.004)
Boldaji RB, Akhlaghi M, Sagheb MM, Esmaeilinezhad Z. Pomegranate juice improves cardiometabolic risk factors, biomarkers of oxidative stress and inflammation in hemodialysis patients: a randomized crossover trial. J Sci Food Agric. 2020;100:846–54. (PMID: 10.1002/jsfa.10096)
Bloedon TK, Braithwaite RE, Carson IA, Klimis-Zacas D, Lehnhard RA. Impact of anthocyanin-rich whole fruit consumption on exercise-induced oxidative stress and inflammation: a systematic review and meta-analysis. Nutr Rev. 2019;9:630–45. (PMID: 10.1093/nutrit/nuz018)
Fallah AA, Sarmast E, Fatehi P, Jafari T. Impact of dietary anthocyanins on systemic and vascular inflammation: systematic review and meta-analysis on randomised clinical trials. Food ChemToxicol. 2020;135:110922. (PMID: 10.1016/j.fct.2019.110922)
Fallah AA, Sarmast E, Jafari T. Effect of dietary anthocyanins on biomarkers of glycemic control and glucose metabolism: A systematic review and meta-analysis of randomized clinical trials. Food Res Int. 2020;137:109379. (PMID: 3323308110.1016/j.foodres.2020.109379)
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Bmj 2021;372:n71. (PMID: 33782057800592410.1136/bmj.n71)
Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. Bmj 2011;343:d5928. (PMID: 22008217319624510.1136/bmj.d5928)
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000;283:2008–12. (PMID: 1078967010.1001/jama.283.15.2008)
Follmann D, Elliott P, Suh I, Cutler J. Variance imputation for overviews of clinical trials with continuous response. J Clin Epidemiol. 1992;45:769–73. (PMID: 161945610.1016/0895-4356(92)90054-Q)
Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;5:13. (PMID: 15840177109773410.1186/1471-2288-5-13)
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557–60. (PMID: 1295812019285910.1136/bmj.327.7414.557)
Hox JL, Leeuw ED. Multilevel models for meta-analysis. Mahwah, NJ, US:Lawrence Erlbaum Associates Publishers; 2003. p. 90–111.
Morris SB, DeShon RP. Combining effect size estimates in meta-analysis with repeated measures and independent-groups designs. Psychol Methods. 2002;7:105–25. (PMID: 1192888610.1037/1082-989X.7.1.105)
Jackson D, Riley RD. A refined method for multivariate meta-analysis and meta-regression. Stat Med. 2014;33:541–54. (PMID: 2399635110.1002/sim.5957)
Thompson SG, Sharp SJ. Explaining heterogeneity in meta-analysis: a comparison of methods. Stat Med. 1999;18:2693–708. (PMID: 1052186010.1002/(SICI)1097-0258(19991030)18:20<2693::AID-SIM235>3.0.CO;2-V)
Berkey CS, Hoaglin DC, Mosteller F, Colditz GA. A random-effects regression model for meta-analysis. Stat Med. 1995;14:395–411. (PMID: 774697910.1002/sim.4780140406)
Castilla P, Echarri R, Dávalos A, Cerrato F, Ortega H, Teruel JL, et al. Concentrated red grape juice exerts antioxidant, hypolipidemic, and antiinflammatory effects in both hemodialysis patients and healthy subjects. Am J Clin Nutr. 2006;84:252–62. (PMID: 1682570310.1093/ajcn/84.1.252)
Castilla P, Dávalos A, Teruel JL, Cerrato F, Fernández-Lucas M, Merino JL, et al. Comparative effects of dietary supplementation with red grape juice and vitamin E on production of superoxide by circulating neutrophil NADPH oxidase in hemodialysis patients. Am J Clin Nutr. 2008;87:1053–61. (PMID: 1840073110.1093/ajcn/87.4.1053)
Janiques AG, Leal Vde O, Stockler-Pinto MB, Moreira NX, Mafra D. Effects of grape powder supplementation on inflammatory and antioxidant markers in hemodialysis patients: a randomized double-blind study. J Bras Nefrol. 2014;36:496–501. (PMID: 2551727910.5935/0101-2800.20140071)
Wu PT, Fitschen PJ, Kistler BM, Jeong JH, Chung HR, Aviram M, et al. Effects of Pomegranate Extract Supplementation on Cardiovascular Risk Factors and Physical Function in Hemodialysis Patients. J Med Food. 2015;18:941–9. (PMID: 2582614310.1089/jmf.2014.0103)
Shema-Didi L, Sela S, Ore L, Shapiro G, Geron R, Moshe G, et al. One year of pomegranate juice intake decreases oxidative stress, inflammation, and incidence of infections in hemodialysis patients: A randomized placebo-controlled trial. Free Radic Biol Med. 2012;53:297–304. (PMID: 2260942310.1016/j.freeradbiomed.2012.05.013)
Jafari T, Fallah AA, Bahrami M, Lorigooini Z. Effects of pomegranate peel extract and vitamin E on oxidative stress and antioxidative capacity of hemodialysis patients: A randomized controlled clinical trial. 2020a;72:104069.
Jafari T, Fallah AA, Reyhanian A, Sarmast E. Effects of pomegranate peel extract and vitamin E on the inflammatory status and endothelial function in hemodialysis patients: a randomized controlled clinical trial. 2020b;11:7987–7993.
Silverstein DM. Inflammation in chronic kidney disease: role in the progression of renal and cardiovascular disease. Pediatr Nephrol. 2009;24:1445–52. (PMID: 1908302410.1007/s00467-008-1046-0)
Prasad GV. Metabolic syndrome and chronic kidney disease: current status and future directions. World J Nephrol. 2014;3:210–9. (PMID: 25374814422035310.5527/wjn.v3.i4.210)
van Timmeren MM, van den Heuvel MC, Bailly V, Bakker SJ, van Goor H, Stegeman CA. Tubular kidney injury molecule-1 (KIM-1) in human renal disease. J Pathol. 2007;212:209–17. (PMID: 1747146810.1002/path.2175)
Reis JF, Monteiro VV, de Souza Gomes R, do Carmo MM, da Costa GV, Ribera PC, et al. Action mechanism and cardiovascular effect of anthocyanins: a systematic review of animal and human studies. J Transl Med. 2016;14:315. (PMID: 27846846511135110.1186/s12967-016-1076-5)
Morena M, Cristol JP, Canaud B. Why hemodialysis patients are in a prooxidant state? What could be done to correct the pro/antioxidant imbalance. Blood Purif. 2000;18:191–9. (PMID: 1085942210.1159/000014418)
Zhu Y, Miao Y, Meng Z, Zhong Y. Effects of Vaccinium Berries on Serum Lipids: A Meta-Analysis of Randomized Controlled Trials. Evid Based Complement Altern Med. 2015;2015:790329. (PMID: 10.1155/2015/790329)
Liu C, Sun J, Lu Y, Bo Y. Effects of anthocyanin on serum lipids in dyslipidemia patients: a systematic review and meta-analysis. PLoS ONE. 2016;11:e0162089. (PMID: 27589062501021910.1371/journal.pone.0162089)
Shah K, Shah P. Effect of anthocyanin supplementations on lipid profile and inflammatory markers: a systematic review and meta-analysis of randomized controlled trials. Cholesterol 2018;2018:8450793. (PMID: 29850238593757710.1155/2018/8450793)
Qin Y, Xia M, Ma J, Hao Y, Liu J, Mou H, et al. Anthocyanin supplementation improves serum LDL- and HDL-cholesterol concentrations associated with the inhibition of cholesteryl ester transfer protein in dyslipidemic subjects. Am J Clin Nutr. 2009;90:485–92. (PMID: 1964095010.3945/ajcn.2009.27814)
Zhu Y, Huang X, Zhang Y, Wang Y, Liu Y, Sun R, et al. Anthocyanin supplementation improves HDL-associated paraoxonase 1 activity and enhances cholesterol efflux capacity in subjects with hypercholesterolemia. J Clin Endocrinol Metab. 2014;99:561–9. (PMID: 2428568710.1210/jc.2013-2845)
Clifford MN. Anthocyanins - nature, occurrence and dietary burden. J Sci Food Agric. 2000;80:1063–72. (PMID: 10.1002/(SICI)1097-0010(20000515)80:7<1063::AID-JSFA605>3.0.CO;2-Q)
Gilligan S, Raphael KL. Hyperkalemia and Hypokalemia in CKD: Prevalence, Risk Factors, and Clinical Outcomes. Adv Chronic Kidney Dis. 2017;24:315–8. (PMID: 2903135810.1053/j.ackd.2017.06.004)
Brookes EM, Snider J, Hart GK, Robbins R, Power DA. Serum potassium in chronic kidney disease: prevalence, patient characteristics and clinical outcomes. Intern Med J. 2020;11:1906–1918.
Speer H, D'Cunha NM, Alexopoulos NI, McKune AJ, Naumovski N. Naumovski N. Anthocyanins and Human Health-A Focus on Oxidative Stress, Inflammation and Disease. Antioxidants (Basel). 2020;5:366. (PMID: 10.3390/antiox9050366)
Libetta C, Sepe V, Esposito P, Galli F, Dal, Canton A. Oxidative stress and inflammation: implications in uremia and hemodialysis. Clin Biochem. 2011;44:1189–98. (PMID: 2177757410.1016/j.clinbiochem.2011.06.988)
Himmelfarb J, Hakim RM. Oxidative stress in uremia. Curr Opin Nephrol Hypertens. 2003;12:593–8. (PMID: 1456419510.1097/00041552-200311000-00004)
Cobo G, Lindholm B, Stenvinkel P. Chronic inflammation in end-stage renal disease and dialysis. Nephrol Dial Transpl. 2018;33:iii35–iii40. (PMID: 10.1093/ndt/gfy175)
Hollman PCH, Cassidy A, Comte B, Heinonen M, Richelle M, Richling E, et al. The biological relevance of direct antioxidant effects of polyphenols for cardiovascular health in humans is not established. J Nutr. 2011;141:989S–1009S. (PMID: 2145112510.3945/jn.110.131490)
Czank C, Cassidy A, Zhang Q, Morrison DJ, Preston T, Kroon PA, et al. Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a (13)C-tracer study. Am J Clin Nutr. 2013;97:995–1003. (PMID: 2360443510.3945/ajcn.112.049247)
Hollman PCH. Unravelling of the health effects of polyphenols is a complex puzzle complicated by metabolism. Arch Biochem Biophys. 2014;1:100–5. (PMID: 10.1016/j.abb.2014.04.013)

0 (Anthocyanins)
0 (Cholesterol, HDL)

Date Created: 20220713 Date Completed: 20230321 Latest Revision: 20230327

20250114

10.1038/s41430-022-01175-6

35831559