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

Abstract

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, I2 = 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, I2 = 99%) and myeloperoxidase (std. mean: −1.28 ηg.mL, 95% CI: [−2.11, −0.45], P = 0.003, I2 = 77%) against placebo group. Decrease inflammatory parameters (std. mean: −0.57, 95% CI: [−0.98, −0.16], P = 0.007, I2 = 79%), increase HDL cholesterol levels (std. mean: 0.58 mg.dL, 95% CI: [0.23, 0.94], P = 0.001, I2 = 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.

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Data availability

Registration and protocol; Template data collection forms; data extracted from included studies; data used for all analyses; analytic code; any other materials used in the review will be made available on request.

References

  1. 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.

    Article  Google Scholar 

  2. 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.

    Article  PubMed  Google Scholar 

  3. 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.

    Article  PubMed  Google Scholar 

  4. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lv JC, Zhang LX. Prevalence and Disease Burden of Chronic Kidney Disease. Adv Exp Med Biol. 2019;1165:3–15.

    Article  CAS  PubMed  Google Scholar 

  6. Liu B, Lan H, Lv L. Renal Fibrosis: Mechanisms and Therapies. Advances in Experimental Medicine and Biology. Singapure: Springer; 1st ed. 2019.

  7. Himmelfarb J, Ikizler TA. Hemodialysis. N Engl J Med. 2010;363:1833–45.

    Article  CAS  PubMed  Google Scholar 

  8. 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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  10. 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.

    Article  PubMed  Google Scholar 

  11. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  12. 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.

  13. 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.

    PubMed  PubMed Central  Google Scholar 

  14. 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.

    Article  PubMed  Google Scholar 

  15. 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.

    Google Scholar 

  16. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. 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.

    Article  Google Scholar 

  18. 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.

    Article  CAS  PubMed  Google Scholar 

  19. Smeriglio A, Barreca D, Bellocco E, Trombetta D. Chemistry, Pharmacology and Health Benefits of Anthocyanins. Phytother Res. 2016;30:1265–86.

    Article  CAS  PubMed  Google Scholar 

  20. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  21. 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.

    Article  CAS  PubMed  Google Scholar 

  22. 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.

    Article  CAS  PubMed  Google Scholar 

  23. 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.

    Article  CAS  PubMed  Google Scholar 

  24. 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.

    Article  CAS  Google Scholar 

  25. 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.

    Article  CAS  PubMed  Google Scholar 

  26. 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.

    Article  Google Scholar 

  27. 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.

    Article  Google Scholar 

  28. 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.

    Article  Google Scholar 

  29. 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.

    Article  CAS  PubMed  Google Scholar 

  30. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  31. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  32. 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.

    Article  CAS  PubMed  Google Scholar 

  33. 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.

    Article  CAS  PubMed  Google Scholar 

  34. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557–60.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Hox JL, Leeuw ED. Multilevel models for meta-analysis. Mahwah, NJ, US:Lawrence Erlbaum Associates Publishers; 2003. p. 90–111.

  37. Morris SB, DeShon RP. Combining effect size estimates in meta-analysis with repeated measures and independent-groups designs. Psychol Methods. 2002;7:105–25.

    Article  PubMed  Google Scholar 

  38. Jackson D, Riley RD. A refined method for multivariate meta-analysis and meta-regression. Stat Med. 2014;33:541–54.

    Article  PubMed  Google Scholar 

  39. Thompson SG, Sharp SJ. Explaining heterogeneity in meta-analysis: a comparison of methods. Stat Med. 1999;18:2693–708.

    Article  CAS  PubMed  Google Scholar 

  40. Berkey CS, Hoaglin DC, Mosteller F, Colditz GA. A random-effects regression model for meta-analysis. Stat Med. 1995;14:395–411.

    Article  CAS  PubMed  Google Scholar 

  41. 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.

    Article  CAS  PubMed  Google Scholar 

  42. 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.

    Article  CAS  PubMed  Google Scholar 

  43. 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.

    Article  PubMed  Google Scholar 

  44. 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.

    Article  CAS  PubMed  Google Scholar 

  45. 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.

    Article  CAS  PubMed  Google Scholar 

  46. 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.

  47. 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.

  48. Silverstein DM. Inflammation in chronic kidney disease: role in the progression of renal and cardiovascular disease. Pediatr Nephrol. 2009;24:1445–52.

    Article  PubMed  Google Scholar 

  49. Prasad GV. Metabolic syndrome and chronic kidney disease: current status and future directions. World J Nephrol. 2014;3:210–9.

    Article  PubMed  PubMed Central  Google Scholar 

  50. 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.

    Article  PubMed  Google Scholar 

  51. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  52. 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.

    Article  CAS  PubMed  Google Scholar 

  53. 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.

    Article  Google Scholar 

  54. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  55. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  56. 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.

    Article  CAS  PubMed  Google Scholar 

  57. 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.

    Article  CAS  PubMed  Google Scholar 

  58. Clifford MN. Anthocyanins - nature, occurrence and dietary burden. J Sci Food Agric. 2000;80:1063–72.

    Article  CAS  Google Scholar 

  59. Gilligan S, Raphael KL. Hyperkalemia and Hypokalemia in CKD: Prevalence, Risk Factors, and Clinical Outcomes. Adv Chronic Kidney Dis. 2017;24:315–8.

    Article  PubMed  Google Scholar 

  60. 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.

    Google Scholar 

  61. 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.

    Article  Google Scholar 

  62. 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.

    Article  CAS  PubMed  Google Scholar 

  63. Himmelfarb J, Hakim RM. Oxidative stress in uremia. Curr Opin Nephrol Hypertens. 2003;12:593–8.

    Article  CAS  PubMed  Google Scholar 

  64. Cobo G, Lindholm B, Stenvinkel P. Chronic inflammation in end-stage renal disease and dialysis. Nephrol Dial Transpl. 2018;33:iii35–iii40.

    Article  CAS  Google Scholar 

  65. 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.

    Article  CAS  PubMed  Google Scholar 

  66. 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.

    Article  CAS  PubMed  Google Scholar 

  67. Hollman PCH. Unravelling of the health effects of polyphenols is a complex puzzle complicated by metabolism. Arch Biochem Biophys. 2014;1:100–5.

    Article  Google Scholar 

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Funding

This study was supported by São Paulo Research Foundation (FAPESP). CSP received a Post Doctorate scholarship from the FAPESP (Process 2018/23402-0).

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ICVSM and CSP coordinated all the review steps and contributed to the interpretation and revised paper. MGM, JLMdN, DM, and AFS contributed to write and revise the paper.

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Correspondence to Isabelle C. V. S. Martins.

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Martins, I.C.V.S., Maciel, M.G., do Nascimento, J.L.M. et al. Anthocyanins-rich interventions on oxidative stress, inflammation and lipid profile in patients undergoing hemodialysis: meta-analysis and meta-regression. Eur J Clin Nutr 77, 316–324 (2023). https://doi.org/10.1038/s41430-022-01175-6

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