The effect of Vitamin E and N-acetyl cysteine on oxidative status and hemoglobin level in transfusion-dependent thalassemia patients: A systematic review and meta-analysis

Haghpanah, Sezaneh; Hosseini-Bensenjan, Mahnaz; Zekavat, Omid reza; Bordbar, Mohammadreza; Karimi, Mehran; Ramzi, Mani; Asmarian, Naeimehossadat

doi:10.58209/ijbc.15.1.22

Volume 15, Issue 1 ( March 2023 2023) Iranian Journal of Blood and Cancer 2023, 15(1): 22-35 | Back to browse issues page

‎ 10.58209/ijbc.15.1.22

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Haghpanah S, Hosseini-Bensenjan M, Zekavat O R, Bordbar M, Karimi M, Ramzi M et al . The effect of Vitamin E and N-acetyl cysteine on oxidative status and hemoglobin level in transfusion-dependent thalassemia patients: A systematic review and meta-analysis. Iranian Journal of Blood and Cancer 2023; 15 (1) :22-35
URL: http://ijbc.ir/article-1-1332-en.html

The effect of Vitamin E and N-acetyl cysteine on oxidative status and hemoglobin level in transfusion-dependent thalassemia patients: A systematic review and meta-analysis

Sezaneh Haghpanah¹

, Mahnaz Hosseini-Bensenjan¹

, Omid reza Zekavat¹

, Mohammadreza Bordbar¹

, Mehran Karimi¹

, Mani Ramzi¹

, Naeimehossadat Asmarian ^*

1- Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
2- Anesthesiology and Critical Care Research Center, Shiraz University of Medical Science, Shiraz, Iran , shirinparand47@gmail.com

Abstract: (959 Views)

Background: This meta-analysis was conducted to summarize the comparative effect of Vitamin E and N-acetyl cysteine (NAC) on oxidative status, including total antioxidant capacity (TAC), total oxidative stress (TOS), oxidative stress index (OSI), and hemoglobin (Hb) in patients with TDT.
Methods: This systematic review and meta-analysis was done according to the PRISMA checklist. We searched databases including Web of Science (ISI), Scopus, Medline (via PubMed), and Embase. Meta-analysis was done using Stata statistical software version 16.0.
Results: Finally, four randomized-controlled trials (RCT) for Vitamin E and three RCTs for NAC were included. Our meta-analyses and review showed a significant increase in the weighted mean differences (WMD) of Hb and a significant decrease in the WMD of TOS and OSI in children subgroup of Vitamin E. Also, based on the results of the review in the NAC group, a significant increase in the WMD of Hb and a significant decrease in the WMD of TOS and OSI were found in children.
Conclusions: Vitamin E showed a beneficial effect on improving anemia in TDT children. Moreover, both NAC and Vitamin E seems to be effective antioxidant supplements in children with TDT. More well-designed randomized, controlled trials for the effect of NAC and Vitamin E in TDT patients are recommended with more focus on the essential influencing factors on the oxidative status in these patients.

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Keywords: Acetyl cysteine, Meta-Analysis, Transfusion-dependent thalassemia, Vitamin E

Full-Text [PDF 1081 kb] (513 Downloads)

Subject: Adults Hematology & Oncology
Received: 2023/01/4 | Accepted: 2023/02/28 | Published: 2023/03/30

References

1. Haghpanah S, Cohan N, Bordbar M, Bazrafshan A, Karimi M, Zareifar S, Safaei S, Aramesh A, Moghadam M, Fard SAZ, Zekavat OR. Effects of three months of treatment with vitamin E and N-acetyl cysteine on the oxidative balance in patients with transfusion-dependent β-thalassemia. Annals of hematology. 2021;100(3):635-44. [DOI:10.1007/s00277-020-04346-2]

2. Siri-Angkul N, Chattipakorn SC, Chattipakorn N. Diagnosis and treatment of cardiac iron overload in transfusion-dependent thalassemia patients. Expert review of hematology. 2018;11(6):471-9. [DOI:10.1080/17474086.2018.1476134]

3. Hashemieh M. Assessment of Organ Specific Iron Overload in Transfusion-dependent Thalassemia by Magnetic Resonance Imaging Techniques. Iranian Journal of Blood and Cancer. 2019;11(2):39-46. [DOI:10.18502/ijpho.v9i4.1575]

4. Bhat RR, Lashkari H, Ramprakash S, Pereira D. Triple Drug Iron Chelation Therapy in Thalassemia Major; A Case Report. Iranian Journal of Blood and Cancer. 2021;13(2):62-4.

5. Eghbali A, Mehrabi S, Ghandi Y, Eghbali A, Dabiri M, Mousavi_Hasanzadeh M. The Correlation between Serum Ferritin, Serum Troponin T, cardiac T2* MRI and Echocardiographic Findings in Patients withThalassemia Major. Iranian Journal of Blood and Cancer. 2020;12(1):1-5.

6. Ozdemir ZC, Koc A, Aycicek A, Kocyigit A. N-acetylcysteine supplementation reduces oxidative stress and DNA damage in children with β-thalassemia. Hemoglobin. 2014;38(5):359-64. [DOI:10.3109/03630269.2014.951890]

7. Pattanakuhar S, Phrommintikul A, Tantiworawit A, Srichairattanakool S, Chattipakorn SC, Chattipakorn N. N-acetylcysteine Restored Heart Rate Variability and Prevented Serious Adverse Events in Transfusion-dependent Thalassemia Patients: a Double-blind Single Center Randomized Controlled Trial. International journal of medical sciences. 2020;17(9):1147. [DOI:10.7150/ijms.45795]

8. Sengsuk C, Tangvarasittichai O, Chantanaskulwong P, Pimanprom A, Wantaneeyawong S, Choowet A, Tangvarasittichai S. Association of Iron Overload with Oxidative Stress, Hepatic Damage and Dyslipidemia in Transfusion-Dependent β-Thalassemia/HbE Patients. Indian journal of clinical biochemistry : IJCB. 2014;29(3):298-305. [DOI:10.1007/s12291-013-0376-2]

9. Kampa M, Nistikaki A, Tsaousis V, Maliaraki N, Notas G, Castanas E. A new automated method for the determination of the Total Antioxidant Capacity (TAC) of human plasma, based on the crocin bleaching assay. BMC clinical pathology. 2002;2(1):3. [DOI:10.1186/1472-6890-2-3]

10. Katerji M, Filippova M, Duerksen-Hughes P. Approaches and Methods to Measure Oxidative Stress in Clinical Samples: Research Applications in the Cancer Field. Oxidative medicine and cellular longevity. 2019;2019:1279250. [DOI:10.1155/2019/1279250]

11. Pedre B, Barayeu U, Ezeriņa D, Dick TP. The mechanism of action of N-acetylcysteine (NAC): The emerging role of H(2)S and sulfane sulfur species. Pharmacology & therapeutics. 2021;228:107916. [DOI:10.1016/j.pharmthera.2021.107916]

12. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Annals of internal medicine. 2009;151(4):264-9, w64. [DOI:10.7326/0003-4819-151-4-200908180-00135]

13. Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA. Cochrane handbook for systematic reviews of interventions: John Wiley & Sons; 2019. [DOI:10.1002/9781119536604]

14. Borenstein M, Hedges, L. V., Higgins, J. P. T., and Rothstein, H. R. Introduction to meta-analysis. Hoboken: John Wiley & Sons. 2011.

15. Higgins J. Cochrane handbook for systematic reviews of interventions. Version 5.1. 0 [updated March 2011]. The Cochrane Collaboration. www cochrane-handbook org. 2011.

16. Rashidi M, Aboomardani M, Rafraf M, Arefhosseini SR, Keshtkar A, Joshaghani H. Effects of Vitamin E and Zinc Supplementation on Antioxidants in Beta thalassemia major Patients. Iranian journal of pediatrics. 2011;21(1):8-14.

17. Hamed EM, Meabed MH, Hussein RRS, Aly UF. Recent insight on improving the iron chelation efficacy of deferasirox by adjuvant therapy in transfusion dependent beta thalassemia children with sluggish response. Expert opinion on drug metabolism & toxicology. 2020;16(3):179-93. [DOI:10.1080/17425255.2020.1729353]

18. Hershko C. Pathogenesis and management of iron toxicity in thalassemia. Annals of the New York Academy of Sciences. 2010;1202:1-9. [DOI:10.1111/j.1749-6632.2010.05544.x]

19. Allen A, Perera S, Mettananda S, Rodrigo R, Perera L, Darshana T, Moggach F, Jackson Crawford A, Heirene L, Fisher C, Olivieri N, Rees D, Premawardhena A, Allen S. Oxidative status in the β-thalassemia syndromes in Sri Lanka; a cross-sectional survey. Free Radical Biology and Medicine. 2021;166:337-47. [DOI:10.1016/j.freeradbiomed.2021.02.028]

20. Manafikhi H, Drummen G, Palmery M, Peluso I. Total Antioxidant Capacity in beta-thalassemia: A systematic review and meta-analysis of case-control studies. Critical reviews in oncology/hematology. 2017;110:35-42. [DOI:10.1016/j.critrevonc.2016.12.007]

21. Hamed EA, ElMelegy NT. Renal functions in pediatric patients with beta-thalassemia major: relation to chelation therapy: original prospective study. Italian journal of pediatrics. 2010;36:39. [DOI:10.1186/1824-7288-36-39]

22. Waseem F, Khemomal KA, Sajid R. Antioxidant status in beta thalassemia major: a single-center study. Indian journal of pathology & microbiology. 2011;54(4):761-3.

23. Arman Bilir Ö, Kirkiz S, Fettah A, Ok Bozkaya İ, Kara A, Çakar N, Yaralı N. Renal function and the oxidative status among children with thalassemia major and healthy controls: A cross-sectional study. Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2020;59(4):102746. [DOI:10.1016/j.transci.2020.102746]

24. Bazvand F, Shams S, Borji Esfahani M, Koochakzadeh L, Monajemzadeh M, Ashtiani MT, Rezaei N. Total Antioxidant Status in Patients with Major β-Thalassemia. Iranian journal of pediatrics. 2011;21(2):159-65.

25. Ondei Lde S, Estevão Ida F, Rocha MI, Percário S, Souza DR, Pinhel MA, Bonini-Domingos CR. Oxidative stress and antioxidant status in beta-thalassemia heterozygotes. Revista brasileira de hematologia e hemoterapia. 2013;35(6):409-13. [DOI:10.5581/1516-8484.20130122]

26. Trangsuwan D, Wongchanchailert M, Mo-suwan L, Chotsampancharoen T, Kalpravidh R, Apiromruck P, Chu-ngan T, Khotchawan S, Duangchu S. Effects of Vitamin E on Transfusion Requirements in TransfusionDependent Beta-Thalassemia Patients. Journal of Health Science and Medical Research. 2018;36(3):225-34. [DOI:10.31584/jhsmr.2018.36.3.19]

27. Sovira N, Lubis M, Wahidiyat PA, Suyatna FD, Gatot D, Bardosono S, Sadikin M. Effects of α-tocopherol on hemolysis and oxidative stress markers on red blood cells in β-thalassemia major. Clinical and experimental pediatrics. 2020;63(8):314-20. [DOI:10.3345/cep.2019.00542]

28. El-Aal AA, El-Ghffar EAA, Ghali AA, Zughbur MR, Sirdah MM. The effect of vitamin C and/or E supplementations on type 2 diabetic adult males under metformin treatment: A single-blinded randomized controlled clinical trial. Diabetes & metabolic syndrome. 2018;12(4):483-9. [DOI:10.1016/j.dsx.2018.03.013]

29. Shokrpour M, Asemi Z. The Effects of Magnesium and Vitamin E Co-Supplementation on Hormonal Status and Biomarkers of Inflammation and Oxidative Stress in Women with Polycystic Ovary Syndrome. Biological trace element research. 2019;191(1):54-60. [DOI:10.1007/s12011-018-1602-9]

30. Lewis ED, Meydani SN, Wu D. Regulatory role of vitamin E in the immune system and inflammation. IUBMB life. 2019;71(4):487-94. [DOI:10.1002/iub.1976]

31. Dissayabutra T, Tosukhowong P, Seksan P. The benefits of vitamin C and vitamin E in children with beta-thalassemia with high oxidative stress. Journal of the Medical Association of Thailand = Chotmaihet thangphaet. 2005;88 Suppl 4:S317-21.

32. Yanpanitch OU, Hatairaktham S, Charoensakdi R, Panichkul N, Fucharoen S, Srichairatanakool S, Siritanaratkul N, Kalpravidh RW. Treatment of β-Thalassemia/Hemoglobin E with Antioxidant Cocktails Results in Decreased Oxidative Stress, Increased Hemoglobin Concentration, and Improvement of the Hypercoagulable State. Oxidative medicine and cellular longevity. 2015;2015:537954. [DOI:10.1155/2015/537954]

33. Mahjoub S, Tamadoni A, ZANJANCHI NM, Moghadamnia AA. The effects of beta-carotene and vitamin E on erythrocytes lipid peroxidation in beta-thalassemia patients. Journal of Research in Medical Sciences. 2007;12:301-7.

34. Peivandi Yazdi A, Razavi M, Sheikh S, Boroumand N, Salehi M, Hashemy SI. Clinical Trial Assessment of Intermittent and Continuous Infusion Dose of N-Acetylcysteine on Redox Status of the Body in Patients with Sepsis Admitted to the ICU. Journal of intensive care medicine. 2020;35(12):1383-8. [DOI:10.1177/0885066618823152]

35. Safe IP, Amaral EP, Araújo-Pereira M, Lacerda MVG, Printes VS, Souza AB, Beraldi-Magalhães F, Monteiro WM, Sampaio VS, Barreto-Duarte B, Andrade AMS, Spener-Gomes R, Costa AG, Cordeiro-Santos M, Andrade BB. Adjunct N-Acetylcysteine Treatment in Hospitalized Patients With HIV-Associated Tuberculosis Dampens the Oxidative Stress in Peripheral Blood: Results From the RIPENACTB Study Trial. Frontiers in immunology. 2020;11:602589. [DOI:10.3389/fimmu.2020.602589]

36. Kumar P, Liu C, Hsu JW, Chacko S, Minard C, Jahoor F, Sekhar RV. Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial. Clinical and translational medicine. 2021;11(3):e372. [DOI:10.1002/ctm2.372]

37. Molnar Z, MacKinnon KL, Shearer E, Lowe D, Watson ID. The effect of N-acetylcysteine on total serum anti-oxidant potential and urinary albumin excretion in critically ill patients. Intensive care medicine. 1998;24(3):230-5. [DOI:10.1007/s001340050555]

38. Rhodes K, Braakhuis A. Performance and Side Effects of Supplementation with N-Acetylcysteine: A Systematic Review and Meta-Analysis. Sports medicine (Auckland, NZ). 2017;47(8):1619-36. [DOI:10.1007/s40279-017-0677-3]

39. Bansal D. Hepcidin and Thalassemia. Indian journal of pediatrics. 2017;84(10):731-2. [DOI:10.1007/s12098-017-2439-5]

40. Buico A, Cassino C, Ravera M, Betta PG, Osella D. Oxidative stress and total antioxidant capacity in human plasma. Redox report : communications in free radical research. 2009;14(3):125-31. [DOI:10.1179/135100009X392557]

41. Allen A, Fisher C, Premawardhena A, Bandara D, Perera A, Allen S, St Pierre T, Olivieri N, Weatherall D. Methemoglobinemia and ascorbate deficiency in hemoglobin E β thalassemia: metabolic and clinical implications. Blood. 2012;120(15):2939-44. [DOI:10.1182/blood-2012-06-435875]

42. Boudrahem-Addour N, Izem-Meziane M, Bouguerra K, Nadjem N, Zidani N, Belhani M, Djerdjouri B. Oxidative status and plasma lipid profile in β-thalassemia patients. Hemoglobin. 2015;39(1):36-41. [DOI:10.3109/03630269.2014.979997]

43. Li S, Tan HY, Wang N, Zhang ZJ, Lao L, Wong CW, Feng Y. The Role of Oxidative Stress and Antioxidants in Liver Diseases. International journal of molecular sciences. 2015;16(11):26087-124. [DOI:10.3390/ijms161125942]

44. Millea PJ. N-acetylcysteine: multiple clinical applications. American family physician. 2009;80(3):265-9.

45. Das N, Das Chowdhury T, Chattopadhyay A, Datta AG. Attenuation of oxidative stress-induced changes in thalassemic erythrocytes by vitamin E. Polish journal of pharmacology. 2004;56(1):85-96.

46. Miller LF, Rumack BH. Clinical safety of high oral doses of acetylcysteine. Seminars in oncology. 1983;10(1 Suppl 1):76-85.

47. Miller ER, 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Annals of internal medicine. 2005;142(1):37-46. [DOI:10.7326/0003-4819-142-1-200501040-00110]

48. Sandilands EA, Bateman DN. Adverse reactions associated with acetylcysteine. Clinical toxicology (Philadelphia, Pa). 2009;47(2):81-8. [DOI:10.1080/15563650802665587]

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