Skip to main content
SpringerLink
Log in

Curcuminoids supplementation ameliorates iron overload, oxidative stress, hypercoagulability, and inflammation in non-transfusion-dependent β-thalassemia/Hb E patients

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Curcuminoids, polyphenol compounds in turmeric, possess several pharmacological properties including antioxidant, iron-chelating, and anti-inflammatory activities. Effects of curcuminoids in thalassemia patients have been explored in a limited number of studies using different doses of curcuminoids. The present study aims to evaluate the effects of 24-week curcuminoids supplementation at the dosage of 500 and 1000 mg/day on iron overload, oxidative stress, hypercoagulability, and inflammation in non-transfused β-thalassemia/Hb E patients. In general, both curcuminoids dosages significantly lowered the levels of oxidative stress, hypercoagulability, and inflammatory markers in the patients. In contrast, reductions in iron parameter levels were more remarkable in the 1000 mg/day group. Subgroup analysis revealed that a marker of hypercoagulability was significantly decreased only in patients with baseline ferritin ≤ 1000 ng/ml independently of curcuminoids dosage. Moreover, the alleviation of iron loading parameters was more remarkable in patients with baseline ferritin > 1000 ng/ml who receive 1000 mg/day curcuminoids. On the other hand, the responses of oxidative stress markers were higher with 500 mg/day curcuminoids regardless of baseline ferritin levels. Our study suggests that baseline ferritin levels should be considered in the supplementation of curcuminoids and the appropriate curcuminoids dosage might differ according to the required therapeutic effect. Thai Clinical Trials Registry (TCTR): TCTR20200731003; July 31, 2020 “retrospectively registered”

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

Not applicable.

References

  1. Rund D, Rachmilewitz E (2005) Beta-thalassemia. N Engl J Med 353(11):1135–1146. https://doi.org/10.1056/NEJMra050436

    Article  CAS  PubMed  Google Scholar 

  2. Fucharoen S, Winichagoon P (2000) Clinical and hematologic aspects of hemoglobin E beta-thalassemia. Curr Opin Hematol 7(2):106–112

    Article  CAS  Google Scholar 

  3. Taher AT, Saliba AN (2017) Iron overload in thalassemia: different organs at different rates. Hematol Am Soc Hematol Educ Program 2017(1):265–271

    Article  Google Scholar 

  4. Brissot P, Ropert M, Le Lan C, Loreal O (2012) Non-transferrin bound iron: a key role in iron overload and iron toxicity. Biochim Biophys Acta 1820(3):403–410. https://doi.org/10.1016/j.bbagen.2011.07.014

    Article  CAS  PubMed  Google Scholar 

  5. Kohgo Y, Ikuta K, Ohtake T, Torimoto Y, Kato J (2008) Body iron metabolism and pathophysiology of iron overload. Int J Hematol 88(1):7–15. https://doi.org/10.1007/s12185-008-0120-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Franchini M, Mannucci PM (2012) Hypercoagulability in congenital haemolytic anaemias. Blood Transfus 10(4):423–427. https://doi.org/10.2450/2011.0031-11

    Article  PubMed  PubMed Central  Google Scholar 

  7. Sleiman J, Tarhini A, Bou-Fakhredin R, Saliba AN, Cappellini MD, Taher AT (2018) Non-transfusion-dependent thalassemia: an update on complications and management. Int J Mol Sci 19(1). https://doi.org/10.3390/ijms19010182

  8. Amalraj A, Pius A, Gopi S (2017) Biological activities of curcuminoids, other biomolecules from turmeric and their derivatives - a review. J Tradit Complement Med 7(2):205–233. https://doi.org/10.1016/j.jtcme.2016.05.005

    Article  PubMed  Google Scholar 

  9. Pari L, Tewas D, Eckel J (2008) Role of curcumin in health and disease. Arch Physiol Biochem 114(2):127–149. https://doi.org/10.1080/13813450802033958

    Article  CAS  PubMed  Google Scholar 

  10. Thephinlap C, Phisalaphong C, Lailerd N, Chattipakorn N, Winichagoon P, Vadolas J, Fucharoen S, Porter JB, Srichairatanakool S (2011) Reversal of cardiac iron loading and dysfunction in thalassemic mice by curcuminoids. Med Chem 7(1):62–69

    Article  CAS  Google Scholar 

  11. Kalpravidh RW, Siritanaratkul N, Insain P, Charoensakdi R, Panichkul N, Hatairaktham S, Srichairatanakool S, Phisalaphong C, Rachmilewitz E, Fucharoen S (2010) Improvement in oxidative stress and antioxidant parameters in beta-thalassemia/Hb E patients treated with curcuminoids. Clin Biochem 43(4–5):424–429. https://doi.org/10.1016/j.clinbiochem.2009.10.057

    Article  CAS  PubMed  Google Scholar 

  12. Yanpanitch OU, Hatairaktham S, Charoensakdi R, Panichkul N, Fucharoen S, Srichairatanakool S, Siritanaratkul N, Kalpravidh RW (2015) Treatment of beta-thalassemia/hemoglobin E with antioxidant cocktails results in decreased oxidative stress, increased hemoglobin concentration, and improvement of the hypercoagulable state. Oxidative Med Cell Longev 2015:537954–537958. https://doi.org/10.1155/2015/537954

    Article  Google Scholar 

  13. Mohammadi E, Tamaddoni A, Qujeq D, Nasseri E, Zayeri F, Zand H, Gholami M, Mir SM (2018) An investigation of the effects of curcumin on iron overload, hepcidin level, and liver function in beta-thalassemia major patients: a double-blind randomized controlled clinical trial. Phytother Res 32(9):1828–1835. https://doi.org/10.1002/ptr.6118

    Article  CAS  PubMed  Google Scholar 

  14. Nasseri E, Mohammadi E, Tamaddoni A, Qujeq D, Zayeri F, Zand H (2017) Benefits of curcumin supplementation on antioxidant status in beta-thalassemia major patients: a double-blind randomized controlled clinical trial. Ann Nutr Metab 71(3–4):136–144. https://doi.org/10.1159/000479634

    Article  CAS  PubMed  Google Scholar 

  15. Moghaddam NSA, Oskouie MN, Butler AE, Petit PX, Barreto GE, Sahebkar A (2019) Hormetic effects of curcumin: what is the evidence? J Cell Physiol 234(7):10060–10071. https://doi.org/10.1002/jcp.27880

    Article  CAS  PubMed  Google Scholar 

  16. Gupta SC, Patchva S, Aggarwal BB (2013) Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J 15(1):195–218. https://doi.org/10.1208/s12248-012-9432-8

    Article  CAS  PubMed  Google Scholar 

  17. Daily JW, Yang M, Park S (2016) Efficacy of turmeric extracts and curcumin for alleviating the symptoms of joint arthritis: a systematic review and meta-analysis of randomized clinical trials. J Med Food 19(8):717–729. https://doi.org/10.1089/jmf.2016.3705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ito S, Ikuta K, Kato D, Shibusa K, Niizeki N, Tanaka H, Addo L, Toki Y, Hatayama M, Inamura J, Shindo M, Sasaki K, Iizuka N, Fujiya M, Torimoto Y, Kohgo Y (2014) Non-transferrin-bound iron assay system utilizing a conventional automated analyzer. Clin Chim Acta 437:129–135. https://doi.org/10.1016/j.cca.2014.07.013

    Article  CAS  PubMed  Google Scholar 

  19. Stocks J, Dormandy TL (1971) The autoxidation of human red cell lipids induced by hydrogen peroxide. Br J Haematol 20(1):95–111

    Article  CAS  Google Scholar 

  20. Brandt R, Keston AS (1965) Synthesis of diacetyldichlorofluorescin: a stable reagent for fluorometric analysis. Anal Biochem 11:6–9

    Article  CAS  Google Scholar 

  21. Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY (2001) Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21(4B):2895–2900

    CAS  PubMed  Google Scholar 

  22. Lao CD, Ruffin MT, Normolle D, Heath DD, Murray SI, Bailey JM, Boggs ME, Crowell J, Rock CL, Brenner DE (2006) Dose escalation of a curcuminoid formulation. BMC Complement Altern Med 6:10. https://doi.org/10.1186/1472-6882-6-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chaneiam N, Changtam C, Mungkongdee T, Suthatvoravut U, Winichagoon P, Vadolas J, Suksamrarn A, Fucharoen S, Svasti S (2013) A reduced curcuminoid analog as a novel inducer of fetal hemoglobin. Ann Hematol 92(3):379–386. https://doi.org/10.1007/s00277-012-1604-1

    Article  CAS  PubMed  Google Scholar 

  24. Srichairatanakool S, Thephinlap C, Phisalaphong C, Porter JB, Fucharoen S (2007) Curcumin contributes to in vitro removal of non-transferrin bound iron by deferiprone and desferrioxamine in thalassemic plasma. Med Chem 3(5):469–474

    Article  CAS  Google Scholar 

  25. Devanur LD, Evans RW, Evans PJ, Hider RC (2008) Chelator-facilitated removal of iron from transferrin: relevance to combined chelation therapy. Biochem J 409(2):439–447. https://doi.org/10.1042/bj20070823

    Article  CAS  PubMed  Google Scholar 

  26. Kontoghiorghes GJ, Neocleous K, Kolnagou A (2003) Benefits and risks of deferiprone in iron overload in thalassaemia and other conditions: comparison of epidemiological and therapeutic aspects with deferoxamine. Drug Saf 26(8):553–584. https://doi.org/10.2165/00002018-200326080-00003

    Article  CAS  PubMed  Google Scholar 

  27. Nicolas G, Chauvet C, Viatte L, Danan JL, Bigard X, Devaux I, Beaumont C, Kahn A, Vaulont S (2002) The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest 110(7):1037–1044. https://doi.org/10.1172/jci15686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, Brissot P, Loreal O (2001) A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem 276(11):7811–7819. https://doi.org/10.1074/jbc.M008923200

    Article  CAS  PubMed  Google Scholar 

  29. Jiao Y, Wilkinson J, Di X, Wang W, Hatcher H, Kock ND, D’Agostino R Jr, Knovich MA, Torti FM, Torti SV (2009) Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator. Blood 113(2):462–469. https://doi.org/10.1182/blood-2008-05-155952

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Laine F, Laviolle B, Bardou-Jacquet E, Fatih N, Jezequel C, Collet N, Ropert M, Morcet J, Hamon C, Reymann JM, Loreal O (2017) Curcuma decreases serum hepcidin levels in healthy volunteers: a placebo-controlled, randomized, double-blind, cross-over study. Fundam Clin Pharmacol 31(5):567–573. https://doi.org/10.1111/fcp.12288

    Article  CAS  PubMed  Google Scholar 

  31. Esatbeyoglu T, Huebbe P, Ernst IM, Chin D, Wagner AE, Rimbach G (2012) Curcumin--from molecule to biological function. Angew Chem Int Ed Engl 51(22):5308–5332. https://doi.org/10.1002/anie.201107724

    Article  CAS  PubMed  Google Scholar 

  32. Eldor A, Rachmilewitz EA (2002) The hypercoagulable state in thalassemia. Blood 99(1):36–43. https://doi.org/10.1182/blood.v99.1.36

    Article  CAS  PubMed  Google Scholar 

  33. Weeraphan C, Srisomsap C, Chokchaichamnankit D, Subhasitanont P, Hatairaktham S, Charoensakdi R, Panichkul N, Siritanaratkul N, Fucharoen S, Svasti J, Kalpravidh RW (2013) Role of curcuminoids in ameliorating oxidative modification in beta-thalassemia/Hb E plasma proteome. J Nutr Biochem 24(3):578–585. https://doi.org/10.1016/j.jnutbio.2012.02.008

    Article  CAS  PubMed  Google Scholar 

  34. Keihanian F, Saeidinia A, Bagheri RK, Johnston TP, Sahebkar A (2018) Curcumin, hemostasis, thrombosis, and coagulation. J Cell Physiol 233(6):4497–4511. https://doi.org/10.1002/jcp.26249

    Article  CAS  PubMed  Google Scholar 

  35. Ozturk O, Yaylim I, Aydin M, Yilmaz H, Agachan B, Demiralp E, Isbir T (2001) Increased plasma levels of interleukin-6 and interleukin-8 in beta-thalassaemia major. Haematologia (Budap) 31(3):237–244

    Article  CAS  Google Scholar 

  36. Balouchi S, Gharagozloo M, Esmaeil N, Mirmoghtadaei M, Moayedi B (2014) Serum levels of TGFbeta, IL-10, IL-17, and IL-23 cytokines in beta-thalassemia major patients: the impact of silymarin therapy. Immunopharmacol Immunotoxicol 36(4):271–274. https://doi.org/10.3109/08923973.2014.926916

    Article  CAS  PubMed  Google Scholar 

  37. Butthep P, Wisedpanichkij R, Jindadamrongwech S, Fucharoen S (2015) Elevated erythropoietin and cytokines levels are related to impaired reticulocyte maturation in thalassemic patients. Blood Cells Mol Dis 54(2):170–176. https://doi.org/10.1016/j.bcmd.2014.11.007

    Article  CAS  PubMed  Google Scholar 

  38. Atichartakarn V, Chuncharunee S, Archararit N, Udomsubpayakul U, Aryurachai K (2014) Intravascular hemolysis, vascular endothelial cell activation and thrombophilia in splenectomized patients with hemoglobin E/beta-thalassemia disease. Acta Haematol 132(1):100–107. https://doi.org/10.1159/000355719

    Article  CAS  PubMed  Google Scholar 

  39. Elsayh KI, Mohammed WS, Zahran AM, Saad K (2016) Leukocytes apoptosis and adipocytokines in children with beta thalassemia major. Clin Exp Med 16(3):345–350. https://doi.org/10.1007/s10238-015-0361-6

    Article  CAS  PubMed  Google Scholar 

  40. Voskou S, Aslan M, Fanis P, Phylactides M, Kleanthous M (2015) Oxidative stress in beta-thalassaemia and sickle cell disease. Redox Biol 6:226–239. https://doi.org/10.1016/j.redox.2015.07.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Akuri MC, Barbalho SM, Val RM, Guiguer EL (2017) Reflections about osteoarthritis and Curcuma longa. Pharmacogn Rev 11(21):8–12. https://doi.org/10.4103/phrev.phrev_54_16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors would like to thank all participants of this study.

Funding

This study was financially supported by the Agricultural Research Development Agency (Public Organization) or “ARDA” (grant number CRP5805020140), Thailand.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand

    Suneerat Hatairaktham, Patarabutr Masaratana, Chatchawan Srisawat, Vorapan Sirivatanauksorn, Narumol Panichkul & Ruchaneekorn W. Kalpravidh

  2. Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

    Chattree Hantaweepant & Noppadol Siritanaratkul

Authors
  1. Suneerat Hatairaktham
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patarabutr Masaratana
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chattree Hantaweepant
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chatchawan Srisawat
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vorapan Sirivatanauksorn
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Noppadol Siritanaratkul
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Narumol Panichkul
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ruchaneekorn W. Kalpravidh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patarabutr Masaratana.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Human Research Protection Unit, Faculty of Medicine Siriraj Hospital, Mahidol University (Si261/2015) and conducted in accordance with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Consent to participate

Informed consent was obtained from all participants enrolled in the study.

Consent for publication

Not applicable.

Code availability

Not applicable.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

ESM 1

(DOCX 56.5 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hatairaktham, S., Masaratana, P., Hantaweepant, C. et al. Curcuminoids supplementation ameliorates iron overload, oxidative stress, hypercoagulability, and inflammation in non-transfusion-dependent β-thalassemia/Hb E patients. Ann Hematol 100, 891–901 (2021). https://doi.org/10.1007/s00277-020-04379-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-020-04379-7

Keywords

Search

Navigation