Advertisement

Inflammopharmacology

, Volume 25, Issue 1, pp 25–31 | Cite as

Antioxidant effects of curcuminoids in patients with type 2 diabetes mellitus: a randomized controlled trial

  • Yunes Panahi
  • Nahid Khalili
  • Ebrahim Sahebi
  • Soha Namazi
  • Maryam Saberi Karimian
  • Muhammed Majeed
  • Amirhossein Sahebkar
Original Article

Abstract

Background

Oxidative stress has a key role in the pathogenesis of type II diabetes mellitus (T2DM) and its vascular complications. Antioxidant therapy has been suggested as a potential approach to blunt T2DM development and progression. The aim of this study was to assess the effects of supplementation with curcuminoids, which are natural polyphenolics from turmeric, on oxidative indices in diabetic individuals.

Methods

In this randomized double-blind placebo-controlled trial, 118 subjects with T2DM were randomized to curcuminoids (1000 mg/day co-administered with piperine 10 mg/day) or matching placebo for a period of 8 weeks. Serum total antioxidant capacity, superoxide dismutase (SOD) activities and malondialdehyde (MDA) concentrations were measured at baseline and after the supplementation period.

Results

Curcuminoids supplementation caused a significant elevation in serum total antioxidant capacity (TAC) (p < 0.001) and SOD activities (p < 0.001), while serum MDA levels were significantly reduced compared with the placebo group (p < 0.001). These results remained statistically significant after adjustment for potential confounders (baseline differences in body mass index and fasting serum insulin).

Conclusion

The present results support an antioxidant effect of curcuminoids supplementation in patients with T2DM, and call for future studies to assess the impact of these antioxidant effects on the occurrence of diabetic complications and cardiovascular endpoints.

Keywords

Curcumin Diabetes mellitus Oxidative stress Malondialdehyde Total antioxidant capacity Superoxide dismutase 

Notes

Acknowledgements

This study was financially supported by Clinical Trial Research Center (Tehran, Iran). The authors gratefully acknowledge Sami Labs LTD (Bangalore, India) for providing the drug material used in this trial.

Compliance with ethical standards

Conflict of interest

Muhammed Majeed is the CEO of Sabinsa Corporation and Sami Labs Ltd.

References

  1. Amin F, Bano B (2012) Nitric oxide induced damage and preventive effect of curcumin and quercetin on buffalo brain cystatin Current. Proteomics 9:9–17CrossRefGoogle Scholar
  2. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB (2007) Bioavailability of curcumin: problems and promises. Mol Pharm 4:807–818. doi: 10.1021/mp700113r CrossRefPubMedGoogle Scholar
  3. Bajaj S, Khan A (2012) Antioxidants and diabetes. Indian J Endocrinol Metab 16:S267–S271. doi: 10.4103/2230-8210.104057 PubMedPubMedCentralGoogle Scholar
  4. Baum L, Ng A (2004) Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer’s disease animal models. J Alzheimer’s Dis 6:367–377Google Scholar
  5. Biswas J, Sinha D, Mukherjee S, Roy S, Siddiqi M, Roy M (2010) Curcumin protects DNA damage in a chronically arsenic-exposed population of West Bengal. Hum Exp Toxicol 29:513–524. doi: 10.1177/0960327109359020 CrossRefPubMedGoogle Scholar
  6. Boaz M et al (2000) Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lancet 356:1213–1218CrossRefPubMedGoogle Scholar
  7. Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820CrossRefPubMedGoogle Scholar
  8. Ceriello A, Testa R (2009) Antioxidant anti-inflammatory treatment in type 2 diabetes. Diabetes care 32(Suppl 2):S232–S236. doi: 10.2337/dc09-S316 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Chait A, Bornfeldt KE (2009) Diabetes and atherosclerosis: is there a role for hyperglycemia? J Lipid Res 50:S335–S339CrossRefPubMedPubMedCentralGoogle Scholar
  10. Derosa G, Maffioli P, Simental-Mendia LE, Bo S, Sahebkar A (2016) Effect of curcumin on circulating interleukin-6 concentrations: a systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 111:394–404. doi: 10.1016/j.phrs.2016.07.004 CrossRefPubMedGoogle Scholar
  11. DiSilvestro RA, Joseph E, Zhao S, Bomser J (2012a) Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. Nutr J 11:1CrossRefGoogle Scholar
  12. DiSilvestro RA, Joseph E, Zhao S, Bomser J (2012b) Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. Nutr J 11:79. doi: 10.1186/1475-2891-11-79 CrossRefPubMedPubMedCentralGoogle Scholar
  13. Esmaily H, Sahebkar A, Iranshahi M, Ganjali S, Mohammadi A, Ferns G, Ghayour-Mobarhan M (2015) An investigation of the effects of curcumin on anxiety and depression in obese individuals: A randomized controlled trial Chinese journal of integrative medicine 21:332–338. doi: 10.1007/s11655-015-2160-z PubMedGoogle Scholar
  14. Ghandadi M, Sahebkar A (2016) Curcumin: an effective inhibitor of interleukin-6. Curr Pharm Des. doi: 10.2174/1381612822666161006151605
  15. Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107:1058–1070. doi: 10.1161/CIRCRESAHA.110.223545 CrossRefPubMedPubMedCentralGoogle Scholar
  16. Hogan P, Dall T, Nikolov P (2003) Economic costs of diabetes in the US in 2002. Diabetes Care 26:917CrossRefPubMedGoogle Scholar
  17. Huang Y, Cai X, Chen P, Mai W, Tang H, Huang Y, Hu Y (2014) Associations of prediabetes with all-cause and cardiovascular mortality: a meta-analysis. Ann Med 46:684–692CrossRefPubMedGoogle Scholar
  18. Johansen JS, Harris AK, Rychly DJ, Ergul A (2005) Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovasc Diabetol 4:5. doi: 10.1186/1475-2840-4-5 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Karimian MS, Pirro M, Majeed M, Sahebkar A (2016) Curcumin as a natural regulator of monocyte chemoattractant protein-1. Cytokine Growth Factor Rev. doi: 10.1016/j.cytogfr.2016.10.001 PubMedGoogle Scholar
  20. Kasi PD et al (2016) Molecular targets of curcumin for cancer therapy: an updated review. Tumour Biol J Int Soc Oncodev Biol Med. doi: 10.1007/s13277-016-5183-y Google Scholar
  21. Khonche A et al (2016) Adjunctive therapy with curcumin for peptic ulcer: a randomized controlled trial. Drug Res 66:444–448. doi: 10.1055/s-0042-109394 CrossRefGoogle Scholar
  22. Lonn E et al (2001) Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE). Circulation 103:919–925CrossRefPubMedGoogle Scholar
  23. Maheshwari RK, Singh AK, Gaddipati J, Srimal RC (2006) Multiple biological activities of curcumin: a short review. Life Sci 78:2081–2087CrossRefPubMedGoogle Scholar
  24. Miller NJ, Rice-Evans C, Davies MJ, Gopinathan V, Milner A (1993) A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin Sci (Lond) 84:407–412CrossRefGoogle Scholar
  25. Mirzaei H et al (2016) Curcumin: a new candidate for melanoma therapy? Int J Cancer 139:1683–1695. doi: 10.1002/ijc.30224 CrossRefPubMedGoogle Scholar
  26. Mohammadi A, Sahebkar A, Iranshahi M, Amini M, Khojasteh R, Ghayour-Mobarhan M, Ferns GA (2013) Effects of supplementation with curcuminoids on dyslipidemia in obese patients: a randomized crossover trial. PTR 27:374–379. doi: 10.1002/ptr.4715 PubMedGoogle Scholar
  27. Momtazi AA, Sahebkar A (2016) Difluorinated curcumin: a promising curcumin analogue with improved anti-tumor activity and pharmacokinetic profile. Curr Pharm Des 22:4386–4397CrossRefPubMedGoogle Scholar
  28. Momtazi AA, Derosa G, Maffioli P, Banach M, Sahebkar A (2016a) Role of microRNAs in the therapeutic effects of curcumin in non-cancer diseases. Mol Diagn Ther 20:335–345. doi: 10.1007/s40291-016-0202-7 CrossRefPubMedGoogle Scholar
  29. Momtazi AA, Shahabipour F, Khatibi S, Johnston TP, Pirro M, Sahebkar A (2016b) Curcumin as a MicroRNA regulator in cancer: a review. Rev Physiol Biochem Pharmacol 171:1–38. doi: 10.1007/112_2016_3 PubMedGoogle Scholar
  30. Montonen J, Knekt P, Jarvinen R, Reunanen A (2004) Dietary antioxidant intake and risk of type 2 diabetes. Diabetes Care 27:362–366CrossRefPubMedGoogle Scholar
  31. Na LX, Yan BL, Jiang S, Cui HL, Li Y, Sun CH (2014) Curcuminoids target decreasing serum adipocyte-fatty acid binding protein levels in their glucose-lowering effect in patients with type 2 diabetes. BES 27:902–906. doi: 10.3967/bes2014.127 PubMedGoogle Scholar
  32. Palanisamy U, Manaharan T, Teng LL, Radhakrishnan AK, Subramaniam T, Masilamani T (2011) Rambutan rind in the management of hyperglycemia. Food Res Int 44:2278–2282CrossRefGoogle Scholar
  33. Panahi Y, Sahebkar A, Amiri M, Davoudi SM, Beiraghdar F, Hoseininejad SL, Kolivand M (2012a) Improvement of sulphur mustard-induced chronic pruritus, quality of life and antioxidant status by curcumin: results of a randomised, double-blind, placebo-controlled trial. Br J Nutr 108:1272–1279. doi: 10.1017/S0007114511006544 CrossRefPubMedGoogle Scholar
  34. Panahi Y, Sahebkar A, Parvin S, Saadat A (2012b) A randomized controlled trial on the anti-inflammatory effects of curcumin in patients with chronic sulphur mustard-induced cutaneous complications. Ann Clin Biochem 49:580–588. doi: 10.1258/acb.2012.012040 CrossRefPubMedGoogle Scholar
  35. Panahi Y, Khalili N, Hosseini MS, Abbasinazari M, Sahebkar A (2014a) Lipid-modifying effects of adjunctive therapy with curcuminoids-piperine combination in patients with metabolic syndrome: results of a randomized controlled trial. Complement Ther Med 22:851–857. doi: 10.1016/j.ctim.2014.07.006 CrossRefPubMedGoogle Scholar
  36. Panahi Y, Rahimnia AR, Sharafi M, Alishiri G, Saburi A, Sahebkar A (2014b) Curcuminoid treatment for knee osteoarthritis: a randomized double-blind placebo-controlled trial. PTR 28:1625–1631. doi: 10.1002/ptr.5174 PubMedGoogle Scholar
  37. Panahi Y, Badeli R, Karami GR, Sahebkar A (2015a) Investigation of the efficacy of adjunctive therapy with bioavailability-boosted curcuminoids in major depressive disorder. PTR 29:17–21. doi: 10.1002/ptr.5211 PubMedGoogle Scholar
  38. Panahi Y, Ghanei M, Bashiri S, Hajihashemi A, Sahebkar A (2015b) Short-term curcuminoid supplementation for chronic pulmonary complications due to sulfur mustard intoxication: positive results of a randomized double-blind placebo-controlled trial. Drug Res 65:567–573. doi: 10.1055/s-0034-1389986 Google Scholar
  39. Panahi Y, Hosseini MS, Khalili N, Naimi E, Majeed M, Sahebkar A (2015c) Antioxidant and anti-inflammatory effects of curcuminoid-piperine combination in subjects with metabolic syndrome: a randomized controlled trial and an updated meta-analysis. Clin Nutr 34:1101–1108. doi: 10.1016/j.clnu.2014.12.019 CrossRefPubMedGoogle Scholar
  40. Panahi Y, Alishiri GH, Parvin S, Sahebkar A (2016a) Mitigation of systemic oxidative stress by curcuminoids in osteoarthritis: results of a randomized controlled trial. J Diet Suppl 13:209–220. doi: 10.3109/19390211.2015.1008611 CrossRefPubMedGoogle Scholar
  41. Panahi Y, Ghanei M, Hajhashemi A, Sahebkar A (2016b) Effects of curcuminoids-piperine combination on systemic oxidative stress, clinical symptoms and quality of life in subjects with chronic pulmonary complications due to sulfur mustard: a randomized controlled trial. J Diet Suppl 13:93–105. doi: 10.3109/19390211.2014.952865 CrossRefPubMedGoogle Scholar
  42. Panahi Y, Hosseini MS, Khalili N, Naimi E, Simental-Mendia LE, Majeed M, Sahebkar A (2016c) Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: a post hoc analysis of a randomized controlled trial. Biomed Pharmacother Biomedecine Pharmacotherapie 82:578–582. doi: 10.1016/j.biopha.2016.05.037 CrossRefPubMedGoogle Scholar
  43. Panahi Y, Kianpour P, Mohtashami R, Jafari R, Simental-Mendia LE, Sahebkar A (2016d) Curcumin lowers serum lipids and uric acid in subjects with nonalcoholic fatty liver disease: a randomized controlled trial. J Cardiovasc Pharmacol 68:223–229. doi: 10.1097/FJC.0000000000000406 CrossRefPubMedGoogle Scholar
  44. Piper JT, Singhal SS, Salameh MS, Torman RT, Awasthi YC, Awasthi S (1998) Mechanisms of anticarcinogenic properties of curcumin: the effect of curcumin on glutathione linked detoxification enzymes in rat liver. Int J Biochem Cell Biol 30:445–456CrossRefPubMedGoogle Scholar
  45. Poitout V, Robertson RP (2008) Glucolipotoxicity: fuel excess and β-cell dysfunction. Endocr Rev 29:351–366CrossRefPubMedGoogle Scholar
  46. Rahmani S, Asgary S, Askari G, Keshvari M, Hatamipour M, Feizi A, Sahebkar A (2016) Treatment of non-alcoholic fatty liver disease with curcumin: a randomized placebo-controlled. PTR 30:1540–1548. doi: 10.1002/ptr.5659 PubMedGoogle Scholar
  47. Rother KI (2007) Diabetes treatment—bridging the divide. N Engl J Med 356:1499CrossRefPubMedPubMedCentralGoogle Scholar
  48. Ruby A, Kuttan G, Babu KD, Rajasekharan K, Kuttan R (1995) Anti-tumour and antioxidant activity of natural curcuminoids. Cancer Lett 94:79–83CrossRefPubMedGoogle Scholar
  49. Sacco M, Pellegrini F, Roncaglioni MC, Avanzini F, Tognoni G, Nicolucci A (2003) Primary prevention of cardiovascular events with low-dose aspirin and vitamin E in type 2 diabetic patients: results of the Primary Prevention Project (PPP) trial. Diabetes Care 26:3264–3272CrossRefPubMedGoogle Scholar
  50. Sahebkar A (2010) Molecular mechanisms for curcumin benefits against ischemic injury. Fertil Steril 94:e75–e76; author reply e77. doi: 10.1016/j.fertnstert.2010.07.1071
  51. Sahebkar A (2013) Why it is necessary to translate curcumin into clinical practice for the prevention and treatment of metabolic syndrome? BioFactors 39:197–208. doi: 10.1002/biof.1062 CrossRefPubMedGoogle Scholar
  52. Sahebkar A (2014a) Are curcuminoids effective C-reactive protein-lowering agents in clinical practice? Evidence from a meta-analysis. PTR 28:633–642. doi: 10.1002/ptr.5045 PubMedGoogle Scholar
  53. Sahebkar A (2014b) Curcuminoids for the management of hypertriglyceridaemia. Nat Rev Cardiol 11:123. doi: 10.1038/nrcardio.2013.140-c1 CrossRefPubMedGoogle Scholar
  54. Sahebkar A, Henrotin Y (2016) Analgesic efficacy and safety of curcuminoids in clinical practice: a systematic review and meta-analysis of randomized controlled trials. Pain Med 17:1192–1202. doi: 10.1093/pm/pnv024 PubMedGoogle Scholar
  55. Sahebkar A et al (2013) Curcuminoids modulate pro-oxidant–antioxidant balance but not the immune response to heat shock protein 27 and oxidized LDL in obese individuals. Phytother Res 27:1883–1888CrossRefPubMedGoogle Scholar
  56. Sahebkar A, Serban MC, Ursoniu S, Banach M (2015) Effect of curcuminoids on oxidative stress: a systematic review and meta-analysis of randomized controlled trials. J Funct Foods 18:898–909. doi: 10.1016/j.jff.2015.01.005 CrossRefGoogle Scholar
  57. Sahebkar A, Cicero AF, Simental-Mendia LE, Aggarwal BB, Gupta SC (2016) Curcumin downregulates human tumor necrosis factor-alpha levels: a systematic review and meta-analysis ofrandomized controlled trials. Pharmacol Res 107:234–242. doi: 10.1016/j.phrs.2016.03.026 CrossRefPubMedGoogle Scholar
  58. Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS (1998) Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 64:353–356. doi: 10.1055/s-2006-957450 CrossRefPubMedGoogle Scholar
  59. Standl E, Müller M, Schnell O (2009) The impact of glucose-lowering therapy on cardiovascular outcomes. Best Pract Res Clin Endocrinol Metabol 23:401–411CrossRefGoogle Scholar
  60. Uchegbu NN, Ishiwu CN (2016) Germinated Pigeon Pea (Cajanus cajan): a novel diet for lowering oxidative stress and hyperglycemia. Food Sci NutrGoogle Scholar
  61. Vikramadithyan RK et al (2005) Human aldose reductase expression accelerates diabetic atherosclerosis in transgenic mice. J Clin Investig 115:2434–2443CrossRefPubMedPubMedCentralGoogle Scholar
  62. Zabihi NA, Pirro M, Johnston TP, Sahebkar A (2016) Is there a role for curcumin supplementation in the treatment of non-alcoholic fatty liver disease? The data suggest yes. Curr Pharm Des. doi: 10.2174/1381612822666161010115235
  63. Zhou H, Beevers CS, Huang S (2011) The targets of curcumin. Curr Drug Targ 12:332–347CrossRefGoogle Scholar

Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  • Yunes Panahi
    • 1
  • Nahid Khalili
    • 2
  • Ebrahim Sahebi
    • 3
  • Soha Namazi
    • 3
  • Maryam Saberi Karimian
    • 4
  • Muhammed Majeed
    • 5
  • Amirhossein Sahebkar
    • 6
  1. 1.Chemical Injuries Research CenterBaqiyatallah University of Medical SciencesTehranIran
  2. 2.Department of EndocrinologyBaqiyatallah University of Medical SciencesTehranIran
  3. 3.Department of Pharmacotherapy, School of PharmacyShiraz University of Medical SciencesShirazIran
  4. 4.Student Research Committee, Clinical Research Unit, Quaem Hospital, Faculty of MedicineMashhad University of Medical SciencesMashhadIran
  5. 5.Sabinsa IncPrincetonUSA
  6. 6.Biotechnology Research CenterMashhad University of Medical SciencesMashhadIran

Personalised recommendations