Skip to main content

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

Inflammopharmacology volume 25, pages 25–31 (2017)Cite this 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.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

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

References

  • Amin F, Bano B (2012) Nitric oxide induced damage and preventive effect of curcumin and quercetin on buffalo brain cystatin Current. Proteomics 9:9–17

    CAS  Article  Google Scholar 

  • Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB (2007) Bioavailability of curcumin: problems and promises. Mol Pharm 4:807–818. doi:10.1021/mp700113r

    CAS  Article  PubMed  Google Scholar 

  • Bajaj S, Khan A (2012) Antioxidants and diabetes. Indian J Endocrinol Metab 16:S267–S271. doi:10.4103/2230-8210.104057

    PubMed  PubMed Central  Google Scholar 

  • 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 6:367–377

    CAS  Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • Boaz M et al (2000) Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lancet 356:1213–1218

    CAS  Article  PubMed  Google Scholar 

  • Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820

    CAS  Article  PubMed  Google Scholar 

  • 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

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Chait A, Bornfeldt KE (2009) Diabetes and atherosclerosis: is there a role for hyperglycemia? J Lipid Res 50:S335–S339

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • 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 11:1

    Article  Google Scholar 

  • 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

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Ghandadi M, Sahebkar A (2016) Curcumin: an effective inhibitor of interleukin-6. Curr Pharm Des. doi:10.2174/1381612822666161006151605

  • Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107:1058–1070. doi:10.1161/CIRCRESAHA.110.223545

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Hogan P, Dall T, Nikolov P (2003) Economic costs of diabetes in the US in 2002. Diabetes Care 26:917

    Article  PubMed  Google Scholar 

  • 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 46:684–692

    CAS  Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • 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 

  • 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

    CAS  Article  Google Scholar 

  • 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 103:919–925

    CAS  Article  PubMed  Google Scholar 

  • Maheshwari RK, Singh AK, Gaddipati J, Srimal RC (2006) Multiple biological activities of curcumin: a short review. Life Sci 78:2081–2087

    CAS  Article  PubMed  Google Scholar 

  • 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) 84:407–412

    CAS  Article  Google Scholar 

  • Mirzaei H et al (2016) Curcumin: a new candidate for melanoma therapy? Int J Cancer 139:1683–1695. doi:10.1002/ijc.30224

    CAS  Article  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Momtazi AA, Sahebkar A (2016) Difluorinated curcumin: a promising curcumin analogue with improved anti-tumor activity and pharmacokinetic profile. Curr Pharm Des 22:4386–4397

    CAS  Article  PubMed  Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • Montonen J, Knekt P, Jarvinen R, Reunanen A (2004) Dietary antioxidant intake and risk of type 2 diabetes. Diabetes Care 27:362–366

    CAS  Article  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Palanisamy U, Manaharan T, Teng LL, Radhakrishnan AK, Subramaniam T, Masilamani T (2011) Rambutan rind in the management of hyperglycemia. Food Res Int 44:2278–2282

    CAS  Article  Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • 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 30:445–456

    CAS  Article  PubMed  Google Scholar 

  • Poitout V, Robertson RP (2008) Glucolipotoxicity: fuel excess and β-cell dysfunction. Endocr Rev 29:351–366

    CAS  Article  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Rother KI (2007) Diabetes treatment—bridging the divide. N Engl J Med 356:1499

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Ruby A, Kuttan G, Babu KD, Rajasekharan K, Kuttan R (1995) Anti-tumour and antioxidant activity of natural curcuminoids. Cancer Lett 94:79–83

    CAS  Article  PubMed  Google Scholar 

  • 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 26:3264–3272

    CAS  Article  PubMed  Google Scholar 

  • 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

  • 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

    CAS  Article  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Sahebkar A (2014b) Curcuminoids for the management of hypertriglyceridaemia. Nat Rev Cardiol 11:123. doi:10.1038/nrcardio.2013.140-c1

    CAS  Article  PubMed  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • 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 27:1883–1888

    CAS  Article  PubMed  Google Scholar 

  • 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

    CAS  Article  Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • 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

    CAS  Article  PubMed  Google Scholar 

  • Standl E, Müller M, Schnell O (2009) The impact of glucose-lowering therapy on cardiovascular outcomes. Best Pract Res Clin Endocrinol Metabol 23:401–411

    CAS  Article  Google Scholar 

  • Uchegbu NN, Ishiwu CN (2016) Germinated Pigeon Pea (Cajanus cajan): a novel diet for lowering oxidative stress and hyperglycemia. Food Sci Nutr

  • Vikramadithyan RK et al (2005) Human aldose reductase expression accelerates diabetic atherosclerosis in transgenic mice. J Clin Investig 115:2434–2443

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • 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

  • Zhou H, Beevers CS, Huang S (2011) The targets of curcumin. Curr Drug Targ 12:332–347

    CAS  Article  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Yunes Panahi

  2. Department of Endocrinology, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Nahid Khalili

  3. Department of Pharmacotherapy, School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box: 1583, Shiraz, Iran

    Ebrahim Sahebi & Soha Namazi

  4. Student Research Committee, Clinical Research Unit, Quaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Maryam Saberi Karimian

  5. Sabinsa Inc, Princeton, NJ, USA

    Muhammed Majeed

  6. Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

Authors
  1. Yunes Panahi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nahid Khalili
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ebrahim Sahebi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Soha Namazi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maryam Saberi Karimian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Muhammed Majeed
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Amirhossein Sahebkar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amirhossein Sahebkar.

Ethics declarations

Conflict of interest

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

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Panahi, Y., Khalili, N., Sahebi, E. et al. Antioxidant effects of curcuminoids in patients with type 2 diabetes mellitus: a randomized controlled trial. Inflammopharmacol 25, 25–31 (2017). https://doi.org/10.1007/s10787-016-0301-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10787-016-0301-4

Keywords

  • Curcumin
  • Diabetes mellitus
  • Oxidative stress
  • Malondialdehyde
  • Total antioxidant capacity
  • Superoxide dismutase