Download PDF
Drug Res (Stuttg) 2018; 68(07): 403-409
DOI: 10.1055/s-0044-101752
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Effects of Curcuminoids Plus Piperine on Glycemic, Hepatic and Inflammatory Biomarkers in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blind Placebo-Controlled Trial

Yunes Panahi
1   Pharmacotherapy Department, Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran
,
Nahid Khalili
2   Department of Endocrinology, Baqiyatallah University of Medical Sciences, Tehran, Iran
,
Ebrahim Sahebi
3   Department of Pharmacotherapy, School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box: 1583, Shiraz, Iran
,
Soha Namazi
3   Department of Pharmacotherapy, School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box: 1583, Shiraz, Iran
,
Luis E. Simental-Mendía
4   Biomedical Research Unit, Mexican Social Security Institute, Durango, Mexico
,
Muhammed Majeed
5   Sabinsa Corporation, East Windsor, NJ, United States
,
Amirhossein Sahebkar
6   Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
7   Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
8   School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
› Author Affiliations
Further Information

Publication History

received 15 November 2017

accepted 22 January 2018

Publication Date:
19 February 2018 (online)

Also available at
    Permissions and Reprints

Abstract

Introduction Curcuminoids have been shown to reduce glycemia and related complications in diabetes. In the present study, we evaluated the impact of curcuminoids plus piperine administration on glycemic, hepatic and inflammatory biomarkers in type 2 diabetes (T2D) patients.

Methods T2D patients aged 18–65 years were enrolled in a randomized double-blind placebo-controlled trial and randomly allocated to standard-of-care treatment and dietary advises plus either curcuminoids (daily dose of 500 mg/day co-administered with piperine 5 mg/day) or placebo for a period of 3 months. Glycemic, hepatic and inflammatory parameters were measured at baseline and final conditions.

Results A total of 100 subjects (50 in each group) completed the 3-month period of trial. A significant reduction was found in serum levels of glucose (−9±16 mg/dL vs. −3±11 mg/dL in curcuminoids and placebo groups, respectively; p=0.048), C-peptide (−0.6±0.8 ng/mL vs. 0.02±0.6 ng/mL; p<0.001) and HbA1c (−0.9±1.1% vs. −0.2±0.5%; p<0.001) after curcuminoids supplementation versus placebo group. Additionally, participants in the intervention group showed lower serum alanine aminotransferase (−2±6 vs. −1±5; p=0.032) and aspartate aminotransferase (−3±5 vs. −0.3±4; p=0.002) levels compared with the placebo group. Finally, no significant differences in high-sensitivity C-reactive protein (hs-CRP) concentrations were observed between curcuminoids and placebo groups (p>0.05).

Conclusion The results of the present trial revealed a beneficial effect of curcuminoids plus piperine supplementation on glycemic and hepatic parameters but not on hs-CRP levels in T2D patients.

Key words

Curcuminoids - type 2 diabetes mellitus - homeostatic model assessments - hepatic steatosis index - high-sensitivity C-reactive protein

Institute where the work was conducted: Baqiyatallah Univeristy of Medical Sciences, Tehran, Iran.


 

  • References

  • 1 Ganjali S, Blesso CN, Banach M. et al. Effects of curcumin on HDL functionality. Pharmacological research 2017; 119: 208-218
    CrossrefPubMedGoogle Scholar
  • 2 Lelli D, Sahebkar A, Johnston TP. et al. Curcumin use in pulmonary diseases: State of the art and future perspectives. Pharmacological research 2017; 115: 133-148
    CrossrefPubMedGoogle Scholar
  • 3 Mirzaei H, Naseri G, Rezaee R. et al. Curcumin: A new candidate for melanoma therapy?. International journal of cancer 2016; 139: 1683-1695
    CrossrefPubMedGoogle Scholar
  • 4 Momtazi AA, Shahabipour F, Khatibi S. et al. Curcumin as a MicroRNA regulator in cancer: A Review. Reviews of physiology, biochemistry and pharmacology 2016; 171: 1-38
    PubMedGoogle Scholar
  • 5 Panahi Y. KP Mohtashami R. et al. Efficacy and Safety of Phytosomal Curcumin in Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Trial. Drug Res (Stuttg) 2017; 67: 244-251
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Panahi Y, Rahimnia AR, Sharafi M. et al. Curcuminoid treatment for knee osteoarthritis: a randomized double-blind placebo-controlled trial. Phytotherapy research: PTR 2014; 28: 1625-1631
    CrossrefPubMedGoogle Scholar
  • 7 Rahmani S, Asgary S, Askari G. et al. Treatment of non-alcoholic fatty liver disease with curcumin: A randomized placebo-controlled trial. Phytotherapy research: PTR 2016; 30: 1540-1548
    CrossrefPubMedGoogle Scholar
  • 8 Saberi-Karimian M, Katsiki N, Caraglia M. et al. Vascular endothelial growth factor: An important molecular target of curcumin. Critical reviews in food science and nutrition 2017; 1-14
    PubMedGoogle Scholar
  • 9 Sahebkar A, Henrotin Y. Analgesic Efficacy and safety of curcuminoids in clinical practice: A systematic review and meta-analysis of randomized controlled trials. Pain medicine 2016; 17: 1192-1202
    PubMedGoogle Scholar
  • 10 Chuengsamarn S, Rattanamongkolgul S, Luechapudiporn R. et al. Curcumin extract for prevention of type 2 diabetes. Diabetes care 2012; 35: 2121-2127
    CrossrefPubMedGoogle Scholar
  • 11 Na LX, Li Y, Pan HZ. et al. Curcuminoids exert glucose-lowering effect in type 2 diabetes by decreasing serum free fatty acids: A double-blind, placebo-controlled trial. Molecular nutrition & food research 2013; 57: 1569-1577
    CrossrefPubMedGoogle Scholar
  • 12 Hajavi J, MA Johnston TP et al. Curcumin: A naturally occurring modulator of adipokines in diabetes. J Cell Biochem 2017
    PubMed
  • 13 Katsiki N. YJ Gotzamani-Psarrakou A. et al. Adipokines and vascular risk in type 2 diabetes mellitus. Angiology 2011; 62: 601-604
    CrossrefPubMedGoogle Scholar
  • 14 Wahlstrom B, Blennow G. A study on the fate of curcumin in the rat. Acta pharmacologica et toxicologica 1978; 43: 86-92
    PubMedGoogle Scholar
  • 15 Shoba G. JD Joseph T. et al. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 1998; 64: 353-356
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Panahi Y. KN Sahebi E. et al. Antioxidant effects of curcuminoids in patients with type 2 diabetes mellitus: a randomized controlled trial. Inflammopharmacology 2017; 25: 25-31
    CrossrefPubMedGoogle Scholar
  • 17 Panahi Y. KN Sahebi E. et al. Curcuminoids modify lipid profile in type 2 diabetes mellitus: A randomized controlled trial. Complement Ther Med 2017; 33: 1-5
    CrossrefPubMedGoogle Scholar
  • 18 Cicero AFG, Colletti A, Bajraktari G. et al. Lipid-lowering nutraceuticals in clinical practice: Position paper from an International Lipid Expert Panel. Nutrition reviews 2017; 75: 731-767
    CrossrefPubMedGoogle Scholar
  • 19 Cicero AFG, Colletti A, Bajraktari G. et al. Lipid lowering nutraceuticals in clinical practice: Position paper from an International Lipid Expert Panel. Archives of medical science:AMS 2017; 13: 965-1005
    PubMedGoogle Scholar
  • 20 Johnston TP, Korolenko TA, Pirro M. et al. Preventing cardiovascular heart disease: Promising nutraceutical and non-nutraceutical treatments for cholesterol management. Pharmacological research 2017; 120: 219-225
    CrossrefPubMedGoogle Scholar
  • 21 Sahebkar A, Serban MC, Gluba-Brzozka A. et al. Lipid-modifying effects of nutraceuticals: An evidence-based approach. Nutrition 2016; 32: 1179-1192
    CrossrefPubMedGoogle Scholar
  • 22 Ward N, Sahebkar A, Banach M. et al. Recent perspectives on the role of nutraceuticals as cholesterol-lowering agents. Current opinion in lipidology 2017; 28: 495-501
    CrossrefPubMedGoogle Scholar
  • 23 Cicero AF, Colletti A. Role of phytochemicals in the management of metabolic syndrome. Phytomedicine: International journal of phytotherapy and phytopharmacology 2016; 23: 1134-1144
    CrossrefPubMedGoogle Scholar
  • 24 Sahebkar A. Curcuminoids for the management of hypertriglyceridaemia. Nature reviews Cardiology 2014; 11: 123
    PubMedGoogle Scholar
  • 25 Granados-Castro LF. R-RD Fernández-Rojas B. et al. Curcumin prevents paracetamol-induced liver mitochondrial alterations. J Pharm Pharmacol 2016; 68: 245-256
    CrossrefPubMedGoogle Scholar
  • 26 Naik SR. TV Patil SR. Protective effect of curcumin on experimentally induced inflammation, hepatotoxicity and cardiotoxicity in rats: Evidence of its antioxidant property. Exp Toxicol Pathol 2011; 63: 419-431
    CrossrefPubMedGoogle Scholar
  • 27 Yousef MI. OS El-Guendi MI. et al. Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat. Food Chem Toxicol 2010; 48: 3246-3261
    CrossrefPubMedGoogle Scholar
  • 28 Chuengsamarn S. RS Luechapudiporn R. et al. Curcumin extract for prevention of type 2 diabetes. Diabetes care 2012; 35: 2121-2127
    CrossrefPubMedGoogle Scholar
  • 29 Panahi Y. KN Hosseini MS. et al. Lipid-modifying effects of adjunctive therapy with curcuminoids-piperine combination in patients with metabolic syndrome: Results of a randomized controlled trial. Complement Ther Med 2014; 22: 851-857
    CrossrefPubMedGoogle Scholar
  • 30 Lee JH. KD Kim HJ. et al. Hepatic steatosis index: A simple screening tool reflecting nonalcoholic fatty liver disease. Dig Liver Dis 2010; 42: 503-508
    CrossrefPubMedGoogle Scholar
  • 31 Na LX. LY Pan HZ. et al. Curcuminoids exert glucose-lowering effect in type 2 diabetes by decreasing serum free fatty acids: A double-blind, placebo-controlled trial. Mol Nutr Food Res 2013; 57: 1569-1577
    CrossrefPubMedGoogle Scholar
  • 32 Fujiwara H. HM Zhou X. et al. Curcumin inhibits glucose production in isolated mice hepatocytes. Diabetes Res Clin Pract 2008; 80: 185-191
    CrossrefPubMedGoogle Scholar
  • 33 Seo KI. CM Jung UJ. et al. Effect of curcumin supplementation on blood glucose, plasma insulin, and glucose homeostasis related enzyme activities in diabetic db/db mice. Mol Nutr Food Res 2008; 52: 995-1004
    CrossrefPubMedGoogle Scholar
  • 34 Hotamisligil GS. PP Budavari A. et al. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 1996; 271: 665-668
    CrossrefPubMedGoogle Scholar
  • 35 Naugler WE. KM The wolf in sheep's clothing: The role of interleukin-6 in immunity, inflammation and cancer. Trends Mol Med 2008; 14: 109-119
    CrossrefPubMedGoogle Scholar
  • 36 Panahi Y, Alishiri GH, Parvin S. et al. Mitigation of systemic oxidative stress by curcuminoids in osteoarthritis: Results of a randomized controlled trial. Journal of dietary supplements 2016; 13: 209-220
    CrossrefPubMedGoogle Scholar
  • 37 Panahi Y, Ghanei M, Hajhashemi A. et al. 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. Journal of dietary supplements 2016; 13: 93-105
    CrossrefPubMedGoogle Scholar
  • 38 Sahebkar A, Serban MC, Ursoniu S. et al. Effect of curcuminoids on oxidative stress: A systematic review and meta-analysis of randomized controlled trials. Journal of Functional Foods 2015; 18: 898-909
    CrossrefPubMedGoogle Scholar
  • 39 Meghana K. SG Ramesh B. Curcumin prevents streptozotocin-induced islet damage by scavenging free radicals: A prophylactic and protective role. Eur J Pharmacol 2007; 577: 183-191
    CrossrefPubMedGoogle Scholar
  • 40 A.S Are curcuminoids effective C-reactive protein-lowering agents in clinical practice? Evidence from a meta-analysis. Phytother Res 2014; 28: 633-642
    CrossrefPubMedGoogle Scholar
  • 41 Panahi Y. HM Khalili N. et al. 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 2015; 34: 1101-1108
    CrossrefPubMedGoogle Scholar
  • 42 Lloyd-Jones DM. LK Tian L. et al. Narrative review: Assessment of C-reactive protein in risk prediction for cardiovascular disease. Ann Intern Med 2006; 145: 35-42
    CrossrefPubMedGoogle Scholar
  • 43 Ganjali S, Sahebkar A, Mahdipour E. et al. Investigation of the effects of curcumin on serum cytokines in obese individuals: A randomized controlled trial. TheScientificWorldJournal 2014; 2014: 898361
    PubMedGoogle Scholar
  • 44 Mollazadeh H, Cicero AFG, Blesso CN. et al. Immune modulation by curcumin: The role of interleukin-10. Critical reviews in food science and nutrition 2017; 1-13
    PubMedGoogle Scholar
  • 45 Panahi Y, Hosseini MS, Khalili N. et al. Antioxidant and anti-inflammatory effects of curcuminoid-piperine combination in subjects with metabolic syndrome: A randomized controlled trial and an updated meta-analysis. Clinical nutrition 2015; 34: 1101-1108
    CrossrefPubMedGoogle Scholar
  • 46 Sahebkar A, Cicero AFG, Simental-Mendia LE. et al. Curcumin downregulates human tumor necrosis factor-alpha levels: A systematic review and meta-analysis ofrandomized controlled trials. Pharmacological research 2016; 107: 234-242
    CrossrefPubMedGoogle Scholar
  • 47 Moshage HJ. RH van Pelt JF. et al. The effect of interleukin-1, interleukin-6 and its interrelationship on the synthesis of serum amyloid A and C-reactive protein in primary cultures of adult human hepatocytes. Biochem Biophys Res Commun 1988; 155: 112-117
    CrossrefPubMedGoogle Scholar
  • 48 Meng Z. YC Deng Q. et al. Curcumin inhibits LPS-induced inflammation in rat vascular smooth muscle cells in vitro via ROS-relative TLR4-MAPK/NF-κB pathways. Acta Pharmacol Sin 2013; 34: 901-911
    CrossrefPubMedGoogle Scholar
  • 49 Leclercq IA. FG Sempoux C. et al. Curcumin inhibits NF-kappaB activation and reduces the severity of experimental steatohepatitis in mice. J Hepatol 2004; 41: 926-934
    CrossrefPubMedGoogle Scholar
  • 50 Vizzutti F. PA Galastri S. et al. Curcumin limits the fibrogenic evolution of experimental steatohepatitis. Lab Invest 2010; 90: 104-115
    CrossrefPubMedGoogle Scholar
  • 51 Ramirez-Tortosa MC, R-T C, Mesa MD. et al. Curcumin ameliorates rabbits's steatohepatitis via respiratory chain, oxidative stress, and TNF-alpha. Free Radic Biol Med 2009; 47: 924-931
    CrossrefPubMedGoogle Scholar