Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Journal of Complementary and Integrative Medicine

Editor-in-Chief: Lui, Edmund

Ed. by Ko, Robert / Leung, Kelvin Sze-Yin / Saunders, Paul / Suntres, PH. D., Zacharias

CiteScore 2017: 1.41

SCImago Journal Rank (SJR) 2017: 0.472
Source Normalized Impact per Paper (SNIP) 2017: 0.564

See all formats and pricing
More options …

Asymmetric dimethylarginine and soluble inter-cellular adhesion molecule-1 serum levels alteration following ginger supplementation in patients with type 2 diabetes: a randomized double-blind, placebo-controlled clinical trial

Meysam Zarezadeh
  • Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Ahmad Saedisomeolia
  • Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Masoud Khorshidi
  • Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Hamed Kord Varkane
  • Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Motahareh Makhdoomi Arzati
  • Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mina Abdollahi
  • AmirAlam Hospital Complex, Marvasti Hospital, Tehran University of Medical Sciences, Tehran, Iran (Islamic Republic of)
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mir Saeed Yekaninejad
  • Department of Biostatistics and Epidemiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Rezvan Hashemi
  • Department of Geriatric Medicine, Ziaeian Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mohammad Effatpanah / Niyaz Mohammadzadeh Honarvar
  • Corresponding author
  • Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2018-08-11 | DOI: https://doi.org/10.1515/jcim-2018-0019



Patients with type 2 diabetes mellitus (T2DM) are prone to cardiovascular disease (CVD) due to inflammation process and oxidative stress. ADMA (Asymmetric dimethylarginine) and ICAM-1 (inter-cellular adhesion molecule-1) play an important role in CVD pathogenesis. Ginger as an anti-oxidant and anti-inflammation can effect on these biomarkers. The aim of present study was to characterize the effect of ginger supplementation on ADMA and ICAM-1 serum levels in patients with T2DM.


The present study is a randomized double-blind clinical trial which is conducted among 45 diabetic patients (nginger=23, nplacebo=22). The participants were randomly divided into two intervention and placebo groups which were received 2 g ginger powder and 2 g wheat flour for 10 weeks, respectively. ADMA and ICAM-1 concentration were measured by ELISA method.


Ginger supplementation decreased ADMA serum levels significantly (P=0.002) and sICAM-1 serum levels marginally (P=0.097) in supplementation group after intervention. No significant difference was observed between placebo and supplementation groups.


Present study was conducted among patients with type 2 diabetes mellitus to investigate the effect of ginger supplementation on ADMA and sICAM-1 levels. There was a significant decrement in ADMA serum concentration and slight reduction in sICAM-1 levels in intervention group. The amount of reduction in both biomarkers was not statistically significant in between-groups comparison.

Keywords: asymmetric dimethylarginine; ginger; inter-cellular adhesion molecule-1; type 2 diabetes; vascular complications


  • [1]

    Chen L, Magliano DJ, Zimmet PZ. The worldwide epidemiology of type 2 diabetes mellitus – present and future perspectives. Nat Rev Endocrinol. 2012;8:228–36.Web of ScienceCrossrefGoogle Scholar

  • [2]

    Shi Y, Hu FB. The global implications of diabetes and cancer. Lancet. 2014;383:1947.Web of ScienceCrossrefPubMedGoogle Scholar

  • [3]

    Kampoli A-M, Tousoulis D, Briasoulis A, Latsios G, Papageorgiou N, Stefanadis C. Potential pathogenic inflammatory mechanisms of endothelial dysfunction induced by type 2 diabetes mellitus. Curr Pharm Des. 2011;17:4147–58.CrossrefPubMedGoogle Scholar

  • [4]

    Vanessa Fiorentino T, Prioletta A, Zuo P, Folli F. Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases. Curr Pharm Des. 2013;19:5695–703.CrossrefPubMedGoogle Scholar

  • [5]

    Sibal L, Agarwal SC, Home PD, Boger RH. The role of asymmetric dimethylarginine (ADMA) in endothelial dysfunction and cardiovascular disease. Curr Cardiol Rev. 2010;6:82–90.PubMedCrossrefGoogle Scholar

  • [6]

    Giles TD, Sander GE, Nossaman BD, Kadowitz PJ. Impaired vasodilation in the pathogenesis of hypertension: focus on nitric oxide, endothelial‐derived hyperpolarizing factors, and prostaglandins. J Clin Hypertens. 2012;14:198–205.CrossrefWeb of ScienceGoogle Scholar

  • [7]

    Abbasi F, Asagmi T, Cooke JP, Lamendola C, McLaughlin T, Reaven GM, et al. Plasma concentrations of asymmetric dimethylarginine are increased in patients with type 2 diabetes mellitus. Am J Cardiol. 2001;88:1201–03.PubMedCrossrefGoogle Scholar

  • [8]

    Uhlmann T, Geoghegan VL, Thomas B, Ridlova G, Trudgian DC, Acuto O. A method for large-scale identification of protein arginine methylation. Mol Cell Proteomics. 2012;11:1489–99.CrossrefPubMedWeb of ScienceGoogle Scholar

  • [9]

    Förstermann U. Nitric oxide and oxidative stress in vascular disease. Pflügers Archiv-Eur J Physiol. 2010;459:923–39.CrossrefGoogle Scholar

  • [10]

    Arrigoni F, Ahmetaj B, Leiper J. The biology and therapeutic potential of the DDAH/ADMA pathway. Curr Pharm Des. 2010;16:4089–102.PubMedCrossrefGoogle Scholar

  • [11]

    Pitocco D, Zaccardi F, Di Stasio E, Romitelli F, Santini SA, Zuppi C, et al. Oxidative stress, nitric oxide, and diabetes. Rev Diabet Stud. 2010;7:15–25.CrossrefPubMedGoogle Scholar

  • [12]

    Creager MA, Lüscher TF, Cosentino F, Beckman JA. Diabetes and vascular disease. Circulation. 2003;108:1527–32.PubMedCrossrefGoogle Scholar

  • [13]

    Aggarwal BB. Nuclear factor-κB: The enemy within. Cancer Cell. 2004;6:203–08.CrossrefPubMedGoogle Scholar

  • [14]

    Cybulsky MI, Iiyama K, Li H, Zhu S, Chen M, Iiyama M, et al. A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. J Clin Invest. 2001;107:1255–62.CrossrefGoogle Scholar

  • [15]

    Lawson C, Wolf S. ICAM-1 signaling in endothelial cells. Pharmacol Rep. 2009;61:22–32.CrossrefWeb of SciencePubMedGoogle Scholar

  • [16]

    Nathan DM, Buse JB, Davidson MB, Heine RJ. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2006;29:1963.CrossrefGoogle Scholar

  • [17]

    Calixto J. Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents). Braz J Med Biol Res. 2000;33:179–89.PubMedCrossrefGoogle Scholar

  • [18]

    Thomson M, Al-Qattan K, Al-Sawan S, Alnaqeeb M, Khan I, Ali M. The use of ginger (Zingiber officinale Rosc.) as a potential anti-inflammatory and antithrombotic agent. Prostaglandins Leukot Essent Fatty Acids. 2002;67:475–78.PubMedCrossrefGoogle Scholar

  • [19]

    Grzanna R, Lindmark L, Frondoza CG. Ginger – an herbal medicinal product with broad anti-inflammatory actions. J Med Food. 2005;8:125–32.CrossrefPubMedGoogle Scholar

  • [20]

    Masuda Y, Kikuzaki H, Hisamoto M, Nakatani N. Antioxidant properties of gingerol related compounds from ginger. Biofactors. 2004;21:293–96.PubMedCrossrefGoogle Scholar

  • [21]

    Stoilova I, Krastanov A, Stoyanova A, Denev P, Gargova S. Antioxidant activity of a ginger extract (Zingiber officinale). Food Chem. 2007;102:764–70.CrossrefWeb of ScienceGoogle Scholar

  • [22]

    Spoelstra‐de Man A, Teerlink T, Brouwer C, Rauwerda J, Stehouwer C, Smulders Y. No effect of B vitamins on ADMA levels in patients at increased cardiovascular risk. Clin Endocrinol (Oxf). 2006;64:495–501.PubMedCrossrefGoogle Scholar

  • [23]

    Achan V, Broadhead M, Malaki M, Whitley G, Leiper J, MacAllister R, et al. Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase. Arterioscler Thromb Vasc Biol. 2003;23:1455–9.PubMedCrossrefGoogle Scholar

  • [24]

    Teerlink T. ADMA metabolism and clearance. Vasc Med. 2005;10:S73–S81.Google Scholar

  • [25]

    Vallance P, Chan N. Endothelial function and nitric oxide: clinical relevance. Heart. 2001;85:342–50.PubMedCrossrefGoogle Scholar

  • [26]

    Jiang D-J, Cao Y, Xin H-Y, Li X-H, Luo Z-Q, Li Y-J. Asymmetric dimethylarginine induces tissue factor expression in monocytes via NF-kappaB-dependent pathway: role in acute coronary syndromes. Atherosclerosis. 2009;205:554–60.CrossrefWeb of SciencePubMedGoogle Scholar

  • [27]

    Zhang G-G, Bai Y-P, Chen M-F, Shi R-Z, Jiang D-J, Fu Q-M, et al. Asymmetric dimethylarginine induces TNF-α production via ROS/NF–ΚB dependent pathway in human monocytic cells and the inhibitory effect of reinioside C. Vascul Pharmacol. 2008;48:115–21.CrossrefPubMedGoogle Scholar

  • [28]

    Ceriello A, Falleti E, Bortolotti N, Motz E, Cavarape A, Russo A, et al. Increased circulating intercellular adhesion molecule-1 levels in type II diabetic patients: the possible role of metabolic control and oxidative stress. Metabolism. 1996;45:498–501.CrossrefPubMedGoogle Scholar

  • [29]

    Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105:1135–43.PubMedCrossrefGoogle Scholar

  • [30]

    Eid HM, Eritsland J, Larsen J, Arnesen H, Seljeflot I. Increased levels of asymmetric dimethylarginine in populations at risk for atherosclerotic disease. Effects of pravastatin. Atherosclerosis. 2003;166:279–84.CrossrefPubMedGoogle Scholar

  • [31]

    Ngo DT, Sverdlov AL, McNeil JJ, Horowitz JD. Does vitamin D modulate asymmetric dimethylarginine and C-reactive protein concentrations?. Am J Med. 2010;123:335–41.CrossrefPubMedWeb of ScienceGoogle Scholar

  • [32]

    Hosseinzadeh-Attar M, Kolahdouz MR, Eshraghian M, Nakhjavani M, Khorrami E, Ebadi M, et al. Reduction in asymmetric dimethylarginine plasma levels by coenzyme Q10 supplementation in patients with type 2 diabetes mellitus. Minerva Endocrinol. 2015;40:259–66.PubMedGoogle Scholar

  • [33]

    Xia XS, Li X, Wang L, Wang JZ, Ma JP, Wu CJ. Supplementation of folic acid and vitamin B(1)(2) reduces plasma levels of asymmetric dimethylarginine in patients with acute ischemic stroke. J Clin Neurosci. 2014;21:1586–90.Web of ScienceCrossrefGoogle Scholar

  • [34]

    Spinelli FR, Di Franco M, Metere A, Conti F, Iannuccelli C, Agati L, et al. Decrease of asymmetric dimethyl arginine after anti-TNF therapy in patients with rheumatoid arthritis. Drug Dev Res. 2014;75:S67–9.Web of SciencePubMedCrossrefGoogle Scholar

  • [35]

    Teplan V, Schuck O, Racek J, Mareckova O, Stollova M, Hanzal V, et al. Reduction of plasma asymmetric dimethylarginine in obese patients with chronic kidney disease after three years of a low-protein diet supplemented with keto-amino acids: a randomized controlled trial. Wien Klin Wochenschr. 2008;120:478–85.Web of SciencePubMedCrossrefGoogle Scholar

  • [36]

    Kaygusuz I, Turhan NO, Duvan CI, Koca C, Aydin M. Effect of genistein therapy on plasma levels of asymmetric dimethylarginine in healthy postmenopausal women: a randomized, placebo-controlled study. Fertil Steril. 2010;94:764–6.PubMedCrossrefWeb of ScienceGoogle Scholar

  • [37]

    Kruszelnicka O, Chyrchel B, Golay A, Surdacki A. Differential associations of circulating asymmetric dimethylarginine and cell adhesion molecules with metformin use in patients with type 2 diabetes mellitus and stable coronary artery disease. Amino Acids. 2015;47:1951–9.PubMedCrossrefWeb of ScienceGoogle Scholar

  • [38]

    Tormala R, Appt S, Clarkson TB, Mueck AO, Seeger H, Mikkola TS, et al. Impact of soy supplementation on sex steroids and vascular inflammation markers in postmenopausal women using tibolone: role of equol production capability. Climacteric. 2008;11:409–15.PubMedCrossrefWeb of ScienceGoogle Scholar

  • [39]

    Vincent HK, Bourguignon CM, Weltman AL, Vincent KR, Barrett E, Innes KE, et al. Effects of antioxidant supplementation on insulin sensitivity, endothelial adhesion molecules, and oxidative stress in normal-weight and overweight young adults. Metabolism. 2009;58:254–62.CrossrefWeb of SciencePubMedGoogle Scholar

  • [40]

    Touvier M, Kesse-Guyot E, Andreeva VA, Fezeu L, Charnaux N, Sutton A, et al. Modulation of the association between plasma intercellular adhesion molecule-1 and cancer risk by n-3 PUFA intake: a nested case-control study. Am J Clin Nutr. 2012;95:944–50.PubMedCrossrefWeb of ScienceGoogle Scholar

  • [41]

    Eschen O, Christensen JH, Lar MT, Romano P, Sala P, Schmidt EB. Effects of marine n-3 fatty acids on circulating levels of soluble adhesion molecules in patients with chronic heart failure. Cell Mol Biol (Noisy-Le-Grand). 2010;56:45–51.PubMedGoogle Scholar

  • [42]

    Basu A, Du M, Sanchez K, Leyva MJ, Betts NM, Blevins S, et al. Green tea minimally affects biomarkers of inflammation in obese subjects with metabolic syndrome. Nutrition. 2011;27:206–13.PubMedCrossrefWeb of ScienceGoogle Scholar

  • [43]

    Jorde R, Sneve M, Torjesen PA, Figenschau Y, Goransson LG, Omdal R. No effect of supplementation with cholecalciferol on cytokines and markers of inflammation in overweight and obese subjects. Cytokine. 2010;50:175–80.CrossrefWeb of SciencePubMedGoogle Scholar

  • [44]

    Paulo MC, Andrade AM, Andrade ML, Morais MG, Kiely M, Parra D, et al. Influence of n-3 polyunsaturated fatty acids on soluble cellular adhesion molecules as biomarkers of cardiovascular risk in young healthy subjects. Nutr Metab Cardiovasc Dis. 2008;18:664–70.PubMedCrossrefGoogle Scholar

  • [45]

    Eid HM, Arnesen H, Hjerkinn EM, Lyberg T, Ellingsen I, Seljeflot I. Effect of diet and omega-3 fatty acid intervention on asymmetric dimethylarginine. Nutr Metab (Lond). 2006;3:4.PubMedCrossrefGoogle Scholar

  • [46]

    Zebrowska A, Mizia-Stec K, Mizia M, Gasior Z, Poprzecki S. Omega-3 fatty acids supplementation improves endothelial function and maximal oxygen uptake in endurance-trained athletes. Eur J Sport Sci. 2015;15:305–14.PubMedCrossrefWeb of ScienceGoogle Scholar

About the article

Received: 2018-02-15

Accepted: 2018-07-09

Published Online: 2018-08-11

This work was supported by Tehran University of Medical Sciences (Grant number: 95-02-161-32356).

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Journal of Complementary and Integrative Medicine, 20180019, ISSN (Online) 1553-3840, DOI: https://doi.org/10.1515/jcim-2018-0019.

Export Citation

© 2018 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Comments (0)

Please log in or register to comment.
Log in