Nutraceutical Approaches in the Management of Cardiovascular Dysfunctions Associated with Diabetes Mellitus

  • Saloni Daftardar
  • Ginpreet Kaur
  • Veeranjaneyulu Addepalli
Part of the Advances in Biochemistry in Health and Disease book series (ABHD, volume 9)


Diabetes is a prime risk factor in cardiovascular disease (CVD), which includes peripheral vascular disease, coronary artery disease, and cerebrovascular disease. Management of cardiovascular dysfunctions associated with diabetes has been a challenge for decades. The nutraceutical approach for prevention of diabetic cardiovascular complications has been a considerably newer trend. Nutraceuticals are medicinal foods that help in maintaining the health of individuals, thereby preventing or treating diseases. A literature search showed that several nutraceuticals used as dietary supplements have the ability to reduce cardiovascular risk factors. Thus, the nutraceutical approach can be very promising in the treatment of diabetic cardiovascular complications. In this review, we summarize the recent research findings on dietary fiber, antioxidants, prebiotics, and probiotics to highlight the benefits of using nutraceuticals in the management of diabetes-associated cardiovascular dysfunctions.


Insulin resistance Inflammation Antidiabetic Nutraceuticals Herbs 


  1. 1.
    World Health Organization (2008) Traditional medicine.
  2. 2.
    Zarraga I, Schwartz E (2006) Impact of dietary patterns and interventions on cardiovascular health. Circulation 114:961–973PubMedCrossRefGoogle Scholar
  3. 3.
    Retelny VS, Neuendorf A, Roth JL (2008) Nutrition protocols for the prevention of cardiovascular disease. Nutr Clin Pract 23:468–476PubMedCrossRefGoogle Scholar
  4. 4.
    Dureja H, Kaushik D, Kumar V (2003) Developments in nutraceuticals. Indian J Pharmacol 35:363–372Google Scholar
  5. 5.
    Jaap GN, Jerrold MO (2006) Inflamed fat: what starts the fire. J Clin Invest 116:33–35Google Scholar
  6. 6.
    Grundy SM, Brewer HB, Cleeman JI et al (2004) Definition of metabolic syndrome: report of the National Heart, Lung and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 109:433–438PubMedCrossRefGoogle Scholar
  7. 7.
    Jaswinder KS, Gokhan SH (1999) The role of TNF in adipocyte metabolism. Semin Cell Dev Biol 10:19–29CrossRefGoogle Scholar
  8. 8.
    Stefan N, Vozarova B, Funahashi T et al (2002) Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans. Diabetes 51:1884–1888PubMedCrossRefGoogle Scholar
  9. 9.
    He Z, Rask-Madsen C, King GL (2003) Managing heart disease: mechanisms of cardiovascular complications in diabetes and potential new pharmacological therapies. Eur Heart J Suppl 5(Suppl B):B51–B57CrossRefGoogle Scholar
  10. 10.
    Perseghin G, Scifo P, Cobelli FD et al (1999) Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents. Diabetes 48:1600–1606PubMedCrossRefGoogle Scholar
  11. 11.
    Tripathy D, Dandona P (2002) Acute elevation of plasma free fatty acids increases reactive oxygen species (ROS) generation by polymorphonuclear cells, induces nuclear factor-kB (NF-kB) and impairs brachial artery reactivity in healthy subjects. In: 62nd Scientific Sessions of the American Diabetes Association, San FranciscoGoogle Scholar
  12. 12.
    Wellen KE, Hotamisligil GS (2005) Inflammation, stress and diabetes. J Clin Invest 115:1111–1119PubMedCentralPubMedGoogle Scholar
  13. 13.
    Hotamisligil GS, Peraldi P, Budavari A et al (1996) IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 271:665–668PubMedCrossRefGoogle Scholar
  14. 14.
    Dong M, Su D, Coudriet GM, Hyun Kim D et al (2009) FoxO1 links insulin resistance to proinflammatory cytokine IL-1β production in macrophages. Diabetes 58(11):2624–2633PubMedCrossRefGoogle Scholar
  15. 15.
    Dzau V, Braunwald E (1999) Resolved and unresolved issues in the prevention and treatment of coronary artery disease: a workshop consensus statement. Am Heart J 121:1244–1263CrossRefGoogle Scholar
  16. 16.
    Ross R (1999) Atherosclerosis—an inflammatory disease. N Engl J Med 340:115–126PubMedCrossRefGoogle Scholar
  17. 17.
    Woollard KJ, Geissmann F (2010) Monocytes in atherosclerosis: subsets and functions. Nat Rev Cardiol 7:77–86PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Vallance P, Chan N (2001) Endothelial function and nitric oxide: clinical relevance. Heart 85:342–350PubMedCrossRefGoogle Scholar
  19. 19.
    Landmesser U, Hornig B, Drexler H (2004) Endothelial function: a critical determinant in atherosclerosis. Circulation 109:11–27CrossRefGoogle Scholar
  20. 20.
    Deanfield JE, Halcox JP, Rabelink TJ (2007) Endothelial function and dysfunction: testing and clinical relevance. Circulation 115:1285–1295PubMedGoogle Scholar
  21. 21.
    Hamilton CA, Miller WH, Brosnan MJ et al (2004) Strategies to reduce oxidative stress in cardiovascular disease. Clin Sci (Lond) 106:219–234CrossRefGoogle Scholar
  22. 22.
    Taniyama Y, Griendling KK (2003) Reactive oxygen species in the vasculature: molecular and cellular mechanisms. Hypertension 42:1075–1081PubMedCrossRefGoogle Scholar
  23. 23.
    Droge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95PubMedGoogle Scholar
  24. 24.
    Griendling KK, FitzGerald GA (2003) Oxidative stress and cardiovascular injury. Part II: Animal and human studies. Circulation 108:2034–2040PubMedCrossRefGoogle Scholar
  25. 25.
    Jay D, Hitomi H, Griendling KK (2006) Oxidative stress and diabetic cardiovascular complications. Free Radic Biol Med 40:183–192PubMedCrossRefGoogle Scholar
  26. 26.
    Packard CJ, Caslake M, Shepherd J (2000) The role of small, dense low density lipoprotein (LDL): a new look. Int J Cardiol 74:S17–S22PubMedCrossRefGoogle Scholar
  27. 27.
    Ginsberg H, Zhang YL, Antonio H (2005) Regulation of plasma triglycerides in insulin resistance and diabetes. Arch Med Res 36:232–240PubMedCrossRefGoogle Scholar
  28. 28.
    Reaven GM, Chen YD, Jeppesen J et al (1993) Insulin resistance and hyperinsulinemia in individuals with small, dense low density lipoprotein particles. J Clin Invest 92:141–146PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Shaul PW (2003) Regulation of endothelial nitric oxide synthase. Annu Rev Physiol 64(749):774Google Scholar
  30. 30.
    Pariza MW, Park Y, Cook ME (2000) Mechanisms of action of conjugated linoleic acid: evidence and speculation. Proc Soc Exp Biol Med 223:8–13PubMedCrossRefGoogle Scholar
  31. 31.
    Lee K, Kritchevsky D, Pariza M (1994) Conjugated linoleic acid and atherosclerosis in rabbits. Atherosclerosis 8:19–25CrossRefGoogle Scholar
  32. 32.
    Ryder JW, Portocarrero CP, Song XM et al (2001) Isomer-specific antidiabetic properties of conjugated linoleic acid. Diabetes 50:1149–1157PubMedCrossRefGoogle Scholar
  33. 33.
    Evans M, Brown J, McIntosh M (2002) Isomer-specific effects of conjugated linoleic acid (CLA) on adiposity and lipid metabolism. J Nutr Biochem 13:508–516PubMedCrossRefGoogle Scholar
  34. 34.
    Grundy SM, Denke MA (1990) Dietary influences on serum lipids and lipoproteins. J Lipid Res 31:1149–1172PubMedGoogle Scholar
  35. 35.
    De Lorgeril M, Salen P, Martin JL et al (1999) Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon diet heart study. Circulation 99:779–785PubMedCrossRefGoogle Scholar
  36. 36.
    Kris-Etherton PM, Taylor DS, Yu-Poth S et al (2000) Polyunsaturated fatty acids in the food chain in the United States. Am J Clin Nutr 71(Suppl 1):179S–188SPubMedGoogle Scholar
  37. 37.
    Mori TA, Bao DQ, Burke V et al (1999) Docosahexanoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans. Hypertension 34:253–260PubMedCrossRefGoogle Scholar
  38. 38.
    Hartweg J, Farmer AJ, Perera R et al (2007) Meta-analysis of the effects of n-3 polyunsaturated fatty acids on lipoproteins and other emerging lipid cardiovascular risk markers in patients with type 2 diabetes. Diabetologia 50:1593–1602PubMedCrossRefGoogle Scholar
  39. 39.
    Lau FC, Bagchi M, Sen CK et al (2008) Nutrigenomic basis of beneficial effects of chromium (III) on obesity and diabetes. Mol Cell Biochem 317:1–10PubMedCrossRefGoogle Scholar
  40. 40.
    Anderson RA, Cheng N, Bryden NA et al (1997) Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes 46(11):1786–1791PubMedCrossRefGoogle Scholar
  41. 41.
    Broadhurst CL, Domenico P (2006) Clinical studies on chromium picolinate supplementation in diabetes mellitus: a review. Diabetes Technol Ther 8(6):677–687PubMedCrossRefGoogle Scholar
  42. 42.
    Balon TW, Gu JL, Tokuyama Y et al (1995) Magnesium supplementation reduces development of diabetes in rat model of spontaneous non-insulin dependent diabetes mellitus. Am J Physiol 269:E745–E752PubMedGoogle Scholar
  43. 43.
    Kendall MJ, Nuttall SL, Martin U (1998) Antioxidant therapy—a new therapeutic option for reducing mortality from coronary artery disease. J Clin Pharm Ther 23:323–325PubMedCrossRefGoogle Scholar
  44. 44.
    Riccioni G, Bucciarelli T, Mancini B et al (2007) Antioxidant vitamin supplementation in cardiovascular diseases. Ann Clin Lab Sci 37:89–95PubMedGoogle Scholar
  45. 45.
    Devaraj S, Jialal I (2000) Low-density lipoprotein postsecretory modification, monocyte function, and circulating adhesion molecules in type 2 diabetic patients with and without macrovascular complications: the effect of alpha-tocopherol supplementation. Circulation 102:191–196PubMedCrossRefGoogle Scholar
  46. 46.
    Isomaa B, Almgren P, Tuomi T et al (2001) Cardiovascular morbidity and mortality associated with metabolic syndrome. Diabetes Care 24:683–689PubMedCrossRefGoogle Scholar
  47. 47.
    Gaede P, Poulsen HE, Parving HH et al (2001) Double-blind, randomised study of the effect of combined treatment with vitamin C and E on albuminuria in type 2 diabetic patients. Diabet Med 18:756–760PubMedCrossRefGoogle Scholar
  48. 48.
    Singh U, Jiala I (2008) Alpha-lipoic acid supplementation and diabetes. Nutr Rev 66: 646–657PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Kanter M, Meral I, Yener Z et al (2003) Partial regeneration/proliferation of the β-cells in the islets of Langerhans by Nigella sativa L. in streptozotocin-induced diabetic rats. Tohoku J Exp Med 201:213–219PubMedCrossRefGoogle Scholar
  50. 50.
    Fararh KM, Atoji Y, Shimizu Y et al (2002) Insulinotropic properties of Nigella sativa oil in streptozotocin plus nicotinamide diabetic hamster. Res Vet Sci 73:279–282PubMedCrossRefGoogle Scholar
  51. 51.
    Meral I, Yener Z, Kahraman T et al (2001) Effect of Nigella sativa on glucose concentration, lipid peroxidation, antioxidant defense system and liver damage in experimentally-induced diabetic rabbits. J Vet Med A Physiol Pathol Clin Med 48:593–599PubMedCrossRefGoogle Scholar
  52. 52.
    El-Dakhakhny M, Mady N, Lembert N et al (2002) The hypoglycaemic effect of Nigella sativa oil is mediated by extrapancreatic actions. Planta Med 68:463–464CrossRefGoogle Scholar
  53. 53.
    Morikawa T, Xu F, Ninomiya K et al (2004) Nigellamines A3, A4, A5 and C, new dolabellane-type diterpene alkaloids, with lipid metabolism-promoting activities from the Egyptian medicinal food black cumin. Chem Pharm Bull 52:494–497PubMedCrossRefGoogle Scholar
  54. 54.
    Sitasawad SL, Shewade Y, Bhonde R (2000) Role of bitter gourd fruit juice in STZ- induced diabetic state in vivo and in vitro. J Ethnopharmacol 73:71–79PubMedCrossRefGoogle Scholar
  55. 55.
    Karunanayake EH, Jeevathayaparan S, Tennekoon KH (1990) Effect of Momordica charantia fruit juice on streptozotocin-induced diabetes in rats. J Ethnopharmacol 30:199–204PubMedCrossRefGoogle Scholar
  56. 56.
    Welihinda J, Arvidson G, Gylfe E et al (1982) The insulin-releasing activity of the tropical plant Momordica charantia. Acta Biol Med Ger 41:1229–1240PubMedGoogle Scholar
  57. 57.
    Hannan JM, Ali L, Rokeya B et al (2007) Soluble dietary fibre fraction of Trigonella foenum-graecum (fenugreek) seed improves glucose homeostasis in animal models of type 1 and type 2 diabetes by delaying carbohydrate digestion and absorption and enhancing insulin action. Br J Nutr 97:514–521PubMedCrossRefGoogle Scholar
  58. 58.
    Effect of fenugreek on blood sugar and insulin in diabetic humans.
  59. 59.
    Moorthy R, Prabhu KM, Murthy PS (2010) Anti-hyperglycemic compound (GII) from fenugreek (Trigonella foenum-graecum Linn.) seeds: purification and effect in diabetes mellitus. Indian J Exp Biol 48:1111–1118PubMedGoogle Scholar
  60. 60.
    Mohamed GA (2013) Alliuocide A: a new antioxidant flavonoid from Allium cepa L. Phytopharmacology 4:220–227Google Scholar
  61. 61.
    Cheng HY, Lin TC, Yu KH et al (2003) Antioxidant and free radical scavenging activities of Terminalia chebula. Biol Pharm Bull 26:1331–1335PubMedCrossRefGoogle Scholar
  62. 62.
    Kim JH, Hong C, Koo YC et al (2011) Oral administration of ethyl acetate soluble portion of Terminalia chebula conferring protection from streptozotocin-induced diabetes mellitus and its complications. Biol Pharm Bull 34:1702–1709PubMedCrossRefGoogle Scholar
  63. 63.
    Sschmidt AM, Yan SD, Wautier JL et al (1999) Activation of receptor for advanced glycation end products: a mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis. Circ Res 84:489–497CrossRefGoogle Scholar
  64. 64.
    Hartge M, Unger T, Kintscher U (2007) The endothelium and vascular inflammation in diabetes. Diab Vasc Dis Res 4:84–88PubMedCrossRefGoogle Scholar
  65. 65.
    Navarro J, Mora C (2005) Role of inflammation in diabetic complications. Nephrol Dial Transplant 20:2601–2604PubMedCrossRefGoogle Scholar
  66. 66.
    Festa A, Haffner S (2005) Inflammation and cardiovascular disease in patients with diabetes: lessons from the Diabetes Control and Complications Trial. Circulation 111:2414–2415PubMedCrossRefGoogle Scholar
  67. 67.
    Omara E, Kama A, Alqahtani A et al (2010) Herbal medicines and nutraceuticals for diabetic vascular complications: mechanisms of action and bioactive phytochemicals. Curr Pharm Des 16:3776–3807CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Saloni Daftardar
    • 1
  • Ginpreet Kaur
    • 1
  • Veeranjaneyulu Addepalli
    • 1
  1. 1.Department of PharmacologySPP School of Pharmacy & Technology Management, SVKM’s NMIMSMumbaiIndia

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