The journal of nutrition, health & aging

, Volume 21, Issue 10, pp 1277–1283 | Cite as

Iberian cured-ham consumption improves endothelial function in healthy subjects

  • Jose Saban-Ruiz
  • M. Fabregate-Fuente
  • R. Fabregate-Fuente
  • A. Andres-Castillo
  • A. Palomino-Antolin
  • D. Barrio-Carreras
  • L. Martin-Fernandez
  • F. Altamirano
  • C. Fernandez-Fernandez
  • C. Andres-Lacueva



Previous studies have shown that dietary components such as oleic acid or polyphenols exert beneficial effects on endothelium. We aimed to assess the impact of regular consumption of Iberian cured-ham (ICH) on endothelial function.


An open-label, randomized controlled parallel study.


Volunteers recruited through advertisements at a hospital in Madrid, Spain.


102 Caucasian adults (76.8% females) aged 25–55 years, and free from cardiometabolic disease.


Participants were randomized to an ICH-enriched ad libitum diet or an ad libitum diet without ICH for 6 weeks. Subjects in ICH group were randomly provided with either acorn- or mixed-fed ICH, and followed up for an additional 6-week period under their usual diet.


Clinical parameters, biomarkers of endothelial function and oxidative stress, microvascular vasodilatory response to hyperemia and arterial stiffness were measured before and after the intervention.


After 6 weeks, a larger decrease in PAI-1 was observed in subjects consuming ICH compared to the Control group (-6.2±17.7 vs. 0.3±1.4 ng/ml; p=0.020). Similarly, microvascular vasodilatory response to hyperemia showed a significant increase (112.4±391.7 vs. -56.0±327.9%; p=0.007). However, neither oxidative stress, hemodynamic nor clinical parameters differed significantly over the study. Additionally, after stopping ICH consumption, improvements in PAI-1 remained for 6 additional weeks with respect to baseline (p=0.006).


The present study demonstrates, for the first time, that regular consumption of ICH improves endothelial function in healthy adults. Strategies aimed to preserve or improve the endothelial function may have implications in vascular aging beyond the prevention of the atherothrombotic disease.


Iberian cured-ham endothelial function fibrinolysis vascular aging polyphenols 


  1. 1.
    Sitia S, Tomasoni L, Atzeni F, Ambrosio G, Cordiano C, Catapano A, et al. From endothelial dysfunction to atherosclerosis. Autoimmun Rev. 2010;9:830–4.CrossRefPubMedGoogle Scholar
  2. 2.
    Gibbons GH, Dzau VJ. The emerging concept of vascular remodeling. N Engl J Med. 1994;330:1431–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007;115:1285–95.PubMedGoogle Scholar
  4. 4.
    Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004;109:III27-32.Google Scholar
  5. 5.
    Landberg R, Naidoo N, van Dam RM. Diet and endothelial function: from individual components to dietary patterns. Curr Opin Lipidol. 2012;23:147–55.CrossRefPubMedGoogle Scholar
  6. 6.
    Brown AA, Hu FB. Dietary modulation of endothelial function: implications for cardiovascular disease. Am J Clin Nutr. 2001;73:673–86.CrossRefPubMedGoogle Scholar
  7. 7.
    Davis N, Katz S, Wylie-Rosett J. The effect of diet on endothelial function. Cardiol Rev. 2007;15:62–6.CrossRefPubMedGoogle Scholar
  8. 8.
    Egert S, Stehle P. Impact of n-3 fatty acids on endothelial function: results from human interventions studies. Curr Opin Clin Nutr Metab Care. 2011;14:121–31.CrossRefPubMedGoogle Scholar
  9. 9.
    Estruch R, Ros E, Salas-Salvado J, Covas MI, Corella D, Aros F, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368:1279–90.CrossRefPubMedGoogle Scholar
  10. 10.
    Ruano J, Lopez-Miranda J, Fuentes F, Moreno JA, Bellido C, Perez-Martinez P, et al. Phenolic content of virgin olive oil improves ischemic reactive hyperemia in hypercholesterolemic patients. J Am Coll Cardiol. 2005;46:1864–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Urpi-Sarda M, Casas R, Chiva-Blanch G, Romero-Mamani ES, Valderas-Martinez P, Arranz S, et al. Virgin olive oil and nuts as key foods of the Mediterranean diet effects on inflammatory biomakers related to atherosclerosis. Pharmacol Res. 2012;65:577–83.CrossRefPubMedGoogle Scholar
  12. 12.
    Medina-Remon A, Tresserra-Rimbau A, Pons A, Tur JA, Martorell M, Ros E, et al. Effects of total dietary polyphenols on plasma nitric oxide and blood pressure in a high cardiovascular risk cohort. The PREDIMED randomized trial. Nutr Metab Cardiovasc Dis. 2015;25:60–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Jimenez-Colmenero F, Ventanas J, Toldra F. Nutritional composition of dry-cured ham and its role in a healthy diet. Meat Sci. 2010;84:585–93.CrossRefPubMedGoogle Scholar
  14. 14.
    Rebollo AJG, Botejara EM, Cansado AO, Morales PJ, Bellido MM, Sánchez AF, et al. Effects of consumption of meat product rich in monounsaturated fatty acids (the ham from the Iberian pig) on plasma lipids. Nutrition Research. 1998;18:743–50.CrossRefGoogle Scholar
  15. 15.
    Mayoral P, Martinez-Salgado CS, Santiago JM, Rodriguez-Hernandez MV, Garcia-Gomez ML, Morales A, et al. Effect of ham protein substitution on oxidative stress in older adults. J Nutr Health Aging. 2003;7:84–9.PubMedGoogle Scholar
  16. 16.
    Ruiz-Canela Lopez M, Bes-Rastrollo M, Zazpe I, Martinez JA, Cuervo M, Martinez-Gonzalez MA. [Cured ham and incidence of cardiovascular events, arterial hypertension or weight gain]. Med Clin (Barc). 2009;133:574–80.CrossRefPubMedGoogle Scholar
  17. 17.
    Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112:2735–52.CrossRefPubMedGoogle Scholar
  18. 18.
    Fernandez-Ballart JD, Pinol JL, Zazpe I, Corella D, Carrasco P, Toledo E, et al. Relative validity of a semi-quantitative food-frequency questionnaire in an elderly Mediterranean population of Spain. Br J Nutr. 2010;103:1808–16.CrossRefPubMedGoogle Scholar
  19. 19.
    Wilkinson IB, Mac Callum H, Flint L, Cockcroft JR, Newby DE, Webb DJ. The influence of heart rate on augmentation index and central arterial pressure in humans. J Physiol. 2000;525 Pt 1:263–70.CrossRefGoogle Scholar
  20. 20.
    Ainsworth EA, Gillespie KM. Estimation of total phenolic content and other oxidation substrates in plant tissues using Folin-Ciocalteu reagent. Nat Protoc. 2007;2:875–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Brodsky SV, Malinowski K, Golightly M, Jesty J, Goligorsky MS. Plasminogen activator inhibitor-1 promotes formation of endothelial microparticles with procoagulant potential. Circulation. 2002;106:2372–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Perez-Jimenez F, Castro P, Lopez-Miranda J, Paz-Rojas E, Blanco A, Lopez-Segura F, et al. Circulating levels of endothelial function are modulated by dietary monounsaturated fat. Atherosclerosis. 1999;145:351–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Lopez-Segura F, Velasco F, Lopez-Miranda J, Castro P, Lopez-Pedrera R, Blanco A, et al. Monounsaturated fatty acid-enriched diet decreases plasma plasminogen activator inhibitor type 1. Arterioscler Thromb Vasc Biol. 1996;16:82–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Delgado-Lista J, Garcia-Rios A, Perez-Martinez P, Lopez-Miranda J, Perez-Jimenez F. Olive oil and haemostasis: platelet function, thrombogenesis and fibrinolysis. Curr Pharm Des. 2011;17:778–785.CrossRefPubMedGoogle Scholar
  25. 25.
    Celermajer DS, Sorensen KE, Bull C, Robinson J, Deanfield JE. Endotheliumdependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol. 1994;24:1468–74.CrossRefPubMedGoogle Scholar
  26. 26.
    Flammer AJ, Anderson T, Celermajer DS, Creager MA, Deanfield J, Ganz P, et al. The assessment of endothelial function: from research into clinical practice. Circulation. 2012;126:753–67.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Skaug EA, Aspenes ST, Oldervoll L, Mørkedal B, Vatten L, Wisløff U, et al. Age and gender differences of endothelial function in 4739 healthy adults: the HUNT3 Fitness Study. Eur J Prev Cardiol. 2013;20:531–40.CrossRefPubMedGoogle Scholar
  28. 28.
    Sader MA, Celermajer DS. Endothelial function, vascular reactivity and gender differences in the cardiovascular system. Cardiovasc Res. 2002;53:597–604.CrossRefPubMedGoogle Scholar
  29. 29.
    Gong M, Wilson M, Kelly T, Su W, Dressman J, Kincer J, et al. HDL-associated estradiol stimulates endothelial NO synthase and vasodilation in an SR-BI-dependent manner. J Clin Invest. 2003;111:1579–87.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Kellogg DL, Jr, Zhao JL, Coey U, Green JV. Acetylcholine-induced vasodilation is mediated by nitric oxide and prostaglandins in human skin. J Appl Physiol. 2005;98:629–32.CrossRefPubMedGoogle Scholar
  31. 31.
    Meigs JB, Larson MG, Fox CS, Keaney JF, Jr., Vasan RS, Benjamin EJ. Association of oxidative stress, insulin resistance, and diabetes risk phenotypes: the Framingham Offspring Study. Diabetes Care. 2007;30:2529–35.CrossRefPubMedGoogle Scholar
  32. 32.
    O’Reilly JD, Mallet AI, McAnlis GT, Young IS, Halliwell B, Sanders TA, et al. Consumption of flavonoids in onions and black tea: lack of effect on F2-isoprostanes and autoantibodies to oxidized LDL in healthy humans. Am J Clin Nutr. 2001;73:1040–4.CrossRefPubMedGoogle Scholar
  33. 33.
    Duffy SJ, Keaney JF, Jr., Holbrook M, Gokce N, Swerdloff PL, Frei B, et al. Shortand long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease. Circulation. 2001;104:151–6.CrossRefPubMedGoogle Scholar
  34. 34.
    Higashi Y, Noma K, Yoshizumi M, Kihara Y. Endothelial function and oxidative stress in cardiovascular diseases. Circ J. 2009;73:411–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Khan F, Ray S, Craigie AM, Kennedy G, Hill A, Barton KL, et al. Lowering of oxidative stress improves endothelial function in healthy subjects with habitually low intake of fruit and vegetables: a randomized controlled trial of antioxidant-and polyphenol-rich blackcurrant juice. Free Radic Biol Med. 2014;72:232–7.CrossRefPubMedGoogle Scholar
  36. 36.
    McEniery CM, Wallace S, Mackenzie IS, McDonnell B, Yasmin, Newby DE, et al. Endothelial function is associated with pulse pressure, pulse wave velocity, and augmentation index in healthy humans. Hypertension. 2006;48:602–8.CrossRefPubMedGoogle Scholar
  37. 37.
    Ferrara LA, Raimondi AS, d’Episcopo L, Guida L, Dello Russo A, Marotta T. Olive oil and reduced need for antihypertensive medications. Arch Intern Med. 2000;160:837–42.CrossRefPubMedGoogle Scholar
  38. 38.
    Kamat CD, Thorpe JE, Shenoy SS, Ceriello A, Green DE, Warnke LA, et al. A longterm «memory» of HIF induction in response to chronic mild decreased oxygen after oxygen normalization. BMC Cardiovasc Disord. 2007;7:4.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Ihnat MA, Thorpe JE, Kamat CD, Szabo C, Green DE, Warnke LA, et al. Reactive oxygen species mediate a cellular ‘memory’ of high glucose stress signalling. Diabetologia. 2007;50:1523–31.CrossRefPubMedGoogle Scholar
  40. 40.
    Ford I, Murray H, McCowan C, Packard CJ. Long-Term Safety and Efficacy of Lowering Low-Density Lipoprotein Cholesterol With Statin Therapy: 20-Year Follow-Up of West of Scotland Coronary Prevention Study. Circulation 2016;133:1073–80.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Murray P, Chune GW, Raghavan VA. Legacy effects from DCCT and UKPDS: what they mean and implications for future diabetes trials. Curr Atheroscler Rep. 2010;12:432–9.CrossRefPubMedGoogle Scholar
  42. 42.
    Choi SW, Friso S. Epigenetics: A New Bridge between Nutrition and Health. Adv Nutr. 2010;1:8–16.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Le Couteur DG, Lakatta EG. A vascular theory of aging. J Gerontol A Biol Sci Med Sci. 2010;65:1025–7.CrossRefPubMedGoogle Scholar
  44. 44.
    Seals DR, Jablonski KL, Donato AJ. Aging and vascular endothelial function in humans. Clin Sci (Lond). 2011;120:357–75.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Rodriguez-Manas L, El-Assar M, Vallejo S, Lopez-Doriga P, Solis J, Petidier R, et al. Endothelial dysfunction in aged humans is related with oxidative stress and vascular inflammation. Aging Cell. 2009;8:226–38.CrossRefPubMedGoogle Scholar
  46. 46.
    Donato AJ, Gano LB, Eskurza I, Silver AE, Gates PE, Jablonski K, et al. Vascular endothelial dysfunction with aging: endothelin-1 and endothelial nitric oxide synthase. Am J Physiol Heart Circ Physiol. 2009;297:H425-32.Google Scholar
  47. 47.
    Csiszar A, Wang M, Lakatta EG, Ungvari Z. Inflammation and endothelial dysfunction during aging: role of NF-κB. J Appl Physiol. 2008;105:1333–41.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Semba RD, Nicklett EJ, Ferrucci L. Does accumulation of advanced glycation end products contribute to the aging phenotype? J Gerontol A Biol Sci Med Sci. 2010;65:963–75.CrossRefPubMedGoogle Scholar
  49. 49.
    Yamamoto K, Takeshita K, Kojima T, Takamatsu J, Saito H. Aging and plasminogen activator inhibitor-1 (PAI-1) regulation: implication in the pathogenesis of thrombotic disorders in the elderly. Cardiovasc Res. 2005;66:276–85.CrossRefPubMedGoogle Scholar
  50. 50.
    Ungvari Z, Kaley G, de Cabo R, Sonntag WE, Csiszar A. Mechanisms of vascular aging: new perspectives. J Gerontol A Biol Sci Med Sci. 2010;65:1028–41.CrossRefPubMedGoogle Scholar

Copyright information

© Serdi and Springer-Verlag France 2017

Authors and Affiliations

  • Jose Saban-Ruiz
    • 1
    • 2
    • 3
    • 5
  • M. Fabregate-Fuente
    • 1
    • 2
  • R. Fabregate-Fuente
    • 1
  • A. Andres-Castillo
    • 1
  • A. Palomino-Antolin
    • 1
  • D. Barrio-Carreras
    • 1
  • L. Martin-Fernandez
    • 1
  • F. Altamirano
    • 1
  • C. Fernandez-Fernandez
    • 1
  • C. Andres-Lacueva
    • 4
  1. 1.Endothelial and Cardiometabolic Medicine Unit, Internal Medicine ServiceRamon y Cajal University HospitalMadridSpain
  2. 2.Ramon y Cajal Health Research Institute (IRYCIS)MadridSpain
  3. 3.Faculty of MedicineUniversity of AlcalaMadridSpain
  4. 4.Biomarkers and Nutrimetabolomic Lab., Nutrition and Food Science Department, XaRTA, INSA, Pharmacy SchoolUniversity of BarcelonaBarcelonaSpain
  5. 5.Unidad de Patología Endotelial. Edificio Consultas Externas. Planta 0. Hospital Ramón y CajalBarcelonaSpain

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