European Journal of Nutrition

, Volume 55, Issue 1, pp 227–236 | Cite as

Dietary total antioxidant capacity and mortality in the PREDIMED study

  • P. Henríquez-SánchezEmail author
  • A. Sánchez-Villegas
  • C. Ruano-Rodríguez
  • A. Gea
  • R. M. Lamuela-Raventós
  • R. Estruch
  • J. Salas-Salvadó
  • M. I. Covas
  • D. Corella
  • H. Schröder
  • M. Gutiérrez-Bedmar
  • J. M. Santos-Lozano
  • X. Pintó
  • F. Arós
  • M. Fiol
  • A. Tresserra-Rimbau
  • E. Ros
  • M. A. Martínez-González
  • L. Serra-Majem
Original Contribution



The aim of the present study was to assess the association between the dietary total antioxidant capacity, the dietary intake of different antioxidants and mortality in a Mediterranean population at high cardiovascular disease risk.


A total of 7,447 subjects from the PREDIMED study (multicenter, parallel group, randomized controlled clinical trial), were analyzed treating data as an observational cohort. Different antioxidant vitamin intake and total dietary antioxidant capacity were calculated from a validated 137-item food frequency questionnaire at baseline and updated yearly. Deaths were ascertained through contact with families and general practitioners, review of medical records and consultation of the National Death Index. Cox regression models were fitted to assess the relationship between dietary total antioxidant capacity and mortality. Dietary total antioxidant capacity was estimated using ferric-reducing antioxidant power assays.


A total of 319 deaths were recorded after a median follow-up of 4.3 years. Subjects belonging to the upper quintile of antioxidant capacity were younger, ex-smokers, with high educational level, and more active and had higher alcohol intake. Multivariable-adjusted models revealed no statistically significant difference between total dietary antioxidant capacity and mortality (Q5 vs. Q1 ref HR 0.85; 95 % CI 0.60–1.20) neither for the intake of all the vitamins studied.


No statistically significant association was found between antioxidant capacity and total mortality in elderly subjects at high cardiovascular risk.


Dietary antioxidant capacity Antioxidant intake Mortality PREDIMED 



The authors want to thank the participants of the study for their collaboration and the PREDIMED personnel for their excellent assistance with all aspects of the trial. This study was funded by the Spanish Ministry of Health (ISCIII), CIBEROBN, PI1001407, G03/140, RD06/0045 and the Autonomous Government of Catalonia, and Caixa Tarragona (10-1343). The Fundación Patrimonio Comunal Olivarero and Hojiblanca SA (Málaga, Spain), California Walnut Commission (Sacramento, CA), Borges SA (Reus, Spain) and Morella Nuts SA (Reus, Spain), donated the olive oil, walnuts, almonds and hazelnuts, respectively. None of the funding sources played a role in the design, collection, analysis, interpretation or publication of the data. AG is supported by a FPU fellowship from the Spanish Government.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Leenders M, Sluijs I, Ros MM, Boshuizen HC, Siersema PD, Ferrari P, Weikert C, Tjønneland A, Olsen A, Boutron-Ruault MC, Clavel-Chapelon F, Nailler L, Teucher B, Li K, Boeing H, Bergmann MM, Trichopoulou A, Lagiou P, Trichopoulos D, Palli D, Pala V, Panico S, Tumino R, Sacerdote C, Peeters PH, van Gils CH, Lund E, Engeset D, Redondo ML, Agudo A, Sánchez MJ, Navarro C, Ardanaz E, Sonestedt E, Ericson U, Nilsson LM, Khaw KT, Wareham NJ, Key TJ, Crowe FL, Romieu I, Gunter MJ, Gallo V, Overvad K, Riboli E, Bueno-de-Mesquita HB (2013) Fruit and vegetable consumption and mortality: European prospective investigation into cancer and nutrition. Am J Epidemiol 178:590–602CrossRefGoogle Scholar
  2. 2.
    Agudo A, Cabrera L, Amiano P, Ardanaz E, Barricarte A, Berenguer T, Chirlaque MD, Dorronsoro M, Jakszyn P, Larrañaga N, Martínez C, Navarro C, Quirós JR, Sánchez MJ, Tormo MJ, González CA (2007) Fruit and vegetable intakes, dietary antioxidant nutrients, and total mortality in Spanish adults: findings from the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain). Am J Clin Nutr 85:1634–1642Google Scholar
  3. 3.
    Dauchet L, Amouyel P, Hercberg S, Dallongeville J (2006) Fruit and vegetable consumption and risk of coronary heart disease: a meta-analysis of cohort studies. J Nutr 136:2588–2593Google Scholar
  4. 4.
    He FJ, Nowson CA, MacGregor GA (2006) Fruit and vegetable consumption and stroke: meta-analysis of cohort studies. Lancet 367:320–326CrossRefGoogle Scholar
  5. 5.
    Saura-Calixto F, Goñi I (2006) Antioxidant capacity of the Spanish Mediterranean diet. Food Chem 94:442–447CrossRefGoogle Scholar
  6. 6.
    Pellegrini N, Serafini M, Colombi B, Del Rio S, Salvatore S, Bianchi M, Brighenti F (2003) Total antioxidant capacity of plant foods, beverages and oils consumed in Italy assessed by three different in vitro assays. J Nutr 133:2812–2819Google Scholar
  7. 7.
    Serafini M, Del Rio D (2004) Understanding the association between dietary antioxidants, redox status and disease: is the total antioxidant capacity the right tool? Redox Rep 9:145–152CrossRefGoogle Scholar
  8. 8.
    Rautiainen S, Larsson S, Virtamo J, Wolk A (2012) Total antioxidant capacity of diet and risk of stroke: a population-based prospective cohort of women. Stroke 43:335–340CrossRefGoogle Scholar
  9. 9.
    Puchau B, Zulet MA, de Echávarri AG, Hermsdorff HH, Martínez JA (2009) Dietary total antioxidant capacity: a novel indicator of diet quality in healthy young adults. J Am Coll Nutr 28:648–656CrossRefGoogle Scholar
  10. 10.
    Bates CJ, Hamer M, Mishra GD (2011) Redox-modulatory vitamins and minerals that prospectively predict mortality in older British people: the national diet and nutrition survey of people aged 65 years and over. Br J Nutr 105:123–132CrossRefGoogle Scholar
  11. 11.
    Fletcher AE, Breeze E, Shetty PS (2003) Antioxidant vitamins and mortality in older persons: findings from the nutrition add-on study to the Medical Research Council Trial of Assessment and Management of Older People in the Community. Am J Clin Nutr 78:999–1010Google Scholar
  12. 12.
    Buijsse B, Feskens EJ, Schlettwein-Gsell D, Ferry M, Kok FJ, Kromhout D, de Groot LC (2005) Plasma carotene and alpha-tocopherol in relation to 10-year all-cause and cause-specific mortality in European elderly: the Survey in Europe on Nutrition and the Elderly, a Concerted Action (SENECA). Am J Clin Nutr 82:879–886Google Scholar
  13. 13.
    Ray AL, Semba RD, Walston J, Ferrucci L, Cappola AR, Ricks MO, Xue QL, Fried LP (2006) Low serum selenium and total carotenoids predict mortality among older women living in the community: the women’s health and aging studies. J Nutr 136:172–176Google Scholar
  14. 14.
    Khaw KT, Bingham S, Welch A, Luben R, Wareham N, Oakes S, Day N (2001) Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. European Prospective Investigation into Cancer and Nutrition. Lancet 357:657–663CrossRefGoogle Scholar
  15. 15.
    Del Rio D, Agnoli C, Pellegrini N, Krogh V, Brighenti F, Mazzeo T, Masala G, Bendinelli B, Berrino F, Sieri S, Tumino R, Rollo PC, Gallo V, Sacerdote C, Mattiello A, Chiodini P, Panico S (2011) Total antioxidant capacity of the diet is associated with lower risk of ischemic stroke in a large Italian cohort. J Nutr 141:118–123CrossRefGoogle Scholar
  16. 16.
    Serafini M, Jakszyn P, Luján-Barroso L, Agudo A, Bas Bueno-de-Mesquita H, van Duijnhoven FJ, Jenab M, Navarro C, Palli D, Boeing H, Wallström P, Regnér S, Numans ME, Carneiro F, Boutron-Ruault MC, Clavel-Chapelon F, Morois S, Grioni S, Panico S, Tumino R, Sacerdote C, Ramon Quirós J, Molina-Montes E, Huerta Castaño JM, Barricarte A, Amiano P, Khaw KT, Wareham N, Allen NE, Key TJ, Jeurnink SM, Peeters PH, Bamia C, Valanou E, Trichopoulou A, Kaaks R, Lukanova A, Bergmann MM, Lindkvist B, Stenling R, Johansson I, Dahm CC, Overvad K, Jensen M, Olsen A, Tjonneland A, Lund E, Rinaldi S, Michaud D, Mouw T, Riboli E, González CA (2012) Dietary total antioxidant capacity and gastric cancer risk in the European prospective investigation into cancer and nutrition study. Int J Cancer 131:E544–E554CrossRefGoogle Scholar
  17. 17.
    Rautiainen S, Levitan EB, Mittlema MA, Wolk A (2013) Total antioxidant capacity of diet and risk of heart failure: a population-based prospective cohort of women. Am J Med 126:494–500CrossRefGoogle Scholar
  18. 18.
    Brighenti F, Valtueña S, Pellegrini N, Ardigò D, Del Rio D, Salvatore S, Piatti P, Serafini M, Zavaroni I (2005) Total antioxidant capacity of the diet is inversely and independently related to plasma concentration of high-sensitivity C-reactive protein in adult Italian subjects. Br J Nutr 93:619–625CrossRefGoogle Scholar
  19. 19.
    Valtueña S, Pellegrini N, Franzini L, Bianchi MA, Ardido D, del Rio D, Piatti P, Scazzina F, Zavaroni I, Brighenti F (2008) Food selection based on total antioxidant capacity can modify antioxidant intake, systemic inflammation, and liver function without altering markers of oxidative stress. Am J Clin Nutr 87:1290–1297Google Scholar
  20. 20.
    Martínez-González MÁ, Corella D, Salas-Salvadó J, Ros E, Covas MI, Fiol M, Wärnberg J, Arós F, Ruíz-Gutiérrez V, Lamuela-Raventós RM, Lapetra J, Muñoz MÁ, Martínez JA, Sáez G, Serra-Majem L, Pintó X, Mitjavila MT, Tur JA, Portillo MP, Estruch R, PREDIMED Study Investigators (2012) Cohort profile: design and methods of the PREDIMED study. Int J Epidemiol 41:377–385Google Scholar
  21. 21.
    Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pintó X, Basora J, Muñoz MA, Sorlí JV, Martínez JA, Martínez-González MA, PREDIMED Study Investigators (2013) Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 368:1279–1290Google Scholar
  22. 22.
    Willet W (1998) Issues in analysis and presentation of dietary data. In: Willet W (ed) Nutritional epidemiology, 2nd edn. Oxford University Press, Oxford, pp 321–346CrossRefGoogle Scholar
  23. 23.
    Fernández-Ballart JD, Piñol JL, Zazpe I, Corella D, Carrasco P, Toledo E, Perez-Bauer M, Martínez-González MA, Salas-Salvadó J, Martín-Moreno JM (2010) Relative validity of a semi-quantitative food-frequency questionnaire in an elderly Mediterranean population of Spain. Br J Nutr 103:1808–1816CrossRefGoogle Scholar
  24. 24.
    de la Fuente-Arrillaga C, Vázquez Z, Bes-Rastrollo M, Sampson L, Martínez-González MA (2010) Reproducibility of an FFQ validated in Spain. Public Health Nutr 13:1364–1372CrossRefGoogle Scholar
  25. 25.
    Mataix L (2003) Tabla de composición de Alimentos Españoles. Granada, SpainGoogle Scholar
  26. 26.
    Elosua R, Marrugat J, Molina P, Pons S, Pujol E (1994) Validation of the Minnesota leisure time physical activity questionnaire in Spanish men. The MARATHOM investigators. Am J Epidemiol 139:1197–1209Google Scholar
  27. 27.
    Wang Y, Yang M, Lee SG, Davis CG, Koo SI, Chun OK (2012) Dietary total antioxidant capacity is associated with diet and plasma antioxidant status in healthy young adults. J Acad Nutr Diet 112:1626–1635CrossRefGoogle Scholar
  28. 28.
    Yang M, Chung SJ, Floegel A, Song WO, Koo SI, Chun OK (2013) Dietary antioxidant capacity is associated with improved serum antioxidant status and decreased serum C-reactive protein and plasma homocysteine concentrations. Eur J Nutr 52:1901–1911CrossRefGoogle Scholar
  29. 29.
    Valtueña S, Del Rio D, Pellegrini N, Ardigò D, Franzini L, Salvatore S, Piatti PM, Riso P, Zavaroni I, Brighenti F (2007) The total antioxidant capacity of the diet is an independent predictor of plasma beta-carotene. Eur J Clin Nutr 61:69–76CrossRefGoogle Scholar
  30. 30.
    La Vecchia C, Decarli A, Serafini M, Parpinel M, Bellocco R, Galeone C, Bosetti C, Zucchetto A, Polesel J, Lagiou P, Negri E, Rossi M (2013) Dietary total antioxidant capacity and colorectal cancer: a large case–control study in Italy. Int J Cancer 133:1447–1451CrossRefGoogle Scholar
  31. 31.
    Rautiainen S, Levitan EB, Orsini N, Åkesson A, Morgenstern R, Mittleman MA, Wolk A (2012) Total antioxidant capacity from diet and risk of myocardial infarction: a prospective cohort of women. Am J Med 125:974–980Google Scholar
  32. 32.
    Devore EE, Feskens E, Ikram MA, den Heijer T, Vernooij M, van der Lijn F, Hofman A, Niessen WJ, Breteler MM (2013) Total antioxidant capacity of the diet and major neurologic outcomes in older adults. Neurology 80:904–910CrossRefGoogle Scholar
  33. 33.
    Okubo H, Syddall HE, Phillips DI, Sayer AA, Dennison EM, Cooper C, Robinson SM, Hertfordshire Cohort Study Group (2014) Dietary total antioxidant capacity is related to glucose tolerance in older people: the Hertfordshire Cohort Study. Nutr Metab Cardiovasc Dis 24:301–308Google Scholar
  34. 34.
    Bahadoran Z, Golzarand M, Mirmiran P, Shiva N, Azizi F (2012) Dietary total antioxidant capacity and the occurrence of metabolic syndrome and its components after a 3-year follow-up in adults: Tehran lipid and glucose study. Nutr Metab (Lond) 9:70CrossRefGoogle Scholar
  35. 35.
    Genkinger JM, Platz EA, Hoffman SC, Comstock GW, Helzlsouer KJ (2004) Fruit, vegetable, and antioxidant intake and all-cause, cancer, and cardiovascular disease mortality in a community-dwelling population in Washington County, Maryland . Am J Epidemiol 160:1223–1233Google Scholar
  36. 36.
    Roswall N, Olsen A, Christensen J, Hansen L, Dragsted LO, Overvad K, Tjønneland A (2012) Micronutrient intake in relation to all-cause mortality in a prospective Danish cohort. Food Nutr Res 56:5466Google Scholar
  37. 37.
    Tresserra-Rimbau A, Rimm EB, Medina-Remón A, Martínez-González MA, López-Sabater MC, Covas MI, Corella D, Salas-Salvadó J, Gómez-Gracia E, Lapetra J, Arós F, Fiol M, Ros E, Serra-Majem L, Pintó X, Muñoz MA, Gea A, Ruiz-Gutiérrez V, Estruch R, Lamuela-Raventós RM, PREDIMED Study Investigators (2014) Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial. BMC Med 12:77Google Scholar
  38. 38.
    Hjartåker A1, Knudsen MD, Tretli S, Weiderpass E (2014) Consumption of berries, fruits and vegetables and mortality among 10,000 Norwegian men followed for four decades. Eur J Nutr [epub ahead of print]Google Scholar
  39. 39.
    Serafini M, Miglio C, Peluso I, Petrosino T (2011) Modulation of plasma non enzimatic antioxidant capacity (NEAC) by plant foods: the role of polyphenol. Curr Top Med Chem 11:1821–1846CrossRefGoogle Scholar
  40. 40.
    Takashima M, Horie M, Shichiri M, Hagihara Y, Yoshida Y, Niki E (2012) Assessment of antioxidant capacity for scavenging free radicals in vitro: a rational basis and practical application. Free Radic Biol Med 52(7):1242–1252CrossRefGoogle Scholar
  41. 41.
    Frankel EN, Meyer AS (2000) Review: the problems of using one-dimensional methods to evaluate multifunctional food and biological antioxidants. J Sci Food Agric 80:1925–1941CrossRefGoogle Scholar
  42. 42.
    Wacholder S, Hartge P, Lubin JH, Dosemeci M (1995) Non-differential misclassification and bias towards the null: a clarification. Occup Environ Med 52(8):557–558CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • P. Henríquez-Sánchez
    • 1
    • 2
    Email author
  • A. Sánchez-Villegas
    • 1
    • 2
  • C. Ruano-Rodríguez
    • 1
    • 2
  • A. Gea
    • 1
    • 3
  • R. M. Lamuela-Raventós
    • 1
    • 4
  • R. Estruch
    • 1
    • 5
  • J. Salas-Salvadó
    • 1
    • 6
  • M. I. Covas
    • 1
    • 7
    • 8
  • D. Corella
    • 1
    • 9
  • H. Schröder
    • 10
    • 11
  • M. Gutiérrez-Bedmar
    • 1
    • 12
  • J. M. Santos-Lozano
    • 1
    • 13
  • X. Pintó
    • 1
    • 14
  • F. Arós
    • 1
    • 15
  • M. Fiol
    • 1
    • 16
    • 17
  • A. Tresserra-Rimbau
    • 1
    • 4
  • E. Ros
    • 1
    • 18
  • M. A. Martínez-González
    • 1
    • 3
  • L. Serra-Majem
    • 1
    • 2
  1. 1.Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y NutriciónInstituto de Salud Carlos IIIMadridSpain
  2. 2.Research Institute of Biomedical and Health SciencesUniversity of Las Palmas de Gran CanariaLas Palmas de Gran CanariaSpain
  3. 3.Department of Preventive Medicine and Public HealthUniversity of NavarraPamplonaSpain
  4. 4.Nutrition and Food Science Department, XaRTA, INSA, School of PharmacyUniversity of BarcelonaBarcelonaSpain
  5. 5.Department of Internal Medicine, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)University of BarcelonaBarcelonaSpain
  6. 6.Human Nutrition Unit, School of MedicineUniversity Rovira i VirgiliReusSpain
  7. 7.Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y NutriciónInstituto de Salud Carlos IIMadridSpain
  8. 8.Cardiovascular Risk and Nutrition Research UnitInstitut Municipal d’Investigació Mèdica (IMIM)BarcelonaSpain
  9. 9.Department of Preventive Medicine and Public HealthUniversity of ValenciaValenciaSpain
  10. 10.CIBER Epidemiología y Salud Pública (CIBERESP)Instituto de Salud Carlos IIIMadridSpain
  11. 11.Cardiovascular Risk and Nutrition Research GroupInstitut Municipal d’Investigació Medica (IMIM)-Institut de Recerca del Hospital del MarBarcelonaSpain
  12. 12.Department of Preventive MedicineUniversity of MalagaMálagaSpain
  13. 13.Department of Family Medicine, Primary Care Division of SevillaSan Pablo Health CenterSevilleSpain
  14. 14.Lipids and Vascular Risk Unit, Internal MedicineHospital Universitario de BellvitgeBarcelonaSpain
  15. 15.Department of CardiologyUniversity Hospital of AlavaVitoriaSpain
  16. 16.Institute of Health SciencesUniversity of Balearic IslandsPalma de MallorcaSpain
  17. 17.Hospital Son EspasesPalma de MallorcaSpain
  18. 18.Lipid Clinic, Endocrinology and Nutrition Service, Institut d’Investigacions Biomèdiques August Pi SunyerHospital ClinicBarcelonaSpain

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