Open Access Research article

Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial

Anna Tresserra-Rimbau12, Eric B Rimm3, Alexander Medina-Remón172, Miguel A Martínez-González24, M Carmen López-Sabater12, María I Covas25, Dolores Corella26, Jordi Salas-Salvadó27, Enrique Gómez-Gracia28, José Lapetra29, Fernando Arós102, Miquel Fiol112, Emili Ros122, Lluis Serra-Majem132, Xavier Pintó142, Miguel A Muñoz152, Alfredo Gea24, Valentina Ruiz-Gutiérrez162, Ramón Estruch172, Rosa M Lamuela-Raventós12* and on behalf of the PREDIMED Study Investigators

Author Affiliations

1 Nutrition and Food Science Department, XaRTA, INSA, Pharmacy School, University of Barcelona, Barcelona, Spain

2 CIBER CB06/03 Fisiopatología de la Obesidad y la Nutrición (CIBERObn), Institute of Health “Carlos III”, Government of Spain, Madrid, Spain

3 Harvard Medical School and Harvard School of Public Health, Boston, MA, USA

4 Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, Pamplona, Spain

5 Cardiovascular Epidemiology Unit, Municipal Institute for Medical Research (IMIM), Barcelona, Spain

6 Department of Epidemiology, Preventive Medicine and Public Health, School of Medicine, University of Valencia, Valencia, Spain

7 Human Nutrition Unit, School of Medicine, IISPV, University Rovira i Virgili, Reus, Spain

8 Department of Epidemiology, School of Medicine, University of Malaga, Málaga, Spain

9 Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain

10 Department of Cardiology, Hospital Txangorritxu, Vitoria, Spain

11 Institut Universitari d´Investigació en Ciències de la Salut (IUNICS), Palma de Mallorca, Spain

12 Lipid Clinic, Endocrinology and Nutrition Service, Institut d’Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, Barcelona, Spain

13 Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Palmas de Gran Canaria, Spain

14 Lipid Unit, Department of Internal Medicine, IDIBELL-Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, FIPEC, Barcelona, Spain

15 Primary Care Division Catalan Institute of Health, Barcelona, Spain

16 Nutrition and Lipids Metabolism, Instituto de la Grasa, Consejo Superior de Investigaciones Cientificas, Sevilla, Spain

17 Department of Internal Medicine, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain

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BMC Medicine 2014, 12:77  doi:10.1186/1741-7015-12-77

Published: 13 May 2014



Polyphenols may lower the risk of cardiovascular disease (CVD) and other chronic diseases due to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on blood pressure, lipids and insulin resistance. However, no previous epidemiological studies have evaluated the relationship between the intake of total polyphenols intake and polyphenol subclasses with overall mortality. Our aim was to evaluate whether polyphenol intake is associated with all-cause mortality in subjects at high cardiovascular risk.


We used data from the PREDIMED study, a 7,447-participant, parallel-group, randomized, multicenter, controlled five-year feeding trial aimed at assessing the effects of the Mediterranean Diet in primary prevention of cardiovascular disease. Polyphenol intake was calculated by matching food consumption data from repeated food frequency questionnaires (FFQ) with the Phenol-Explorer database on the polyphenol content of each reported food. Hazard ratios (HR) and 95% confidence intervals (CI) between polyphenol intake and mortality were estimated using time-dependent Cox proportional hazard models.


Over an average of 4.8 years of follow-up, we observed 327 deaths. After multivariate adjustment, we found a 37% relative reduction in all-cause mortality comparing the highest versus the lowest quintiles of total polyphenol intake (hazard ratio (HR) = 0.63; 95% CI 0.41 to 0.97; P for trend = 0.12). Among the polyphenol subclasses, stilbenes and lignans were significantly associated with reduced all-cause mortality (HR =0.48; 95% CI 0.25 to 0.91; P for trend = 0.04 and HR = 0.60; 95% CI 0.37 to 0.97; P for trend = 0.03, respectively), with no significant associations apparent in the rest (flavonoids or phenolic acids).


Among high-risk subjects, those who reported a high polyphenol intake, especially of stilbenes and lignans, showed a reduced risk of overall mortality compared to those with lower intakes. These results may be useful to determine optimal polyphenol intake or specific food sources of polyphenols that may reduce the risk of all-cause mortality.

Clinical trial registration


Polyphenol intake; All-cause mortality; PREDIMED; Mediterranean diet; Stilbenes; Lignans