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Dietary Flavonoid and Lignan Intake and Mortality in a Spanish Cohort

Zamora-Ros, Raula; Jiménez, Carolinaa; Cleries, Ramónb; Agudo, Antonioa; Sánchez, María-Joséc,d; Sánchez-Cantalejo, Emilioc,d; Molina-Montes, Estherc,d; Navarro, Carmend,e,f; Chirlaque, María-Doloresd,e; Huerta, José Maríad,e; Amiano, Pilard,g; Redondo, M. Luisah; Barricarte, Aurelioi; González, Carlos A.a

doi: 10.1097/EDE.0b013e31829d5902

Background: Dietary flavonoids and lignans may protect against several chronic diseases, but there is little evidence on the relationship between flavonoid and lignan intake and mortality. We investigated the association between both all-cause and specific-cause mortality and intake of flavonoids and lignans in the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC-Spain) cohort.

Methods: The EPIC-Spain study follows 40,622 participants (38% men) aged 29–69 years. A validated diet history questionnaire was administered at recruitment. A food composition database was compiled based on US Department of Agriculture and Phenol-Explorer databases. Cox proportional hazards models, adjusted for confounders, were used in the analyses.

Results: During a mean follow-up of 13.6 years, 1915 deaths were reported, with 416 from cardiovascular diseases (CVDs) and 956 from cancer. After adjustment for several potential confounders, the hazard ratios (HRs) for the highest versus the lowest quintile of dietary flavanone and flavonol intakes were 0.60 (95% confidence interval = 0.38–0.94) and 0.59 (0.40–0.88). Total flavonoid intake was also associated with a decrease in all-cause mortality (0.71 [0.49–1.03]). Lignan intake was not associated with all-cause mortality. In cause-specific mortality analyses, using competing risk regressions, doubling total flavonoid intake was inversely related to mortality from CVD (HR for log2 0.87 [0.77–0.98]), but not to mortality from either cancer (HR for log2 0.96 [0.89–1.04]) or other causes (HR for log2 0.97 [0.87–1.09]).

Conclusions: A diet high in flavonoids, particularly in flavanones and flavonols, is associated with a reduction in all-cause mortality, mainly of mortality from CVD.

From the aUnit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain; bCancer Registry of Catalonia - Plan for Oncology of the Catalan Government. IDIBELL, Hospital Duran i Reynals, Barcelona, Spain; cAndalusian School of Public Health, Granada, Spain; dCIBER Epidemiología y Salud Pública (CIBERESP), Spain; eDepartment of Epidemiology, Murcia Regional Health Council, Murcia, Spain; fDepartment of Sociosanitary Sciences, University of Murcia School of Medicine, Spain; gPublic Health Division of Gipuzkoa, BIODonostia Research Institute, Department of Health of the Regional Government of the Basque Country, San Sebastian, Spain; hPublic Health Directorate, Asturias, Spain; and iNavarre Public Health Institute, Pamplona, Spain.

This study is part of the EPIC-Spain Study. The EPIC Study in Spain has received financial support from the Spanish Ministry of Health (ISCIII RETICC RD06/0020), Spanish Regional Governments of Andalusia, Asturias, Basque Country, Murcia (No 6236) and Navarra and the Catalan Institute of Oncology. R.Z.-R. is grateful for the postdoctoral “Sara Borrell” program (CD09/00133) from the MEC and ISCIII.

The authors report no conflicts of interest.

Correspondence: Raul Zamora-Ros, Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Avda Gran Via 199-203 08907 L’Hospitalet de Llobregat, Spain. E-mail

Received December 14, 2012

Accepted March 4, 2013

© 2013 by Lippincott Williams & Wilkins, Inc