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Michaël G. L. Hertog, PhD; Daan Kromhout, PhD; Christ Aravanis, MD; Henry Blackburn, MD; Ratko Buzina, MD; Flaminio Fidanza, MD; Simona Giampaoli, MD; Annemarie Jansen, RD; Alessandro Menotti, MD; Srecko Nedeljkovic, MD; Maija Pekkarinen, PhD; Bozidar S. Simic, MD; Hironori Toshima, MD; Edith J. M. Feskens, PhD; Peter C. H. Hollman, MSc; Martijn B. Katan, PhD

Arch Intern Med. 1995;155(4):381-386.

Abstract
Objective
To determine whether flavonoid intake explains differences in mortality rates from chronic diseases between populations.

Design
Cross-cultural correlation study.

Setting/Participants
Sixteen cohorts of the Seven Countries Study in whom flavonoid intake at baseline around 1960 was estimated by flavonoid analysis of equivalent food composites that represented the average diet in the cohorts.

Main Outcome Measures
Mortality from coronary heart disease, cancer (various sites), and all causes in the 16 cohorts after 25 years of follow-up.

Results
Average intake of antioxidant flavonoids was inversely associated with mortality from coronary heart disease and explained about 25% of the variance in coronary heart disease rates in the 16 cohorts. In multivariate analysis, intake of saturated fat (73%; P=.0001), flavonoid intake (8%; P=.01), and percentage of smokers per cohort (9%; P=.03) explained together, independent of intake of alcohol and antioxidant vitamins, 90% of the variance in coronary heart disease rates. Flavonoid intake was not independently associated with mortality from other causes.

Conclusions
Average flavonoid intake may partly contribute to differences in coronary heart disease mortality across populations, but it does not seem to be an important determinant of cancer mortality.

(Arch Intern Med. 1995;155:381-386)

Author Affiliations
From the Department of Chronic Diseases and Environmental Epidemiology, National Institute of Public Health and Environmental Protection, Bilthoven, the Netherlands (Drs Hertog, Kromhout, and Feskens and Ms Jansen); the Greek Society for the Study of Atherosclerosis and the Medical Center of Athens (Dr Aravanis); Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis (Dr Blackburn); Institute of Diabetes, Endocrinology, and Metabolic Diseases, Zagreb, Croatia (Dr Buzina); Institute of Food Sciences and Nutrition, University of Perugia (Italy) (Drs Fidanza and Menotti); Laboratory of Epidemiology and Biostatistics, National Institute of Health, Rome, Italy (Dr Giampaoli); Internal Clinic B (Dr Nedeljkovic) and Institute of Hygiene, Medical Faculty (Dr Simic), University of Belgrade (Serbia); Department of Nutrition, University of Helsinki (Finland) (Dr Pekkarinen); Kurume (Japan) University, School of Medicine, Third Department of Internal Medicine (Dr Toshima); State Institute for Quality Control of Agricultural Products, Wageningen, the Netherlands (Mr Hollman); and Department of Human Nutrition, Agricultural University, Wageningen (Dr Katan). Dr Menotti is now with the Department of Epidemiology, School of Public Health, University of Minnesota, Minneapolis.

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