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Etiology

High dietary intake of flavonoids was associated with decreased mortality

ACP J Club. 1996 July-Aug;125:22. doi:10.7326/ACPJC-1996-125-1-022


Source Citation

Knekt P, Järvinen R, Reunanen A, Maatela J. Flavonoid intake and coronary mortality in Finland: a cohort study. BMJ. 1996 Feb 24;312;478-81. [PubMed ID: 8597679]


Abstract

Objective

To determine the relation between intake of dietary flavonoids and all-cause and coronary artery disease (CAD) mortality.

Design

Cohort study with 20- to 26-year follow-up.

Setting

30 communities in Finland.

Participants

2748 men and 2385 women were enrolled between 1966 and 1972. They were between 30 and 69 years old, did not have heart disease, and had completed questionnaires and interviews on food intake at baseline. Follow-up for death was complete.

Assessment of risk factors

Flavonoid consumption was calculated from the reported intake of 28 vegetables and 9 fruits, when the mean intake for each was > 1 g/d. Total consumption of flavonoids was calculated and reported in quartiles. The relative risk (RR) was taken as 1.00 for the lowest quartile. Questionnaires were used to collect data on other risk factors (socioeconomic data, diseases, medications, smoking status). Height, weight, body mass index, blood pressure, and serum cholesterol were measured.

Main outcome measures

National databases were used to obtain data on mortality (all-cause and from CAD).

Main results

To the end of 1992, 1364 persons died; 473 deaths were from CAD. Mean flavonoid intake was 3.7 mg/d in those who died of CAD compared with 4.1 mg/d in those who lived. Apples and onions contributed 64% of the flavonoid intake. The RRs were adjusted for age, smoking, serum cholesterol levels, hypertension, and body mass index. Women in the highest quartile of flavonoid intake compared with women in the lowest quartile had a decreased risk for all-cause mortality (RR 0.69, 95% CI 0.53 to 0.90) and CAD mortality (RR 0.54, CI 0.33 to 0.87). Men in the highest quartile had a reduction in all-cause mortality (RR 0.76, CI 0.63 to 0.93) but not in CAD mortality. Further adjustment for the intake of β-carotene; vitamins E and C; fiber; saturated, monounsaturated, and polyunsaturated fatty acids; and calories weakened the associations in women (RR for all-cause mortality 0.78, CI 0.57 to 1.08 and RR for CAD mortality 0.73, CI 0.41 to 1.32). When the sources of flavonoids were analyzed, women in the highest quartile of intake compared with the lowest quartile had a reduced risk for all-cause and CAD mortality with consumption of apples, berries, and other fruits; men in the highest quartile had a reduced risk for all-cause mortality with consumption of onions and fruits other than apples and berries.

Conclusion

Adults who consumed large amounts of flavonoids had a lower risk for all-cause mortality than did those who consumed small amounts.

Source of funding: No external funding.

For article reprint: Dr. P. Knekt, National Public Health Institute, Mannerheimintie 166, 00300 Helsinki, Finland. FAX 358-94744-8675.


Updated Commentary

Increased fiber intake in men was associated with reduced MI

What we eat affects our risk for CAD. The best evidence that supports the "diet-heart" hypothesis comes from the many studies that have examined the effects of saturated fat and cholesterol consumption on the risk for CAD. Other dietary factors, such as intake of alcohol, fiber, omega-3 polyunsaturated fatty acids, and nutrient antioxidants, however, may also affect CAD risk. The studies by Knekt and Rimm and their colleagues examined the role of flavonoid and fiber consumption as predictors of incident CAD.

Dietary flavonoids are water-soluble antioxidants found in fruits (e.g., apples, cranberries, and strawberries); vegetables (e.g., onions and broccoli); red wine; and tea. In the study by Knekt and colleagues, Finnish men and women with very low flavonoid consumption were at increased risk for CAD mortality. The association was stronger among women than men but appeared to be confounded by other dietary factors, particularly dietary fat and fiber. Although this study concurs with 2 previously published reports (1, 2), flavonoids have not been consistently associated with CAD risk (3, 4). Because of the relative weakness of the associations; the inability to control for important CAD risk factors, such as diabetes mellitus, alcohol consumption, and high-density lipoprotein (HDL) cholesterol level; and a study population of Finnish adults who consume very low levels of flavonoids compared with other populations (5) should be interpreted cautiously.

Rimm and colleagues examined the relation between dietary fiber consumption and risk for CAD among men. Because increased dietary fiber intake may lower glucose and cholesterol levels and, perhaps, caloric intake, it may be associated with CAD risk. Previous studies reported an inverse association between fiber consumption and CAD risk (6). After controlling for potential confounders, including dietary fat intake, Rimm and colleagues found that each 10-gram increase in daily fiber intake was associated with an approximately 20% reduction in CAD risk. Unexpectedly, insoluble fiber (rather than soluble fiber) and cereal fiber (rather than fruit or vegetable fiber) accounted for this association. A biologic explanation for the protective association between insoluble fiber and CAD risk is lacking. Although the authors controlled for the effects of many variables, the possibility that increased cereal fiber intake is a marker for a healthy lifestyle cannot be discounted.

Should physicians counsel their patients to consume large quantities of onions and apples for their flavonoid content and cereal products for their insoluble fiber content? These 2 studies provide evidence of the potential importance of specific dietary components, but their findings should be placed in the context of previous research, particularly because the few prospective studies that have examined the relation of flavonoids and CAD have produced inconsistent findings and there is, as yet, no biologic explanation about how insoluble cereal fiber may act to reduce CAD risk. Based on existing evidence, current recommendations about fruit, vegetable, and fiber consumption seem reasonable: Consume 5 or more servings of fruits and vegetables daily, and 6 or more servings of breads, cereals, and legumes daily (3). A decreased risk for CAD was observed by Knekt and colleagues at flavonoid intakes of 4.8 to 5.5 mg/d or greater. Comparable intakes should be readily achievable by following current recommendations for fruit and vegetable consumption. Rimm and colleagues found that men who consumed the most fiber had the lowest risk for CAD. On average, American men and women consume approximately 18 grams and 12 grams of fiber/d, respectively (4). Current guidelines recommend a higher level of consumption: 20 to 30 grams daily. Achieving this goal may be difficult, but most persons should be encouraged to increase their fiber intake.

Joel A. Simon, MD, MPH
San Francisco Veterans Affairs Medical CenterUniversity of California, San FranciscoSan Francisco, California, USA


References

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2. Yochum L, Kushi LH, Meyer K, Folsom AR. Dietary flavonoid intake and risk of cardiovascular disease in postmenopausal women. Am J Epidemiol. 1999;149:942-9.

3. Rimm EB, Katan MB, Ascherio A, Stampfer MJ, Willett WC. Relation between intake of flavonoids and risk for coronary heart disease in male health professionals. Ann Intern Med. 1996;125:384-9.Hertog MGL, Swetnam PM, Fehily AM, Elwood PC, Kromhout D

4. Hertog MGL, Swetnam PM, Fehily AM, Elwood PC, Kromhout D. Antioxidant flavonols and ischemic heart disease in a Welsh population of men: the Caerphilly Study. Am J Clin Nutr. 1997;65:1489-94.

5. Hertog MG, Kromhout D, Aravanis C, et al. Flavonoid intake and long-term risk of coronary heart disease and cancer in the Seven Countries Study. Arch Intern Med. 1995;155:381-6.

6. Committee on Diet and Health, Food and Nutrition Board, National Research Council. In: Diet and health: implications for reducing chronic disease risk. Washington, DC: National Academy Press. 1989:19:5-6.