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Flavonoids, heart disease and the French paradox

Dr Karine Nohr takes a detailed look at how diet can influence health.

Although we encourage patients to modify their diet, how much more energy seems to be focused on pharmaceutical interventions than on modifying dietary habits?

The plant-based ‘Mediterranean diet' has been associated with a lower incidence of cardiovascular disease relative to the Western animal-based diet.

The Lyons Diet Heart study was an RCT that compared the Mediterranean Diet with a ‘prudent' diet in secondary prevention post-MI. The end points were cardiac death and non-fatal MI. The study had to be stopped after 27 months because the outcome of the two groups was so radically different and the Mediterranean Diet showed an overwhelming benefit: 50-70% lower risk of recurrent heart disease and cardiac death. Compare this to the benefit of statins and our other conventional interventions!

Attempts to identify the key ingredients in this diet have been unsuccessful, studies evaluating reduced cholesterol, saturated fats, and even glycemic loads in the diet, all components of the Mediterranean diet, failed to significantly impact cardiovascular mortality (Hooper et al., 2001; Liu, 2000; Liu et al., 2001). Much attention has thus been placed on flavanoids, the nutritional dietary components of plants.

Despite having a higher smoking rate and higher fat intake than that of the United States, the ‘French paradox' describes how the French have an incidence of myocardial infarction that is one-third of that seen in the U.S. (Renaud & de Lorgeril M, 1992). This is thought to be due to cardioprotection afforded by a high flavonoid intake (from red wine and fresh fruits).

Recently, the 10-year follow-up of the large Seven Countries Study was completed and strengthened the original findings, with a clear dose-response relationship seen between flavonoid intake and coronary heart disease mortality.

An intake in the lowest tertile (0-19 mg/day) was associated with a coronary heart disease mortality of 18.5 per 1000 person-years, versus a rate of 7.8 in those consuming the most flavonoids daily (>29.9 mg), despite the differing sources of flavonoids in the diet. For example, tea was the predominant source of flavonoids in Japan, while red wine was the major source among Italian subjects.

The prospective cohort Zutphen Elderly Study examined the dietary habits and risk factors of over 800 elderly Dutchmen and its relationship to chronic disease. This 5-year longitudinal study that began in 1985 was an extension of the Dutch contribution to the Seven Countries Study, demonstrated that high intakes of flavonoids predicted significantly lower mortality from coronary heart disease, even when the results were adjusted for non-dietary risk factors (such as age, BMI, serum cholesterol levels, blood pressure, physical activity, antioxidant vitamin consumption, and coffee consumption). The major source of flavonoids was found to be tea, as opposed to fruits and vegetables. Tea accounted for 61 % of flavonoid intake, with onions (13%) and apples (10%) following.

In a Finnish study, over 5000 middle-aged men and women were followed for 20 years (few cohort studies testing the role of flavonoids in CVD have included women (Knekt et al., 1996)). Adjustments were performed for other coronary risk factors. A significant inverse relationship between total flavonoid intake (particularly apples and onions) and CVD mortality was identified for both men and women. Researchers concluded that people with very low intakes of flavonoids have higher risks of cardiovascular disease.

Not all of the epidemiological studies point to significant benefits of increased flavonoid intake with respect to CVD. A very large cohort (38,000 subjects) of women with no history of CVD was examined as a part of the Women's Health Study (Sesso et al., 2003) and concluded that flavonoid intake was not strongly associated with a reduced risk of CVD.

Finally, a British study found a weak but positive increase in cardiac mortality in subjects from the top three quartiles of flavonoid intake, relative to the lowest flavonoid intake (Hertog et al., 1997).

In conclusion, most epidemiological evidence favours the protective effect of dietary flavonoids in cardiovascular disease, and the risk:benefit ratio is about as good as it gets. These findings are supported by plausible biological mechanisms (antioxidant activity, nitric oxide synthesis, inhibition of platelet aggregation).

Dr Karine Nohr is a GP in Sheffield

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