Category Archive for: ‘Nutrients’

Flavan-3-ols (catechins) and cardiovascular disease

Flavan-3-ol intake related to CHD but not to stroke

An average intake of monomeric flavan-3-ols of 124 mg/d, compared to an average intake of 25 mg/d, was associated with a 51% lower 10-year CHD mortality in the Zutphen Elderly Study. Tea is a rich source of both flavan-3-ols and flavonols. Therefore we analyzed also the intake of tea, flavan-3-ols not from tea and flavonols not from tea in relation to fatal CHD. Tea and flavan-3-ols not from tea were inversely related to fatal CHD but flavonols from other sources than tea were not associated. These results suggest that a high intake of flavan-3-ols is related to a low risk of fatal CHD independent of flavonols. In contrast, flavan-3-ols intake was not associated with 10-year stroke incidence.

Measuring flavan-3-ols (catechins)

Flavan-3-ols are a subclass of flavonoids, an extended class of chemically related compounds ubiquitously present in plant foods. Evidence from controlled experiments in people shows that one of the flavan-3-ols, epicatechin, has favorable effects on endothelial function, blood pressure and insulin resistance. The richest sources of flavan-3-ols are tea, apples and chocolate (cocoa).

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Nutrient intake and depressive symptoms

Omega-3 fatty acids associated with lower risk of depressive symptoms

A cross-sectional analysis of the Zutphen Elderly Study showed that men with an average daily intake of the fish fatty acids EPA-DHA (407 mg per day), followed for 10 years, had a 54% lower risk of depressive symptoms compared to those with an average daily intake of 21 mg/d. An explanation for this association might be that low levels of EPA-DHA are associated with low levels of neurotransmitters and with markers of inflammation and endothelial dysfunction.

B-vitamins not related to depressive symptoms

Major depression is associated with with lower blood levels of B-vitamins. The B-vitamins folate, vitamin B6 and B12 are involved in the production of neurotransmitters and low levels are associated with depression. However, in a cross-sectional analysis the intake of B-vitamins was not related to depressive symptoms in the Zutphen Elderly Study.

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Studies in the elderly

The Zutphen Elderly, HALE and FINE studies researched the indicators of healthy ageing.

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Fish, omega-3 fatty acids and cognitive decline

Fish consumption related to lower cognitive decline.

In the Zutphen Elderly Study fish consumers had significantly less cognitive decline after 5 years than non-users. Similar results were obtained for the intake of the omega-3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid).

Fish consumption related to lower cognitive decline

In the Zutphen Elderly Study fish consumers had less cognitive decline than non-users after 3 years of follow-up. However, this association was not statistically significant. After extending the follow-up period to 5 years this association became statistically significant.

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Fish and cognitive decline
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Moderate intake fatty acids EPA-DHA associated with lower cognitive decline

An average difference in consumption of 380 mg of EPA-DHA per day was associated with a significant difference in cognitive decline after 5 years of follow-up. These results suggest that a moderate intake of EPA-DHA may postpone cognitive decline.

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Studies in the elderly

The Zutphen Elderly, HALE and FINE studies researched the indicators of healthy ageing.

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Lignans and coronary heart disease

The lignan MAT might be inversely related to CHD

The median total lignan intake in elderly men in Zutphen was 977 microgram/d. The intake of the lignan MAT (matairesinol) was significantly inversely related to 15-year fatal CHD – in contrast to the total lignan intake which was unrelated. The inverse association between MAT and CHD mortality could be due to an associated factor such as wine consumption.

How to measure lignans

Lignans are diphenolic compounds present in plant foods (and not to be confused with lignin, one of the dietary fibers). We studied the lignans LARI (lariciresinol), PINO (pinoresinol), SECO (secoisolariciresionol) and MAT. These molecules are converted to enterolignans by the intestinal microflora and possess estrogen-like activities.

We developed a method to measure the four lignans in foods and beverages. The most abundant lignan sources are flaxseed and sesame seeds. In the Zutphen Elderly Study most of the lignans came from tea, vegetables, bread, coffee, fruit and wine.

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Mediterranean style diets and cardiovascular disease

A Mediterranean style diet was consistently associated with lower cardiovascular risk

Adhering to a Mediterranean style diet was associated with a 39% lower coronary mortality risk and a 29% lower cardiovascular mortality risk in middle-aged and elderly European men and women in the HALE project. The Mediterranean diet score we used was based on eight basic food groups: bread, legumes, vegetables, fruit, fish, fats, dairy products and meats. A high intake of bread, legumes, vegetables, fruit and fats rich in unsaturated fatty acids, a moderate intake of fish and a low intake of dairy and meat was characteristic of a Mediterranean diet.

Measuring habitual diets

The HALE project dealt with European elderly men and women participating in the FINE and the SENECA Studies. They were 70-90 years old at baseline and were followed for 10 years. In both studies the dietary history was recorded as the measure of habitual food consumption.

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Nutrients, smoking and coronary heart disease rates in the 16 cohorts

A high saturated fat intake, a low flavonoid intake and smoking are associated with high CHD mortality rates

Three factors combined – saturated fat, flavonoids and smoking – account for 90% of the differences in 25-year CHD mortality rates among the 16 cohorts in the Seven Countries Study. In univariable models average saturated fat intake at baseline was strongly associated with CHD mortality, while average flavonoid intake was inversely related. The prevalence of smoking at baseline was not related to CHD mortality rates. However, multivariable modeling showed that saturated fat and smoking were positively and that flavonoid intake was inversely related to CHD mortality rates.

Multivariate model for average saturated fat and flavonoids intake and CHD mortality rates
Interpretation of the results

Based on mechanistic studies confirming these associations we conclude that saturated fat increases the cholesterol rich LDL-lipoprotein fraction and the risk of atherosclerosis. Smoking promotes LDL oxidation that might be offset by the strong antioxidant effects of flavonoids. Trials showed that replacing saturated with polyunsaturated fat reduces CHD risk. Prospective cohort studies found that stopping smoking and a high intake of flavonoids are associated with a lowered CHD risk. These results found at the population level in the Seven Countries Study are thus in agreement with those obtained in experimental and prospective cohort studies, strenghtening the interpretation of cause and prevention.

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Antioxidant vitamins and cardiovascular disease

Only carotenoid intake associated with CVD risk

A 0.6 mg/d alpha-carotene greater intake at entry was associated with a 19% lower 15-year risk of CVD mortality in elderly men in Zutphen. Men with a 1.5 mg/d beta-carotene greater intake had a 20% lower  CVD mortality risk. Carrots are the primary source of alpha- and beta-carotene and a high consumption of carrots was related to a 17% lower risk of CVD mortality. Alpha- and gamma tocopherol, and vitamin C intake were not related to cardiovascular mortality.

Conflicting results on carotenoids

Early reports of others in prospective cohort studies suggested that a high intake of beta-carotene was associated with a lower CVD risk. But in sharp contrast, large-scale trials conducted in high risk persons (e.g. smokers) showed that supplements of a large amount of beta-carotene apparently did not decrease but rather increased CVD risk. The role of carotenoids in CVD prevention, therefore, remains controversial.

The Zutphen Elderly Study results suggest that only the intake alpha- and beta-carotene was inversely related to CVD mortality.

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Trans fat and coronary heart disease

The higher the trans fat intake the greater the CHD risk

In the Zutphen Elderly Study a difference of 2% of energy from trans fat at baseline was associated with a 28% difference in risk of 10-year coronary heart disease (CHD) incidence. The strength of the association was similar for trans fat from manufactured and natural sources. We calculated that the decrease in trans fat of 2.4 % of energy between 1985 and 1995 could have contributed to 23% less coronary deaths (equal to about 4,600 of 20,000 coronary deaths in the Netherlands per year).

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Trans fatty acid intake (en%) and risk for CHD
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Phenomenal decrease in trans fat intake in the diet of the Zutphen men

One of the characteristics of the Dutch diet in 1960 was its high amount of trans fat, due to the high content of hydrogenated hardened fish oils in solid fats. The decrease in trans fat intake between 1960 and 2000 has been the most important change in the Dutch diet. The average intake decreased from 19 gram/day (7% of energy) to 4 g/d (1% of energy) in the Zutphen Study. The spectacular decrease in trans fat between 1960 and 2000 started already before the Dutch margarine producers decided, in 1994, to reduce the trans fat content of margarines.

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Mediterranean dietary patterns in the 1960s

Many Mediterranean diets

Ancel Keys and his Italian colleague Flaminio Fidanza and their SCS colleagues were central to the modern recognition, definition, and promotion of the eating pattern they found in Italy and Greece in the 1950s and ’60s, now popularly called “The Mediterranean Diet”. Ancel Keys was the first researcher who associated the traditional Mediterranean diet with a low risk of CHD. However, the Mediterranean diet does not exist. The Mediterranean Sea borders 18 countries that differ markedly in geography, economic status, health, lifestyle and diet.

Traditional Mediterranean diets had olive oil as their principal component of fat, were high in cereal products, legumes, fruit and vegetables, moderate in fish and low in dairy and meat products. Moderate amounts of wine were taken with meals. The traditional Mediterranean diets were nutritionally adequate with a varying amounts of total fat, low in saturated fat and very low in trans fat, rich in fiber and in antioxidant vitamins or flavonoids.

Mediterranean diets in the the Seven Countries Study in the 1960s

The Seven Countries Study included four Mediterranean cohorts: Crete and Corfu in Greece, Dalmatia in Croatia and Montegiorgio in Italy. In the 1960s the Greek diet had the highest content of olive oil and was high in fruit, the Dalmatian diet was highest in fish and the Italian diet was high in vegetables. In line with their diet, these cohorts were characterized by low mortality rates from CHD.

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Fiber and coronary heart disease

High fiber associated with low CHD mortality

Every additional amount of 10 g/d of recently consumed fiber was associated with a significant 17% lower risk of fatal CHD during 40 years of follow-up. A non-significant 13% lower risk was observed for long-term fiber intake.

A dietary fiber intake of more than 36 g/d at entry in 1960 was also associated with a 4 times lower risk of fatal CHD during 10 years of follow-up, when compared to an intake of less than 20 g/d. However, this association became non-significant in multivariable analysis.

Dietary fiber intake in 1960 and 2000

Between 1960 and 2000 seven dietary surveys were carried out in the Zutphen Study. The average dietary fiber intake was 33 g/d in middle-aged men in 1960 and 21 g/d among survivors in 2000. The average energy intake amounted to 3100 kcal/d in 1960 and 2100 kcal/d in 2000.

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