A number of prospective epidemiological studies clearly point to the protective effect of whole grain cereals on myocardial infarctions (MIs). A corresponding protective association with diabetes and ischaemic stroke (brain infarcts) has only recently been demonstrated. Many mechanisms have been put forward to explain the protective effects.

There is a striking similarity between the risk factor pattern of the two major forms of cardiovascular disease (CVD), stroke and myocardial infarctions (MIs). For preventive purposes, it is important to focus on the control of diabetes, blood cholesterol, blood pressure, smoking cessation, and a reduction in weight, but also on some other risk indicators/factors such as insulin/proinsulin and fibrinolytic factors.

Many large-scale epidemiological studies strongly support the protective effect of dietary fibre rich food, especially whole grain products, on CVD (Hu 2003, Slavin 2004, Jacobs and Gallaher 2004, Seal 2006). A study on whole grain rye consumption that covered nearly 22,000 middle-aged Finnish men showed an inverse association between the amount of dietary fibre in the diet and coronary heart disease (Pietinen et al. 1996). These men were followed over 6 years, and it was found that the intake of cereal fibre, to a large extent deriving from rye, was more strongly negatively associated with the risk of MI than was vegetable or fruit fibre. The positive effect of fibre was strongest for fatal events. The relative risk of fatal myocardial infarction was 0.45 among the men with the highest intake of fibre (median, 28.9 g/day) compared with the men with the lowest intake of fibre (median, 12.4 g/day).

Some studies have shown the same associations, where cereal fibre has been strongly associated with a protective effect on MI (Wolk et al. 1999, Liu et al. 2002, Jensen et al. 2004). Similarly, the protective effects of whole grain food on ishaemic stroke have now also been shown in postmenopausal women, independent of other known CVD risk factors. There are probably several mechanisms behind the protective effects, including the effects on lipids and fibrinolysis.

Components in whole grain cereals, such as alkylresorcinols, phenols, lignans and phytic acid, can also act as antioxidants (Jacobs et al. 1998, Vanharanta et al. 2002, Kris-Etherton et al. 2002, Hallmans et al. 2003). Some suggested mechanisms are:

Insulin

In some prospective studies, a high insulin or proinsulin concentrations (Lindahl et al. 1999) has been associated with an increased risk of MI. There is a general agreement that insulin resistance with high insulin concentrations associated with an increased risk of MI. The effects of a rye bran bread-based high-fibre diet versus a wheat bread-based low-fibre diet have been studied experimentally (Leinonen et al. 2000, Lundin et al. 2001a, Juntunen et al. 2003a).

Cholesterol

The b-glucan in oats has been proven to reduce blood cholesterol concentration. In the United States, the following health claim is allowed in the marketing of oat products: The soluble fibre from oatmeal, as part of a low saturated fat, low cholesterol diet, may reduce the risk of heart disease (FDA 1997). Whole grain rye contains high amounts of soluble arabinoxylans, which theoretically may have a similar function in lowering cholesterol levels as the b-glucan in oats. A diet high in rye, especially rye fibre, has been shown to have positive effects in reducing serum total and LDL cholesterol in men with elevated serum cholesterol. The reduction of cholesterol was greatest among men that had consumed large amounts of rye bread (195-240 g rye bread/day). White wheat bread did not have a cholesterol-lowering effect (Leinonen et al. 2000). Also in the study of Lundin et al (2004) plasma free-cholesterol, total cholesterol, triglycerides and phospholipids were significantly lower after high fibre rye diet than after low fibre wheat diet.

In ileostomy studies, increased excretion of bile acids has been observed, with a slightly lowered (Lundin et al. 2001a) or no effect (Zhang et al. 1994) on the blood cholesterol concentration. An increased excretion of bile acids and cholesterol is believed to reduce the blood cholesterol concentration. In earlier studies with rats, it was found that rye reduced serum cholesterol, probably due to reduced absorption of bile acids and cholesterol (Lund et al. 1993, Zhang et al. 1994). Rye bran also lowered blood cholesterol in hamsters (Zhang et al. 1994). The cholesterol lowering effect of rye bran has been evaluated by Asp and Åman (2000). They concluded that so far the evidence for a cholesterol-lowering effect associated with rye bran is insufficient, from health claim point of view.

More long-term experimental studies on humans are obviously needed to explore the possible association of a relevant cholesterol-lowering effect with a high intake of rye bran. In an epidemiological study from Finland, a high intake of rye products was associated with a decreased risk of MI, independent of the serum cholesterol concentration (Pietinen et al. 1996). This observation is consistent with results from other prospective studies. Thus, the major protective effect on MI associated with a high intake with whole grain cereals does not seem to be related to the blood cholesterol concentration.

Prevention of blood clot (thrombosis) formation

The formation of a thrombosis is usually crucial for the MI event. An association has been observed between a high-fibre intake and a lowered concentration of variables associated with blood thrombosis dissolution (fibrinolysis) (Djoussé et al. 1998, Boman et al. 1994). Fibrinolysis can be defined as a breakdown of components (fibrin) that are an important part of a thrombosis. High concentrations of these fibrinolytic variables are associated with an increased risk of MI (Thögersen et al. 1998). The effect of whole grain diet/rye bran on the fibrinolytic system is a possible pathway for the protective effect of whole grain products. However, a diet high in rye did not show any significant changes in coagulation and fibrinolytic parameters in subjects with elevated blood cholesterol (Turpeinen et al. 2000). There is a very close relationship between high concentrations of insulin and high concentrations of one fibrinolytic factor (PAI-1). The two systems are linked together with insulin as the primary factor.

Antioxidative or anti-inflammatory factors related to
the whole grain complex

There are a large number of potential candidates with antioxidative and anti-inflammatory properties in the whole grain complex. The alkylresorcinols have the highest concentration of the substances with this potential in rye. From a theoretical point of view, anti-inflammatory effect of a factor present in the vessel wall may prevent "plaque rupture" and subsequent thrombosis formation. A study on the absorption of alkylresorcinols in humans has recently been performed. Ten ileostomy-operated subjects were fed diets containing whole rye bread rich in alkylresorcinols or sifted wheat bread with no alkylresorcinols. Diet and ileostomy samples were analysed for alkylresorcinols and the apparent digestibility was calculated. The average absorption of alkylresorcinols in humans was between 50 and 70% for all major homologues (Ross et al. 2003). Alkylresorcinols may, therefore, be considered as good markers for whole cereal grain intake. Their biological effects and distribution in the body should be studied in the future (Linko et al. 2005).

In the field of cardiovascular disease, especially myocardial infarctions, there is a general agreement between prospective studies using biomarkers with antioxidative properties in blood such as enterolactone (Vanharanta et al. 1999) and ascorbic acid (Khaw 2001), and the results of prospective studies using dietary questionnaires. In a recent study from Finland, a high serum concentration of enterolactone was clearly associated with a decreased risk of myocardial infarction (Vanharanta et al. 1999). Thus, in this study, serum enterolactone was evaluated as a useful biomarker for the intake of lignan-rich foods. Like ascorbic acid and other antioxidants in blood a negative correlation may be expected to occur between enterolactone and markers of inflammation in blood, a hypothesis that has not yet been tested.

It is, however, unlikely that plasma enterolactone is confounded by the effect of a low-grade inflammation associated with advanced artherosclerocis. In fact in study by Vanharanta et al. (2002), serum enterolactone is associated with a decreased in vivo peroxidation. Also, after an adjustment for plasma antioxidative vitamins (alpha-tocopherol, beta-carotene, ascorbic acid) and dietary folic acid, the decreased peroxidation remained associated with enterolactone. It is thus suggested that enterolactone or some of its precursors may contribute to the antioxidative defence system in blood. Some other biomarkers/ phytochemicals such as alkylrecorsinols, which also are absorbed in large amounts from rye, may of course be the active antioxidative agent.

Diabetes

Diabetes is a well-established risk factor for CVD. A clear association between a high intake of dietary fibre from cereal grain and a reduced risk of diabetes has been observed as pointed out earlier. The outcome of the epidemiological and experimental studies suggest that substituting refined grain products with whole grain products may decrease the risk of both diabetes and CVD. It is probable that the protective effect is associated with some factor in the dietary fibre complex (Hallmans et al. 2003).

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