CVD

There is ample epidemiological and clinical evidence that relates the consumption of wholegrain cereals with a reduced risk of coronary disease⁽Reference Rizkalla, Laromiguiere and Champ^10, Reference Gil, Ortega and Lozano¹¹⁾. Subjects who ingest three or more rations of foods per day based on integral cereals have a 20–30 % lower risk than subjects who ingest low quantities of cereals, and this level of protection is not observed with the ingestion of refined cereals, these being even higher than with the intake of fruits and vegetables⁽Reference Liu, Stampfer and Hu^1, Reference Jensen, Koh-Banarjee and Hu^6, Reference Zarzuelo and Gálvez^12–Reference Pietinen, Rimm and Korhonen¹⁶⁾.

Morris et al.⁽Reference Morris, Marr and Clayton¹⁷⁾, after studying 337 subjects for 10–20 years, concluded that the reduction in the risk of CVD was attributable to a greater consumption of cereal fibre, whereas other sources of soluble fibre such as pectin and guar gum did not present the same effect. In addition, an analysis of several cohort studies on dietary fibre and coronary disease risk showed that the consumption of dietary fibre from cereals and fruits was inversely associated with the risk of coronary disease⁽Reference Pereira, O'Reilly and Augustsson¹⁸⁾. Other large surveys have found a moderate association between the intake of wholegrain cereal and the lowering of CVD risk. In an extensive prospective health study in Iowa (USA), 34 492 postmenopausal women aged 55–69 years and free of CVD were tracked to determine the occurrence of mortality by CVD (n 387) from 1986 to 1994⁽Reference Jacobs, Meyer and Kushi¹⁵⁾. The lowering of the risk in the highest quintile of wholegrain cereal intake was controlled for more than fifteen variables and was not explained by the adjustment of the consumption of dietary fibre. This suggests that other components of wholegrain cereal that are not dietary fibre may reduce the risk of CVD.

A Finnish study of 21 930 men who smoked (50–69 years of age) was monitored for 6·1 years⁽Reference Pietinen, Rimm and Korhonen¹⁶⁾. The lower risk of CVD was associated with the increase in the intake of products containing rye. Rimm et al.⁽Reference Rimm, Ascherio and Giovannucci¹⁹⁾ examined the association between cereal consumption and the risk of myocardial infarction (MI) in 43 757 health professionals in the USA, aged 40–75 years. Cereal fibre was the factor most strongly associated with a reduced risk of MI, with a 0·71 decline in the risk per 10 g increase in the ingestion of cereal fibre.

The Nurses’ Health Study, an extensive prospective cohort study tracking women in the USA for 10 years, was also used to examine the relationship between cereal consumption and cardiovascular risk⁽Reference Liu, Stampfer and Hu¹⁾. A total of 68 782 women aged between 37 and 64 years without prior diagnosis of angina, MI, apoplexy, cancer, hypercholesterolaemia or diabetes were examined at the beginning of the study. The authors controlled for age, cardiovascular risk factors, dietary factors and the use of multivitamin supplements. For an increase of 10 g/d in the total consumption of fibre, the risk of CVD was 0·81 (95 % CI 0·66, 0·99). Among the different sources of dietary fibre (cereal, vegetables and fruit), only cereal fibre proved to be strongly associated with a lower risk of CVD.

As wholegrain cereals are a major source of dietary fibre in many countries, it is difficult to separate the protection of dietary fibre from that of wholegrain cereals. In a study tracking health professionals, Jensen et al.⁽Reference Jensen, Koh-Banarjee and Hu⁶⁾ examined the consumption of wholegrain cereals, bran and germ in relation to the risk of coronary disease from the data on food consumption frequency. Added germ was not associated with CVD risk, leading the authors to conclude that the study supported the association of the benefits described between the consumption of wholegrain cereals and the reduction of CVD, suggesting that the bran of wholegrain cereal could be a key factor in this relation. The regular consumption of foods that include wholegrain cereals appears to protect against CVD. Van Dam et al.⁽Reference Van Dam, Grievink and Ocké²⁰⁾ reported that the consumption of refined diets that did not include wholegrain cereals was associated with higher levels of blood cholesterol and lower consumption of micronutrients. Prudent eating habits, including the intake of wholegrain cereals, was associated with a lower level of reactive protein C and endothelial dysfunction, an early step in the development of atherosclerosis⁽Reference Lopez-Garcia, Schulze and Fung²¹⁾. The consumption of foods based on wholegrain cereals was also associated with lower reactive protein-C concentrations in the Nurses’ Health Study⁽Reference Wu, Giovannucci and Pischon²²⁾. In addition, a prospective cohort study of post-menopausal women found that the consumption of cereal fibre and the ingestion of whole-grain cereal reduced the progression of atherosclerosis in the coronary artery⁽Reference Erkkilä, Herrington and Mozaffarian²³⁾. In a subsample of the Study Tracking Health Professionals and the Nurses’ Health Study II, a broad range of biomarkers related to CVD⁽Reference Jensen, Koh-Banerjee and Franz²⁴⁾ was measured. Greater consumption of wholegrain cereal was associated with lower homocisteine and total cholesterol. Thus, these results suggest a lower risk of cardiac disease in persons who consume diets high in whole grains. In this sense, Sayoun et al.⁽Reference Sahyoun, Jacques and Zhang²⁵⁾, have published a significant inverse trend between the intake of wholegrain cereal and mortality by CVD, independently of demography, lifestyle or dietary factors. In addition, glucose while fasting and the BMI diminished as the quartiles increased in the category of wholegrain consumption.

Type 2 diabetes mellitus

Nutrition is considered by health professionals to be a basic tool to control the blood glucose levels and therefore to treat diabetes. Several epidemiological studies have shown that the high intake rates of wholegrain cereals and their products, such as whole-wheat bread, are associated with a 20–30 % reduction in the risk of DM2⁽Reference Sahyoun, Jacques and Zhang^25, Reference Murtaugh, Jacobs and Jacob²⁶⁾. Furthermore, evidence from observational and interventional studies indicates that the consumption of wholegrain cereals improves the plasma glucose levels as well as insulinaemia, reducing tissue resistance to insulin⁽Reference Slavin^2, Reference Murtaugh, Jacobs and Jacob²⁶⁾. On the other hand, the data available indicate that the components of wholegrain cereals overall are responsible for the lowering of risk, as the fibre from fruit and vegetables does not exert the same effects⁽Reference Montonen, Knekt and Järvinen²⁷⁾. In fact, Montonen et al.⁽Reference Montonen, Knekt and Järvinen²⁷⁾ found an inverse relation between the intake of total fibre, especially cereal fibre, and the risk of type 2 diabetes, whereas fibre derived from fruit or vegetables did not have an effect on diabetes risk. Adjustment for cereal fibre considerably weakened the association between wholegrain consumption and type 2 diabetes risk, which suggests that the relation of whole grain may be due to cereal fibre or to factors related to cereal fibre intake.

With the exception of a few foods, most contain carbohydrates in different proportions. However, from the nutritional standpoint, not only the quantity is important but also the speed with which it is absorbed, this being influenced by a number of factors such as the type of carbohydrate (glucose, fructose, sucrose, lactose), the nature of the starch (amylose, amylopectin, RS), the method of preparation (manner and time of cooking, quantity of heat used), the degree of processing of the foods (degree of gelatinisation of the starch, particle size, the form of the food) and other components (e.g. natural substances that slow down digestion like pectins, phytates and tannins)⁽Reference Englyst, Kingman and Cummings^8, Reference Gil, Ortega and Lozano¹¹⁾.

With the aim of comparing the effects of specific foods in the blood sugar response, in 1981 the concept of GI was introduced. For this index to be established, healthy volunteers who had fasted for the night had their glycaemia levels measured after ingesting a set quantity of the food in question (the quantity of food was adjusted to provide 50 g of glycaemic or biologically available carbohydrate). The glycaemia was measured in previously established time intervals up to a maximum of 120 min. These measurements were compared with those of a reference product such as glucose (50 g), to which an index of 100 was arbitrarily assigned. The quotient between the areas of the respective curves was called the GI⁽Reference Venn and Green³⁾. Initially, the reference product for the determination of the GI was white bread, but the bread generated a variable glycaemic curve, depending on its composition and preparation, especially the variable content of RS. In fact, traditional white breads can vary their GI with respect to glucose from 74 % to 100 %⁽Reference Englyst, Kingman and Cummings⁸⁾.

The concept of GI appears to be a useful tool for glycaemic tracking in diabetic patients. In addition, diets with a low GI have the capacity to reduce the secretion of insulin and diminish blood lipid concentrations, as demonstrated in several clinical tests⁽Reference Riccardi, Rivellese and Giacco²⁸⁾. Diabetic patients who ingested bread having a low GI and made with the addition of fibre from wholegrain cereals registered a reduction in the blood glucose values⁽Reference Henry, Lightowler and Tydeman²⁹⁾ as well as in the cholesterol and TAG levels, compared with those who followed a diet with a high GI⁽Reference Livesey, Taylor and Hulshof^5, Reference Marangoni and Poli³⁰⁾. However, the GI did not take into account the quantity of carbohydrates consumed, an important determinant of the glycaemic response. For example, most fruits have a high GI and would appear not to be a good choice as part of a diet with a low GI. Nevertheless, fruit usually have a low content of carbohydrates, and therefore their glycaemic effect is minimal. Given that foods differ in carbohydrate content, Willett et al. defined the glycaemic load (GL) in 1997 as the arithmetic product of GI and the quantity of carbohydrates ingested⁽Reference Venn and Green³⁾.

Another important concept is that of the glycaemic glucose equivalent (GGE) of a food. The GGE refers to the relative tendency of a given quantity of food consumed at a single time, such as a portion, to induce a postprandial glycaemic response. The GGE is measured directly by the quantity of reference glucose necessary to give the same glycaemic response as a relevant quantity of a given food⁽Reference Monro and Shaw³¹⁾.

Bread belongs to a group of foods that increase the insulin response, as its main carbohydrate is gelatinised starch, easily digested by human amylases, and therefore usually gives rise to high glycaemic responses. Wholegrain breads have a lower GL than do corresponding white breads and therefore offer better control for postprandial glycaemia⁽Reference Englyst, Kingman and Cummings⁸⁾.

Breads made with wholegrain cereals, for reasons discussed for the whole grains in terms of their content of fibre and resistant starches, present lower GI values. The incorporation of soluble fibre in great quantities (bread made of oat bran) augments viscosity of the bolus, limits the access of amylotic enzymes and diminishes the diffusion of the glucose through the mucosa, giving these products a far lower GI. In addition, rye breads made with sour dough, due to the presence of organic acids, appear to diminish postprandial glycaemia and insulinaemia. In addition, flatbread has a more compact structure and therefore slower digestion and a lower GI. For all the above, breads made traditionally with high fibre contents are useful for controlling postprandial glycaemia in subjects with intolerance to glucose and with diabetes⁽Reference Englyst, Kingman and Cummings⁸⁾.

It has been reported that the ingestion of fibre from wholegrain cereals is inversely related to DM2. In a long-term study of almost 90 000 women⁽Reference Monro and Shaw³¹⁾, and in a similar study of nearly 45 000 men⁽Reference Salmerón, Manson and Stampfer³²⁾, it was found that those who consumed more cereal fibre had an approximately 30 % lower risk of developing DM2, compared with those with lower consumption. In addition, in the study on women's health in Iowa (USA), it was found that the consumption of dietary fibre and wholegrain cereal protected against DM2⁽Reference Salmerón, Ascherio and Rimm³³⁾. In another study, individuals who consumed mainly refined cereals and little wholegrain cereal had a 57 % greater risk of DM2 than those who consumed higher quantities of wholegrain cereals⁽Reference Meyer, Kushi and Jacobs³⁴⁾. In the Study Tracking Health Professionals, one part monitoring 42 898 men consuming approximately three rations of wholegrain cereal per day associated this consumption with a 37 % lower risk of DM2⁽Reference Liu, Manson and Stampfer³⁵⁾. In addition, when the data were brought together for prospective cohort studies, the consumption of wholegrain cereal was found to reduce the relative risk of DM2 by 30 %⁽Reference Fung, Hu and Pereira^36, Reference Liu³⁷⁾.

Pereira et al.⁽Reference Pereira, Jacobs and Pins³⁸⁾, studying hyperinsulinaemic subjects who were overweight or obese, tested the hypothesis that the consumption of wholegrain cereal improves the tissue sensibility of the insulin in overweight and obese adults. Eleven adults followed two diets, each for 6 weeks. The two diets were identical except that in one of them the products of refined cereal, mainly bread, were replaced by wholegrain products. The insulin during fasting proved 10 % lower during the diet with the integral cereal. Thus, the authors concluded that sensitivity to insulin may be an important mechanism by which foods based on whole grains reduce the risk of DM2 and cardiac disease.

Juntunen et al.⁽Reference Juntunen, Niskanen and Liukkonen³⁹⁾ evaluated the factors affecting plasma glucose and the insulin response after the ingestion of cereal products. Several subjects consumed different cereal products: bread with wholegrain rye, wholegrain rye bread with a β-glucan concentrate from oats, pasta made of dark Durum wheat and wheat bread made from white wheat flower. The glucose responses and the index of gastric emptying after the consumption of the two rye breads and the pasta did not differ from those after the consumption of white wheat bread. However, the insulin, the glucose-dependent insulinotropic polypeptide and the peptide analogous to type-1 glucagon were lower after the consumption of the rye breads and dark pasta than after the consumption of white wheat bread. Thus, the postprandial insulin responses to cereal products may be determined by the form of the food and the botanical structure more than by the quantity of fibre or the type of cereal in the food. McKeown et al.⁽Reference McKeown, Meigs and Liu⁴⁰⁾ have reported that the consumption of wholegrain cereal in the Framingham Children's Study is inversely associated with the index of body mass and insulin during fasting.

Juntunen et al.⁽Reference Juntunen, Laaksonen and Poutanen⁴¹⁾, studying postmenopausal women who consumed high-fibre rye bread and white wheat bread, measured the glucose and insulin metabolism. The acute response of insulin significantly augmented more during the period of consuming rye bread than during that of consuming white wheat bread. This suggests that high-fibre rye bread favours the secretion of insulin. In another study, foods based on rye and wheat was offered to middle-aged overweight men⁽Reference McIntosh, Noakes and Royle⁴²⁾. The men consumed cereals low in fibre that provided 5 g of dietary fibre in the diet of refined cereals and 18 g of fibre in the diet of the wholegrain cereal, whether high in rye or wheat. All this was additional to a basal diet that contained 14 g of fibre. The postprandial insulin fell 46–49 % and postprandial glucose dipped 16–19 % after the consumption of the wholegrain diet.

Qi et al.⁽Reference Qi, van Dam and Liu⁴³⁾, examining whether the ingestion of wholegrain cereals and dietary fibre was associated with inflammatory indicators among 902 diabetic women in the Nurses’ Health Study, suggested that the wholegrain cereals and a diet with a low GI could reduce systemic inflammation among women with DM2. In addition, Jensen et al.⁽Reference Jensen, Koh-Banerjee and Franz²⁴⁾ found in 938 healthy men and women that the consumption of wholegrain cereal was inversely related more strongly to the plasma markers of glycaemic control (insulin during fasting, glycosylated Hb A1c, peptide C and leptin).

Cancer

The consumption of wholegrain cereals has in several studies been associated with a reduced risk of some types of gastrointestinal cancer. In a meta-analysis on the consumption of wholegrain cereals and cancer that analysed all the studies conducted up to 1998 indicated protection against the risk of colorectal cancer and polyps, other cancers of the digestive tract, cancers related to hormones and pancreatic cancer⁽Reference Jacobs, Marquart and Slavin⁴⁴⁾. In addition, a systematic review of case–control studies carried out using a common protocol in northern Italy between 1983 and 1996 indicated that a greater frequency in the consumption of wholegrain cereal is associated with a lower risk of cancer⁽Reference Chatenoud, Tavani and La Vecchia⁴⁵⁾. Wholegrain cereal is consumed primarily as wholegrain bread and some as wholegrain pasta. Cohort studies have shown a lower risk for specific cancers, such as colorectal in women⁽Reference Larsson, Giovannucci and Bergkvist⁴⁶⁾, stomach⁽Reference Terry, Lagergren and Ye⁴⁷⁾, mouth/throat and the upper digestive tract⁽Reference Kasum, Jacobs and Nicodemus⁴⁸⁾ and endometrium⁽Reference Kasum, Nicodemus and Harnack⁴⁹⁾.

A review of forty studies on gastrointestinal cancer has found a reduction in cancer risk from 21 % to 43 % in subjects with high consumption of wholegrain cereals compared to those with low consumption⁽Reference Slavin²⁾. In addition, in more recent cohort studies, the intake of wholegrain cereals has been associated with a moderate reduction in colorectal cancer risk⁽Reference Jacobs, Andersen and Blomhoff^50, Reference Schatzkin, Mouw and Park⁵¹⁾. Furthermore, in a recent meta-analysis, it was shown that the intake of products having a low GI and GL, including products based on cereals with a high fibre content, was associated with a lower risk of colorectal, pancreatic, endometrium and breast cancer⁽Reference Gnagnarella, Gandini and La Vecchia⁵²⁾. However, a recent study published jointly between the World Cancer Research Fund and the Institute for Cancer Research on the relative risk of different types of cancer in relation to different lifestyles found no association between the specific consumption of cereals and colorectal cancer⁽⁵³⁾. On the other hand, another meta-analysis indicated that the consumption of foods with a low GI or GL was not associated with a reduction in colorectal or pancreatic cancer⁽Reference Mulholland, Murray and Cardwell⁵⁴⁾. However, the studies that examine the association of the consumption of cereals with hormone-dependent cancers are very limited.

Several mechanisms have been proposed for the action of cereals in relation to cancer. The fibre and certain resistant starches found in cereals and their products, as in the case of bread, ferment in the colon and contribute to reduction of the intestinal transit and improvement of intestinal health. Cereals also contain antioxidants that can protect against oxidative damage, which can play a fundamental role in the development of cancer. Other bioactive compounds in wholegrain cereals may affect the hormonal levels and probably the hormone-dependent cancers. The potential mechanisms include shifts in the plasma-glucose values and weight loss⁽Reference Slavin²⁾. In addition, the lowering of insulin levels by wholegrain cereals can be an indirect way by which cancer risk is reduced, given that several epidemiological studies have suggested that higher levels of insulin are associated with a greater risk of colon, breast and possibly other types of cancer.

Dietary factors, such as the intake of fibre, vegetables, fruits, antioxidants, vitamin B₆ and phytoestrogen, as well as lifestyle factors such as exercise, smoking and alcohol intake, which are controlled for in most epidemiological studies, do not explain the apparent protective effect of wholegrain cereals against cancer, again suggesting that it is the complete package of the wholegrain cereal that is effective⁽Reference Gil, Ortega and Lozano¹¹⁾.

Various theories have been proposed to explain the protective effects of wholegrain cereals. Thus, the increase in the faecal mass and the decrease in transit time give less opportunity to the faecal mutagens to interact with the intestinal epithelium. Secondarily, it is thought that the sequestration by fibre of the bile acids, which promote cell proliferation, can diminish the frequency of mutations. Wholegrain cereals also contain anti-nutrients, such as protease inhibitors, phytic acid, phenolic compounds and saponins, which until recently were thought to have only a negative nutritional consequence. Some of these anti-nutrient compounds may act as cancer inhibitors by preventing the formation of carcinogens and blocking the interaction of carcinogens with cells. Other potential mechanisms of wholegrain cereals to lower cancer risk include effects of lignans. Lignans are compounds that have a 2,3-dibenzylbutane structure, and there are minority constituents of many plants that form construction blocks to create lignin in the cell wall of the plant. Owing the relation of the excretion of lignans with fibre consumption, it is assumed that vegetal lignans are contained in external layers of the grain. Concentrated sources of lignans include whole wheat, whole oats and whole rye. Seeds are also a concentrated source of lignans, including flax seeds (the most concentrated source), pumpkin seeds, caraway seeds and sunflower seeds⁽Reference Slavin²⁾.

Cereals and other foods rich in fibre increase the urinary excretion of lignans, an indirect measure of the lignan content in food⁽Reference Borriello, Setchell and Axelson^55, Reference Adlercreutz, Fotsis and Bannwart⁵⁶⁾. In addition, they are positively related to the consumption of products based on wholegrain cereals⁽Reference Kilkkinen, Valsta and Virtamo⁵⁷⁾. Similar results were found in a study in the USA⁽Reference Jacobs, Pereira and Stumpf⁵⁸⁾ in which the subjects consumed either wholegrain-based foods or refined-grain foods (especially bread) for 6 weeks. Most of the increase in serum enterolactone occurred when the subjects consumed the diet based on wholegrain bread. Serum enterolactone has been associated not only with a decline in the risk of cancer, but also with a lower CVD related to all the causes of mortality in middle-aged Finnish men⁽Reference Vanharanta, Voutilainen and Rissanen⁵⁹⁾.

Gastrointestinal pathologies

The components of wholegrain cereals, including fibre, RS and oligosaccharides, play a fundamental role in the maintenance of intestinal homeostasis. Several studies have suggested that the dietary fibre from grains and whole cereals augments the weight of the stool and absorb water, and the partial fermentation of the fibre in the colon as well as of the oligosaccharides promotes the growth of beneficial bacteria in the faeces⁽Reference Slavin^2, Reference Montonen, Knekt and Järvinen²⁷⁾. RS is not digested in the same way as ordinary starch, passing through the intestine to the colon, where it is fermented, and behaving in all senses like soluble dietary fibre. The main content of faecal residue facilitates intestinal peristalsis and defecation. All this helps alleviate symptoms of constipation and contributes to lowering the risk of developing diverticulosis and diverticultitis⁽Reference Marlett, McBurney and Slavin⁶⁰⁾.

McIntosh et al.⁽Reference McIntosh, Noakes and Royle⁴²⁾ offered foods based on rye and wheat to overweight middle-aged men and measured markers of intestinal health. The food based on rye and wheat with high fibre content increased the faecal evacuation by 33–36 % and diminished the activity of faecal β-glucuronidase by 29 %.