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Wholegrains: A Whole New Story

National Seminar Series Summary of Presentation

Graeme H McIntosh

CSIRO Health Sciences Nutrition


"The protective role of wholegrains in cancers and other diseases"

Introduction

Recent research has identified wholegrains as a significant contributor, along with fruits and vegetables, to diets that prevent colorectal cancers, coronary heart disease, maturity onset diabetes and possibly breast cancer. However, most emphasis to date has been given to fruits and vegetables, almost to the exclusion of cereals.

Wholegrains are deservedly at the base of the recommended food guide pyramid. They contribute energy (starch), protein, dietary fibre (soluble and insoluble) and resistant starch, and other nutrients and non-nutrient phytochemicals which are only now becoming recognised for the significant contribution they may make to our health.

While the food guide pyramid recommends 5-6+ servings of cereal foods per person per day it is unlikely this is being practised in Australia, except by a health conscious minority.

In the United States, wholegrain and wholemeal foods have been defined in legislation to make sure such foods are readily identified and obtainable. They must contain 51% or more of wholegrain in them.

Australia also needs good definitions and identification of wholegrain and cereal fibre rich foods to be applied in our marketplace, and recommendations on the amounts we should be eating to be effective in reducing risk of ill health and/or premature death.

Sources of dietary fibre

All plant foods contain plant cell walls containing dietary fibre and a range of other agents (phytochemicals, not necessarily nutrients) which are suspected of being protective or anticarcinogenic. These agents include vitamins E and Bs including folate, antioxidants (phytate, phenolics, diphenolics or lignans, and polyphenolics), minerals and trace elements (eg selenium which is an effective anticarcinogenic agent).

Vegetables and fruits are modest providers of dietary fibre (40%), soluble and insoluble, whereas cereals are potentially major contributors (45%), as well as being valuable sources of anticarcinogens.

That is providing most of the fibre and associated components in the outer layers of grain have not been milled off and removed, which can happen. Otherwise known as aleurone/subaleurone (bran layer), these outer protective layers are good sources also of protein and essential fats, vitamins, minerals, phytate and polyphenolics. Fibre is in fact a useful marker of their presence in a food, provided the fibre itself hasnít been further refined

Cereal fibre-rich foods are therefore ones that have also retained most of these valuable factors. Millers refer to high extraction and low extraction in relation to removal of the grain (up to 20-40% can be extracted). The reasons for this removal are to do with avoidance of antinutrients and other factors, eg fats which can increase rancid or off flavours. Also they can influence manufacturing processes and quality control.

What Is A Cereal Food?

High fibre cereal implies unrefined or high extraction cereal food, eg wholemeal flour products. Most grains have a white centre to the grain consisting largely of starch or energy stores. Brown or wholemeal bread is made from high extraction flour, white bread from low extraction flour, from here on referred to as refined.

According to a report on the European Consensus Conference in the European Journal of Cancer Prevention (vol. 6: page 512, 1998), food groups rich in whole cereals and cereal fibres need better definition for food intake studies. Future food studies should analyse for food groups, eg cereals, rather than nutrients or anutrients.

A diet rich in high fibre cereal is associated with a reduced risk of colorectal cancer (CRC)

A consensus statement prepared in Italy in 1998 by 17 European cancer experts has provided an important benchmark with regard to agreement regarding the evidence for protection based on case control studies. Cereal fibre-rich foods have been shown to lower risk of CRC (odds ratio of 0.66 for men and women), based on a meta-analysis of case control studies. With careful analysis of 19 studies which measured cereal foods, 16 showed an inverse association between cereal fibre intake and colon cancer. Three showed no relationship. Breast cancer studies showed a lesser response (odds ratio of 0.88 for cereal foods intake), and was therefore referred to as suggestive evidence only.

Interestingly, no relationship was seen between fruit and starchy root vegetable intake and these cancers.

Relative Risk Factors for Colon Cancer

According to Sandler et al (1996) GI Clinics of North America 25:717, a high red meat diet moderately increases the risk of colon cancer, with modest increases in risk attributed to alcohol, high sucrose, cholecystectomy and high fat diets. Factors moderately decreasing the risk were found to be high physical activity and aspirin, with modest decreases attributed to high intakes of vegetables/fruit, cereal fibre, folate/methionine, and carbohydrates.

Clearly a high fat/low dietary fibre diet is a calorie rich diet and this has been shown repeatedly in animal studies to promote cancer. However, some fats, eg fish oil, and some fibres, eg some soluble fibres, appear to contradict this generalisation, probably due to specific effects. Insoluble fibre is generally recognised as protective in colon cancer, and cereals offer the best source.

Protective Mechanisms of Dietary Fibre

Following on from the fibre hypothesis first stated by Burkett and Trowel 30 years ago, here are the mechanisms by which dietary fibre and fibre rich foods are considered to act in anticancer terms.

Dietary fibre has a significant bulking effect in the colon and stool as a result of undigested fibre and microbiological activity. The degree of bulking is determined by the type/source of fibre - wheat and rye have a significant bulking effect (x 5.4) relative to pectin (x 1.2) from apples and oranges.

Bulking offers dilution of mutagens and other toxic metabolites in the gut as well as reducing transit time, also an important factor. Cummings et al (1992) reported that in a 23 population study that risk of colon cancer was in inverse proportion to daily amount of stools produced. Bulky stools are associated with reduced transit time.

Another effect of dietary fibre in wheatbran is its ability to bind certain toxic metabolites, such as secondary bile acids, oxidised fatty acids and mutagens and carcinogens, and remove them from the bowel. This binding ability has not been found to the same degree with fruit and vegetable fibres.

Fermentation of fibre is another mechanism. The generation of short chain fatty acids by bacterial breakdown of fibre can have interesting effects in the large bowel, increasing moisture content and lowering pH, which reduces solubility of some mutagens (eg. secondary bile acids). One of these fatty acids called butyrate has a powerful effect on colon epithelium, at high concentrations increasing differentiation and destroying mutated cells (apoptosis). It is an essential energy source for colon cells.

Animal studies

The 1,2-dimethylhydrazine hydrochloride (and azoxymethane) model of colon cancer in rats and mice relies on the induction of colon cancer by free radicals released from this chemical. Incidentally, DMH a procarcinogen can be found in some rocket fuels, some mushrooms, cigarette smoke and cycad nuts.

When used in disease-free high fat rats with purified diets, it is possible to provide a controlled medium in which studies can be run to identify protective components in the diet. CSIRO research has shown wheat bran, whole wheat and barley bran are all protective in this model, reducing risk by approximately 50% relative to cellulose as the source of fibre.

Fecal butyrate correlated inversely with intestinal tumor incidence in DMH induced rats, and was highest in feces of rats ingesting wheat and barley bran at 5% dietary fibre or in human terms, 25g of dietary fibre per day.

Resistant Starch (High Amylose) Study on Human Bowel Function

Along with the dietary fibre which may include resistant starches (they are not digested in the small intestine), a number of phytochemicals which are non-nutrients (having nevertheless significant functional effects in the large bowel) come from amylose forms of starch (long unbranched polysaccharides).

A published CSIRO study of a resistant starch-rich maize flour called Hylon 7ô (Starch Australasia Pty Ltd), found that when hylon 7 was included in significant amounts in cereal foods to men and women it produced a significant increase in fecal water butyrate and reduction in fecal water deoxycholate (a secondary bile acid), relative to low RS foods.

This we interpreted as showing a possible reduction in risk of colon cancer. However this is a preliminary result, and more research is needed to fully understand the implications of increasing resistant starch in the human diet, as well as understanding the influence of differing forms of RS, (inaccessible, chemically modified).

Phytochemicals Associated with Cereal Fibre

Four groups have been studied, although there are many more. These are richly represented in the outer aleurone and subaleurone layers of cereals. While dietary fibre is a useful marker for these layers, in functional terms it represents only a fraction of the protective components. Many of these phytochemicals have antioxidant effects, ie they prevent the production of free radicals (active oxygen species).

Phytate is a powerful binder of metals, including zinc and iron, which can promote the production of free radicals. Its antioxidant effect may relate to this. It has been shown to reduce colon cancer incidence when provided in drinking water to rats at 1% Na phytate. It also reduced cell proliferation in the gut wall, a marker of inflammation and increased vulnerability toward cancer. Cereals contain significant levels of phytate, as do also nuts and legumes such as soybean.

Phenolics, present in the outer layers of cereals, fruits and vegetables, are thought to provide protection. They are also antioxidant, and although present in low concentrations, 70-90ppm total, they may together offer significant protection. Protocatechuic acid (PCA) is the most powerful antioxidant (PCA>chlorogenic>gentisic>ferulic>vanilin>syringic>p coumaric), and is capable of significantly reducing colon cancer in the rat AOM model in proportion to the concentration in the diet.

Lignans: Another group of compounds present are the lignans or diphenolics of which there are a number, and two in particular which have an estrogenic like structure and effect: matairesinol and secoisolariciresinol.

Lignans have a number of possible functions, are metabolised to mammalian lignans enterodiol and enterolactone by gut bacteria, and these lignans are thought to be the actively functional molecules.

As they influence estrogen activity, lignans are thought to be of particular relevance to hormonally sensitive cancers such as breast and prostate cancers. Herman Adlercreutz who has been a significant researcher in this area over years has shown daily urinary enterolactone excretion was directly proportional to grain fibre ingestion in postmenopausal women studied.

A significant 1997 study by David Ingram and colleagues of Perth reported the results of a case control study involving 144 pairs of women, half of whom had breast cancer diagnosed. Their diets were analysed carefully and three 24 hour urine samples were provided for lignan/isoflavone analysis. This study reported an inverse correlation between enterolactone excretion and equol excretion and breast cancer risk, with the highest excretors having approximately 1/3 the risk of breast cancer. Because it was important that a good gut flora was present any recent intake of antibiotics excluded them from urine sampling for six weeks, to allow the gut flora to return to normal.

Phytosterols: effective also in colon cancer prevention, according to animal studies.

Coronary heart disease deaths inversely related to total and cereal fibre intake

Pietinen and coworkers reported from Finland results of the ATBC Cancer Prevention trial, which ran over six years and included 21,930 men all smokers between the ages of 50-60 years at entry.

A 276 food item dietary questionnaire was used as part of the study. There were 1399 CHD events (581 were deaths) in the study. Intake of dietary fibre ranged two fold between the highest (34.8g/d) and lowest (16.1g/d) quintile. Incidentally, a major contributor was rye, with the highest group of cereal foods being 161g rye/day. There was an inverse association between total dietary fibre and CHD events. For total dietary fibre energy adjusted the RR was 0.84. Coronary deaths were more strongly negatively associated with total dietary fibre. They were also significantly inversely associated with soluble and insoluble cereal fibre (RR 0.77). An unusual feature of this study besides its large size was the relatively large range of fibre intakes, which significantly increased the power of the study. The overall mean fibre intake for the study was 18.9g insoluble fibre and 5.4g soluble fibre/day, close to that reported for Australians (ABS ,1995).

David Jacobs and coworkers have published two papers about the Iowa Womenís Health Cohort Study, which related risk of coronary heart disease deaths to whole grain intake. 34,492 menopausal women were followed for nine years, of whom 3320 women died, 438 from CHD. A 127 food item food frequency questionnaire was used. There was a striking inverse association of whole grain intake with risk of death from heart disease. Age and energy adjusted relative risks from lowest to highest quintiles of whole grain intakes were 1.0. 0.99, 0.58, 0.45, 0.60 (p for trend was 0.0002). For refined grain food intakes there was no significant association (p= 0.57).

The types of wholegrain foods responsible included were mainly wholemeal and dark breads and wholegrain breakfast cereals. Popped corn and cooked oatmeal were other contributors.

Recommendations

In summary, I have reviewed a little of the evidence with regard to the potential of wholegrains to offer protection and risk reduction against colon and breast cancers and coronary heart disease. The evidence is very promising for disease risk reduction. Clearly refined cereal food products offer little other than energy by comparison. Risk reduction could be as much as halved by choosing wholegrain options in place of other cereal food choices on a regular basis.

 

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