Are dietary fiber-induced alterations in colonic epithelial cell proliferation predictive of fiber's effect on colon cancer?

Alterations in cell proliferation of the colon have been observed as a result of changes in amount and type of dietary fiber and in relation to risk of developing colon cancer. Although some human observational and intervention studies contribute to the database, most information results from experiments on rodents. Because of numerous contradictory reports linking dietary fiber, cell proliferation, and colon cancer, we undertook a critical review of existing methods in an attempt to explain the inconsistencies. Although there may be some individual types of dietary fiber that protect against chemically induced colon cancer, dietary fiber as a single entity does not appear to afford any consistent protection. Because of significant differences in experimental protocols among laboratories, it is not yet possible to state with certainty that increases in cell proliferation, induced by fiber consumption, are predictive of increased tumorigenesis. Much of what has been observed and interpreted as elevation of risk may simply be normal homeostatic changes in cell proliferation. Even though fermentation to short-chain fatty acids is a mechanistically attractive hypothesis to explain why fiber modulates cytokinetics, data do not consistently support short-chain fatty acids as biological intermediates in risk of colon cancer. The state of the art in this field has not yet progressed to the point where a clear effect of dietary fiber on cytokinetics and colon carcinogenesis can be assessed with any degree of certainty. Additional markers of apoptosis, differentiation, and cell-cell communication may be required for a more accurate analysis of the relation among fiber, cytokinetics, and colon cancer.     

Fiber intake in different populations and colon cancer risk

It has been suggested that consumption of fiber may reduce the risk for colon cancer. A negative association has been reported between national rates of mortality from colon cancer and estimates of dietary fiber from cereals, based on the fiber content of foods available in the national diets. Total dietary fiber consumption estimated from dietary surveys also was negatively associated with bowel cancer rates in a comparison of four regions of Denmark and Finland, and nonstarch polysaccharides were negatively associated with regional cancer rates in Britain. However, no association with estimates of fiber consumption has been observed in three case-control studies, and one case-control study reported a positive association between fiber intake and colorectal cancer among women. Other epidemiological investigations have examined the relationship between bowel cancer and use of cereals, fruit, and vegetables, foods that contain fiber as well as other nutrients but have failed to produce consistent results among investigations employing different study designs. The National Academy of Sciences found in 1982 that there was "no conclusive evidence to indicate that dietary fiber exerts a protective effect against colorectal cancer in humans," and the present data still do not satisfy the epidemiological criteria required to establish beyond doubt a protective effect of fiber. Nevertheless, dietary guidelines, such as those from the National Academy of Sciences, which recommend reduced fat consumption and increased consumption of cereals, fruit, and vegetables represent the current state of knowledge and form the basis of a diet that is unlikely to do harm and may have the potential for reducing cancer rates in North America.     

Dietary fiber intake and risk factors for cardiovascular disease in French adults

BACKGROUND: Increased consumption of dietary fiber is widely recommended to maintain or improve health, but knowledge of the relation between dietary fiber sources and cardiovascular disease risk factors is limited. OBJECTIVE: We examined the relation between the source or type of dietary fiber intake and cardiovascular disease risk factors in a cohort of adult men and women. DESIGN: In a cross-sectional study, quintiles of fiber intake were determined from dietary records, separately for 2532 men and 3429 women. Age- and multivariate-controlled logistic models investigated the odds ratios of abnormal markers for quintiles 2-5 of fiber intake compared with the lowest quintile. RESULTS: The highest total dietary fiber and nonsoluble dietary fiber intakes were associated with a significantly (P < 0.05) lower risk of overweight and elevated waist-to-hip ratio, blood pressure, plasma apolipoprotein (apo) B, apo B:apo A-I, cholesterol, triacylglycerols, and homocysteine. Soluble dietary fiber was less effective. Fiber from cereals was associated with a lower body mass index, blood pressure, and homocysteine concentration; fiber from vegetables with a lower blood pressure and homocysteine concentration; and fiber from fruit with a lower waist-to-hip ratio and blood pressure. Fiber from dried fruit or nuts and seeds was associated with a lower body mass index, waist-to-hip ratio, and fasting apo B and glucose concentrations. Fiber from pulses had no specific effect. CONCLUSION: Dietary fiber intake is inversely correlated with several cardiovascular disease risk factors in both sexes, which supports its protective role against cardiovascular disease and recommendations for its increased consumption.     

Position of the American Dietetic Association: health implications of dietary fiber

It is the position of the American Dietetic Association that the public should consume adequate amounts of dietary fiber from a variety of plant foods. Populations that consume more dietary fiber have less chronic disease. In addition, intake of dietary fiber has beneficial effects on risk factors for developing several chronic diseases. Dietary Reference Intakes recommend consumption of 14 g dietary fiber per 1,000 kcal, or 25 g for adult women and 38 g for adult men, based on epidemiologic studies showing protection against cardiovascular disease. Appropriate kinds and amounts of dietary fiber for children, the critically ill, and the very old are unknown. The Dietary Reference Intakes for fiber are based on recommended energy intake, not clinical fiber studies. Usual intake of dietary fiber in the United States is only 15 g/day. Although solubility of fiber was thought to determine physiological effect, more recent studies suggest other properties of fiber, perhaps fermentability or viscosity are important parameters. High-fiber diets provide bulk, are more satiating, and have been linked to lower body weights. Evidence that fiber decreases cancer is mixed and further research is needed. Healthy children and adults can achieve adequate dietary fiber intakes by increasing variety in daily food patterns. Dietary messages to increase consumption of high-fiber foods such as whole grains, legumes, fruits, and vegetables should be broadly supported by food and nutrition professionals. Consumers are also turning to fiber supplements and bulk laxatives as additional fiber sources. Few fiber supplements have been studied for physiological effectiveness, so the best advice is to consume fiber in foods. Look for physiological studies of effectiveness before selecting functional fibers in dietetics practice.     

Dietary fiber: classification, chemical analyses, and food sources

Dietary fiber's role in the prevention and treatment of constipation has long been known, but now fiber is touted as a cure for many of the ills in Western countries. Although some data exist to relate dietary fiber intake to certain diseases, lack of agreement on what dietary fiber is and how it should be measured make interpreting the data difficult. Further, not all dietary fiber is created equal. Water-soluble fibers, such as pectin and gums, have little effect on stool weight and hence are not appropriate treatment for patients with constipation. Water-insoluble fibers, such as cellulose and hemicellulose, are most effective in aiding laxation but may also limit absorption of minerals and possibly vitamins. Wheat bran is a good source of hemicellulose; vegetables supply cellulose to the diet. Most agencies are recommending a doubling or tripling of dietary fiber intake. Typical recommendations are set at 25 to 50 grams of dietary fiber daily. Different analytical methods for dietary fiber yield conflicting fiber values, and dietary fiber values do not exist for many foods, making fiber recommendations controversial and difficult to achieve. Fiber in the diet should ideally be increased by the consumption of unrefined breads and cereals and more fruits and vegetables. Vegetarians routinely consume 40 to 50 gm dietary fiber daily without ill effect. Fiber supplements may be appropriate for some patients, but the composition of the fiber should be known and be appropriate for the disease being treated. Before fiber supplements are marketed, clinical trials should be conducted to support the use of the supplements in the prevention and treatment of disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Identifying Practical Solutions to Meet America’s Fiber Needs: Proceedings from the Food & Fiber Summit

Fiber continues to be singled out as a nutrient of public health concern. Adequate intakes of fiber are associated with reduced risk for cardiovascular disease, cancer, diabetes, certain gastrointestinal disorders and obesity. Despite ongoing efforts to promote adequate fiber through increased vegetable, fruit and whole-grain intakes, average fiber consumption has remained flat at approximately half of the recommended daily amounts. Research indicates that consumers report increasingly attempting to add fiber-containing foods, but there is confusion around fiber in whole grains. The persistent and alarmingly low intakes of fiber prompted the “Food & Fiber Summit,” which assembled nutrition researchers, educators and communicators to explore fiber’s role in public health, current fiber consumption trends and consumer awareness data with the objective of generating opportunities and solutions to help close the fiber gap. The summit outcomes highlight the need to address consumer confusion and improve the understanding of sources of fiber, to recognize the benefits of various types of fibers and to influence future dietary guidance to provide prominence and clarity around meeting daily fiber recommendations through a variety of foods and fiber types. Potential opportunities to increase fiber intake were identified, with emphasis on meal occasions and food categories that offer practical solutions for closing the fiber gap.     

Dietary intake and colon cancer: sex- and anatomic site-specific associations

A case-control study was conducted in Utah between July 1979 and June 1983 in which 231 cases of colon cancer identified through the Utah Cancer Registry and 391 controls identified through random digit dialing were interviewed. Odds ratios (OR) were calculated comparing the highest exposure categories with the lowest exposure categories. The highest quintile of body mass index (weight (kg)/height (m)2 for males; weight (kg)/height (m)1.5 for females) was associated with increased risk in both males (OR = 2.1) and females (OR = 2.3). In females, total dietary fat (OR = 1.9) and energy intake (OR = 1.5) were associated with an increased colon cancer risk after adjusting for age, body mass index, and crude fiber. Fiber was protective in females (OR = 0.5) after adjusting for age, body mass index, and energy intake, as was beta-carotene (OR = 0.5) after also adjusting for crude fiber. Adjusted risk estimates in males were 2.0 for total dietary fat, 3.8 for polyunsaturated fat, 2.1 for monounsaturated fat, 2.1 for energy intake, 2.5 for protein, 0.3 for fiber, 0.4 for beta-carotene, and 0.3 for cruciferous vegetables. Risk estimates differed by site of cancer within the colon. In males, protein (OR = 3.8) was a risk factor for cancer of the descending colon, while fats (OR = 2.7-8.8) increased the risk of cancer of the ascending colon. The hypotheses that dietary fat increases colon cancer risk while dietary fiber decreases colon cancer risk and that fat and protein may be independently associated with colon cancer risk are supported.     

Position of the American Dietetic Association: health implications of dietary fiber

Dietary fiber consists of the structural and storage polysaccharides and lignin in plants that are not digested in the human stomach and small intestine. A wealth of information supports the American Dietetic Association position that the public should consume adequate amounts of dietary fiber from a variety of plant foods. Recommended intakes, 20-35 g/day for healthy adults and age plus 5 g/day for children, are not being met, because intakes of good sources of dietary fiber, fruits, vegetables, whole and high-fiber grain products, and legumes are low. Consumption of dietary fibers that are viscous lowers blood cholesterol levels and helps to normalize blood glucose and insulin levels, making these kinds of fibers part of the dietary plans to treat cardiovascular disease and type 2 diabetes. Fibers that are incompletely or slowly fermented by microflora in the large intestine promote normal laxation and are integral components of diet plans to treat constipation and prevent the development of diverticulosis and diverticulitis. A diet adequate in fiber-containing foods is also usually rich in micronutrients and nonnutritive ingredients that have additional health benefits. It is unclear why several recently published clinical trials with dietary fiber intervention failed to show a reduction in colon polyps. Nonetheless, a fiber-rich diet is associated with a lower risk of colon cancer. A fiber-rich meal is processed more slowly, which promotes earlier satiety, and is frequently less calorically dense and lower in fat and added sugars. All of these characteristics are features of a dietary pattern to treat and prevent obesity. Appropriate kinds and amounts of dietary fiber for the critically ill and the very old have not been clearly delineated; both may need nonfood sources of fiber. Many factors confound observations of gastrointestinal function in the critically ill, and the kinds of fiber that would promote normal small and large intestinal function are usually not in a form suitable for the critically ill. Maintenance of body weight in the inactive older adult is accomplished in part by decreasing food intake. Even with a fiber-rich diet, a supplement may be needed to bring fiber intakes into a range adequate to prevent constipation. By increasing variety in the daily food pattern, the dietetics professional can help most healthy children and adults achieve adequate dietary fiber intakes.     

Dietary factors in colon cancer: international relationships

The relationship between dietary factors and mortality from colon cancer was explored by an analysis of the correlation between age-adjusted colon cancer death rates for men in 38 countries and estimates of the availability of a number of dietary components. Cereals were the only source of fiber found to be negatively associated with colon cancer mortality after adjustment for the availability of total or animal fats, or total or red meats, foods that were themselves positively associated with mortality. The estimate of dietary fiber from cereals was more closely associated with mortality than that of crude fiber. The previously postulated protective effects of vitamins C and A and of cruciferous vegetables were not supported by the international data; we found no evidence of a negative association between colon cancer mortality and availability of these dietary factors. The positive association previously reported between colon cancer and beer consumption disappeared following adjustment for animal fat.     

Dietary fiber and colon cancer: animal model studies

Support for a protective role for certain dietary fibers in the etiology of colon cancer has come from nutritional epidemiologic studies. Recommendations to increase consumption of fiber-containing food and decrease the intake of dietary fat should form the basis of a diet that is unlikely to do harm, and may have the potential for reducing the development of colon cancer, in humans. Studies examining the role of dietary fiber as an inhibitor of colon cancer in animal models appear to have provided some conflicting results, due mostly to differences in the nature and amount of carcinogen used to induce colon tumors, variation in the composition of the experimental diets, and relative difference in food intake by animals, to cite a few of the methodological problems. However, overall, the feeding of wheat bran appears to inhibit color tumor development to a greater degree than do other dietary sources of fiber.     

Dietary patterns and colon cancer in western New York.

Seven dietary patterns were identified among control subjects in the Western New York Diet Study (1975-1986) by application of principal components analysis to data from a 95-item food frequency interview. The results of case-control analyses of colon cancer risk for these patterns are presented. Cases were matched with neighborhood controls on the bases of age and sex; 205 colon case-control male and 223 female pairs were obtained. The dietary patterns and intakes of energy, total fat, and dietary fiber were examined with logistic regression for their individual contributions to risk. In males, three of these dietary patterns were associated positively with fat and energy consumption; they elevated risk for colon cancer and accounted for more risk than did the specific nutrients. Control for energy and fat intakes allowed the protective influences of additional dietary patterns to be expressed. No patterns elevated risk in women; two patterns were protective for colon cancer. Controlling for energy and fat intake enhanced the protection afforded by one of these patterns but had no influence on that of the other. Measures of foods rather than single nutrients may be more inclusive of dietary exposures to risk as well as being related more directly to underlying health behaviors. Therefore they may be better able to account for risk in diseases with multiple causation.     

Dietary patterns and colon cancer in western New York

Seven dietary patterns were identified among control subjects in the Western New York Diet Study (1975–1986) by application of principal components analysis to data from a 95‐itemfood frequency interview. The results of case‐control analyses of colon cancer risk for these patterns are presented. Cases were matched with neighborhood controls on the bases of age and sex; 205 colon case‐control male and 223 female pairs were obtained. The dietary patterns and intakes of energy, total fat, and dietary fiber were examined with logistic regression for their individual contributions to risk. In males, three of these dietary patterns were associated positively with fat and energy consumption; they elevated risk for colon cancer and accounted for more risk than did the specific nutrients. Control for energy and fat intakes allowed the protective influences of additional dietary patterns to be expressed. No patterns elevated risk in women; two patterns were protective for colon cancer. Controlling for energy and fat intake enhanced the protection afforded by one of these patterns but had no influence on that of the other. Measures of foods rather than single nutrients may be more inclusive of dietary exposures to risk as well as being related more directly to underlying health behaviors. Therefore they may be better able to account for risk in diseases with multiple causation.     

Dietary fiber in the reduction of colon cancer risk

The evidence for an inverse association between a diet of foods high in fiber and colon cancer risk is reviewed in the context of the epidemiological criteria for causality. Five criteria are assessed: consistency of the association, strength of the association, specificity of the hypothesis, temporal relationship of the association, and coherence of the association. Forty epidemiological studies, described in 55 original reports, are analyzed in terms of an association between fiber intake and colon cancer. This evaluation clearly suggests a relationship between colon cancer and diet low in fiber. The epidemiological studies focus on dietary patterns in which fiber usually occurs as a complex mixture with other foods. At present, information on the chemistry and function of various types of fiber as well as the mechanisms of cancer inhibition still is quite limited. As dietary fiber may interact with or be linked to other dietary factors, the impact of total diet and dietary interactions should be considered in studies of colon cancer risk and in dietary counseling.     

Dietary factors in colon cancer: International relationships

The relationship between dietary factors and mortality from colon cancer was explored by an analysis of the correlation between age‐adjusted colon cancer death rates for men in 38 countries and estimates of the availability of a number of dietary components. Cereals were the only source of fiber found to be negatively associated with colon cancer mortality after adjustment for the availability of total or animal fats, or total or red meats, foods that were themselves positively associated with mortality. The estimate of dietary fiber from cereals was more closely associated with mortality than that of crude fiber. The previously postulated protective effects of vitamins C and A and of cruciferous vegetables were not supported by the international data; we found no evidence of a negative association between colon cancer mortality and availability of these dietary factors. The positive association previously reported between colon cancer and beer consumption disappeared following adjustment for animal fat. (Nutr Cancer 6, 160–170, 1984)     

Dietary fiber and breast cancer

Evidence from epidemiological studies suggests that dietary fiber, as well as fat, has the potential for affecting breast cancer risk. Fiber may have a protective role because of its influence on estrogen metabolism and excretion or because of the endocrine effects of the lignans, a family of compounds formed in the intestine from fiber-associated precursors. Future research should include additional mechanistic studies and dietary intervention trials in groups of women that have a high risk of breast cancer.     

Colorectal cancer protective effects and the dietary micronutrients folate, methionine, vitamins B6, B12, C, E, selenium, and lycopene

The data reported here were obtained from the case-control arm of a large, comprehensive, population-based investigation of colorectal cancer incidence, etiology, and survival, the Melbourne Colorectal Cancer Study, conducted in Melbourne, Australia. This part of the case-control study was designed to identify dietary factors associated with colorectal cancer risk in 715 incident cases compared with 727 age/sex frequency-matched randomly chosen community controls, in which a quantitative assessment of all foods eaten was made. New data are presented on the potential of two groups of micronutrients as protective agents, namely, those involved in DNA methylation, synthesis, and repair (folate, methionine, and vitamins B6 and B12) and those with antioxidant properties (selenium, vitamins E and C, and lycopene). The adjusted odds ratios showed that for folate there was significant protection for rectal cancer in second and third quintiles of consumption but not for colon cancer, and this was similar for methionine consumption. Vitamin B6 consumption was significantly protective for both colon and rectal cancer at the higher quintiles, and this was similar for vitamin B12. Dietary selenium was significantly protective at middle quintiles of consumption at both cancer sites. Dietary vitamins E and C were statistically significantly protective for both colon and rectal cancer at all levels of consumption, and for both vitamins there was a dose-response effect of increasing protection, particularly so for colon cancer. Lycopene was not associated with colorectal cancer risk. A combined model included vitamins E, C, and B12 and selenium as micronutrients protective for colorectal cancer and folate, which, however, showed an increased risk at the highest level of consumption. These data support the proposition that a diet containing the dietary micronutrients involved in DNA methylation (folate, methionine, and vitamins B6 and B12) and some of those with antioxidant properties (selenium and vitamins E and C) may have a role to play in lowering colorectal cancer risk and also that such protection can be achieved by dietary means alone.     

Diet,body weight,and colorectal cancer: a summary of the epidemiologic evidence

Colorectal cancer is the second leading cause of cancer death in the United States, and the number of new cases annually is approximately equal for men and women. Several nutritional factors are likely to have a major influence on risk of this cancer. Physical inactivity and excessive adiposity, especially if centrally distributed, clearly increase the risk of colon cancer. Hyperinsulinemia may be an important underlying risk factor. In conjunction with obesity and physical inactivity, which induce a state of insulin resistance, certain dietary patterns that stimulate insulin secretion, including high intakes of red and processed meats, saturated and trans-fats, and highly processed carbohydrates and sugars, may increase the risk of colon cancer. There is evidence suggesting that some component of red meat may independently increase the risk of colorectal cancer, and some micronutrients may be important as protective agents. Currently, the evidence is strongest for folate and calcium. Folate may be especially important in alcohol drinkers because alcohol appears to increase the risk, particularly when folate intake is low. This interaction may be related to the antifolate properties of alcohol. In contrast to earlier studies, more recent epidemiologic studies have generally not supported a strong influence of dietary fiber or fruits and vegetables, although these have other health benefits, and their consumption should be encouraged. The majority of colon cancers, as well as many other conditions, may be prevented by lifestyle alterations in the intake of these nutritional factors, in addition to other factors, such as smoking.     

Diet and cancer of the large bowel

The incidence of large bowel cancer correlates internationally with the consumption of fat, protein or meat. Etiological hypotheses have been proposed, suggesting that a high-fat diet is related to an increased risk of large bowel cancer, while dietary fiber is claimed to have a modifying effect. However, while these hypotheses were derived from the analysis of the geographical distribution of colon cancer in humans, they are not unequivocally supported by the results of further epidemiological studies. This is particularly true for case-control studies which generally have not confirmed an association between diet and the risk of colorectal cancer at the individual level. Lack of uniformity among the findings of epidemiological studies concerned with the role of diet in the etiology of bowel cancer could be explained by 1. lack of sensitive and reproducible methods for assessment of diet in epidemiological studies, 2. lack of knowledge of the mode of action of dietary factors responsible either for the development of the tumor or for protection against it. Future epidemiological research on diet and large bowel cancer should deal with more precisely defined hypotheses in which the possible multifactorial nature of this tumor would be taken into account.     

The role of dietary phytosterols in colon carcinogenesis.

Epidemiological and experimental studies have shown that increased intake of plant foods and decreased meat consumption are correlated with a decreased risk for colon cancer. Many components of plant foods are suggested to mitigate colon carcinogenesis, including vitamins, minerals, and dietary fiber. Phytosterols are a common component of plant foods consumed in relatively large quantities by vegetarians, who are at lower risk for colon cancer development than individuals on a Western diet low in phytosterols. In addition, phytosterols have been shown experimentally to inhibit colon cancer development. Dietary cholesterol, although structurally similar to the phytosterols, is correlated etiologically to the incidence of colon cancer, with changes in serum cholesterol levels and fecal bile acid profiles suggested to increase susceptibility to colon tumorigenesis. The objective of this paper is to discuss the effect of dietary phytosterols on cholesterol and bile acid metabolism and how these effects may lead to a decreased risk for colon cancer development.     

Dietary fiber, phytoestrogens, and breast cancer.

The hypothesis that diet exerts an influence on breast cancer risk has emphasized a role for fat, and current dietary intervention trials to reduce that risk are designed specifically to decrease fat consumption to 15-20% of total calories. There is, however, mounting evidence that dietary fiber has a protective effect and may favorably modify the enhanced breast cancer risk associated with the typical American high-fat low-fiber diet. These data come largely from epidemiological studies, but a few experiments with animal models have also been performed. The mechanisms concerned probably involve estrogen metabolism and bioactivity, both by effects on the enterohepatic circulation of estrogens and the actions of fiber-associated phytoestrogens. More studies are essential to determine the specific types of dietary fiber that are likely to affect the risk of breast cancer, and an appropriate modification in fiber intake should then be added to dietary fat reduction in any future clinical intervention trials designed to demonstrate a favorable influence on breast cancer incidence.