Wheat Bran Fiber Research Articles

Plant Stanol Ester and Bran Fiber in Childhood: Effects on Lipids, Stool Weight and Stool Frequency in Preschool Children

Objectives: The objective of the study was to evaluate the effects of plant stanol esters and bran fiber on lipids, stool weight and stool frequency in preschool children.Methods: The present study was a 13 week open cross-over study designed to evaluate the effects of plant stanol ester in healthy two to five year old preschool children. After a one week lead-in, eligible children were randomly assigned to begin with either Diet Phase A (plant stanol ester) or Phase B (wheat bran fiber). Each diet phase was four weeks long, followed by a two-week wash-out, and then cross-over to the alternate diet. During Diet Phase A children consumed three eight-gram servings of a spread, each containing one gram of plant stanols, for total daily dose of three grams. During Diet Phase B, children added five grams of dietary fiber to their diet for the first two weeks and then ten grams for the second two weeks.Results: Overall, for the whole study group, plant-stanol-ester spread use yielded a decrease in total cholesterol of 19.9 mg/dL (12.4% reduction from baseline) and a 14.6 mg/dL decrease in LDL cholesterol (15.5% reduction from baseline). There were no significant changes in HDL-cholesterol or triglyceride levels. A predominately insoluble dietary fiber supplement derived from wheat bran, as expected, yielded a small but non-significant decrease in total cholesterol of 6.1 mg/dL, a four percent reduction from baseline.Conclusions: Results demonstrated that preschool age children could adhere to a program requiring consumption of three daily servings of spread containing plant stanol ester and that this level of consumption resulted in a significant decrease in total cholesterol and LDL cholesterol after a four week period. In addition, consumption of plant stanol ester was not associated with any short-term adverse health effects.

Protective role of wheat bran fiber: data from marker trials

The effects of wheat bran fiber on surrogate endpoint biomarkers for colon cancer risk have been studied in rats and humans. In both species, there is little evidence that wheat bran fiber significantly modifies epithelial cell proliferation. In rat studies, however, dietary supplementation with wheat bran fiber has decreased mucosal formation of aberrant crypt foci, an important marker currently used to estimate the efficacy of colon cancer chemoprevention agents. In humans, wheat bran fiber has been shown to consistently decrease fecal bile acid concentrations, mainly by reducing toxic secondary bile acids.

Protective role of wheat bran fiber: preclinical data

Although animal data relating to the effects of dietary fiber on experimentally induced colon tumors are not easily summarized, it appears that wheat bran fiber protects against colon cancer. In a recent direct comparison, an ad libitum diet containing wheat bran fiber led to a 40% lower incidence of colon tumors, compared with a cellulose-containing diet. In addition, the greater protective effect of wheat bran fiber as compared with the cellulose was shown in rats fed 10% or 20% energy-restricted diets containing wheat bran or cellulose.

Wheat bran fiber and development of adenomatous polyps: evidence from randomized, controlled clinical trials

Mutations in oncogenes and tumor suppressor genes are thought to initiate and promote the pathway to colorectal cancer, leading to hyperproliferation, the development of adenomas, and progression to gross malignancy. Intervention at any of these steps can potentially prevent the development of cancer. Several randomized, controlled trials have investigated the effect of dietary interventions, including the addition of wheat bran fiber, on the development of adenomatous polyps. In a familial adenomatous polyposis trial, patients were treated with 4 g of ascorbic acid plus 400 mg of α-tocopherol per day alone or with a grain fiber supplement (22.5 g/day) over a 4-year period. On an actual-intake basis, the combined intervention inhibited the development of rectal polyps. However, the Toronto Polyp Prevention Trial found no significant differences in polyp recurrence rates between patients who were counseled to follow a low-fat, high-fiber diet and patients consuming a typical Western diet with placebo fiber. A 9-month study of patients with resected colon adenomas found that dietary wheat bran fiber significantly reduced total, primary, and secondary fecal bile acid concentrations and excretion rates. Such bile acid levels are thought to be related to the risk of developing cancer. The Australian Polyp Prevention Project reported that the combination of fat reduction and a supplement of wheat bran reduced the incidence of large colorectal adenomas. These latter results suggest that intervention with a low-fat wheat bran supplemented diet inhibits the transition from smaller to larger adenomas, which may be a critical step in determining which adenomas progress to malignancy.

Implementation of dietary modifications

Recommendations for dietary fiber intake for adults fall within the range of 20–35 g/day, or 10–13 g/1,000 kcal. However, popular U.S. foods are not high in dietary fiber, and common serving sizes of grains, fruits, and vegetables contain only 1–3 g of dietary fiber. In spite of the widespread dissemination of the recommendations for fiber consumption, however, the usual intake of dietary fiber in the United States remains lower than these recommended levels, averaging only 14–15 g/day. It is generally recommended that constipation be treated with a concentrated source of insoluble fiber, and cholesterol can be lowered with soluble fiber, as suggested by claims made for oat bran and psyllium. Scientific evidence supports the role of wheat bran fiber in reducing the risk of colorectal cancer, yet this message needs to be delivered to the average consumer. Most surveys suggest that coarse, brown fiber is not well accepted, as consumers say such foods “taste bad.” Implementation of guidelines for increased intake of wheat bran fiber will require public education on the importance of this recommendation. Further, consumers need to be convinced that wheat bran fiber can taste good by the development of a wide range of products high in wheat bran fiber that can be consumed throughout the day.

Potential protective mechanisms of wheat bran fiber

Experimental studies using high-fiber supplements show that of all the fibers tested, wheat bran is the most effective in protecting against colon tumor development. The mechanisms behind this protective effect have not been elucidated completely, and the effect is most likely multifactorial. Some mechanisms, such as luminal dilution of potential carcinogens and accelerated transit through the colon, are well established. The fermentation of wheat fiber to short-chain fatty acids—especially butyric, which has been shown to inhibit tumor growth in vitro—is documented, but interpretation of the data from animal studies and clinical trials is subject to debate. Several potential mechanisms, such as effects of phytochemicals and phytates contained in wheat bran, have not yet been explored.

Progress report: the Arizona phase III study of the effect of wheat bran fiber on recurrence of adenomatous colon polyps

A double-blind, placebo-controlled Phase III cancer prevention trial in subjects with previous resection of adenomatous colon polyps is nearing completion. The study’s primary objective is to evaluate the effects of daily dietary supplementation with large (13.5 g/day) versus small (2.0 g/day) doses of wheat bran fiber for 3 years. A summary of the study design and a progress report are presented.

Primary prevention of colon cancer with dietary and micronutrient interventions

Overall, colorectal carcinoma is the second leading cause of cancer death and the third most common carcinoma in both females and males in the United States. Adjusted incidence rates for whites are consistently higher than those for African Americans, whereas case-fatality rates are consistently lower for whites. Its etiology appears to be related to a complex interaction of environmental and genetic factors. Proposed dietary risk factors for colon carcinoma include excess fat intake and low intakes of fruits, vegetables, dietary fiber, calcium, and other micronutrients. Phase III clinical dietary and micronutrient trials are being conducted with the support of the National Cancer Institute for low fat-high fruits and vegetables, wheat bran fiber, calcium, folic acid, and selenium employing colonic adenoma recurrence as the primary outcome endpoint. If these studies are positive, then the implementation of dietary and/or micronutrient interventions could have an immense public health impact by reducing colon carcinoma mortality. Cancer 1998;83:1734-1739. © 1998 American Cancer Society.

Mechanisms by which wheat bran and oat bran increase stool weight in humans

Generally, stool weight is significantly increased by adding sources of insoluble fiber to the diet. Comparable amounts of fiber provided by wheat and oat brans have the same effect on daily stool output, even though > 90% of wheat bran fiber but only 50-60% of oat bran fiber is insoluble. To determine the bases for these increases in stool weight, stool samples collected from 5 men in 2 constant diet studies that determined the effects of wheat and oat brans on large-bowel physiology were fractionated by using a physicochemical procedure into plant, bacterial, and soluble fractions, which were weighed and analyzed for sugar content and composition. Nitrogen, crude fat, and ash outputs were also determined. Wheat bran increased the fecal concentration of sugars and mass of plant material more than did oat bran, whereas oat bran increased fecal bacterial mass more. Each fiber source increased nitrogen, ash, and fat excretion, but excretion of fat was greater with oat bran. The apparent digestibility of plant-derived neutral sugars decreased significantly when wheat but not oat bran was consumed. The apparent digestibility of neutral sugars provided by wheat bran was 56%; the apparent digestibility of those provided by oat bran was 96%. We conclude that bacteria and lipids are major contributors to the increase in stool weight with oat bran consumption, whereas undigested plant fiber is responsible for much of the increase in stool weight with wheat bran consumption. Results are consistent with the hypothesis that oat bran increases stool weight by providing rapidly fermented soluble fiber in the proximal colon for bacterial growth, which is sustained until excretion by fermentation of the insoluble fiber.

Short-chain fatty acids induce cell cycle inhibitors in colonocytes

Background & Aims: We tested the hypothesis that short-chain organic acids in the colon derived from dietary pectin, wheat bran, and oat bran are protective against the development of colon cancer because they induce transforming growth factor (TGF)-β1, which in turn inhibits cell growth by inducing cyclin-directed kinase (cdk) inhibitors. Methods: U4 human colon carcinoma cells differentiate into water- and salt-transporting columnar enterocytes and therefore model normal colonocytes. The composition and kinase activity of cdk/cyclin complexes were determined by immunoprecipitation and Western blotting studies in U4 cells treated in vitro with short-chain fatty acid (SCFA) mixtures that mimic the digestion products of wheat bran, oat bran, pectin, and cellulose (as control), which is largely unfermentable. Results: Induction of the cdk inhibitors p21cip1 and p27kip1 by fiber-mimicking SCFA mixtures occurs much more rapidly and is many-fold greater than their induction by TGF-β1. The SCFA mixtures most effective in causing growth inhibition and cdk inhibitor production mimicked those from wheat bran > oat bran > pectin. Conclusions: cdk inhibitor induction by SCFA mixtures is not mediated by TGF-β1. The SCFA mixture mimicking digested wheat bran fiber was the most effective of all mixtures tested in inhibiting cell growth through induction of cdk inhibitors. GASTROENTEROLOGY 1998;114:940-946

Effect of wheat bran fiber on the development of mammary tumors in female intact and ovariectomized rats treated with 7,12-dimethylbenz(a)anthracene and in mice with spontaneously developing mammary tumors.

We examined the effect of consumption of graded increases of dietary fiber (soft white wheat bran) on the development of mammary gland carcinomas in intact female Sprague-Dawley rats during the promotion stage of carcinogenesis, induced with 7,12-dimethylbenz(a)anthracene (DMBA). The percent of rats with mammary carcinomas, the total number of mammary carcinomas and the mean number of mammary carcinomas per rat were reduced significantly at all fiber levels examined compared to rats fed a control diet. Inclusion of 9.6% fiber in the diets of ovariectomized rats that had been treated with a single i.v. dose of 2.5 mg DMBA/100 g body weight 2 weeks prior to removal of the ovaries resulted in a significant decrease of carcinomatous and benign mammary tumors compared to ovariectomized rats fed a control diet. Development of spontaneous mammary carcinomas in virgin C3H/HeOuJ female mice and growth of a transplantable mammary gland tumor in such mice were reduced by inclusion of 9.6% fiber in the diet, a reduction that was significant or just barely missed significance, depending on the source of the fiber. Our observations provide evidence that inclusion of soft white wheat bran in the diet is effective in the suppression of mammary gland tumorigenesis in an array of experimental animal models.

Suppression of intestinal polyp development by low-fat and high-fiber diet in Apc(delta716) knockout mice.

Most epidemiological and animal studies show a positive correlation of the dietary intake of fat with the incidence of colon cancer, whereas an inverse correlation of the dietary intake of fiber. In rats fed a diet low in fat and high in wheat bran fiber and calcium, a significant decrease was reported in the number of azoxymethane-induced aberrant crypt foci compared with those fed a high-fat, low-fiber and low-calcium diet. Mutations in the human APC gene play a key role, not only in familial adenomatous polyposis, but also in many sporadic cancers of the entire digestive tract. We previously constructed a mouse strain Apc(delta716), carrying a truncation mutation at codon 716 of the Apc gene, the homolog of human APC (10). The heterozygous mice developed numerous intestinal polyps, and all microadenomas dissected from the earliest polyps had already lost the wild-type allele, indicating the loss of heterozygosity. Using these Apc(delta716) knockout mice, we have investigated the effect of a low-fat and high-fiber diet (LRD for 'low-risk' diet) on intestinal polyposis, and compared it with that of a high-fat and low-fiber diet (HRD for 'high-risk' diet). The mice were fed either diet for 7 weeks, and the number and size of intestinal polyps were scored. The LRD-fed mice had fewer polyps than the HRD-fed mice, by 36% in the small intestine and by 64% in the colon. As for the polyp size distribution, there was no significant difference between the HRD- and LRD-fed mice. These results indicate that LRD can suppress intestinal polyposis compared with HRD which does not, and suggest that its suppression is at the initiation of polyp formation. This is likely to be due to a decreased frequency of loss of heterozygosity, rather than a retarded growth of the polyp adenomas.

Inhibition by wheat bran cereals of the development of aberrant crypt foci and colon tumours

As variation in both type of fibre and its physical properties can influence physiological effects, the efects of different dietary levels (1, 4, 8%, w/w) of unprocessed wheat bran (WB) were compared with those of two of its processed commercial formulations used in breakfast cereals, on the formation of aberrant crypt foci (ACF) and colon tumours in Fischer 344 rats following azoxymethane (AOM) administration. All diets were high in fat (20 g/100 g) and low in calcium (0.2%, w/w). The rats were fed the experimental diets for 2 wk before receiving two sc injections of AOM (15 mg/kg body weight/wk). 8 wk following the first injection of AOM, five rats per group were killed and the formation of ACF was measured. 23 wk following the first injection of AOM, 12 rats per group were killed and the colon tumour incidence in different dietary groups was measured. The results showed that increasing the dietary concentration of fibre from 1 to 8% (w/w), using all the wheat bran formulations, significantly reduced the number of ACF per rat. None of the diets showed any significant effect on the normal growth of rats. No statistically significant differences were observed between the protective properties of WB and the two commercial formulations under investigation in terms of the reduction of the number of ACF, or in terms of the reduction of the colon adenocarcinoma incidence. The results suggest that wheat bran and its two commercial formulations can offer protection against colon cancer even when they are consumed with a high-fat/low-calcium diet. The addition of any of these formulations of wheat bran fibre is likely to be equally effective in the prevention of colon cancer in human populations that habitually consume high-fat/low-fibre Western-style diets.

Characterisation of the binding capacities and affinities of wheat bran, fruit and vegetable fibres for MeIQx, before and after fermentation

Binding capacities and affinities of dietary fibres and fermented fibre residues for MeIQx are much higher for brans than for fruit and vegetable fibres. Bran residues concentrated distally in the colon would provide a substantial binding matrix. Small intestinal conditions are not so conducive to hydrophobic adsorption.

Release of Covalently Bound Ferulic Acid from Fiber in the Human Colon

The action of wheat bran as a potential colon anticarcinogen is related partly to its low fermentability in the large intestine. Phenolic acids are highly bioactive components and also limit degradability of wheat bran in ruminants. Therefore, the solubilization of covalently bound phenolic acids during the fermentation of wheat bran in a human model colon was examined. Phenolics were only partially and relatively slowly solubilized from wheat bran, but were rapidly and fully solubilized from sugarbeet fiber; the levels of free ferulic acid in fermentation liquors remained very low and did not reflect the amounts solubilized from fiber sources. Xylanase and ferulic acid esterase activities were shown to be present. The released ferulic acid did not appear to bind noncovalently to the residual wheat bran fiber. Thus, fermentation in the gut alters the partition of esterified phenolic acids from the insoluble residue and the soluble fraction, where microbial ferulic acid esterase(s) can potentially yield fr...

Hard wheat bran and hard wheat bran fiber energy values measured in rats after 6 and 16 weeks.

The difficulties in determining the energy values of dietary fiber (DF) sources in human studies include the following: 1) The control over food intake, 2) the long-term maintenance of dietary changes (Stevens et al., 1987), 3) the cost and the large number of dietary combinations to be assessed. Models for predicting the energy value of DFs in humans have improved over the last decade (Livesey, 1995) but energy-balance experiments in animals are important due to the limited number of human studies (Livesey, 1990a). The rat model is particularly useful for long-term experiments and it has been recommended for predicting the digestibility of dietary components and energy (Bach Knudsen et al., 1994; Wisker et al.,1996).

The effects of pH and bile salts on the binding of MeIQx to wheat bran fibre

The effects of pH and of the bile salts, sodium cholate, chenodeoxycholate, taurocholate, deoxycholate and glycodeoxycholate on the adsorption of the heterocyclic aromatic amine mutagen and carcinogen 2-amino-3,8-dimethylimidazo[4,5- f]-quinoxaline (MeIQx) onto wheat bran cell wall material have been examined. The highest binding affinity of MeIQx for bran was at pH 5.5. Binding affinity declined more rapidly with pH > 5.5 than with pH < 5.5. Bile salts in solution did not appreciably affect the binding of MeIQx to bran, but where the bile salts formed a suspension then the adsorption was reduced. Where precipitation of bile salts occurred then the free concentration of MeIQx was also reduced, indicating that MeIQx binding/immobilisation could be enhanced through interaction with bile salts.

Genetic screening for colorectal cancer and intervention

There is a complex interaction between environmental/dietary factors and genetics underlying the pathogenesis of colon carcinogenesis. Little data exist concerning the impact of diet on the phenotypic expression of genetically linked colon cancer. As a result, it has been difficult to develop rationally designed dietary intervention studies in first-degree relatives of patients with established familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC) and other familial colon cancer syndromes. Only 2 double-blinded, placebo-controlled trials have been published concerning the use of preventive strategies in patients with genetically inherited colorectal cancer syndromes, both in patients with FAP. One study evaluated the effects of vitamin C plus vitamin E with or without a high-dose wheat bran fiber supplement on the recurrence of rectal adenomas. Over a 48-month intervention period, only the wheat bran fiber intervention significantly reduced polyp growth. A second study reported that intervention with the NSAID sulindac for 9 months in young patients with FAP resulted in a significant reduction in both polyp number and size in the rectosigmoid colon. All of the large-scale (i.e., >500 randomized participants) phase III nutrient or chemopreventive agent intervention studies thus far have targeted participants with a history of non-familial, sporadic colorectal adenomas. Current clinical adenoma trials do not measure whether the regimen being tested can prevent genotoxic events occurring in early stages of abnormal cell development that contribute to the eventual formation of adenomas nor whether the agent(s) can inhibit events occurring during the progression of adenomas to carcinomas. Therefore, future clinical trial designs may have to consider (i) lengthening the clinical trial period before adenomas develop, (ii) testing at early patient ages and/or (iii) measuring the growth of adenomas as they progress to carcinomas.

Genetic screening for colorectal cancer and intervention

There is a complex interaction between environmental/dietary factors and genetics underlying the pathogenesis of colon carcinogenesis. Little data exist concerning the impact of diet on the phenotypic expression of genetically linked colon cancer. As a result, it has been difficult to develop rationally designed dietary intervention studies in first-degree relatives of patients with established familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC) and other familial colon cancer syndromes. Only 2 double-blinded, placebo-controlled trials have been published concerning the use of preventive strategies in patients with genetically inherited colorectal cancer syndromes, both in patients with FAP. One study evaluated the effects of vitamin C plus vitamin E with or without a high-dose wheat bran fiber supplement on the recurrence of rectal adenomas. Over a 48-month intervention period, only the wheat bran fiber intervention significantly reduced polyp growth. A second study reported that intervention with the NSAID sulindac for 9 months in young patients with FAP resulted in a significant reduction in both polyp number and size in the rectosigmoid colon. All of the large-scale (i.e., >500 randomized participants) phase III nutrient or chemopreventive agent intervention studies thus far have targeted participants with a history of non-familial, sporadic colorectal adenomas. Current clinical adenoma trials do not measure whether the regimen being tested can prevent genotoxic events occurring in early stages of abnormal cell development that contribute to the eventual formation of adenomas nor whether the agent(s) can inhibit events occurring during the progression of adenomas to carcinomas. Therefore, future clinical trial designs may have to consider (i) lengthening the clinical trial period before adenomas develop, (ii) testing at early patient ages and/or (iii) measuring the growth of adenomas as they progress to carcinomas. © 1996 Wiley-Liss, Inc.

Randomized, Double-Blinded, Placebo-Controlled Study of Effect of Wheat Bran Fiber and Calcium on Fecal Bile Acids in Patients With Resected Adenomatous Colon Polyps

Ongoing epidemiologic and nutritional studies suggest that colorectal carcinogenesis is consistent with complex interactions between genetic susceptibility and environmental and dietary factors. Among the dietary components found to reduce colon cancer risk are high intakes of dietary fiber and calcium. We designed and conducted a randomized, double-blinded, placebo-controlled trial involving supplementation of the customary dietary intake with fiber and calcium and measurements of fecal bile acids to examine the potential mechanisms by which added dietary interventions might reduce colorectal cancer risk. In a randomized, double-blinded, phase II study, we used a factorial design to measure the effects of dietary wheat bran fiber (2.0 or 13.5 g/day) in the form of cereal and supplemental calcium carbonate (250 or 1500 mg/day elemental calcium) taken as a tablet on fecal bile acid concentrations and excretion rates. Measurements were made at base-line randomization (i.e., after a 3-month placebo run-in period using 2.0 g wheat bran fiber plus 250 mg calcium carbonate) and after 3 and 9 months on treatment in a randomly selected 52-patient subsample of the 95 fully assessable study participants who had a history of colon adenoma resection. Concentrations of fecal bile acids, total, primary (i.e., chenodeoxycholic and cholic), and secondary (i.e., deoxycholic, lithocholic, and ursodeoxycholic), were measured in 72-hour stool samples by gas-liquid chromatography. All P values resulted from two-sided tests. All geometric mean fecal bile acid concentrations and excretion rates were lower at 9 months than at 0 months or 3 months on treatment in the high-dose fiber, high-dose calcium, and high-dose fiber/high-dose calcium treatment groups. The high-dose fiber effect at 9 months of supplementation was statistically significant with respect to virtually all geometric mean fecal bile acid concentrations and excretion rates. For example at 9 months versus 0 months, high-dose fiber supplementation caused a reduction in fecal concentrations of total bile acids (52% reduction; P = .001) and deoxycholic acid (48% reduction; P = .003). High-dose calcium supplementation also had a significant, but lower, effect at 9 months versus 0 months on the geometric mean total bile acid (35% reduction; P = .044) and deoxycholic fecal bile acid (36% reduction; P = .052) concentrations. High-dose wheat bran fiber and calcium carbonate supplements given for 9 months are associated with statistically significant reductions in both total and secondary fecal bile acid concentrations and excretion rates in patients with resected colon adenomas. This study supports the hypothesis that one of the important ways in which a high intake of wheat bran fiber and calcium may reduce the risk of colorectal neoplasia and cancer is by reduction of the concentrations of fecal bile acids. Phase III studies of these agents in the prevention of adenoma recurrence are necessary to confirm this hypothesis and have now been initiated at multiple institutions.