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The potential toxicity of corn starch fiber was assessed and compared to polydextrose, a commonly used bulking agent with a long history of safe use in the food supply. Groups of male and female Crl:CD(SD) rats were fed 0 (control), 1,000, 3,000, or 10,000 mg/kg-bw/day corn starch fiber in the diet for 90 days. The polydextrose reference article was offered on a comparable regimen at 10,000 mg/kg-bw/day. Following a single gavage dose of [ 14 C]-corn starch fiber on study day 13 or 90, the mass balance of the test article was assessed by analysis of excreta samples collected from 0 to 168 h post-dose. There were no toxicologically or biologically relevant findings in any of the test article-treated groups. The few minor differences observed between the corn starch fiber and polydextrose exposed groups were considered to be due to normal biological variation. Following [ 14 C]-corn starch fiber dosing, nearly complete excretion of the administered dose occurred over 168 h post-dosing, with the majority excreted in the feces. The dietary no-observed-adverse-effect level of corn starch fiber after 90 days was 10,000 mg/kg-bw/day. Similar toxicity profiles for corn starch fiber and polydextrose were observed due to the structural and compositional similarities of these materials., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Resistant glucan mixture (RGM), a water-soluble dietary fiber produced by the random polymerization of glucose with activated carbon as a catalyst at a high temperature, has been recently developed by our group. There has been little physiological and safety research into RGM and therefore we now present our research into its safety. A reverse mutation assay indicated that RGM is not mutagenic either with or without metabolic activation. We conducted a 90-day subchronic oral toxicity study in rats. Male and female rats fed either a 3% or 5% w/w RGM diet had no muddy or watery stools, and there was no RGM-related death in any group. Although some parameters in the 3% and 5% w/w groups were significantly different from those in the control group, these changes were not due to any toxicity from RGM. The results indicated that the No Observed Adverse Effect Level (NOAEL) of RGM was 3.3 and 3.9 g/kg body weight (BW) per day in male and female rats, respectively. We then studied the gastrointestinal effects of RGM in healthy adult humans. Gastrointestinal symptoms, such as gurgling sounds, flatus and tenesmus, were mild and transient. In men and women, the maximum no-effect dose for diarrhea was more than 0.9 g RGM /kg BW. The results of our current safety assessment studies suggest that RGM is safe for human consumption.

Organic farming does not allow the use of conventional mineral fertilizers and crop protection products. As a result, in our experiments we chose to grow different species of cereals and to see how cereal species affect mycotoxin accumulation. This study describes the occurrence of deoxynivalenol (DON), zearalenone (ZEA) and T-2/HT-2 toxin in a survey of spelt and common wheat and their bran as well as flour. The analysis was conducted using an enzyme-linked immunosorbent assay (ELISA) method. The concentrations of DON, ZEA and T-2/HT-2 in Triticum spelta and T. aestivum were influenced by species, cereal type and year interaction. The highest concentrations of these mycotoxins were found in spelt grain with glumes, in spelt glumes and in spring wheat. These results show significantly higher concentrations of Fusarium toxins in glumes than in dehulled grain, which indicates the possible protective effect of spelt wheat glumes. The lowest DON, ZEA and T-2/HT-2 concentrations were determined in spelt grain without glumes. The research shows that it is potentially risky to produce bran from grain in which mycotoxin concentrations are below limits by European Union Regulation No. 1881/2006, since the concentration of mycotoxins in bran can be several times higher than that in grain. As a result, although bran is a dietary product characterised by good digestive properties, it can become a harmful product that can cause unpredictable health damage.

Fermentation of dietary fibre by the gut microflora may enhance levels of SCFA, which are potentially chemoprotective against colon cancer. Functional food containing wheat aleurone may prevent cancer by influencing cell cycle and cell death. We investigated effects of fermented wheat aleurone on growth and apoptosis of HT29 cells. Wheat aleurone, flour and bran were digested and fermented in vitro. The resulting fermentation supernatants (fs) were analysed for their major metabolites (SCFA, bile acids and ammonia). HT29 cells were treated for 24-72 h with the fs or synthetic mixtures mimicking the fs in SCFA, butyrate or deoxycholic acid (DCA) contents, and the influence on cell growth was determined. Fs aleurone was used to investigate the modulation of apoptosis and cell cycle. The fermented wheat samples contained two- to threefold higher amounts of SCFA than the faeces control (blank), but reduced levels of bile acids and increased concentrations of ammonia. Fs aleurone and flour equally reduced cell growth of HT29 more effectively than the corresponding blank and the SCFA mixtures. The EC(50) (48 h) ranged from 10 % (flour) to 19 % (blank). Markedly after 48 h, fs aleurone (10 %) significantly induced apoptosis and inhibited cell proliferation by arresting the cell cycle in the G0/G1 phase. In conclusion, fermentation of wheat aleurone results in a reduced level of tumour-promoting DCA, but higher levels of potentially chemopreventive SCFA. Fermented wheat aleurone is able to induce apoptosis and to block cell cycle - two essential markers of secondary chemoprevention.

Recent advances in endoscopic techniques such as capsule endoscopy have revealed that nonsteroidal anti-inflammatory drugs (NSAIDs) often cause ulcers in the small intestine in humans, but there are few effective agents for treatment of small intestinal ulcers. Although the pathogenesis of NSAID-induced intestinal ulcer has been widely studied, dietary factors have seldom been considered. In the present review, the role of dietary fiber (DF) in the formation of NSAID-induced intestinal ulcers is discussed. In previous studies, small intestinal lesions were not observed when NSAIDs were administered to fasted rats, dogs, and cats, but were observed in conventionally-fed animals, suggesting the importance of feeding in the formation of intestinal lesions induced by NSAIDs. However, in animals fed diets containing low or no DF, indomethacin (IND) did not produce lesions in the small intestine, but did produce lesions in animals fed diets supplemented with insoluble dietary fiber (IDF, cellulose). The results suggest that IDF in the diet plays an important role in the formation of NSAID-induced intestinal lesions. On the other hand, addition of soluble dietary fibers (SDFs) such as pectin or mucin to regular diet markedly decreased NSAID-induced intestinal lesions. Thus, IDF and SDF have opposing effects on IND-induced intestinal lesions, i.e., IDF is harmful while SDF is protective. SDFs potentially represent a novel and safe means for protecting the small intestine against NSAID-induced intestinal lesions.

PolyGlycopleX (PGX), a novel dietary fiber, produces no mutagenic effects in bacterial tester strains Salmonella typhimurium TA 98, TA 100, TA 1535, and TA 1537 and Escherichia coli WP2 uvrA at concentrations of 0.316, 1.00, 3.16, 10.0, 31.6, and 100 microg/plate. No biologically relevant increases in revertant colonies of any of the 5 strains are observed at any concentration; however, a reduction at 100 microg/plate in TA 1537 is noted. PGX, analyzed for polychromatic erythrocyte micronuclei induction in mice following a single 1x, 0.5x, and 0.2x maximum tolerable dose intraperitoneal treatment, produces no biologically relevant increase in any dose group. Males at 1x maximum tolerable dose show a reduction of micronuclei-containing cells. High-dose animals show signs of systemic toxicity, including a reduction of spontaneous activity, rough fur, palpebral closure, prone position, and constricted abdomen. These genotoxicity studies show PGX to be nonmutagenic in both the Ames bacterial reverse mutation assay and the mammalian erythrocyte micronucleus test.

Background: This study was designed to evaluate the safety of PolyGlycopleX (PGX), a novel viscous dietary polysaccharide (fiber), when administered to Sprague Dawley(R) rats in the diet for 90 days., Methods: Groups of ten male and ten female rats each consumed PGX mixed in the diet at levels of 0, 1.25, 2.5 or 5.0% for 90 days, then evaluated for toxicological effects on parameters that included neuromotor activity, body weight, clinical chemistry, urinalysis, hematology, and histopathology., Results: Mean body weight, mean feed consumption and food efficiency in the treated groups were generally comparable to controls for both male and female rats. No changes were noted in neuromotor behavior, and histopathological analysis revealed no significant changes between treated and control animals. There were no differences in mean organ weight, organ-to-body weight or organ-to-brain weight values between controls and treated animals. Decreased red blood cell count occurred in the high dose males and increases in aspartate and alanine aminotransferase enzyme levels and triglycerides, while significant decreases in serum sodium, potassium and chloride concentrations were observed in the females fed 5.0% PGX. However, the decreased mineral concentrations may be the result of significantly increased urinary volume in both males and females at the high dose, with a concomitant decrease in urinary specific gravity (males and females) and protein concentration (females). These results were within historical control values, did not correlate with any histopathological changes, and were not considered adverse., Conclusion: The results indicate a no observed adverse effect level (NOAEL) for PGX at 5.0% of the diet, corresponding to an average daily intake of 3219 and 3799 mg/kg bw/day in male and female rats, respectively.

Rice bran glycosphingolipid (RBGSL), one of the glycosphingolipids (GSLs), has been widely used as a food additive, a base of cosmetics, and so on. As a part of the safety assessment of RBGSL, a 13-week repeated dose toxicity study was performed in Wistar Hannover (GALAS) rats. Male and female rats were divided into 4 groups consisting of 8 animals and were given 0, 60, 250, and 1000 mg/kg BW of RBGSL orally 5 times weekly for 13 weeks. During the experiment, no deaths were observed in any groups, and there were no remarkable changes in general appearance, body weight, food and water consumption, hematological and serum biochemical parameters, organ weight and histopathological findings between the control and treated groups. On the basis of these data, the no-observed-adverse effect level (NOAEL) of RBGSL in Wistar Hannover rats was considered to be 1000 mg/kg BW/ day or more.

Soluble soybean fiber (SSF) is a food ingredient intended for human consumption. SSF was administered in the diet to Sprague-Dawley CD(R) rats at concentrations up to 40,000 ppm for three months. Unformed stool was detected during the early and middle part of the treatment period and was considered an exaggeration of a normal physiological response to the fibre content in the diets, to which the animals appeared to adapt. This finding has been reported with other water-soluble fibres and was not considered an adverse effect. Decreased weight gain and food intake during the first half of the treatment period are possible sequelae of increased intestinal throughput. Adaptation was indicated by subsequently improved weight gain and food consumption. Decreased serum cholesterol occurred in males receiving 30,000 or 40,000 ppm and this has been reported before in rats fed soluble fibre. Haemoconcentration (indicated by increased erythrocyte count, haematocrit and haemoglobin concentration) and decreased spleen weight are likely related to minor fluid imbalances during exposure to high concentrations of dietary fibre and occurred at all SSF concentrations. The spleen was microscopically normal. In conclusion, the no-observed-adverse-effect level (NOAEL) for SSF in this study was 40,000 ppm (equivalent to 2.43 g/kg bodyweight/day for males and 2.91 g/kg bodyweight for females).

The cholesterol-lowering effect observed following consumption of oats and barley is attributable to the beta-glucan component of the soluble fiber fraction of these cereal grains. beta-Glucan has also been reported to modulate immune activity, however, few studies have evaluated the hematological effects of beta-glucan following oral exposure. In the current study, a concentrated beta-glucan (64%) preparation from barley (Barley Betafiber) was blended into mouse feed at concentrations of 1, 5, or 10% (corresponding to approximately 0.7, 3.5, and 7% beta-glucan) and evaluated in CD-1 mice. Plasma was collected for clinical chemistry and hematological measurements at the initiation of the study and again following 14 and 28 days of exposure. Plasma was also collected from animals that consumed the same diets for 28-days but were switched to control diet (containing no supplemental beta-glucan) for an additional 14-day period to evaluate reversibility or delayed occurrence of treatment-related changes. Half of the animals were sacrificed for histopathologic analysis following the 28-day exposure period and the other half were evaluated following the recovery period. Histopathologic analysis focused on primary lymphoid organs and lymph nodes proximal and distal to the route of exposure. An additional group of untreated animals (nai;ve) was bled and sacrificed at day 0, 14, 27 and 41 for comparison of the hematology parameters with those of the control group because it was not known if multiple blood draws would affect hematology parameters. Compared to animals consuming the control diet, no treatment-related adverse effects were observed in hematological or clinical chemistry measurements or in organ weights and immunopathology in either sex following consumption of concentrated barley beta-glucan for 28-days or following the recovery period. Likewise, no differences were observed between the nai;ve and control groups. Results from this study showed that consumption of concentrated barley beta-glucan did not cause treatment-related inflammatory or other adverse effects in CD-1 mice.

Beta-glucans are water-soluble cell-wall polysaccharides consisting of (1-->3,1-->4)-linked beta-D-glucopyranosyl monomers that comprise a considerable proportion of soluble fiber from certain grains including oats and barley. Consumption of foods containing beta-glucan or beta-glucan-enriched fractions prepared from these grains lower serum cholesterol concentrations in humans and in animal models of hypercholesterolemia. The present study was conducted to evaluate the toxicity of beta-glucan-enriched soluble fiber from barley in Wistar rats on dietary administration at concentrations of 0.7, 3.5 and 7% beta-glucan for 28 days. There were no adverse effects on general condition and behavior, growth, feed and water consumption, feed conversion efficiency, red blood cell and clotting potential parameters, clinical chemistry values, and organ weights. Necropsy and histopathology findings revealed no treatment-related changes in any organ evaluated. A dose-dependent increase in full and empty cecum weight was observed. This is a common physiological response of rodents to high amounts of poorly digestible, fermentable carbohydrates, and was of no toxicological concern. The only finding of possible biological relevance was an increase in the number of circulating lymphocytes observed in males. However, the increase was not dose-dependent and was not observed in females. Results of this study demonstrated that consumption of concentrated barley beta-glucan was not associated with any obvious signs of toxicity in Wistar rats even following consumption of large quantities., (Copyright 2003 Elsevier Science Ltd.)

We developed a branched corn syrup (BCS, average molecular weight: 500, content of indigestible portion: 45%) by heat treatment of indigestible dextrin with hydrochloric acid. To confirm the safety of BCS, we conducted both an acute toxicity test and a mutagenicity test. Moreover, we observed gastroenteric effects of BCS in fifty healthy humans. The results are summarized as follows. 1) There was no death observed after oral administration of BCS in Sprague-Dawley-strain rats. Lethal dose (LD)50, value was estimated to be more than 10 g/kg body weight. 2) No mutagenicity was observed in Salmonella typhimurium TA98, TA100, TA1535, TA1537, or Escherichia coli WP2uvrA. 3) Fifty adults were divided into five groups often (five of each sex) and orally administered BCS at 0.2, 0.3, 0.4. 0.5 and 0.6 g/kg body weight as indigestible portion. Although no diarrhea was observed in females, BCS at 0.6 g/kg as indigestible portion caused diarrhea in two out of five males. The maximum non-effective dose of indigestible portion of BCS was estimated to be 0.5 g/kg in males and more than 0.6 g/kg in females.

We investigated the preventive effect of germinated barley foodstuff (GBF) added to the diet on diarrhea induced by the dietary water-soluble dietary fibers, polydextrose, hemicellulose, and poly-acrylic acid sodium salt, in Sprague-Dawley rats. The minimum content of GBF necessary for blocking diarrhea was 3% (by weight) of the diet. Since GBF is mainly derived from the aleurone and scutellum of malted barley, we assessed the physiological effects of the aleurone and scutellum fractions derived from barley grains before and after germination. The addition of fractions containing only germinated barley, and not barley collected before germination, increased the fecal output and jejunal mucosal protein content. The effects of malted barley were very similar to those of GBF. It was concluded that germination was necessary to bring about the physiological effects of GBF. Since non-lignified hemicellulose and Gln-rich protein were newly synthesized during germination, these might have contributed to the increased fecal output and jejunal mucosal protein content.

The hypolipidaemic and antisteatotic effects of refined amorphophallus konjac (RAK) have been reported. In order to further evaluate the effect of RAK on osteoporosis in the aged female SD rats, forty one month aged female SD rats were divided into three groups: a normal diet group (S), another normal diet group (A) and a test group (B) in which the animals were fed on a diet similar to that of the normal diet group with the addition of RAK at a dosage of 1%. At the end of the sixth month of the diet treatment, all the animals in S group were killed. Animals of the other two groups were sacrificed at the end of experiments for 18 months. Blood and right femora samples were collected for serum Ca, P, and for bone mineral contents (BMC), respectively. Inorganic matter (ash content), and calcium and phosphorus contents of the left femur were measured. Meanwhile, undecalcified sections of left tibia were processed for bone histomorphometry. The results showed that trabecular bone volume (Vv), trabecular perimeters (TRP), bone mineral contents (BMC) as well as the Ca, P contents of bone were lower in A and B than in S, but no significance was found between A and B in all of the above indices. These data exhibited: (1) Similar to the postmenopausal osteoporosis in aged women, the bone mass of the aged female rats was markedly lost in A and B. (2) A diet treatment with 1% RAK would not aggravate osteoporosis.

Dietary fat, protein and fibre have been shown to modulate cancer risk in humans and the present study examined the biological effects in human-flora-associated (HFA) rats of altering intake levels within the normal human range. Two control groups, one HFA and the other germfree (GF), consumed a human diet low in fat, fibre and beef for 4 weeks; three other groups consumed human diets similar except for independent 3-fold increases in fat, beef protein or fibre. After 2 weeks on the diets, magnetically recoverable microcapsules were given orally to the rats and subsequently recovered from the faeces to assess endogenous cross-linking agents. After 4 weeks, measurements were made of gut microfloral enzyme activities, hepatic activation of dietary mutagens and hepatic DNA adducts by 32P-postlabelling. Activation in vitro of the dietary mutagens 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) by hepatic S9, formation of endogenous hepatic DNA adducts in vivo and the beta-glucuronidase activity of caecal contents were all increased in the sequence high fat > high fibre > high beef = control. Of the two DNA adducts found in all HFA rats, only one was present in GF controls, indicating that the human gut microflora (subject to human dietary modulation) either releases a DNA-adducting product able to act outside the gastrointestinal tract, or stimulates the generation of such a product by mammalian processes. Caecal nitrate reductase activity was highest in rats fed the high beef diet, whilst entrapment of cross-linking agents was highest in those fed the high fibre diet. These results show that risk-related components of human diets interact with human gut microflora to modulate the production of endogenous DNA-adducting and cross-linking substances.

A model of intra-abdominal (IA) abscess formation has been developed in mice. Intraperitoneal (i.p.) injection of a mixture of a potentiating agent (autoclaved colonic and caecal contents (ACC), 0.2 mg dry wt/mouse or sterile bran, 1 mg dry wt/mouse), Escherichia coli (1 X 10(6) colony forming units (cfu)/mouse) and Bacteroides fragilis (5 X 10(8) cfu/mouse) induced abscesses in 98% of mice inoculated. The abscesses persisted for at least 4 weeks in 60% of inoculated animals, and for 10 weeks in 36%. From 1 to 5 abscesses per mouse were found. Abscess formation was quantified by weighing the dissected abscesses and by culturing bacteria from them. Histologically, the abscesses were characterized by a central region of polymorphonuclear leucocytes, often with a thin mononuclear phagocyte infiltrate surrounding it, and an outer wall of vascularized connective tissue. Fluorescent antibody studies demonstrated that antigens from both bacterial species were distributed throughout the abscess. At the concentrations used, neither ACC nor sterile bran induced formation in the absence of viable bacteria.

The effects of unavailable carbohydrate on the cecum and colon were investigated in rats raised on diets containing 20% of glucomannan or cellulose for 8 weeks. Glucomannan ingestion caused the increase of cecum and colon weights, and the effect was greater in the cecum than in the colon. However, on ingestion of cellulose, a remarkable increase in tissue weight was observed in the colon rather than in the cecum. Measurement of DNA, RNA and protein in cecal and colonic mucosa demonstrated that the cecal enlargement caused by glucomannan was dependent on the increases in both number and size of mucosal cells, and that the cecal and colonic enlargements caused by cellulose and the colonic enlargement caused by glucomannan resulted from an increase in the number of mucosal cells; i.e., hyperplasia. (Na + K)ATPase activity of the cecal and colonic mucosa in the cellulose and glucomannan groups was significantly higher than that in the control group. Thus, (Na + K)ATPase activity was increased proportionally to the intensity of the process of tissue enlargement.

The use of diets rich in unabsorbable carbohydrate ("fiber") has been advocated for the treatment of noninsulin-dependent diabetes mellitus (NIDDM). The soluble viscous fibers such as guar gum are most effective in normalizing carbohydrate intolerance in such patients; particulate fibers such as cellulose have little or no effect. While the latter are known to affect many aspects of nutrition when consumed in great quantity, little is known of the toxicity of guar gum. Eight adults with NIDDM are reported here who consumed at least 30 grams of guar gum for at least 16 weeks without any change in hematologic, hepatic, or renal function. Serologic screening revealed no change in lipid, protein or mineral metabolism, and no change in electrolyte balance. It is concluded that consumption of 30 grams of guar gum per day for prolonged periods is without serious consequences.

The effect on intestinal carcinogenesis of feeding a 20% wheat bran dietary supplement, either during and/or after the stage of carcinogen administration with 1,2-dimethylhydrazine, was examined in 48 male Sprague-Dawley rats fed defined diets for 31 weeks. Nutrient intake and body weight gain were equivalent in all groups of animals. In the rats fed bran during carcinogen administration, tumor yield was significantly greater. Benign and malignant tumors increased by 3.4-fold (p less than 0.005), adenomas by 3.5-fold (p less than 0.025), and adenocarcinomas by 3.25-fold (p less than 0.05) over the yield found in the group fed a fiber-free diet. Consumption of wheat bran, after completion of carcinogen exposure, reduced the yield of benign adenomas by 71.4% when compared with the group fed the fiber-free diet (p less than 0.025). Those rats fed a wheat bran supplement during carcinogen administration and then switched to a fiber-free diet afterwards had the highest tumor yield, 4.5 times as many benign and malignant tumors as in those rats consistently fed the fiber-free diet (p less than 0.05) and at least 6 times as many adenomas as any of the other dietary groups (p less than 0.05). These results demonstrate that dietary wheat bran, a fiber which produces a hyperproliferative response in the colon, significantly increases colon carcinogenesis when fed to rats during the stage of carcinogen administration. This effect appears to be further enhanced when the wheat bran is totally removed from the diet following the stage of carcinogen administration. These data indicate that the hyperproliferative effects of wheat bran appear to outweigh any preventive actions that bran may have on colon carcinogenesis by altering the bulk of intestinal contents and their transit time through the bowel.

The effect of the plant cellulose metamucil on the tumorigenicity of 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) was studied in random-bred Swiss mice. Three groups of mice, which were 5, 6 and 6 weeks old at the beginning of the experiment, were given the following treatments: (1) metamucil (20%, w/w) in powdered diet for their lifespan; (2) 1,2-DMH, ten weekly subcutaneous injections at 20 mg/kg body weight; (3) combination of treatments given to groups 1 and 2. The administration of metamucil enhanced the appearance of colon tumours induced by 1,2-DMH in males only. Metamucil had no statistically significant effect on the development of tumours elicited by 1,2-DMH at seven additional sites. It was expected that a high amount of dietary fibre would inhibit carcinogenesis in the large intestine. Instead, metamucil increased the incidence of colon tumours induced by 1,2-DMH, although only in males.