Wheat bran affects the site of fermentation of resistant starch and luminal indexes related to colon cancer risk: a study in pigs.

BACKGROUND: Recent studies suggest that resistant starch (effective in producing butyrate and lowering possibly toxic ammonia) is rapidly fermented in the proximal colon; the distal colon especially would, however, benefit from these properties of resistant starch. AIMS: To determine whether wheat bran (a rich source of insoluble non-starch polysaccharides), known to hasten gastrointestinal transit, could carry resistant starch through to the distal colon and thus shift its site of fermentation. METHODS: Twenty four pigs were fed four human type diets: a control diet, or control diet supplemented with resistant starch, wheat bran, or both. Intestinal contents and faeces were collected after two weeks. RESULTS: Without wheat bran, resistant starch was rapidly fermented in the caecum and proximal colon. Supplementation with wheat bran inhibited the caecal fermentation of resistant starch, resulting in an almost twofold increase (from 12.9 (2.5) to 20.5 (2.1) g/day, p<0.05) in resistant starch being fermented between the proximal colon and faeces. This resulted in higher butyrate (133%, p<0.05) and lower ammonia (81%, p<0.05) concentrations in the distal colonic regions. CONCLUSIONS: Wheat bran can shift the fermentation of resistant starch further distally, thereby improving the luminal conditions in the distal colonic regions where tumours most commonly occur. Therefore, the combined consumption of resistant starch and insoluble non-starch polysaccharides may contribute to the dietary modulation of colon cancer risk.

Modulation of fecal markers relevant to colon cancer risk: a high-starch Chinese diet did not generate expected beneficial changes relative to a Western-type diet.

In a randomized, crossover dietary intervention study, 12 Australians (of white descent) consumed a diet typical of low-income communities in China and an average Australian diet so that effects on fecal markers thought to be relevant to colon cancer risk could be compared. The Chinese diet contained 35.3 g starch/MJ daily [including 2 g resistant starch (RS)/MJ and 1.5 g nonstarch polysaccharides (NSPs)/MJ]; the Australian diet contained 12 g starch/MJ daily (including 0.8 g RS and 2.7 g NSPs/MJ). Subjects followed each diet for 3 wk. Serum cholesterol concentrations were significantly lower after the low-fat, high-starch Chinese diet than after the Australian diet (mean +/- SEM: 4.17 +/- 0.30 compared with 5.04 +/- 0.28 mmol/L, respectively, P < 0.05), a difference indicative of dietary compliance. Fecal pH was lower after the Chinese diet (6.51 +/- 0.04) than after the Australian diet (6.63 +/- 0.05; P < 0.05). For all other fecal markers examined, however, the Chinese diet produced less favorable changes, including lower fecal bulk (86 +/- 11 compared with 141 +/- 20 g wet wt/d, P < 0.01), slower transit through the gut (69 +/- 6 compared with 56 +/- 7 h, P = 0.06), lower fecal concentrations of short-chain fatty acids [72.8 +/- 7.3 compared with 98 +/- 7.6 mmol/L (including butyrate: 12.2 +/- 1.3 compared with 18.4 +/- 2.3 mmol/L), P < 0.05], and higher fecal concentrations of potentially damaging ammonia (540 +/- 50 compared with 450 +/- 40 mg/L, P < 0.01) and phenols (109.2 +/- 13.2 compared with 68.5 +/- 12.9 mg/L, P < 0.01). These results suggest that consumption of a high-starch diet alone is insufficient to reduce the risk of developing colon cancer.

Mechanisms of the intestinal effects of dietary fats and milk products on colon carcinogenesis.

Dietary fat may promote colon cancer by increasing fatty acids (FA) and secondary bile acids (BA) in the colonic lumen. These cytotoxic surfactants can damage colonic epithelial cells and thus induce a compensatory hyperproliferation of crypt cells. Our studies show that the hyperproliferative effect of type and amount of dietary fat is not simply due to changes in colonic FA and BA. This indicates that an additional, at present unknown, cytotoxic factor is involved. The hyperproliferative effect of dietary fat is inversely related to the amount of calcium in the diet. In rat and man, dietary calcium precipitates colonic cytotoxic surfactants and thus inhibits luminal cytotoxicity. These inhibitory effects on metabolic risk factors suggest a preventive effect of dietary calcium on colon carcinogenesis.

Calcium in milk products precipitates intestinal fatty acids and secondary bile acids and thus inhibits colonic cytotoxicity in humans.

Dietary calcium may reduce the risk of colon cancer, probably by precipitating cytotoxic surfactants, such as secondary bile acids, in the colonic lumen. We previously showed that milk mineral, an important source of calcium, decreases metabolic risk factors and colonic proliferation in rats. We now report the effects of the habitual intake of milk calcium on metabolic risk factors in healthy subjects. A double-blind, cross-over metabolic study was performed in 13 healthy males. Placebo milk products (calcium, 3 mM) were compared with regular milk products (calcium, 30 mm). In each 1-week period, the habitual diet was recorded, and urine and feces were collected for 1 and 3 days, respectively. Milk calcium significantly increased fecal pH and fecal excretion of phosphate (132%), total fat (139%), free fatty acids (195%), and bile acids (141%), indicating intestinal complexation. In fecal water, the concentrations of long-chain fatty acids, secondary bile acids (deoxycholic and lithocholic acid), neutral sterols, and phospholipids were about halved (P <0.05). Consistent with these changes in soluble hydrophobic surfactants, calcium decreased the cytotoxicity of fecal water from 68 +/- 9 to 28 +/- 12% (P < 0.005). Calcium in milk products precipitates luminal cytotoxic surfactants and thus inhibits colonic cytotoxicity. Therefore, habitual dietary calcium may contribute to a nutritional modulation of colon cancer risk.

Mechanism of the antiproliferative effect of milk mineral and other calcium supplements on colonic epithelium.

Recently we have shown that supplemental dietary calcium precipitates luminal cytolytic surfactants and thus inhibits colonic epithelial proliferation, which may decrease the risk of colon cancer. In Western diets, milk products are quantitatively the most important source of dietary calcium. However, they also contain large amounts of phosphate, which has been hypothesized to inhibit the antiproliferative effect of calcium. Therefore, we studied in rats the possible differential antiproliferative effects of dairy calcium, calcium carbonate, and calcium phosphate, supplemented to a Western high-risk control diet. We observed that fecal bile acid excretion was similar in the various diet groups, whereas fatty acid excretion was stimulated by the calcium supplements in the order calcium carbonate > calcium phosphate > milk mineral. In fecal water, concentrations of bile acids and fatty acids were drastically decreased in the supplemented groups, resulting in decreased cytolytic activity of fecal water. In vitro incubation of fecal water from the control group with insoluble calcium phosphate also decreased the high concentrations of surfactants and their cytolytic activity. The response of the colonic epithelium to these primary luminal effects of calcium was a decrease in cell damage and cell proliferation. Only minor differences between the supplements were observed. The concentration of serum gastrin, the possible trophic effect of which could counteract the antiproliferative effect of calcium, was increased by the supplements, but no significant correlation was observed between serum gastrin concentration and epithelial proliferation. We conclude that dietary calcium precipitates luminal surfactants and thus inhibits cytolytic activity, epithelial cell damage, and colonic proliferation. The similar efficacy of calcium carbonate, calcium phosphate, and milk mineral indicates that the antiproliferative effect of milk mineral is mediated by its calcium content and is not inhibited by phosphate.

Dietary soybean protein compared with casein damages colonic epithelium and stimulates colonic epithelial proliferation in rats.

Recently we showed that soybean protein compared with casein stimulates the fecal excretion of endogenous magnesium. In the present study we investigated whether this differential effect of soybean protein is due to intestinal epithelial cell damage and thus results in a compensating increase in proliferation of epithelial cells. Two groups of six rats were fed purified high fat, low calcium diets, differing only in the type of protein. When compared with casein feeding, soybean protein feeding stimulated the fecal excretion of magnesium, fat and fatty acids, but had no effect on the excretion of bile acids. In fecal water, the concentration of bile acids was lower when soybean protein was fed. In contrast, free fatty acid concentration, as well as luminal cytolytic activity, was higher in fecal water of rats fed soybean protein. Furthermore, epithelial cell damage and proliferation of colonic epithelium (measured as in vivo incorporation of tritiated thymidine into DNA) were greater in rats fed soybean protein. The stimulation of colonic proliferation by soybean protein is consistent with the observed increase in luminal cytolytic activity and epithelial cell damage. We conclude that the stimulatory effect of soybean protein on endogenous magnesium excretion is due to a soybean protein-specific damage of colonic epithelial cells, which results in a compensatory epithelial cell hyperproliferation.

Effects of dietary calcium and phosphate on the intestinal interactions between calcium, phosphate, fatty acids, and bile acids.

Luminal free fatty acids and bile acids may damage the colonic epithelium and stimulate proliferation, which may increase the risk of colon cancer. It has been suggested that only soluble calcium ions (Ca2+) precipitate fatty acids and bile acids, thus reducing their lytic activity. Consequently, precipitation of luminal Ca2+ by dietary phosphate should inhibit these effects. To evaluate the proposed antagonistic effects of dietary calcium and phosphate, we studied the intestinal interactions between calcium, phosphate, fatty acids, and bile acids in rats fed purified diets that differed only in the concentrations of calcium and phosphate. Increased dietary calcium drastically decreased the solubility of fatty acids in the ileum, colon, and faeces, as well as the solubility of bile acids in the colon and faeces. Although dietary calcium strongly increased the total faecal fatty acid concentration and hardly affected the total faecal bile acid concentration, the fatty acid and bile acid concentrations in faecal water were drastically decreased by dietary calcium. Consequently, the lytic activity of faecal water was decreased. Dietary phosphate did not interfere with these intestinal effects of calcium. These results indicate that dietary phosphate does not inhibit the protective effects of dietary calcium on luminal solubility and the lytic activity of fatty and bile acids.