Beneficial effect of a bile acid resin binder on enteral feeding induced diarrhea.

OBJECTIVES: Diarrhea is a complication of enteral feeding, occurring in up to 68% of critically ill patients. We hypothesized that prolonged fasting results in abnormal bile acid homeostasis. Subsequent enteral feeding then causes a relative luminal excess of bile acids, which leads to choleretic diarrhea. Hence, diarrhea induced by enteral feeding should improve with the use of a bile acid binding agent, such as Colestid Granules. METHODS: We evaluated the effect of Colestid on enteral feeding-induced diarrhea in a double-blind placebo-controlled study. Nineteen patients who were nil per os (NPO) for 5 days before initiation of enteral feeding were enrolled in the study and treatment continued for 7 days. The severity and frequency of diarrhea were quantified. Fecal bile acids were measured enzymatically. Stool nutrient loss was measured by fat extraction, microkjeldahl determination of nitrogen, and bomb calorimetry of dried fecal specimens. RESULTS: Enteral feeding resulted in a high frequency of diarrhea (95%) at some time during the observation period. The majority of episodes of diarrhea in both groups were of low volume. Colestid significantly decreased the prevalence and severity of diarrhea. Colestid had no significant effect on fecal calorie or nutrient losses. The average bile acid concentration in the stool increased significantly after enteral feeding. CONCLUSION: Enteral feeding-induced diarrhea is, at least in part, due to malabsorption of bile acids. The bile acid resin binding agent Colestid improves diarrhea induced by enteral feeding.

Effect of aspirin on prostaglandin E2 and leukotriene B4 production in human colonic mucosa from cancer patients.

Results from epidemiological studies indicate that chronic administration of aspirin reduces the incidence of colon cancer. The mechanism that accounts for this reduction is not known, but it may be related to the decreased production of prostanoids that results from aspirin inhibition of cyclooxygenase. However, it is not known whether aspirin has a local effect on prostanoid production in the colonic mucosa and whether this effect is dose dependent. In this study, we determined the effect of oral administration of aspirin on the production of the prostanoid prostaglandin E2 (PGE2) in the intact human colonic mucosa. Inhibition of cyclooxygenase could result in an increased availability of arachidonic acid and a corresponding increase in production of other eicosanoids. To determine whether such an effect occurs, we also quantitated the concentration of leukotriene B4 (LTB4) in colonic mucosal samples. Mucosal samples were obtained during sigmoidoscopy from the colons of 17 subjects with a history of colonic cancer prior to and following 60 days of self-administration of 325 mg aspirin/day and again 60 days after administration of 650 mg aspirin/day. PGE2 and LTB4 concentrations were determined by enzyme immunoassay for tissue samples that were flash frozen after removal from the biopsy forceps and also in medium that was collected from tissue samples that were incubated for 4 h following removal from the subject. PGE2 concentrations were decreased significantly in samples collected after 60 days of consumption of 325 mg aspirin. An additional 60 days of consuming 650 mg aspirin/day did not result in a further significant decrease relative to that attained after consumption of 325 mg/day. Similar results were obtained using colonic explants, and the addition of aspirin to medium further reduced PGE2 production. LTB4 in tissue and medium was not significantly different in pre-versus post-aspirin samples, with the exception of an increased concentration in medium samples collected after consumption of 650 mg/day relative to pre-aspirin samples. The results indicate that aspirin affects eicosanoid production in the colonic mucosa of humans, but the effect is most likely restricted to products of the cyclooxygenase-dependent pathway. It appears that 325 mg of aspirin is sufficient to affect PGE2 production and that increasing the dosage to 650 mg daily provides an additional decrease in PGE2 synthesis. However, the higher dosage was associated with a considerable increase in complaints of gastric discomfort. Additional study is needed to establish whether doses less than 325 mg also provide a significant decrease in PGE2 production.

beta-Carotene supplementation results in an increased serum and colonic mucosal concentration of beta-carotene and a decrease in alpha-tocopherol concentration in patients with colonic neoplasia.

The aim of this study was to evaluate the colonic mucosal beta-carotene (BC) concentration following supplementation with BC and to determine if an increase in BC concentration influences vitamin E (alpha-tocopherol) status. The concentration of BC and alpha-tocopherol was assessed in serum and colonic tissue obtained from subjects with a history of colonic polyps or resected cancer (Dukes A, B1, or B2). Serum and mucosal biopsy samples were obtained prior to and following 3 months daily p.o. supplementation with 30 mg of BC or placebo. The concentration of BC was significantly increased in serum and colonic mucosa from both polyp and cancer subjects following supplementation as compared to presupplementation values and values from subjects receiving a placebo. The concentration of alpha-tocopherol in serum from cancer subjects was significantly decreased in samples obtained at the end of 3 months of BC supplementation as compared to placebo-matched controls. In BC-supplemented polyp subjects the tissue concentration of alpha-tocopherol was also significantly decreased relative to presupplementation values. The results indicate that BC supplementation does result in a significant accumulation of BC in the colonic mucosa but that the alpha-tocopherol concentration in both serum and colonic tissue may be compromised by an increased intake of BC. The mechanism for the decrease in alpha-tocopherol in conjunction with the increase in BC will require further study in order to develop strategies which will prevent vitamin E deficiency in BC-supplemented individuals.