The Influence of Food Additives and Related Materials on Lower Bowel Structure and Function

Abstract

Food additives, drugs, and other chemicals are known to influence the lower gastrointestinal tract under some defined conditions, resulting in morphological alterations in the mucosa and other tissues, deranged absorption and excretion of nutrients, and, in some cases, injury to other organs and tissues as a secondary phenomenon. Generally, in rats, hamsters, and dogs, there is increased absorption and urinary excretion of calcium, soft stools or diarrhea, and cecal enlargement. In the rat, hamster, and dog, renal lesions accompany the hypercalcemia and elevated excretion of calcium. These signs, symptoms, and lesions are typical of exposure to sugar alcohols (sorbitol, mannitol, xylitol, lactitol), lactose and caramel, some of the chemically modified food starches, and synthetic polydextrose. Soft stools and diarrhea, as well as cecal enlargement and variable hyperplasia of the colon mucosa, occur frequently when substances are absorbed incompletely in the small intestine and subjected to microbial metabolism in the cecum and colon. The remarkable cecal enlargement, mucosal hyperplasia and, when present, colonic mucosal hyperplasia are reversible, even when long-standing. Renal lesions are reversible only if exposure is of short duration, before significant mineralization and scarring has occurred. Morphological and functional anomalies associated with some of these substances are described and illustrated.

Subchronic oral toxicity studies with α-cyclodextrin in rats

“…The few changes that could be attributed in this study to the a-CD treatment, are normally seen in rats fed high dietary levels of incompletely digested carbohydrates and are generally accepted to lack relevance for human safety (B€ ar, 1985;Newberne et al, 1988;WHO, 1987). In the 20% a-CD group, these changes included slightly yet significantly reduced body weights in males during the last week of the study, softer stools during the first two to three weeks of treatment (mainly in males) and a significant enlargement of the full and empty cecum.…”

Subchronic (13-week) oral toxicity study of α-cyclodextrin in dogs

“…It is generally accepted that these effects represent a physiological response to an increased load of incompletely absorbed nutrients and have no relevance to human safety (Newberne et al, 1988;WHO, 1987).…”

Adipsin, a Biomarker of Gastrointestinal Toxicity Mediated by a Functional γ-Secretase Inhibitor

“…The small intestine can be a site of injury associated with drug treatment (1)(2)(3). Tissue organization within the small intestine relies upon a small number of stem cells in the intestinal crypts to continuously produce several types of differentiated cells that together comprise the villous epithelium (enterocytes, goblet cells, paneth cells, and enteroendocrine cells) (4).…”