Resistant starch--an adjunct to oral rehydration solution: not yet ready for prime time.

Abstract

Oral rehydration therapy for the treatment of acute diarrhea has been acclaimed as one of the most important therapeutic advances of the past century (1). The development of oral rehydration solution (ORS) some 4 decades ago was an immediate consequence of physiologic studies of glucose-stimulated Na absorption in the small intestine in humans and experimental animals. The physiologic basis for ORS was the demonstration that absorption and secretion are separate and distinct processes in the intestine; cyclic nucleotides induce fluid secretion without affecting glucose-stimulated Na absorption; and glucose enhances Na and fluid absorption without modifying fluid secretion. Oral rehydration therapy, using a relatively isoosmolar glucose-electrolyte solution with the addition of a base (either bicarbonate or citrate), rapidly became adapted throughout the developing world and was found to reduce substantially the morbidity and mortality of acute diarrhea in children, especially in those younger than 5 years. The efficacy of the standard World Health Organization (WHO)-ORS was based on the correction of the dehydration and metabolic acidosis that occurs during an episode of severe diarrhea, e.g., cholera. Unfortunately, WHO-ORS did not dramatically reduce stool output (i.e., diarrhea), so during the next 20 years there were multiple efforts to develop a “super” or “supersuper” (i.e., an improved ORS that would reduce diarrhea, in addition to its correction of dehydration and metabolic acidosis). Most of these efforts focused on the inclusion of different dietary substrates and were directed to stimulation of Na absorption in the small intestine. Thus, several studies evaluated amino acids without evidence of dramatic improvement compared with the gold standard of WHO-ORS. Additional studies with food-based sources of glucose (e.g., rice-based, cereal-based ORS) demonstrated improved efficacy in the treatment of acute diarrhea (2). In general, these newly developed ORSs were found to be most effective in adults with cholera but substantially less so in children with diarrheal episodes secondary to noncholera etiologies. These different foodbased ORSs all contained polymers that, following their digestion by pancreatic and intestinal enzymes, resulted in glucose production. As a consequence, these solutions frequently were used with a reduced osmolality. Subsequent studies proposed that the primary efficacy of these food-based solutions was their hypo-osmolar composition (3). All of these solutions are generally believed to result in enhanced small intestinal fluid absorption. Nonetheless, efforts continued to develop other improved ORSs. These more recent approaches have sought to use short-chain fatty acid (SCFA)-stimulated Na absorption in the large intestine as an adjunct to glucose-stimulated Na absorption in the small intestine (4). SCFAs are not normal constituents of the diet but are produced primarily in the colon by colonic bacteria from nonabsorbed carbohydrate (5). This approach with SCFAs was based on the unexpected observation that cholera toxin and cyclic nucleotides did not inhibit SCFA-stimulated Na absorption from the colon either in vivo or in vitro (6,7). These experimental observations were surprising because the mechanism of SCFAstimulated Na-Cl absorption includes a luminal membrane Na-H exchange (NHE) that was coupled to SCFA uptake via luminal membrane SCFA-HCO3 and ClSCFA exchanges (8). Previous studies had established that intestinal Na-Cl absorption represented the coupling of Na-H and Cl-HCO3 exchanges in the luminal membrane and that cyclic nucleotides inhibit small intestinal Na-Cl absorption as a result of their inhibition of Na-H exchange. Thus, it appeared that cyclic nucleotides reduced HCO3-dependent Na-Cl absorption by virtue of their inhibition of Na-H exchange but did not affect Na-H exchange when the latter is linked to SCFAstimulation of Na-Cl absorption. Supported in part by Wellcome Trust. Journal of Pediatric Gastroenterology and Nutrition 39:325–327 © October 2004 Lippincott Williams & Wilkins, Philadelphia