Enhancing clinical efficacy of oral rehydration therapy: is low osmolality the key?

Many empirical clinical trials have used complex carbohydrate as substrate in oral rehydration solutions (ORSs) instead of glucose and have shown a number of important clinical benefits. Foremost among these are reduced stool volumes, shorter duration of diarrheal illness, and lower ORS intake. The underlying mechanisms to explain this clinical advantage have not been fully established, but a number of possible factors have been proposed: (1) increased substrate availability, (2) a "kinetic advantage" for glucose absorption by glucose polymer, (3) differential handling of glucose monomer and polymer by the small intestine, (4) low osmolality, (5) a separate effect of peptides and amino acids on solute-linked sodium absorption, (6) an antisecretory moiety in rice, and (6) enhanced mucosal repair and regeneration by luminal nutrients. In this report, we assess the relative contribution of these factors using evidence from laboratory-based studies, mainly in disease-related intestinal perfusion systems in animals and humans, and the relevant clinical studies available to date. We advance the hypothesis that of all the possible mechanisms proposed to underlie the enhanced clinical efficacy of complex carbohydrate ORSs, their hypotonicity plays the dominant role. If confirmed, this concept could guide future development of glucose and complex carbohydrate-based ORSs.