Viewpoints in Digestive DiseasesEnhancing clinical efficacy of oral rehydration therapy: Is low osmolality the key?☆
Section snippets
Background physiology
This review does not provide an exhaustive discussion of digestive processes and transport mechanisms in the small intestine, but a brief mention of the salient aspects may help put the focus of this review in its proper physiological perspective.
Toward a super-ORS
During the last 15 years, many clinical trials have been performed using ORSs containing complex carbohydrate as substrate in place of glucose to treat acute diarrhea of diverse etiology.55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66 These trials were performed on the basis that inclusion of complex carbohydrate would allow more substrate to be made available for cotransport without incurring an osmotic penalty.67, 68 These cereal-based ORSs, using various carbohydrate staples such as
Increased substrate availability?
Diarrhea is associated, at least temporarily, with nutritional deficits. Hence, the concept of developing energy-dense ORSs to provide “extra” calories during the fluid therapy of diarrheal disease was one of the concepts providing the impetus for the use of complex carbohydrate in ORT.72 Clinical investigators have tested the maximum quantity of rice that could be made into a drinkable ORS.56 Another reason complex carbohydrate was ever considered stems from the osmotic penalty incurred by
Kinetic advantage?
Many human and animal studies have shown that glucose oligomers may be associated with rapid glucose absorption from the small intestine compared with glucose monomer. This has been proposed as the rationale for using glucose polymer mixtures derived from starch hydrolysis as substrate in ORS. The concept of kinetic advantage was first proposed by Crane78 who, on the basis of in vitro studies, postulated sodium-independent, hydrolase-related glucose transport in which some, but not all, mucosal
Differences in small intestinal handling of glucose polymer?
Differential small intestinal handling of glucose presented as polymer compared with monomer is another possible mechanism for the enhanced efficacy of ORSs containing complex carbohydrate. Studies of starch digestion have shown that even infants and young children can absorb and digest large amounts of rice starch.90 The digestion of starch to glucose is thought to occur slowly, thereby reducing the risk of osmotic diarrhea and malabsorption.91 It has been suggested that this slow digestion of
Low osmolality?
Table 2 shows the composition of currently available ORSs in the United Kingdom and United States as well as two experimental polymeric ORSs.
ORS Na+ (mmol/L) K+ (mmol/L) Cl− (mmol/L) HCO3− (mmol/L) Citrate (mmol/L) Glucose (mmol/L) Rice derivative or glucose polymer Osmolality (mOsm/kg) WHO (formula C)a 90 20 80 — 10 111 — 311 WHO (formula B)a 90 20 80 30 — 111 — 331 BP 1993b 90 20 80 — 10 111 — 311 USP 23c 90 20 80 — 10 111 — 311 Diocalm Juniord (SmithKline Beecham,
Role of peptides and amino acids as substrate in ORT
The protein content of rice can be in the order of 11% and comprises important amino acids such as glycine (30-36 mg/100 g), lysine (30-40 mg/100 g), leucine and isoleucine (30-40 mg/100 g), and various oligopeptides.111 Oligopeptides and amino acids can promote sodium absorption independently of glucose by specific sodium-linked carrier mechanisms as discussed earlier. The protein content of wheat and other major cereal grains can be even higher than that of rice. Therefore, some of the
Luminal nutrients and epithelial recovery
In addition to the reduced stool volumes and ORS intake, some studies have shown that ORSs containing complex carbohydrate, particularly those based on rice, can also shorten the duration of the diarrheal illness and can be associated with improved growth and weight gain in affected children.122 In particular, the improvement in anthropometric indices is an important clinical outcome and may be related to an improved rate of intestinal recovery in acute diarrhea.
The exact role of specific
An intrinsic antisecretory property for rice?
Some clinical investigators have suggested on the basis of recent in vitro experiments that the decrease in stool output after treatment with rice ORS may be accounted for by a hydrophobic, nonpeptide, nonglycoprotein, low-molecular-weight (<1.5-kilodalton) moiety that may be a chloride channel blocker.71 A fraction extracted from rice inhibited cell shrinkage and chloride efflux in fresh suspended guinea pig crypt cells by inhibiting adenosine 5'-cyclic monophosphate. This effect has not yet
Hypothesis
We consider therefore that among the putative mechanisms said to underlie the enhanced clinical efficacy of ORSs containing complex carbohydrate, their low osmolality is preeminent. Recent clinical trials showing improved efficacy of hypotonic glucose monomer ORSs may indicate that it is unnecessary to decrease osmolality further by using polymers, although experimental studies in animal models would suggest that this is not the case. The final proof of the hypotonicity hypothesis, and the
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Address requests for reprints to: Michael J.G. Farthing, M.D., Digestive Diseases Research Centre, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Turner Street, Whitechapel, London E1 2AD, England. Fax: (44) 171-295-7192.