Oral Therapy for Cholera: Amino Acids Added to Electrolyte Solutions Containing Rice or Glucose

To the Editor—The study by Rabbani et al. [1] demonstrating that l-histidine– supplemented rice-based oral rehydration solution (ORS) reduces diarrheal volume and duration in patients with cholera is interesting and potentially important, but the article omitted reference to the original demonstration of such an effect when an ORS of glucose and electrolytes with added glycine is used [2–4]. Similar data have been obtained in studies conducted on a more limited scale of added alanine and other potential substrates that are capable of enhancing salt and water absorption during cholera. We agree with Rabbani et al. that glycine, alanine, and possibly other sodium-transport promoters need to be studied further. Additionally, comparative efficacy, safety, and cost/ availability studies in patients with cholera (and in patients with diarrhea caused by enterotoxigenic Escherichia coli) of glucose- or rice-based ORSs with or without glycine or l-histidine—and possibly other combinations—not only are needed but are long overdue. We chose glycine as the actively transported amino acid to add to the glucoseelectrolyte–based ORS because it is cheap, widely available as a food additive, and, importantly, has the highest amino acid absorption rate in animal models (see figure 53 in Wilson [5]). In our clinical trials [2, 3], the glucose plus glycine ORS resulted in reductions in the volume and duration of cholera diarrhea of 39% and 23%, respectively. In patients with cholera caused by nonvibrio pathogens (later linked chiefly to enterotoxigenic E. coli), the respective reductions were 73% and 24%. The reductions in patients with cholera were larger than those reported for lhistidine, a finding that is consistent with animal data on absorption rates [5]; a comparative trial would be needed to confirm this. l-histidine also is an actively transported amino acid, but Rabbani et al. suggested that possible alternative mechanisms of action might be at work. If so, combinations of glucose with glycine plus l-histidine might merit testing. It should be noted that the glucose plus glycine ORS we used in 1970 [2, 3] significantly improved outcomes despite having the highest osmolality of any ORS yet tested (400 and 510 mOsm/kg), illustrating that substrate absorbability trumps osmolality in patients with cholera and nonvibrio cholera. The refocusing of scientific effort on the identification of the most effective, safe, and practical ORS (a super ORS), coupled with recognition that patients with cholera need an ORS formulation that not only rehydrates but also reduces the volume and duration of diarrhea [6], is useful.