Oral hydration solutions in experimental osmotic diarrhea: enhancement by alanine and other amino acids and oligopeptides

doi:10.1093/ajcn/48.1.84

The American Journal of Clinical Nutrition

Volume 48, Issue 1, July 1988, Pages 84-90

https://doi.org/10.1093/ajcn/48.1.84 Get rights and content

ABSTRACT

Improvement of sodium absorption during the administration of oral hydration solutions (OHS) could increase the efficacy of formulations used in the treatment of infantile diarrhea. To test this hypothesis, selected protein breakdown products were evaluated as absorption enhancers in OHS of different osmolalities and Na-to-glucose ratios in an animal model of osmotic diarrhea induced by cathartics. A very significant increase in water and Na absorption occurred in rats with diarrhea when they were perfused with a 90-mmol/L-Na, 111-mmol/L-glucose OHS containing 30 mmol/L of L-alanine (Ala). The same effect on Na retention was observed with a protein hydrolysate (PrH) in rats with diarrhea. Glycine was not effective. Other experimental OHS were ineffective in rats with diarrhea. The data indicate that in this animal model of chronic diarrhea Na transport enhancers, such as Ala and a PrH, are most efficacious in the presence of higher Na concentration.

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Cited by (28)

Effects of protein addition to carbohydrate-electrolyte solutions on postexercise rehydration
2015, Journal of Exercise Science and Fitness
This study aimed to examine the effects of the addition of whey or casein protein, the two major proteins in milk, to carbohydrate–electrolyte (CE) solutions on postexercise rehydration.
Ten young men aged 20.7 ± 1.4 years with an average VO_2max of 60.7 mL/kg/min ran for 60 minutes at 65% VO_2max on three occasions followed by 4 hours' recovery. During recovery, the participants consumed either CE solution with 66 g/L carbohydrate (CHO), or CE plus whey protein solution (CW trial, 44 g/L CHO, 22 g/L whey), or CE plus casein protein solution (CC trial, 44 g/L CHO, 22 g/L casein); the solutions were matched for energy and electrolyte content.
The participants lost 2.36 ± 0.32% of their pre-exercise body weight after the exercise. Total urine output after recovery was greater in the CE and CC trials than CW trial (CE vs. CW vs. CC: 1184 ± 378 mL vs. 1005 ± 214 mL vs. 1256 ± 413 mL; p < 0.05). Fluid retention after ingestion of CW solution was greater than CE and CC solutions (CE vs. CW vs. CC: 46.9 ± 16.5% vs. 54.9 ± 9.2% vs. 45.8 ± 17.3%; p < 0.05). Lower urine specific gravity and urine osmolality were observed by the end of recovery in the CE trial compared with CW trial (p < 0.05). No difference was found in the changes in plasma volume in all trials.
These results suggest that during the 4 hours' recovery after a 60-minute run, the CW solution was more effective for rehydration compared with the CE or CC solution.
Increases in guanylin and uroguanylin in a mouse model of osmotic diarrhea are guanylate cyclase C-independent
2001, Gastroenterology
Background & Aims: Guanylin and uroguanylin are peptide hormones that are homologous to the diarrhea-causing Escherichia coli enterotoxins. These secretagogues are released from the intestinal epithelia into the intestinal lumen and systemic circulation and bind to the receptor guanylate cyclase C (GC-C). We hypothesized that a hypertonic diet would result in osmotic diarrhea and cause a compensatory down-regulation of guanylin/uroguanylin. Methods: Gut-to-carcass weights were used to measure fluid accumulation in the intestine. Northern and/or Western analysis was used to determine the levels of guanylin, uroguanylin, and GC-C in mice with osmotic diarrhea. Results: Wild-type mice fed a polyethylene glycol or lactose-based diet developed weight loss, diarrhea, and an increased gut-to-carcass ratio. Unexpectedly, 2 days on either diet resulted in increased guanylin/uroguanylin RNA and prohormone throughout the intestine, elevated uroguanylin RNA, and prohormone levels in the kidney and increased levels of circulating prouroguanylin. GC-C–deficient mice given the lactose diet reacted with higher gut-to-carcass ratios. Although they did not develop diarrhea, GC-C–sufficient and—deficient mice on the lactose diet responded with elevated levels of guanylin and uroguanylin RNA and protein. A polyethylene glycol drinking water solution resulted in diarrhea, higher gut-to-carcass ratios, and induction of guanylin and uroguanylin in both GC-C heterozygous and null animals. Conclusions: We conclude that this model of osmotic diarrhea results in a GC-C–independent increase in intestinal fluid accumulation, in levels of these peptide ligands in the epithelia of the intestine, and in prouroguanylin in the kidney and blood.
GASTROENTEROLOGY 2001;121:1191-1202
Proabsorptive effect of glycerol as a glucose substitute in oral rehydration solutions
1999, Journal of Nutritional Biochemistry
We hypothesized that glycerol, a readily diffusable hydrophilic substance, may effectively substitute for glucose and enhance intestinal water and sodium absorption in an oral rehydration solution (ORS). This was evaluated using a low osmolality (230–240 mOsm/kg) ORS containing 75 mmol/L sodium and a combination of glucose:glycerol (in mmol/L) 75:0, 50:25; 37.5:37.5, 25:50, 10:65, or 0:75 during 3-hour long in vivo rat jejunal perfusions. Water, sodium, potassium, glucose and glycerol absorption, and unidirectional fluid movement (J_in, J_eff) were determined. Sodium and net water absorptions were maximal at glucose:glycerol ratios between 37.5:37.5 and 10:65 mmol/L. In the absence of glucose (0:75), absorption of water and electrolytes was lower than at any other concentration. The greater net rehydration seemed to be due to a higher J_in as glycerol was increased up to 65 mmol/L. Potassium absorption followed a similar pattern. With 50 mmol/L glycerol and 25 mmol/L glucose, there was a marked expansion of the lamina propria extracellular space and increased intercellular expansion between enterocytes. These results indicate that glycerol may be an effective partial substitute for glucose in ready-to-use ORS by producing an improved rate of water and electrolyte absorption.
Diarrhea in intensive care: diagnosis and treatment
1993, International Journal of Antimicrobial Agents
Diarrhea is a common complication in critically ill patients. The use of ready-to-use sterile formulas, disposable feeding lines, and flow regulated pumps should decrease the frequency of diarrhea due to enteral nutrition. Antimicrobial agents are an important cause of diarrhea, because they modify the digestive flora and may induce Clostridium difficile colitis. Occurrence of diarrhea is also correlated with several factors reflecting the severity of the underlying disease, such as shock and sepsis. Treatment of diarrhea includes rehydratation, agents that delay transit, restoration of a normal flora, treatment of a specific cause and of the underlying disease.
Improved water and sodium absorption from oral rehydration solutions based on rice syrup in a rat model of osmotic diarrhea
1991, The Journal of Pediatrics
Rice syrup solids, rice protein, and casein hydrolysate were added to experimental oral rehydration solutions in various combinations and tested in a rat intestinal perfusion system. Chronic osmotic diarrhea was induced in juvenile rats by supplying the cathartic agents, magnesium citrate and phenolphthalein, in their drinking water for 1 week. The experimental oral rehydration solutions were compared with standard oral rehydration solutions containing 20 gm/L or 30 gm/L of glucose and with each other to determine if there were significant differences in net water, sodium, or potassium absorption. An oral rehydration solution containing 30 gm/L of rice syrup solids had a net water absorption rate significantly higher than that of the standard 20 gm/L glucose-based oral rehydration solution (2.1±0.62 versus 1.5±0.48 μl/[min x cm], p<0.05). Casein hydrolysate did not significantly affect net water absorption. However, combinations of 30 gm/L rice syrup solids and 5 gm/L casein hydrolysate significantly increased (p<0.05) net sodium and potassium absorption compared with the 20 gm/L glucose-based oral rehydration solution but not versus rice syrup solids alone. Oral rehydration solutions containing 30 gm/L rice syrup solids plus 5 gm/L rice protein, and 30 gm/L rice syrup solids plus 5 gm/L casein hydrolysate, had net water absorption rates significantly higher than the rate of a 30 gm/L glucose-based oral rehydration solution (2.5±0.36 and 2.4±0.38, respectively, versus 0.87±0.40 μl/[min x cm], p<0.05). Rice protein and casein hydrolysate, however, did not significantly affect net water, sodium, or potassium absorption when added to rice protein glucose-based oral rehydration solutions. An inverse correlation between osmolality and net water absorption was observed (r=−0.653, p<0.02). The data suggest that substitution of rice syrup solids for glucose in oral rehydration solutions will improved water absorption and that rice syrup solids in combination with protein hydrolysates may, in addition, promote better sodium and potassium uptake.
Alanine-based oral rehydration therapy for infants with acute diarrhea
1991, The Journal of Pediatrics
Twenty male infants less than 1 year of age with acute diarrhea and dehydration were randomly assigned to a study group and studied in blind fashion in a metabolic unit to assess the efficacy of the addition of 30 mmol/L alanine to the standard World Health Organization (WHO) oral rehydration solution (ORS). Patients were exclusively rehydrated with one of two types of ORS during the first 24 hours of treatment. On the second day, oral feedings were started with a lactose-free formula, and ORS was given to replace stool losses. Body weight, ORS, food intake, vomitus, stool, and urine output were recorded at 6-hour intervals. Blood was drawn at the time of admission, after rehydration, and at 24 and 48 hours of hospitalization to monitor blood gases and electrolytes. Rehydration was satisfactory in both groups of patients. ORS that contained alanine did not reduce the purging rates of the infants compared with those who received standard ORS. Clinically no adverse effect of the alanine-based ORS was observed during hospitalization. None of the patients had significant hypernatremia or hyponatremia, and serum amino acid levels were not altered. These data show that the addition of 30 mmol/L alanine to the standard WHO-ORS produces no further improvement in the outcome of the infants with acute diarrhea compared with those fed the standard WHO-ORS.

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Oral hydration solutions in experimental osmotic diarrhea: enhancement by alanine and other amino acids and oligopeptides

ABSTRACT

Am J Clin Nutr

J Pediatr

J Pediatr

J Pediatr

Biochim Biophys Acts

Biochim Biophys Acts

J Biol Chem

J Biol Chem

Biochim Biophys Acts

J Pediatr

Oral rehydration therapy (ORT) for childhood diarrhea.

Popul Rep [L]

Oral hydration therapy: recent advances.

World Health Forum

Oral therapy for dehydration in diarrheal diseases as a global problem.

J Pediatr Gastroenterol Nutr

Oral rehydration therapy in acute diarrhoea in childhood.

J Pediatr Gastroenterol Nutr

Oral rehydration of neonates and young infants with dehydrating diarrhea: comparison of low and standard sodium content in oral rehydration solutions.

J Pediatr Gastroenterol Nutr

Safe oral rehydration of hypertonicdehydration.

J Pediatr Gastroenterol Nutr

Effect ofglycine and glucose on sodium and water absorption in patients with cholera.

Gut

In search of a super oral rehydration solution: can optimum use oforganic-solute mediated sodium absorption lead to the development of an absorption promoting drug?

J Diarrhoeal Dis Res