Further Technical Aspects of KRYPTADE and ENERVADE Formulations

Carbohydrate Form:
Food digestion of reducing substances (carbohydrates such as glucose requiring the enzyme lactase for digestion) occurs predominantly in the upper small intestine. The majority of solutes and passive water absorption occurs in the lower small intestine. Absorption of fluids is glucose and/or amino-acid dependant. When infant diarrhoea cereals (rice starch) are added to electrolytes there is a reduction of faecal volumes from 18 – 36% (non-cholera v cholera origin diarrhoeas). This additional absorption occurs in the colon based on fermentation of fermentable carbohydrates to n-butyrate. Large structural carbohydrates such as resistant maltodextrins and betacyclodextrin add carbohydrates (energy) without significantly altering the tonicity as would occur with high levels of smaller carbohydrate molecules such as glucose (dextrose). Given the rate of recovery from dehydration remains a primary goal formulations of ENERVADE and KRYPTADE avoid increases in tonicity so as to avoid reduction in the rate of gastric emptying.

Infections and Damage to Intestine:
Pathological changes associated with some infections may lead to different requirements in an electrolyte formulation. Rotavirus is especially affecting the upper small intestine and responsible for a mal-absorption diarrhea, whereas cryptosporidiosis affects the lower small intestine and is a secretory and mal-absorptive diarrhea. In infants, the ideal electrolyte formulations are not found to be equivalent when measuring outcomes for secretory (mainly cholera) compared with mal-absorptive (rotavirus and cryptosporidial) diarrhoeas (Raghupathy et al 2006).
This should serve as an indication that calf scours with a secretory component (i.e. some mixed infections – and especially those with cryptosporidiosis), may not respond equivalently to different electrolyte formulations compared to mal-absorptive causes of diarrhoea (rotavirus). Some research shows rotavirus also has been shown to produce a secretory stimulating enterotoxin (Ball et al 1996). There are greater effects on acid-base balances of an osmotic (mal-absorptive) diarrhea for the higher small intestinal infections with rotavirus, compared with lower small intestinal infections with cryptosporidiosis where dehydration from mal-absorption dominates the clinical signs. (Kukuruzovic et al 2002).

Energy:
Energy of electrolytes has been indicated in terms of kcal, and typically this is derived from the addition of dextrose (glucose). This simply defines one aspect of energy without regard to specific energy requirements of tissue type, and irrespective of tissues specifically affected by infectious agents. Frequently amino-acids, in particular glycinw or alanine are added as an alternative source for intestinal Na+ energy dependent activity; though even these alternative amino-acid pathways may be affected in cryptosporidiosis (Topouchian et al 2001).

Sodium Concentration:
Recent trial work suggests that there are major effects on the rate of influx v efflux of water, sodium, and glucose by changes in the mMol concentration of sodium(Subramanya et al 2006). This work (rat model normal intestine) suggests that minor ingredients can play a significant role in rates of passage of each component and that low sodium (60mMol/litre) is preferable to 90mMol/litre. Sodium concentration interacts to have major effects on this rate of influx v efflux of glucose, and water. Particular amino-acids, specifically arginine at very low concentrations can provide a significant enhancement in rates of influx over efflux and that this is also sensitive to sodium concentrations, with lower levels of sodium having higher ratios of influx/efflux (Wapnir et al, 1997).

KRYPTADE Features:
Kryptade has

  • arginine at low concentration,
  • moderately low concentration of sodium,
  • source of glucose and glycine to aid uptake of sodium but not as total body energy source,
  • source of fermentable carbohydrate as resistant maltodextrin – 10% digestible in small intestine and 50% fermentable in large intestine to provide a source of n butyrate for colonic fluid uptake.
  • maintains a low viscosity which could affect stomach emptying, and an isotonic solution to be gentle on the recovering gut lining.
  • Seaweed flavouring to enhance flavouring.

References
Ball, JM, Tian P, Zeng C Q-Y, Morris A P, & Estes M K. (1996) Age-dependent diarrhoea induced by a rotaviral nonstructural glycoprotein. Science, 101-103.
Kukuruzovic R, Robins-Browne RM, Anstey NM, Brewster DR (2002). Enteric pathogens, intestinal permeability and nitric oxide production in acute gastroenteritis. The Pediatric infectious disease journal, 21(8), 730-739.
Raghupathy P, Ramakrishna B, Oommen SP, Ahmed MS, Priyaa G, Dziura J, Young GP, Binder HJ (2006). Amylase-resistant starch as adjunct to oral rehydration therapy in children with diarrhea. Journal of pediatric gastroenterology and nutrition, 42(4), 362-368.
Subramanya S,Ramakrishna BS, Binder HJ, Farthing MJ, Young GP (2006) Evaluation of Oral rehydration Solution by Whole-Gut Perfusion in Rats: Effect of osmolarity, sodium concentration and Resistant Starch. Jl of pediatric Gastroenterology and Nutrition 43, 568-575
Topouchian A, Kapel N, Huneau JF, Barbot L, Magne D, Tome D, & Gobert JG. (2001). Impairment of amino-acid absorption in suckling rats infected with Cryptosporidium parvum. Parasitology research, 87(11), 891-896.
Wapnir RA, Wingertzahn MA, Teichberg S (1997). L-arginine in low concentration improves rat intestinal water and sodium absorption from oral rehydration solutions. Gut, 40(5), 602-607.

Technical Aspects of Electrolyte Formulations