Brain-Damaging Potential of Protein Hydrolysates

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Abstract
Casein and fibrin hydrolysates commercially available for use in human parenteral alimentation therapy were administered subcutaneously to 90 10-day-old mice at five doses (20, 40, 60, 80 and 100 μl per gram of body weight). Casein hydrolysate at each dose tested and fibrin hydrolysate at 80 and 100 μl per gram induced acute degeneration of neurons in the developing hypothalamus. Hypothalamic lesions were identical to those occurring in various animal species after oral or parenteral administration of acidic amino acids such as glutamic, aspartic and cysteic acids. A control amino acid mixture excluding glutamic, aspartic and cysteic acids induced no brain damage in similar experiments on 30 additional mice. A relatively low combined concentration of acidic amino acids thus appears to be one of the criteria that a parenteral alimentation preparation should meet to be maximally safe as well as nutritionally effective. (N Engl J Med 289:391–395, 1973)