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Effect of Excess Dietary L-Histidine on Plasma Cholesterol Levels in Weanling Rats^{1, 2,}

Biomedical Research Unit, Waisman Center and the Department of Nutritional Sciences, University of Wisconsin, Madison, Wisconsin 53706

Supplementation of a closed formula, cereal based stock diet with excess L-histidine at a 5% or 8% level for 4 days reduced growth and induced hepatomegaly and an increase in plasma cholesterol levels in weanling rats. The enlargement of the liver was in part due to glycogen accumulation; plasma glucose concentration was unchanged. Feeding four different amino acids (L-phenylalanine, L-glutamic acid, glycine and L-tryptophan), at levels which caused reduction of growth comparable to the 5% and 8% L-histidine supplementation, did not affect liver weight or plasma cholesterol levels. L-Threonine added, at a 2% level, to the 8% L-histidine diet did not alleviate any of the histidine effects. Rats fed a diet containing 5% urocanic acid, the first metabolite of the histidine degradative pathway, grew at a normal rate but had higher plasma cholesterol levels compared to rats fed stock diet. When rats fed L-histidine- or urocanic acid-supplemented diets were returned to stock diet, a normal growth rate was resumed immediately and plasma cholesterol levels returned to normal within 6 days. These results suggest that L-histidine and/or urocanic acid induce a hypercholesterolemia which disappears several days after the supplementation ceases.

KEY WORDS: • L-histidine • liver glycogen • plasma cholesterol • urocanic acid

¹ Supported by a grant, 5-T01-HD-00131-08, from the National Institutes of Health, United States Public Health Service.

² A preliminary report of this work was presented at the 61st Annual Meeting of the Federation of American Societies for Experimental Biology, Chicago, Illinois, April 1–8, 1977, abstract No. 4688.

³ Present address: Sigma Chemical Co., P.O. Box 14508, St. Louis, Missouri 63178.

Manuscript received 12 August 1977.