I-Methylhistidine Excretion by Vitamin E-deficient Rabbits*

The creatinuria of rabbits maintained on the diet of Goettsch and Pappenheimer (l), which was first reported by Morgulis and Spencer (2), has been considered by most investigators to be the earliest detectable sign of nutritional muscular dystrophy. Increased urinary excretion of creatine usually is observed in vitamin E-deficient rabbits several days before the appearance of the physical signs of nutritional muscular dystrophy described by Mackenzie and McCollum (3) and can be reversed if the animals are placed on a complete diet (2) or a diet supplemented with cr-tocopherol (3). As an adjunct to studies in this laboratory dealing with metabolic changes in tissues of vitamin E-deficient rabbits, urine specimens from many of these animals were analyzed routinely for creatinine, creatine, and amino acids. A major result of these urine studies to be reported here was the observation that after about a week on the vitamin E-deficient diet, and generally before the appearance of creatinuria, the rabbits began excreting easily detectable and progressively increasing levels of l-methylhistidine. This methylhistidinuria has been reported in preliminary papers (4, 5), and confirmed by McManus (6). Earlier data of Dinning et al. had shown an increased urinary amino acid nitrogen excretion in nutritional muscular dystrophy of the rabbit (7) and the monkey (8), but changes in individual amino acids were not determined. Several investigators have studied urinary amino acids in human patients with progressive muscular dystrophy. Thus, Ames and Risley (9) reported an aminoaciduria; Hurley and Williams (10) found increases in threonine, valine, leucine, arginine, and taurine in urines from dystrophic males; Blahd et al. (11) noted that dystrophic patients and their close relatives showed an increased tendency to excrete detectable levels of various ninhydrin-sensitive substances including, in female subjects, methylhistidine.