Exogenous Creatine Research Articles

Creatine Retention Capacity of Boys in Relation to Androgen Function12

It is known that prepuberal boys and girls and adult women exhibit a creatinuria though the adult male does not. Also that the tolerance for exogenous creatine is much less in the former group than in the adult male. The difference in tolerance between the sexes is, apparently, not due to a difference in sex, per se, since some muscular women exhibit a marked capacity to retain exogenous creatine (1). It is believed that a poor creatine tolerance occurs until about the age of 13 years and parallels the physiological creatinuria of adolescence (2). Castrates, eunuchoids, aged humans and those exhibiting hypogonadism also show impaired creatine retention. Thus interest is focused on the relation of hormones to the metabolism of creatine. Remen (3) found a creatinuria in elderly men (70–90 years), one eunuch and one castrate. These behaved like infants and children in that they excreted most of the injected creatine. Thus he concludes the male gonad has a definite effect on creatine excretion.

EFFECT OF TESTOSTERONE PROPIONATE ON CREATINURIA OF EXPERIMENTAL HYPERTHYROIDISM IN MALE AND FEMALE MONKEYS1

CREATINURIA is known to occur in spontaneous and experimental hyperthyroidism in both animals and man (1, 2, 3). Palmer, Carson and Sloan (4) and Kepler and Boothby (5), have used Lugol's solution in reducing the spontaneous creatinuria occurring in exophthalmic goiter and toxic adenoma of the thyroid. The administration of testosterone propionate2 reduces the creatinuria which occurs in the eunuchoid (6) and in the rat as a result of creatine feeding (7). Immature and castrate male monkeys exhibit a creatinuria which can be abolished by testosterone propionate. The capacity to retain exogenous creatine is also enhanced by androgen treatment (8). Since androgens reduce or abolish creatinuria in eunuchoids and castrates, it was of interest to determine the relation of androgens to the creatinuria induced by thyroxin. Three male (2 castrate and 1 normal) and 3 spayed female rhesus monkeys (Macacus mulatta) were used in this study.

STUDIES IN DISEASES OF MUSCLE

In a previous report 1 we discussed various factors influencing the ability of patients with progressive muscular dystrophy to retain ingested creatine. In the series of twenty cases investigated the creatine tolerance was impaired so that a large part of an administered dose of creatine was excreted unchanged in the urine. The defect in the ability to retain exogenous creatine varied with the degree of muscular disability. In adult patients in the early stages of the disease as much as 82 per cent of the ingested creatine was retained, whereas in patients showing advanced muscular wasting the creatine tolerance was impaired to the extent that all the ingested dose of creatine was excreted unchanged. The amount of creatine usually administered in performing the creatine tolerance tests in our studies was 1.32 Gm. However, other workers have used widely different amounts. Thus, Boothby and his associates 2 gave 1 Gm.; one

Exogenous Arginine as the Precursor of Creatine in the Dog

Of the substances normally present in the diet, structural relationships point to arginine as the most logical precursor of creatine and creatinine. In view of the recent work of Benedict and Osterberg, who fed creatine over long periods of time, and the confirmation of their work in man by Rose, Helming and Ellis, it seemed possible that earlier attempts to demonstrate that creatine may originate from exogenous arginine failed because the amino acid was administered over too short a period to observe any significant change in the excretion of creatine or creatinine. Therefore it was decided to study the effect of arginine on the creatine-creatinine elimination, when the arginine was fed daily to a dog over a period of several weeks. After the completion of the experiment, Hyde and Rose published the results of a similar study of prolonged administration of arginine to a normal man and woman. Although their results showed no evidence of the conversion of exogenous arginine to creatine or creatinine, they have suggested that other species, particularly the pig, may differ in their response to arginine feeding. Our results presented in Table I, with another species, the dog, confirm those of Hyde and Rose, in that oral administration of arginine for a period of 35 days failed to influence the excretion of urinary creatine or creatinine, although exogenous creatine (Periods XIII and XIV) in small amounts resulted in prompt increases in both these catabolites, thus confirming the earlier work of Benedict and Osterberg. Our experiment was carried out with a trained metabolism dog, female, of about 14 kg. weight. Urine was collected by catheterization daily and analyzed for creatine and creatinine by the standard micromethods of Folin.