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The Mechanism of the Thiamine-Sparing Effect of Penicillin in Rats¹

Graduate School of Nutrition, Cornell University, Ithaca, New York

By means of a technique for the complete prevention of coprophagy in the rat it has been possible to study the mechanism by which an antibiotic, penicillin, spares thiamine. The following conclusions have been drawn:

1. Thiamine which is synthesized in the intestinal tract is not directly absorbed, but is utilized only after excretion in the feces, and the ingestion of those feces.

2. No significant quantity of free thiamine is released in that region of the upper intestine where absorption takes place.

3. The sparing of thiamine by penicillin and by certain dietary carbohydrates is abolished when coprophagy is prevented.

4. Penicillin does not alter the extent of thiamine absorption from the intestinal tract nor does it affect tissue requirements.

5. Penicillin in the diet increases the amount of thiamine synthesized in the large intestine and is reflected by an increase in fecal thiamine.

6. This increase in fecal thiamine can account entirely for the growth response observed, since penicillin does not alter the proportion of fecal thiamine available to the rat.

7. Approximately 35% of the total thiamine excreted in the feces is utilized by the rat when the feces are eaten.

8. The minimal thiamine requirement for optimal growth during the first three-weeks' post-weaning in the rat, during which coprophagy is prevented, has been calculated to be approximately 9 µg of thiamine hydrochloride per day.

Manuscript received 20 January 1960.