Toxic Effects in Scorbutic Guinea Pigs Produced by Large Doses of Thiamin. ∗

Abstract

During the study of the effects of administration of thiamin to scorbutic and non-scorbutic animals, it was observed that young scorbutic pigs fed large amounts of thiamin sometimes develop irreversible symptoms after the resumption of a normal diet. The strength of the jaw muscles decreases and the animals are unable to chew their food properly, although they appear hungry and persistently try to eat. There is also decreased control of jaw muscles and the animals often spend long periods with jaws constantly opening and closing in a rapid chewing motion. This condition sometimes becomes permanent until death. The lack of muscle control is also often manifested by a shivering movement of the face accompanied by chattering of the teeth. In some cases the mouth is distorted and the muscles involved are in spastic contraction, causing the animals to claw the face in attempts to relieve the spasm. These muscle dyscrasias are usually accompanied by increased salivation or loss of saliva which may be due to difficulty in swallowing.

The symptoms, once established, have been found irreversible and the animals inevitably die. Attempts to avert death by forced feeding, administration of large amounts of synthetic ascorbic acid or by offering green food have failed to keep the animals alive longer than one month.

Death is not primarily due to starvation, for if the food offered is well macerated these animals consume amounts normal for their size. At death the animals are extremely emaciated. (Pigs weighing 400 g initially, decreased to 270-300 g). At autopsy macroscopic hemorrhagic areas are found to vary inversely with the length of time the animals have lived after the onset of symptoms.

Several methods of producing the thiamin effect have been tried. The procedure giving the highest incidence was as follows: