According to the studies of Chittenden,[16] low protein diet improves the general metabolism of the body, fatigue is diminished, and bodily vigor, therefore, correspondingly increased. The expectation is, therefore, justified that the defense of the organism against deleterious substances introduced into the body is much improved by such a diet, thus increasing its resistance to poisons. Hunt's experiment on this subject, also quoted by Chittenden, lends support to this view. He found that mice fed on carbohydrates chiefly, or on foods containing only a small amount of protein, were more resistant to acetonitril. It was interesting, therefore, to inquire whether the toxicity of caffein differs under similar conditions of diet.
A fixed diet of the same calorific value was provided for all dogs of this series, but the protein content for three of the animals was approximately one-third of the amount usually fed to dogs. Caffein was at first administered subcutaneously, but all the dogs on a low protein diet developed abscesses at the site of injection, while none of those on high protein diet showed a local reaction. Feeding by mouth was then begun and continued throughout the experiment in each case. The initial dose was 50 mg per kilo, which was given daily for seven to nine days. It was then increased progressively by 25 mg per kilo; 75 mg per kilo were administered for one to two days, 100 mg for two to three days, 125 mg for one to two days, 150 mg for one to two days, and a single dose of 175 mg. It will be remarked that sometimes an interval of one day had to be allowed during which no caffein was fed.
Dog 30. Black and tan hound, male.
The dog was under observation for about eight weeks before the experiment was begun and had received a high protein diet. He was then given 50 mg caffein for nine consecutive days. On the tenth day the dose was increased to 75 mg per kilo. As no symptoms developed, this dose was increased to 100 mg per kilo, and was fed one day apart. It was then raised to 125 mg per kilo. For the first time since the drug was fed, symptoms appeared; they were noticed a few hours after feeding and persisted during the next day. Although the appetite was good, no caffein was given on this day. On the following day this dose was repeated. As the symptoms were not serious, 150 mg per kilo were given daily for the next three days, until 175 mg per kilo was reached. This dose proved fatal within six hours. Record of experiment follows:
October 9: Weight, 9 kilos, on full nitrogen diet, received daily 0.724 gram nitrogen per kilo or 87 calories per kilo, received 18 grams meat per kilo, 4 grams lard per kilo, 3 grams carbohydrates per kilo, bone dust, ad libitum.
November 3: Weight, 9.10 kilos.
November 10: Weight, 9 kilos.
November 20: Weight, 9.55 kilos.
November 29: Weight, 8.70 kilos.
December 6, 7, 8, and 9: Received subcutaneously 22 cc 2 per cent caffein. Condition good, site of injection normal.