In any consideration of this question it is important to distinguish sharply between the nervous control of muscular conditions and the metabolism of the brain and nerve substance itself. As emphasized particularly by Mathews, the brain receives a copious blood supply, and the blood coming to the brain is arterial, while that leaving the brain is venous, indicating that considerable oxidative metabolism occurs in brain tissue. Recently also Tashiro has shown that the carbon dioxide production of nerve fiber is increased when the nerve is stimulated to activity. , But since the entire weight of brain and nerve substance constitutes only about 2 per cent of the body weight, it remains questionable whether, even if its metabolism increases with "mental activity," the increase would be appreciable in measurements of the energy expenditure of the body as a whole. Probably the best-controlled experiments upon this problem, certainly the ones affording most accurate measurement of the energy expenditure, are those of Benedict and Carpenter, in which a number of college students were given course examinations in the respiration calorimeter and their energy metabolism during the three-hour period covered by the examination was compared with that during the same period on another day when the student sat in the calorimeter at rest. In some individuals the metabolism was higher during the examination period, while in others it was lower - results much more likely due to involuntary increase or decrease of muscular tension than to altered metabolism of the brain tissue. In the average of the entire series of experiments there appeared a slight increase of oxygen consumption, carbon dioxide output, and heat production during the examination, but the increase was so small and the exceptions so numerous that the investigators were not willing to conclude from their results that mental work has any positive effect upon the total metabolism, but rather infer the opposite.

Apparently we must conclude that such changes in energy metabolism as may result from differences in activity of the brain and nerves involved in the performance of mental work are so small, in comparison with the energy exchanges always going on in the muscles, that the former are quite obscured by the unavoidable fluctuations of the latter, and so play no measurable part in determining the total food requirement of the body.

Internal secretions, notably that of the thyroid gland, may exert a significant influence upon energy metabolism through augmenting the heart action and respiration rate, probably also through heightened muscular tension, and possibly in other ways. Lusk says: "With the possession of such a gland as the thyroid, whose suppression may diminish metabolism twenty per cent and whose stimulation may increase it 100 per cent, it is truly strange that the normal person should have a basal metabolism so regulated as to correspond to a definite heat loss per square meter of body surface." If, however, the thyroid gland is conspicuously over- or under-developed in size or activity the condition is regarded as a departure from health (goiter, myxedema); the effect of these and some other diseases upon energy metabolism has been summarized recently by DuBois l as follows:

"Basal metabolism is higher than normal in exophthalmic goiter, in fever, in lymphatic leukemia and pernicious anemia, in severe cardiac disease, and in some cases of severe diabetes and cancer. It is lower than normal in cretinism and myxedema, in old age, in some wasting diseases, and perhaps in some cases of obesity." "Diseases of the ductless glands other than thyroid show in some cases an increase, in some a decrease; but these are comparatively small."

1 Archives of Internal Medicine, Vol. 17, page 916 (1916).

Benedictl also holds, in opposition to some other authorities, that "when a carbohydrate-free diet is eaten an acidosis is developed which distinctly increases the cellular activity and results in a very noticeable increase in the basal metabolism."

In a recent general review of the factors affecting normal basal metabolism Benedict2 concludes" that the basal metabolism of an individual is a function, first, of the total mass of active protoplasmic tissue, and, second, of the stimulus to cellular activity existing at the time the measurement of the metabolism was made." And that: "Perhaps the most striking factors causing variations in the stimulus to cellular activity are age, sleep, prolonged fasting, character of the diet, and the after effect of severe muscular work."