In considering the part played by any factor in the nutrition of an animal it is necessary to distinguish between what is adequate for maintenance and what is required for optimum growth. This has been repeatedly emphasized by students of nutrition, especially in connection with protein metabolism.1

With regard to the vitamins it seems clear that both A and B are required for maintenance and growth, although the relative amount necessary and the precise part played in the physiological processes are still unsolved problems. The role of C, apart from its antiscurvy effect, is also questionable.1a.

The early experimenters believed that maintenance could be secured on diets free from A, but this has since been shown to be a misconception.2 McCollum and Kennedy say:3

Judging from the appearance of serious nutritional disturbances ending in death, which result from a shortage of the fat-sohible A, and the emaciation, weakness, and death which follow restriction to a diet inadequate in its content of the water-soluble B, it seems certain that both these classes of unknown dietary constituents are essential for maintenance as well as for growth. . . . The fat-soluble A appears to be dispensable when maintenance alone is involved, for a somewhat longer period than is the factor B. This is inferred from the fact that pigeons can be brought into the polyneuritic state by feeding a diet free from both the essential factors A and B. and can be completely cured and maintained in a normal condition for at least 35 days on the same diet which brought on the disease, plus the water extract of a foodstuff (rolled oats) on which rats cannot grow without the addition of butter-fat, but on which they do grow when the latter is added.

1 McCollum, Am. J. Physiol. 29, 235, 1911; Osborne, Mendel and Ferry, Zeitechr. Physiol. Chem. 1912, 80, 307; Osborne and Mendel, Cam, Pub. 156, 1911, Sci. 34, 722; J. Biol. Chem. 12, 473; 13, 232; 15, 311; 17, 325; 23, 439.

1a Ganassini and Mancini (Bull. gen. Therap. 171, 125 1920; Endocrinology 4, 457) express the opinion that the physiological role of vitamins is to regulate trophic exchanges in synergic connection with the trophic regulatory function of the products of the glands of internal secretion.

Pigeons on a diet devoid of vitamin B exhibited degeneration of the tubules and hyperplasia of the interstitial tissue in the testis. (Novaro, Physiol. Abe. 5, 473).

Many experiments on pigeons carried out by Green (Physiol. Abe. 5, 305) show that the daily demand for the vitamin B is not definite, but varies with the exogenous metabolism. There appears to be no reason to think that vitamin consumption is related to carbohydrate metabolism any more than that of fat or protein. Vitamin B is also required for tissue building. The term "vitamin index" is used to denote the ratio of vitamin absorbed in digestion to the energy value of the digested food.

2 Osborne and Mendel, J. Biol. Chem. 16, 428, 1913-14; McCollum and Davis, 15, 168, 1913.

3 McCollum and Kennedy, J. Biol. Chem. 24, 500, 1915-16.

Emmett and Allen 4 report that tadpoles require both A and B for normal growth and development, lack of B being possibly more apparent than lack of A.

McCollum and Simmonds5 conducted a series of experiments on rats designed to show a quantitative difference in the vitamin requirements (A and B) for maintenance and growth. Their basal ration consisted of 18 per cent casein, 76.3 per cent dextrin, 3.7 per cent salt mixture and 2 per cent of agar-agar, to which was added varying amounts of butter-fat as source of A and of wheat germ as source of B. They state:

Results indicate that there is no low plane of intake of either of these substances which can be said to maintain an animal without loss of vitality. When the minimum amount necessary for the prevention of loss of weight is approached the life of the animal is jeopardised if the diet is continued. A quantity of either the fat-soluble A or the water-soluble B which may be just sufficient when all other dietary factors are of satisfactory quality, will not, when a second factor is less well constituted, induce well-being in the same degree as when a more generous supply is furnished. The animal can tolerate being limited to a very low intake of either the dietary A or B much better with an otherwise excellent diet than when it is less well constituted.

It is to be noted that Von Groer6 has succeeded in obtaining practically normal growth in two babies for the first six months of life on a diet almost devoid of fat6a and correspondingly poor in A. The children were not in a satisfactory nutritive condition, however, as was shown by their susceptibility to illness. In any case the experiment cannot be considered an argument against the indispensability of A since the centrifuged milk which formed a large portion of the diet was not entirely free from A, and the experimental period represented only a very small fraction of the life span of a human being. There are frequent similar instances in animal experimentation of periods of growth on a diet which subsequently proved insufficient to maintain life.7

4 Emmett and Allen, J. Biol. Chem. 38, 325, 1919.

5 McCollum and Simmonds, J. Biol. Chem. 32, 185, 1917.

6 Von Groer, Bioch. Z. 97, 311, 1920.

6a Bee Mackay, Biochem. J. 15, 19, 1921, and Toier, lb. 28, on the effect on kittens of a diet deficient in fat.

It is generally believed that animals have the power of storing up a certain amount of vitamin in the body from which they can draw in case of need, although this store is soon depleted when the food is entirely lacking in vitamins.8 It is difficult to get direct evidence on this point, since it is impossible to be sure that a supposedly vitamin-free food does not contain traces of the essentials which may be sufficient for the particular individual or species under consideration for a certain length of time, although long continuance on a subminimal supply eventually results in nutritional failure. Chick and Hume9 argued from the very close approximation between the daily ration of wheat germ or yeast10 required to prevent the onset of polyneuritis and the dose necessary to cure a bird in the acute condition, that a considerable store of B is available somewhere in the animal body which may be drawn upon to maintain the metabolism of the nerve tissue. This store becomes suddenly exhausted, but can be temporarily restored by the administration of a small quantity of the missing factor in the food.

McCarrison11 judged from their atrophy, out of all proportion to other tissues during vitamin starvation, that the thymus, the testicles, the ovary, and the spleen provide a reserve of accessory food factors for use on occasions of metabolic stress. This reserve is, however, rapidly exhausted. Osborne and Mendel were formerly inclined to believe that young animals maintained a store of A in their cells on which they could grow for a time, but later12 experience has not led to definite confirmation of this hypothesis. With regard to C, the work of Parsons,13 referred to below, would seem to indicate that this is more probably synthesized, by certain animals at any rate, rather than stored in the tissue to any considerable extent.14

7 McCollum and Davis, J. Biol. Chem. 23, 233, 1915; Osborne and Mendel, Ibid. 45, 148, 1920.

8 Lumiere, Par. Med. 10, 474, 1920, dissents from this view.

9 Chick and Hume, Proc. Roy. Soc. 90B, 55.

10 Cooper, J. Hyg. 12, 436, 1913; Bioch. J. 8, 250, 1914.

11 McCarrison, Ind. J. Med. Res. 6, 275, 550, 1917.

12 Osborne and Mendel, J. Biol. Chem. 15, 319; 16, 143.

13 Parsons, J. Biol. Chem. 44, 587, 1920.

14 Osborne and Mendel, J. Biol. Chem. 44, 148, 1920.