Chapter XXIV: Section XV: The Relation of Diet to Disease (1)

BY

DR. E. P. CORSON-WHITE

Food in the widest acceptation of the term, means every thing ingested that goes, directly or indirectly, to growth, repair of the body, or production of energy, all of which phenomena must continue when food is withheld or supplied in insufficient quantities. Under the latter condition the processes go on at the expense of the body tissues as these are protected only when the diet is adequate in every way. A proper diet, therefore, must be one on which an animal will attain maximum development, maintain a normal weight curve, show a minimum susceptibility to disease, live out a full term of life, breed normally, and rear healthy offspring, capable of normal independent life after they are weaned. It must fulfill the caloric needs of the body, and in young animals it must also supply the growth impulse. In its physical properties it must fit the morphological demands of each type of gastrointestinal tract. In its chemical content it must supply all the elements found in the body in usable form, and in amounts sufficient to cover the needs of the body for growth, repair and waste. To evaluate fully the influence of food on the individual animal it is necessary to study its relation: (1) to the type of alimentary tract, (2) to the type of bacterial flora and their metabolic processes, (3) to the chemical needs of the body, (4) to the changes arising in the catabolism and anabolism of all types of food, (5) to exercise or its lack, keeping in mind always the constant interdependence of all factors. Our knowledge of nutrition has to a very large extent paralleled the advances in chemistry, especially the researches into the structural makeup of living cells, the intermediate stages in their upbuilding and degradation and the products resulting from their physiological activities.

Incorrect feeding both qualitative and quantitative undoubtedly plays an important rôle in producing disease. In the early works on nutrition, the proportion of fats, carbohydrates and proteins was regarded as the essential point of a normal diet. The researches on the composition of foods marked the first real epoch in this history and Fischer’s[57] studies on the variation in the composition of proteins from different sources first introduced the idea of quality. Later Mendel and Osborne investigated the biological values of purified proteins, while at the same time McCollum and others were studying the value of the groups of proteins occurring in a single natural food stuff, were calling attention to the so-called vitamines, and were emphasizing the need of balanced inorganic materials. These studies have practically revolutionized our knowledge, particularly of the effects of badly balanced foods. They have clearly demonstrated that dietary values can, in all probability, be discovered only by careful biological study of feeding experiments together with the finer analysis of the components of the diet, especially of the protein and fat radicles. At the same time a definite appreciation of the rôle of each element in metabolism must be kept in mind.

These varied studies on nutrition have shown that the chemical requirements of a diet are in their ultimate analysis essentially the same for all species of the higher animals—that is all require approximately the same amount of protein, fat, carbohydrate, etc., per kilo of body weight, while the morphology of the tract decides the physical properties of the diet.

RELATION OF FOOD TO ALIMENTARY TRACT.

Food derived from animal sources is high in protein, readily digested, and highly putrefactive. This type of diet is suited to an alimentary tract which permits rapid passage through its length, and is fitted with sturdy walls. The gastric section is simple, the intestine short and narrow with ill-defined separation of its parts into small gut, cecum and colon. This type is found in all land Carnivora. The fish-eating carnivores have a strong tubular stomach and an enormous length of intestine, but no cecum. The omnivores occupy a middle place. In them the alimentary tract consists of a simple stomach, a short wide intestinal tube, and a more complex, although still comparatively simple, cecum which is generally longer than that found in the carnivores. This tract is too small to manipulate the bulky vegetable masses necessary to provide their minimum protein requirement, and too long and complicated to dispose quickly of the putrefactive animal tissue. Among these animals colitis is common, due to the fact that the shape and position of this part of the tract favors stasis, or at least a sluggish movement of its contents at a point in the digestive scheme where the food residue is rich in protein by-products, ready for bacterial growth.

The herbivores with food derived from plants which requires a long period of time for its digestion, have, on the other hand, voluminous stomachs, or large ceca or both; and very long small intestine. In this tract the concentrated food of the carnivores would provide an enormously excessive protein intake or if only the protein requirement is supplied would leave the tract so empty that it would be unable to functionate.

All studies in comparative anatomy demonstrate the fact that while neither a complex stomach nor a large cecum is essential to the digestion of vegetable food, a capacious and complex alimentary canal, as a whole, bears a relation to vegetable diet, particularly in the mammals. Either a highly developed concentrated glandular apparatus is added to the stomach, as in the wombats, beavers and dormice, or the stomach is subdivided, sacculated, or otherwise amplified as in the ruminants and herbivorous marsupials. Sometimes both complexities are combined as in the case of the sloths. If the simple stomach is retained, it is supplemented by a large sacculated colon or cecum, as in the horse. In birds, the proventricle is larger in meat- and fish- eaters, while the gizzard is more muscular in grain- and insect-feeders, and the intestines are longer in those devouring coarse green grass and leaves. The length of the ceca is related entirely to the diet, the long ones corresponding to the diet which needs protracted periods of time to exhaust its nutriment.

THE BACTERIAL FLORA.

The bacterial flora harbored in the intestinal tract is closely related to the type of food and to the character of the alimentary tract. Levin[58] found sterile intestinal tracts in white bears, seals, reindeer, eider ducks and penguins when in the Arctic regions; but these same animals when they are brought to a temperate climate rapidly acquire intestinal bacteria. The function of the normal inhabitants of the tract is, probably, to protect the body against invasions of obnoxious species. Herter found in man that a few species adapt themselves to the digestive tract and control the growth of newcomers capable of doing injury. These common varieties become a source of danger only when present in large numbers.

Bacteria which produce decomposition of food in the digestive tract are of three types: (1) Pure putrefactive anaerobes, (2) organisms both fermentative and putrefactive, but tending generally to antagonize the putrefactive anaerobes, and (3) fermentative organisms. In the stomach, fermentation of carbohydrates with the production of organic acids is a frequent occurrence. Putrefactive types are very rare except with pyloric stenosis, a condition which favors excessive fermentation by diminishing the tone and motility of the stomach and the amount of hydrochloric acid. This condition is further increased by excessive carbohydrate food. In general the products of fermentation tend to restrict putrefaction, yet both may be operative. In the small intestines, bacteria are always present because of the protein richness of secretions, the rapid digestion of food and the slight or ineffectual antiseptic properties of intestinal juice, bile and pancreatic secretions. The putrefactive bacteria rapidly increase and decompose any protein that is unabsorbed—a process most marked in the colon because its shape and position favor stasis or slow movement of its contents. In general the greater the amount of unabsorbed and digestible protein and the longer the material stays in the intestinal tract, the greater the putrefaction. The meat-eating animals develop Gram-negative bacilli, while the carbohydrate-eaters show a predominance of Gram-positive types.

Ingested food never contains the enormous amount of bacteria found in the feces. The alimentary tract with its contents forms a most efficiently combined incubator and culture medium, in which bacterial growth exceeds that of any known location both in intensity and complexity. The range of reaction and composition of nutritive substances at different levels of the intestinal tract is such that a great variety of bacteria capable of growth at body temperature develop. The prominent types that appear in the flora of each order of mammals are fairly constant in their occurrence. They depend primarily on food ingested, and show well marked seasonal variations, dependent again on changes in food. Faulty feeding may itself give rise to a toxic condition of the gastrointestinal tube, and thus often prepares this soil for the development of organisms.

The intestinal flora also changes along rather definite lines as the diet of the host changes from the monotony of the infant to the variety of the adult. At birth the tract is sterile, but bacteria soon make their entry through the mouth in food and water. The majority of these organisms pass to the stomach where many are destroyed, but a number travel to the intestines where they may gain a foothold. There is always a mechanical transportation of intestinal bacteria from higher to lower levels. A continued preponderance of protein in the diet of all animals leads to a partial or complete suppression of the Gram-positive acid- forming groups and an increase of the proteolytic Gram-negative types; while on the other hand an excess of carbohydrate leads to diminution or suppression of proteolytic activity and an increase in the fermentative organisms. Therefore the most important normal factor in determining the intestinal flora in health is the chemical composition of the ingested foods.

The nature of the dominant organisms which develop in diets rich in carbohydrates varies with the carbohydrate itself. In all ordinary diets there are (1) starches—forms not readily fermentable, and (2) sugars— which are largely absorbed from the higher levels of the small intestine, leaving residual starches and proteins in relatively great concentration in the lower levels. Therefore the obligate fermentative organisms are prominent only in the higher levels, the facultative appear in the intermediate places, and the obligate proteolytic organisms in the lower intestines. This accounts in a measure for the great increase of lower intestinal disturbances in omnivores. Complete proteins resist putrefaction, but the products of protein digestion and of the intestinal secretions constitute the main substrata for putrefactive bacteria. Animal protein develops more active proteolytic bacteria than vegetable protein, which accounts for the greater predominance of putrefactive infections in carnivores than in omnivores.

There are two important factors to consider in discussing the influence of diet on intestinal bacteria: (1) The substitution of types, which frequently follows a monotonous diet, and (2) the change in metabolism of existing types of bacteria when dietary conditions are such that the intestinal medium at one or another level fluctuates in its content of usable carbohydrate and other nutrient. The nature and extent of these modifications and their effects upon the host vary greatly, not only qualitatively but quantitatively. An invasion of the tract by exogenous bacteria, as the dysentery bacillus, cholera, typhoid, etc., in food or water may lead to a more or less pronounced replacement of some of the normal intestinal types by these alien organisms, and to the production of disease.

The importance of all the foregoing facts concerning the changes in the food, in the intestinal cultural substrata and in the advent of new kinds of organisms was emphatically demonstrated in the marked fall in gastrointestinal diseases in carnivores after proper screening of meats. The simple protection of the food given to these animals eliminated the air bacteria which, entering from dust and flies, alter the chemistry of the meat before consumption or change the flora of the intestine after consumption. Normal organisms, or types indistinguishable from them, may multiply, through unusual conditions, extend their normal habitat, and eventually lead to abnormal reactions detrimental to the host. These facts throw considerable light on the site and character of gastrointestinal lesions found in various orders, a subject to be discussed more fully later.

There are many intestinal disturbances of unknown causation, in some of which bacteria presumably play a secondary part. The primary disturbance is due to the products resulting from the action of bacteria upon food. Many toxic bodies are produced either before or after ingestion by the bacterial decomposition of carbohydrate, fat or protein, independent of any actual infection. The symptoms arising from bacterial decomposition of foods depend largely on the organism concerned and vary from a mild intoxication to a severe toxemia.

RELATION OF DIETARY GROUPS TO AUTOPSY DIAGNOSES.

Analysis of the autopsies on file from sole point of view of dietary habits of the animals gives rather interesting groupings of disease states, which apparently and, in some cases definitely, emphasize the relationship between food, metabolism and disease. (Table 19.)

From this table a few facts stand out prominently. It is definitely shown that both birds and mammals on a diet of mixed animal and plant tissue show a low percentage of disease in the gastrointestinal tube, liver, pancreas and kidney. The mammals on this diet give the highest figures for anemias and degenerative osseous conditions. Birds on this diet show very little osteomalacia, but a fair amount of anemia. Possibly this may be accounted for by the fact that all of them pick gravel and may be able from this to supply some of the inorganic deficiency. Carnivorous birds and mammals, on the other hand, show an exceedingly large assortment of gastrointestinal disorders, diseases of the accessory glands of digestion, and of the kidneys. Disorders of the thyroid gland are almost entirely confined to carnivorous mammals—7.5 per cent., compared to 0.25 per cent. in all other orders. Gout, while common among birds, was not present in any mammalian autopsy, while arthritis in mammals reached its highest record among grass- and grain- eating herbivora. The percentage of rickets was highest in the young carnivores (2.6 carnivores as against .4 per cent. in all other mammals), and was very rare among all birds.

The succulent vegetable diet was lowest in its relation to degenerative visceral disorders and highest in acute gastritis; the latter fact was probably due to the fermentation of soft moist food that requires rather a long time for its primary digestion. This type of food has also a high and easily available sugar content which makes it a very favorable medium for many of the fermentative types of bacteria. Most of the lesions in this group were around the pylorus and upper duodenum.

TABLE 19. _An Analysis of the Pathological Findings Described in the 5,365 Autopsies from the Point of View only of the Dietary Habits of the Animals. The Percentage Results Represent the Proportionate Number of Cases of Each Pathological Lesion Found in the Entire Group of Animals on Each Special Diet without Reference to Zoological Orders._ ═════════════════╤═══════════════════════════════╤═══════════════════════════════ Disease states │ Mammalia 1860 │ Aves 3505 ─────────────────┼──────┬───────┬────────────────┼──────┬───────┬──────────────── „ │Omniv-│Carniv-│ Herbivora │Omniv-│Carniv-│ Herbivora │ ora │ ora │ │ ora │ ora │ ─────────────────┼──────┼───────┼──────────┬─────┼──────┼───────┼─────┬────────── „ │ „ │ „ │Succulent │Grain│ „ │ „ │Seeds│Succulent │ │ │Vegetables│ │ │ │ │Vegetables ─────────────────┼──────┼───────┼──────────┼─────┼──────┼───────┼─────┼────────── Malnutrition │ .1│ 1.6│ .6│ 2.2│ .05│ .4│ .1│ Food Poisoning │ .3│ │ │ 2.5│ .05│ .2│ .08│ Acute Gastritis │ 3.2│ 6.3│ 9.3│ 3.1│ .9│ 2.│ 1.3│ 13.5 Acute Duodenitis │ .5│ .3│ │ .5│ .1│ 1.4│ 1.2│ 5.4 Acute Enteritis │ 2.5│ 3.4│ 3.│ 3.1│ 7.│ 1.│ 8.│ 5.4 Acute │ 26.3│ 53.2│ 19.9│ 29.2│ 25.3│ 38.6│ 35.6│ 64.8 Gastroenteritis│ │ │ │ │ │ │ │ Chronic Gastritis│ 1.1│ 6.│ 2.│ .8│ .2│ 1.4│ .3│ 5.4 Chronic Enteritis│ 2.│ 5.6│ 3.│ 2.2│ 1.1│ 3.3│ 1.3│ 13.5 Colitis │ 1.9│ │ │ │ │ │ │ Acute │ .1│ 2.2│ 1.│ 3.1│ .4│ .6│ .08│ Pancreatitis │ │ │ │ │ │ │ │ Chronic │ .5│ 1.7│ │ │ .2│ 1.2│ .5│ Pancreatitis │ │ │ │ │ │ │ │ Acute Liver │ .8│ 1.3│ .3│ 1.4│ 4.2│ 2.8│ 2.5│ 2.7 Disease │ │ │ │ │ │ │ │ Chronic Liver │ 3.│ 6.3│ 3.3│ 6.│ 1.1│ 2.5│ 1.6│ 13.5 Disease │ │ │ │ │ │ │ │ Acute Nephritis │ 9.1│ 12.2│ 12.7│ 12.4│ 5.1│ 6.7│ 4.1│ 8.1 Chronic Nephritis│ 4.5│ 11.6│ 6.7│ 7.8│ 2.9│ 6.7│ 2.1│ 13.5 Myocardial │ .1│ .34│ │ 1.1│ .3│ 2.│ .4│ 8.1 Degeneration │ │ │ │ │ │ │ │ Arterial Disease │ .1│ 3.1│ .3│ 2.2│ .3│ 3.1│ .66│ 1.8 Anemia pernicious│ .3│ .32│ │ │ │ │ │ Anemia secondary │ 4.2│ .32│ 1.2│ 1.5│ 1.1│ 2.5│ 1.5│ Thyroid Disease │ │ 7.5│ .3│ .7│ .3│ .2│ .3│ Adrenal Disease │ 1.6│ 1.3│ .3│ 1.5│ │ │ .08│ Diabetes │ │ .2│ │ │ │ │ │ Osteomalacia │ 5.2│ .4│ 2.3│ .2│ .1│ .6│ 2.8│ Osteitis │ .6│ │ │ │ │ │ │ deformans │ │ │ │ │ │ │ │ Arthritis │ │ .3│ .3│ 2.2│ │ .2│ .08│ Rickets │ .1│ 2.6│ .6│ .7│ │ │ .08│ Gout │ │ │ │ │ │ .4│ .08│ Sore Eyes │ │ .3│ │ .2│ .1│ │ .3│ Malignancy │ .05│ .9│ .6│ │ .05│ │ .6│ Tuberculosis │ 32.6│ 3.5│ 4.5│ 9.6│ 12.│ 1.7│ 17.2│ 5.7 ─────────────────┴──────┴───────┴──────────┴─────┴──────┴───────┴─────┴──────────

Overeating is a factor that must be borne in mind when considering the hay- and grass-eating herbivora. Packing of the rumen is a not infrequent discovery. This condition is also found in certain seed- eating birds. As a supply of food is constantly at the disposal of these animals and exercise is prevented by captivity, continuous eating becomes their principal diversion. In this group also food poisoning was highest, a condition which may be due to (1) spoiled food, (2) poisonous substances in the foods, (3) fermentation of grass foods (spoiled hay or musty fodder). Malnutrition also, is higher than with any other diet, due probably to the somewhat meagre nutritious value of the food. This group also shows a high percentage of acute pancreatitis, degeneration of the liver, myocardium and arteries. Arthritis was present in this group 2.2 per cent., against 0.2 per cent. in all other groups.

A study of Table 19 demands a constant recollection of the morphology of the tract involved and its main points of vulnerability, the bacteria capable of living on the particular type of food or its constituents and the by-products produced during the digestion and absorption of these foods. Not one of these factors can be ignored in evaluating the influence of diet, which to be correct must supply elements in proportions that are chemically available for body needs (for instance, Von Wendt[59] found that more iron was required if the diet was deficient in calcium). These proportions must be worked out by carefully combined chemical and biological experiments.

MALNUTRITION.

There was one omnivorous beast, a Hamadryas Baboon, which represented the only true case of starvation, probably induced by nostalgia, as it never ate after coming into the Garden. Thirty cases of partial starvation or malnutrition are listed in our records, the majority among the rarer specimens, ten carnivorous, seven herbivorous and one omnivorous mammals, ten carnivorous and two seed-eating birds, due possibly to inappropriate diet or to some unknown factor that rendered the diet inadequate. At the autopsy nothing was found to account for death except the draining of all storage supplies.

STARVATION.

The reports of studies conducted during long laboratory fasts have been among the most valuable records for the understanding of the chemical requirements of diet and of the close chemical interrelationship existing between the different food factors. In absolute starvation life is very short, primarily because water is necessary for respiration, for dissolving products of metabolism and for preventing changes in digestive intestinal secretions. The amount of water needed varies with different species of animals. If the water is supplied, the organism is enabled to maintain its energy for continued existence from the destruction of its own tissues. The length of life depends upon the amount of protein ingested before the fast commenced, and the amount of stored fat and glycogen, especially that stored in the liver. The mechanism of the results is similar. The animal body uses first its available glucose, and when this is partially exhausted burns its stored fat and protein. The fat combustion is usually defective, ketone bodies appearing in the urine in large quantities. The change from fat to protein metabolism accounts for the premortal rise in metabolism which occurs usually a few days before death. The chemical composition and corpuscular richness of the blood is tenaciously preserved; glucose and protein concentration are practically normal up to the day of death. There is at times a slight increase in globulins and always an increase in fat due to its transportation from storage depots. The cause of death is primarily due to loss of substance in organs necessary to life and to an acid intoxication.

Wasting occurs first in stored substances, fat, glycogen, etc., then in the least used organs. The bones usually show some rarefication. The animal, as a rule, dies from acid intoxication before atrophy of the organs is marked.

In the wild, when animals are forced to seek their food with the expenditure of much energy and where feasts are often followed by fasts, this using up of storage supplies cannot help being a factor in preserving the integrity of the storage and eliminative organs. In captivity this cannot occur. Food is supplied regularly, exercise is lacking, consequently overloading and disease of storage and eliminative organs is more or less constant—a situation very marked in the Carnivora.

TABLE 20. _Detailed Analysis of the Various Diets Used at the Philadelphia Garden on Basis of 100 Grams of Mixed Food._ ═════════════╤══════════════╤═════════════╤══════════════╤═════════════ │ Omnivora │ Carnivora │ Herbivora │ Herbivora │ │ │ Succulent │ Coarse Food │ │ │ Vegetables │ ─────────────┼───────┬──────┼──────┬──────┼───────┬──────┼──────┬────── „ │Mammals│Birds │ Meat │ Fish │Mammals│Birds │ Hay │ Seed │ │ │ │ │ │ │ Food │ Food ─────────────┼───────┼──────┼──────┼──────┼───────┼──────┼──────┼────── Protein │ 14.3│ 11.5│ 15.6│ 17.2│ 6.1│ 3.2│ 6.4│ 7.1 Fat │ 9.5│ 7.2│ 18.8│ .3│ 2.6│ .5│ 2.2│ 1.3 Carbohydrate │ 26.7│ 41.2│ │ │ 18.5│ 25.7│ 35.9│ 51.2 Calcium │ .034│ .068│ .058│ .109│ .067│ .025│ .071│ .044 Magnesium │ .058│ .093│ .118│ .133│ .164│ .119│ .289│ .16 Potassium │ .497│ .713│ 1.694│ 1.671│ .538│ .242│ .644│ .324 Sodium │ .103│ .284│ .421│ .373│ .08│ .291│ .089│ .261 Phosphorus │ .263│ .484│ 1.078│ 1.148│ .556│ .342│ .692│ .458 Chlorine │ .117│ .377│ .378│ .528│ .038│ .044│ .073│ .063 Sulphur │ .338│ .486│ 1.146│ 1.119│ .134│ .125│ .217│ .163 Iron │ .0032│ .0063│ .015│ .0055│ .0018│ .0012│ .0022│ .0012 ─────────────┴───────┴──────┴──────┴──────┴───────┴──────┴──────┴──────

A further study of Table 19 in the light of the finer analysis of the ingredients of the diets, shown in Table 20, explains, at least in part, the high percentage of certain types of disease in relation to particular diets.

In the food of the first group, the omnivorous mammals, there is a moderately increased carbohydrate content and an unevenly balanced inorganic content, the last being the factor most at fault. The calcium and phosphorus are both so low that at the best the animal could only be in equilibrium, while any drain of the fixed bases would sooner or later have to be replenished from the calcium and phosphorus storage depots, the bones. Osteomalacia is most marked in the Cebidæ, monkeys whose diet is even lower in these same elements: calcium .025, phosphorus .116, and iron .0008 per 100 grams of food. The inorganic composition of all animals is grossly similar; the typical digestion developed from the habitual diet of the animal explains the more apparent changes and variations in their reactions to certain deprivations.

IRREGULARITIES OF INORGANIC METABOLISM.

Twelve essential elements are present in the body, namely: carbon, nitrogen, hydrogen, oxygen, phosphorus, calcium, sulphur, sodium, chlorine, potassium, iron, magnesium. Of these, five are furnished by the protein molecule and three of the five are duplicated in the fats and carbohydrates; the remaining seven must be present in the mineral ash. These elements functionate in three ways, (1) as constituents of bone, (2) as essential elements of organic compounds, (3) as soluble salts in body fluids. Chlorine, sodium, sulphur are supplied in sufficient quantity with most diets. In the case of chlorine, marked differences exist between the herbivores and carnivores. The meat-eating mammals easily acquire sufficient sodium chloride from the flesh and blood of their victims, while the herbivores on the other hand, find in their vegetable food large amounts of potassium and very little sodium or chlorine which must therefore be acquired separately. Both omnivores and herbivores crave salt, probably because this large potassium content of vegetable food tends to increase the sodium elimination. A deprivation of salt always leads to a distaste for foods rich in potassium. So far as is known excessive sodium stimulates protein catabolism, and through the overstimulation of the digestive tract, may interfere with the absorption of food.

Sulphur is largely taken into the body in organic combination with the protein, (a very little inorganic sulphur appears in the drinking water) therefore if the protein requirements are adequate the sulphur will usually be adequate.

Magnesium is abundant in meat and most plant tissues; so that except in diets of highly refined foods, it is more often excessive than deficient.

The other elements, calcium, phosphorus and iron are frequently insufficient, especially for animals on omnivorous diet (cf. Table 20). Phosphorus enters into every living cell, and in cases of starvation is excreted up to the last. It is involved in practically all the cell functions. In the body it is present (1) as an inorganic compound in the bone tissues and blood where it helps to maintain neutrality, (2) as phosphorus-containing protein, phosphatids and phosphoric esters of a carbohydrate, all closely associated with the cell and its nucleus. In foods, phosphorus occurs in the same positions, that is, inorganically or combined with protein, fat or carbohydrate. It is not entirely proved but is very probable that the phosphorus in organic combination has the greater metabolic value, inasmuch as there is greater storage of nitrogen and stimulation of tissue growth on foods containing phosphorized proteins, fats, etc. It has been shown, however, that the animal body can satisfactorily supply its phosphorus requirements by inorganic phosphates. The omnivorous diet, even the widely varied diet of man, is very often deficient in phosphorus, a fact which becomes very important when we consider that the omnivorous diet produces many acid residues which must be neutralized, and that phosphorus is largely responsible for the maintenance of tissue neutrality. Voit showed that the phosphates excreted during starvation were withdrawn from the bones; and there is much proof that during the daily metabolism a certain slight movement of phosphorus takes place. The metabolized phosphorus is excreted by carnivores practically from the kidney alone; by herbivores almost entirely through the intestinal wall, while in the omnivores it is excreted by kidney and intestinal tract. Whether these facts have any real influence on the phosphorus need of different types is not altogether determined.

Calcium also enters into many of the essential functions of life, coagulation of the blood, contractility of the heart, etc. Omnivorous diet is usually deficient in this element, which is very irregularly distributed both in animal bodies and plants. Insufficient amounts lead to deprivation of body tissues and to the production of osteomalacia- like conditions. Voit produced marked thinning of the skull bones and sternum by a diet poor in calcium. Steenbok and his associates had the same results in cattle by feeding “shorts” a diet rich in magnesium. Etienne[60] showed that an excess of magnesium in an otherwise well balanced food caused a continual loss of calcium. Adults stand a deprivation of calcium much better than children or young animals. They often show no symptoms and retain a normal blood content as the losses from the blood and soft tissues are promptly replaced from the bones. Sooner or later all these animals show weakness and flexibility of the bones. Osteomalacia occurred in 5.2 per cent. of the animals on an omnivorous diet, that is this number showed gross evidence of absorption of bone salts. This condition occurring in man and the lower animals is a generalized softening of adult bones that were at one time normally calcified. Three clinical varieties are recognized in man: a mild form seen in pregnant, puerperal and lactating women, a senile form in which the lesions are usually limited to the pelvis, and a severe progressive form encountered in both sexes and at any age. This last form ends in marasmus. Its chemical characteristic is a loss of calcium and phosphorus with retention of sulphur and magnesium.

The progressive type has occurred very frequently among the Cebidæ whose diet on careful examination, showed a protein content low in quantity, poor in quality, and especially deficient in the phosphorus-containing proteins and total fat. The carbohydrate was high. The ash was small in amount and predominatingly acid. The daily ration often showed only an unweighable trace of calcium, phosphorus or iron. Sodium, potassium, sulphur and magnesium, on the contrary, were present in amounts sufficient for equilibrium or in excess. The Vitamines A.B.C. were present but were not always correctly proportioned. The fat soluble A was low and in some daily rations was entirely lacking.

Diet has at various times been proposed as at least one factor in the production of this condition, a premise that has gained considerable weight through the increase in the number of cases, both in man and in the domesticated animals, reported from the war-famine district of Central Europe where the dietary was restricted and unbalanced. It has been shown that when calcium is low in the diet, the amount excreted materially exceeds the intake. Benedict[61] has further shown that even during absolute fasts calcium is excreted. The requirements of this element for man have been fairly well worked out, but for animals we have no standards. Still it seems certain from the foregoing observations that storage supplies are called upon very early in cases of deprivation, while in pregnancy and lactation when the calcium requirements are greatly increased, a reason is found for a higher incidence of osteomalacia, Steenbok and Hart[62] have shown that the skeletons of cows and goats gave evidence of a drain of inorganic salts during the production of milk unless the calcium and phosphorus of the diet were liberally supplied. In osteomalacia it would seem that inefficient diet, if not the cause, was at least a very potent factor in pathogenesis. The disturbance of the calcium-phosphorus-metabolism may be due to the deprivation of the alkaline salts as in the famine osteomalacia, to a drain from the alkaline storage of the body associated with an inefficient diet as in the osteomalacia of pregnancy and lactation or to the combined action of a diet faulty in more than its salt content, which by the production of acid in its oxidation and by favoring the development of acid-forming bacteria, causes a drain of the body alkali for neutralization of the acid; or it may possibly be due to a combination of all these factors acting through their influence on the ductless glands.

Paget’s disease or Osteitis Deformans is a chronic constitutional process which usually involves all the bones of the adult skeleton. DaCosta[63] believed it to be a disorder of bone metabolism probably dependent upon absence or perversion of some internal secretion. We have had the unique opportunity of observing three cases of this disease in Cebidæ, the family of monkeys which has presented the highest incidence of osteomalacia. The experience is all the more interesting because of the typical picture presented by the specimens, and of the absence of references in the literature on the subject, to the occurrence of the malady in wild animals. The interesting point about these cases lies in the fact that the disease appeared in all three only after lime water was added to the diet to supply the deficiency of calcium.

Search for literary record of the disease brought to light a case in a horse that Barthelemy[64] described, but this involved the epiphyses of the bone while osteitis deformans is confined as a rule to the diaphyses. This case was probably more closely allied to osteitis fibrosa cystica. Goldman[65] described examples in fowls and Rossweg[66] refers to specimens in domestic goats and monkeys. Many of these cases first come under observation through fractures, an accident common to osteomalacia, but very rare in well developed osteitis deformans. The diet of our monkeys was exceeding low in those substances essential to bone development. Sherman[67] has shown that the calcium balance is regulated to a certain extent by the calcium ingested, and that when the diet is poor in this element, the output materially exceeds the intake, a condition which is definitely changed when the animal is put on a diet high in calcium.

So far as we could find there are no recorded studies of the mineral metabolism of beginning cases of Paget’s disease. It seems possible from the study of osteomalacia that the low mineral and otherwise faulty diet, added to the symptoms produced by that diet might so disturb the chemical equilibrium, directly through the neurotrophic mechanism or through the perversion of the ductless glands, that the mere addition of the lime water might entirely change the pathological picture. This is in accord with the histology where the initial lesion is resorption of bone followed by irregular proliferation. It is also in accord with the probable chemistry of calcification. These animals all showed a lowered carbon-dioxide-carrying-power of the blood, and therefore lowered ability to carry calcium in solution. It is possible that Paget’s disease is but a stage in a deficiency disease, a faulty reparative response through a disordered neurotrophic mechanism, or through a perversion of the glands governing calcium metabolism. Such perversion could be caused by an improperly balanced diet, or by the addition of an excess of calcium to the diet of an animal whose body fluids were unable by reason of previous faulty diet or other disorder, to hold it in solution. In young animals the calcium demands are much higher than in adults, a need met in the high calcium content of breast milk, a content in excess of almost every other food, but apparently just sufficient to maintain calcium equilibrium. After it is weaned the young animal frequently shows disorders of its inorganic metabolism. Herter estimated that a child should store at least 0.1 gram of calcium daily and he described many cases of arrested bone development occurring during infancy and early childhood, because of an inefficient assimilation of calcium. One case, probably of this character, was found in a Hamadryas Baboon (_Papio hamadryas_) a typical example of infantilism. The animal was an adult male about half the size of an adult female. His skin was fine and more delicate than normal, the bones were small and slender, contour of body was that of a young animal, genitalia were imperfectly developed, thyroid gland apparently normal, gastrointestinal tract atrophic, associated was a slight arthritis, portal cirrhosis of liver and diffuse nephritis.

First among the results of inorganic insufficiency in youth stands Rickets. This disease occurs in children starting usually at about the sixth month and continuing with irregular remissions for several years. The bone changes, which are the most prominent, are always associated with more or less severe anemia, a general lowered resistance and flabby musculature. The excretion of calcium is very high in the feces and low in the urine. There is a frequent negative calcium balance dependent upon the great loss in the feces. Healing is preceded by a hyperretention of calcium and a relative increase in the urinary calcium. The excessive loss of calcium in the feces is not brought about through the agency of fats because fat could only remove calcium as insoluble soaps and these are not at all increased. This fact contradicts the idea of fat starvation as a cause of rickets. Howland and Kramer found that the blood in active rickets had a normal or slightly lowered calcium content, but a regularly reduced phosphorus content. The latter deficiency was extreme at times. They ascribe to this deficiency the failure of the bones to calcify. It can be readily understood that a decrease of phosphorus in the blood would render difficult the precipitation of calcium phosphate.

Recently two series of studies, the first by Pappenheimer, Zucher and McCann and the second by Shipley, McCollum, Park and Simonds have shown that rats fed on a diet low in calcium but with a sufficient amount of fat soluble vitamine and phosphorus develop a bone condition with many fundamental resemblances to rickets. They were also able to produce the condition with an excess of calcium and deficiency of phosphorus. On the first diet, the condition differs from rickets in that the arrangement of the proliferating zone of cartilage cells is maintained and the evidence of bone resorption in the diaphyses is excessive. A diet deficient in both calcium and phosphorus leads to an atypical rickets.

In the animals autopsied at this Garden rickets occurred very much more frequently in the flesh-eaters than in any of the other dietary groups. On closer analysis it was found that rickets in almost every case appeared in the carnivores which did not receive bones as a part of the food. Rickets occurred frequently in the omnivorous macaques which however did not show osteomalacia, although they belong to the same dietary group as the Cebidæ. The reason they did not suffer the latter disease while adult but had rachitic young is probably due to the fact that this monkey group, which breeds best in our Garden, receives in addition to the diet given to Cebidæ one raw egg. This increased the calcium content of their food more nearly to the requirements of these mammals. These monkeys also have mouth sacs, which enable them to acquire more food per kilo of body weight than the smaller Cebidæ which are not so advantageously equipped. The food even in the amounts consumed by the macaques is low in calcium, phosphorus and iron. It is very possible that there are enough of these ingredients present as a rule, to maintain the animal in organic equilibrium, during normal life, and possibly even enough to supply the needs of the embryo but not sufficient to maintain the young during the period of lactation. A few macaques dying during the delivery of young showed slight osteomalacic changes in the pelvis. This was notably present in one described in detail by E. A. Schumann.

The calcium requirements of the female are always much increased during pregnancy and lactation due to the withdrawal from the mother to meet the needs of the embryo and nursling. Forbes and Beegle[68] found that lactating animals made heavy drains on their storage calcium even when the diet was liberal and the animal was storing nitrogen.

Iron is the essential element of hemoglobin and chromatin—the body constituent most directly concerned with the process of oxidation, secretion, reproduction and development. The iron of the food is absorbed from the small intestines, enters the circulation through the lymphatics, is deposited in the liver, spleen, and bone marrow and eliminated through the intestinal walls. There is very little iron reserve in the adult body; and as a result any failure of the intake to equal the output causes an immediate reduction of the hemoglobin. Voit found that the iron eliminated in the feces of starving dogs, or dogs on a diet low in iron comes from the body through the intestinal walls. Medicinal iron stimulates the production of hemoglobin and red blood cells but whether it is directly employed in the production of hemoglobins has not been proved. Undoubtedly most of the extra iron given with the food passes through the alimentary tract without being absorbed or metabolized. The greater the amount of iron in the food, the greater the influence of the inorganic iron. Anemia occurred in all the animals we examined at least four times as frequently in omnivorous as in all the other dietary groups, a fact probably explained by the low content of iron and calcium in this diet. Both Von Wendt[69] and Sherman[70] demonstrated that larger amounts of iron were required to maintain the iron equilibrium when the amount of calcium was low.

Herter has shown that many anemias are associated with intestinal putrefaction. The carnivores, however, on a diet that putrefies very easily and on one in which the iron content is apparently of distinctly lower nutritive value than that of the iron found in milk, eggs and vegetables, presented an anemic incidence of only 0.32 per cent. This is probably due to the excellent hygienic care of the meat foods and to the morphology of the carnivorous intestinal tract, which is short, straight and fashioned for quick elimination. The cases of anemia steadily increase among the animals as the conformation of the tract approaches the omnivorous type with the longer and wider hind-gut.

Herbivora, obtaining their iron from vegetable sources, are much less liable to blood disorders. The iron needs of the female are greater than those of the male because of the drains of pregnancy and lactation. Young animals demand more iron than adults. All exclusively breast- feeding animals have a considerable storage of iron in the body at birth, while those that eat food immediately have no such supply. Bunge’s[71] experiments showed that breast-fed animals contained about six times as much iron as the milk that nourished them. The iron content of all these animals is highest at birth, remains constant during the suckling period and then rapidly decreases to the adult standard. After this level is reached the iron metabolized must be supplied from the food if the hemoglobin is to be spared.

The functions of all these inorganic substances are intimately interrelated and in places interchangeable. Calcium is capable of correcting disturbances of inorganic equilibrium in the animal body whatever the direction of the deviation from the normal may be. These interrelationships are most involved in the maintenance of body neutrality. The normal processes of metabolism involve a continual production of carbonic, phosphoric and sulphuric acid which must be immediately disposed of if the neutrality of the body is to be permanent.

The factors involved in this are carbonates, phosphates, ammonia and proteins. Carbon dioxide is the chief excretory product but is at the same time a normal constituent of the blood and as such, is an important factor in this physicochemical regulation. There is a tendency for the respiratory mechanism to hold its carbon dioxide tension nearly constant. Late investigations have shown that lowering of this tension is an early sign of beginning acidosis. When food such as protein, is taken in excess the strongly acid residues are neutralized by the sodium and potassium carbonates which are eliminated with a corresponding loss of sodium and potassium. The carbon dioxide tension diminishes, 37.2 per cent. on a high protein as against 43.3 per cent. on a vegetable diet. If this excess is long continued, the result may be, and often is, an increased elimination of the base-forming elements which if not made good tends to diminish the body’s reserve alkalinity. A diet with a preponderance of basic elements leads to an alkaline urine with an increased uric acid solvency and an increased carbon dioxide tension and reserve alkalinity. A diet with a preponderance in the acid-forming elements, on the contrary, leads to an increased urinary acidity and urinary ammonia, decreased ability to dissolve uric acid and lowered carbon dioxide tension and alkaline reserve.

DEFICIENCIES OF VITAMINES.

Recent investigations have shown that diets furnishing sufficient amounts of protein, fat, carbohydrate and inorganic salts may yet prove inadequate for growth or even for maintenance. Hopkins,[72] feeding rats on purified food mixture was unable to obtain any growth until he added small quantities of milk or of the ether-soluble portion of milk but with this addition growth progressed in the normal manner, but it was out of all proportion to the energy or protein value of the addition. Five substances of this character, called by Funk[73] Vitamines, have been described, two of which have definitely established a place as essential food factors. According to him, pellagra, rickets, scurvy and beriberi are the result of a lack of these unidentified but specific and indispensable food complexes.

The first vitamine isolated was the fat soluble A, an adequate supply of which is necessary, not only because of its stimulating growth properties, but because its absence produces a serious condition of the eyes and, at times, marasmus leading to death. Xerophthalmia is a common condition in animals on experimental diets. The eyes are swollen, the cornea inflamed and often opaque while blindness and death invariably occur unless the dietary error is corrected. McCollum[74] rescued animals almost at the point of death by butter or other fat rich in this vitamine. Opacities of the cornea are often seen in the animals in this and other gardens among ungulates—hay-eating mammals; four advanced cases were found, three in seed-eating birds and one in a fox on a diet made up solely of horse muscle. The quantity of vitamine A present in muscle, hay and seeds is very small. It is supplied in largest amounts in milk, eggs, glandular organs and leaves, substances which were very low or absent in the diet of all the affected animals. This xerophthalmia has been reported in man on several occasions, especially by Hrdlicka[75] in American Indians, by Mori[76] in 1400 Japanese during a period of food shortage (this epidemic was cured by the addition of chicken livers to the diet), by Bloch[77] in forty-seven children of Copenhagen fed on a fat free milk who were cured by the administration of cod liver oil. The disease is not however a fat starvation, as it is entirely uninfluenced by vegetable fats which do not contain this vitamine.

Beriberi is an established deficiency disease, frequently seen among the poorer classes of the Orient whose diet is limited to polished rice and fish. It has appeared in Labrador coincident with the excessive use of bolted flour. A similar condition has been induced in pigs and cattle by a diet made up of an excess of cotton seed meal and tankage. Two forms of the disease are described: (1) acute or wet, characterized by marked edema, ascites, hydropericardium, hydrothorax, edema of the lungs, and a congestion of the spleen, liver, kidney, and heart muscle, (2) chronic or dry, characterized by polyneuritis. The disease was first produced experimentally in pigeons by Eijkman[78] in 1897 by means of a diet of polished rice. The paralysis appeared in 2–3 weeks after the diet was initiated. Fraser and Stanton[79] in 1907, found that it could be cured by an alcoholic extract of rice polishings. Funk[80] later determined the vitamine character of this extract. In pigeons and fowls experimental feeding usually results in the chronic or polyneuritic form, expressed by a typical degenerative inflammatory condition of the peripheral nerves. In pigs, on the contrary, Rommel and Vedder[81] produced both types, though the acute or wet beriberi appeared more frequently. In rats the same deficiency causes multiple hemorrhages in the cerebellum and midbrain followed by a degeneration of the associated nervous structures. It is possible that the pathology following a lack of the vitamine B or in fact any of the vitamines will vary with the different species or with varying demands of different individuals. This antineuritic vitamine affects more than the nervous system, and it is possible that all vitamines may have wider effects than are at present described.

Scurvy was the first condition to call attention to diet as a cause of disease. It occurs in man when deprived of fresh vegetables. That faulty diet was in some way the cause of scurvy has been known for many years, but only since 1905 has there been any systematic attempt to determine the peculiar value of the curative foods. At this time Theobald Smith[82] called attention to a disease suggestive of scurvy which developed in guinea-pigs fed on a diet of oatmeal. This observation was confirmed by Holst and Frölich[83] who stated that the disease could be prevented by the addition of fresh milk or cabbage, because in these foods there was present an antiscorbutic or C vitamine. This unidentified substance was easily destroyed or diminished by heat or an alkaline medium. It was found in rather large amounts in succulent vegetables and fruits. McCollum[84] and his coworkers showed that the oat kernel was low in inorganic salts and vitamine A and poor in the quality of its protein; but with these faults corrected it proved to be a complete food for rats. McCollum also found that scurvy developed more readily in animals if the physical properties of the diet favored constipation. He was able to delay the onset of the disease in guinea- pigs for a considerable period by the addition of mineral oil which has no food value, or phenolphthalein, a cathartic. At the same time, Jackson and Moore,[85] found the cecum of all guinea-pigs dying of scurvy, packed with putrefying feces. They were able to produce a mild type of the disease by the injection of the diplococci isolated from the swollen joints.

From these observations it seems safe to conclude that scurvy may not be purely a deficiency disease, or even a simple dietary one, although the presence of a vitamine influence is not excluded; but it is probably the result of a bacterial invasion of tissues debilitated by a faulty diet and by the toxins produced by the putrefactive bacteria developing in a diet unsuited to the anatomical demands of the alimentary tract. This theory receives support from the fact that pasteurization destroys all aciduric bacteria, allowing only the spore-forming putrefactors to develop; and from the fact that scurvy develops more frequently in children on stale pasteurized than on stale raw or boiled milk. In this Garden no suggestion of scurvy has been noted.

Pellagra is very definitely a disease of poverty endemic for years among the poor, especially in the mountains of Northern Italy. It has been under observation in the United States since 1907. So far as is known no cases have been observed among animals. Opinions differ as to the rôle of diet in the etiology but the results of recent studies seem to show that uncomplicated cases of average severity clear up entirely on a diet rich in animal protein. No vitamine deficiency has so far been determined. Wilson’s careful studies of the diets known to have produced the condition show that the etiological factor lies in a deficiency of the protein molecule. The results of Goldberger[86] corroborate this fact, and he concludes from his latest studies that “the dominating rôle of diet in the prevention and causation of pellagra is referable primarily to the character of the protein supply or to the specific quality of the aminoacid makeup of the protein supply.” Just what aminoacid or combination of aminoacids it is, has not been determined, nor has the possibility of a vitamine alone or in combination with the aminoacid factor been absolutely excluded.

The principal influence of the omnivorous diet is toward those degenerations arising primarily from imbalances in the inorganic makeup, or to insufficiencies of certain necessary factors. The vitamine deficiencies are markedly less prevalent in animals than in man whose food is less often consumed in its natural state. It is now known that much of the injury and loss of nutritive value in foods is produced by the processes involved in preparation, preservation, refinement and storage. Whenever the choice of food is not restricted, vitamine deficiencies do not occur. The vitamine requirements probably differ in different species and in individuals from the same species according to their environmental and individual variations. It is very possible that if the diet is low in vitamine content there may arise conditions of relative deficiencies; and McCarrison has shown that a vitamine deficiency associated with a high fat or carbohydrate content may disturb the balance of the endocrine glands. It is however to the inorganic content of the omnivorous food that most of the disturbances peculiar to this diet are to be assigned.

With the flesh eating animals and birds the records present a very different picture. Disorders of the digestive tube, of the storage organs, of the organs of elimination and of the endocrine glands predominate. Their diet is low in carbohydrates and, at times, in fats and very high in protein. Bone supplies the inorganic salts, which in this Garden is fed only to the larger mammals. The carnivorous birds get their inorganic supply from mice which are eaten entire. The carnivores are as a rule large and are given to active fighting or to long flights. In the wild, very probably there are long periods between feasts, while in captivity the food is always plentiful and regularly supplied. This regularity added to the lack of exercise, particularly among the larger animals, must lead to excessive demands upon the storage and eliminating organs. Storage is always promoted by rest and liberal diet, and cleared away by exercise and starvation. The life of these birds and mammals, moreover favors inactivity of the bowels, which, together with the highly putrefactive diet adds another serious factor to a problem which in gardens is almost insurmountable.

IRREGULARITIES OF CARBOHYDRATE METABOLISM.