Transcriber’s notes:

The text of this e-book has been preserved in its original form apart from correction of the typographic errors listed below. Illustrations have been repositioned adjacent to relevant tabulated data, and the List of Illustrations adjusted accordingly. On p.72 an image of the Xanthin formula incorrectly shows a double bond between a carbon and nitrogen atom – the correct formula is shown on the next page – and there is a date discrepancy on p. 248 between the text and the illustration caption (November 18/February 27). Page numbers are shown in the right margin and footnotes are located at the end. Footnotes are located at the end.

Typographic corrections:
enyzmes → enzymes
oxgyen → oxygen
enyzme → enzyme
Futher → Further
mechancial → mechanical
rythmical → rhythmical
economcially → economically
circulirinden → circulirenden
SUBJECT → SUBJECTS
equibrium → equilibrium
availibility → availability
(166) grams → (166 grams)
accusstomed → accustomed
Glassner → Glässner
strach → starch

THE NUTRITION OF MAN

BY

RUSSELL H. CHITTENDEN, Ph.D., LL.D., Sc.D.

AUTHOR OF “PHYSIOLOGICAL ECONOMY IN NUTRITION,” ETC.
PROFESSOR OF PHYSIOLOGICAL CHEMISTRY
AND DIRECTOR OF THE SHEFFIELD
SCIENTIFIC SCHOOL OF YALE UNIVERSITY

WITH ILLUSTRATIONS

NEW YORK

FREDERICK A. STOKES COMPANY

Publishers

Copyright, 1907,
By Frederick A. Stokes Company
All rights reserved
May, 1907
FIFTH PRINTING

PREFACE

The present book is the outcome of a course of eight lectures delivered before the Lowell Institute of Boston in the early part of 1907.

In this presentation of the subject the attempt has been made to give a systematic account of our knowledge regarding some of the more important processes of nutrition, with special reference to the needs of the body for food. In doing this, the facts accumulated by painstaking observations and experiments during recent years in our laboratory have been incorporated with data from other sources and brought into harmony, so far as possible, with the modern trend of physiological thought.

Numerous experimental results, hitherto unpublished, have been introduced, notably in Chapter VII, in which a few of the data recently obtained in our laboratory with dogs are presented in some detail, since they afford evidence of the error of the current arguments concerning the necessity of a high proteid intake by man, as based on the results of earlier investigators with high proteid animals.

It is hoped that the facts and arguments here presented will help to arouse a more general interest in the subject of human nutrition, as right methods of living promise so much for the health and happiness of the individual and of the community.

CONTENTS

LIST OF ILLUSTRATIONS

THE NUTRITION OF MAN

CHAPTER I

FOODS AND THEIR DIGESTION

Topics: The purpose of nutrition. The food of man. Proteid foods. Carbohydrate foods. Fats. Food as fuel. Composition of foodstuffs. Availability of foods. Food as source of energy. Various factors in the nourishment of the body. Processes of digestion. Secretion of saliva. Function of saliva. Enzymes. Reversible action of enzymes. Specificity of enzymes. Mastication. Gastric secretion. Components of gastric juice. Action of gastric juice. Muscular movements of stomach. Time foods remain in stomach. Importance of stomach digestion. Processes of the small intestine. Secretion of pancreatic juice. Chemical changes in small intestine. Destruction of proteid food. Significance of the breaking down of proteid. Change of fatty foods and carbohydrates in intestine. Digestion practically complete at end of small intestine. Putrefaction held in check. Digestion a prelude to utilization of food.

One of the great mysteries of life is the power of growth, that harmonious development of composite organs and tissues from simple protoplasmic cells, with the ultimate formation of a complex organism with its orderly adjustment of structure and function. Equally mysterious is that wonderful power of rehabilitation by which the cells of the body are able to renew their living substance and to maintain their ceaseless activity through a period, it may be of fourscore years, before succumbing to the inevitable fate that awaits all organic structures. This bodily activity, visible and invisible, is the result of a third mysterious process, more or less continuous as long as life endures, of chemical disintegration, decomposition, and oxidation, by which arises the evolution of energy to maintain the heat of the body and the power for mental and physical work.

These three main functions constitute the purpose of nutrition. The growth of the adult man from the tiny cell or germ that marks his simple beginning is at the expense of the food material he absorbs and assimilates. The rehabilitation of the cells, or the composite tissues of the fully developed organism, is accomplished through utilization of the daily food, whereby cell substance is renewed and all losses made good. The energy which manifests itself in the form of heat and mechanical or mental work, i. e., the energy by which the vital machinery is maintained in ceaseless activity, comes from the breaking down of the food materials by means of which, as the saying goes, the body is nourished. The body thus becomes the centre of different lines of activity, the food serving as the material out of which new cells and tissues are constructed, old cells revivified, and energy for running the bodily machinery derived. Development, growth, and vital activity all depend upon the availability of food in proper amounts and proper quality.

The food of man is composed mainly of organic materials, for while, as Dr. Curtis[1] has expressed it, “the plant can make organic matter out of inorganic elements, just this the animal cannot do at all. The thing of legs and locomotion, of spine and speech, can build his organic walls only out of organic bricks ruthlessly ripped from existing walls of other animals or plants.” It is true that man has need of certain inorganic salts in his daily diet, but they are in the nature of aids to nutrition (aside from such as are necessary for the formation of bone and teeth), contributing in some measure toward regulation and control of nutritive processes rather than as a source of energy to the body. Inorganic substances, however, are an integral part of the essential tissues and organs of the body, being combined with the organic constituents of the living cells. Indeed, electrolytes are perhaps the substances that put life into the proteids of the protoplasm, and it is truly important for the integrity and functional power of living cells that the proportion of inorganic constituents therein be kept in a constant condition of quality and quantity. Still, the food of mankind is essentially organic in nature, and while it may be exceedingly varied in character, ranging from the simple vegetable dietary of the natives of India and the Far East to the voluminous admixture of varied forms of animal and vegetable foodstuffs so acceptable to the bon vivant of our western civilization, the principles contained therein are few in number.

The organic foodstuffs are of three distinct types and are classified under three heads, viz.: Proteids or Albuminous foodstuffs, Carbohydrates, and Fats. All animal and vegetable foods, whatever their nature and whatever their origin, are composed simply of representatives of one or more of these three classes of food principles.

Proteid substances are characterized by containing about 16 per cent of nitrogen. In addition, they contain on an average 52 per cent of carbon, 7 per cent of hydrogen, 23 per cent of oxygen, and 0.5–2.0 per cent of sulphur. A certain class of proteids, known as nucleoproteids because of their occurrence in the nuclei of cells, contain likewise a small amount of phosphorus in organic combination. Proteid or albuminous substances constitute the chemical basis of all living cells, whether animal or vegetable. This means, expressed in different language, that the organic substance of all organs and tissues, whether of animals or plants, is made up principally of proteid matter. Proteid substances occupy, therefore, a peculiar position in the nutrition of man and of animals in general. They constitute the class of essential foodstuffs without which life is impossible. For tissue-building and for the renewal of tissues and organs, or their component cells, proteid or albuminous foodstuffs are an absolute requirement. The vital part of all tissue is proteid, and only proteid food can serve for its growth or renewal. Hence, no matter how generous the supply of carbohydrates and fats, without some admixture of proteid food the body will weaken and undergo “nitrogen starvation.” It is to be noted, however, that while the element nitrogen (16 per cent) gives character to the proteid or albuminous foodstuffs, so that they are frequently spoken of or classified as the “nitrogenous foodstuffs,” it is not the nitrogen per se that is so essential for the nutrition of the body. Man lives in an atmosphere of oxygen and nitrogen. He can and does absorb and utilize the free oxygen of the air he breathes; indeed, it is absolutely essential for his existence, but the free nitrogen likewise drawn into the lungs at each inspiration is of no avail for the needs of the body. Further, there are many compounds of nitrogen, some of them closely allied to the proteid foodstuffs in chemical composition, which are just as useless as free nitrogen in meeting the wants of the body for nitrogenous foods.

Dame Nature is very discriminating; she demands a definite form of nitrogenous compound, some peculiar or specific grouping of the nitrogen element with other elements in the food that can make good the waste of proteid tissue. In the inactive and fibrous tissues of animals, such as are found in bones, tendons, and ligaments, there is present a substance known as collagen, which, when boiled with water, as in the making of soups, is transformed into gelatin. This body, because of its close chemical relationship to proteid or albuminous substances, is known as an albuminoid. Yet, though it has essentially the same chemical composition as ordinary albuminous substances and shows many of the reactions characteristic of the latter, it cannot take the place of true proteid in building up or repairing the tissues of the body. To quote again from Dr. Curtis: “Tissue is nitrogenous, so that, of course, only nitrogenous food can serve for its making; but of the two kinds of nitrogenous principles, proteids and albuminoids, behold, proteids only are of avail! Why this is so is unknown, since albuminoid is equally nitrogenous with proteid; but so it is—proteid and proteid alone can fulfil the high function of furnishing the material basis of life. Gelatin cannot even go to make the very kind of tissue of which itself is a derivative. Alongside of its brother proteid, gelatin stands as a prince of the blood whose escutcheon bears the ‘bend sinister.’ Such a one, though of royal lineage, may never aspire to the throne.” It is thus quite clear that the true proteid foods are tissue builders in the broadest sense of the term, and it is equally evident that they are absolutely essential for life, since no other kind or form of foodstuff can take their place in supplying the needs of the body. Every living cell, whether of heart, muscle, brain, or nerve, requires its due allowance of proteid material to maintain its physiological rhythm. No other foodstuff stands in such intimate relationship to the vital processes, but so far as we know at present any form of true proteid, whether animal or vegetable, will serve the purpose.

Carbohydrates include two closely related classes of compounds, viz., sugars and starches. They are entirely free from nitrogen, containing only carbon (44.4 per cent), hydrogen (6.2 per cent), and oxygen (49.4 per cent), and hence are classified as non-nitrogenous foods. Obviously, they cannot serve as tissue builders, but by oxidation they yield energy for heat and work. They constitute an easily oxidizable form of fuel, and when supplied in undue amounts they may undergo transformation within the body into fat, which is temporarily deposited in tissues and organs for future needs.

Fats, like carbohydrates, are free from nitrogen, but differ from them in containing a much larger percentage of carbon, and hence have greater fuel value per pound. Fats contain on an average 76.5 per cent of carbon, 11.9 per cent of hydrogen, and 11.5 per cent of oxygen. With their larger content of carbon and smaller proportion of oxygen, fats are less easily oxidizable than sugars, requiring a larger intake of oxygen for their combustion, but when oxidized they yield more heat per pound than carbohydrates.

Fats and carbohydrates are thus seen to be the natural fuel foodstuffs of the body. They cannot serve for the upbuilding or renewal of tissue, but by oxidation they constitute an economical fuel for maintaining body temperature and for power to run the bodily machinery. It should be remembered, however, that anything capable of being burned in the body may serve as fuel material; hence proteid food, though of specific value as a tissue builder, may likewise by its oxidation yield energy for heat and work, but its combustion, owing to the content of nitrogen, is never complete. Further, its use as fuel is uneconomical and undesirable for reasons to be discussed later, but it is well to know that its oxidation, though incomplete, is accompanied by the liberation of energy, as in the oxidation of non-nitrogenous foods. A portion of the carbon, hydrogen, and oxygen of the proteid molecule will burn within the body to gaseous products, as do sugars and fats, but there remains a nucleus of nitrogen, with some carbon, hydrogen, and oxygen, which resists combustion and must be gotten rid of by the combined labors of liver and kidneys. Fats and carbohydrates, on the other hand, undergo complete combustion to simple gaseous products, carbon dioxide and water, which are easily removed by the lungs, skin, etc.

These three classes of foodstuffs exist in a great variety of combinations or admixtures in nature. In many cases, noticeably in milk, all three occur together in fairly large quantities. In animal foods, such as meats, fish, etc., proteid and fat alone are found, while in perfectly lean meat proteid only is present, excepting a small amount of fat. Again, the white of the egg contains proteid alone. Hence, a meat and egg diet would be essentially a proteid diet. In vegetable foods, as in the cereals, there is found an admixture of proteid and starch, the latter predominating in many cases, as in wheat flour. The following table,[2] showing the chemical composition of various food materials, may be of service in throwing light on the relative distribution of the three classes of foodstuffs in natural products.

THE CHEMICAL COMPOSITION OF SOME COMMON FOOD MATERIALS

In commenting on these figures, reference to which will be made from time to time in other connections, it may be wise to emphasize the large amount of water almost invariably present in natural foodstuffs. Further, it is to be noted that, in animal products especially, the variations in proteid-content are in large measure coincident with variations in the amount of water present. In other words, foods of animal origin if freed entirely of water would, as a rule, show essentially the same percentage of proteid matter. Fat is naturally variable, according to the condition of the animal at the time it was slaughtered. Among the vegetable products, carbohydrate, mainly in the form of starch, becomes exceedingly conspicuous, though proteid is by no means lacking. Indeed, in some cereals, as in oatmeal, in dried peas and beans, the content of proteid will average as high as in fresh beef, while in addition 50–70 per cent of the entire substance is made up of carbohydrate. Again, in the edible nuts, the content of proteid runs high, in some cases higher than in fresh beef, while at the same time carbohydrate and fat are noticeably large. Further, it is to be noted that in nuts there is here and there some striking individuality, as in pine nuts and Brazil nuts, both of which show a noticeable lack of carbohydrate as contrasted with peanuts, almonds, and walnuts; a fact of some importance in cases where a vegetable food rich in proteid is desired, but with freedom from starch.

Another generality, to be thoroughly understood, is that while the figures given for proteid express quite clearly and with reasonable degree of accuracy the relative amounts of proteid matter present in the foodstuffs in question, there may be important differences in availability of which the percentage figures give no suggestion. In other words, the analytical data deal solely with the total content of proteid, while there is needed in addition information as to the relative digestibility, or availability by the body, of the different kinds of proteid food. For example, roast mutton, cream cheese, and dried peas contain approximately the same amount of proteid. Are we then to infer that these three foods have the same nutritive value so far as proteid is concerned? Surely not, since no account is taken of the relative digestibility of the three foods. It is one of the axioms of physiology that the true nutritive value of any proteid food is dependent not alone upon the amount of proteid contained therein, but upon the quantity of proteid that can be digested and absorbed; or, in other words, made available for the needs of the body. The same rule holds good for both fats and carbohydrates, but as proteid is the more important foodstuff, and is as a rule taken more sparingly, the question of availability has greater import with the proteid foods.

The availability or digestibility of foods can be determined only by physiological experiment. By making a comparison for a definite period of time of the amount of a given food ingredient consumed and the amount that passes unchanged through the intestine, an estimate of its digestibility can be made. The result, to be sure, is not wholly free from error, since we cannot always distinguish between the undigested food and so-called metabolic products coming from the digestive juices and from the walls of the intestine; but the errors are not large, and results so obtained are full of meaning. In a general way it may be stated that with animal foods, such as meats, eggs, and milk, about 97 per cent of the contained proteid is digested and thereby rendered available for the body. With ordinary vegetable foods, on the other hand, as they are usually prepared for consumption, only about 85 per cent of the proteid is made available. This is partially due to the presence in the vegetable tissue of cellulose, which in some measure prevents that thorough attack of the proteid by the digestive juices which occurs with animal foods. With a mixed diet, i. e., with a variable admixture of animal and vegetable foods, it is usually considered that about 92 per cent of the proteid contained therein will undergo digestion.

Regarding differences in the availability of fats, it may be stated that, as a rule, the fatty matter contained in vegetable foods is less readily, or less thoroughly, digested than that present in foods of animal origin. In the latter, about 95 per cent of the fat is digested and absorbed. This figure, however, is generally taken as representing approximately the digestibility or availability of the fat contained in man’s daily dietary, since by far the larger proportion of the fat consumed is of animal origin. Carbohydrates, on the other hand, are much more easily utilized by the body. Naturally, sugars, owing to their great solubility and ready diffusibility, offer little difficulty in the way of easy digestion; but starches likewise, though not so readily assimilable, are digested, as a rule, to the extent of 98 per cent or more of the amount consumed. It is thus evident that in any estimate of the food value of a given diet, chemical composition is to be checked by the digestibility or availability of the food ingredients.

As has been stated several times, the proteid foodstuffs are the more important, since proteid matter is essential to animal life. Man must have a certain amount of proteid food to maintain the body in a condition of strength and vigor. The other essential is that the daily food furnish sufficient energy to meet the needs of the body for heat and power. This means that in addition to proteid, which primarily serves a particular purpose, there must be enough non-nitrogenous food (either carbohydrate or fat or both) to provide the requisite fuel for oxidation or combustion to meet the demands of the body for heat and for work; both of which are subject to great variation owing to differences in the temperature of the surrounding air, and especially because of variations in the degree of bodily activity. The energy which a given foodstuff will yield can be ascertained by laboratory experiment, in which a definite weight of the substance is burned or oxidized in a calorimetric bomb under conditions where the exact amount of heat liberated can be accurately measured. The fuel, or energy, value so obtained is expressed in calories or heat units. A calorie may be defined as the amount of heat required to raise 1 gram of water 1° C., or, to be more exact, the amount of heat required to raise 1 gram of water from 15° to 16° C. This unit is usually spoken of as the small calorie, to distinguish it from the large calorie, which represents the amount of heat required to raise 1 kilogram of water 1° C. Hence, the large calorie is equal to one thousand small calories. When burned in a calorimeter, 1 gram of carbohydrate yields on an average 4100 gram-degree units of heat, or small calories; 1 gram of fat yields 9300 small calories. Both of these non-nitrogenous foods burn or oxidize to the same products—viz., carbon dioxide and water—when utilized in the body as when burned in the calorimeter; hence, the figures given represent the physiological heat of combustion, per gram, of the two classes of foodstuffs. Obviously, the fuel values of different foods belonging to the same group or class will show slight variation, but the above figures represent average values.

Unlike fats and carbohydrates, proteids are not burned completely in the body; hence, the physiological fuel value of a proteid is less than the value obtained by oxidation in a bomb calorimeter. In the body, proteids yield certain decomposition products which are removed through the excreta, and which represent a certain quantity of potential energy thus lost to the economy. The average fuel value of proteids burned outside of the body is placed at 5711 calories per gram,[3] or 5.7 large calories. Deducting the heat value of the proteid decomposition products contained in the excreta, the physiological fuel value of proteids is reduced on an average to about 4.1 large calories per gram.[4] Rubner considers that the physiological fuel value of vegetable proteids is somewhat less than that of animal proteids; conglutin, for example, yielding 3.96 calories, as contrasted with 4.3 calories furnished by egg-albumin, or 4.40 calories from casein. On a mixed diet, where 60 per cent of the ingested proteid food is of animal origin and 40 per cent vegetable, the fuel value available to the body would be about 4.1 calories per gram of proteid, on the assumption that the physiological heat value of vegetable proteids averages 3.96 calories per gram and that of animal proteids 4.23 calories per gram (Rubner).

At present, we accept for all purposes of computation the following figures as representing the physiological or available (to the body) fuel value of the three classes of organic foodstuffs:

From these data, it is evident at a glance that 1 gram of fat is isodynamic with 2.27 grams of either carbohydrate or proteid; and since carbohydrate and fat are of use to the body mainly because of their energy value, it is obvious that 50 grams of fat taken as food will be of as much service to the body as 113 grams of starch. In view of the relatively high fuel value of fats, it follows that the physiological heat of combustion of any given food material will correspond largely with the content of fat therein. This is quite apparent from the data given in the table showing chemical composition of food materials, where the fuel value per pound is seen to run more or less closely parallel with the percentage of fat. Experience, as well as direct physiological experiment, teaches us, however, that fat and carbohydrate cannot be interchanged indefinitely, because of the difficulty in utilization of fat when the amount is increased beyond a certain point. Personal experience provides ample evidence of the difference in availability between the two classes of foodstuffs. Carbohydrates are easily utilizable, fats with more difficulty. Palate, as well as stomach, rebels at large quantities of fat; a statement that certainly holds good for most civilized people, though exceptions may be found, as in the Esquimeaux and certain savage races.

In the nourishment of the body, the various factors that aid in the utilization of food are of great moment and must not be overlooked. It is not enough that the body be supplied with the proper proportion of nutrients, with sufficient proteid to meet the demand for nitrogen, and with carbohydrate and fat adequate to yield the needed energy; but all those physiological processes which have to do with the preparation of the foodstuffs for absorption into the circulating blood and lymph must be in effective working order. There is an intricacy of detail here which calls for careful oversight, and it is one of the functions of the nervous system to control and regulate both the mechanical and the chemical processes that are concerned in this seemingly automatic progression of foodstuffs from their entry into the mouth cavity to their final discharge from the alimentary tract, after removal of the last vestige of true nutritive material.

Mastication; deglutition; secretion of the various digestive juices, saliva, gastric juice, pancreatic juice, bile, intestinal juice, etc.; peristalsis, or the rhythmical movements of the muscular walls of the gastro-intestinal tract; the solvent action of the several digestive fluids on the different types of foodstuffs; the absorption of the products formed as a preliminary step in their transportation to the tissues and organs of the body, where they are to serve their ultimate purpose in nutrition; the interaction of these several processes one on the other; and, finally, the influence of the various nerve fibres and nerve centres concerned in the control of these varied activities,—all must work together in harmony and precision if the full measure of available nitrogen and energy-yielding material is to be extracted and absorbed from the ingested food, without undue expenditure of physiological labor. Further, the various processes of cell and tissue metabolism, by which the absorbed food material is built up into living protoplasm, and the chemical processes of oxidation, hydrolysis, reduction, etc., by which the intra and extra cellular material is broken down progressively into varied katabolic or excretory products, with liberation of energy; all these must move forward harmoniously and with due regard to the preservation of an even balance between intake and outgo, if the nutrition of the body is to be maintained at a proper level, and with that degree of physiological economy which is coincident with good health and high efficiency.

We may well pause here and consider briefly some of these processes which play so prominent a part in the proper utilization of the three classes of organic foodstuffs. The first digestive fluid which the ingested food comes in contact with is the saliva. Sensory nerve fibres, chiefly of the glossopharyngeal and lingual nerves which supply the mouth and tongue, are stimulated by the sapid substances of the food, and likewise by mere contact of the food particles with the mucous membrane lining the mouth cavity as the food is masticated and rolled about prior to deglutition. Impulses communicated in this way to the above sensory nerves are transmitted to certain nerve centres in the medulla oblongata, whence impulses are reflected back through secretory nerves going to the individual salivary glands, thereby calling forth a secretion. The production of saliva is thus a simple reflex act, in which the food consumed serves as a true stimulant or excitant. Pawlow,[5] indeed, claims a certain degree of adaptability of the secretion to the character of the food taken into the mouth. Thus, he finds that dry, solid food excites a large flow of saliva, such as would be needed to masticate it properly and bring it into a suitable condition for swallowing. On the other hand, foods containing an abundance of water cause only a scanty flow of saliva. The situation of this secretory centre in the medulla, and the many branchings of nerve cells in this locality would naturally suggest the possibility of salivary secretion being incited by stimuli from a variety of sources. This is indeed the case, and it is worthy of note that a flow of saliva may result from stimulation of the sensory fibres of the vagus nerves as well as of the splanchnic and sciatic, thus indicating how a given secreting gland may be called into activity by impulses or stimuli which come to the centre through very indirect and devious pathways. Further, the secretory centre may be stimulated, and likewise inhibited, by impulses which have their origin in higher nerve centres in the brain. These facts are of great importance in throwing light upon the ways in which a secretion like saliva is called forth and its digestive action thus made possible. The thought and the odor of savory food cause the mouth to water, the flow of saliva so incited being the result of psychical stimulation. Similarly, fear, embarrassment, and anxiety frequently cause a dry mouth and parched throat through inhibition of the secretory centre by impulses which have their origin in higher centres in the brain.

The application of these facts to our subject is perfectly obvious, since they suggest at once how the production or secretion of an important digestive fluid—upon which the utilization of a given class of foodstuffs may be quite dependent—is controlled and modified through the nervous system by a variety of circumstances. We might reason that the appearance, odor, and palatability of food are factors of prime importance in its utilization by the body; that the æsthetics of eating are not to be ignored, since they have an important influence upon the flow of the digestive secretions. A peaceful mind, pleasurable anticipation, freedom from care and anxiety, cheerful companionship, all form desirable table accessories which play the part of true psychical stimuli in accelerating the flow of the digestive juices and thus pave the way for easy and thorough digestion. Further, it is easy to see how thorough mastication of food may prolong mechanical stimulation of the salivary glands and thus increase the flow of the secretion, while the longer stay of sapid substances in the mouth cavity increases the duration of the chemical stimulation of the sensory fibres of the lingual and glossopharyngeal nerves. In this connection, we may cite the view recently advanced by Pawlow that the individual salivary glands respond normally to different stimuli. Thus, there are three pairs of salivary glands concerned in the production of saliva,—the submaxillary, parotid, and sublingual,—all of which pour their secretions through separate ducts into the mouth cavity. By experiment, Pawlow has found that in the dog the submaxillary gland yields a copious flow of saliva when stimulated by acids, the chewing of meats, the sight of food, etc., while the parotid gland fails to respond. On the other hand, the latter gland responds with an abundant secretion when dry food, such as dry powdered meat, dried bread, etc., is placed in the mouth. With this gland, the inference is that dryness is the active stimulus.

As a digestive secretion, saliva serves several important purposes. By moistening the food it renders mastication and deglutition possible; its natural alkalinity tends to neutralize somewhat such acidity as may be present in the food; it dissolves various solid substances, thus making a solution capable of stimulating the taste nerves; lastly, and most important, it has a marked digestive and solvent action on starchy foods. A large proportion of the non-nitrogenous food consumed by man—in most countries—is composed of some form of starch, and this the body cannot use until it has undergone conversion into soluble forms, such as dextrins and sugar. This it is the function of saliva to accomplish, and it owes its activity in this direction to the presence of a soluble ferment or enzyme known as ptyalin.

Enzymes, which play so important a part in all digestive processes, are a peculiar class of substances produced by the living cells which constitute the various secreting glands. They are of unknown composition, and are peculiar in that the chemical changes they induce are the result of what is termed catalysis, i. e., contact. That is, the enzyme or catalyzer does not enter into the reaction, it is not destroyed or used up, but by its mere presence sets in motion or accelerates a reaction between two other substances. The ordinary illustration from the inorganic world is spongy platinum, which, if placed in contact with a mixture of oxygen and hydrogen, causes the two gases to unite with formation of water, although the two gases alone at ordinary temperature will not so combine. In this reaction the platinum is not altered, neither does it apparently enter into the reaction; it is a simple catalyzer. The chemical nature of the change which most digestive enzymes produce is usually defined as hydrolytic, in which the substance undergoing transformation is made to combine with water, thus becoming hydrolyzed, this reaction generally being accompanied by a cleavage or splitting of the molecule into simpler substances. It is to be noted further that enzymes are specific in their action. An enzyme that acts upon starch, for example, cannot act on proteids or fats. Some digestive fluids have the power of producing changes in different classes of foodstuffs, but such diversity of action is always assumed to be due to the presence in the same fluid of different enzymes. Emil Fischer[6] has advanced the theory that the specificity of an enzyme is related to the geometrical structure of the substance undergoing change; i. e., that each enzyme is capable of acting upon or attaching itself only to such molecules as have a definite structure with which the enzyme is in harmony. Or, the enzyme may be considered as a key which will fit only into the lock (structure) of the molecule it acts upon.

One characteristic feature of enzymes is the incompleteness of their action. Thus, the enzyme of saliva transforms starch by a series of progressive changes into soluble starch, two or more dextrins, and the sugar maltose as the chief end-product. A mixture of starch paste and saliva under ordinary conditions, however, never results in the formation of a hundred per cent of maltose, but there always remains a variable amount of dextrin which appears to resist further change. This is apparently due to what is known as the reversible action of enzymes. Thus, the chemical reactions involved here are reversible actions, i. e., they take place in opposite directions. The catalyzer not only accelerates or incites a reaction in the direction of breaking down the substance acted upon, but it also aids in the recomposition of the products so formed into the original or kindred substance. With reversible reactions of this sort the opposite changes sooner or later strike an equilibrium, which remains constant until some alteration in the conditions brings about an inequality and the reactions proceed until a new equilibrium is established. In the body, however, where the circulating blood and lymph provide facilities for the speedy removal by absorption of the soluble products formed, the reaction may proceed until the original substance undergoing change is completely transformed into the characteristic end-product. This reversible action of enzymes is an important feature, and helps explain certain nutritional changes to be referred to later. Whether all enzymes behave in this way is not as yet determined.

Another peculiarity of digestive enzymes is their extreme sensitiveness to changes in their environment. Powerful in their ability to transform relatively large quantities of a given foodstuff into simple products better adapted for absorption and utilization by the body, they are, however, quickly checked in their action, and even destroyed, when the conditions surrounding them are slightly interfered with. They require for their best action a temperature closely akin to that of the healthy body, and any great deviation therefrom will result at once in an inhibition of their activity. Further, they demand a certain definite reaction of the fluid or mixture, if their working power is to be maintained at the maximum. Indeed, many enzymes, like the ptyalin of saliva, are quickly destroyed if the reaction is greatly changed. Enzymes are thus seen to be more or less unstable substances, endowed with great power as digestive agents, but sensitive to a high degree and working advantageously only under definite conditions. Many perversions of digestion and of nutrition are connected not only with a lack of the proper secretion of some one or more digestive enzyme, but also with the lack of proper surroundings for the manifestation of normal or maximum activity.

With these statements before us, we can readily picture for ourselves the initial results following the ingestion of starch-containing foods properly cooked; and it may be mentioned here that the cooking is an essential preliminary, for uncooked starch cannot be utilized in any degree by man. With the mind in a state of pleasurable anticipation, with freedom from care and worry, which are so liable to act as deterrents to free secretion, and with the food in a form which appeals to the eye as well as to the olfactories, its thorough mastication calls forth and prolongs vigorous salivary secretion, with which the food becomes intimately intermingled. Salivary digestion is thus at once incited, and the starch very quickly commences to undergo the characteristic change into soluble products. As mouthful follows mouthful, deglutition alternates with mastication, and the mixture passes into the stomach, where salivary digestion can continue for a limited time only, until the secretion of gastric juice eventually establishes in the stomach-contents a distinct acid reaction, when salivary digestion ceases through destruction of the starch-converting enzyme. Need we comment, in view of the natural brevity of this process, upon the desirability for purely physiological reasons of prolonging within reasonable limits the interval of time the food and saliva are commingled in the mouth cavity? It seems obvious, in view of the relatively large bulk of starch-containing foods consumed daily, that habits of thorough mastication should be fostered, with the purpose of increasing greatly the digestion of starch at the very gateway of the alimentary tract. It is true that in the small intestine there comes later another opportunity for the digestion of starch; but it is unphysiological, as it is undesirable, for various reasons, not to take full advantage of the first opportunity which Nature gives for the preparation of this important foodstuff for future utilization. Further, thorough mastication, by a fine comminution of the food particles, is a material aid in the digestion which is to take place in the stomach and intestine. Under normal conditions, therefore, and with proper observance of physiological good sense, a large proportion of the ingested starchy foods can be made ready for speedy absorption and consequent utilization through the agency of salivary digestion.

Nowhere in the body do we find a more forcible illustration of economical method in physiological processes than in the mechanism of gastric secretion. Years ago, it was thought that the flow of gastric juice was due mainly to mechanical stimulation of the gastric glands by contact of the food material with the lining membrane of the stomach. This, however, is not the case, as Pawlow has clearly shown, and it is now understood that the flow of gastric juice is started by impulses which have their origin in the mouth and nostrils; the sensations of eating, the smell, sight, and taste of food serving as psychical stimuli, which call forth a secretion from the stomach glands, just as the same stimuli may induce an outpouring of saliva. These sensations, as Pawlow has ascertained, affect secretory centres in the brain, and impulses are thus started which travel downward to the stomach through the vagus nerves, and as a result gastric juice begins to flow. This process, however, is supplemented by other forms of secretion, likewise reflex, which are incited by substances, ready formed in the food, and by substances—products of digestion—which are manufactured from the food in the stomach. Soups, meat juice, and the extractives of meat, likewise dextrin and kindred products, when present in the stomach, are especially active in provoking secretion. Substances which in themselves have less flavor, as water, milk, etc., are far less effective in this direction, while the white of eggs and bread are entirely without action in directly stimulating secretion. When the latter foods have been in the stomach for a time, however, and the proteid material has undergone partial digestion, then absorption of the products so formed calls forth energetic secretion of gastric juice. It is thus seen that there are three distinct ways—all reflex—by which gastric juice is caused to flow into the stomach as a prelude to gastric digestion. Further, it has been shown by Pawlow that there is a relationship between the volume and character of the gastric juice secreted and the amount and composition of the food ingested, thus suggesting a certain adjustment in the direction of physiological economy well worthy of note. A diet of bread, for example, leads to the secretion of a smaller volume of gastric juice than a corresponding weight of meat produces, but the juice secreted under the influence of bread is richer in pepsin and acid, i. e., it has a greater digestive action than the juice produced by meat. The suggestion is that gastric juice assumes different degrees of concentration, with different proportions of acid and pepsin, to meet the varying requirements of a changing dietary.

As has been indicated, pepsin and hydrochloric acid are the important constituents of gastric juice. It is noteworthy, however, that it is the combination of the two that is effective in digestion. Pepsin without acid is of no avail, and acid without pepsin can accomplish little in the digestion of food. Pepsin and acid are secreted by different gland cells in the stomach, and gastric insufficiency, or so-called indigestion, may arise from either a condition of apepsia or from hypoacidity. It is worthy of comment that the amount of hydrochloric acid secreted during 24 hours by the normal individual, under ordinary conditions of diet, amounts to what would constitute a fatal dose of acid if taken at one time in concentrated form. At the outset of gastric secretion, the fluid shows only a slight degree of acidity, but as secretion proceeds, the acidity rises to 0.2–0.3 per cent of hydrochloric acid. The main action of gastric juice is exerted on proteid foods, which under its influence are gradually dissolved and converted into soluble products known as proteoses and peptones. It is a process of peptonization, in which the proteid of the food is gradually broken down into so-called hydrolytic cleavage products. The enzyme, like the ptyalin of saliva, is influenced by temperature, maximum digestive action being manifested at about 38° C., the temperature of the body. Further, a certain degree of acidity is essential for procuring the highest degree of efficiency. Ordinarily, it is stated that digestive action proceeds best in the presence of 0.2 per cent hydrochloric acid, but what is more essential for vigorous digestion is a certain relationship between the acid, pepsin, and proteid undergoing digestion. As pepsin and the amount of proteid are increased, the amount of acid, and its percentage somewhat, must be correspondingly increased if digestion is to be maintained at the maximum.

Another important function of gastric juice is that of curdling milk, due to the presence in the secretion of a peculiar enzyme known as rennin. The latter ferment acts upon the casein of milk,—the chief proteid constituent,—transforming it into a related substance commonly called paracasein. This then reacts with the calcium salts present in milk, forming an insoluble curd or calcium compound. From this point on, the digestion of milk-casein by gastric juice is the same as that of any other solid proteid, it being gradually transformed by the pepsin-acid into soluble cleavage products. Why gastric juice should be provided with this special enzyme, capable of acting solely on the casein of milk, can only be conjectured, but we may assume that it has to do with the economical use of this important food. As the sole nutriment of the young, milk occupies a peculiar position as a foodstuff, and being a liquid, its proteid constituent might easily escape complete digestion were it to pass on too hastily through the gastro-intestinal tract. Experiment has shown that when liquid food alone is taken into the stomach it is pushed forward into the small intestine in a comparatively short time. Curdled as it is by rennin, however, casein must stay for a longer period in the stomach, like any other solid food, and its partial digestion by gastric juice thereby made certain. For the reasons above stated, it is apparent why milk should not be treated as a drink in our daily diet. Remembering that when milk reaches the stomach it is converted into a solid clot or curd, there is obvious reason for sipping it, instead of taking it by the glassful, thereby favoring the formation of small, individual clots instead of one large curd, and thus facilitating instead of retarding digestion.

Among other factors in gastric digestion, the muscular movements of the stomach walls are to be emphasized, since we have here a mechanical aid to digestion of no small moment, and likewise a means of accomplishing the onward movement of the stomach contents. The outer walls of the stomach are composed of a thick layer of circular muscular fibres, especially conspicuous at the pyloric end of the organ, where the latter is joined on to the intestine; a smaller, less conspicuous layer of longitudinal muscle fibres, and some oblique fibres. At the pylorus, the circular fibres are so arranged as to form a structure which, aided by a peculiar folding of the inner mucous membrane, serves as a sphincter, closing off the stomach from the duodenum, the beginning of the small intestine. The movements of the stomach were first made the subject of careful investigation by Dr. Beaumont in his study of the celebrated case of Alexis St. Martin, a French Canadian, who, in 1822, was accidentally wounded by the discharge of a musket, with the resultant formation of a permanent fistulous opening in the stomach. Dr. Beaumont, in the description[7] of his observations, writes that “by the alternate contractions and relaxations of these bands (of muscle) a great variety of motion is induced on this organ (the stomach), sometimes transversely, and at other times longitudinally. These alternate contractions and relaxations, when affecting the transverse diameter, produce what are called vermicular or peristaltic motions. . . . When they all act together, the effect is to lessen the cavity of the stomach, and to press upon the contained aliment, if there be any in the stomach. These motions not only produce a constant disturbance, or churning of the contents of this organ, but they compel them, at the same time, to revolve around the interior, from point to point, and from one extremity to the other.” Of more recent investigations, the most important are those made by Cannon,[8] with the X-ray apparatus. From these later studies, it is evident that Dr. Beaumont’s view of the entire stomach being involved in a general rotary movement is not correct, since in reality the movements are confined mainly to the pyloric end of the stomach, the fundus or portion nearer the œsophagus not being directly involved. This means that when food material passes into the stomach, it may remain at the fundic end for some time more or less undisturbed before admixture with the gastric juice occurs, and under such conditions, until acidity creeps in, the salivary digestion of starch can continue.

According to the observations of Cannon, the contractile movements of the stomach commence shortly after the entrance of food, the contractions starting from about the middle of the stomach and passing on toward the pylorus. These waves of contraction follow each other very closely, certainly not more than one or two minutes apart, and perhaps less, while the resulting movements bring about an intimate commingling of food and gastric juice in the pyloric portion of the stomach; followed by a gradual diffusion of the semi-fluid mixture into the fundus accompanied by a gradual displacement of the more solid food in the latter region. These movements of the stomach are more or less automatic, arising from stimuli—the acid secreted—originating in the stomach itself, although it is considered that the movements are subject to some regulation from extrinsic nerve fibres, such as the vagi and the splanchnics. As digestion proceeds and the mass in the stomach becomes more fluid, the pyloric sphincter relaxes and a certain amount of the fluid material is forced into the intestine by the pressure of the contraction wave. This is repeated at varying intervals, depending presumably in some measure upon the consistency of the mass in the stomach, until after some hours of digestion the stomach is completely emptied.

Especially interesting and suggestive are the experiments made by Cannon[9] on the length of time the different types of foodstuffs remain in the stomach. Using cats as subjects, he found that fats remain for a long period in the stomach; they leave that organ slowly, the discharge into the intestine being at about the same rate as the absorption of fat from the small intestine or its passage into the large intestine. Carbohydrate foods, on the other hand, begin to leave the stomach soon after their ingestion. They pass out rapidly, and at the end of two hours reach a maximum amount in the small intestine almost twice the maximum for proteids, and two and a half times the maximum for fats, both of which maxima are reached only at the end of four hours. Carbohydrates remain in the stomach about half as long as proteids. Proteids, Cannon finds, frequently do not leave the stomach at all during the first half-hour after they are eaten. After two hours, they accumulate in the small intestine to a degree only slightly greater than that reached by carbohydrates an hour and a half earlier. The departure of proteids from the stomach is therefore slower at first than that of either fats or carbohydrates. When a mixture of equal parts of carbohydrates and proteids is fed, the discharge from the stomach is intermediate in rapidity. When fat is added to either carbohydrates or proteids it retards the passage of both foodstuffs through the pylorus.

It is evident from what has been stated that the gastric digestion of proteid foods is a comparatively slow process, involving several hours of time; and further, that food material in general remains in the stomach for varying periods, dependent upon its chemical composition. It would appear further, that relaxation of the pyloric sphincter, allowing passage of chyme into the intestine, must depend somewhat upon chemical stimulation, as this offers the most plausible explanation of the diversity of action seen with the different foodstuffs. As has been pointed out, gastric digestion is primarily a process for the conversion of proteid food into soluble products. It would be a mistake, however, to assume that the digestion of proteid foods is complete in the stomach. Stomach digestion is to be considered more as a preliminary step, paving the way for further changes to be carried forward by the combined action of intestinal and pancreatic juice in the small intestine. The importance of gastric digestion is frequently overrated. It is unquestionably an important process, but not absolutely essential for the maintenance of life. Dogs have lived and flourished with their stomachs removed, the intestine being joined to the œsophagus. The intestine is a much more important part of the alimentary tract; it is likewise far more sensitive to changing conditions than the stomach, and undoubtedly one function of the latter organ is to protect the intestine and preserve it from insult. The stomach may be compared to a vestibule or reservoir, capable of receiving without detriment moderately large amounts of food, together with fluid, in different forms and combinations, with the power to hold them there until by action of the gastric juice they are so transformed that their onward passage into the intestine can be permitted with perfect safety. Then, small portions of the properly prepared material may be discharged from time to time through the pylorus without danger of overloading the intestine, and in a form capable of undergoing rapid and complete digestion. Further, the stomach as a reservoir is very useful in bringing everything to a proper and constant temperature before allowing its entry into the intestine. Another fact of some importance is that, contrary to the general view, absorption from the stomach of the products of digestion is not very rapid under ordinary conditions. Even water and soluble salts pass very slowly into the circulation from the stomach. Like the partially digested food material, they are carried forward through the pyloric sphincter into the intestine, where absorption of all classes of material is most marked.

It is in the small intestine that both digestion and absorption are seen at their best. It is here that all three classes of foodstuffs are acted upon simultaneously through the agency of the pancreatic juice, intestinal juice, and bile. Here, too, are witnessed some of the most complicated and interesting reactions and changes occurring in the whole range of digestive functions. Especially noteworthy is the peculiar mechanism by which the secretion of pancreatic juice is set up and maintained. On demand, pancreatic juice is manufactured in the pancreas and poured into the intestine just beyond the pylorus through a small duct—the duct of Wirsung. Secretion is started by contact of the acid contents of the stomach with the mucous membrane of the small intestine, so that as soon as the acid chyme passes through the pyloric sphincter there commences an outflow of pancreatic juice into the intestine. While acid is plainly the inciting agent in this secretory process, its action is indirect. It does not cause secretion through reflex action on nerve fibres, but it acts upon a substance formed in the mucous membrane of the intestine, transforming it into secretin, which is absorbed by the blood and carried to the pancreas, where it excites secretory activity. As would be expected from the foregoing statements, the secretion of pancreatic juice commences very soon after food finds its way into the stomach, and naturally increases in amount with the onward passage of acid chyme into the intestine, the maximum flow being obtained in the neighborhood of the third or fourth hour, after which the secretion gradually decreases. In man, it is estimated on the basis of one or two observations that the amount secreted during 24 hours is about 700 cc., or a pint and a half. Careful experiments, however, tend to show that the quantity of secretion depends in some measure at least upon the character of the food, and also that the composition of the secretion varies with the character of the food. Thus, on a diet composed mainly of meat, the proteid-digesting enzyme is especially conspicuous, while on a bread diet, with its large content of starch, the starch-digesting enzyme is increased in amount. In other words, there is suggested the possibility of an adaptation in the composition of the secretion to the character of the food to be digested.

Pancreatic juice is an alkaline fluid, rather strongly alkaline in fact, from its content of sodium carbonate, and is especially characterized by the presence of at least three distinct enzymes; viz., trypsin, a proteid-digesting ferment; lipase, a fat-splitting enzyme; and amylopsin, a starch-digesting enzyme. It has already been pointed out how dependent the secretion of pancreatic juice is upon the co-operation of the intestinal mucous membrane. A similar dependence is found when the digestive activity of the secretion is studied. As just stated, pancreatic juice contains a proteid-digesting enzyme. This statement, however, is not strictly correct, for if the secretion is collected through a cannula so that it does not come in contact with the mucous membrane of the intestine, it is found free from any digestive action on proteids. The secretion is activated, however, by contact with the duodenal membrane. Expressed in different language, pancreatic juice as it is secreted by the gland does not contain ready-formed trypsin; it does contain, however, an inactive pro-enzyme, which, under the influence of a specific substance contained in the intestinal mucous membrane, known as enterokinase, is transformed into the active enzyme trypsin. There is thus seen another suggestive example of the close physiological relationship between the small intestine and the activity of the pancreatic gland, or its secretion.

The chemical changes taking place in the small intestine are many and varied. The acid chyme, with its admixture of semi-digested food material, as it passes through the pyloric sphincter into the small intestine, is at once brought into immediate contact with bile, pancreatic juice, and intestinal juice, all of which are more or less alkaline in reaction. As a result, the acidity of the gastric juice is rapidly overcome, and the enzyme pepsin, which up to this point could exert its characteristic digestive action, is quickly destroyed by the accumulating alkaline salts. Pepsin digestion thus gives way to trypsin digestion,—most effective in an alkaline medium,—and the proteids of the food, already semi-digested by pepsin-acid, are further transformed by trypsin; aided and abetted by another enzyme, known as erepsin, secreted by the mucous membrane of the intestine. These two enzymes are much more powerful agents than pepsin. It is true that they begin work where pepsin left off, but most striking is the character of the end-products which result from their combined action, since they are small molecules and there is a surprising diversity of them. In other words, while gastric digestion breaks down the proteid foodstuffs into soluble bodies, such as proteoses and peptones closely related to the original proteids, in pancreatic digestion as it takes place in the intestine there is a profound breaking down, or disruption of the proteid molecule into a row of comparatively simple nitrogenous fragments, many of them crystalline bodies; such as leucin, tyrosin, glutaminic acid, aspartic acid, arginin, lysin, histidin, etc., known chemically as monoamino-acids and diamino-acids. We have no means of knowing to how great an extent these more profound disruptive changes of the proteid molecule take place in the intestine. Whether practically all of the ingested proteid food is broken down into these relatively simple compounds prior to absorption, or whether only a small fraction suffers this change, cannot be definitely stated.

A few years ago, the majority of physiologists held to the view that in the digestion of proteid food all that was essential was its conversion into soluble and diffusible forms which would permit of ready absorption into the blood. The belief was prevalent that, since the proteid of the food was destined to make good the proteid of the blood and through the latter the proteids of the tissues, any change beyond what was really necessary for absorption of the proteid would be uneconomical and indeed wasteful. On the other hand, due weight must be given to the fact that in trypsin digestion, proteid can be quickly broken down into simple nitrogenous compounds, and that in the enzyme erepsin, present in the mucous membrane of the intestine, we have an additional ferment very efficient in bringing about cleavage of proteoses and peptone into amino-acids. From these latter facts it might be argued that, in the digestion of proteid foodstuffs by the combined action of gastric and pancreatic juice in the alimentary tract, a large proportion of the proteid is destined to undergo complete conversion into amino-acids, and that from these fragments the body, by a process of synthesis, can construct its own peculiar type of proteid.

This latter suggestion is worthy of a moment’s further consideration. As is well known, every species of animal has its own particular type of proteid, adapted to its particular needs. The proteids of one species directly injected into the blood of another species are incapable of serving as nutriment to the body, and frequently act as poisons. Man in his wide choice of food consumes a great variety of proteids, all different in some degree from the proteids of his own tissues. Is it not possible, therefore, that it is the true function of pancreatic and intestinal digestion to break down the different proteids of the food completely into simple fragments, so that the body can reconstruct after its own particular pattern the proteids essential for its nourishment? Or, we can follow the suggestion contained in the work of Abderhalden,[10] who finds that in the long continued digestion of various proteids by pancreatic juice there results in addition to the amino-acids a very resistant residue, non-proteid in nature, which is termed polypeptid. In other words, Abderhalden believes that pepsin, trypsin, and erepsin are not capable of bringing about a complete breaking down of proteids into amino-acids, but that there always remains a nucleus of the proteid not strictly proteid in nature, though related thereto,—polypeptid,—which may serve as a starting-point for the synthesis or construction of new proteid molecules, the various amino-acids being employed to finish out the structure and give the particular character desired. This view, however, is rendered somewhat untenable by the more recent experiments of Cohnheim,[11] who claims that proteids can be completely broken down by pepsin, trypsin, and erepsin, and consequently polypeptids would hardly be available for the synthesis of proteids. Moreover, Bergell and Lewin[12] have ascertained that there is present in the liver an enzyme or ferment which has the power of digesting or breaking down certain dipeptids and polypeptids into amino-acids. Hence, it follows that if any polypeptids are absorbed from the intestine, they would naturally be carried to the liver, where further cleavage into fragments suitable for synthetical processes might occur. In any event, there is good ground for the belief that the more or less complete disruption of the proteid molecule into small fragments renders possible a synthetical construction of new proteid to meet the demands of the organism; a fact of great importance in our conception of the possibilities connected with this phase of proteid nutrition.

Fatty foods undergo little or no chemical alteration until they reach the small intestine. During their stay in the stomach they naturally become liquid from the heat of the body, and there is more or less liberation of fat from the digestive action of gastric juice on cell walls, connective tissues, etc. Most food fat is in the form of so-called neutral fat, which must undergo hydrolysis or saponification before it can be absorbed and thus made available for the body. This is accomplished by the enzyme lipase, or steapsin, of the pancreatic juice, aided indirectly by the presence of bile. Under the influence of this fat-splitting enzyme all neutral fats, whether animal or vegetable, are broken apart, through hydrolysis, into glycerin and a free fatty acid; the latter reacting in some measure with the sodium carbonate of the pancreatic juice to form a sodium salt, or soluble soap, while perhaps the larger part of the fatty acid is held in solution by the bile present. Soap, free acid, and glycerin are then absorbed from the intestine and are found again combined in the lymph as neutral fat. In this way the fats of the food are rendered available for the nourishment of the body.

The next important chemical change taking place in the small intestine is that induced by the amylopsin of the pancreatic juice, which, acting in essentially the same manner as the ptyalin of saliva, converts any unaltered starch into dextrins and sugar. The latter substance, maltose, is exposed to the action of another enzyme contained in the intestinal secretion termed maltase, which transforms it into dextrose, a monosaccharide.

In these ways the proteids, fats, and carbohydrates of the food are gradually digested, so far as conditions will admit, digestion being practically completed by the time the material reaches the ileocæcal valve at the beginning of the large intestine. Throughout the length of the small intestine absorption proceeds rapidly; water, salts, and the products of digestion passing out from the intestine into the circulating blood and lymph. At the ileocæcal valve, however, the contents of the intestine are practically as fluid as at the beginning of the small intestine, due to the fact that water is continually being secreted into the intestine. In the large intestine, the contents become less and less fluid through reabsorption of the water, and as the propulsive movements of the circular and longitudinal muscle fibres of the intestinal wall carry the material onward toward the rectum, the last portions of available nutriment are absorbed. Finally, in varying degree, certain putrefactive changes are observed in the large intestine involving a breaking down of some residual proteid matter, through the agency of micro-organisms almost invariably present, with formation of such substances as indol, skatol, phenol, fatty acids, etc. These processes, however, in health are held rigidly in check, and count for little in fitting the food for absorption. Digestion, on the other hand, extending as we have seen from the mouth cavity to the ileocæcal valve, is the handmaiden of nutrition, preparing all three classes of organic foodstuffs for their passage into the circulating blood and lymph, and thus paving the way for their utilization by the hungry tissue cells.

CHAPTER II

ABSORPTION, ASSIMILATION, AND THE PROCESSES OF METABOLISM

Topics: Physiological peculiarities in absorption. Chemical changes in epithelial walls of intestine. Two pathways for absorbed material. Function of the liver as a regulator of carbohydrate. Absorption of proteid products. Assimilation of food products. Anabolism. Katabolism. Metabolism. Processes of metabolism. Older views regarding oxidation. Discoveries of Lavoisier. The views of Liebig. Theory of luxus consumption. Oxidation in the body not simple combustion. Oxygen not the cause of the decompositions. Oxidation not confined to any one place. Intracellular enzymes. Living cells the guiding power in katabolism. Some intermediary products of tissue metabolism. Chemical structure of different proteids. Decomposition products of nucleoproteids. Relation to uric acid. Action of specific intracellular enzymes. Creatin and creatinin. Relation to urea. Proteid katabolism a series of progressive chemical decompositions. Intracellular enzymes as the active agents.

Digestion being completed, and the available portion of the foodstuffs thereby converted into forms suitable for absorption, the question naturally arises, In what manner are these products transported from the alimentary tract to the tissues and organs of the body? In attempting to answer this question, we shall find many illustrations of the precise and undeviating methods which prevail in the processes of nutrition. For example, it would seem plausible to assume that the different forms of sugar entering into man’s ordinary diet, all of them being soluble, would be directly absorbed and at once utilized, but such is far from being the case. Milk-sugar and cane-sugar, both appearing in greater or less degree in our daily dietaries, if introduced directly into the blood, are at once excreted through the kidneys unchanged. The body cannot use them, and they are gotten rid of as speedily as possible, much as if they were poisons. When taken by way of the mouth, however, they are utilized, simply because in the intestine two enzymes are present there, known as lactase and invertase, which break each of the sugars apart into two smaller molecules. In other words, milk-sugar and cane-sugar are disaccharides, and if they are to be absorbed in forms capable of being made use of by the body they must be split apart into simpler sugars, viz., monosaccharides, such as dextrose, levulose, etc. The great bulk of the carbohydrate food consumed by man is in the form of starch, and this, as we have seen, is converted into maltose by the action of saliva and pancreatic juice. Maltose, however, like cane-sugar, is a disaccharide, and the body has no power to burn it or utilize it directly; but in the intestine and elsewhere is an enzyme termed maltase, which breaks up maltose into two molecules of the monosaccharide dextrose, and this the body can use. Man frequently consumes starch to the extent of a pound a day, and if utilized it must all undergo transformation into maltose, and then into dextrose. There is no apparent reason why maltose should not be absorbed and assimilated as readily as dextrose, but so urgent is the necessity for this conversion into dextrose that in the blood itself there is present maltase, to effect the transformation of any maltose that may gain entrance there. We are here face to face with a simple fact in nutrition. The body cannot utilize disaccharides directly. Why it is so we cannot say, but the fact is a good illustration of the principle that nothing can be taken for granted in our study of nutrition.

For years, physiologists assumed that the ordinary physical laws of osmosis, imbibition, and diffusion were quite adequate to explain the passage of digested food materials into the blood and lymph. If a substance was soluble and diffusible, that was sufficient; it would quite naturally be absorbed in harmony with its diffusion velocity. This, however, is not wholly true, since experiment shows that the rapidity of absorption of diffusible substances through the wall of the intestine is by no means always proportional to the diffusion velocity of the substance. The lining membrane of the small intestine, where absorption mainly takes place, is not to be compared to a dead parchment membrane. On the contrary, it is made up of living protoplasmic cells; absorption is not a physical, but a physiological, process, in which the living epithelium cells stand as guardians of the portals, ready to challenge and, if need be, modify the rate of passage. Osmosis and diffusion undoubtedly play some part in absorption, but they alone are not sufficient to account for what actually takes place in the absorption of digestion products, and other substances from the living intestine.

The primary products formed in the digestion of proteid foods—the proteoses and peptones—afford another illustration of physiological peculiarity in absorption. These bodies are readily soluble and quite diffusible, yet they are never found to any extent in the circulating blood and lymph during health. It is of course possible, as has been previously suggested, that as soon as formed they undergo transformation into simpler decomposition products in the small intestine; but this is by no means certain. If proteoses and peptones are injected directly into the blood, they cause a marked disturbance, influencing at once blood-pressure, affecting the coagulability of the blood, and in many other ways exhibiting a pronounced deleterious action which at once indicates they are out of their normal environment. They are not at home in the circulating blood, and the latter medium gets rid of them as speedily as possible; they behave like veritable poisons, and yet they are the primary products formed in the digestion of all proteid foodstuffs. On the basis of all physical laws governing diffusion they should be absorbed, and help to renew the proteids of the blood and later the proteids of the tissues. Yet, as we have said, they are not normally present in the blood or lymph. Apparently, in the very act of absorption, as they pass through the epithelial cells of the intestinal wall, before they gain entrance to the blood stream, they undergo transformation into serum-albumin and globulin, the characteristic blood proteids. The other alternative is that, as previously mentioned, they are completely broken down in the intestine into amino-acids, etc., and these simpler products synthesized, as they pass through the intestinal wall toward the blood, into serum-albumin and globulin. Certainly as yet, there is no evidence that the amino-acids, as such, go through the epithelial cells of the intestine; they are not found in the blood or lymph to any appreciable extent, yet the proteids of the blood are reinforced in some manner by the products of proteid digestion. Whichever view is correct, one thing is perfectly obvious, viz., that in the act of absorption the products resulting from the gastric and pancreatic digestion of proteid foods are exposed to some influence, presumably in the epithelial cells of the intestinal wall, by which there is a reconstruction of proteid. Further, the proteid substances so formed are of the type peculiar to the blood of that particular species of animal. The proteids of beef, mutton, chicken, oatmeal, or bread go to make the proteids of human blood.

From these statements, it is obvious that what we term absorption is something more than a simple diffusion of soluble substances from the alimentary tract into the blood current. The process is much more complex than appears on the surface, and our lack of definite knowledge, in spite of numerous efforts to unravel the mystery, merely strengthens the view that we are dealing here with an obscure physiological problem, and not a simple physical one. Digestion induces a splitting up of the food proteid into fragments, large or small, while incidental to absorption there is apparently a reconstruction, or synthesis, of proteid from the fragments so formed. The process seems somewhat costly, physiologically speaking, yet when one considers the variety of proteids consumed as food, it is easy to comprehend how essential it is that in some manner, as in absorption, there be opportunity for construction of the specific proteids of the blood and lymph.

We find an analogous process in the absorption of fats. As we have seen, the fats of the food are broken apart in the small intestine into glycerin and free fatty acid, a portion of the latter, and perhaps all, combining with the alkali of the intestinal juices to form soluble soaps, or sodium salts of the respective fatty acids. The neutral fats present in animal and vegetable foods are all alike in containing the glyceryl radicle, but they differ in the character of the fatty acids present. Further, one form of animal fat, like that from beef, may contain quite a different proportion of stearin, palmitin, and olein than is present in the fat of another animal, like mutton. By digestion, however, they are all broken apart into fatty acid and glycerin. These acids and their salts can be readily detected in the intestine, but they are not found in the blood or lymph, yet shortly after fatty food is taken the lymph is seen to be milky from fat. Obviously, the fatty acids liberated in the intestine are absorbed, either as soluble soaps or as free fatty acids dissolved in bile, but as they pass through the epithelial cells of the intestine into the lacteal radicles, there is a synthesis or reconstruction of fat; and as a result, neutral fats and not soaps are found in the lymph. Here, then, we have a process quite analogous to what apparently occurs in the absorption of proteid, though less complex; and it is possible that this is one of the factors which aids in the formation of a specific fat mixture corresponding, in a measure, to the type of fat present in the particular species. It is well understood that the fat of an animal’s tissues may be modified somewhat by the character of the fat fed, yet in spite of this there is a certain degree of constancy in composition which calls for explanation. Sheep and oxen feeding in the same pasture have fat widely different in the proportion of stearin, palmitin, etc. The fat of man’s tissues is fairly definite in composition, yet he eats a great variety of fatty foods. One man may consume large amounts of hard mutton fat with its relatively large content of stearin, while another individual may take his fat mainly in the form of the soft butter fats, with their relatively large content of olein and palmitin. In both cases, the fat of the man’s tissues will be essentially the same. To be sure, the changes that take place in the tissue cells, reinforced by the construction of fat from other sources, may be partly responsible for this constancy of composition, but the transformations incidental to absorption are quite possibly, in some measure, helpful thereto.

The great bulk of the digested food material is absorbed from the small intestine, and there are two pathways open through which the absorbed material can gain access to the blood. The one path leads directly to the liver, and substances taking this course are exposed to the action of this organ, before they enter into the general circulation. The other path is through the lacteal or lymphatic system, and constitutes a roundabout way for substances to enter the blood stream, since they must first pass through the thoracic duct before entering the main circulation. As a general truth, it may be stated that fats are absorbed through the latter channel, while carbohydrates and proteids follow the first path. The innumerable blood capillaries in the villi of the intestine take up the products resulting from the digestion of proteids and carbohydrates, through which they are passed into the portal vein, and thereby distributed throughout the liver. This means that both carbohydrates and proteids—or their decomposition products—are exposed to a variety of possible changes in this large glandular organ, before they can enter into the tissues of the body. As we have seen, practically all carbohydrate food is converted into a monosaccharide, principally dextrose, in the alimentary tract; and it is in this form of a simple sugar that the carbohydrate passes into the blood. This might easily mean a pound of sugar absorbed during the twenty-four hours, and would obviously give to the blood a high degree of concentration, unless the excess was quickly disposed of. Sugar is very diffusible, and if it accumulates to any extent in the blood it is quickly gotten rid of by excretion through the kidneys. This, however, is wasteful, physiologically and otherwise, and does not ordinarily occur except in diseased conditions. Further, physiologists have learned that a certain small, but definite, amount of sugar in the blood is a necessary requirement in nutrition, and it is the function of the liver to maintain the proper carbohydrate level.

We must again emphasize the great importance of carbohydrate food; there is a far larger amount of starchy food consumed than of any other foodstuff, and it is more readily available as a source of energy. Its presence in the blood, in the form of sugar, is constantly demanded, but it must be kept within the proper limits for the uses of the different tissues and organs of the body. The liver serves as an effective regulator, maintaining, in spite of all fluctuations in the supply and demand, a definite percentage of sugar such as is best adapted to keep the tissues of the body in a normal and healthy condition. This regulation by the liver is rendered possible through the ability of the hepatic cells to transform the sugar brought to the gland into glycogen, so-called animal starch, which is stored up in the liver until such time as it is needed by the body. The process is one of dehydration, the reverse of what takes place in the intestine when ordinary starch is converted into maltose and dextrose. The efficiency of this regulating mechanism depends also upon the ability of the liver to transform glycogen into sugar, presumably through the agency of an enzyme in the hepatic cells. Hence, glycogen may be looked upon as a temporary reserve supply of carbohydrate, manufactured and stored in the liver during digestion, when naturally large amounts of sugar are passing into the portal blood, and to be drawn upon whenever from any cause the content of sugar in the blood threatens to fall below normal. Obviously, there must be some delicate machinery for the adjustment of these opposite changes in the liver, and we may well believe that it is associated with the composition of the blood itself, which in some fashion stimulates and inhibits, as may be required, the functional activity of the liver, or its component cells. In any event, we have in this so-called glycogenic function of the liver a most effective means for accomplishing the complete and judicious utilization of all the sugar formed from the carbohydrates of the food, after it has once passed beyond the confines of the alimentary tract into the blood; preventing all loss, and at the same time guarding against all danger, from undue accumulation of sugar in the circulation. We see, too, how wise the provision that all sugar should pass from the alimentary canal into the portal circulation and not by way of the lymphatics, since by the latter channel the regulating action of the liver would be mainly lost. Further, recalling how soluble and diffusible sugar is, we may well marvel that it practically all passes from the intestine by way of the blood, and escapes entry into the lymphatics. Surely, this marked shunning of the other equally accessible pathway affords a striking illustration of selective action such as might be expected in a physiological process, but not in harmony with the ordinary physical laws of osmosis or diffusion. In conformity with this statement, it may be mentioned that appropriate experiments have clearly demonstrated that the different sugars available as food are not absorbed from the intestine in harmony with their diffusion velocity, but show deviations therefrom which can be explained only on the ground that the intestinal wall exercises some selective action, due to the living cells composing it. Likewise interesting in their bearing on nutrition are the observations of Hofmeister,[13] who finds by experiments on dogs that the assimilation limit of the different sugars shows marked variation. Thus, dextrose, levulose, and cane-sugar have the highest assimilation, while milk-sugar is far less easily and completely assimilated. If this is equally true of man, it indicates that starchy foods, with their ultimate conversion into dextrose, are to be ranked as having a high assimilation limit, thus affording additional evidence of their high nutritive value.

In the absorption of proteid products, their passage from the intestine by way of the portal circulation insures exposure to the action of the hepatic cells, before they are distributed by the general circulation throughout the body. It is only under conditions of an excessive intake of proteid foods that their products are absorbed by way of the lymphatics. These points are clearly established, and there is every ground for believing that substantial reasons exist to account for this single line of departure. Just what the liver does, however, is uncertain. In fact, as already indicated, there is lack of definite knowledge as to how far the proteid foods are broken down in digestion, prior to absorption. The combined action of pepsin, trypsin, and erepsin, if sufficiently long continued, can accomplish a complete disruption of the proteid molecule. We are inclined to assume in a general way that the “proteids taken as food cannot find a place in the economy of the animal body till they have been, as it were, melted down and recast.”[14] How far this melting down or disruption extends in normal digestion, we do not at present know. As already stated, neither proteoses and peptones, nor the amino-acids, are found in the blood stream in sufficient amounts, or with that frequency, to suggest absorption in these forms. Possibly, as some physiologists have suggested, the amount of any of these products to be found at any one time in a given quantity of blood is too small for certain recognition, yet in the twenty-four hours the amount passing from intestine to liver might be sufficiently large to equal the total proteid absorbed. We can, however, at present only conjecture, and must rest content with the simple statement that in the digestion of the proteid foodstuffs, proteoses, peptones, and amino-acids are formed, and that by transformation or total reconstruction of these products, special types of proteid are manufactured either in the epithelial cells of the intestinal walls during absorption, or elsewhere in the body after absorption. If this latter is the case, the liver might readily be regarded as a likely spot for the synthesis to occur.

Bearing in mind what has been said regarding the production of specific types of proteid by every species of animal, we can the more readily conceive of a synthesis “out of fragments of the original molecules rearranged and put together in new combinations, by processes in which the intestine can hardly be supposed to play a part.” This, the liver might well be assumed as capable of accomplishing, and if we were disposed to accept this view we might use as an argument the fact that the products of proteid digestion are taken directly to this organ, before being cast loose in the tissues and organs of the body. There is perhaps as good ground for assuming that a synthesis or reconstruction of proteid takes place all over the body; that, as suggested by Leathes, “the synthesis of proteids is a function of every cell in the body, each one for itself, and that the material out of which all proteids in the body are made is not proteid in any form, but the fragments derived from proteids by hydrolysis, probably the amido-acids, which in different combinations and different proportions are found in all proteids, and into which they are all resolved by the processes, autolytic or digestive, which can be carried out in every cell in the body.” It is certainly a reasonable hypothesis, and since we lack positive knowledge it cannot at present be disproved. All that we can affirm in the light of established fact is that the products of proteid digestion are absorbed from the intestine by way of the portal circulation, and that either in their passage through the intestinal wall, or later on in the liver or elsewhere, there is a construction of new proteid to meet the wants of the body. The liver, indeed, may be effective in both construction and destruction of proteid, but there is no way of telling at present just how far it acts in either direction.

Regarding the absorption of fats, a single statement will suffice, in addition to what has already been said. Fats gain access to the general circulation by passing from the intestine into the lacteal radicles, thence into the lymphatics, whence they move onward into the thoracic duct, and from there are emptied into the great veins at the neck. A small amount is apparently absorbed in the form of soap by the portal circulation, but by far the larger amount of fat gains access to the blood stream without going through the liver.

In these ways, the blood and lymph are continually supplied with proteid, fat, and carbohydrate from the ingested food, and as these fluids surround and permeate the organized elements of the tissues, the latter are enabled to gain what they need to maintain their nutritive balance. Living matter is essentially unstable; it is the seat of chemical changes of various kinds, anabolic or constructive, and katabolic or destructive. The more comprehensive term “metabolic” is applied to all of these changes that take place in living matter. In anabolism, the dead, inert proteids, fats, and carbohydrates are more or less assimilated and made a part of the living matter of the tissue cells, while at the same time a certain amount of the food material, probably the larger amount, is simply stored as such, or left to circulate in the blood and lymph, without being raised to the higher level of living protoplasm. In katabolism, this accumulated material, and in some degree the living substance itself, is broken down or disintegrated with liberation of the stored-up energy, which manifests itself in the form of heat and mechanical work. At times, the anabolic processes predominate and there is a relatively large accumulation of stored-up materials; while at other times, katabolism, with its attendant chemical decompositions, predominates, and the body loses correspondingly. The point to be emphasized here is that the living body, with its multitude of living cells, is the seat of incessant change. Construction and destruction are continually going forward side by side; sometimes the one and sometimes the other predominating, according to existing conditions. The living protoplasm with its attendant storage material is, under ordinary conditions, constantly being made good from the assimilated food, a part of which is raised to the dignity of living matter and becomes an integral part of the living cells, while the larger portion is simply stored for future uses, or circulates in the blood and lymph which bathe them. Doubtless, this storage or circulating material is the main source of the energy which constantly flows from the cells in the form of heat and of work, as a result of the disruptive changes that constitute katabolism.

Worthy of special notice is the fact that cell protoplasm is essentially proteid in nature; water and proteid make up the larger part of its substance, to which are added small proportions of carbohydrate, fat, and mineral matter. Proteid is the basis of cell protoplasm; it is the chemical nucleus of living matter, and owing to the large size of its molecule, with its large number of contained atoms, is capable of many combinations and many alterations. Most of the reactions characteristic of katabolism centre around this proteid, but the disruptive changes that occur undoubtedly involve more largely the circulating materials present in the blood and lymph, and which bathe the cells, rather than the so-called fixed, or organ proteid, of the cell substance itself. Still, while the circulating blood and lymph furnish largely the substances which are made to undergo disintegration in katabolism, the living protoplasmic cell is the controlling power which regulates the extent and character of the decompositions, and proteid matter is the chemical basis of protoplasm. From these statements, we again have suggested the significant importance of the proteid foods in nutrition, since they alone can furnish the material which constitutes the chemical basis of living cells. The human body, which represents the highest form of animal life, is merely, as stated by another, “literally a nation of cells derived from a single cell called the ovum, living together, but dividing the work, transformed variously into tissues and organs, and variously surrounded by protoplasm products” (Waller).

The processes involved in metabolism are not easily unravelled. The word itself is simple, but it is employed to designate that complex of “chemical changes in living organisms which constitute their life, the changes by which their food is assimilated and becomes part of them, the changes which it undergoes while it shares their life, and finally those by which it is returned to the condition of inanimate matter. Gathered together under this one phrase are some of the most intricate and inaccessible of natural phenomena. It implies also, and gently insists on the idea, that all the phenomena of life are at bottom chemical reactions” (Leathes). Regarding the processes of anabolism, as in the construction of living protoplasm out of inert food materials, we can say nothing. This is altogether beyond our ken at present, and doubtless will remain so, since it involves a chemical alteration, or change, akin to that of bringing the dead to life. With the processes of katabolism, however, we may hope for more satisfactory results; and, indeed, to-day we have considerable information of value as to some of the methods, at least, which are the cause of this phase of nutrition. This knowledge, however, has been slow of attainment.

In the earlier years of the sixteenth century, when anatomy and physiology were beginning to make progress, the savants of that day, hampered as they were by grave misconceptions and by the lack of any understanding of chemical phenomena, could not take advantage, naturally, of the suggestion that as wood burns or oxidizes in the air with liberation of heat, so might the food substances, absorbed by the body, undergo oxidation in the tissues and thus give rise to animal heat. Such suggestions were at that time as a closed book, and so we find Vesalius, in 1543, teaching the Galenic doctrines in physiology then prevalent. The conception of heat production, as it existed at that time, may be inferred from the following quotation:[15] “The parts of the food absorbed from the alimentary canal are carried by the portal blood to the liver, and by the influence of that great organ are converted into blood. The blood thus enriched by the food is by the same great organ endued with the nutritive properties summed up in the phrase ‘natural spirits.’ But blood thus endowed with natural spirits is still crude blood, unfitted for the higher purposes of the blood in the body. Carried from the liver by the vena cava to the right side of the heart, some of it passes from the right ventricle through innumerable invisible pores in the septum to the left ventricle. As the heart expands it draws from the lungs through the vein-like artery air into the left ventricle. And in that left cavity, the blood which has come through the septum is mixed with the air thus drawn in, and by the help of that heat, which is innate in the heart, which was placed there as the source of the heat of the body by God in the beginning of life, and which remains there until death, is imbued with further qualities, is laden with ‘vital spirits,’ and so fitted for its higher duties. The air thus drawn into the left heart by the pulmonary vein, at the same time tempers the innate heat of the heart and prevents it from becoming excessive.” In other words, heat was considered as a divine gift, and as can readily be seen, there was an utter lack of appreciation of the use of air in breathing. Even van Helmont, who lived in 1577–1644, and was in a sense an alchemist, still gave credence to the spirits, viz., that the food absorbed from the stomach and intestine is in the liver endued with natural spirits, while in the heart the natural spirits are converted into vital spirits, and in the brain the vital spirits are transformed into animal spirits.[16] Later, Malpighi discovered the true structure of the lungs, and Borelli, in 1680, exposed the erroneous views then prevalent regarding the purpose of breathing. It is not true, says Borelli, that the use of breathing is to cool the excessive heat of the heart or to ventilate the vital flame, but we must believe that this great machinery of the lungs, with their accompanying blood vessels, is for some grand purpose. In a long and vigorous argument, he contends that the “air taken in by breathing is the chief cause of the life of animals, far more essential than the working of the heart and the circulation of the blood.” He quotes the experiments of Boyle, who showed in 1660 “that even in a partial vacuum brought about by his air pump, flame was extinguished and life soon came to an end; the candle went out and the mouse or the sparrow died.”

At this time, and for long afterwards, the belief was prevalent that the air taken up by the blood in the lungs was the air of the atmosphere in its entirety. No one appears to have thought of the possibility of only a part of the air being used, for at that time there was no suspicion that air was a mixture of substances. Mayow, however, in 1668, showed that it was not the whole air which was employed for respiration, but a particular part only. At this time, great attention was being given to a study of nitre or saltpetre; its wonderful properties in combustion were being recognized, and Mayow, who was a chemist of repute, claimed that it had its origin partly in the air and partly in the earth. The air “which surrounds us, and which, since by its tenuity escapes the sharpness of our eyes, seems to those who think about it to be an empty space, is impregnated with a certain universal salt, of a nitro-saline nature, that is to say, with a vital, fiery, and in the highest degree fermentative spirit,” to which the name of “igneo-aereus” was applied. Nitre was shown to be composed of a sal fixum or sal alkali,—potash as it is now called,—and was obviously derived from the earth, while the other part of nitre was made up of the spiritus acidus, or nitric acid. For a time it was supposed that the whole of this spiritus acidus was contained in the atmosphere, but it was soon recognized that this could not be the case, since nitric acid was found to be a corrosive liquid, destructive to life and quite incapable of supporting combustion. Hence, Mayow concluded that only a part of the acid exists in the atmosphere, viz., that part which he termed spiritus nitro-aereus. In combustion, there is something in the air which is necessary for the burning of every flame, unless perchance igneo-aereal particles should pre-exist in the thing to be burnt. These igneo-aereal particles form “the more active and subtle part of air which is thus necessary for combustion, exist in nitre and indeed constitute its ‘more active and fiery part.’” Mayow fully recognized that burning and breathing involved in a measure the same process; both consisted in the consumption of the igneo-aereal particles present in the air. “If a small animal and a lighted candle be shut up in the same vessel, the entrance into which of air from without be prevented, you will see in a short time the candle go out, nor will the animal long survive its funeral torch. Indeed, [says Mayow] I have found by observation that an animal shut up in a flask together with a candle will continue to breathe for not much more than half the time than it otherwise would, that is, without the candle.” Something contained in the air, necessary alike for supporting combustion and for sustaining life, passes from the air into the blood. Mayow expressed his thoughts in these words: “And indeed it is very probable that certain particles of a nitro-saline nature, and those very subtle, nimble, and of very great fermentative power, are separated from the air by the aid of the lungs and introduced into the mass of the blood. And so necessary for life of every kind is that aereal salt (constituent) that not even plants can grow in earth the access of air to which is shut off. But if that same earth be exposed to air and so forthwith impregnated with that fecundating salt, it at once becomes fit again for growing.”[17] Mayow fully appreciated the importance of his nitro-aereal particles in the processes of life; he had indeed a fairly accurate conception of a sound theory of animal heat; he saw that they were equally necessary for burning, or combustion, and for respiration, and so was enabled to draw a parallelism between the two processes; he pointed out that they were essential for the ordinary activity of the muscles of the body, that as muscle work was increased more particles from the air were required; indeed, he clearly foresaw the need which the body had for these igneo-aereal particles in all the chemical processes of life. And thus was foreshadowed a conception of oxidation, a hundred years before Priestley evolved his phlogiston theories and Lavoisier discovered oxygen.

The discoveries of Lavoisier, published in 1789, led to a clear understanding of combustion as a process of oxidation, and paved the way for a fuller knowledge of the part played by the oxygen of the air in the chemical reactions going on in the animal body. Lavoisier showed that the oxygen drawn into the lungs with the air breathed was used in the body for the oxidation of certain substances, carbon being transformed thereby into carbon dioxide, and hydrogen into water. Further, he noted that these oxidations were carried forward on a large scale, and he emphasized the importance of oxygen as being the true cause of the varied decompositions taking place in the living body. The larger the amount of oxygen inspired, the more extensive the oxidation, and consequently the rate of respiration as modifying the intake of oxygen served in his opinion as a regulator to control the extent of the oxidative processes. He pointed out that a definite relationship existed between the amount of work done by the body and the oxygen consumed; greater muscular activity, lower temperature of the surrounding air, the activities attending the digestive functions, all seemed to be associated with a greater utilization of oxygen. Oxidation was the pivot around which all the chemical reactions of the body seemed to centre. Lavoisier, however, was not a physiologist, and he was, quite naturally perhaps, led into some errors. For example, he considered that the process of combustion or oxidation took place in the lungs, certain fluids rich in carbon and hydrogen formed in the different organs of the body being brought there for exposure to the inspired oxygen. Further, his views implied a simple and complete combustion, in which complex substances rich in carbon were directly and completely oxidized to carbon dioxide and water, in much the same manner as combustion occurs outside the body. Again, he assumed that the amount of oxygen taken into the lungs determined the extent of oxidation, just as the use of the bellows, by increasing the draft of air, causes the fire to burn more brightly.

To Liebig (1842) the next great advance was due. This phenomenally clear-minded man, while recognizing at their full value the fundamental theories advanced by Lavoisier, saw and fully appreciated their incompleteness, and he likewise understood their failure to explain many of the phenomena of life more familiar to the physiological mind than to that of a simple chemist like Lavoisier. Liebig had made a special study of the chemical composition of foodstuffs, and likewise of the tissues and organs of the body. He had, moreover, given great attention to the decomposition products formed in the body, especially the nitrogenous substances excreted through the kidneys, as well as the carbon dioxide and water passed out through the lungs and skin. It was not strange, therefore, that he should take exception to Lavoisier’s view that oxidation in the body consisted in the combustion of a fluid, rich in carbon and hydrogen, which was brought to the lungs. On the contrary, Liebig contended that it was the organic compounds, proteids, fats, and carbohydrates, that underwent oxidation, and not necessarily in the lungs, but all over the body, wherever organs and tissues were active. Especially noteworthy was the view advanced by Liebig, and upheld for many years, that of these three classes of compounds the proteids alone served for the construction of organized tissues, like muscle, and that in the activity of this tissue, as in muscle contraction or muscle work, the energy for the work was derived solely from the breaking down or oxidation of this organized proteid. On this ground he termed the proteid foodstuffs “plastic,” or tissue-building foods. Liebig further pointed out that the substances of the body have the power of combining with and holding on to the inspired oxygen, and that fats and carbohydrates, i. e., the non-nitrogenous compounds, easily undergo oxidation or combustion, and thereby furnish the heat of the body. For this reason he termed the corresponding foodstuffs “respiratory” foods. Proteids, on the other hand, according to Liebig’s view, are capable of combustion only in slight degree. The cause of the decomposition of proteid substances in the body was to be traced solely to muscle work, i. e., the energy of muscle contraction, or muscle work, was derived from the breaking down of the proteids of the muscle tissue, and work was the stimulus which brought about proteid decomposition. Non-nitrogenous substances played no part in these reactions; muscle work was without influence on these compounds, oxygen being the sole stimulus which led to their combustion, and heat was the sole product of the combustion.

If Liebig’s theory is correct, that the proteids of the body are decomposed only as the result or the accompaniment of muscle work, and the proteids of the food are used up only as they take the place of the organized proteid so metabolized, it follows that with a like degree of muscular activity a given body will always decompose the same amount of proteid. If excess of proteid food is taken, the surplus will be stored in the tissues, or, in other words, the excretion of nitrogen will not be influenced by the amount of proteid consumed in the food. This was the line of argument made use of by various physiologists[18] who were disposed to criticise Liebig’s view, and quite naturally the question was soon made the subject of many experiments. It will suffice here merely to say that many concordant results were obtained, showing that an abundance of proteid food leads to an increase in the excretion of nitrogen, muscle activity remaining at a constant level. Hence, as Voit states, some other ground than muscle work must be sought as the true cause of proteid katabolism. Consequently, we find this hypothesis of Liebig replaced by the theory of “luxus consumption,” in which it is maintained that while whatever proteid is used up by the work of the muscle must be made good from the proteid of the food, any excess of proteid absorbed from the intestinal canal is to be considered as “luxus,” and like the non-nitrogenous foods may be burned up in the blood, by the oxygen therein, without being previously organized. Hence, we see suggested two causes for the decomposition of proteid in the body, viz., the work of the muscle and the oxygen of the blood. Further, as stated by C Voit,[19] the nitrogen excretion of the hungry or fasting animal affords, according to these views, a measure of the extent to which tissue proteid must be broken down in the maintenance of life, and of the amount of proteid food necessary to be consumed in order to make good the loss; viz., the minimum proteid requirement. Again, since any excess of proteid food beyond this minimal requirement, according to the theory, is destined to be burned up in the blood, or elsewhere, to furnish heat the same as non-nitrogenous foods, it follows that the excess of proteid food can be replaced by non-nitrogenous aliment.

Oxidation, however, is the keynote in any explanation of the processes of metabolism, whether nitrogenous or non-nitrogenous matter is involved. Both alike undergo oxidation, but it is not simple oxidation or combustion that we have to deal with. In the time of Lavoisier, as already stated, it was thought that oxygen alone was the cause of the decomposition going on in the body, but simply increasing the intake of air or oxygen, as in quickened breathing or deeper inspiration, does not increase correspondingly the rate of oxidation. In other words, it is not a direct combination of oxygen with the carbon and hydrogen of the foodstuffs, or tissue elements, that takes place in the body, but rather a gradual, progressive decomposition of complex organic compounds into simpler products; made possible, however, by the agency of the oxygen carried from the lungs by the circulating blood. It was demonstrated years ago that animals breathing pure oxygen do not consume any more of the gas than when breathing ordinary air, and likewise no more carbon dioxide is produced in the one case than in the other. Fifty years ago, Liebig and other physiologists showed that frogs’ muscle placed in an atmosphere free of oxygen could be made to contract or do work for some considerable time, and with liberation of heat. This fact implies a breaking down of muscle substance into simpler bodies, but there is here no free oxygen to act as the inciting cause; indeed, what actually occurs is a cleavage or splitting up of substances in the muscle tissue, but at the expense of oxygen in some form of combination in the muscle. This oxygen must have been taken from the blood at some previous time and stored in the tissue for future use. Again, as C Voit has expressed it, if oxygen were really the immediate cause of the decompositions taking place in the organism, we should expect combustion to occur in harmony with the well-known relationship of the three classes of organic foodstuffs to oxygen. In other words, fats would undergo combustion most readily, carbohydrates next, and lastly the nitrogenous or albuminous compounds. In reality, however, proteid matter is decomposed in largest quantity; a generous addition of proteid food is always accompanied by an increased consumption of oxygen. Yet oxygen is not the inciting cause of the proteid decomposition, as is seen from the fact that in muscle work, where the intake of oxygen is greatly increased, there is no noticeable change in the amount of proteid material broken down. Plainly, in the body we have to deal not with a direct oxidation of the complex compounds of the tissues or of the food, but rather with a gradual cleavage of these higher compounds into simpler substances, these latter undergoing progressively a still further breaking down with intake of oxygen. To repeat, oxygen is not the cause of the decompositions within the body, but the extent of the breaking down of the tissue or food material is the determining factor in the amount of oxygen taken on and used up. The products of decomposition contain more oxygen than the original substances undergoing the breaking down process, which means that oxygen is taken from the blood and used in the physiological combustion that is going on. It is not, however, strictly a combustion process; it is more complicated and more gradual than ordinary combustion, involving first of all a series of what may be termed oxidative cleavages, in which large molecules are gradually, step by step, broken down into simpler molecules, and these latter then oxidized to still simpler forms. Hence, we find the oxidative changes preceded by a variety of alterations in which oxygen may take no part whatever; such as hydrolytic cleavage, where the elements of water are taken on as a necessary step in the cleavage process; dissociation of a simple sort, as when a large molecule breaks up directly into smaller molecules, etc.

These statements by no means detract from the importance of oxygen in the katabolic processes of the body, but it is physiological oxidation that we have to do with, and not simple combustion. Oxygen is not the direct cause of the transformations taking place in the body. As one looks over the history of progress in our knowledge of nutrition from the time of Lavoisier to the present, it is easy to note the gradual change of view regarding oxidation in the living organism. Step by step, it has been demonstrated that there are many factors involved in this breaking down of complex substances; that while oxygen is an ever present requirement, there are other equally important factors to be taken into account. The contrast between the older views and those now current is clearly shown by the difference in attitude regarding the place in the body where oxidation occurs. Thus, in the earlier days, when the view was gradually gaining ground that nutritional changes were mainly the result of oxidation, and that the oxygen drawn into the lungs in inspiration was a primary factor, then, as we have seen, the lungs were considered as the laboratory where the transformation takes place. This view, however, was soon exploded, and next we find the blood, the lymph, and other fluids, but especially the blood, looked on as the locality where oxidation occurs. This was indeed quite a natural view to hold, since the blood is the carrier of oxygen, but we now know, in harmony with the fact that the breaking down of complex food material is a complicated process, involving various kinds of chemical change, that these katabolic processes are not located in any one place, but occur all over the body wherever there are active tissues. As has been previously stated, the human body is a “nation” of cells, all of which are more or less active, and it is in these miniature laboratories mainly that oxidation and all the other nutritional changes coincident to life take place. Muscle tissue and nerve tissue, the large secreting glands, such as the liver, stomach, and pancreas, all are the seat of oxidative and other changes which we class under the broad term of nutritional. To these cells, therefore, we must look for an explanation of the causes of oxidation, and the other transformations of a kindred nature that take place in the body.

In our brief survey of digestion, and of the methods there followed for the proper utilization of the organic foodstuffs, it was seen that the unorganized ferments or enzymes are the active agents in accomplishing the breaking down of proteids, and the less profound alteration of fats and carbohydrates. Is it not possible that the tissues of the body are likewise supplied with enzymes of various types, and that upon these powerful agents rests the responsibility for the different kinds of decomposition, oxidation and other changes, that take place in the body? Some years ago much interest was aroused by the observation that certain glands in the body, if simply warmed at body temperature with water, in the presence of some germicidal agent sufficient to prevent putrefactive changes, underwent what is now termed autodigestion, i. e., a process of self-digestion, with formation of various products, notably such as would naturally result from the breaking down of proteid material by ordinary proteolytic enzymes. This would seem to imply the presence in the glands of a proteid-splitting enzyme, the products formed being proteoses, peptones, amino-acids, etc., just such products as result from the action of trypsin. To-day, we know that practically all tissues and organs can, under suitable conditions, undergo autolysis, and in many instances the enzymes themselves can be separated from the tissues by appropriate treatment. Liver, muscle, lymph glands, spleen, kidneys, lungs, thymus, etc., all contain what are very appropriately called intracellular enzymes. These enzymes are of various kinds. Especially conspicuous are the hydrolytic, proteid-splitting enzymes, which behave in a manner quite similar to, if not identical with, that of the digestive enzymes of the gastro-intestinal tract, i. e., pepsin, trypsin, and erepsin. Further, there are other hydrolytic cleavages taking place in tissue cells, such as the cleavage of fats, due as we now know to intracellular enzymes of the lipase type, and by which neutral fats are split apart into glycerin and fatty acid. Again, there are in many organs intracellular enzymes which act upon the complex nucleoproteids of the tissue, causing them to break apart into proteid and nucleic acid, the latter being further broken down by other enzymes with liberation of the contained nuclein or purin bases. Many other chemical reactions are brought about by specific enzymes of various kinds, present in the cells of particular glandular organs. Thus, intracellular enzymes have been found, as in the liver, which are able to transform amino-acids into amides, and still others capable of splitting up amides.

Equally important, and even more suggestive, are the data which have been collected recently regarding oxidative processes in the tissues of the body. Specific ferments, known as oxidases, are found widely distributed in many organs and tissues, and it is difficult to escape the conclusion that as intracellular enzymes they have an important part to play in some, at least, of the transformations characteristic of tissue katabolism.[20] As a single example, mention may be made of aldehydase, which accomplishes the oxidation of substances having the structure of aldehydes into corresponding acids. Ferments or enzymes of this class are found in the liver, spleen, salivary glands, lungs, brain, kidneys, etc., and they may well be considered as important agents in the chemical transformations going on in the tissues of the body. It would take us too far afield to enter into a detailed consideration of these intracellular enzymes; it must suffice to emphasize the general fact that in all the tissues and organs of the body there are present a large number of enzymes of different types, endowed with different lines of activity, and consequently capable of accomplishing a great variety of results in metabolism. Oxidation may still be a dominant feature in nutrition, oxidative changes may characterize more or less every tissue and organ in the body, but the processes are subtle and are not to be defined in harmony with simple chemical or physical laws. The living cell, with its intracellular enzymes, is the guiding and controlling power by which the processes of katabolism are regulated in harmony with the needs of the body. Complex organic matter is broken down step by step in the various tissues, with gradual liberation of the contained energy; processes of hydrolytic cleavage alternate with processes of oxidation, the molecules acted upon growing smaller with each downward step, until at last the final end-products are reached, viz., carbon dioxide, water, and urea, which the body eliminates through various channels as true physiological waste-products.

It will be advisable for us to consider briefly some of these intermediary products of tissue metabolism, since in any discussion of nutritive changes it is quite essential to have some understanding of the chemical relationship existing between the various products which result from the breaking down of proteid and other materials in tissue katabolism. This is especially true of proteid material, since in the gradual disintegration of this substance in tissue metabolism many intermediary bodies are formed, which undoubtedly exercise some physiological influence prior to their transformation into simpler bodies, with ultimate formation of the final product, urea. As has been pointed out so many times, the proteid foods are peculiar in that they alone contain the necessary nitrogen, and in the peculiar form able to meet the physiological requirements of the body. Variations in the proteid intake are of necessity accompanied by variations in the formation of nitrogenous intermediary products, and both quality and quantity of these substances must be given due attention in any study of nutrition. Further, it is only by an understanding of the general or ground structure of proteids that we can hope to attain knowledge of the processes going on in the different tissues and organs in connection with metabolism, while a true appreciation of the chemical peculiarities of the individual proteids will help to explain the different nutritional value of vegetable as contrasted with animal proteids.

Our understanding of the chemical structure of any organic substance is based primarily upon a study of the decomposition products which result from its breaking down, under the influence of various chemical agencies. Simple proteid substances when acted upon by pancreatic juice reinforced by the enzyme erepsin, or when boiled with dilute acids, undergo hydrolytic cleavage with ultimate formation of a large number of relatively simple bodies, mostly amino-acids, the chemical structure of which throws some light upon the nature of the proteid. Thus, in the pancreatic digestion of proteid in the intestine we may adopt the following scheme as showing in a general way the progressive transformation that occurs, understanding at the same time that like transformations may be accomplished by corresponding intracellular enzymes in the tissues and organs of the body; and further, that by the long-continued action of hydrolytic agents there is a complete breaking down into amino-acids and other simple products.

Native proteid, Protoproteose, Deuteroproteose, Heteroproteose, Primary proteoses, Secondary proteoses, Peptone, Amino-acids

Among these end-products, or amino-acids, are leucin, tyrosin, aspartic acid, glutaminic acid, glycocoll, arginin, lysin, histidin, and likewise the peculiar aromatic body tryptophan. The chemical make-up of these substances may be indicated by the following structural formulæ, which, if even only partially understood, will suggest to the non-chemical mind some idea of close chemical relationship:

Glutaminic acid Aspartic acid

Glycocoll Leucin

Tyrosin

Tryptophan

Arginin Lysin Histidin

In these various decomposition products there is apparent certain definite lines of resemblance, on which is based one or more suggestions regarding possible ways in which these chemical groups are linked, or bound together, in the proteid molecule. Thus, there is apparently present a complex or nucleus which may be indicated as

The proteid molecule is presumably built up of amino-acids variously joined together, this synthesis being accomplished, doubtless, by the condensation of different types of amino-acids, in which the first of the above groups represents the more common method of union. We may indeed conjecture that such methods of condensation take place in the human body, in the epithelial cells of the intestine, and in the tissues in general; and that by such methods, construction of proteid is accomplished out of the various fragments split off by digestion, etc. In a tentative way, the principle may be illustrated by the fusion of leucin and glutaminic acid,—following Hofmeister’s suggestion,—in which a still larger complex is formed:

Leucin Glutaminic acid

In this way, step by step, the proteid molecule is built up, and naturally in katabolism the proteid breaks down along certain definite lines of cleavage, with formation of katabolic products containing those groups, or chemical nuclei, which characterize the different proteid molecules. For it is to be clearly understood that there are many different forms of proteid, perhaps superficially alike, but possessed of physiological individuality. This is well illustrated by the two primary proteoses formed in digestion. As will be recalled, there are at first two proteoses produced, protoproteose and heteroproteose. These are, superficially at least, not radically unlike; they possess essentially the same percentage composition, but when broken down by vigorous chemical methods they show a totally different make-up. In other words, at the very beginning of digestion there is a splitting up of the proteid into two parts, which have quite a different chemical structure, as is clearly indicated by the difference in the character and amount of the decomposition products yielded by hydrolytic cleavage. Thus, heteroalbumose as derived from blood-fibrin contains 39 per cent of its total nitrogen in basic form, i. e., in a form which goes over into the basic bodies, arginin, lysin, and histidin, etc. On the other hand, protoalbumose from the same source yields hardly 25 per cent of basic nitrogen. Further, heteroalbumose yields only a very small amount of tyrosin, while protoalbumose gives on decomposition a large amount of this substance. Again, heteroalbumose furnishes a large yield of leucin and glycocoll, while protoalbumose gives no glycocoll and only a little leucin. Obviously, these two proteoses have an inner structure quite divergent one from the other, and owing to this fact they must play a quite different rôle in metabolism.

Even greater differences in inner chemical structure are found among native proteids. By way of illustration, we may take egg-albumin, the casein of cow’s milk, gliadin of wheat, and the edestin of hemp seed. These are all typical proteids; they are all useful as food, but they are radically different in their inner chemical structure, as is clearly indicated by the following data,[21] which show the percentage yield of the different amino-acids and ammonia:

These are not mere technical differences, but they represent divergences of structure which cannot help counting as material factors in nutritional processes. Especially noticeable is the large yield of glutaminic acid from wheat proteid, as contrasted with the proteid (casein) of animal origin. As a rule, glutaminic acid forms a larger proportion of the decomposition products of vegetable than of animal proteids. Similarly, arginin is present in much larger proportion in most vegetable proteids than in most animal proteids. While many other data more or less trustworthy might be added, these figures will suffice to emphasize the main point under discussion, viz., that individual proteids show marked variation in the amount of the several amino-acids which serve as corner-stones or nuclei in the building up of the molecule, and consequently they must yield correspondingly different katabolic products when serving the body as food.

Turning now to another phase of tissue metabolism, we may consider briefly the nucleoproteids and their characteristic decomposition products; bodies which are widely distributed as cleavage products formed in the disintegration of most cell protoplasm, and having special interest in nutrition because of their chemical relationship to that well-known substance, uric acid. Nucleoproteids of some type are found in all cells; consequently they are present in all tissues, in all glandular organs, and their widespread distribution constitutes evidence of their great physiological importance. Nucleoproteids are compound substances made up of some form of proteid and nucleic acid. By simple hydrolysis with dilute mineral acids they are broken down into proteid, phosphoric acid, and one or more bodies known as nuclein bases. Of these latter substances, there are four well-defined bodies, viz., adenin, hypoxanthin, guanin, and xanthin, which from their peculiar chemical constitution are known as “purin bases.” In the body, there is present in many cells a peculiar intracellular enzyme termed nuclease, which has the power of liberating these purin bases from their combination as a component part of tissue nucleoproteids, or of the contained nucleic acid. In autolysis or self-digestion of many glands, such as the spleen, thymus, etc., this chemical reaction is easily induced by action of the contained nuclease. Further, the liberated purin bases then undergo change because of the presence of certain deamidizing enzymes, and as a result guanin is transformed into xanthin, and adenin is converted into hypoxanthin. These ferments are true intracellular enzymes, and are termed respectively guanase and adenase. The real essence of the reaction they accomplish is clearly indicated by the following formulæ, which likewise show the chemical nature and relationship of the four substances:

Guanin Xanthin

Adenin Hypoxanthin

These two enzymes are typical hydrolyzing enzymes, but it is to be noted that there is not only a taking on of water with a retention of the oxygen, but there is also a giving off of ammonia, by which the transformation is made possible. Adenin is known as an amino-purin and guanin as an amino-oxypurin, while hypoxanthin is an oxypurin and xanthin a dioxypurin. In other words, the two intracellular enzymes are able to transform the two amino-purins into the corresponding oxypurins; i. e., the enzymes are deamidizing ferments, liberating the NH₂ group of the adenin and guanin and thus forming two new compounds. These reactions, though more or less technical, are emphasized in this way not merely because they illustrate the action of intracellular enzymes in intermediary metabolism, thus affording a striking example of the gradual changes that take place in ordinary katabolic processes, but especially because they throw light upon the production of another substance common in body metabolism, viz., uric acid. It has long been known that nucleoproteids, nucleins, and other compounds containing these purin radicles, when taken as food, cause at once an increased output of uric acid, and it has been clearly recognized that in some way this latter substance, as a product of metabolism, must come from the transformation of nuclein bases. To-day, we understand that in many tissues, as in the liver, spleen, lungs, and muscle, there is present a peculiar oxidizing ferment, an oxidase, by the action of which hypoxanthin can be converted into xanthin, and the latter directly oxidized to uric acid. This conversion into uric acid is purely a process of oxidation, brought about by a typical intracellular oxidase, known specifically as “xanthin oxidase,” the reaction involved being as follows:

Xanthin Uric acid

From these several reactions, it is clear how various intracellular enzymes working one after the other are able gradually to evolve uric acid from tissue nucleoproteids. Further, it is to be noted that there is another tissue oxidase—contained principally in the kidneys, muscle, and liver—which has the power of oxidizing and thus destroying uric acid, with formation, among other substances, of urea. Remembering that urea has the following chemical constitution

it is easy to see, by comparison of the formulæ, how uric acid might easily yield two molecules of urea through simple oxidation. In this way, excess of uric acid produced in the body can be converted into urea, and in this harmless form be excreted from the system.

Finally, reference should be made here to several other products of tissue metabolism, products of the breaking down of proteid matter in the body, since they are liable to prove of interest to us in other connections. Thus creatin, abundant in the muscle and other places; the related substance creatinin, present in the urine; methyl guanidin, a decomposition product of creatin; and urea, all call for a word of description. The chemical relationship of these bodies is clearly indicated by the following formulæ:

Creatin          Creatinin

Methyl guanidin Urea

Creatinin is chemically the anhydride of creatin, i. e., it can be formed from creatin by the simple extraction of one molecule of water, H₂O. Creatin, by hydrolytic cleavage, will break down into one molecule of urea and one molecule of sarcosin or methyl glycocoll, as shown in the following equation:

Creatin Sarcosin Urea

Methyl guanidin is a decomposition product of creatin, while guanidin, as can be seen from the formula, is like urea, excepting that the group NH replaces the oxygen of urea. These simple statements will suffice for our present purpose, viz., to indicate the more or less close chemical relationships existing between many of these nitrogenous decomposition products resulting from proteid katabolism; also to suggest how by slight chemical alteration one decomposition product may be resolved into another related substance in the processes of katabolism. Our conception of the processes involved in proteid katabolism is that of a series of progressive chemical decompositions, in which intracellular enzymes play the all-important part. The intermediary products formed are definite bodies because of the specific nature of the active enzymes, and, secondly, because of the chemical nature of the substances acted upon. In other words, oxidation in the animal body takes the shape of a series of well-defined chemical reactions, in which chemical constitution and specific enzyme action are the predetermining cause. In the absence of the particular chemical groups, the oxidase is unable to bring about oxidation, or, given the proper compound or mother substance in the absence of the specific oxidase, there is no oxidation. Hence, oxidation in the animal body is not the result of simple combustion, but, on the contrary, it consists of a series of orderly chemical processes, each one of which is presided over by an intracellular enzyme, specific in its nature, in that it is capable of acting only upon substances having a certain definite constitution, and leading invariably to a certain definite result. The processes which years ago were considered as due to the peculiar vital properties of the tissue cells, and which were supposed to be entirely dependent upon their morphological and functional integrity, are now seen to be due primarily to a great variety of enzymes, manufactured indeed by the living cells, but capable of manifesting their activity even when free from the influence of the living protoplasm. The varied processes of tissue katabolism are the result of orderly and progressive chemical changes, in which cleavage, hydrolysis, reduction, oxidation, deamidization, etc., alternate with each other under the influence of specific enzymes, where chemical constitution and the structural make-up of the various molecules are determining factors in the changes produced.

CHAPTER III

THE BALANCE OF NUTRITION

Topics: Body equilibrium. Nitrogen equilibrium. Carbon equilibrium. Loss of nitrogen during fasting. Influence of previous diet on loss of nitrogen in fasting. Output of carbon during fasting. Influence of pure proteid diet on output of nitrogen. Influence of fat on proteid metabolism. Effect of carbohydrate on nitrogen metabolism. Storing up of proteid by the body. Transformation of energy in the body. Respiration calorimeter. Basal energy exchange of the body. Circumstances influencing energy exchange. Effect of food on heat production. Respiratory quotient and its significance. Influence of muscle work on energy exchange. Elimination of carbon dioxide during work and with different diets. Effect of excessive muscular work on energy exchange. Oxygen consumption under different conditions. Output of matter and energy subject to great variation. Body equilibrium and approximate nitrogen balance to be expected in health.

Man, strictly speaking, is always in a condition of unequilibrium. If placed upon a large and sensitive pair of scales with the opposite side exactly counterpoised, he will be found to lose weight constantly until water or food are taken, when the losses of an hour or two may be made good, or perchance more than balanced. The human body is a maelstrom of chemical changes; chemical decompositions are taking place continuously at the expense of the proteids, fats, and carbohydrates of the tissues and of the food, the stored-up energy of these organic compounds being thereby transformed into the active or “kinetic” forms of heat and motion; while carbon dioxide, water, urea, and some few other nitrogenous substances are being continually formed as the normal waste products of these tissue changes, and constantly or intermittently excreted. In other words, the body is in a perpetual condition of chemical oscillation, constantly consuming its own substance, rejecting the waste products which result, and giving off energy in the several forms characteristic of living beings. The condition of the body plainly depends upon the relation which it is able to maintain between the income and the expenditure of matter and energy. If the income equals the output, the body is kept in a condition approaching equilibrium; if the intake exceeds the outgo, the body adds to its capital of matter and energy; while if the expenditure is greater than the income, the accumulated capital is drawn upon; and this, if continued indefinitely, results in a drain upon the bank which must eventually end in disaster. It is comparatively easy, however, for man to maintain his body in a condition of equilibrium from day to day; i. e., the losses of the morning can be made good at luncheon, or the expenditures of an entire day counterbalanced by a corresponding addition to capital the following day, in which case the body may be said to be in balance. It is necessary, however, to discriminate between body equilibrium, meaning thereby the maintenance from day to day of a constant body-weight, and nitrogen equilibrium, or carbon equilibrium. In the latter cases, what is meant is that the intake of nitrogen, or of carbon, exactly equals the output of these two elements. It is quite possible, however, to have a condition of nitrogen equilibrium without the body being in a state of balance, as when the outgo of carbon exceeds the intake of carbon, or when there is an increased output of water.

As a rule, it may be stated that when a man puts out less carbon and less nitrogen than he takes in he must be gaining in weight; the only exception being the possible case of an increased excretion of water, which might more than counterbalance the gain. On the other hand, if he gives off more carbon and more nitrogen than he takes in, the body must lose in weight. Where the output of carbon is beyond the amount of carbon ingested, the lost carbon represents a drain upon body fat. In a reversal of this condition, i. e., where the carbon taken in is in excess of the outgo, the body is gaining in fat. Theoretically, gain or loss of carbon may mean gain or loss of either carbohydrate or fat, but practically stored-up carbon generally stands for accumulated fat; and, correspondingly, loss of carbon represents a withdrawal from the store of adipose tissue, since glycogen and sugar from a quantitative standpoint figure only slightly in these metabolic processes. When the body excretes more nitrogen than is taken in during a given period, there is only one interpretation possible, viz., that the body is losing proteid or flesh. If, on the other hand, the nitrogen import exceeds the outgo, then the body must be gaining flesh. Here, again, there is the theoretical possibility that gain or loss of nitrogen might represent increase or decrease of proteid in some glandular organ, or even in the blood; but practically it is the relatively bulky muscle tissue, with its high content of proteid matter, that is most subject to change in metabolism. Finally, it is easy to see how, knowing the percentage of nitrogen in proteid and the percentage of carbon in fat, one can calculate from the nitrogen and carbon lost or gained the amounts of proteid or fat added to the capital stock, or withdrawn from the store of nutritive material.

When there is no income, as in fasting, the body loses rapidly, living during the hunger period upon its store of energy-containing material. Many careful observations have been made upon people who have fasted for long periods, some as long as thirty days, the income consisting solely of water. The following figures[22] show the daily excretion of nitrogen in several notable cases:

In Succi’s case, the fasting was continued for thirty days. The daily average loss of nitrogen from the 11th to the 15th day was 5.8 grams; from the 16th to the 20th day, 5.3 grams; from the 20th to the 25th day, 4.7 grams; and from the 26th to the 30th day, 5.3 grams. A daily loss of 5.3 grams of nitrogen means a breaking down, or using up, of 33 grams of proteid, or a little more than one ounce. On the sixth day of fasting, all three of these subjects showed essentially the same daily loss of nitrogen; viz., 10 grams, which implies a using up of 62.5 grams of proteid material. We must not be led astray by these figures, however, or draw too hasty conclusions therefrom regarding the requirements of the body for proteid food. Noting the close agreement in the nitrogen output of the three subjects on the sixth day, combined with the fact that their body-weight was essentially the same, we might infer that 62.5 grams of proteid matter represents the amount of nitrogenous food necessary to maintain nitrogen equilibrium and keep the body in a condition of balance. Such a conclusion, however, would be quite erroneous for several reasons. First, a man fasting, if he was in an ordinary condition of nutrition prior to the fast, has in his tissues a large store of fat. It is considered that in fasting only about 10–12 per cent of the total energy of the body is derived from tissue proteid; the major part comes from the fat stored up. When there is no income to make good the loss, the body must naturally draw upon its own store. A certain amount of proteid must be used up daily, but in addition there are the energy requirements to be considered. These are met mainly by fat and carbohydrate, and so long as fat endures proteid will be drawn upon only, or mainly, to meet the nitrogen requirement; but if the fat gives out, then proteid must be used in larger quantity, as a source of energy. Hence in fasting, the daily loss of nitrogen will be governed largely by the condition of the body as regards fat. Thus, Munk has reported the case of a well-nourished and fat person, suffering from disease of the brain, who gave off daily in the later stages of starvation only one-third the amount of nitrogen voided by Cetti, who had been poorly nourished. Obviously, in fasting, as soon as the adipose tissue of the body has been largely used up, there will be an increase in the amount of tissue proteid consumed, since under such conditions the heat of the body and the energy of muscular work (work of the heart and involuntary muscles) must come from the decomposition of proteid. In harmony with this statement, it is frequently observed that in cases of starvation there comes toward the end a sudden and marked increase in the output of nitrogen.

Secondly, the elimination of nitrogen during the earlier days of fasting is governed in large measure by the character and extent of the diet on the days just preceding the fast. This is well illustrated by some experiments conducted by C Voit on a dog. In the first series of experiments, the dog received daily 2500 grams of meat prior to fasting; in the second series, 1500 grams of meat were fed daily before the fast; while in the third series, a mixed diet relatively poor in proteid was given. The following figures[23] show the amounts of proteid used up by the dog (calculated from the nitrogen excreted) each day of the fasting period, under the different conditions:

We see very clearly in these experiments the effects of the large quantities of proteid fed on the destruction of proteid in the early days of fasting. When the body is rich in proteid from food previously taken, the metabolism of nitrogenous matter is very large at first, as in the first series of experiments. Indeed, in this series, even on the fifth day of fasting, the amount of proteid metabolized was larger than on the second day of the third series. We have here a forcible illustration of the physiological axiom that excess of proteid matter in the tissues, or in the blood, stimulates proteid metabolism; and it affords convincing proof of the contention that in the first days of fasting the output of nitrogen, or the amount of proteid used up, will depend in large measure upon the proteid condition of the body at the time of the fast. Equally noticeable is the fact that there comes a time—the sixth day in the above experiment—when the nitrogen output reaches a common level, irrespective of the previous proteid condition of the body. Further, it is easy to see that the greater loss of nitrogen, i. e., the large breaking down of proteid during the first few days of fasting, in those cases where proteid food has been freely taken, suggests the existence in the tissues of two forms of proteid. We may term them, following the nomenclature of Voit, as circulating and morphotic, or tissue, proteid; or, we may designate them as labile and stable forms of proteid. In other words, following the usually accepted view, this circulating or labile proteid represents reserve or surplus material which is easily decomposed and hence rapidly gotten rid of, while the stable proteid is more slowly oxidized, and its metabolism may be taken as representing more nearly the real necessities of the body. However this may be, it is plainly manifest that the nitrogen output, meaning the metabolism of proteid matter, during hunger or fasting is modified by a variety of circumstances, notably the previous nutritive condition of the body as regards both fat and proteid. It is hardly necessary to add that the amount of muscular work performed is another factor of importance in this connection. Fat in the body represents inert material stored up mainly for nutritive purposes; hence, in hunger it is used largely, and serves to protect more important tissues. Thus, experiments have shown that in long periods of fasting, adipose tissue may be consumed to the extent of 97 per cent of the total amount present, while the heart and nervous tissue will not lose over 3 per cent of their tissue substance. The influence of tissue fat upon the consumption of proteid during hunger can thus be fully appreciated.

The output of carbon during fasting may be illustrated by the following experiment[24] made upon a young man, the nitrogen data being included for comparison, and likewise the intake of food, in terms of nitrogen and carbon, preceding the fast and for two days following the fast. The fasting was of five days’ duration.

On the non-fasting days, the intake consisted of an ordinary food mixture of proteids, fats, and carbohydrates, with a small addition of alcohol. The point to be emphasized here, however, is that the carbon-content was more than sufficient to meet the needs of the body. Thus, it will be observed that on all three of the days when food was taken, the income of carbon was far in excess of the output. In other words, on the day preceding the beginning of the fast the body stored up 135 grams of carbon, and on the day following the fast the body retained 169 grams of carbon to help make good the loss. Similarly, the amount of proteid food taken in on the day prior to the fast was considerably in excess of the needs of the body, 5.1 grams of nitrogen equivalent to 31.8 grams of proteid being stored for future use. Plainly, the man was not in either carbon or nitrogen balance prior to the fast, but was taking far more food than the needs of the body called for. This fact may be emphasized by noting that the total fuel value of the daily food, plus the fuel value of the alcohol, amounted on an average to about 4200 large calories, while the fuel value of the material metabolized on the feeding days averaged only 2500 calories. Looking at the figures showing the output of carbon, as well as of nitrogen, during the fasting days, it is to be seen that in the early days of fasting, the metabolism of the body tends to remain at a fairly constant level, especially when figured per kilogram of body-weight.

To fully appreciate what takes place in a man of the above body-weight fasting for five days (though living on a large excess of food prior to the fast), the daily losses of carbon and nitrogen may be translated into terms of fat and proteid. If it is assumed that the total carbon, aside from what necessarily belongs to the proteid indicated by the nitrogen figures, comes from the oxidation of fat, it is easy to compute the amounts of fat and proteid metabolized, or destroyed, each day of the fasting period. These are shown in the following table:

Finally, if from these figures we calculate the fuel value of the proteid and fat oxidized per day, it is possible to gain a fairly clear conception of the part played by these two classes of tissue material during fasting, in furnishing the heat of the body and the energy for muscular motion, etc.

These somewhat general statements, with the illustrations given, will serve in a brief way to emphasize some of the essential features of metabolism in the fasting individual; where there is no income of energy-containing material, and where the body must draw entirely upon its store of accumulated fat and proteid to keep the machinery in motion, maintain body temperature, and do the tasks of every-day life. When it is remembered that persons have fasted for periods of thirty days or longer without succumbing, it is evident that the body of the well-nourished man has a large reserve of nutritive material, which can be drawn upon in cases of emergency. At the same time, the facts presented show us that in the early days of fasting the actual amounts of tissue proteid and body fat consumed are not large. In Cetti’s case, on the sixth day of fasting the metabolized nitrogen amounted to 10 grams, which implies a loss of 62.5 grams of proteid. At this rate of loss, one pound of dry proteid matter in the form of tissue proteid would meet the wants of a man of 130 pounds body-weight for seven and a half days, provided of course there was a reasonable stock of fat to help satisfy the energy requirements. Finally, we may again emphasize the fact that the loss of nitrogen in the fasting man is by no means a measure of the minimal proteid requirement. By feeding fat, or carbohydrate, or both, the output of nitrogen can be materially diminished, although naturally we cannot establish a nitrogen balance by so doing, since the income is free from nitrogen; but we can postpone for a time the approach of nitrogen starvation.

We may next profitably consider the effect of a pure proteid diet—such as lean meat free from fat—on the output of nitrogen. In studying this problem, we at once meet with several important and surprising facts. First, we are led to see that, strange as it may seem, every addition of proteid to the diet results in an increased excretion of nitrogen. In other words, increase of proteid income is followed at once by an increase in the metabolism of proteid, with a corresponding outgo of nitrogen. The hungry or fasting man with his income entirely cut off, and consequently suffering from a heavy drain upon his capital stock, would be expected, when suddenly supplied with fresh capital in the form of meat or other kind of proteid food, to hold on firmly to this all-important foodstuff; but such is not the case. It is impossible, for example, to establish nitrogen equilibrium by an income of proteid equal to what the individual during fasting is found to metabolize. As stated by another, “It is one of the cardinal laws of proteid metabolism that the store of nitrogenous substances in the body is not increased by, or not in proportion to, an increase in the nitrogen intake.” The principle is well illustrated in the fasting experiment just described. On the fifth day of fasting, the nitrogen output amounted to 11.4 grams. On the day following, the man took 35.6 grams of nitrogen in the form of proteid, while the excretion of nitrogen for that day rose to 26.8 grams. In other words, although deprived of all proteid income for five days, and during that period drawing entirely upon his proteid capital, the man was wholly unable to avail himself of the proteid so abundantly supplied at the close of the fast and make good the losses of the preceding days; only a small proportion of the proteid income could be retained. If a dog fed on a definite quantity of meat suddenly has his proteid income increased, there is at once an acceleration of proteid metabolism, and a corresponding increase in the output of nitrogen. Addition of still more proteid to his income is followed by an accumulation of a portion of the proteid; but this tends to decrease gradually, while there is a corresponding daily increase in the excretion of nitrogen. In this manner, there finally results a condition of nitrogenous equilibrium or nitrogen balance.

Again, an animal brought into nitrogen equilibrium by excessive proteid feeding, if suddenly given a small amount of meat per day, tends to put out nitrogen from its own tissues. This tissue loss, however, decreases slowly, and eventually the animal is quite likely to re-establish nitrogen equilibrium at a lower level. There is, in other words, a strong tendency for the body to pass into a condition of nitrogen balance under different conditions of proteid feeding, even after a long period of nitrogen loss and with an abundance of proteid in the intake. The starving body, as we have seen, cannot make use of all the nitrogen fed, although we can well conceive its great need for all the proteid available. A certain amount of the proteid fed, or its contained nitrogen, is at once passed out of the body and lost, even though the organism be gasping, as it were, for proteid to make good the drain incidental to long fasting. A recent writer[26] has suggested that some explanation for these anomalies may be found in the supposition “that a long succession of generations in the past, which have lived from choice or necessity on a diet rich in proteids, have handed down to us, as an inheritance, a constitution in which arrangements exist for the removal of nitrogen from a considerable part of this proteid. The fact that the amount of proteid taken is re-adjusted to suit the actual needs of the body, though it makes these arrangements unnecessary, will not necessarily remove them. The denitrifying enzyme, which has been trained to keep guard over the entrances by which nitrogenous substances are admitted into the body, will continue to levy its toll of nitrogen, even when the amount of proteid presented to it is no more than the tissues which it serves actually require.”

As an illustration of how the body behaves with a low nitrogen intake followed by a sudden increase in the income of proteid, some data from an experiment performed by Sivén[27] on himself may be cited:

I have ventured to give these data in some detail, because of their exceeding great interest in several directions aside from the point under discussion. Confining our attention to the nitrogen exchange, it is to be observed that for a period of two weeks Sivén lived on less than 3 grams of nitrogen per day, and without any excessive intake of carbohydrate or fat. During this time, the body naturally was in a condition of minus balance as regards nitrogen, the output being considerably larger than the income. The total amount of nitrogen lost in the period, 31 grams, corresponds to a breaking down of 193 grams of tissue proteid, or over one-third of a pound. On increasing the income of nitrogen to 4 grams per day, the nitrogen loss still continued, though at a much lower rate; indeed, the body is seen to approach very closely to a condition of nitrogen equilibrium. Still further increase of the nitrogen income to 13 grams per day was followed at once by a slight accumulation of proteid, and the body showed a decided plus balance of nitrogen, as on November 27. This, however, is seen to decrease gradually with a corresponding daily increase in the outgo of nitrogen, until on December 2 the body was once more practically in nitrogenous equilibrium. On again increasing the nitrogen income, to 23 grams per day, the same process was repeated, although in this case the body more quickly approached a condition of nitrogen balance.

We see in these data striking confirmation of the statement that the nitrogen outgo tends to keep pace with the income of nitrogen, the body always striving to maintain a condition of nitrogen equilibrium. Consequently, the fasting man having lost largely of his store of proteid can replace the latter only slowly, even though he eats abundantly of proteid food. Thus, Sivén in the week ending December 2, though taking over 13 grams of nitrogen a day, retained in his body only 14.5 grams of nitrogen during the entire seven days; while in the six days following, with a daily intake of 23 grams of nitrogen, he gained only about 8 grams additional. The human body does not readily store up proteid, and this is true no matter how greatly the tissues are in need of replenishment.

If the daily income is reinforced by the addition of carbohydrate or fat, there is observed a decided influence on the outgo of nitrogen; the rate or extent of proteid metabolism is at once modified, fat and carbohydrate both having a direct saving effect on proteid. Neither fat nor carbohydrate can prevent the katabolism of proteid, but they can and do decrease it, and thus serve as proteid-sparers. In the fasting body, or where there is only an intake of proteid, the latter material, except for the fat contained in the tissues, must serve the double purpose of meeting the specific nitrogen requirements of the body and furnishing the requisite energy. The energy requirements, however, can be met more advantageously by either of the non-nitrogenous foodstuffs, and just so far as they are oxidized, so far will there be a saving of proteid. Herein lies the philosophy of a mixed diet, with its natural intermingling of proteid, fat, and carbohydrate. For the same reason, the body of a man rich in fat will in fasting lose far less proteid per day than the lean man; or, if fed with a given amount of proteid food, the fat man may attain nitrogen equilibrium, or even store up a little proteid, while on the same diet the lean man will lose proteid. Further, if a man is in nitrogen balance with a given amount of proteid food, the addition of fat or carbohydrate to the diet will permit of a reduction in the amount of proteid necessary to maintain nitrogenous equilibrium. Fat, however, when added to food, does not always protect proteid to the extent possibly suggested by the preceding statements. The following data from oft-quoted experiments by Voit[28] on dogs will serve to illustrate:

It is to be observed that in both of these experiments the fairly large addition of fat results in a saving of proteid, but the sparing effect in the first experiment amounts to only 38 grams of proteid for the 150 grams of fat added. In the second experiment, however, there is a saving of 36 grams of proteid, although only 100 grams of fat were fed. The radical point of difference in the two experiments is the amount of proteid ingested. Proteid food stimulates proteid metabolism; it likewise accelerates the metabolism of non-nitrogenous matter, consequently the sparing or protecting effect of fat on proteid is most conspicuous when the intake of proteid is relatively small. Only under such conditions, does fat protect in large degree the consumption of proteid in the body. In the ordinary, daily, dietary of man, with its great variety of food materials and with its proteid-content not exceeding 125 grams, fat is apt to be a conspicuous element, and under such conditions its sparing effect on proteid metabolism is most marked. Further, it must not be forgotten, as Voit originally pointed out, that the adipose tissue of the body acts like the food-fat, and consequently the proteid-sparing effect of the former may be added to that of the latter.

The addition of carbohydrate to a meat diet produces at once a saving in the decomposition of proteid, as shown in the following figures, covering an experiment of two days:

Without the sugar, there was a minus balance of 64 grams of proteid, but addition of the carbohydrate caused practically a saving of all of this, with establishment of essentially a nitrogen balance. The sparing of proteid by carbohydrate is greater than by fats, a fact of considerable dietetic importance which is well illustrated by the following experiments (on dogs) taken from Voit:

In considering the results of this experiment, it must be remembered that the calorific or fuel value of fat as compared with carbohydrate is as 9.3 : 4.1; in other words, fats have a fuel value of more than twice that of carbohydrates. In spite of this fact, it is clearly evident that carbohydrates as a class—for the different sugars and starches act alike in this respect—are far more efficient than fats in saving proteid. Thus, with an income of 500 grams of meat and 250 grams of fat, the body of the animal lost 58 grams of proteid, while with a like amount of meat and 300 grams of sugar the body not only saved the 58 grams, but in addition stored 34 grams of proteid, showing a plus balance to that extent. The sparing of proteid by carbohydrate amounts on an average, according to Voit, to 9 per cent—in the highest cases to 15 per cent—of the proteid given, while the saving produced by fat averages only 7 per cent. Further, increasing quantities of carbohydrates in the food diminish the rate of proteid metabolism much more regularly and constantly than increasing quantities of fat. We may attribute this difference in action, in a measure at least, to the greater ease in oxidation and utilization of the carbohydrate. In any event, starches and sugars are most valuable adjuncts to the daily diet, because of this marked proteid-saving power, while their fuel value adds just so much to the total energy intake.

A more striking illustration of the action of carbohydrate in sparing proteid is seen in experiments on man, where the nitrogen intake is reduced to a minimum, so as to constitute a condition of specific nitrogen-hunger. In such a case, increasing amounts of carbohydrate added to the intake reduce enormously the using up of tissue proteid. The following experiment with a young man 22 years old and 71.3 kilos body-weight, reported by Landergren,[29] affords good evidence of the extent to which this proteid sparing power may manifest itself.

We see here the nitrogen consumption fall to the exceedingly low level of 3.34 grams per day, or 0.047 gram per kilo of body-weight. To appreciate the full significance of this drop in the extent of proteid metabolism, we may recall that Succi, with a body-weight of only 62.4 kilos, on the seventh day of fasting excreted 9.4 grams of nitrogen, corresponding to a metabolism of 58.7 grams of tissue proteid. In other words, with an intake of only 5.6 grams of proteid, the addition of 908 grams of carbohydrate, with a total fuel value of 3745 calories, reduced the consumption of tissue proteid to 20.8 grams. The same individual, if fasting, would undoubtedly have used up at least 70 grams of tissue proteid.

It is evident from what has been said that both of these non-nitrogenous foods, fat and carbohydrate, play a very important part in nutrition, because of their ability to maintain in a measure the integrity of tissue proteid. When we recall that a diet of pure proteid, such as meat or eggs, must be excessive in quantity in order to meet the energy requirements of the body, and that the stimulating action of proteid food serves to whip up body metabolism, we can appreciate at full measure the great physiological economy which results from the addition of carbohydrate and fat to the daily diet. The establishment of nitrogenous equilibrium is made possible at a much lower level by the judicious addition of these two non-nitrogenous foodstuffs. The same principle may be illustrated in another way, viz., by noting the effect on tissue proteid of withdrawal of a portion of the fat or carbohydrate of the intake, in the case of a person nearly or quite in nitrogen balance. The following experiment[30] affords a good example of what will occur under such treatment:

Starting with the body in a condition of plus nitrogen balance, i. e., with a mixed diet more than sufficient to maintain the tissue proteid intact, the reduction of the fuel value of the food from 1955 to 1493 calories by cutting off 112 grams of carbohydrate per day was followed by a gradual, but marked, increase in the output of nitrogen; indicating thereby the extent to which the body proteid was then drawn upon to make good the loss of energy-containing income. The body showed at the close of the experiment a minus nitrogen balance averaging 2.2 grams per day, or a loss of 13.8 grams of tissue proteid, which would obviously have continued, under the above conditions, until the body was exhausted. In other words, the 112 grams of carbohydrate, if added to the diet on December 3 and the following days, would have quickly saved the daily loss of 2.4 grams of nitrogen, and thus changed the drain of tissue proteid to an actual gain, with consequent establishment of a growing plus balance.

It is obvious from what has been stated, that in man the body can accomplish a storing of proteid only when the intake is reinforced by substantial additions of fat or carbohydrate. It is plainly a matter of great physiological importance that the body should be able to increase at times its reserve of proteid. This, however, cannot apparently be accomplished on a large scale under ordinary conditions. Any storing up of nutritive material in excess, whether it be proteid or fat, necessarily involves overfeeding, i. e., the taking of an amount of food beyond the capacity of the body to metabolize at the time. Fat, as we know, may be stored in large quantities, and it is in cases of overfeeding with non-nitrogenous foods that we find accumulation of fat most marked. Overfeeding with proteid, however, does not lead to corresponding results, owing primarily to the peculiar physiological properties of proteid; its general stimulating effect on metabolism, the tendency of the body to establish nitrogenous equilibrium at different levels, and the fact emphasized by von Noorden that flesh deposition is primarily a function of the specific energy of developing cells. In other words, the protoplasmic cells of the body are more important factors in the storing or holding on to proteid than an excess of proteid-containing food.

It is generally considered as a settled fact, that in man it is impossible to accomplish any large permanent storing or deposition of flesh by overfeeding. Similarly, it is understood that the muscular strength of man cannot be greatly increased by an excessive intake of food. The only conditions under which there is ordinarily any marked and permanent flesh deposition are such as are connected with the regenerative energy of living cells. Thus, as von Noorden has stated, an accumulation or storing of tissue proteid is seen especially in the growing body, where new cells are being rapidly constructed; also in the adult where growth may have ceased, but where increased muscular work has resulted in an hypertrophy or enlargement of the muscular tissue; and lastly in those cases where, owing to previous insufficient food or to the wasting away of the body incidental to disease, the proteid content of the tissues has been more or less diminished, and consequently an abundance of proteid food is called for and duly utilized to make good the loss. In some oft-quoted experiments by Krug, conducted on himself, it was observed that with an abundant food intake, sufficient to furnish 2590 calories per day (44 calories per kilo of body-weight), a condition approaching nitrogenous equilibrium was easily maintained. On then increasing the fuel value of the food to 4300 calories (71 calories per kilo of body-weight) by addition of fat and carbohydrate, there was during a period of fifteen days a sparing of 49.5 grams of nitrogen or 309 grams of proteid, which would correspond to about 1450 grams, or three pounds, of fresh muscle. It is to be noted, however, that of this excess of calories added to the intake only 5 per cent was made use of for flesh deposit, the remaining 95 per cent going to make fat.

Again, we may call attention to the well-known fact that in feeding animals for food, while fat may be laid on in large amounts, flesh cannot be so increased by overfeeding. In this matter, however, race and individuality count for considerable. Thus, there is on record a more recent series of experiments conducted by Dapper[31] on himself which shows some remarkable results. Starting with a daily diet not excessive in amount, he was able by an addition of only 80 grams of starch to accomplish a laying up of 3.32 grams of nitrogen per day for a period of twelve days, or a total gain of 39.8 grams of nitrogen, equal to 248 grams of proteid. It may be said that the gain of proteid or flesh here for the twelve days was no greater than in the preceding case (fifteen days), but the difference lies in the fact that Krug accomplished his gain by increasing the daily intake from 2590 to 4300 calories, an amount which he found too large to be eaten with comfort, while the later investigator raised the fuel value of his daily food from 2930 to only 3250 calories. As the experiments by Dapper contain other points of interest bearing on the question before us, we may advantageously consider them somewhat in detail. The following table gives the more important results:

As we look at these results, the nitrogen gain for the first and second days of the third experiment and the first day of the second experiment may well attract our attention, since they show an astonishing laying by of proteid, or gain of flesh, under the influence of a comparatively small increase in the fuel value of the food. A gain of 5.98 grams of nitrogen means 37.3 grams of proteid, or more than an ounce; by no means an inconsiderable addition for one day to the store of tissue proteid. In the third experiment, where plasmon (dried, milk proteid) was added to the diet, there is to be noted a gradual falling off in the proteid-sparing power, which may perhaps be interpreted as implying that the body was practically saturated with proteid, and that owing to this fact the body was unable to continue its laying hold of nitrogen. In the entire period of 21 days, however, the body had succeeded in accumulating a store of 62.8 grams of nitrogen, or 392 grams of proteid, and this without adding very largely to the intake of non-nitrogenous matter. This experiment affords a striking illustration of the ability of the body to “fatten on nitrogen,” but it is very doubtful if such results can generally be obtained. Lüthje,[32] however, has reported a large retention of nitrogen on a diet containing 50 grams of nitrogen daily, with a fuel value of 4000 calories. It is more than probable that there existed in these particular cases some personal peculiarity or idiosyncrasy which favored the proteid-sparing power. The personal coefficient of nutrition is not to be ignored; it shows itself in many ways, and the above results are to be counted among those that are exceptional and not the rule. In the words of Magnus-Levy, “a given diet with Cassius may lead to different results than with Anthony.”

For the study of many questions in nutrition, it becomes necessary to determine accurately the transformations of energy within the body as contrasted with the transformation of matter; the total income and outgo of energy, measured in terms of heat, are to be compared one with the other and a balance struck. Further, in studying the metabolism of carbohydrate and fat it is necessary to determine the output of gaseous products through the lungs and skin; to estimate the excretion of carbon dioxide and water, and the intake of oxygen. For these purposes, a special form of apparatus known as a respiration calorimeter is employed. The double name is indicative of the twofold character of the apparatus, viz., a suitably constructed chamber so arranged as to permit of measuring at the same time the respiratory products and the energy given off from the body. The form of apparatus best known to-day, and with which exceedingly satisfactory work has been done, is the Atwater-Rosa apparatus, as modified by Benedict. It consists essentially of a respiration chamber, in reality an air-tight, constant-temperature room (with walls of sheet metal, outside of which are two concentric coverings of wood completely surrounding it, with generous air spaces between), sufficiently large to admit of a man living in it for a week or more at a time. Connected with the chamber is a great variety of complex apparatus for maintaining and analyzing the supply of oxygen, determining the amount of carbon dioxide and of water, etc., etc. As an apparatus for measuring heat, the chamber may be described as “a constant-temperature, continuous-flow water calorimeter, so devised and manipulated that gain or loss of heat through the walls of the chamber is prevented, and the heat generated within the chamber cannot escape in any other way than that provided for carrying it away and measuring it.”[33]

In illustration of the efficiency of an apparatus of this description, and of the close agreement obtainable by direct calorimetric measurement with the estimated energy, as figured from the materials oxidized in the body, we may quote the following data from Dr. Benedict’s report, referred to in the footnote. The subject was a young man who had been fasting for five days. The experiment deals with the metabolism on the first day after the fast, when a diet composed mainly of milk was made use of, containing 53.31 grams of proteid, 211.87 grams of fat, and 75.41 grams of carbohydrate. The following table shows the results of the experiment:

As is seen from the above figures, the total fuel value of the food was 2569 calories. The fuel value of the unoxidized portion of the food contained in the excreta was 149 + 103 calories, leaving as the available energy of the food 2317 calories. This must be further corrected by the fact, mentioned in the footnote, that a portion of the food was stored as fat and glycogen, while the body lost at the same time a small amount of proteid. Making the necessary correction for these causes, we find 2088 calories as the energy from material oxidized in the body. The actual output of energy as measured by the calorimeter was 2113 calories, only 1.2 per cent greater than the estimated amount.

By aid of the respiration calorimeter, many important questions in nutrition can be more or less accurately answered, especially such as relate to the total energy requirements of the body. The law of the conservation of energy obtains in the human body as elsewhere, and if we can measure with accuracy the total heat output, with any energy liberated in the form of work, and at the same time determine the total excretion of carbon dioxide, water, nitrogen, etc., together with the intake of oxygen, it becomes not only possible to ascertain the energy requirements of the body under different conditions, but, aided by data obtainable through study of the exchange of matter, we can draw important conclusions concerning the sources of the energy, i. e., whether from proteid, fat, or carbohydrate.

It is obvious that a man asleep, or lying quietly at rest, in the calorimeter, especially when he has been without food for some hours, furnishes suitable conditions for ascertaining the minimal energy requirements of the body. Under such conditions, bodily activity and heat output are at their lowest, and we are thus afforded the means of determining what is frequently called the basal energy exchange of the body. The following table taken from Magnus-Levy, and embodying results from many sources, shows the heat production during sleep, calculated for 24 hours, of various individuals of different body-weight and of different body surface.

I venture to present these individual results, rather than make a general statement simply, because it is important to recognize the fact that the basal energy exchange differs according to body-weight, extent of body surface, and the condition of the body. In the table, the results are arranged in the order of body-weight, and it is plain to see that the absolute energy exchange is greater with heavy persons than with light, yet the energy exchange does not increase in proportion to increase of body-weight. With a man of 83 kilos body-weight, the basal exchange is only 30–40 per cent higher than in a man of 43 kilos body-weight. In other words, the man of small body-weight has, per kilo, a much higher basal exchange than the heavier man. The energy exchange is more closely proportional to the extent of body surface than to weight.

As Richet has expressed it, the basal energy exchange is inversely proportional to the body-weight and directly proportional to the body surface. This is in harmony with the view advanced by v. Hösslin, “that all the important physiological activities of the body, including of course its internal work and the consequent heat production, are substantially proportional to the two-thirds power of its volume, and that since the external surface bears the same ratio to the volume, a proportionality necessarily exists between heat production and surface.”[35]

There are, however, many circumstances that modify, or influence, energy exchange. Thus, the taking of food, with all the attendant processes of digestion, assimilation, etc., involves an expenditure of energy not inconsiderable. This has been experimentally demonstrated on man by several investigators. With fatty food, Magnus-Levy found that his subject lying upon a couch, as completely at rest as possible, produced in the 24 hours 1547 calories when 94 grams of fat were eaten, and 1582 calories when 195 grams of fat were consumed. The increase of heat production over the basal energy exchange was 10 and 58 calories respectively. With a mixed diet, where proteid food is a conspicuous element, the increase in heat production is much more marked. Thus, in some experiments reported from Sweden the following data were obtained:[36]

We see here an increase of 495 calories per day in heat production, due to metabolism of the food ingested. In other words, with a basal energy exchange of 2022 calories, the average of the five fasting days, energy equivalent to 495 calories was expended in taking care of the ingested food. It should be added, however, that the daily ration here was somewhat excessive, 4193 calories being considerably in excess of the requirements of the body. Finally, it should be stated that of the several classes of foods, proteids cause the greatest increase in metabolism and fats the least.

In studying heat production in the body under varying conditions, one of the important aids in drawing conclusions as to the character of the body material burned up is the respiratory quotient. This is the relationship, or ratio, of the oxygen absorbed to the oxygen of the carbon dioxide eliminated, viz., CO₂/O₂. Carbohydrates (C₆H₁₂O₆, C₁₂H₂₂O₁₁) all contain hydrogen and oxygen in the proportion to form water, H₂O, and in their oxidation they need of oxygen only such quantity as will suffice to oxidize the carbon (C) of the sugar to carbon dioxide (CO₂). Carbohydrates, starch and sugars, have a respiratory quotient of 1.00. Fat, on the other hand, has a respiratory quotient of 0.7, and proteid, 0.8. Hence, it is easy to see that the respiratory quotient will approach nearer to unity as the quantity of carbohydrate burned in the body is increased. Similarly, the respiratory quotient will grow smaller the larger the amount of fat burned up. Practically, we never find a respiratory quotient of 1.0 or 0.7, because there is always some oxidation of proteid in the body. If, by way of illustration, we assume that the energy of the body under given conditions comes from proteid to the extent of 15 per cent, while the remaining 85 per cent is derived from the oxidation of carbohydrate, the respiratory quotient will be 0.971. If, however, the 85 per cent of energy comes from fat, the respiratory quotient will change to 0.722. In the resting body, as in the early morning hours, after a night’s sleep and before food is taken, the respiratory quotient is generally in the neighborhood of 0.8. When, however, as sometimes happens, the quotient at this time of day approaches 0.9, it must be assumed that sugar is being burned in the body, presumably from carbohydrate still circulating from the previous day’s intake.

As can easily be seen, any special drain upon either fat or carbohydrate in the processes of the body will be indicated at once by a corresponding change in the respiratory quotient. This we shall have occasion to notice later on, in considering the source of the energy of muscle contraction. Further, the respiratory quotient will naturally change in harmony with transformations in the body which involve alterations in oxygen-content, without the oxygen of the inspired air being necessarily involved; as in the formation of a substance poor in oxygen, such as fat, from a substance rich in oxygen, such as carbohydrate. Moreover, the reversal of this reaction, as in the formation of sugar from proteid with a taking on of oxygen, will produce a corresponding effect upon the respiratory quotient. As Magnus-Levy has clearly pointed out, in the formation of fat from carbohydrate, carbon dioxide is produced in large amount without the oxygen of the inspired air being involved at all. In such a change, 100 grams of starch will yield about 42 grams of fat, while at the same time 45 grams of carbon dioxide will be produced. This might cause the respiratory quotient to rise as high as 1.38. Again, in the formation of sugar from proteid, the respiratory quotient may sink very decidedly, the changes involved being accompanied by a taking on of oxygen from the air, without, however, any corresponding increase of carbon dioxide in the expired air. Assuming a manufacture of 60 grams of dextrose from 100 grams of proteid, i. e., from the non-nitrogenous moiety of the proteid molecule, a respiratory quotient of 0.613 would be possible. Thus, a diabetic patient, living upon a carbohydrate-free diet, consuming only proteid and fat, may show a respiratory quotient of 0.613–0.707. These illustrations will suffice to show how chemical alterations taking place in the body, involving transformations of proteid, fat, and carbohydrate of the tissues and of the food, may produce alterations in the respiratory quotient without necessarily being directly connected with intake of oxygen or output of carbon dioxide through the lungs; and how, conversely, the respiratory quotient becomes a factor of great significance in throwing light upon the character of the nutritive changes taking place in the body.

Among the various conditions that influence the energy exchange of the body, muscle work stands out as the most conspicuous. It needs no argument to convince one that all forms of muscular activity involve liberation of the energy stored up in the tissues of the body; and consequently that all work accomplished means chemical decomposition, in which complex molecules are broken down into simple ones with liberation of the contained energy, the energy exchange being proportional to the amount of work done. As we have seen, the basal energy exchange of the normal individual is ascertained by studying his heat production while at rest—best during sleep—without food, when involuntary muscle activity and heat production are at their lowest. The maximum energy exchange is seen in the individual at hard muscular work. Heat production is then at its highest, as can be ascertained by direct calorimetric observation; or, by studying the output of excretory products, which measure the extent of the oxidative processes from which comes the energy for the accomplishment of the work. As an illustration of the general effect of muscular work on the energy exchange of the body, we may cite a summary of some results reported by Atwater and Benedict,[37] the figures given being average results, from several individuals, and covering different periods of time. Though not strictly comparable in all details, they are sufficiently so to illustrate the main principle.

HEAT GIVEN OFF BY BODY, INCLUDING FOR WORK EXPERIMENTS THE HEAT EQUIVALENT OF THE EXTERNAL MUSCULAR WORK.

The work done in these experiments was on a stationary bicycle in the calorimeter, and the heat equivalent was calculated from measurements made by an ergometer attached to the bicycle. We are not concerned here with details, but simply with the general question of the influence of muscular work upon the energy exchange of the body. We note that the work of the day periods, 7 A. M. to 7 P. M., resulted, in the several cases brought together under the average figures, in an increased heat production amounting to more than 100 per cent. Further, we observe that in the body, as in all machines, only a fraction of the energy liberated by the accelerated chemical decomposition, or oxidation, was manifested as mechanical work, the larger part by far being heat eliminated and lost. Thus, Zuntz has found that, in man, about 35 per cent of the extra energy of the food used in connection with external muscular work is available for that work. This, however, shows a noticeably higher degree of efficiency than is generally obtainable by the best steam or oil engines. Lastly, attention may be called to the fact that after the work of the day was finished at 7 P. M., the next period of six hours still showed an accelerated metabolism, as contrasted with what took place during absolute rest.

As bearing upon the exchange of matter in the body in connection with muscular work, and as showing the relationship which exists here between energy exchange and exchange of matter, we may quote a few data relating to the elimination of carbon dioxide; remembering that this substance represents particularly the final oxidation product in the body of carbonaceous materials, such as fat and carbohydrate. The following data, taken from Atwater and Benedict,[38] being results of experiments upon the subject “J. C. W.,” are of value as showing the variations in output of carbon dioxide that may be expected under the conditions described:

In considering these figures bearing on the output of carbon dioxide under the conditions specified, we note at once a correspondence with the total energy exchange, as indicated in the preceding table. As previously stated, we are at present dealing simply with generalities, and the important point to be observed here is that muscular work—7 A. M. to 7 P. M.—in the work experiments, increases enormously the output of carbon dioxide. We see clearly emphasized a connection between the total energy exchange of the body, as expressed in calories or heat units, and the oxidation of carbonaceous material, of which carbon dioxide is the natural oxidation product. We note that on the cessation of work—7 P. M. to 7 A. M.—the output of carbon dioxide tends to drop back to the level characteristic of the corresponding period in rest, with or without food. In the experiment with “extra severe muscular work,” the results are different simply because here the subject worked sixteen hours, necessitating a portion of the work being done at night-time. Finally, it should be mentioned that the differences in output of carbon dioxide in these experiments are somewhat greater than in many experiments of this type, although all show the same general characteristics. This may be explained, as stated by the authors from whom the data are taken, “by the fact that J. C. W. was a larger and heavier man than any of the others; that the differences in diet were wider, and that the amounts of external muscular work were larger in these experiments than in those with the other subjects.”

If we pass from experiments of this type, conducted in a calorimeter, to those cases where competitive trials of endurance are held by trained athletes, i. e., where external muscular activity is pushed to the extreme limit, we then see even more strikingly displayed the effect of work in increasing the energy exchange of the body. One of the best illustrations of this type of experiment is to be found in the observations made in connection with the six-day bicycle race held in New York City, at the Madison Square Garden, in December, 1898.[39] The observations in question were made upon three of the athletes, one of whom withdrew early in the fourth day, while the others continued until the close of the race—142 consecutive hours—winning the first and fourth places, respectively. The following table gives the computation of energy of the material metabolized, exclusive of body-fat lost:

Miller, the winner of the race, who averaged a daily energy exchange of 4820 calories, rode 2007 miles during the week, and finished the race without physical or mental weakness resulting from the fatigue and strain. During the first five days, he rode about 21 hours a day and slept only 1 hour. Albert, who weighed a few pounds less than Miller, covered 1822 miles in 109 hours, with an average daily exchange of 6074 calories. We may add a table (on the following page) showing the balance of income and outgo of nitrogen in these three subjects, as being of general interest in this connection. The figures given are averages per day.

The special significance of these data, as bearing upon the topic under discussion, is that apparently all three of the subjects were drawing in a measure upon their body material. As stated by Atwater and Sherman, Pilkington lost per day 5.1 grams of nitrogen; that is to say, the total nitrogen excreted exceeded the total nitrogen of the food by 5.1 grams per day, corresponding to 33 grams of proteid, which must have been drawn from the supply in the body. If we assume that lean flesh contains 25 per cent of proteid, this would mean about 4 3/4 ounces per day. The other two subjects, Miller and Albert, lost from the body per day 8.6 grams and 7.1 grams respectively of nitrogen, which would imply a loss of about 54 grams and 44 grams of body proteid respectively, or 8 ounces and 6 1/4 ounces of lean flesh per day. It is evident, therefore, that none of the three subjects consumed sufficient food to avoid loss of body proteid, under the existing conditions of muscular activity. Indeed, it may be noted in Miller’s case that the average fuel value of the food per day was 4770 calories, while the average expenditure of energy per day was 4820 calories. We should naturally expect, however, that any small deficiency in fuel value would be made good by a call upon body fat. “Why the body should use its own substance under such circumstances is a question which at present cannot be satisfactorily answered. The fact that such was the case, each of the contestants who finished the race consuming during the period body protein equivalent to 2 or 3 pounds of lean flesh, and that no injury resulted therefrom, would seem to indicate that these men had stores of protein which could be metabolized to aid in meeting the demands put upon the body by the severe exertion, without robbing any of the working parts, and at the same time relieving the system of a part of the labor of digestion. Possibly, the ability to carry such a store of available protein is one of the factors which make for physical endurance.”[40] This possibility we shall have occasion to discuss in another connection. At present, the facts presented are to be accepted as accentuating the general law that the energy exchange of the body, everything else being equal, is increased proportionally to increase in the extent of external muscular activity. It may be noted that Albert, who did considerably less work than Miller, showed a much larger exchange of energy than the latter athlete. This, however, is to be connected with the fact that his fuel intake was 1300 calories larger per day than Miller’s; in other words, the conditions were not equal. This fact also calls to mind the observations of Schnyder,[41] who, studying the relationship between muscular activity and the production of carbon dioxide, maintained that the quantity of this excretory product formed depends less upon the amount of work accomplished than upon the intensity of the exertion; efficiency in muscular work varying greatly with the condition of the subject, and his familiarity with the particular task involved.

From what has been said, it is obvious that oxygen consumption, as well as output of carbon dioxide, must vary enormously with variations in the muscular activity of the body. The one important factor influencing the quantities of oxygen and carbon dioxide exchanged in the lungs, i. e., the extent of the respiratory interchange, is muscular activity; and since, as we have seen, carbonaceous material is the substance mainly oxidized in muscle work, it follows, as carbon dioxide is excreted principally through the lungs, that the respiratory interchange becomes in good measure an indicator of the extent of chemical decomposition incidental to external work. If we recall that man, on an average, at each inspiration draws in about 500 cubic centimeters of air (30 cubic inches), and that for the 24 hours he averages 15 breaths a minute, it is easy to see that in one minute the average man will inspire 7.5 litres of air, or 450 litres an hour, with a total of 10,800 litres for the entire day, which is equivalent to about 380 cubic feet. This would be a volume of air just filling a room 7 1/3 feet in length, width, and height. Inspired air loses to the body 4.78 volumes per cent of oxygen, while expired air contains an excess of 4.34 volumes per cent of carbon dioxide. In muscular work, respiration is increased in frequency and in depth. The volume of air exchanged in the lungs during severe labor may be increased sevenfold, while oxygen consumption and carbon dioxide excretion are frequently increased 7–10 times. The following figures, being values for one minute, show the effect on oxygen consumption of walking on a level and climbing, the subject being a man of 55.5 kilos body-weight:[42]

Remembering that these figures represent the oxygen consumption for only one minute of time, it is easy to see the striking effect of moderate and vigorous exercise on respiratory interchange. Simply walking along a level suffices to increase the consumption of oxygen threefold over what occurs when the body stands at rest. When the more vigorous exercise attendant on lifting the body up a steep incline is attempted, most striking is the great increase in the amount of oxygen consumed. We thus see another forcible illustration of the influence of muscular activity upon the exchange of matter in the body, and a further confirmation of the statement, so many times made, that oxidation—especially the oxidation of fats and carbohydrates by which large quantities of heat are set free, easily convertible into mechanical energy—is a primary factor in the metabolic processes, by which the machinery of the living man is able to work so efficiently.

Finally, we cannot avoid the conclusion that the outgoings of the body, in the form of matter and energy, are subject to great variation, incidental to the degree of activity of the day or hour. The ordinary vicissitudes of life, bringing days of physical inaction, followed perhaps by periods of unusual activity; changes in climatic conditions, with their influence upon heat production in the body; alterations in the character and amount of the daily dietary, etc.,—all seemingly combine as natural obstacles to the maintenance of a true nutritive balance. Outgo, however, must be met by adequate amounts of proper intake if there is to be an approach toward a balance of nutrition. In some way the normal, healthy man does maintain, approximately at least, a condition of balance; not necessarily for every hour or for every day, but the intake and outgo if measured for a definite period, not too short, say for a week or two, will be found to approach each other very closely. Body equilibrium and approximate nitrogen balance may be reasonably looked for, as well as a balance of total energy, in the case of a healthy man leading a life which conforms to ordinary physiological requirements. The man who, on the other hand, consciously or unconsciously, continues an intake way beyond the outgo, whose daily income of nitrogen and total fuel value far exceeds the requirements of his body, obviously lives with an accumulating plus balance, which ordinarily shows itself in increasing body-weight and with a storing away of fat.

Equally conspicuous is the effect of an inadequate income of proper nutriment; a food supply which persistently fails to furnish the available nitrogen and total energy value called for by the body under the conditions prevailing, will inevitably result in a minus balance, which, if continued too long, must of necessity tax the body’s store to the danger limit. At the same time, the well-nourished individual, without being unduly burdened by a bulky store of energy-containing material, is always supplied with a sufficient surplus to meet all rational demands, when from any cause the intake fails, for brief periods of time, to be commensurate with the needs of the body. It is reasonable to believe, however, that in the maintenance of good health, and the preservation of a high degree of efficiency, the body should be kept in a condition approaching a true nutritive balance.

CHAPTER IV

SOURCE OF THE ENERGY OF MUSCLE WORK, WITH SOME THEORIES OF PROTEID METABOLISM

Topics: Relation of muscle work to energy exchange. Views of Liebig. Experimental evidence. Relation of nitrogen excretion to muscle work. Significance of the respiratory quotient in determining nature of the material oxidized. Fats and carbohydrates as source of energy by muscles. Utilization of proteid as a source of energy. Formation of carbohydrate from proteid. Significance of proteid metabolism. Theories of Carl Voit. Morphotic proteid. Circulating proteid. General conception of proteid metabolism on the basis of Voit’s theories. Pflüger’s views of proteid metabolism. Rapidity of elimination of food nitrogen. Methods by which nitrogen is split off from proteid. Theories of Folin. Significance of creatinin and of the percentage distribution of excreted nitrogen. Endogenous or tissue metabolism. Exogenous or intermediate metabolism. Needs of the body for proteid food possibly satisfied by quantity sufficient to meet the demands of tissue or endogenous metabolism. Bearings of Folin’s views on current theories and general facts of proteid metabolism. Large proteid reserve and voluminous exogenous metabolism probably not needed. Importance of feeding experiments in determining the true value of different views.

As we have already seen, every form of muscular activity begets an increase in the energy exchange of the body. Between the two extremes of absolute rest and excessive muscular exertion, we find differences of 2000 calories or more per day as representing the degree of chemical decomposition corresponding to the particular state of muscular activity. The work of the involuntary muscles, such as have to do with peristalsis, respiration, rhythmical beat of the heart, etc., is a relatively constant factor, though naturally subject to some variation, as has been pointed out in other connections. External muscular activity, however, is the one factor above all others that modifies the rate of energy exchange. A little longer walk, a heavier load to carry, a steeper hill to climb, any increase great or small in the activity of the muscles of the body, means a corresponding increase in chemical decomposition, with increased output of the ordinary products of tissue oxidation. The material so consumed, or oxidized, must be made good to hold the body in equilibrium; the supplies drawn upon are to be replaced, if the tissues of the body are to be kept in a proper state of efficiency.

What is the nature of the material used up in connection with muscle work? As can readily be seen, this is an important question, for on its answer depends, in some measure at least, the character of the proper intake, or food, to be supplied in order to make good the loss. If the energy of mechanical work, the energy of muscle contraction, comes from the breaking down of proteid matter alone, then obviously excessive muscular work would need to be accompanied, or followed, by a generous supply of proteid food. If, on the other hand, external work means liberation of energy solely from non-nitrogenous materials, then it is equally clear that fats and carbohydrates are the proper foods to offset the drain incidental to vigorous muscular action.

The views of Liebig, briefly referred to in a previous chapter, held sway over physiologists for many years. His dictum that proteid foods were true plastic foods, entering into the structure of the tissues of the body, and that they alone were the real sources of muscular energy, met for a time with no opposition. It was not until the advent of a more critical spirit, accompanied by a fuller appreciation of the necessity of experimental evidence, that physiologists began to test with scientific accuracy the validity of the current views. It is worthy of note that long prior to this time, even before oxygen was discovered, the far-sighted and resourceful John Mayow, in his work with the various “spirits” of the body and their relation to respiration, etc., evolved the view that muscular power has its origin in the combustion of fat brought to the muscles by the blood and burned there by aid of a gas or “spirit” taken from the air by the lungs, and likewise carried to the muscles by the circulating blood. Considering the time when Mayow lived and the dearth of true scientific knowledge as we measure it to-day, his hypothesis was a wonderful forestalling of present views.

It is quite obvious that the views of Liebig, if true, admit of easy proof; since, if the energy of muscular power comes from the breaking down of proteid, there should be a certain parallelism between the output of nitrogen from the body and the amount of muscular work accomplished, everything else being equal. As stated in a previous chapter, such study of this question as was made soon disclosed the fact that the one element above all others that seemed to influence the output of nitrogen was the intake of proteid food. Thus, the English investigators, Lawes and Gilbert, found by experimenting with animals that when the latter were kept under uniform conditions of muscular work, the amount of nitrogen excreted ran parallel with the intake of nitrogen. Further, in the early experiments of Voit, the results obtained clearly showed that variations in the amount of work performed were practically without influence on the excretion of nitrogenous waste products.

The experiment, however, that came as a death blow to the theories of Liebig was that of Fick and Wislicenus,[43] who in 1865 made an ascent of the Faulhorn, 6500 feet high, using a diet wholly non-nitrogenous. From the nitrogen excreted they were able, of course, to calculate the amount of proteid oxidized in the body during the period of work, and found that the proteid consumed could not have furnished, at the most, more than one-half the energy required to lift the weights of their bodies to the top of the high peak. Further, they observed that neither during the work period, nor immediately after, was there any noticeable increase in the excretion of nitrogen. Obviously, as they state, the oxidation of proteid matter in the body cannot be the exclusive source of the energy of muscular contraction, since the measurable amount of external work performed in the ascent of the mountain was far greater than the equivalent of the energy capable of being furnished by the proteid actually burned. To which may be added the fact that considerable energy, not measurable in their experiment, must have been employed in the work of the involuntary muscles of the body; thus increasing by so much the difference between the muscular work actually accomplished and the available energy from proteid consumed. It is true that minor criticisms regarding certain details of the experiment can be offered to-day, such as the fact that the men were, in a measure, in a state of “nitrogen starvation,” etc., but these criticisms do not in any degree militate against the main thesis that the energy of muscular contraction does not come exclusively from the consumption or breaking down of proteid, either of food or tissue. Vigorous and even severe muscular work does not necessarily increase the decomposition of proteid material. Dogs made to run in large treadmills, with the same diet as on resting days, were found to excrete practically no more nitrogen than during the days of rest. Occasionally, however, in some one experiment the output of nitrogen would show an increase over the output on resting days. Further, experiments made with horses led to essentially the same result, except that greater increase in the excretion of nitrogen was observed than with dogs. This increase in nitrogen output, however, as a concomitant of increased muscular activity, could be prevented by adding to the amount of carbohydrate food.

While experiments of this nature, on man and animals, all tended to show little or no increase in the excretion of nitrogen, as a result of muscle work; and likewise no increase in the output of sulphur and phosphorus, thus strengthening the view that muscular energy is not the result of proteid disintegration, there was observed marked increase in the consumption of oxygen, and in the excretion of carbon dioxide. Non-nitrogenous matter was thus at once suggested as the material with which muscle chiefly does its work. There is to-day no question of the general truth of this statement, yet there are other aspects of the problem to be considered before we can lay it aside. Pflüger, working with dogs, and Argutinsky, experimenting on himself by arduous mountain climbing, reached conclusions seemingly quite opposed to what has just been said. Their results, however, admit of quite a different interpretation from what they were disposed to attach to them. Thus, Pflüger[44] would go back to the old view that all muscle work is at the expense of proteid material, because lean dogs fed mainly, or entirely, on meat and made to do an excessive amount of work were found by him to excrete nitrogen somewhat in proportion to the amount of work done. Argutinsky,[45] likewise, in his mountain climbing carried to the point of fatigue, and with a high proteid intake likewise, saw in the increased output of nitrogen a suggestion of the same idea. In reality, however, their results merely prove that, under some circumstances, proteid may serve as the chief source of muscular energy; as when the body is poor in fat and carbohydrate, or when the intake consists solely of proteid matter. In other words, muscular work may result in an increased excretion of nitrogen when the work is very severe, and there is not a corresponding increase in the fats or carbohydrates (fuel ingredients) of the food. In the words of Bunge,[46] “we might assume à priori, on teleological grounds, that in the performance of its most important functions the organism is to a certain extent independent of the quality of its food. As long as non-nitrogenous food is supplied in adequate quantity or is stored up in the tissues, muscular work is chiefly maintained from this store. When it is gone the proteids are attacked.”

There is no question that the energy of muscular contraction can come from all three classes of organic foodstuffs. Voluntary muscular movement is under the control of the nervous system, and when the stimulus is applied the muscle is bound to contract, provided of course there is sufficient energy-containing material present to furnish the means. Muscle tissue, like other tissues and organs, has a certain power of adaptability, by which it is able to do its work, even though it is not adequately supplied with its preferred nutrient. While proteid is plainly not the material from which the energy of muscular contraction is ordinarily derived, it is equally evident that in emergency, as when the usual store of carbohydrate and fat is wanting, proteid can be drawn upon, and in such cases vigorous work may be attended with increased nitrogen output. In harmony with this statement, we find on record in recent years many experiments, both with man and animals, where severe muscular labor is accompanied by an excretion of nitrogen beyond what occurs on days of rest; but by simply adding to the intake of non-nitrogenous food this increased outgo of nitrogen is at once checked. With moderate work, the nitrogen outgo is rarely influenced; it is only when the work becomes excessive, or the store of non-nitrogenous reserve is small and the intake of the latter food is limited, that proteid matter is drawn upon to supply the required energy.

Recalling what has been said regarding the significance of the respiratory quotient, it is obvious that we have here a means of acquiring information as to the character of the material that is burned up in the body during muscular work. Increased metabolism of carbohydrate will necessarily result in raising the respiratory quotient, and if the latter food material alone is involved the respiratory quotient must naturally approach 1.0. Zuntz, however, has clearly shown that vigorous muscular activity does not materially change the respiratory quotient; except in cases of very severe work, where the oxygen-supply of the muscles is interfered with. Indeed, the muscles may be made to do work sufficient to increase the consumption of oxygen threefold or more, without any change in the respiratory quotient being observed. And as there is frequently no change whatever in the output of nitrogen under these conditions, it follows that the energy of the muscle work must have come from the decomposition of non-nitrogenous material. If carbohydrates alone were involved, the respiratory quotient would obviously undergo change. Since, however, this remains practically stationary, we are led to the conclusion that fat must be involved in large degree, in addition to carbohydrate.

In this connection, it is a significant fact that with fasting animals, where the store of carbohydrate material is more or less used up, severe muscle work may be accomplished without any appreciable increase in nitrogen output, thus showing that proteid material is not involved and clearly pointing to fat as the source of the muscular energy. Thus, in an experiment referred to by Leathes, a dog on the sixth and seventh day of starvation was made to do work in a treadmill equivalent to climbing to a height of 1400 meters, yet the output of nitrogen was increased from six to only six and a half grams. Obviously, not much of the energy of this muscle work could have come from the breaking down of proteid, but it must have been derived mainly from the oxidation of fat. There is abundant evidence that fat can be used as a source of energy by muscles, as well as carbohydrates and proteids, and there is every reason for believing that the yield of work for a given amount of chemical energy in the form of fat is as good as in the case of either of the other two substances. In fact, the observations of Zuntz show that fat can be used just as economically by the body for muscle work as either carbohydrates or proteid. Thus, in one experiment,[47] he determined the oxygen-consumption and respiratory quotient in a man resting and working on three different diets—one principally fat, one principally carbohydrate, and the other principally proteid—and found that slightly less oxygen and energy were required to do work on the fat diet than on the others. This is clearly shown in the following table:

From these data, we see that per kilogram-meter of work less energy was required and less oxygen consumed with fat than with either of the other two foodstuffs; but practically, fat and carbohydrate as sources of muscle energy have about the same value.

Much stress is ordinarily laid upon the importance of a large intake of proteid food whenever the body is called upon to perform severe, or long-continued, muscular work; but in view of what has been stated it may be questioned whether there is any real physiological justification for such custom. The pedestrian Weston,[48] who in 1884 walked 50 miles a day for 100 consecutive days, was found by Blyth during a period of five days to consume in his food 37.2 grams of nitrogen a day, while he excreted only 35.3 grams, leaving a balance of 1.9 grams of nitrogen per day apparently stored in the body. His daily food during this period was composed of 262 grams of proteid, 64.6 grams of fat, and 799 grams of carbohydrate, with an estimated fuel value of 4850 calories. Yet he performed this large amount of work daily, and still laid by a certain amount of proteid on a ration, the energy value of which would not ordinarily be considered high for the muscular work to be done. Fourteen years prior to this, Weston, while in New York, was carefully studied by Dr. Flint during a period of 15 days, on 5 of which he walked a total of 317 miles. His diet was essentially a proteid diet, consisting principally of beef extract, oatmeal gruel, and raw eggs. Nitrogen intake and output were carefully compared during the days of rest and during the days of work, with the results tabulated.

Period.	Occupation.	Duration of Test.		Nitrogen.
				In Food.	In Urine.	In Excre- ment.	Gain + or Loss -
		days		grams	grams	grams	grams
Fore period	Comparative rest	5		22.0	18.7	1.4	+1.9
Working period	Walking 62 miles per day		5	13.2	21.6	1.6	–10.0
After period	Rest	5		28.6	22.0	2.2	+4.4

In this case it will be noted that the daily ration was comparatively small, and, further, that during the working period the subject consumed much less proteid than on the resting days. Moreover, when we remember that the total energy value of his diet must have been quite small, it is not at all strange that in the laborious task of walking 62 miles a day he should have temporarily drawn upon his store of body proteid to the extent of 62.5 grams, or 10 grams of nitrogen a day. Such experiences, however, do not by any means constitute proof that in excessive muscular work there is need for the consumption of correspondingly increased quantities of proteid food, or that the energy of muscular work comes preferably from the breaking down of proteid material. Carbohydrate and fat unquestionably take precedence over proteid in this respect, and we may accept as settled the view that in all practical ways carbohydrate and fat stand on an equal footing as sources of muscular energy. Less clear, perhaps, is the question as to how these two radically different types of organic material are utilized by the muscle. It has been a favorite belief among some physiologists that the contracting muscle makes use of only one substance as the direct source of its energy, and that this substance is the sugar dextrose. This view would seemingly imply that fat and proteid must undergo alteration prior to their utilization by the muscle; that, possibly, the carbon of the fat and proteid is transformed into sugar before the muscle can make use of it. So far as fat is concerned, this view is not supported by the facts available, since experiments show that the heat and energy liberated in the utilization of a given amount of fat in muscle work are in harmony with the energy value of the fat; in other words, the fat is apparently burned, or oxidized, directly, without undergoing previous transformation into any form of carbohydrate; or, if transformation does occur, under some conditions, it must take place within the muscle and without loss of energy. The practical significance of these facts is at once apparent, for if fat, in order to be available as a source of muscle energy, must first undergo conversion into sugar, it would be far more economical from a physiological standpoint to replace the fat of the diet with carbohydrate in any attempt to provide suitable nourishment for the working muscle. We may safely conclude, however, that fat and carbohydrate, as previously suggested, are in reality both capable of direct metabolism by the muscular tissue, and that each is of value as a source of muscular energy in proportion to its heat of combustion, yielding substantially the same proportion of its potential energy in the form of mechanical work.

Regarding the utilization of proteid as a source of energy by the muscle, there are many grounds for believing that here the body has to deal with certain alterations, before the proteid can be made available. We may indeed conjecture the transformation of a non-nitrogenous portion of the proteid molecule into carbohydrate, as a necessary step in its utilization for muscle work. It is certainly true that in the ordinary katabolic processes, through which proteid passes, there is a tendency for the nitrogen-containing portion to be quickly split off and eliminated, leaving a carbonaceous residue which may represent as much as 80 per cent of the total energy of the original proteid. This so-called carbon moiety of the proteid molecule is apparently much less rapidly oxidized than the nitrogenous portion, and may indeed be temporarily stored in the body, in the form of fat or carbohydrate.[49] We have very convincing proof that the carbohydrate glycogen can be formed from proteid. Thus, the feeding of proteid to warm-blooded animals may be accompanied by an accumulation of glycogen in the liver. This is interpreted as meaning that in the cleavage of proteid by digestion the various nitrogenous products formed are somewhere, probably in the liver, still further acted upon; the contained nitrogen with some of the carbon being converted into urea, while the non-nitrogenous residue is transformed into glycogen, or sugar. That some such change takes place, or, more specifically, that carbohydrate does result from proteid is more strikingly shown in human beings suffering with diabetes. In severe forms of this disease, all carbohydrate food consumed is rapidly eliminated through the kidneys in the form of sugar, the body having lost the power of burning sugar. If such a person is placed upon a diet composed exclusively of proteid, sugar still continues to be excreted, and there is observed a certain definite relationship between the nitrogen output and the excretion of sugar, thus implying that they have a common origin.

Further, there are certain drugs, such as phloridzin, which, when introduced into the circulation, set up a severe diabetes and glycosuria. Dogs treated in this way, fed solely on proteid or even starved for some time, will continue to excrete sugar, and as in the previous instance, there is observed a certain definite ratio between the nitrogen output and the elimination of sugar; thus leading to the conclusion that both arise from the destruction of the proteid molecule. Careful study of this ratio of dextrose to nitrogen has led Lusk to the conclusion that full 58 per cent of the proteid may undergo conversion into sugar in the body. Hence, it is easy to see how in muscle work, when proteid is the sole source of the energy of muscular contraction, the work accomplished may still result from the direct oxidation of carbohydrate material, indirectly derived from the proteid molecule. It requires no argument, however, to convince one that such a procedure for the normal individual is less economical physiologically than a direct utilization of carbohydrate and fat, introduced as such and duly incorporated with the muscle substance. Consequently, in the nourishment of the body for vigorous muscular work, there is reason in a diet which shall provide an abundance of carbohydrate and fat; proteid being added thereto only in amounts sufficient to meet the ordinary requirements of the body for nitrogen and to furnish, it may be, proper pabulum for the development of fresh muscle fibres, where, as in training, effort is being made to strengthen the muscle tissue and so enable it to do more work. Increase in proteid food may help to make new tissue, but the source of the energy of muscle work is to be found mainly in the breaking down of the non-nitrogenous materials, carbohydrate and fat.

In view of these facts, we may advantageously consider next the real significance of the proteid metabolism of the body. As we have seen, a meal rich in proteid leads at once—within a few hours—to an excretion of urea equivalent to full 50 per cent of the nitrogen of the ingested proteid, while a few hours later finds practically all of the nitrogen of the intake eliminated from the body. Further, it is to be remembered that in a general way this occurs no matter what the condition of the body may be at the time and no matter how large or small the amount of proteid consumed. In other words, there is practically no appreciable storing of nitrogen or proteid for future needs,—at least none that is proportional to the increase in nitrogen intake, even though the body be in a condition approximating to nitrogen starvation. Moreover, it is to be recalled that the increased proteid metabolism attendant on increased intake of proteid food is accompanied by an acceleration of the metabolism of non-nitrogenous matter; thus resulting in a stirring up of tissue change, with consequent oxidation and loss of a certain proportion of accumulated fat and carbohydrate. Coincident with this increased excretion of nitrogen, the output of carbon dioxide is likewise increased somewhat, due as is believed mainly to increased metabolism of the involuntary muscle fibres of the gastro-intestinal tract, by action of which the accelerated peristalsis so characteristic of food intake is accomplished. Further, the increased output of carbon dioxide, under these conditions, is to be attributed also to the greater activity of the digestive and excretory organs, naturally stimulated to greater functional power by the presence of proteid foods and their decomposition products. Still, as stated by Leathes, “the two main end-products of proteid metabolism, urea and carbonic acid, are, to a great extent, produced independently of each other, and the reactions which result in the discharge of the nitrogen are not those in which energy is set free, work done, and carbonic acid produced.” In other words, there is suggested what we have already referred to, viz., that in proteid metabolism a nitrogenous portion of the proteid molecule is quickly split off and gotten rid of, while the non-nitrogenous part may be reserved for future oxidation, serving as a source of muscle energy or for other purposes. This being so, it is plain that “proteid metabolism in so far as it is concerned with the evolution of energy, proteid metabolism in its exothermic stages, may be almost entirely non-nitrogenous metabolism” (Leathes).

Is there any advantage to the body, however, in this carbonaceous residue of the proteid molecule over simple carbohydrate and fat? Can the processes of the body be accomplished more economically, or more advantageously, with a daily diet so constructed that the tissues and organs must depend mainly upon this carbon moiety of the proteid molecule for their energy-yielding material? It has been one of the physiological dogmas of the past, that the tissues and organs of the body, or rather their constituent cells, preferred to use proteid for all their needs whenever it was available. If proteid were wanting, either because of insufficient intake, or because of excessive activity, then the tissue cells would draw upon their store of non-nitrogenous material. Food proteid and tissue proteid, however, were the materials preferred by the organism, so ran the argument, and the large and incessant output of nitrogen which accompanied the intake of proteid was accepted as proof of the general truth of this idea. We might well question wherein lies the great advantage to the body in this continual excretion of nitrogen; whether the loss of energy in handling and removing the nitrogenous portion of the necessarily large proteid intake, in order to render available the non-nitrogenous part of the molecule, might not more than compensate for the supposed gain? But the truly astonishing fact that the output of nitrogen runs parallel with the intake of proteid, that the body cannot store up nitrogen to any large extent, has been taken as conclusive evidence that the organism prefers to use proteid for all of its requirements. Truly, we might just as well argue that this significant rise in the excretion of nitrogen after partaking of a proteid meal is an indication that the body has no need of this excess of nitrogen; that it is indeed a possible source of danger, since the system strives vigorously to rid itself of the surplus, and that the energy-needs of the body can be much more advantageously and economically met from fat and carbohydrate than from the carbonaceous residue resulting from the disruption of the proteid molecule.

In discussing these questions, we shall need to refer to several of the current theories concerning proteid metabolism, notably, the theories of Voit, Pflüger, and Folin. In 1867 Carl Voit,[50] of Munich, advanced the view that the proteid material of the body exists in two distinct forms, viz., as “morphotic” or “organized” proteid, representing proteid which has actually become a part of the living units of the body, i. e., an integral part of the living tissues; and “circulating” proteid, or that which exists in the internal meshes of the tissue, or in the surrounding lymph and circulating blood. The real point of distinction here is that while one portion of the body proteid is raised to the higher plane of living matter, i. e., becomes a component part of the living protoplasm, another and perhaps larger portion is outside of the morphological framework of the tissue, constituting a sort of internal medium which bathes the living cells, and acts as middleman between the blood and lymph on the one side and the living cells on the other. According to Voit’s view, it is this circulating proteid that undergoes metabolism; the proteid of the food after digestion and absorption being carried to the different tissues and organs, and then, without becoming an integral part of the living protoplasm of the cells, it is broken down under the influence of the latter. Obviously, small numbers of tissue cells are constantly dying, their proteid matter passing into solution, where it likewise undergoes metabolism. In other words, according to Voit, the great bulk of the proteid undergoing katabolism is the circulating proteid, derived more or less directly from the food, and which at no time has been a part of the tissue framework; while a smaller, but more constant amount, represents the breaking down of tissue cells. This conception of proteid metabolism is akin to our conception of morphological and physiological destruction. In the words of Foster: “We know that an epithelial cell, as notably in the case of the skin, may be bodily cast off and its place filled by a new cell; and probably a similar disappearance of and renewal of histological units takes place in all the tissues of the body to a variable extent. But in the adult body these histological transformations are, in the cases of most of the tissues, slow and infrequent. A muscle, for instance, may suffer very considerable wasting and recover from that wasting without any loss or renewal of its elementary fibres. And it is obvious that the metabolism of which we are now speaking does not involve any such shifting of histological units. On the other hand, we find these histological units, the muscle fibre or the gland cell, for instance, living on their internal medium, the blood, or rather on the lymph, which is the middleman between themselves and the actual blood flowing in the vascular channels.”

Voit claims that the proteid dissolved in the fluids of the body is more easily decomposable than that which exists combined in organized form, or as more or less insoluble tissue proteid; and it is this soluble and circulating form which, under the influence of the living cells, undergoes destruction or metabolism. We know, as has been previously stated, that oxidation does not take place to any extent in the circulating blood, and similarly there is every reason for believing that proteid metabolism does not occur in this menstrum. Metabolism is limited mainly to the active tissues of the body, but according to the present conception of the matter it does not occur at the expense of the proteid of the living cells, but involves material contained in the fluids bathing the cells; i. e., it is not the organized proteid that undergoes metabolism, but the proteid circulating in and about the internal meshes of the cells and tissues, the living cell being the active agent in controlling the process. Further, this view lessens the difficulty of understanding the elimination of nitrogen after a meal rich in proteid. If it was necessary to assume that all the proteid of our daily food is built up into living protoplasm before katabolism occurs, it would be exceedingly difficult to explain the sudden and rapid elimination of nitrogen which follows the ingestion of proteid. For example, we can hardly imagine that merely eating an excess of proteid food will lead to an actual breaking down of the living framework of the tissues, equivalent to the amount of nitrogen which the body at once eliminates. Voit’s theory, on the other hand, supposes a twofold origin of the nitrogen excreted; one part, the larger and variable portion, comes from the direct metabolism of the circulating proteid, being the immediate result of the ingested food and varying in amount with the quantity of proteid food consumed; the other, smaller and less variable in amount, has its origin in the metabolism of the true tissue proteid, or the actual living framework of the body.

In a fasting animal, the tissues and organs of the body still contain a large proportion of proteid matter, yet only a small fraction of this proteid is eliminated each day, hardly 1 per cent. If, however, proteid is absorbed from the intestine, proteid metabolism is at once increased, and the excretion of nitrogen may be fifteen times greater than during hunger. In other words, the extent of proteid metabolism is not at all proportional to the total amount of proteid contained in the body as a whole, but runs parallel in a general way with the quantity of proteid absorbed from the intestine. Obviously, the newly absorbed proteid is quite different in nature from the proteid which in much larger amounts is deposited throughout the body, since it is not organized and is so much more easily decomposable (Voit). This is the circulating proteid of the body; it exists in solution, and it is a significant fact that, according to Voit, the chemical transformations that characterize proteid katabolism occur only in solution. The organized proteid, on the other hand, is in a state of suspension, and its katabolism, which is relatively very small, is preceded by solution of the proteid in the fluids of the tissue, after which its further breaking down is assumed to be the same as that of the circulating proteid. This latter view is a fundamental part of the Voit theory; in long-continued fasting, for example, the living protoplasm of the various tissues and organs is of necessity drawn upon for the nourishment of the more vital parts of the body, such as the brain, spinal cord, etc., consequently the organized proteid is gradually dissolved and then decomposed, after it has become liquefied and has thus lost its organized structure.

In this conception of proteid metabolism, we picture the different organs and tissues of the body as being permeated by a fluid which carries variable amounts of nutritive material, the quantity of the latter determining in a way the extent of the proteid katabolism which shall take place. As the proteid of the food passes into the blood and lymph, the fluids bathing the cells are correspondingly enriched, and as a result, proteid katabolism is accelerated in parallel degree. During hunger, on the other hand, the organized proteid of the tissue cells is gradually liquefied and passes out into the current of the circulating fluids. As before stated, the organized proteid as such is never decomposed; it must first enter into solution, and then under the influence of the living cells it undergoes disruption in the same manner as the circulating proteid. It is thus evident that the tissue cells and the circulating fluids permeating them bear an ever changing relationship to each other. Excess of circulating proteid will be attended by increased katabolism, while at the same time there may be some accumulation of proteid in the cells, and indeed some conversion into organized proteid. During fasting, hunger, or with an insufficient intake of proteid food, the current will naturally be in the opposite direction, and organized proteid will slowly, but surely, be drawn upon.

Again, we may ask in view of these facts, of what real use to the body is this large katabolism of circulating proteid? We can easily understand the need of proteid to supply the loss incidental to the breaking down of organized or true tissue proteid, but this we are led to believe is very small in amount. Is there any real need for proteid beyond this requirement? The physiological fuel value of proteid is no greater than that of carbohydrate and considerably less than half that of fat, consequently there is on the surface no apparent reason why proteid should be used for its energy value in preference to the non-nitrogenous foodstuffs. Further, as we have seen, the energy of muscle work comes mainly, at least, from the breaking down of fat and carbohydrate; proteid, in the case of the well-nourished individual, ordinarily playing no part in this important line of energy exchange. Lastly, in the katabolism of proteid there is the large proportion of nitrogenous matter to be split off and disposed of before the carbon moiety of the molecule can be rendered available. Here, we have involved not only a loss of energy, but in addition a certain amount of what appears to be useless labor thrown upon the liver, kidneys, and other organs. Is there any wonder that the thoughtful physiologist, looking at the facts and theories presented by the Voit conception of proteid katabolism, should ask wherein lies the value to the body of this high rate of metabolism of circulating proteid, a rate of metabolism which is seemingly governed primarily by the amount of proteid food ingested?

Turning next to Pflüger’s[51] views regarding proteid katabolism, we find a totally different outlook. Here, the supposition prevails that the plasma of the blood and lymph, with its contained proteid, is the food of the organs or their cells, but that before this food material can undergo katabolism it must first be absorbed by the cell and built up into the living protoplasm of the tissue. In other words, according to the views expressed by Pflüger, katabolism must be preceded by organization of the proteid. Expressed in still different language, the proteid material circulating in blood and lymph must be eaten up by the hungry cells and, by appropriate anabolic processes, made an integral part of the living protoplasm before disassimilation can occur. Further, according to Pflüger’s conception of these processes, there is a radical difference in the chemical nature of living protoplasm as compared with that of the so-called circulating proteid. The latter is looked upon as being comparatively stable, resisting oxidation in high degree, and hence not prone to undergo metabolism. Living protoplasm, on the other hand, is characterized by instability, suffering oxidation with the greatest ease, and hence readily broken down in the ordinary processes of katabolism. Assuming for the moment the correctness of this theory, we see at a glance that all disruption of proteid matter in the body must be preceded by the upbuilding of the proteid into living protoplasm. There can be no destruction of proteid until the latter has been raised to the high plane of living matter. The dead, inert circulating proteid can serve simply as food for the living cells, and cannot undergo katabolism until it has been built up into the organized structure of the tissue or organ. Even though we grant that a small proportion of proteid may suffer katabolism without previous organization, it does not materially modify the general trend of the argument that, according to Pflüger’s hypothesis, proteid katabolism is essentially a process involving the disruption of living protoplasm.

Consider what this means in the light of facts already presented. Remembering that the one factor above all others influencing the rate of proteid katabolism is the amount of proteid food taken in, and that the output of nitrogen, no matter what the previous condition of the body or the amount of proteid food ingested, runs more or less parallel with the consumption of proteid, we are forced to the conclusion, in accepting this hypothesis, that there must be superhuman activity in the building up of living protoplasm, only to be followed, however, by its immediate and more or less complete breaking down. Further, think of the daily or periodical fluctuation in the construction of bioplasm, coincident with variations in the amount of proteid food consumed, and the corresponding destruction of bioplasm as indicated by the daily output of nitrogen. Imagine, if you will, the concrete case of a man of 70 kilos body-weight eating a daily ration containing 125 grams of proteid, the nitrogen equivalent of which is practically excreted within twenty-four hours, and are we not wise in hesitating to believe that all of that proteid has been so quickly built up into living or organized tissue only to be immediately broken down and thrown out of the body? Think of the enormous activity implied in the manufacture of this bioplasm in the time allotted, and for what? Apparently, so that it can be broken down again. But such energy as is liberated in the breaking-down process might be derived far more economically by simple destruction of the proteid, as contained in the meshes of the tissue elements, without assuming a preliminary conversion into living protoplasm. Obviously, we have here a theory which does not help us in arriving at any very satisfactory conception of proteid metabolism. The facts which Pflüger and his followers bring forward in support of the theory are not very convincing, or at least not sufficiently so to carry conviction in the face of a natural disinclination to believe in the necessity of such a profound anabolic process, merely as a prelude to the speedy destruction of the finished product. Finally, we may add that if all proteid katabolized in the body must first be raised to the high level of living protoplasm before the final disruption can occur, it may be prudent to keep the daily intake of this foodstuff down to a level somewhat commensurate with the real needs of the body.

As has been stated many times in the course of this presentation, the most striking feature of proteid metabolism is the rapidity with which large quantities of proteid consumed as food are broken down, and the contained nitrogen eliminated from the body as urea. A few hours will suffice to accomplish the more or less complete destruction of food proteid; and any theory of proteid metabolism, to be at all satisfactory, must explain this peculiar phenomenon. According to recent investigations, it seems probable that some, at least, of the cleavage products of proteid formed during intestinal digestion are not built up into new proteid, but are at once eliminated mainly in the form of urea, without becoming a part of either the so-called circulating proteid, or the living protoplasm of the body. It will be recalled that under the influence of the digestive enzymes, trypsin and erepsin, proteid foodstuffs may be broken down while undergoing intestinal digestion into monamino- and diamino-acids, such as leucin, tyrosin, arginin, lysin, etc. A certain proportion of these comparatively simple substances may be directly absorbed by the portal circulation and carried to the liver, where they may undergo conversion into urea. In this way, some portion of the nitrogen of the ingested food may be quickly eliminated from the system. As has been stated in another connection, we are not sure at present how far proteid decomposition of the kind indicated takes place normally in the body. We merely know that there are present in the intestine, enzymes capable of splitting up proteid into these small fragments, and that substances of this type when made to circulate through the liver are transformed into urea. These facts, coupled with the well-known tendency of the nitrogen of proteid food to appear in the excretions a few hours after the food in question has been consumed, naturally suggests a direct breaking down of proteid along the lines indicated, with a possible retention of a carbonaceous residue (nitrogen-free) for subsequent oxidation, as a source of energy for heat or work. Obviously, all of the proteid food cannot behave in this manner, for if such were the case there would be no proteid available for making good the normal waste incidental to tissue changes. Either a certain amount of proteid escapes this profound alteration produced by the proteolytic enzymes in question, or else a certain proportion of these simple decomposition products is synthesized in the intestine, or in the tissues of the body, to form new proteid for the regeneration of cell protoplasm. However this may be, we have presented in this view a plausible explanation of the prompt appearance of food nitrogen in the excretions, and without compelling belief in a theory, such as Pflüger’s, which taxes one’s credulity to the utmost. To be sure, as a prominent writer on physiology has recently said, such a view stands opposed to our conceptions of the importance of proteid food; but it seems possible, in the light of accumulating knowledge, that our conceptions of the part played by proteid foods in the nutrition of man have not been strictly logical, or quite in accord with true physiological reasoning.

Again, in this connection, we may ask the question, why is it that the body provides such an effective method for the speedy breaking down of proteid food and the prompt elimination of the contained nitrogen? Whatever the means made use of by the organism in accomplishing this, the result is the same; the nitrogen of the ingested food is, in large measure, quickly gotten rid of. We clearly recognize the all-important position of proteid foods in the nutrition of the body, but there appears a certain inconsistency in this prompt removal of the nitrogen-containing portion of the proteid molecule. The nitrogenous part of the proteid food is, physiologically considered, the all-important part. It is the only source of nitrogen available to the system, and yet apparently the larger proportion of this nitrogenous material is not utilized in any recognizable way, but is eliminated as quickly as possible. Is it not within the limits of possibility that these methods, whatever may be the exact mechanism involved, are merely a means of getting rid of a surplus of proteid for which the body has no real need? This question I shall try to answer later on in another connection, but we may advantageously keep this possibility in mind while we are discussing these theories of proteid metabolism.

It is obvious, in the light of present knowledge, that there must be a certain amount of true tissue proteid broken down each day, independent of that larger metabolism coincident with the intake of proteid food. However much this more voluminous proteid katabolism may fluctuate, owing to variations in the intake of proteid, and whatever the significance of this latter phase of metabolism, it is self-evident that there must be a steady, constant metabolism, upon which the life of the various tissues and organs of the body depends, and by which the proteid integrity of the tissue cells is maintained. This implies a certain degree of true tissue change, in which definite amounts of proteid material are broken down and the resultant loss made good from the proteid intake. No matter what specific name be applied to this form of proteid katabolism, its existence is clearly recognized. It is obviously a form of metabolism distinct, and probably quite different, from that form, more variable in extent, which is associated with the intake of proteid food. Plainly, if there is truth in these statements, there should be some data available by means of which these two lines of proteid katabolism can be more or less sharply differentiated.

Thanks especially to the work of Folin,[52] these data are now apparently at hand, and the facts which he has accumulated with painstaking care seem destined to throw additional light upon our conception of proteid metabolism. It will be remembered that in the breaking down of proteid, the great bulk of its contained nitrogen is eliminated in the form of urea. In addition, a certain smaller amount of nitrogen is excreted in the forms of creatinin and uric acid. As we have seen, the total output of nitrogen, which measures the extent to which proteid is decomposed in the body, varies with the intake of proteid food; but it is found that the proportion of nitrogen excreted in the forms of urea and uric acid varies with the extent of the metabolism. In other words, quantitative changes in the daily proteid katabolism are accompanied by pronounced changes in the distribution of the excreted nitrogen. Let us take a single illustration from Folin’s results; the case of a healthy man who on one day—July 13—consumed a proteid-rich diet, and on the other day—July 20—was living on a diet containing only about 1 gram of nitrogen. The composition of the excretion through the kidneys on these two days is shown in the following table:

Here we see, as would be expected, that on the high proteid diet, there was a large excretion of total nitrogen and of urea; while on the low proteid diet, nitrogen and urea were correspondingly diminished. The point to attract our attention, however, is the marked difference in the percentage of urea-nitrogen in the two cases; a difference which amounts to about 26 per cent. A similar difference is to be noted in the percentage of uric acid-nitrogen. Lastly, it is to be observed that in spite of the great difference in the extent of metabolism on the two days—an excretion of 16.8 grams of nitrogen, as contrasted with 3.6 grams—the amount of creatinin-nitrogen is essentially the same. Folin finds that these peculiarities in the percentage distribution of excreted nitrogen hold good in all cases where there is this wide divergence in the amount of proteid katabolized, and, further, that there is a gradual and regular transition from the one extreme to the other. He sees in these results evidence that there are in the body two forms of proteid katabolism, essentially independent and quite different. One kind is extremely variable in quantity, while the other tends to remain constant. The variable form has its own particular kind of waste products, of which urea is the chief. The constant katabolism, on the other hand, is largely represented by creatinin and to a lesser degree by uric acid. The more the total katabolism is reduced, the more prominent become creatinin and uric acid, products of the constant katabolism; while urea, as chief representative of the variable katabolism, becomes less conspicuous. Folin suggests the term endogenous or tissue metabolism for the constant variety, while the variable form he would name exogenous or intermediate metabolism.

In these suggestions we have not theory only, but a number of very important facts which plainly must have some significance. Take, for example, the excretion of creatinin. It is a characteristic nitrogenous waste product, but its elimination from the body is wholly independent of quantitative changes in the total amount of nitrogen excreted. In other words, the amount of creatinin eliminated is a constant quantity for a given individual under ordinary conditions, no matter how great the variation in the amount of proteid food, provided no meat is eaten. Meat must be avoided in testing this point, since meat contains a certain amount of creatin, or other components, which would be excreted as creatinin. Further, it is found that every individual has his own specific creatinin excretion, which fact again emphasizes the idea that this substance is a product of true tissue katabolism, having no connection with that variable metabolism, of which urea is the striking representative. These are facts which cannot be ignored. They are well established by the careful observations of Folin, and they are confirmed by a large number of observations made in our own laboratory. Turn now to that other, more conspicuous, product of proteid katabolism, urea. With a so-called average proteid intake, about 88–90 per cent of the excreted nitrogen will be in the form of urea, but, as Folin states, “with every decided diminution in the quantity of total nitrogen eliminated, there is a pronounced reduction in the per cent of that nitrogen represented by urea. When the daily total nitrogen elimination has been reduced to 3 grams or 4 grams, about 60 per cent of it only is in the form of urea.” Here, we have the chief product of exogenous metabolism, a substance quite distinct from creatinin, just as the process by which it originates is likewise quite distinct.

Exogenous metabolism is plainly a process of quite a different order from that of endogenous, or tissue metabolism. The latter involves oxidation, while the former consists essentially of a series of hydrolytic cleavages which result in a rapid elimination of the proteid-nitrogen as urea. In this conception of exogenous katabolism, we have essentially the same viewpoint as was previously taken in attempting to explain how excess of proteid food can be so quickly decomposed, and its nitrogen removed from the body. Whether the hydrolytic cleavage is accomplished solely by trypsin and erepsin, whether it takes place only in the intestine and in the liver, or whether other glands and tissues are involved, is at present immaterial; the essential point is that we have in the body a variety of proteid katabolism, quite different from true tissue katabolism, the extent of which is dependent primarily upon the amount of proteid food consumed. The process involved is one which aims at the rapid removal of the proteid-nitrogen as urea; without incorporation of the absorbed proteid, or its decomposition products, either as an integral or adherent part of the tissue proteid. Hydrolytic cleavage is eminently fitted to accomplish this with the least expenditure of energy, while the carbonaceous residue of the proteid thus freed from nitrogen can be transformed into carbohydrate, or directly oxidized as the needs of the body demand.

As one considers these views so admirably worked out by Folin, the question naturally arises, if the real demands of the body for proteid food will not be adequately met by the quantity necessary to satisfy the true tissue metabolism? We may well believe, with Folin, that “only a small amount of proteid, namely, that necessary for the endogenous metabolism, is needed. The greater part of the proteid furnished with so-called standard diets, like Voit’s, i. e., that part representing the exogenous metabolism, is not needed; or, to be more specific, its nitrogen is not needed. The organism has developed special facilities for getting rid of such excess of nitrogen, so as to get the use of the carbonaceous part of the proteid containing it.” In endogenous metabolism, we have a steady, constant process quite independent of the amount of proteid food, and absolutely indispensable for the maintenance of life. So far as we know at present, its representative creatinin is, for a given individual, the same in amount during fasting as when a rich, meat-free, proteid diet is taken. The one factor that seemingly determines the amount of creatinin eliminated is the weight of the individual, or more exactly the weight of the true tissue elements of the body, as distinct from fat or adipose tissue. Endogenous or tissue katabolism obviously calls for a certain quantity of proteid to maintain equilibrium, but this is small in amount as compared with the usual intake of proteid foods. The average man, with his ordinary dietetic habits, consumes more nitrogen than the body can possibly make use of. The excess is not stored up, “because the actual need of nitrogen is so small that an excess is always furnished with the food, except, of course, in carefully planned experiments” (Folin).

We have seen at what low levels of proteid intake, nitrogen equilibrium can be established, and we may well have faith in the conception of an endogenous proteid katabolism which involves only minimal quantities of proteid. Further, we have observed the constant tendency of the body to maintain a condition of nitrogenous equilibrium, even with varying income, and how slow the body is to lay by nitrogen on a rich proteid diet, even when long deprived of proteid food; a fact difficult of explanation except on the assumption that the real need of the body for nitrogen is small, and that the tissues habitually carry a relatively large reserve of nitrogenous material. We may assume with Folin that “all the living protoplasm in the animal organism is suspended in a fluid very rich in proteid, and on account of the habitual use of more nitrogenous food than the tissues can use as proteid the organism is ordinarily in possession of approximately the maximum amount of reserved proteid in solution that it can advantageously retain. When the supply of food proteid is stopped, the excess of reserve proteid inside the organism is still sufficient to cause a rather large destruction of proteid during the first day or two of proteid starvation, and after that the proteid katabolism is very small, provided sufficient non-nitrogenous food is available. But even then, and for many days thereafter, the protoplasm of the tissues has still an abundant supply of dissolved proteid, and the normal activity of such tissues as the muscles is not at all impaired or diminished. When 30 grams or 40 grams of nitrogen have been lost by an average-sized man during a week or more of abstinence from nitrogenous food the living muscle tissues are still well supplied with all the proteid they can use. That this is so, is indicated on the one hand by the unchanged creatinin elimination, and on the other by the fact that one experiences no feeling of unusual fatigue or of inability to do one’s customary work. Because the organism at the end of such an experiment still has an abundance of available proteid in the nutritive fluids, it is at once seemingly wasteful with nitrogen when a return is made to nitrogenous food. This is why it only gradually, and only under the prolonged pressure of an excessive supply of food-proteid again acquires its original maximum store of this reserve material.”

We may reasonably suppose that the reserve of proteid present in the body is contained in the fluid media, and not as a part of the living protoplasm. Further, we are apparently justified in the belief that the sole form of proteid katabolism which is vitally important for the welfare of the body is the endogenous katabolism. This must be provided for adequately and indeed liberally, and in addition there should be sufficient intake to keep up an abundant supply of reserve proteid, but beyond these necessities there would seem to be no legitimate demand for additional proteid. The voluminous exogenous proteid katabolism so conspicuous in most individuals would seem to have no justification in fact, or in physiological reasoning. What good, for example, can be accomplished by this constant splitting off of nitrogen, with its subsequent speedy removal from the body? The organism can neither use it nor store it up, and why therefore should this daily burden of an excessive and accelerated proteid katabolism be borne? As we have seen, the energy of muscle work is derived mainly, and can come wholly, from the breaking down of non-nitrogenous materials, fats and carbohydrates. The very fact that an intake of say 120 grams of proteid is followed at once by the removal of the larger part of the contained nitrogen, as a result of the exogenous katabolism of the body, would seemingly warrant the view that the proteid so decomposed might advantageously be replaced by a corresponding amount of carbohydrate. In muscle work, as in heat production, carbohydrate and fat are the materials burned up, or oxidized. Proteid, on the other hand, is not so oxidized, at least not the nitrogen-containing portion of the molecule.

There are apparent only two possible reasons for assuming a need on the part of the body for the high exogenous katabolism of proteid so commonly observed. The one is that the carbonaceous residue left after the cleavage of nitrogen from the proteid molecule is better adapted for the needs of the body than either carbohydrate or fat. Although this does not seem very probable, it is of course a possibility and merits consideration. Feeding experiments, with a comparatively small proteid intake, continued over a sufficient length of time, would show conclusively how much weight should be attached to this hypothesis. The other possibility is that the body may derive some advantage from the presence, in the tissues and fluids, of the varied nitrogenous cleavage products split off from proteid so abundantly in exogenous katabolism. These substances are mainly amino-acids on their way to urea, and there is no apparent reason why they should be of service to the organism. Still, the processes going on in the tissues and organs of the body are intricate and not wholly understood, and we can conceive of some useful function of which as yet we have no knowledge. In the construction of tissue proteid, for example, as in a possible synthesis out of the fragments formed by hydrolytic cleavage, it is not impossible that certain corner-stones are needed, and that in order to obtain these there must be a more or less wasteful breaking down of food-proteid. However improbable this may seem, it, like the preceding hypothesis, can be tested in a way by adequate feeding experiments, which shall determine the effect on the body of a low proteid intake continued over a long period of time. On the other hand, it is equally plausible, and for some reasons more probable, to assume that this excessive exogenous katabolism may be in a measure prejudicial to the best interests of the body; that the many nitrogenous fragments formed in the efforts of the organism to prevent undue accumulation of reserve proteid may in the long run do as much harm as good.

Further, there is reason in the question whether the continual carrying of excessive amounts of nitrogen reserves in the shape of soluble proteid in the blood and lymph, and in the meshes of tissue and cell protoplasm, is advantageous for the maintenance of the highest degree of efficiency? We all recognize that an excessive accumulation of fat is distinctly disadvantageous to the welfare of the body, and there is, physiologically speaking, equally good ground for considering that the storage of unorganized proteid in amounts beyond all possible requirements of the body may be equally undesirable. Because less tangible to the eye, the accumulation of unnecessary proteid is not so easily recognizable, but this fact does not diminish the possible danger which such accumulation may constitute. It must be granted, however, that we are dealing here with hypotheses and not facts, but though hypothetical the suggestions made are of sufficient moment to merit attention and experimental study. In a later chapter, we shall have occasion to present some facts bearing on these questions.

In the meantime, we may lay due stress upon the significance of these views regarding proteid katabolism. We must accept as settled the general idea that there are two distinct forms of proteid katabolism within the body; one form representing the decay of tissue or cell protoplasm, small in amount, with its own particular decomposition products, and absolutely essential for the continuance of life. The other form, the so-called exogenous katabolism, runs a totally different course with distinctive side-products and end-products; it is variable in extent, in harmony with variations in proteid intake, and subject to the suspicion that at the level ordinarily maintained it constitutes a menace to the preservation of that high degree of efficiency which is an attribute of good health.

CHAPTER V

DIETARY HABITS AND TRUE FOOD REQUIREMENTS

Topics: Dietetic customs of mankind. Origin of dietary standards. True food requirements. Arguments based on custom and habit. Relationship between food consumption and prosperity. Erroneous ideas regarding nutrition. Commercial success and national wealth not the result of liberal dietary habits. Instinct and craving not wise guides to follow in choice and quantity of food. Physiological requirements and dietary standards not to be based on habits and cravings. Old-time views regarding temperate use of food. The sayings of Thomas Cogan. The teachings of Cornaro. Experimental results obtained by various physiologists. Work of the writer on true proteid requirements. Studies with professional men. Nitrogen equilibrium with small amounts of food. Sample dietaries. Simplicity in diet. Nitrogen requirement per kilogram of body-weight. Fuel value of the daily food. Experiments with university athletes. Nitrogen balance and food consumption. Sample dietaries. Adequacy of a simple diet.

Having acquired information regarding the principles of metabolism and the general laws governing the nutrition of the body, we may next consider briefly the dietetic habits of mankind, with a view to learning how far such habits coincide with actual nutritive requirements. Eventually, we shall need to ask the questions: What are the true nutritive requirements of the body? How much food and what kinds of food does the ordinary individual doing an average amount of work need each day in order to preserve body equilibrium, and to maintain health, strength, and vigor under the varying conditions of life? What amount of nitrogen or proteid, and what the total calorific value required to supply the physiological needs of the body? How closely do the so-called “normal diets” and “standard diets,” which have met with such general acceptance, conform to a rational conception of true physiological needs? These are vital questions of great physiological and economic importance, and they are not easily answered; but theoretical considerations based on scientific data, and experimental evidence combined with practical experience, should point the way to some very definite conclusions.

Observations made in many countries regarding the dietetic customs and habits of the people have resulted in the establishment of certain dietary standards, which have been more or less generally adopted as representing the requirements of the body. As a prelude to the discussion of this question, let us consider briefly some of the results of these dietary studies. In Sweden, laborers doing hard work were found by Hultgren and Landergren to consume daily, on an average, 189 grams of proteid, 714 grams of carbohydrate, and 110 grams of fat, with a total fuel value for the day’s ration of 4726 large calories. In Russia, workmen at moderately hard labor, having perfect freedom of choice in their food, were found by Erisman to take daily 132 grams of proteid, 584 grams of carbohydrate, and 79 grams of fat, this ration having a fuel value of 3675 calories. In Germany, soldiers in active service consumed daily, according to Voit, 145 grams of proteid, 500 grams of carbohydrate, and 100 grams of fat, with a fuel value of 3574 calories. In Italy, laborers doing a moderate amount of work were found by Lichtenfelt to consume daily 115 grams of proteid, 696 grams of carbohydrate, and 26 grams of fat, with a fuel value of 3655 calories. In France, Gautier states that the ordinary laborer working eight hours a day must have 135 grams of proteid, 700 grams of carbohydrate, and 90 grams of fat daily, with a fuel value of 4260 calories. In England, weavers were found to take daily 151 grams of proteid, with carbohydrates and fats sufficient to make the total fuel value of the day’s ration equal to 3475 calories. In Austria, farm laborers consumed daily 159 grams of proteid, with carbohydrates and fats sufficient to raise the fuel value of the food to 5096 calories.

Observations of this order might be multiplied indefinitely, but the above will suffice to give a general idea of the average food consumption of European peoples doing a moderate amount of work. These data, however, must be supplemented by the observations made in our own country, which have been very extensive, through the “investigations on the nutrition of man in the United States,” carried on by the Office of Experiment Stations in the Department of Agriculture, under the efficient leadership of Atwater. As stated by Messrs. Langworthy and Milner, in an official bulletin issued in 1904, dietary studies of the actual food consumption of people of different classes in different parts of the United States have been made during the years 1894 to 1904 on about 15,000 persons,—men, women, and children,—as a result of which it is indicated that “the actual food requirements of persons under different conditions of life and work” vary from 100 to 175 grams of proteid per day, with a total fuel value ranging from 2700 to 5500 calories. For comparison, the various data may be tabulated as shown on page [155].

These figures by no means represent maximum food consumption. Thus, studies have been made on fifty Maine lumbermen,[53] where the intake of proteid food averaged 185 grams per day, with a total fuel value of 6400 calories. Further, dietary studies of university boat crews[54] have shown fairly high results. The Yale University crew, while at Gales Ferry, averaged per man during seven days 171 grams of proteid, 171 grams of fat, and 434 grams of carbohydrate, with a total fuel value of 4070 calories per day. The members of the Harvard University crew showed an average daily consumption of 160 grams of proteid, 170 grams of fat, and 448 grams of carbohydrate, with a total fuel value of 4074 calories. It is also reported that a football team of college students in the University of California consumed daily, per man, 270 grams of proteid, 416 grams of fat, and 710 grams of carbohydrate, with a total fuel value of 7885 calories. These figures may be contrasted, however, with the data obtained in a study of the dietary habits of fourteen professional men’s families, where the average amount of proteid consumed daily was 104 grams, fat 125 grams, and carbohydrate 423 grams, with a total fuel value of 3325 calories.

Leaving out of consideration the extremes given, it is undoubtedly true that, within certain rather wide limits, there is an apparent tendency for people of different nations, having a free choice of food and not restricted by expense, to consume daily approximately the same amounts of nutrients; to use what may be called liberal rather than small amounts of food; and, lastly, to consume food somewhat in proportion to the amount of work done. It is perhaps, therefore, not strange that students of nutrition should have taken these results, obtained by the statistical method, as indicating the actual needs of the body for food, and that so-called “standard diets” and “normal diets” should have been constructed, based upon these and corresponding data. Thus, we have the widely adopted “Voit standard,” composed of proteid 118 grams, carbohydrate 500 grams, and fat 56 grams, with a total fuel value of 3055 calories, as the amount of food required daily by a man of 70 kilos body-weight doing a moderate amount of work. These figures were obtained by Voit as an average of the food consumption of a large number of laboring men in Germany, and they carried additional weight because at that time Voit and others thought they had evidence that nitrogenous equilibrium could not be maintained for any length of time on smaller amounts of proteid.

The figures given in the preceding table under the head of American subjects constitute the “Atwater standards,” and as already indicated, are based upon the dietetic habits of over 15,000 persons under different conditions of life and physical activity. In the words of the official Bulletin, these standards covering the quantities of food per day “are intended to show the actual food requirements of persons under different conditions of life and work.” Here, however, lies an assumption which seems to meet with wide acceptance, but for which it is difficult to conceive any logical reason. The thousands of dietary studies made on peoples all over the world, affording more or less accurate information regarding the average amounts of proteid, fat, and carbohydrate consumed under varying conditions, are indeed most interesting and important, as affording information regarding dietetic customs and habits; but, the writer fails to see any reason why such data need be assumed to throw any light on the actual food requirements of the body. In the words of another, “Food should be ingested in just the proper amount to repair the waste of the body; to furnish it with the energy it needs for work and warmth; to maintain it in vigor; and, in the case of immature animals, to provide the proper excess for normal growth, in order to be of the most advantage to the body” (Benedict).

Any habitual excess of food, over and above what is really needed to meet the actual wants of the body, is not only uneconomical, but may be distinctly disadvantageous. Voit, among others, has clearly emphasized the general principle that the smallest amount of proteid, with non-nitrogenous food added, that will suffice to keep the body in a state of continual vigor is the ideal diet. My own conception of the true food requirements of the body has been expressed in the statement that man needs of proteids, fats, and carbohydrates sufficient to establish and maintain physiological and nitrogen equilibrium; sufficient to keep up that strength of body and mind that is essential to good health, to maintain the highest degree of physical and mental activity with the smallest amount of friction and the least expenditure of energy, and to preserve and heighten, if possible, the ordinary resistance of the body to disease germs. The smallest amount of food that will accomplish these ends is, I think, the ideal diet. There must truly be enough to supply the real needs of the body, but any great surplus over and above what is actually called for may in the long run prove an undesirable addition. With these thoughts in mind, may we not reasonably ask why it should be assumed that there is any tangible connection between the dietetic habits of a people and their true physiological needs?

Arguments predicated on custom, habit, and usage have no physiological basis that appeals strongly to the impartial observer. Man is a creature of habits; he is quick to acquire new ones when his environment affords the opportunity, and he is prone to cling to old ones when they minister to his sense of taste. The argument that because the people of a country, constituting a given class, eat a certain amount of proteid food daily, the quantity so consumed must be an indication of the amount needed to meet the requirements of the body, is as faulty as the argument that because people of a given community are in the habit of consuming a certain amount of wine each day at dinner their bodies must necessarily be in need of the stimulant, and that consequently alcohol is a true physiological requirement. A large proportion of mankind is addicted to the tobacco habit, and to many persons the after-dinner cigar is as essential to comfort as the dinner itself; but would any one think of arguing that tobacco is one of the physiological needs of the body?

It is said that dietary studies made all over the civilized world “show that a moderately liberal quantity of protein is demanded by communities occupying leading positions in the world. . . . It certainly seems more than a remarkable coincidence that peoples varying so widely in regard to nationality, climatic and geographical conditions, and dietetic habits, should show such agreement in respect to consumption of protein and energy.” Again, we hear it said that “whatever may be true of a few individuals, with communities a generally low condition of mental and physical efficiency, thrift, and commercial success, is coincident with a low proportion of protein in the diet.” The writer, however, fails to find evidence in the results afforded by dietary studies that there is any causal relationship between the amount of proteid food consumed and the mental or physical supremacy of the people of a given nation or community. Cause and effect are liable to become reversed in arguments of this kind. It is certainly just as plausible to assume that increase in the consumption of proteid follows in the footsteps of commercial and other forms of prosperity, as to argue that prosperity or mental and physical development are the result of an increased intake of proteid food.

Proteid foods are usually costly, and the ability of a community to indulge freely in this form of dietetic luxury depends in large measure upon its commercial prosperity. The palate is an extremely sensitive organ, and the average individual properly derives great satisfaction from the pleasurable effects of tasty articles of food. Furthermore, there are many curious and quite unphysiological notions abroad regarding foods, which tend to incite persons to unnecessary excess and extravagance whenever they acquire the means to do so. The latter point is well illustrated by the more or less prevalent opinion that a cut of tenderloin steak is more nutritious than a cut of round steak. It is true that the former is apt to be more tender, to have a little finer flavor; but the round steak, when properly prepared, is just as nutritious, and equally capable of meeting the needs of the body, as the more expensive tenderloin. With increasing prosperity, we turn at once, as a rule, to the more tasty and appetizing viands, partly to satisfy the craving of appetite and palate, and partly because there is an inherent belief that these varied delicacies, accessible to the prosperous community, count as an aid to health and strength. The poor laborer, with his small wage, is restricted to a certain low level of dietary variety, and must likewise be economical as to quantity, but on the first opportunity afforded by a fuller purse he is apt to pass from corned beef to a fresh roast with its more appetizing flavor; to eschew brown bread in favor of the white loaf, and in many other ways to evince his desire for a dietary which, though perhaps no more nutritious, appeals because of its finer flavor, more appetizing appearance, and greater variety. He is in the same position as the smoker who, limited by his purse to a five-cent cigar after dinner, quickly passes to a cigar of better flavor as soon as his finances warrant the indulgence. At the same time, if prosperity continues, our laborer will speedily pass to a higher level of proteid intake and greater fuel value, through increased consumption of meat and butter, together with other articles rich in proteid and fat.

In this connection, we may emphasize a fact of some significance in its bearing on dietetic customs; viz., that ever since Liebig advanced his theory that proteid material is the sole source of muscular energy, there has been a deep-rooted belief that meat is the most efficient kind of food for keeping up the strength of the body, and hence especially demanded by all whose work is mainly physical. Although this view, as we have seen, has been thoroughly disproved, the idea is still more or less generally held that an abundance of meat is a necessary requisite for a good day’s work, a view which undoubtedly accounts in some measure for the tendency toward a high proteid intake, evinced by many of the laboring class whose means will permit the necessary outlay.

Increased consumption of proteid food may be coincident with thrift and commercial success, but there is no justification for the belief that these are the result of changed dietary conditions. The dietary of our New England forefathers was, according to all accounts, exceedingly limited as compared with that of to-day, but it is doubtful if the present generation is any better developed, physically or mentally, than the stalwart and vigorous people who opened up this country to civilization. To-day, as a nation, we have greater wealth, and our commercial prosperity has become phenomenal; but would any one think for a moment that these characteristics are attributable to the large consumption of proteid food so common to this generation of the American people? No, increased wealth simply paves the way for greater freedom in the choice of food; increased commercial success and business prosperity throw open avenues which formerly were closed; greater variety of animal foods, and vegetable foods as well, rich in proteid, are made easily accessible, and appeal to eye and palate on all sides; appetite and craving for food are abnormally stimulated, and dietetic habits and customs change accordingly. In the words of another, “the one thing that primitive, barbarous, and civilized man alike long for is an abundance of the ‘flesh-pots of Egypt.’ The very first use the latter makes of his increased power and financial resources is to buy new, rare, and expensive kinds of meat.” With these facts before us, it is difficult to accept the assumption that dietetic customs afford any indication of the food requirements of the body. To the physiologist such a view does not appeal, since there is a lack of any scientific evidence that carries conviction.

But it may be asked, is not appetite a safe guide to follow? Do not the cravings of the stomach and the so-called pangs of hunger merit consideration? Is it not the part of wisdom to follow inclination in the choice and quantity of our food? Can we not safely rely upon these factors as an index of the real needs of the body? If these questions are to be answered in the affirmative, then it is plain that a study of dietetic customs will tell us definitely how much food and what kinds of food are required daily to supply the true wants of the body. There are writers who claim that instinct is a perfectly safe guide to follow; that it is far superior to reason; but it is to be noticed that most of these writers, if they have any physiological knowledge to draw upon, are sooner or later prone to admit that the body has certain definite needs which it is the purpose of food to supply, with the added implication that any surplus of food over and above what is necessary to meet these demands is entirely uncalled for. Thus, one such writer states that “the man in the street follows his God-given instincts and plods peacefully along to his three square meals a day, consisting of anything he can find in the market, and just as much of it as he can afford, with special preference for rich meats, fats, and sugars.” Yet this same writer, a little later, emphasizes the fact that “every particle of the energy which sparkles in our eyes, which moves our muscles, which warms our imaginations, is sunlight cunningly woven into our food by the living cell, whether vegetable or animal. Every movement, every word, every thought, every aspiration represents the expenditure of precisely so much energy derived from food.” Why, then, would it not be wise to ascertain how much energy is so expended, on an average, during the day’s activity and govern the intake of food accordingly? Why not apply an intelligent supervision in place of following an instinct which, in the words of the author just quoted, leads one on to consume “anything he can find in the market and just as much of it as he can afford”? Truly, if dietetic customs and the habits of mankind are the results of instinct working in this fashion, there cannot be much value in the data obtained by observing the quantities of food mankind is in the habit of eating. Dietary standards based on such observations must be open to the suspicion of representing values far above the actual needs of the body.

Habits and cravings are certainly very unreliable indices of true physiological requirements. Man is constantly acquiring new habits, and these in time become second nature, forcing him to practise that which he has become accustomed to, regardless of whether it is beneficial or otherwise. The celebrated philosopher, John Locke, in his essay on education, says: “I do not think all people’s appetites are alike . . . but this I think, that many are made gourmands and gluttons by custom, that were not so by nature; and I see in some countries, men as lusty and strong, that eat but two meals a day, as others that have set their stomachs by a constant usage, like Larums, to call on them for four or five.” Again, the so-called cravings of appetite are largely artificial and mainly the result of habit. A habit once acquired and persistently followed soon has us in its grasp, and then any deviation therefrom is very apt to disturb our physiological equilibrium. The system makes complaint, and we experience a craving, it may be, for that to which the body has become accustomed. There has thus come about a sentiment that the cravings of the appetite for food are to be fully satisfied, that this is merely obedience to nature’s laws. In reality, there is no foundation for such a belief; any one with a little persistence can change his or her habits of life, change the whole order of cravings, thereby indicating that the latter are essentially artificial, and that they have no necessary connection with the welfare or needs of the body. The man who for some reason deems it advisable to adopt two meals a day in place of three or four, at first experiences a certain amount of discomfort, but eventually the new habit becomes a part of the daily routine, and the man’s life moves forward as before, with perfect comfort and without a suggestion of craving, or a pang of hunger. Dietetic requirements, and standard dietaries, are not to be founded upon the so-called cravings of appetite and the instinctive demands for food, but upon reason and intelligence, reinforced by definite knowledge of the real necessities of the bodily machinery.

The standards which have been adopted more or less generally throughout the civilized world, based primarily on the assumption that man instinctively and independently selects a diet that is best adapted to his individual needs, are open to grave suspicion. The view that the average food consumption of large numbers of individuals and communities must represent the true nutritive requirements of the people is equally untenable. Naturally, there is general recognition of the principle that food requirements are necessarily modified by a variety of circumstances, such as age, sex, body-weight, bodily activity, etc. It is obvious that the man of 140 pounds body-weight needs less proteid than the man of 170 pounds, and that the man who does a large amount of physical work demands a larger calorific value in his daily diet, i. e., more carbohydrate and fat, than the sedentary individual. The growing child, in proportion to his body-weight, plainly needs more proteid for the upbuilding of tissue, and there are many conditions of disease where special dietetic treatment is undoubtedly called for. Our contention, however, and one which we believe to be perfectly justifiable, is that the true food requirements of the body, under any conditions, cannot be ascertained with any degree of accuracy by observations of what people are in the habit of eating; that customs and habits are not a safe index of true physiological needs. On the contrary, we are inclined to the belief that direct physiological experimentation, covering a sufficient length of time and with an adequate number of individuals, will prove far more efficient in affording a true estimate of the quality and quantity of food best adapted for the maintenance of good health, strength, and vigor.

Before considering these latter points, it is interesting to note, in passing, that during the last four centuries many thoughtful men have called attention to the apparent excessive use of food. There seems to have been in many quarters a more or less prevalent opinion that custom and habit were leading people on to methods of living, which were not in accord with the best interests of the community. It must be remembered, however, that arguments of this kind, even fifty years ago, could have been founded only on general observation and the application of common sense, since there were then no sound physiological data on which to predicate an opinion, or base a conclusion. Still, there were men of authority who attempted to lay before the people a proper conception of the temperate use of food. We have not the time here to consider many of these pleas, but I venture to call attention to the somewhat celebrated book published by the physician Thomas Cogan in 1596, under the title “The Haven of Health,” and dedicated “to the right honorable and my verie good lord, Sir Edward Seymour, Knight and Earl of Hertford.” Under the subject of diet, this old-time writer says: “The second thing that is to be considered of meates is the quantitie, which ought of all men greatly to be regarded, for therein lyeth no small occasion of health or sickness, of life or death. For as want of meate consumeth the very substance of our flesh, so doth excesse and surfet extinguish and suffocate naturall heat wherein life consisteth.” Again, “Use a measure in eating, that thou maist live long: and if thou wilst be in health, then hold thine hands. But the greatest occasion why men passe the measure in eating, is varitie of meats at one meale. Which fault is most common among us in England farre above all other nations. For such is our custome by reason of plentie (as I think) that they which be of abilitie, are served with sundry sortes of meate at one meale. Yea the more we would welcome our friends the more dishes we prepare. And when we are well satisfied with one dish or two, then come other more delicate and procureth us by that meanes, to eate more than nature doth require. Thus varietie bringeth us to excesse, and sometimes to surfet also. But Phisicke teacheth us to faede moderately upon one kinde of meate only at one meale, or at leastwise not upon many of contrarie natures. . . . This disease, (I mean surfet) is verie common: for common is that saying and most true: That more die by surfet than by the sword. And as Georgius Pictorius saith, all surfet is ill, but of bread worst of all. And if nature be so strong in many, and they be not sicke upon a full gorge, yet they are drowsie and heavie, and more desirous to loyter than to labor, according to that old maeter, when the belly is full, the bones would be at rest. Yea the minde and wit is so oppressed and overwhelmed with excesse that it lyeth as it were drowned for a time, and unable to use his force.”

Cogan likewise makes some interesting statements regarding the effects of custom on the consumption of proteid food, especially meats. Quoting further from this author: “The fourth thing that is to be considered in meats is custome. Which is of such force in man’s bodie both in sicknesse and in health, that it countervaileth nature itselfe, and is therefore called of Galen in sundry places, an other nature. Whereof he giveth a notable example, where he sheweth that an olde woman of Athens used a long time, to eate Hemlocke (which is a ranke poison) first a little quantitie, and afterwarde more, till at length she could eate so much without hurt as would presently poison another. . . . So that custome in processe of time may alter nature.” Finally, we may quote one last saying of Cogan’s, because of the good sense and wisdom displayed in the sentiment, as true to-day as when it was written more than three hundred years ago: “Neither is it good for any man that is in perfect health, to observe any custome in dyet precisely, as Arnoldus teacheth upon the same verses in these wordes: Every man should so order himselfe, that he might be able to suffer heate and cold, and all motions, and meats necessary, so as he might change the houres of sleeping and waking, and his dwelling and lodging without harme: which thing may be done if we be not too precise in keeping custome, but otherwise use things unwonted. Which sentence of Arnoldus agraeth verie well to that of Cornelius Celsus: He that is sound and in good health, and at libertie, should bind himselfe to no rules of dyet. To need neither Phisition or Chirurgion, he must use a diverse order of life, and be sometimes in the countrie, sometime in the towne, sometimes hunt, and sometime hawke. But some man may demand of me how this may agree with that saying of the scholar of Salernus ‘if you would be free from physicians, let these three be your physician, a cheerful mind, rest, and a moderate diet.’ Whereunto I answer, that a moderate dyet is alwaies good, but not a precise dyet: for a moderate diet is, as Terence speaketh in Andria: To take nothing too much: which alwaies is to be observed. But if a man accustome himselfe to such meats and drinks as at length will breed some inconvenience in his bodie, or to sleepe or to watch, or any other thing concerning the order of his life, such custome must naedes be amended and changed, yet with good discretion, and not upon the sudden: because sudden changes bring harme and weaknesse, as Hippocrates teacheth. He therefore that will alter any custome in dyet rightly, must do it with three conditions, which are expressed by Hippocrates. Change is profitable, if it be rightly used, that is, if it be done in the time of health, and at leisure, and not upon the sudden.”

This noteworthy book written by Cogan was preceded by the writings of Louis Cornaro, the Venetian, who forty years before had published the first edition of his celebrated book, “The Temperate Life,” and who was a most ardent advocate of the benefits to be derived by living temperately, especially in matters of diet. The simple diet which served for the nourishment of the oldest peoples of Syria, Greece, Egypt, and of the Romans when they were at the height of their prosperity and culture, was advocated by Cornaro as conducing to longevity, better health, and greater comfort of mind and body. Himself a striking example of the effects of a reasonable abstinence in diet (the last edition of his book having been written at the age of ninety-five), his teachings have continued to attract attention down to the present day; and although we have no values in grams or calories expressive of his average food consumption, it is quite evident that Cornaro lived a very abstemious life, eating little of the heavier articles of diet common to his time and country. It is perhaps not strictly physiological to refer to these cases, yet they have value as representing a sentiment, common to the centuries now passed, that benefit was to be derived by mankind from greater care in the taking of food; that prevalent customs and habits were leading the people into intemperate modes of life, and that these were surely tending toward the physical and mental deterioration of the nation. We may attach much or little weight to these conclusions, but there is a certain degree of significance in the views, current then as now, that dietetic customs and habits have no real connection with bodily requirements.

Passing down to our own times, we find physiologists, by the aid of scientific methods, studying the effects of smaller amounts of food (smaller than custom prescribes) on the condition of the body, thereby evincing a certain degree of skepticism concerning the dietary standards based on habit and usage. This has been especially true regarding the nitrogen requirement, or the need for proteid food. As has been clearly pointed out in other connections, there are two distinct needs which the body has for food; one for proteid or nitrogen, the other for energy-yielding material. According to the Voit standard, a man of average body-weight doing a moderate amount of work requires daily 118 grams of proteid food, or about 16 grams of metabolizable nitrogen, with fat and carbohydrate sufficient to yield a total fuel value of over 3000 large calories. As we have seen, the fuel value of the food must of necessity be a variable quantity because of variations in bodily activity. The more muscular work performed, the greater must be the intake of carbohydrate and fat, if the body is to be kept in equilibrium. With proteid or nitrogen, however, the case is quite different, since with adequate amounts of non-nitrogenous food, proteid is not drawn upon for the energy of muscular work. We can conceive of the nitrogen requirement, therefore, as being a constant factor in the well-nourished individual and dependent primarily upon body-weight, or more exactly, upon the weight of true proteid-containing tissue. Obviously, whatever else happens, there must be enough proteid food taken daily to maintain the body in nitrogen equilibrium. If this can be accomplished only by the ingestion of 16 grams of metabolizable nitrogen, then it is plain that the daily ration must contain at least 118 grams of proteid food; i. e., it must conform approximately at least to ordinary usage.

This question has been studied by many investigators, with very interesting and suggestive results. Thus, in 1887, Hirschfeld[55] reported some experiments on himself, twenty-four years of age and weighing 73 kilos. His ordinary diet contained daily 100 to 130 grams of proteid, and the amount of nitrogen excreted varied from 16 to 20 grams per day, corresponding to a metabolism of proteid equal to the amount ingested. In other words, the body was essentially in nitrogen equilibrium. Then, for a period of fifteen days, during which he was unusually active, he lived on a diet in which the content of proteid corresponded to only 6 grams of nitrogen per day, and yet he remained in nitrogen equilibrium. The diet made use of was composed essentially of milk, eggs, rice, potatoes, bread, butter, sugar, and coffee, with some wine and beer, and on two days a little meat. It is to be observed that the nitrogen or proteid intake per day was only one-third of what he was accustomed to consume. In a second experiment, covering ten days, similar results were obtained. So that evidence was afforded that a young and vigorous man can maintain his body in nitrogen equilibrium, for fifteen consecutive days at least, on an amount of proteid food equal to only one-third of the minimal requirement called for by common usage. Plainly, the difference between a daily consumption of 118 grams of proteid food and 40 grams represents a large percentage saving, both of proteid and in the metabolism of proteid matter with all the attendant transformations. In these experiments, however, the subject consumed relatively large amounts of non-nitrogenous food, notably butter, of which on some days he took as much as 100 grams. The average fuel value of his food ranged from 3750 to 3916 calories per day; a fact of some importance, since it is to be remembered that both fat and carbohydrate tend to protect proteid metabolism.

In an experiment reported in 1889 by Carl Voit[56], on a vegetarian weighing about 57 kilos, it was found that with a purely vegetable diet the subject was able, for a few days at least, to maintain his body in essentially a condition of nitrogen equilibrium on a daily diet containing 8.4 grams of nitrogen, corresponding to 52.5 grams of proteid. In addition, there was a large consumption of starchy food with some fat. Klemperer,[57] experimenting with two young men, having a body-weight of 64 and 65.5 kilos, respectively, was able to keep them in a condition of nitrogenous equilibrium for a period of eight days on 4.38 grams and 3.58 grams of nitrogen per day. The diet, however, had a large fuel value, 5020 calories per day, and contained in addition to the small amount of proteid, 264 grams of fat, 470 grams of carbohydrate, and 172 grams of alcohol. Breisacher,[58] in an experiment on himself, using a mixed diet composed of 67.8 grams of proteid, 494.2 grams of carbohydrate, and 60.5 grams of fat per day, with a total fuel value of 2866 calories, observed a daily excretion of nitrogen during thirty days of 8.23 grams. This corresponds to a metabolism of 51.4 grams of proteid, thus showing that the 67 grams of food-proteid taken was quite sufficient to maintain nitrogen equilibrium for the above length of time.

Caspari and Glässner[59] have reported observations made on two vegetarians, a man and his wife, aged 49 and 48 years respectively, who had lived for some years exclusively on a vegetable diet. The man had a body-weight of 68.8 kilos, while the woman weighed 58 kilos. During five days, the man consumed per day, on an average, 7.83 grams of nitrogen and 4559 calories. This corresponds to 0.114 gram of nitrogen per kilo of body-weight, and 66 calories per kilo. On this diet, the man gained slightly in weight and showed a plus nitrogen balance of 5.2 grams for the five days. In other words, even this low nitrogen or proteid intake was more than sufficient to meet the wants of his body. The wife, during the same period of time, consumed per day 5.33 grams of nitrogen and 2715 calories, corresponding to 0.092 gram of nitrogen per kilo of body-weight and 47 calories per kilo. On this diet, the woman gained 0.9 kilo in weight during the five days, and like the man, she showed a plus nitrogen balance of 2.45 grams for the entire period. The somewhat noted experiments of Sivén have been referred to in another connection, and it will suffice to recall the fact that he was able, with a body-weight of 60 kilos, to establish nitrogen equilibrium on 6.26 grams of nitrogen, and for a day or two on 4.5 grams of nitrogen, with a total fuel value of only 2444 calories in the day’s ration.

These few illustrations will serve to indicate that, so far as the maintenance of nitrogen equilibrium is concerned during short periods of time, there is no necessity for the consumption of proteid food in such amounts as common usage dictates. The high proteid intake called for by the “standard dietaries,” and the ordinary practices of mankind, is not needed to establish a condition of nitrogen equilibrium. It would seem, however, as if results of this nature, presented from time to time by various investigators, have been considered more in the light of scientific curiosities than as data having an important bearing on physiological processes. So strong has been the hold upon the medical and physiological mind of the necessity of high proteid that such figures as the above have merely excited comment, without weakening in any measure the prevalent conviction that health, strength, and the power to work necessitate a high rate of proteid exchange.

To one willing to accept the data as having possible significance there arises at once the question, How long can the body be maintained in nitrogen equilibrium on such relatively small quantities of proteid food? In other words, can experiments of this nature, extending over comparatively short periods of time, be safely accepted as a reliable means of measuring the proteid requirements of the body for indefinite periods? Suppose, says the critic, we grant that the body can maintain itself in nitrogen equilibrium for a week or two on a very small amount of proteid food, what proof have we that in the long run the body will be benefited thereby, or even able to exist in a condition of normal strength and vigor? In other words, is a low proteid diet, one that seems sufficient to maintain the body in nitrogen equilibrium, a wholly safe one to follow? May there not be other elements to be considered, aside from nitrogen equilibrium, which, if fully understood, would satisfactorily account for the customs of mankind, in which perhaps man’s instincts have been followed for the betterment of the race? It was with a view to learning more concerning these questions that five years ago the writer commenced systematic, experimental, work upon the nutrition of man, with special reference to his nitrogen requirements. The experiments and observations have been continued up to the present time, with many suggestive results, some of which will now be referred to.[60]

One group of subjects was composed of professional men, professors and instructors in the university, whose work was mainly mental rather than physical, though by no means excluding the latter. Of this group, two cases will be referred to with some regard for detail, since in no other way can so striking a picture be presented of the effects produced. The first subject weighed 65 kilos in the fall of 1902, and at that time was nearly 47 years of age. His dietetic habits were in accord with common practice, and his daily consumption of proteid food averaged close to 118 grams. With a clear recognition of the principle that the habits of a lifetime should not be too suddenly changed, a very gradual reduction in the total amount of food, and especially of proteid matter, was made. This finally resulted, with this particular subject, in the complete abolition of breakfast, with the exception of a small cup of coffee. A light lunch was taken at noontime, followed by a more substantial dinner at night. There was no change to a vegetable diet, but naturally any attempt to cut off largely the amount of proteid food necessarily results in a marked diminution in the quantity of animal food or meats. It is a somewhat singular though suggestive fact, that a change of this order gradually results in a stronger liking for simple foods, with their more delicate flavor, accompanied by a diminished desire for the heavier animal foods.

As the day’s ration was gradually reduced in amount, the body-weight began to fall off, until after some months it became stationary at 57 kilos, at which point it has remained practically constant for over three years. The sixteen pounds of weight lost was composed, mainly at least, of superfluous fat. For a period of nine months, from October, 1903, to the end of June, 1904, the amount of proteid material broken down in the body was determined each day. The average daily metabolism of nitrogen for the entire period of nearly nine months amounted to 5.69 grams. For the last two months, it averaged 5.4 grams per day. Analyses made from time to time since these figures were obtained show that the subject is still living at the same low level of nitrogen metabolism. In fact, the data available afford satisfactory proof that for a period covering over three years this particular person has subsisted on an amount of proteid food equal to a metabolism of not more than 5.8 grams of nitrogen per day. It may be asked why the subject should have continued such a low proteid diet after the nine months’ period was completed? In reply, it may be said that the new habit has taken a firm hold, and entirely supplanted the dietetic desires and cravings of the preceding years. Further, the improved condition of health, freedom from minor ailments that formerly caused inconvenience and discomfort, and the greater ability to work without fatigue, have all combined to place the new habit on a firm basis, from which there is no desire to change.

Consider for a moment what this lowered consumption of proteid food really amounts to, as compared with ordinary usage and the so-called dietary standards. The latter call for at least 118 grams of proteid or albuminous food daily, of which 105 grams should be absorbable, in order to maintain the body in a condition of nitrogen equilibrium, and in a state of physical vigor and general tone. This would mean a daily metabolism and excretion of at least 16 grams of nitrogen. Our subject, however, excreted per day, during nine months, only 5.69 grams of nitrogen, which means a metabolism of 35.6 grams of proteid; i. e., about one-third the amount ordinarily deemed necessary to meet man’s requirement for proteid food. But was our subject in nitrogen equilibrium on this small amount of proteid food? We answer yes, as the following balance period shows:

In this particular period of six days, the body was really gaining a little nitrogen, i. e., storing away a small amount of proteid for future use, although it may be granted that the amount was too small to have any special significance. During this period, the average daily intake of nitrogen was 6.4 grams, equal to 40 grams of proteid food. The average daily output of nitrogen through kidneys and excrement was 6.24 grams. The average daily output of metabolized nitrogen, through the kidneys, was 5.44 grams, corresponding to the breaking down of 34 grams of proteid material. Further, it should be stated that the total calorific value of the daily food during this period was less than 2000 calories. Let me add now a final balance period taken at the close of the nine months’ trial:

In this period of five days, the average daily intake of nitrogen was 5.86 grams, corresponding to 36.6 grams of proteid food. The average daily output of metabolized nitrogen was 4.92 grams, implying the breaking down in the body of only 30.7 grams of proteid material per day. The fuel value of the daily food, calculated as closely as possible, was less than 2000 calories. The body was essentially in nitrogen equilibrium, the minus balance being too small to have any special significance.

It will be instructive to consider next the actual character and amount of the diet made use of on several of these balance days:

March 21.

Breakfast.—Coffee 119 grams, cream 30 grams, sugar 9 grams.

Lunch.—One shredded wheat biscuit 31 grams, cream 116 grams, wheat gem 33 grams, butter 7 grams, tea 185 grams, sugar 10 grams, cream cake 53 grams.

Dinner.—Pea soup 114 grams, lamb chop 24 grams, boiled sweet potato 47 grams, wheat gems 76 grams, butter 13 grams, cream cake 52 grams, coffee 61 grams, sugar 10 grams, cheese crackers 16 grams.