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 experiment30 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 Dapper31 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.

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: