Physiological economy in nutrition, with special reference to the minimal proteid requirement of the healthy man / an experimental study

by R. H. Chittenden

IV. THE SYSTEMIC VALUE OF PHYSIOLOGICAL ECONOMY IN NUTRITION.

It is one of the axioms of physiology that the majority of the diseases of mankind are due to, or are connected with, perversions of nutrition. General or local disturbances of metabolism are broadly responsible for disease, and with a due recognition of this fact it may be well to consider more specifically whether greater economy in the consumption of food, i. e., a restriction of the daily diet to amounts more commensurate with the physiological needs of the body, may not be of value in preventing disease, or prove of use in combating disease when the latter has manifested itself.

Broadly speaking, the extent and character of the metabolic processes of the body are dependent in large measure upon the amount and character of the diet. Further, it is equally certain that the chemical composition of the blood and lymph is quickly affected by the amount and character of the food materials absorbed from the alimentary canal. Even in the matter of secretion of the digestive juices, we have learned, through the recent experiments of Pawlow, that the chemical composition and solvent action of these fluids may be modified by the amount and character of the food fed. How much more, then, may we expect the intricate processes of cell and tissue metabolism to be modified by changes in the chemical composition of the blood and lymph that bathe them.

Further, recognizing as we must the extreme sensitiveness of the central and peripheral parts of the nervous system to changes in the composition of the blood, we see suggested indirect ways by which metabolism, both general and local, may be modified by influences exerted upon the nervous system, whereby the nutritive condition of individual structures may undergo change. Vasomotor influences, controlled as they are by nerve fibres, which in turn are sensitive to the conditions of their environment, likewise indirectly affect the rate and character of tissue metabolism; a fact which may serve to emphasize the many ways whereby the metabolism of an organ or tissue may be modified through the primary influence of a diet which, controlling in a measure the volume and character of the circulating blood and lymph, must of necessity exert an influence more or less extended.

The one factor above all others that tends to increase the extent of proteid katabolism is the amount of proteid food ingested. Increase in the amount of the albuminous foodstuffs is at once, or speedily, followed by an increase in the output of nitrogenous waste products, the latter constituting a good measure of the extent of proteid metabolism going on in the body. We have been taught to believe that the healthy adult under ordinary conditions of life needs for the maintenance of health, strength, bodily and mental vigor, about 118 grams of proteid food daily. This amount of albuminous food, if metabolized, means at least 16 grams of nitrogen in the urine, in the form of urea, uric acid, creatinin, purin bases, and other nitrogenous products more or less closely related. Under the stress of modern conditions and following the dictates of an acquired taste, the daily intake of proteid food in many individuals at least far exceeds the above figures, with an increase of proteid katabolism equal to 18 or more grams of nitrogen in the 24 hours’ urine.

When we recall that these 18 grams, or more, of nitrogen in the urine reach the final stage of urea, etc., only by passing through a series of stages, each one of which means the using up of a certain amount of energy, to say nothing of the energy made use of in digestion, absorption, etc., we can easily picture to ourselves the amount of physiological labor which the daily handling by the body of such amounts of proteid food entails. Further, it needs very little imagination to see that a large amount of energy is used up in passing on these nitrogenous waste products from organ to organ, or from tissue to tissue, on the way to elimination, and we can fancy that liver and kidneys must at times rebel at the excessive labor they are called upon to perform.

Moreover, the thought suggests itself that possibly these waste products of proteid metabolism, the leucomaines so abundantly formed in the breaking down of proteid material, are not wholly free from objectionable features. If so, an excess of such products might be advantageously dispensed with. Indeed, we have what seems abundant evidence tending to show that many of the nitrogenous waste products elaborated in the body through the breaking down of proteid materials are possessed of more or less physiological action. Even that direct antecedent of urea, ammonium carbamate, which we have reason to believe is formed more or less generally throughout the tissues of the body, is not above suspicion. To be sure, Nature has provided a mechanism in the hepatic cells whereby it is quickly transformed into the harmless urea, but it is only necessary to join the portal vein to the hepatic vein, thereby throwing the liver out of the circuit, in order to see the effect of an excess of proteid food. Under such conditions, this is followed by the appearance of all the symptoms of poisoning with ammonium carbamate, i. e., convulsions ending in death.[45]

Further, we may refer to the observations of Mallet[46] with creatin and creatinin, two conspicuous nitrogenous bases present in muscle, which show unmistakably that these bodies tend to retard slightly the action of the heart. This seems to be their most decided physiological effect, although large doses likewise cause a slight frontal headache, with some general nervous agitation. Attention may also be called to the extremely important experiments of Minkowski,[47] in which he found that adenin—one of the purin bases formed in the breaking down of cell nuclei—has a most marked toxic action, both on man and on dogs. Adenin affects the circulatory apparatus very strikingly, increasing the heart’s action, etc.; it acts on the mucous membrane of the duodenum, causing an acute inflammation, thus leading to continuous vomiting, and in addition it has a local action on the kidneys, giving rise to a deposition in the kidney itself of spheroliths of uric acid, or urates, which leads to an acute nephritis with albuminuria, from which the animal speedily dies.

The alloxuric bases likewise cause fever when injected into the circulation or taken per os,[48] and according to the recent observations of Mandel[49] there is a very noticeable relationship between the amount of alloxuric bases eliminated through the urine and the temperature of the body in cases of aseptic fevers, indicating that these substances, with possibly other incomplete products of tissue metabolism, are important factors in the production of febrile temperatures.

Reference may also be made to our general knowledge regarding the relationship between uric acid and gouty affections, including rheumatism, to say nothing of the possible relationship between uric acid and many other diseases less clearly established. The broader question deserving attention just here, however, is that all of the so-called leucomaines which, as Gautier states, are being formed continuously in the animal tissues side by side with the formation of urea and carbonic acid, and at the expense of the nitrogenous elements or proteid matter, are more or less toxic in their properties, at least under certain conditions of the body. It is perfectly clear that there are a large number of leucomaines, or nitrogenous waste products, which are indissolubly connected with the metabolism of cell protoplasm, and the formation of these substances is augmented by a diet rich in proteid matter.

It is well understood that the excretions of all living organisms, both plant and animal, are more or less poisonous to the organisms which produce and excrete them. The substances so formed originate in the metabolic changes by which complex organic molecules are broken down into simpler compounds. As stated by Vaughan and Novy,[50] “we have good reason for believing that the proteid molecule has certain lines of cleavage along which it breaks when certain forces are applied, and that the resulting fragments have also lines of cleavage along which they break under certain influences, and so on until the end-products, urea, ammonia, water, and carbon-dioxide, are reached; also that some of these intermediate products are highly poisonous has been abundantly demonstrated.” It would therefore seem self-evident that the nitrogenous waste products of the body, i. e., the products of proteid katabolism, may be more or less dangerous to the welfare of the body, and consequently there would seem to be reason in the assumption that greater freedom from disease—especially from the so-called autogenous diseases—might be expected where greater care is exercised in the amount of proteid food consumed.

It is generally understood, or at least is frequently stated by medical writers, that certain febrile conditions are autogenous, and Brunton has made the assertion that the condition termed “biliousness,” and which is most prone to occur in persons who eat largely of proteid foods, is due to the formation of poisonous alkaloidal-like substances which might well be classified under the broad term of leucomaines. To repeat, there are a great many observations and some facts which warrant the view that the nitrogenous waste products of the body—the products of proteid katabolism—are more or less dangerous to the well-being of the organism, and hence there seems justification for the belief that there is greater safety for health and longevity in adopting dietetic habits that are more in accord with the real needs of the body.

The writer’s opinion upon this question has been greatly strengthened by the large numbers of letters he has received—during the course of this inquiry—from persons all over the world, many of whom in their search for health and strength have adopted more frugal methods of living, and who have found relief in an abstemiousness which, compared with ordinary dietetic standards, would seem quite inadequate to support life, yet they have recovered health and strength, and by the judicious practice of physiological economy in their diet have maintained health and vigor, with capability for work that has proved a perpetual surprise to themselves and their friends. The writer’s faith in these spontaneous statements made by persons wholly unknown to him has been augmented by his personal knowledge of people suffering with various troubles, who have found relief by the simple use of reason and judgment in the taking of food, with a view to lowering the rate of proteid metabolism. There is no question in the mind of the writer that excessive proteid decomposition within the body entails possible danger.

If it is true, on the other hand, that the healthy organism needs a daily intake of 118 grams of proteid food more or less, in order to maintain physiological equilibrium, to keep up physical and mental vigor, and to preserve the normal power of resistance to the incursions of disease, then we must consider that the good overbalances the evil, and that evil exists in order that good may be accomplished. We are certainly justified, however, in saying, on the basis of our daily observations made on a large number of individuals and extending over many months, that there is no apparent need for any such amount of proteid food as is ordinarily consumed by the average individual.

We can point to various persons who, for periods ranging from six months to a year, have metabolized daily 5.5 to 7.5 grams of nitrogen instead of 16 to 18 grams, i. e., they have subsisted quite satisfactorily on an amount of proteid food daily, equal to one-third or one-half the amount ordinarily considered as necessary for the maintenance of health and strength, and this without unduly increasing the amount of non-nitrogenous food. Further, our observations have shown that with this great reduction in the consumption of proteid food, with corresponding diminution of proteid katabolism, body-weight can be maintained at a stationary figure, after the body has once adjusted itself to the new conditions. Moreover, there is marked increase in physical strength as demonstrated by repeated dynamometer tests on many individuals, which may perhaps be ascribed to the greater freedom of blood and lymph, as well as of muscle-plasma, from nitrogenous extractives. Lastly, we have failed to find any falling off in physical or mental vigor, any change in the hæmoglobin-content of the blood, or in the number of erythrocytes. In fact, all our observations agree in showing that it is quite possible to reduce with safety the extent of proteid katabolism to one-third or one-half that generally considered as essential to life and strength. In other words, there is perfect safety in a lowered proteid metabolism, and we are inclined to raise the question whether a daily diet containing one-half, or even less, the amount of proteid food ordinarily consumed does not come nearer to the normal and natural requirements of the healthy body than the more elaborate standards we have gradually adopted.

Here, then, we have suggested a radical change in diet which experiment shows is perfectly safe, and we are disposed to urge that there is great systemic value, both in health and in many forms of disease, in such a change. It is obvious, as previously stated, that the smallest amount of food that will serve to maintain bodily and mental vigor, keep up bodily strength, and preserve the normal powers of resistance to disease, is the ideal diet. Any excess over and above what is really needed for these purposes imposes just so much of an unnecessary strain upon the organism. It entails a wasteful expenditure of energy that might better be preserved for future emergencies. It imposes upon the excretory organs the needless labor of removing waste products which could well be dispensed with, to say nothing of the possible physiological action of these products as they circulate through the body.

Dr. Walker Hall,[51] in his interesting article in “The Practitioner” on “Metabolism in Gout,” states that “under normal circumstances a man weighing eleven stone and performing average work requires twenty grams of nitrogen and three hundred grams of carbon per day.” This statement is in perfect harmony with generally accepted views, but I should like to emphasize the fact that all of the twenty-six men we have been experimenting with at New Haven, representing different types, ages, and degrees of activity, have been able to maintain health, strength, and vigor, from six months to a year on a daily quantity of nitrogen equal to one-half, one-third, and even one-quarter the amount of this so-called necessary twenty grams. Further, nitrogenous equilibrium was easily maintained on such quantities of proteid food, and, as before stated, there was great gain in physical strength. Are we not justified, therefore, in raising the broad question whether such a radical change in diet as these facts suggest might not be of systemic value in gout, and especially in cases where there is a predisposition to gout. Speaking as a physiologist, the writer is strongly of the opinion, based in part upon his own observations and in part upon both the voluntary and unconscious testimony of others, that there is possible great gain to the gouty and rheumatic individual by a practice of physiological economy in nutrition.

Physiological economy, as the writer defines it, is not prohibition, but temperance. Moderation in diet, especially in the taking of proteid foods, means a great saving in the wear and tear of the body machinery. It must presumably mean greater freedom from many diseases in which individual organs, such as the liver and kidneys, are frequently involved. It suggests, likewise, greater freedom from many disturbances of general metabolism which eventually terminate in a perversion of nutrition, so marked as to constitute a serious condition of disease. More specifically, lowered proteid metabolism means diminished introduction and diminished formation of nitrogenous products of the purin type, such as xanthin, hypoxanthin, guanin, adenin, etc., as well as of other nitrogenous bodies less clearly defined. Consequently, we have as one of the results of such a systemic change in diet a decreased formation of uric acid, or at least a diminished output of uric acid through the urine.

Obviously, a lowered proteid intake means, in some measure at least, a decreased consumption of meat and similar products more or less rich in free and combined purin bases. This quite plainly must result in a diminished production of uric acid, but the writer is strongly of the opinion that we do not as yet possess sufficiently full knowledge regarding all the ways in which uric acid results in the body. It is true, we differentiate between endogenous and exogenous uric acid, and further, we understand quite clearly that variations in the intake of free and combined purin bases exercise a potent influence upon the output of uric acid through the urine. We still lack, however, concise information as to the various ways in which uric acid may be produced, and its ultimate fate in the body. This is well illustrated by a recent paper from the Marburg laboratory, in which Kutscher and Seemann[52] point out the possibility of a production of uric acid in the animal body synthetically, and likewise suggest that uric acid may be utilized for the formation of nuclein bases, i. e., a reversal of the oxidative process by which uric acid results from the ingestion of free or combined nuclein bases, suggesting indeed the possibility of uric acid and the nuclein bases being produced from each other, according to the circumstances. Thus, when nucleins or free purin bases are taken with the food, the organism may utilize this material at once in the synthesis of nucleins for the use of the body cells. There is no need of a reduction of the formed uric acid to nuclein bases, and consequently there is an increased excretion of uric acid through the urine, but this does not result from a direct transformation of the ingested purin material into uric acid, but is the result of a sparing of the already formed uric acid. The nuclein bases thus act as sparers of uric acid. This view explains, according to Kutscher and Seemann, why feeding with nuclein bases increases the output of uric acid, and feeding with uric acid—a sudden overflow of uric acid into the circulation—is followed, as a rule, by an increased elimination of urea, the uric acid being thus transformed by energetic oxidation. This hypothesis is brought forward not merely because it is an interesting suggestion, but mainly because it illustrates that we do not as yet know fully all the steps in the production of uric acid, nor do we know how far the uric acid we find and determine in the urine is a measure of the formation of uric acid in the body.

Taking our knowledge on these matters as it stands to-day, however, we find by experiment that lowering the intake of proteid food, with its consequent corresponding diminution in proteid katabolism, is followed at once by a marked decrease in the output of uric acid. Let us consider a few of the data obtained in our experiments. The first case I will refer to is that of a college athlete (Callahan). For a period of ten days on his ordinary diet, the average amount of nitrogen in the urine per day was 22.8 grams, equal to the metabolism of 142.5 grams of proteid food. During this same period the average daily output of uric acid was 1.103 grams. For the following four months and a half, on a more restricted diet, with a marked cutting down of the proteid food, but with no exclusion of meat, the average daily output of nitrogen through the urine was 9.04 grams. In other words, for this period of over four months the extent of proteid katabolism was reduced considerably more than 50 per cent. The average daily output of uric acid for this same period was 0.624 gram, equal to a reduction of about 40 per cent from his normal excretion.

Another college athlete (Stapleton), on his normal diet, showed an average excretion of nitrogen through the urine per day, for ten days, of 19.70 grams, while the daily average excretion of uric acid for the same period was 0.893 gram. On a more restricted diet, with diminished proteid katabolism, the daily average excretion of nitrogen through the urine for a period of over four months was 11.06 grams, while the daily average excretion of uric acid for the same period fell to 0.699 gram. In the first of these two cases the average daily ratio of uric acid to total nitrogen during the period of lowered proteid metabolism was 1:14. In the second case the ratio was 1:16.

A third college student (G. W. Anderson), on his ordinary diet, excreted through the urine for a period of nine days 17.17 grams of nitrogen as the daily average, while the average daily output of uric acid for the same period was 0.956 gram. On the more restricted diet of the next four or five months his average daily excretion of nitrogen fell to 9.37 grams per day, while the average daily excretion of uric acid was reduced to 0.632 gram. On his ordinary diet, the ratio of uric acid to nitrogen was 1:18, while later with the diminished proteid metabolism the ratio was 1:14.

Turning to another class, viz., professional men, reference may be made to the writer, whose average daily nitrogen excretion through the urine for a period of nearly nine months was 5.699 grams, corresponding to the metabolism of 35.6 grams of proteid per day. During this same period of nearly nine months the average daily excretion of uric acid amounted to 0.392 gram, the ratio of uric acid to total nitrogen being 1:14. In passing, it may be repeated that the subject of this experiment succeeded in maintaining a constant body-weight, and he further avers that in physical and mental vigor he can find no evidence of deterioration, although the amount of proteid food consumed daily during this long period was less than 40 grams per day. Further, he was in nitrogenous equilibrium during this period, although the nitrogen metabolized daily amounted to only 99 milligrams per kilo of body-weight. Another case in this same group may be mentioned, principally because the subject for over a year became a vegetarian, abstaining from all meat. During the last nine months, this man (Beers) eliminated 8.28 grams of nitrogen through the urine as the daily average, indicating a metabolism of 51 grams of proteid material per day. During this same period, the average daily excretion of uric acid was 0.349 gram, the ratio of uric acid to total nitrogen being 1:23.

The main point to be emphasized in these results is that they show quite conclusively how greatly the daily output of uric acid may be reduced by diminishing the intake of proteid food, and thereby restricting the extent of the proteid metabolism. The ratio of uric acid to the total nitrogen excreted may or may not be altered; this will depend in large measure upon the character of the diet, the relative proportion of free and combined purin bases introduced with the food, etc. As already stated, we do not know with certainty how far the excreted uric acid represents the formation of uric acid in the body, but presumably there is a more or less close relationship, and hence we are doubtless warranted in saying that the formation of uric acid is diminished, in essentially the same proportion as its excretion is reduced, with a lowered proteid intake. Certain it is that several of the persons under observation, who had troubles of a gouty and rheumatic nature in the past, have during the course of the experiment experienced relief, with complete and permanent abeyance of all symptoms. The writer is firmly of the opinion that ordinary gout and rheumatism are entirely preventable by reasonable care and judgment in the matter of diet. Whether, when once firmly established, in aggravated form, they will prove amenable to dietetic treatment is not so certain, but undoubtedly mild cases will respond to the beneficial influences of a rational diet, reinforced by treatment adapted to the removal of urates already deposited. In any event, due regard for the well known deleterious effects of purin-containing foods as a source of exogenous uric acid, and with restriction of proteid metabolism to the true necessities of the body, should serve as an effective means of preventing all those troubles for which uric acid is generally held responsible.

The two following tables give a summary of results bearing upon the excretion of uric acid and its relation to nitrogen and body-weight, for all the subjects belonging to the “professional group” and the “student group.” Emphasis should be laid upon the fact that these figures represent the average daily excretion for the different individuals through the entire period of the experiment.