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ethanol are required for the same protection from freezing. It shows further that there are no special advantages, either in freezing point or boiling point, in the use of mixtures of the two alcohols, while one disadvantage is obvious. Whereas determination of the gravity of a mixed alcohol solution after use for a period of time will give a fairly close estimate of the total alcohol content, since solutions of the same alcohol content have approximately the same specsc gravity, this determination does not constitute a measure of the individual percentages of the two alcohols present. Gravity therefore fails to indicate the freezing point, and hence the extent of protection from freezing as time progresses becomes more and more uncertain.
71 1
Acknowledgment This work was undertaken as part of a cooperative investigation on the properties of alcohol solutions and was made possible by a contribution from the Carbide and Carbon Chemicals Corporation. Literature Cited (1) Cottrell, J . Am. Chem. Soc., 41, 721 (1919). (2) Cummings, J . SOC.Automotive Eng., 19, 93 (1926). (3) International Critical Tables, Vol. 111, p. 309-10. (4) Ibid., Vol. IV. p. 262. (5) Kanolt, Bur. Standards, Sci. Page, 630 (1925). ( 8 ) Olsen, Brunjes, and Olsen, IND. ENG. CHEM., 22, 1315 (1930). (7) Standards, Bur. of, Letter Circ. 28 (1925).
Dietary Facts and Fads’ William C. Rose LABORATORY OF PHYSIOLOGICAL CHEMISTRY, UNIVERSITY OF ILLINOIS, URBANA, ILL.
EARLY ninety years have elapsed since one of the greatest chemists of all time, Justus Liebig, urgently pled for the application of chemical methods to the study of physiological phenomena. Having demonstrated with the clearness and conviction of the logician that the complex functions of the body are the results of underlying chemical changes, and therefore must be investigated by the same means found applicable to similar phenomena in the non-living, Liebig closed his argument with these significant words:
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The time will come, although the present generation will hardly live to see it, when we shall have obtained a numerical expression, in the shape of chemical formulas, for all the normal processes or powers of the organism, when we shall measure the variations in the functions of its individual parts by corresponding variations in the composition of the matter of which these parts consist, or of the products which that matter yields; when the effects produced by morbific causes or by remedies shall be quantitatively determined; when a better method shall bring us a knowledge of all the conditions of the vital phenomena, and shall introduce clearness and certainty into our explanations. Men will then look upon it as incomprehensible that there ever was a time when the share which chemistry is destined to take in these conquests of science was contested, or when doubts could be entertained concerning the mode in which her aid was to be given to physiology.
On the other hand, an unfortunate by-product of this commendable interest in what we eat is a marked increase in the number of faddists, dietary quacks, and self-styled nutrition “experts,” who are exploiting the public through the sale of inaccurate advice, harmful books, and worthless food products. Perhaps some of these faddists are sincere, but certainly the majority are fakers of the worst sort, whose unscrupulous methods are matched only by their monumental ignorance of nutrition. It is not my purpose to undertake a detailed consideration of the teachings of these human parasites. But inasmuch as the latter, for personal gain, are sacrificing many human lives each year, I wish to call attention to a few of the incredible methods which are being employed to beguile the unwary.2 Some Dietary Fads
Not all the predictions included in this remarkable prophecy have yet been realized, but the astounding role which chemistry has played and is playing in the elucidation of the problems of physiology and other medical sciences has abundantly justified Liebig’s expectations. One after another the intricacies of the digestive processes, the relation of blood composition to disease, the nature of the secretions of the so-called ductless glands, and many other extremely complicated phenomena have been clarified or explained by chemical means. But we will confine our attention to one aspect of biochemical investigation-namely, the problem of an adequate diet. Here also progress during the past two decades has been phenomenal. Discoveries have succeeded each other so rapidly that previous conceptions of nutrition have been practically revolutionized. As the result of widespread propaganda relating to some of these modern discoveries, the public has become interested in nutrition as never before. In a word, we have developed a “food consciousness” which is extremely gratifying.
One of the farorite precepts of the quack is the statement that two kinds of foods must not be eaten a t the same meal. Thus we are told that proteins and starches must never be consumed together, that fruits and starchy foods are incompatible, that combinations of two or more kinds of starches or two or more kinds of proteins are extremely bad, and that stewed tomatoes and creamed potatoes, in combination with each other, tend to “tear up the mucous lining of the stomach.” One quack informs us that citrous fruits must not be consumed in “northern countries” except perhaps in very warm weather. When the weather isn’t excessively warm, he says, such foods result in “crystallization of the starch atom.” He then enumerates the ills that result from the alleged “crystallization” of an atom that doesn’t exist. Equally amazing chemistry is taught by another nutrition “expert” when he says that illness usually indicates “too much carbon in the body.” This may be readily remedied, we are told, by the external application of a solution of Epsom salt of suitable purity. Epsom salt, he says, has a “wonderful affiity for carbon, fairly pulling it out of the body.” The same individual advertises rather loosely “a lecture on ‘Foods That Explode in the Intestines,’ t o women only.” The Journal of the American Medical Association remarks: “Just what foods do explode in the intestines, presumably of ‘women only,’ is not mentioned, but the subject may have interesting possibilities.” Still another faddist has much to say regarding the harmful
1 Received April 13, 1931. Presented before the General Meeting a t the Slst Meeting of the American Chemical Society, Indianapolis, Ind., March 30 to April 3, 1931.
2 Much of the information concerning dietary quackery was secured through the courtesy of A. J. Cramp, director of the Bureau of Investigation, American Medical Association, Chicago, Ill.
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effects of white bread. But, to quote again from the Journal of the American iVedica1 Association, he appears to be open to conviction i b this matter, for in connection with an exposition in which he participated a t Scranton, Pa., in 1929, he “accepted $25 from a baker who wished t o have an exhibit devoted exclusively to white bread.” Common table salt is accused of many things. Its use has been credited with responsibility for cancer, high and low blood pressure, tuberculosis, Bright’s disease, gray hair, and bald heads. To meet this “terrible” situation, one “expert” has prepared in his “laboratories” a substitute consisting of ground “vitamin vegetables” carefully combined with sodium chloride. He supplies this mixture for the modest sum of one dollar per package. Evidently, he trusts t o the ignorance of the public regarding the identity of table salt and sodium chloride, and apparently succeeds in his deception. Others tell us that too much cheese, cream, and butter may produce deafness, that the use of pasteurized milk is an important factor in the etiology of heart lesions in children, and that cancer may be cured by prolonged fasts. In every case, of course, the patient must purchase a book or pamphlet giving full information as to the particular diagnosis or treatment in question. These publications are sold a t prices commensurate with the remarkable benefits which they are supposed to bestow. When other measures fail to entrap the prospective victim, an appeal is made to the fear instinct. “Fertilizer is good, but who wants to become a fertilizer,’’ says one. “Remember my address in the hour of approaching death,” another cheerfully remarks. The above illustrations suffice to indicate some of the methods which are being employed to capitalize a t the expense of human welfare. The advertisements of these fakers appear in many of our newspapers and popular magazines. Sometimes the radio stations also participate in the public deception. Until recently one of the faddists quoted above was “on the air” each week from a prominent Chicago station. The thought that the sick and the poor are being subjected to such exploitation a t a time when we are in possession of more real knowledge concerning diet than ever before is not a pleasant one to consider. Really Goethe was correct when he said: “Nothing is more terrible than active ignorance.” Requirements of an Adequate Ration I n contrast to the absurd claims above, which, of course, have not been and cannot be confirmed by experience, the facts regarding diet have been established through the most critical and painstaking researches. Let us see, therefore, what the prerequisites of an adequate ration are. Investigations have shown that every dietary r6gime, in order to be satisfactory, must possess the following characteristics: First, it must supply a sufficient amount of protein of suitable nutritive quality; second, it must provide enough energy for the maintenance of body temperature and for the performance of physical work; third, it must carry the necessary inorganic materials in correct proportions; and fourth, it must furnish liberal quantities of the vitamins. There are other desirable characteristics of a diet, as we shall see, but the four qualities listed above are absolutely indispensable, and must therefore be considered in some detail in a review of present-day knowledge of diet. Protein in t h e Diet The optimal protein consumption is a matter of supreme importance, inasmuch as most tissue constituents are nitrogenous compomds and hence, of necessity, have their origin in proteins. The first attempts to arrive a t suitable protein intakes were based upon statistical studies. Early investigators conceived the idea that an examination of a sufficiently
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large number of human diets should yield an average value which would not be far from the optimal. The assumption appears to have been made that the race, through ages of dietary experimentation, had probably selected involuntarily the correct proportion of protein in the food. Of such “standards,” the one which received widest acceptance was that formulated by the distinguished German physiologist, Carl Voit, who reached the conclusion that an adult should consume about 118 grams of protein per day. It is easy to show that this method of reasoning is fallacious. It assumes that physiological need is the only influence which plays a part in determining the kind of food ingested. As a matter of fact, availability, cost, climate, prejudice, and a variety of other conditions modify both the quality and quantity of foods consumed. Bananas are not important articles of diet for the Eskimo, but the inhabitants of equatorial regions eat liberal amounts of fruits to the exclusion of meat, which is so essential for the dwellers in the Far North. For obvious reasons Voit’s studies were made upon German subjects. Had he investigated the dietaries of the Japanese, he would have arrived a t a much lower average protein intake. These and other considerations suffice to demonstrate that appetite is not a safe criterion to follow in estimating the amount of protein which should be incorporated in the ration. I n contrast to the method of Voit, Russell H. Chittenden of Yale University, founder of American biochemistry, applied the experimental method to a study of the problem. When his investigations were first undertaken in 1902 the Voit standard was quite generally accepted. I n experiments upon himself, his students, and others, Chittenden (3) showed that nitrogen equilibrium can be secured and maintained with a daily intake of 45 to 55 grams of protein. Inasmuch as the primary purpose of protein ingestion is to replace the wear and tear of the tissues as represented by the output of nitrogen in the excreta, the continuous maintenance of nitrogen equilibrium in experiments of long duration clearly demonstrated that physiological well-being may be attained with an intake of protein less than one-half that of the Voit standard, The importance of Chittenden’s investigations, in showing the extent to which the protein content of the diet may be reduced under suitable experimental conditions, cannot be overemphasized, The determination of the minimal nitrogen intake compatible with the maintenance of the status quo of the cells was fundamental for all subsequent studies involving the protein portion of the ration. On the other hand, it does not follow that a very low intake is under all circumstances also the optimal. Not infrequently in scientific matters, as in problems of political or economic expediency, the pendulum of opinion swings from one extreme to another, but eventually comes to rest a t some intermediate point. Thirty years ago much less was known concerning the chemical composition of proteins than is recognized today. Application of modern technic has demonstrated the remarkable differences which exist between proteins of different sources. We now know that they are composed of a t least twenty amino acids, and that the proportions in which these acids occur may vary enormously. Sometimes one or more amino acid may be entirely missing. Thus gliadin, a protein of the wheat kernel, is deficient in lysine; zein of corn is practically devoid of lysine and tryptophane; and gelatin is lacking in tryptophane, tyrosine, cystine, valine, and hydroxyglutamic acid. The recognition of these facts naturally raises the question as to the nutritional importance of the individual amino acids. If one of them can be synthesized by the organism out of materials ordinarily available, obviously its absence from the diet is not a serious consideration. On the contrary,
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if it cannot be produced from the materials a t hand, its presence in the food becomes a matter of the utmost importance. One is justified in asking, therefore: Do the deficiencies of gliadin, zein, and other “incomplete” proteins modify their behavior in the animal body? The answer is emphatically in the affirmative. Osborne and Mendel (11) have shown that when zein is the only dietary protein, young rats receiving such rations not only fail to grow but rapidly lose weight. The addition of tryptophane to the diet leads to maintenance but no growth, while the inclusion of both tryptophane and lysine results in rapid growth. I n like manner, when gliadin of wheat serves as the sole protein of the diet, growth does not occur until lysine is incorporated in the ration. Similar experiments have demonstrated the nutritive importance of cystine (12) and histidine ( I S ) . Thus, these four amino acids-tryptophane, lysine, cystine, and h i s t i d i n e a r e known to be absolutely indispensable dietary components. I n the absence of either nutrition fails, and eventually death from starvation results, no matter how much other food is consumed. In the light of the above facts one would scarcely be justified in limiting the protein intake to that amount which under favorable conditions just suffices for the maintenance of nitrogen equilibrium. It would seem to be a safer procedure, in view of the well-known deficiencies of maqy proteins, particularly those of plant origin, to consume more than the minimal amounts. Thus, a rational daily intake of protein for an adult of average size might be placed a t 70 to 75 grams, or about 1 gram per kilogram of body weight per day. Such an intake allows approximately 50 per cent surplus, as compared with the average Chittenden standard, in order to insure the presence of the essential amino acids. During the period of rapid growth from birth to puberty the protein consumption should be still larger on account of the greater utilization of amino acids for synthetic purposes. I n infancy 2 or perhaps 2.5 grams of protein per kilogram of body weight should be provided daily. This requirement gradually decreases with the diminished rate of increase in body weight until adult life is attained, and then remains constant a t approximately 1 gram per kilogram. Thus throughout the life cycle between 10 and 15 per cent of the total calorific intake should be consumed in the form of proteins. Energy Requirements
-4s to the second prerequisite of an adequate diet-namely, a satisfactory calorie intake-we find that nature has safeguarded the consumption of food for energy purposes in a very interesting fashion. A marked deficiency in the ingestion of certain dietary components, particularly the essential amino acids and vitamins, leads to a failure in appetite. In contrast to this, the consumption of a diet deficient in calories but adequate in other respects creates the sensation of hunger. Under ordinary circumstances this mechanism tends to prevent the ingestion of insufficient food for fuel purposes. Some of us consume too many calories, as indicated by the “excess baggage” which we carry in the form of adipose tissue, but few experience a deficiency in the calorie intake. However, it is a matter of great interest and importance in a discussion of diet to know how much energy is necessary for man. Perhaps we may best approach the problem by considering first the minimal energy requirements. It should be borne in mind that the physiological unit of energy is not the small calorie ordinarily employed in expressing heats of reaction or other thermochemical values, but is the so-called large calorie, which is one thousand times the smaller unit. If we place a fasting individual flat on his back a t perfect rest in an atmosphere the temperature of which is equal to that of his own body, the energy transformations will then
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represent the so-called basal heat production. Obviously, under such circumstances the individual will require no heat for the maintenance of body temperature inasmuch as the temperature of the environment is that of the body. Nor does the subject utilize energy in the performance of voluntary work, since he is flat on his back a t rest. Thus, under the conditions specified, the energy output represents the lowest amount compatible with health. Inasmuch as heat loss is proportional to body surface, basal heat production can be expressed most correctly in terms of body area. However, for our purposes it is sufficiently accurate, and somewhat more intelligible, to refer it to body weight. For individuals of average build the basal heat production amounts to approximately 25 large calories per kilogram of body weight per day. Thus, for a man of, say, 70 kilograms (154 pounds), the basal heat production will be about 1750 calories. Evidently, this basal heat has its origin in the combustion of the subjects own tissues. It might be expected, therefore, that the administration of 1750 calories in the form of food would suffice to provide calorific equilibrium. However, such is not the case. Food ingestion leads to a stimulation in metabolism. Thus, the administration of 1750 calories in the form of proteins, carbohydrates, and fats, in the proportions ordinarily employed in the diet, would lead to an increase in energy exchange of approximately 10 per cent. This is known as the heat of specific dynamic action. Hence to keep our resting subject in calorific equilibrium it would be necessary to administer 1750 175 or 1925 calories. Additional calories will be required if he is to forsake his bed and become a useful member of society. Sitting up involves a greater expenditure of energy than does lying down; and standing is physiologically more expensive than sitting. But, assuming that our subject protects his body from a low temperature of the environment by the use of suitable clothing, the only energy required over and above the two fractions of basal heat and heat of specific dynamic action will be that necessary for the various forms of physical work. For those engaged in rather sedentary occupations, such as is the case with most business and professional men, ‘perhaps 600 to 1000 calories will cover the energy requirements of work, thus necessitating a total intake of 2500 to 3000 calories per day. For laboring men, engaged in greater expenditures of energy, calorie intakes of 3000 to 6000 or more per day may be necessary. It should be noted, however, that the protein intake need not be increased as a result of greater work, inasmuch as it is physiologically more economical to work a t the expense of carbohydrates and fats. If the subject does not wear suitable clothing designed to prevent rapid radiation to a colder environment, body oxidation will be further accelerated and the energy requirements increased. Inasmuch as the protein of the ration ordinarily supplies only about 300 calories per day, the remaining energy must be secured in the form of carbohydrate and fat. The proportion in which these two foodstuffs should be ingested is, within certain limits, largely a matter of personal choice. As fuel for the organism, carbohydrate and fat are interchangeable in accordance with their energy values. When completely oxidized, each gram of carbohydrate yields approximately 4 large calories of energy, while each gram of fat liberates about 9.3 large calories. A gram of fat, therefore, is equivalent to about 2.3 grams of carbohydrate. Most dietaries contain roughly four to five times as much carbohydrate as fat by weight. Thus a ration made up of 70 grams of protein, 400 grams of carbohydrate, and 80 grams of fat would yield in the organism about 2645 calories, and would be satisfactory for the average business or professional man. If one prefers t o alter the proportion of carbohydrate and fat, considerable freedom of choice may be exercised. It
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should be noted, however, that the diet should contain liberal amounts of both foodstuffs. The fats are important for several reasons. Certain of the vitamins occur largely in the fatty foods. Furthermore, recent investigations indicate that some of the fatty acids may be indispensable dietary components. Thus a deficiency disease resulting from a fat-free diet has been observed in rats ( 2 ) . The animals are said to show regularly a scaly condition of the skin, necrosis of the tail, degeneration of the kidneys, and in some cases sterility. The disease is thought to be due to the absence from the food of linoleic and possibly other unsaturated acids. Carbohydrates likewise are essential constituents of the food. Numerous biochemical researches, particularly those of Shaffer, have shown clearly that the oxidation of fatty acids in the body is dependent upon the simultaneous oxidation of sugar. Some sort of coupled reaction (14) appears to exist in the oxidation of the two foodstuffs. In the absence of sugar oxidation, acetone, acetoacetic acid, and @-hydroxybutyric acid accumulate in the blood and tissues as products of incomplete fatty acid oxidation. It is evident, therefore, that both carbohydrate and fat must be included in the ration. There is little likelihood, however, that a diet too low in either foodstuff would be chosen voluntarily. Indeed, extraordinary measures are necessary in order to exclude all fat. Inorganic Materials
The significance of the inorganic salts as food constituents is probably only partially appreciated a t the present time. Certainly, many of the functions which they perform in the body still await discovery. They are found in greatest abundance in the skeletal structures. Here they account for more than 22 per cent of the moist tissue, and impart to the bones the rigidity so necessary to enable them to serve as the framework of the body. This function is recognized by every one. On the other hand, the essential nature of the inorganic elements as components of the soft structures is not so evident. Yet salts are found in every living cell in amounts averaging about 1 per cent of the moist material. Furthermore, as Mathews says, they are to be regarded, not as “simply clinkers clogging the grates of the protoplasmic fires,” but as absolutely indispensable constituents. Indeed, inorganic compounds are largely involved in the regulation of tissue neutrality and in the maintenance of the osmotic pressure of the cell contents. They play an essential role in the coagulation of the blood, they aid in the processes of digestion, and in a variety of other ways perform extremely useful functions. Moreover, the most profound physiological effects may follow alterations in the proportions of inorganic materials present in living things. By suitable alterations in the ratios of different elements in the cells, it is possible to increase tissue irritability to the point of convulsions, or to diminish it to a state of anesthesia. Even such an amazingly complex phenomenon as the artificial fertilization of ova has been accomplished in marine organisms by the use of inorganic salts. One might expect that a very large number of elements would be involved in the complicated reactions of living things, or even that very rare ones might be necessary. On the contrary, comparatively few are known to occur as regular components of animal cells; and these, strange to say, are among the commonest ones known. Thus, the ashes of animal tissues contain calcium, magnesium, sodium, potassium, sulfur, phosphorus, chlorine, iron, and iodine. Traces of several additional elements-namely, copper, manganese, zinc, aluminum, silicon, fluorine, and possibly others-are usually present, but whether they are all necessary for normal nutrition cannot be stated a t the present time. Copper has acquired a new prominence in recent years because
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of the remarkable property which it displays of stimulating blood regeneration in nutritional anemia (5). Upon certain diets animals become anemic. The inclusion of suitable quantities of iron in such rations fails to improve the condition appreciably. But the addition of minute traces of copper along with iron leads to a rapid return to normal. There are indications also that manganese and zinc may be essential dietary components. Inasmuch as the inorganic elements are being constantly lost in the excreta, our supply of each must be replenished by a suitable intake in the diet. I n the case of most of them no adequate information is available as to the quantities which are needed. We know with reasonable accuracy what amounts of the more common elements are retained when excess quantities are ingested; but one would scarcely be justified, on the basis of these data, in attempting to define the optimal intakes. Investigations indicate that not only the actual amounts, but also the proportions in which the several elements are retained, vary markedly with the age of the individual. Thus, in the very young child the retention of calcium exceeds that of phosphorus, while in the older child the reverse is true. Furthermore, in the case of certain elements, the larger the intake the greater is the retention, a t least for a time, even when all amounts administered are in excess of the growth requirements of the subject. The problem is an exceedingly complex one. Apparently, retention depends not alone upon the actual amounts of minerals present in the food and the previous nutritive condition of the individual, but also upon several other factors, such as the proportions of vitamins, carbohydrates, fats, and perhaps proteins consumed. But lest the rather pessimistic picture painted above may lead to the conclusion that the nutritionist is absolutely in the dark as to the mineral metabolism of man, I hasten to state that, despite our inability to dogmatize regarding the optimal quantity of each which should be consumed, available information indicates that in the adult, under ordinary conditions of diet, most of the inorganic elements are likely to be present in sufficient quantities. Thus the salt employed in food seasoning provides considerably more sodium and chlorine than are necessary. Magnesium and potassium are found rather widely distributed in meats and in many vegetables. Sufficient sulfur is liberated in the oxidation of the sulfur-containing amino acids, cystine and methionine. Calcium and phosphorus are present in milk and milk products, eggs, whole-grain products, leguminous and green vegetables, and fruits. Iron is similarly distributed, except that the amount present in milk is small. It occurs in relative abundance in lean red meats, and in glandular tissues such as liver and kidneys. Of all the necessary inorganic elements, apparently calcium and iodine are the two most likely to be present in the food in inadequate amounts. The more liberal use of milk and vegetables in the diet will prevent a calcium shortage. This is a particularly important consideration in the nutrition of children, in whom the demand for calcium for growth purposes is greater than in the adult. Importance of Iodine
The iodine intake presents unique difficulties which have been solved only partially. This element occurs in the organism primarily in the thyroid gland, where it serves as an essential constituent of thyroxine, the remarkable internal secretion of this gland. Probably the total iodine content of an adult man does not exceed 25 mg., of which perhaps 15 mg. occur in the thyroid. It seems almost incredible that these traces of iodine can play so important a role in human economy, and yet an abundance of proof exists for
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the fact that the element is indispensable for life. This provides one of many illustrations of what Mendel calls the importance of “little things” in nutrition. The relation of an inadequate iodine intake to the incidence of simple goiter has been abundantly demonstrated, and is now rather generally recognized by the public. Most of the iodine on the earth’s surface has been leached out of the soil, and has found its way to the sea. Thus the iodine content of foods and of drinking waters diminishes, as a rule, with increased distance from the coast. Furthermore, regions of endemic goiter have been found to coincide in general with regions of low iodine in the soil. Extensive experiments have demonstrated the beneficial effects of iodine in the prophylaxis and therapy of simple goiter. The classic investigations of Marine and his associates upon the school children of Akron, Ohio, deserve special consideration. These investigators have shown that the ingestion of iodine a t stated intervals greatly reduces the incidence of thyroid hypertrophy, and in subjects with enlarged glands may exert a curative effect. Marine states (7): “Of 2190 pupils (girls) taking 2 grams of sodium iodide twice yearly only 5 developed thyroid enlargement, while of 2305 girls not taking the prophylactic, 495 developed thyroid enlargement.” He points out also that numerous papers have appeared in the European literature confirming his findings and extending the use of iodine in the prevention of goiter. Probably not over 200 mg. of iodine per individual per year are required, although Marine advised an intake in goitrous regions of 5 to 10 mg. per week. The element is effective whether administered as a naturally occurring component of foods or in some artificial way as in iodized salt. Certain cities-notably Rochester, h’. Y.-have found it convenient and satisfactory to iodize the drinking water two or more times per year. It is not necessary to consume the iodine a t daily or weekly intervals. I n contrast to most food components, which must be ingested with great frequency and regularity, the annual iodine supply of the body may be furnished during periods of a week repeated two or three times yearly. We may confidently expect that when further experience indicates the best method to be employed in iodine administration, endemic goiter will disappear from among civilized peoples. I n the meantime, perhaps a word of caution should be spoken against the possibility of overindulgence in iodized foods and drinks. The fact that traces of iodine are essential must not be interpreted as indicating that larger amounts are equally as good. Very little information is available as to the physiological effects of overdoses. While it appears unlikely that the quantities employed in the iodization of salt and of drinking waters can lead to excessive intakes, one mould scarcely be justified, a t this stage of our knowledge, in extending the practice to other food materials. For the present, a t least, an attitude of conservatism should actuate us in this matter. Vitamins
Of the essential dietary components doubtless the vitamins are best known to the general public. Despite the fact that the existence of these accessory substances has been recognized for only two decades, the effects which follow their exclusion from the food are so spectacular that studies involving them seem to have caught the popular imagination as have few scientific investigations. As early as 1739 the Austrian army surgeon, Johann Georg Kramer, pointed out that neither medical nor surgical measures suffice for the cure of scurvy, a disease now recognized as due to a vitamin deficiency. “But,” he says in his Medicina Castrensis, “if you can get green vegetables; if you can prepare a sufficient quantity of fresh antiscorbutic juices, if you have oranges,
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lemons, citrons, or their pulp and juice preserved with whey in cask, so that you can make a lemonade, or rather give to the quantity of 3 or 4 ounces of their juice in whey, you will, without other assistance, cure this dreadful evil (Ib).” Space does not permit a review of the interesting events of nutritive importance which transpired during the 170 years which elapsed after Kramer before vitamins were recognized as definite food components. It remained for F. G. Hopkins (6) in England, and Osborne and Mendel (IO), and McCollum and Davis (8) in America to demonstrate, beyond the possibility of doubt, that animals require more than proteins, carbohydrates, fats, inorganic salts, and water for normal nutrition. In 1912 one of these supplementing materials was named “vitamine” by Funk (4). Obviously, the word was intended to denote an indispensable amine. Inasmuch as we now know that some of the vitamins are not amines, and since the amine nature of none has been definitely established, i t is generally customary to drop the final “e” in Funk’s term and to speak of these food constituents as “vitamins.” At the present time six vitamins are recognized. They are designated by the letters A, B, C, D, E, and G. Three of these-A, D, and E-are usually associated with fatty foods, and for this reason are frequently referred to as the fatwatersoluble vitamins. The others-B, C, and G-are soluble. Of the latter, B and G are usually found together. Indeed, it is only recently that they have been recognized as separate entities. VITAMINB-This vitamin is the so-called antineuritic factor. Its absence from the food leads in man to the disease beriberi, and in animals to a similar involvement of the peripheral nerves known as polyneuritis. Other effects which follow its exclusion from the diet are failure in growth, loss of appetite, degeneration of the lymphoid tissue, and enlargement of the heart and adrenal glands. Beriberi is extremely common among peoples of the Far East whose dietaries include large proportions of polished rice. This vitamin is perhaps more widely distributed than any of the others, and occurs in relative abundance in tomatoes, spinach, legumes, eggs, yeast, and glandular tissues such as liver and kidney. Smaller quantities are found in a variety of other foods. Indeed, for adults having reasonable freedom of choice in the selection of foods there exists little probability of a vitamin B deficiency. Only when the diet is limited largely to highly milled products such as polished rice, degerminated corn meal, or similar materials is there likelihood of a shortage of B. On the other hand, the infant is much more liable to experience a deficiency unless care is taken to avoid it. The content of both human and bovine milk in vitamin B is very variable, and the quantity excreted depends upon the amount consumed. Furthermore, investigations indicate that the mammary glands are rather inefficient in the excretion of vitamin B. Hence, foods rich in this vitamin should be included liberally in the diet of the nursing mother. If the child is artificially fed, the modified milk employed should be supplemented with the accessory factor. VITAMIN&Vitamin G is believed to be the antipellagric substance. Inasmuch as this is the newest addition t o the vitamin family, its distribution and functions have not been determined so thoroughly as in the case of the other vitamins. The most characteristic symptoms of pellagra are skin lesions, gastro-intestinal disturbances, and involvement of the central nervous system. Conditions remarkably similar have been produced in animals by the exclusion of the accessory factor from the diet. The vitamin is also necessary for growth. It is rather widely distributed in fresh regetables, glandular tissues, meat, eggs, yeast, and milk. In milk it appears to be more abundant than the antineuritic
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factor. Vitamin G is quite stable to heat. Yeast autoclaved for an hour a t 120’ C. shows no diminution in activity, although the antineuritic factor is completely destroyed by such treatment. Quantitative data as to the human requirements for vitamin G are not available. The indications are that there is little danger of a deficiency unless the diet is limited to highly milled or purified foods. It is noteworthy, however, that many individuals ordinarily consume rations largely devoid of fresh vegetables, meats, eggs, and other articles of prophylactic value. This condition of affairs is indicated by the prevalence of pellagra, particularly in the South. The United States Public Health Reports show that for the year 1929, in thirteen states and the District of Columbia, more than 25,000 cases of pellagra were reported. I n fortyone states during the same year more than 7000 deaths occurred from this preventable disease. VITAMIN&The antiscorbutic substance, vitamin C, is present in oranges, lemons, tomatoes, spinach, cabbage, and lettuce. Other fresh vegetables contain smaller quantities. The vitamin is readily destroyed by oxidation, and usually by methods of food preservation, such as canning and desiccation. However, it is much more stable in the presence of acid than in neutral or alkaline solutions. Thus canned tomatoes, by reason of the protective effect of the acid reaction, are relatively rich in C. Potatoes, even when boiled, are moderately good sources of the vitamin. Epidemics of scurvy have been observed to follow failures in the potato crop. Milk varies greatly in its vitamin C content. If of average potency, about one pint of raw bovine milk per day is sufficient to protect an infant against scurvy. The modern practice of administering small amounts of orange juice to infants has greatly decreased the incidence of the disease. Epidemics of infantile scurvy were reported from several European cities during the World War. In adults the disease has always been associated with the ingestion of diets lacking in fresh foods. Such rations were formerly employed on polar expeditions or during protracted sea voyages. Concentrated preparations of citrous fruit juices are now available, and in recent years have been used by explorers as prophylactic agents. VITAMINA-Of the fat-soluble vitamins, A was the first to be recognized. Absence of this substance from the food leads to a peculiar eye disease known as xerophthalmia. This disease is characterized by swelling of the lids and inflammation of the conjunctiva, with a bloody or purulent discharge. Later the corneas become involved and permanent blindness may result. It is evident that the abnormality is associated with an infection, and that the dietary deficiency lowers the resistance of the animal to the invasion of microorganisms. It is worthy of note, however, that no sanitary measures suffice to prevent the infection when the diet is inadequate in A, nor are therapeutic procedures other than the administration of the vitamin necessary to effect a cure. Vitamin A deficiency is responsible also for increased susceptibility to many respiratory infections involving the nasal and bronchial passages, and the sinuses. Osborne and Mendel have shown that a large percentage of animals which have been deprived of this vitamin develop phosphate calculi in the renal system. Moreover, its absence from the ration leads to diarrhoea, diminished appetite, and failure in growth. Vitamin A is present in greatest abundance in cod-liver oil. Of the ordinary foods, those showing the largest activity are butter, eggs, animal glandular tissues, green leaves of plants, and yellow root crops such as carrots and sweet potatoes. In yellow foods the vitamin appears to be closely related t o the carotinoid pigment. Indeed, Moore (9) is of the opinion that carotene may be the precursor of vitamin A.
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Many cases of dietary deficiency involving this accessory factor have been reported among children, particularly in certain European nations during or soon after the World War. In Denmark the prevalence of xerophthalmia a t one time reached very serious proportions, and was brought under control only by rigid governmental regulation and rationing of the butter supply. Similar epidemics in Austria and Roumania were checked by the use of foods rich in vitamin A. The possibility of the occurrence of isolated cases of vitamin A deficiency among the poorer classes of our own land cannot be denied, but the data available appear to indicate that such cases are infrequent. VITAMIN D-Greater progress has been made in the study of vitamin D than of any other accessory factor. This substance is necessary for the proper calcification of the bones. I n its absence inadequate deposition of calcium and phosphorus occurs, and rickets results. It is estimated that when no prophylactic measures are taken approximately one-third of all breast-fed babies and two-thirds of all artificially fed babies develop signs of rickets. A very high percentage of adults, who passed their infancy before vitamin D was recognized, carry in their bodies immutable evidence of imperfect calcification. Comparatively few materials are effective sources of the antirachitic factor. Of the naturally occurring products, cod-liver oil is the best. Egg yolk and the flesh of certain fishes are likewise potent. Milk and butter are usually poor in the factor. Indeed, with the exception of the three sources enumerated above, the most important protective agency against rickets is sunlight. It is a peculiar fact that the radiant energy of the sun is capable of exerting the same effect as a chemical agent (vitamin D) present in cod-liver oil. During the past three years this remarkable situation has been clarified. Researches have shown that vitamin D is closely related chemically to ergosterol, an unsaturated sterol found widely distributed in plant and animal structures. When ergosterol is subjected to the action of ultra-violet light, under appropriate conditions, it acquires the physiological activity of vitamin D. Only rays of wave lengths less than about 310 millimicrons manifest the property of activating the sterol. Such rays are few in the light which reaches us from the sun, but occur in great abundance in the radiations from a suitable quartz mercury lamp. Thus it is possible to produce vitamin D artificially by the irradiation of ergosterol or ergosterol-containing foods. Indeed, by the same means activity is imparted to the ergosterol in the skin of the animal or human subject. Truly we appear to be the sons of Apollo in a very real sense. The discovery of the above facts has served to explain why the incidence of rickets in children is greater during the dark winter months than during the sunny summer season; and why negroes, whose skins are less permeable to the rays, are more subject to the disease than are whites. Furthermore, investigations with activated ergosterol, have enabled us to measure with reasonable approximation the astounding physiological potency of this dietary essential. Bills and his associates ( I ) have prepared samples of ergosterol having 400,000 times the activity of ordinary cod-liver oil. Even then the ergosterol had been transformed only partially into vitamin D. As a result of such studies it may be stated with reasonable certainty that the dose of pure vitamin D which is required by a rat does not exceed one-millionth of a milligram daily, or one part of vitamin per ten billion parts of food. When we recall that this infinitesimal quantity represents the difference between complete success and utter failure in growth and normal bone formation, we stand amazed before the marvelous power of “little things” in nutrition.
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INDUSTRIAL A N D ENGINEERING CHEMISTRY
VITAMIXE-The last of the known accessory substances is vitamin E, the antisterility factor. Animals deprived of this lose the power of reproduction. The effects of such a deficiency differ in the two sexes, according t o Evans, who first recognized vitamin E as a specific entity. I n the female ovulation remains unimpaired and the ova may undergo fertilization, but the embryos die and are re-absorbed before they reach maturity. On the other hand, in the male absence of the factor from the food leads to degeneration of the germ cells. Vitamin E occurs in green leafy vegetables, in cereal grains, and in certain oils, notably those of wheat germ, hemp seed, and yellow corn. It appears to be entirely absent from codliver oil. At the present time no data are available demonstrating that it plays a role in human reproduction. It seems not unreasonable, however, to assume that it does. I n any event, the wide distribution of the vitamin appears to justify the belief that a deficiency of it in man is very improbable. Other Desirable Features of Diet Such are the known facts regarding these four classes of indispensable dietary components-the proteins, the energy-yielding foodstuffs, the inorganic elements, and the vitamins. Keedless to say, man requires, in addition to the above, liberal quantities of water. Furthermore, there are other desirable though not indispensable features of the diet, such as the presence of a certain amount of roughage, and the choice of foods with a view to variety. I n the majority of individuals the use of some roughage in the form of cellulose is beneficial, inasmuch as its presence in the alimentary tract promotes peristalsis, and the passage of useless food residues to the exterior. It may be secured in a large number of vegetables and fruits. The question of variety has frequently been overemphasized. Investigations in man and animals have shown that, when all essential components are present, a constant ration may be consumed over long periods of time without difficulty or inconvenience. But variety is important from another point of view-namely, that it tends to minimize the dangers of a deficiency, inasmuch as the several articles of food mutually supplement each other. Most Common Deficiencies in Diet I n summary, available information indicates that of the known essential dietary components the three most likely to be ingested in inadequate amounts are calcium, iodine, and vitamin D. The use each day of a moderate amount of milk is perhaps the simplest way of guarding against a deficiency of calcium as well as of improving the quality of the other inorganic components of the diet. ,4s to the best method of securing iodine, one must await the results of further investigations. In the meantime, the use of iodized salt or of iodized drinking water, or the therapeutic administration of small quantities of sodium iodide a t intervals of four t o six months, may be employed with effective results. Vitamin D may be acquired by outdoor exposure to the rays of the sun, or by the ingestion of moderate doses of cod-liver oil or irradiated ergosterol. Unsolved Problems Many important problems regarding diet still await solution. These must be subjected to searching investigations before the nutritionist will be in position to accurately define a “normal” ration. What are the optimal quantities of each essential in the ideal diet? What physiological effects result from overdosage with the several dietary components? What functions, if any, are performed by the physiologically rare elements? Are there still unknown vitamins to be discovered?
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These and many other questions suggest themselves. The nutritive importance of the amino acids is in itself a vast field which must be thoroughly explored. Of the twenty known components of proteins the indispensable nature of only four has been positively established. The importance of eight others is a t the present time uncertain, while the remaining eight are absolutely unknown quantities in growth physiology. This paucity of positive information is due to lack of available methods for the quantitative removal of single amino acids from the extraordinarily complex mixtures obtained by the hydrolysis of proteins. The ideal method of attack would be to feed diets in which the protein portion is replaced by mixtures of highly purified amino acids. The great difficulty and enormous expense involved in such a procedure hitherto have prevented comprehensive investigations of this sort. During the past year, however, such studies have been under way a t the University of Illinois, and extremely promising data are being secured. Already evidence has been obtained pointing to the presence in proteins of a component which has not been recognized before. This material, the nature of which is not yet known, is certainly an indispensable constituent of the diet. If we succeed in its isolation, as we anticipate, we shall then be in position to determine with comparative ease which of the remaining amino acids are required for normal nutrition. Need for Education of-Public Despite the lack of continuity in our knowledge of what constitutes an adequate diet, one who considers the situation cannot escape the conviction that a great deal more is known to the student of diet than is being practiced by the general public. Perhaps we as investigators are partly responsible for this lack of application in that we do not emphasize as we should the importance of popularizing the results of scientific discoveries. But however that may be, only by the slow method of public education in matters of diet can we hope either to decrease the incidence of deficiency diseases or to dispose of the food faker. When men and women are put in possession of the essential facts of nutrition, not only will they eat more correctly, but they will be less readily led astray by the false doctrines of the faddist. While future progress in science depends, of course, upon the results of high-grade research, it should not be overlooked that public welfare demands adequate provision for the prompt and wide-spread dissemination of such scientific material as is immediately useful. Emerson emphasized both aspects of the problem when he said: “I am impressed with the fact that the greatest thing a human soul ever does in this world is to see something, and tell what it saw in a plain way.” Literature Cited (1) Bills, C. E.,and Wirick, A. M., J . B i d . Chem., 86, 117 (1930). Ibid., 86, 587 (1930). (2) Burr, G. O.,and M. -V., (3) Chittenden, R. H., “Physiological Economy in Nutrition,” Stokes, 1904. (4) Funk, C., J . State M e d . , 20, 341 (1912). (5) Hart, E. B., Steenbock, H., Waddell, J., and Elvehjem, C. A , . J . Bid. Chem., 77, 797 (1928). (6) Hopkins, F. G., Analyst, 31, 385 (1906). (7) Marine, D., Medicine, 3, 453 (1924). (8) McCollum, E.V., and Davis, M., J . B i d . Chem., 15, 167 (1913). (9) Moore, T., Biochem. J . , 24, 692 (1930). (10) Osborne, T. B.,and Mendel, L. B., Carnegie Inst. Wash. Pub. 168 (1911). (11) Osborne, T.B.,and Mendel, L. B., J . B i d . Chem., 17, 325 (1914). (12) Osborne, T.B., and Mendel, L. B., I b i d . , 20, 351 (1915). (13) Rose, W. C.. and Cox, G. J., Ibid., 61, 747 (1924). (14) Shaffer, P.A , , Ibid., 47, 433, 449 (1921). (15) Sherman, H . C., and Smith, S.L., “The Vitamins,” Chemical Catalog, 1922; gives this translation from Kramer.
