NUTRITIONAL RESTORATION AND FORTIFICBTION OF FOODS Papera on pages 707-722 presented before the Divisions of Agricultural and Food Chemistry and of Biological Chemistry at the l O l s t Meeting of the American Chemioal Society, St. Louis, Mo.
Nutritional Requirements of Man C. A. ELVEHJEM University of Wisconsin, Madison, Wis.
The nutritional requirements of man can be expressed in chemical terms to a greater extent than ever before. Individuals suffering from certain deficiencies may be treated successfully through the administration of a single chemical compound. The yearly supply of most of our essential vitamins can be purchased a t a wholesale price approaching the cost of our energy foods. In spite of all this information we should not feel too confident that adequate nutrition involves merely the supply of a few chemical compounds.
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Figures on the daily requirement of the better known nutrients are given. They are limited in value for many reasons. There are additional essential nutrients to be isolated and studied quantitatively. The requirement differs for different age groups and for different individuals in the same age groups. The quantity of one dietary constituent may affect the requirement of another factor. Much of our information has come from animal work and we must, therefore, recognize species differences.
T PRESENT the nutritional requirements of man can be expressed in chemical terms t o a greater extent than
if we add up the cost of the individual components, we get values considerably higher than some of the figures which have recently been suggested. It is impossible even to estimate the cost of the unknown factors. The safest program a t this time is to rely upon the common foods which we have been accustomed to eating rather than to attempt the production of cheap synthetic substitutes. However, we should make every effort to improve the quality of the foods which are now making up the American dietary. I n other words, we must realize that plant and animal materials as produced on the surface of this earth do not necessarily contain the individual nutrients in optimum concentration for the human being. We must use some ingenuity in compounding natural food materials into a complete diet. Improvement in the quality of certain food supplies will not only conserve total quantity of food but will tend toward more optimum nutrition of all individuals. Our problem today centers around the restoration and fortification of foods. The interest in this problem is undoubt-
ever before. However, we as chemists must recognize that there is more to adequate nutrition than the mere combining af the known compounds into a diet and the calculation of the cost of these dietary constituents. Due to the fact that some of the vitamins which used to be the costly part of our diet may now be purchased a t amazingly low prices, certain erroneous suggestions have been made concerning the cost of an average diet. It is true that the individual yearly requirement of thiamin may now be purchased for about 50 cents and the nicotinic acid supply for about 12 cents, wholesale. But we must not forget that the yearly supply of calories is still a significant item. Most of US ignore calories until times of stress. Even in the last war one of the greatest problems in many countries was an adequate supply of total food. It would be difficult to supply the average yearly requirement in energy for much less than $15, and the cost of adequate protein would certainly exceed this value. Thus 707
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edly stimulated by our national defense program, but we should also recognize that we have reached a stage in our knowledge of nutrition which makes i t possible to consider this problem. At first nutrition workers recognized that certain foods were excellent sources of specific nutrients. These foods became known as protective foods, and we relied on them to a considerable extent for our supply of essential factors. When we recognized that inorganic salts were utilized as readily by the body as the mineral elements found in our natural foods and that synthetic vitamins could be produced at a fairly low cost, considerable interest was shown in the use of concentrates or capsules to supply some of the more important nutrients. The value of these preparations in the clinical treatment of deficiency diseases cannot be denied, but we must recognize that the administration of such concentrated forms of nutrients should only be temporary. If large groups of people are living on combinations of natural foods which do not supply the total requirement, the food supply should be modified or fortified. As the chemists showed greater interest in these problems, methods of assay improved so that we can analyze our staple foods for their vitamin content. These foods are not devoid of vitamins, as many would have us believe, but show a low content on the percentage basis. If we multiply the amount present by the total weight of the food consumed daily we find that the result may be an appreciable part of the entire requirement. In the future we will certainly look back upon this work as one of the most important periods in nutritional research. It is obvious that values for the distribution of nutrients in foods are not of much value until we know the requirement for each of these nutrients. If all these values were available, i t would not be difficult for the dietitian to give us adequate nutrition through the use of pleasing foods. The establishment of nutritional requirements has also had an interesting history. In a few cases the actual requirement has been studied on humans. Thus we have a considerable amount of data for the energy requirement of humans of different ages. The data on the protein requirement are somewhat limited, although there is today fairly general agreement among many workers for this constituent of our diet. There have also been a few studies on the requirements for calcium, phosphorus, and iron. In the case of many of the vitamins, the data have been obtained through animal experiments and generally from work which was not initiated to answer this particular question. Many of us have been guilty of concluding from our animal experiments that a vitamin is needed a t a certain level, and then for good measure we suggest that the daily human requirement is 50 per cent greater than the value found. This method may be satisfactory to establish a certain degree of safety. However, if we were to do this in all our calculations, we would soon pile up a considerable excess. The following figures may be used as a guide for the daily requirement of the better known nutrients:
These values will vary, depending upon the age of the individual and whether certain increased requirements are superimposed upon the ordinary requirements. These problems are largely physiological. The above figures are those recognized for the average male adult. How these values have been obtained, the limitations of the figures, and how the chemist can aid in establishing more satisfactory values will be discussed briefly.
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Protein and Fat Perhaps i t is unnecessary to say much about the energy or the protein requirements. I n spite of the extensive values for the caloric requirements of humans under different conditions, little attention has been given to the effect of the external environment on the caloric intake. Mills and Colvin (3) recently showed that excessive external temperatures may reduce the intake of calories to the point that sufficient food is not consumed to supply the normal vitamin requirement. We still speak of the protein requirement in total grams of protein in the diet; but actually it is not the protein requirement that we are interested in, but the amino acid. Some day we may be able to state the actual amino acid requirements and secure values for the amino acid content of all our food supplies. At present this may seem difficult, but the analysis of food materials for vitamins A, B1, and C aIso appeared difficult a few years ago. The value of 70 grams of protein per day for an adult man is probably a safe figure, provided we specify that the protein should be derived from a variety of sources and a good part of i t from animal tissues. No definite figures have been established for the fat content of human dietaries. It is generally concluded that f a t must be a constituent of the normal diet and that it is well to use liberal amounts to supply the fat-soluble vitamins. The latter suggestion is not absolutely essential since we can now get concentrates of these vitamins; however, the importance of fat as a source of linoleic acid must be considered. There is no question about the production of linoleic acid deficiency in rats on fat-low diets, but few studies have been made with other species. There is some difference of opinion concerning the importance of linoleic acid in the human dietary. A high intake of linoleic-acid-containing fats has been used in the treatment of eczema; and Brown, Hansen, Burr, and McQuarrie (1) found a decrease in the amount of linoleic anti arachidonic acids in the serum of an adult man subsisting for 6 months on a diet extremely low in fat. The individual exhibited no other evidence of disease. It has been found in this laboratory that rats maintained on mineralized skim milk fortified with minerals and the fat-soluble vitamins grow better when the skim milk is supplemented with butter fat than when vegetable oils are used. The active substance is present in the fatty acid fraction of the butter fat. It is also well known that fat has a sparing effect on vitamin B1. The general decrease in the fat content of American dietaries has thus tended to aggravate the vitamin I31 deficiency brought about by the use of refined foods.
Mineral Elements
CALCIUM. Logically this heads the list of mineral elements of significance in nutrition since there is more calcium in the human body than any other mineral element. The value generally accepted as an adequate level is 0.7 to 0.8 gram per day. We must first recognize that this calcium requirement holds only when the diet contains an adequate supply of vitamin D. The ratio of calcium to phosphorus is also a factor which needs definite consideration. We still find in certain textbooks that the optimum calcium-phosphorus ratio is 2 to 1. This is obviously incorrect since in all of our work we have found the ratio to approach 1.2 to 1. Experiments with dogs indicate that when the calcium-phosphorus ratio is 2 to 1, i t is impossible to get normal calcification even with tremendous doses of vitamin D. Sherman and co-workers (7) recently reported some improvement in the nutritional wellbeing of rats by increasing the calcium intake from 0.2 to 0.35 or even to 0.8 per cent of the diet. The phosphorus requirement is generally assumed to be a little higher than the
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calcium figures. This may appear contradictory in the light of a calcium-phosphorus ratio of 1.2 to 1; however, the higher value may be advantageous because some of the organic phosphorus may not be completely available. The phosphorus in phytic acid is now known (2) to be available, but it is less efficient for bone production than other sources of phosphorus. IRON.The daily iron requirement is well established although the exact figure has varied between 12 and 15 mg. per day. First we must recognize that the iron is of no value in the body unless it is accompanied by copper which functions in the conversion of iron into hemoglobin. In addition, the iron must be in an available form. Extensive studies have been made on the available iron content of foods, and the values obtained by chemical methods check fairly well with those obtained through the feeding experiments with rats. However, we still do not know whether the availability as measured in rats is similar to that which we may find in the human being. Much has been said about the relative value of ferric and ferrous iron. This problem was recently studied by Tompsett (6). Ferrous iron appears to be the only form to be absorbed from the alimentary tract. The ferric iron consumed is reduced in the stomach by substances which are common constituents of the diet. The diet may also contain substances which tend to oxidize the ferrous to the ferric state. The phosphatides of egg yolk appear to be one group of substances which inhibit the absorption of iron through the autoxidation of the ferrous iron. Tompsett states that it is difficult to give a definite value for iron because the degree of iron absorption is dependent on so many factors. The value of 12-15 mg. per day is probably liberal enough to compensate for the iron present in the food in forms which cannot be utilized. The daily copper requirement is probably about 2 mg. per day, and practically all forms of copper show equal availability. TRACE ELEMENTS. No requirements have been set up for the so-called trace elements and perhaps rightly so, since no specific values are available. But we must recognize that elements such as manganese, zinc, and cobalt are important in the diet, and perhaps values for these additional minerals may soon be available.
Iodine Most of the work on iodine requirements has been done directly on humans. One reason is undoubtedly that it is difficult to produce an iodine deficiency in experimental animals, although many farm animals in the goiter region suffer from iodine deficiency. Balance studies (4) show that 50 to 100 micrograms of iodine per day may be sufficient. The value generally given is 2 micrograms per kg. of body weight. There is ample evidence that these small requirements may not be met by foods and drinking water. To overcome this difficulty, the fortification of salt was started over fifteen years ago. This was the first fortification program in this country. Sufficient sodium or potassium iodide is added to maintain the iodine content of salt at 0.015 per cent.
Vitamins VITAMINA. Even more conflicting data appear in the vitamin field. The main difficulty encountered is that there are several different chemical compounds which may have similar physiological effects. Yet the quantitative activity of these compounds varies to a considerable extent. In the case of vitamin A our foods contain both the classical vitamin A and carotene, as well as other related carotenoids. A value of 5000 International units has been suggested on the basis that the average diet supplies one third of the total activity
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in the form of vitamin A and two thirds in the form of carotene. Two thousand units of vitamin A as such will undoubtedly meet the daily needs. Some day it may be advisable to set specific standards for the carotene and the vitamin A requirements, and to express the distribution of both these compounds in our food materials. The absorption of vitamin A from the intestinal tract is definitely related to the fat content of our diet, and the actual requirement may differ drastically, depending upon the presence of other materials in the diet. VITAMIND. This requirement is dependent upon the total calcium and phosphorus intake as well as the calcium and phosphorus ratio and may differ considerably, depending upon whether the diet contains ample quantities of milk or whether the diet is low in this food. Apparently the different forms of vitamin D do not vary sufficiently to make this a problem in human studies. We are safe in accepting a value of 400 I. U. per day. VITAMINS K AND E. No requirements have been stated for vitamins K or E because so little information is available. Under normal conditions there is sufficient synthesis of vitamin K in the intestinal tract to meet the requirement. However, any change in the intestinal flora might bring about a definite increase in the need for preformed vitamin K in the diet. VITAMINC. This requirement is rather definitely established because the chemist has been able to determine this factor simply, not only in foods but also in the blood stream. Several groups of workers have shown that 70 mg. per day will maintain the vitamin C content of the blood a t high levels. The important question is whether we should supply sufficient vitamin C to produce complete saturation of the blood stream or whether optimum health can be maintained a t lower levels of saturation. VITAMINB1. At present there appears to be greater interest in the vitamin B, requirement than any of the other vitamins. This is perhaps due to the fact that it is practically impossible to study the vitamin B1 content of the blood and we must resort largely to balance studies. Many of the balance studies have been conducted for short periods of time, and such studies may give results considerably higher than those obtained over a long period. Another possible factor is that the vitamin B, requirement is definitely reduced by a high-fat diet. Recent studies a t the Banting Institute have suggested that high-fat diets may eliminate all symptoms of B1 deficiency except the changes taking place in the heart. If this is true, we should perhaps recommend the high level of B1intake, regardless of the fat content of the diet. A level of 1.5 to 2 mg. per day should supply an adequate intake for most individuals. I n studies conducted by Williams, Mason, Wilder, and Smith (8)it was found that about 1 mg. prevented symptoms but higher levels gave a high degree of well-being. RIBOFLAVIN.The recent work on humans (6) seems to establish that the riboflavin content is 3 mg. per day. These studies were conducted on humans receiving average diets, but again, changing the fat and carbohydrate ratio may alter the riboflavin requirement. It was recently shown in this laboratory that when the fat content of the diet is increased, there is a considerable increase in the riboflavin requirement. This we interpret in a preliminary way as being caused by a change in the bacterial flora. That is, under normal conditions there may be a certain degree of riboflavin synthesis in the intestinal tract, and we are merely measuring the riboflavin required above this synthesis. If there are sudden changes in the intestinal flora, the entire riboflavin requirement may have to be supplied through the diet. NICOTINICACID. Apparently this requirement should be established easily since nicotinic acid is a simple chemical
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compound. But tremendous difficulties have been encountered in attempting to determine the nicotinic acid content of foods or to measure the nicotinic acid excreted in the urine. Two recent developments should be of considerable value in establishing this requirement. One is that we are now able to feed dogs on a highly synthetic diet containing no nicotinic acid, and from these studies it would appear that the daily requirement for maintenance is about 0.25 mg. and the requirement for growth about 0.5 mg. per kg. Using these values, it would appear that the nicotinic acid requirement of a human is a t least 15 mg. per day. Bacteriological methods have also recently been developed for nicotinic acid determination, and these procedures give accurate results. By calculation, the nicotinic acid content of an average diet appears to be 15 to 20 mg. per day. As far as we know, there are no factors in the average diet which tend to alter the nicotinic acid requirement although increased exercise may have a definite effect on the requirement of this factor.
Limitations The greatest limitation in the above figures is the lack of recognition of the less known vitamins. Certainly the vitamin B6requirement of a human may be as important as any of the other B vitamins. Yet we have no way of setting a specific figure a t present. We can only make a rough assumption that the vitamin Ba requirement is of the same order of magnitude as vitamin B1. Pantothenic acid is undoubtedly required by the human, but we cannot give quantitative figures even for the requirement in animals. Again the pantothenic acid apparently affects the requirement of some of the unknown members of the B complex in the animal; whether pantothenic acid has a similar effect in humans needs further study. Another factor which has received a great deal of attention in animal work during the past year or two is choline. The serious difficulties which an animal encounters when diets low in choline are used suggest that studies on the importance of choline in the human dietary should be made. Here again we have an example of how the variation in the amino acid content of our diet may affect the choline requirement, since a high methionine intake tends to decrease the choline requirement and a high cystine intake tends to increase the choline requirement. We must recognize that much of our information regarding the human requirements has come from animal experiments. If we had not relied upon animal work we would not have much information. But if we use the results from animals we must realize that there is great variation in the requirements of different species. This was first recognized when rats failed to require vitamin C while the human, monkey, and guinea pig did. We are finding more and more discrepancies. The most interesting perhaps is the variation in
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the nicotinic acid requirement in different species. The rat and chicken apparently do not need this factor performed, while the dog is very sensitive t o a lack of it. Apparently the human and the dog are similar in their requirements for nicotinic acid. We are now finding that the ruminant can get along on diets practically devoid of the vitamin B complex because all these factors are synthesized by the bacteria in the rumen. Recent work indicates that the rat can synthesize some of the unknown members of the B complex and that high levels of pantothenic acid apparently favor this synthesis. The guinea pig gives quite different results from those obtained with other animals. A young guinea pig fails t o grow normally and dies in a fen- weeks when fed purified diets upon which rats and dogs may grow very well. But these animals will grow if the purified diet is supplemented with dried grass, yeast, and fresh milk. Chicks also require additional amino acids and certain factors from yeast before they will develop normally on synthetic diets. How these facts relate t o human nutrition is not known, but the results do suggest the importance of additional work. These problems require all the ingenuity that chemists can contribute.
Conclusion The nutritional requirements of man can be expressed in quantitative terms t o an extensive degree. These values are of great importance in constructing adequate diets, provided we still obtain a considerable proportion of the nutrient from natural foods. The safest program for the future involves the improvement of natural and processed foods through restoration and fortification. Thus recent criticisms leveled a t the fortification program are invalid because we are not adding enriched foods to synthetic diets but to diets that are already fairly adequate. The fortification of foods like bread merely brings the diet from a border line state of adequacy to an optimum and efficient state. We may not have all the knowledge for optimum fortification, but as long as the use of natural foods is continued, the danger of imbalance is greatly reduced. Literature Cited Brown, R. B., Hansen, A. E.. Burr, G. 0.. and McQuarrie, I., J . Nutrition, 16, 611 (1938). Krieger, C. H., Bunkfeldt, R., Thompson, C. R., and Steenbock, H.,Ibid., 21, 213 (1941). Mills, C. A., and Colvin, J. W., Science, 92,Supplement, 9 (1940). Shohl, A. T.,"Mineral Metabolism", New York, Reinhold Publishing Corm. 1939. Strong,>. M-.,'Feeney, R. E., Moore, B., and Parsons, H. T., J . Biol. Chem., 137,363 (1941). Tompsett, S. L., Biochem. J., 34,959 (1940). Van Duyne, F. O., Lanford, C. S., Toepfer, E. W., andsherman, H. C., J . A'utrition, 21,221 (1941). Williams, R. D., Mason, H. L., Wilder, R. M., and Smith, B. F., Arch. Internal M e d . , 66,787 (1940)
