The Synthetic Vitamins and Their Relation to Defense1 MARY JO RAHRIG Nazareth College, Nazareth, Michigan
grabs a cup of coffee in the morning before rushing to the subway, lunches on steak and pie, then blames his jitters on the bustle and rnsh of his hurried existence. The factory worker often goes to work on an empty stomach, and eats his breakfast of coffee and doughnuts during the mid-morning rest period. Often the night shift worker gets up in mid-afternoon, eats a hearty dinner with his family, and fills up the rest of the night on soda drinks and sandwiches, only to retire on a light breakfast. None of these diets is stable enough for good work but the American workman fails to recognize this as the cause of his inefficiency. We all seem to get "more or less enough of the hodybuilding proteins, energy-giving carbohydrates and fats, and minerals; but we are nationally deficient in calcium (for making bones and teeth) and particularly in vitamins, those well-publicized, little-understood, infinitesimal, lifegiving chemical compounds that regulate body operations and without which no one can have strong health or even life" ( 1 ) . This is due in part to the poor quality of the American diet and poor food habits. Over one-half of the average daily food intake of thirteen ounces of white flour, refined sugar, and fat, has almost no vitamins or minerals, and the cakes, pastries, candies, sweet drinks, and cocktails, which compose a large part of the American hill of fare, contain few vitamins and minerals. The calcium intake is low. Even adolescents neglect "fattening" milk only to eat a 20 per cent calorie excess of pastries and soft drinks with "the crowd." According to Dr. Russell Wilder, poor nutrition "can undemtine the nervous stability of the nation; i t can contribute to industrial unrest, cramp the strength and will of workers and industry, and sap their courage and the courage of their wives and children. Malnutrition may undermine o w national military defense" (7). In order to prevent this, the Government has resolved to educate the people in a knowledge of values, give better training for nutrition students, in both graduate and undergraduate work, improve the staple foods, and have physicians cooperate with the nationwide attack on the home front. However, the nutrition program is labile, reacting to many adverse factors. The problem of correcting malnutrition among industrial workers and the people as a whole can be solved only by eliminating the insufficient or improper foods in the diet and by substituting protective foods. 1 Presented at the 105th meeting of the American Chemical SoBut why is our food quality so poor? A century ago. dety in Detroit, Michigan, April 12, 1943, before the Division of children were getting plenty of vitamin D from sunChemical Education. 4cI1
T
HE SYNTHETIC vitamins are becoming more and more important in the field of national nutrition. The various uses of these vitamins and vitamin concentrates have gained new significance in the war effort and in national defense. Proper foods, supplemented by the synthetic vitamins, will make our nation healthy again, after its years of eating improper foods. We shall discuss the general problems of nutritional deficiencies, and explain the role of each vitamin in helping to alleviate the unnecessary suffering of people, especially of those in the service and a t home whose allout production and increased efficiency are necessary for our ultimate victory. The article, "Food is also power" in Fortune, August, 1941, states: "Nutrition has become a matter of national policy. It has moved up to the front rank as a war expedient hut i t will command the same priority in peace, for the people of the United States will never be content to revert to a state of diminished alertness and vitality" ( I ) . Proper nutrition has become increasingly more important to maintain a cool head in battle, courage on a dangerous mission, efficiency on the production line, and civilian morale. Perhaps we may say that the success of the war itself hinges upon good nutrition, for from i t we shall have the good health on which national defense depends. To be fed properly, a nation must supply each individual with the proper proteins, carbohydrates, fats, calories, minerals, and vitamins. After the war, the world will face a definite food shortage. Unless we prepare wisely now we shall he greatly affected for the worse. National defense must make use of present facilities to give proper and adequate diets to all. Here in America, the world's richest country in foodstuffs, the average person is malnourished, not from undereating but from improperly balanced diets. Statistics show that about 40 per cent of our population are on diets deficient in milk, milk products, fruits, vegetables, and meat. Often, people whose occupations bring them very close to nutiitions foods, such as truck gardeners or grocery clerks, do not include these foods in their diets. Further, food habits vary with the different sections of the country and classes of people. For example, take the Southerner who prefers a diet of hominy, molasses, salt pork, and corn mush, and wonders why he has no pep. Or take the businessman in the large city who
shine and vitamin B from whole grain cereals and breads. They ate unrefined sugar and drank spruce beer, rich in vitamin C, instead of soft drinks or sodas. Our grandparents abhorred fruits and vegetables because of their fear of cholera which had decimated the vegetarian Hindus and some people in our American cities. Science progressed. It prepared white flour and in so doing removed over 70 per cent of the vitamins. It polished rice, and taught us to cook, to can, to preserve, and to refine foods according to factory methods. It eased the labor of preserving and cooking food and decreased its natural good nutrient powers. People today prefer the daintily packaged refined foods, white bread, and polished rice, from which nearly all of the vitamins have been removed, to the old-fashioned vitamin-rich diet. However, it is true that excepting pellagra in the South, there are no ontstanding deficiency diseases in this country. Statistics show, nevertheless, that only one-fourth of our people have an adequate diet, and that 45,000,000 are mildly undernourished and have tendencies toward night blindness, indigestion, below-par conditions, lowered resistance, loss of interest in work, emotional instability, low morale, chronic fatigue, soreness of muscle or bacltache, irritability, nervousness--any or all of which have their harmful effects upon the life of a nation a t work. A practical example of the dangerous results of malnutrition may be found in the announcement of General Hershey that in the Army Physical Examinations since the draft began about 40 per cent of the selectees have been rejected, a third of whom were obviously malnourished. Many of those rejected were fed a proper diet, took additional vitamin concentrates, and later passed the physical examinations. Here is evidence that if everyone was on a diet of more protective and nutritive foods, national health would be greatly improved. Knowing all this, however, doesn't seem to do much good. The nation is slow to buy only the right foods; a complete new nutritional program would be likely to encounter social and economic problems. The program to be successful must have national cooperation. A short cut to an improved nutritional level is to put the vitamins back into the inexpensive staples. Science must undo the evil modern industry has done, processing and refining foods, and show us how to regain our health. Prior to the Civil War, meat and potatoes were considered the only safe foods. After the conquest of cholera, fruits and vegetables were preached back into the diet. However, it wasn't until just before the first World War that i t was determined that something besides calories in foods contributed to health. Sir Frederick Gowland Hopkins and his associates first discovered the accessory factors-later to be named vitamins-without which one would weaken and die. Since then, extensive researches have discovered over a dozen vitamins, synthesized most of them, and yet it is likely that they have only scratched the surface.
We have seen, therefore, what modem food preparation has done to our vitamins. Bread is the most common staple, hut due to the refining and milling process of white flour, most of the B vitamins are removed. Now, the synthetic vitamins, thiamin, riboflavin, and nicotinic acid, sometimes vitamin D, and the minerals iron and calcium, are added to bread as enriched flour, yeast, or vitamin tablets. This addition has proved to be a better process than special milling procedures which yield a darker flour but seldom meet the enrichment requirements of the Food and Drug Administration. Endorsement of this program by milling and baking -industries is their contribution to national defense and to permanent public health. Other foods which are enriched are milk with vitamin D and margarine with vitamin A. According to new specifications and in conformity with the Food and Drug Administration, the United States Army, Navy, and Marine Corps use only enriched bread. About 75 per cent of civilian white bread is enriched, and this is approximately equivalent to whole wheat bread in its nutritive properties. Soybean and peanut flours, which embody a large amount of the British baked goods, supplement white and whole wheat flours for cooking. Perhaps the largest problem in the field of nutrition is feeding the soldiers on emergency rations. Deficiencies in diet show up to a greater degree when a soldier is under the severe stress of training and battle, when emotional excitement increases vitamin requirements. Thus the emergency rations for soldiers must consist of concentrated vitamins and this is supplemented by an ample daily supply of the natural food vitamins. This is especially important for aviators, submarine personnel, tank corps men, and others in equally hazardous branches of the military service. Hence it has been found necessary to add two polyvitamin tablets to every daily ration. The Government and nutritional experts have practically standardized the soldier's diet, b u t that of the industrial worker still remains to be taken care of. After World War I, plants and factories were more interested in a worker's brain and brawn than in his physical and nutritional welfare. Very few places had adequate cafeterias or any type of concessions for meals. The worker was left to worry about his own food. Now it has become increasingly more important for the industries to have good cafeterias with wholesome meals a t a cost of 30 cents or less. With a good diet, a worker is more efficient, has increased producfion, and fewer accidents. However, those places which have only poor facilities for lunches are noticing the results in their production. Hot dog stands with no variety of menus offer much less than a third of the daily requirements. The resulting hidden hunger rather than a hollow hunger makes the worker seek other things during the day, such as soft drinks, which he prefers to milk and orange juice, or a sandwich instead of a nutritious, vitamin-packed salad. Irritability, extreme fatigue, and inefficiency increase and
are blamed primarily on the work and worry. Few realize that these symptoms are the result of nutritional deficiencies. Absenteeism is high here too. It is usually due to minor illnesses, ascolds, other respiratory diseases, and bronchial conditions. Numerous investigations have shown that proper diet and sufficient vitamin intake, especially of vitamin A, build up resistance to various types of infection. Experiments (2) have shown that feeding a vitamin-rich material such as cod-liver oil, as a supplement to home dietary, would reduce the economic loss to employer and to employees. Even when the factory has an adequate cafeteria serving a nutritious meal as cheaply as one without many essential nutrients, it can control only one meal a day, and this good meal cannot compensate for two other poorly balancedmeals a t home. Thus synthetic vitamins play an important role in the health of the worker. Many of the vitamins can be obtained as cheaply synthetically as from natural sources, and these are identical with those found in foods. Those who supplement the diet with extra vitamins have less fatigue, fewer accidents, increased energy, and less eye strain. The concentrates are also valuable for those on restricted diets because of allergy, old age, diabetes, surgery, faulty absorption, increased exertion, or deficient metabolism. Nutritive essentials serve their purpose no matter what their source-natural foods, synthetic, or enriched flour, bread, and margarine. The need for vitamins is very evident today for general health. Helen Mitchell says they "prevent or lessen the vague and ill-defined aches and pains and digestive disturbances which we have been prone to accept as inevitable. So many of the little discomforts of middle age and the so-called early signs of senility are not necessary" (3). There have been significant cures effected by vitamin therapy, and long-standing deficiencies, which come to the attention of physicians, have been obviously remedied. However, borderline or subclinical cases-those not definitely ill-just as Miss Mitchell says "lethargic and inefficient,are showing early signs of some deficiency. These latter are likely to ridicule the idea that eating the right food might make them feel better. They may turn to vitamin concentrates as the only expedient" (3). However, the protective foods are the only real solution to nutritional problems for most of the population. The present world crisis, with frequent new restrictions on food, necessarily demands that the nation as a whole buy these protective foods, use them as the foundations of health, and supplement these with the necessary synthetic vitamins. Since we are now dealing with the synthetic vitamins, rather than food, we shall consider the individual vitamins, their positive effects, and their mild and extreme deficiency symptoms. First, the vitamins are classified as fat soluble and water soluble. The fat-soluble vitamins are vitamin A, provitamins alpha-, beta-, and gamma-carotene; vita-
mins D, Dz, and DI; vitamins E, alpha-, beta-, and gamma-tocopherols; and vitamin K. Among the water-solublevitamins are vitamin C and the B complex including thiamin, or vitamin B,, riboflavin, or vitamin G, or vitamin Bz, nicotinic acid, pyridoxin, or vitamin Be, pantothenic acid, biotin, and various other factors. Vitamin A has been isolated and is available for research but not for clinical use in the pure form. It is a complex higher alcohol with unsaturated double bonds. The yellow crystals are sensitive to light, he'at, and oxidation. Concentrates for commercial use are prepared from fish-liver oils. Vitamin A from animal sources is used directly by the body. Plant vitamins A or the precursors of animal vitamin A are known as the provitamins alpha-, beta-, and gamma-carotene. Concentrates of these can be prepared from fresh green plants. The beta-carotene, which consists of dark red crystals when concentrated, is probably the most important provitamin A. These provitamins and cryptoxanthin are known to be changed in the body to yield vitamin A. Both plant and animal forms of vitamin A promote growth, healthy epithelial tissue, normal glandular functions and proper functioning of the visual purple, and increase resistance to infection. Deficiencies cause night blindness, epithelial diseases, poor teeth and gums, lack of vigor, poor appetite, and general weakness. We must emphasize that the increased resistance to infection and the prevention of night blindness, which is so hazardous for pilots, motorists, air-raid wardens, and plane spotters, are the important contributions of vitamin A to the war effort. There are several forms of vitamin D, the antirachitic factor, which are chemically distinct from one another. The most important forms of this vitamin are activated ergosterol, which is calciferol or vitamin D2, and activated 7-dehydrocholesterol, or vitamin D3. Calciferol is not made by total synthesis but is formed following the irradiation of ergosterol and is available commercially as "viosterol." Vitamin D is necessary for good bone and teeth development and good body form. It is very necessary for children to get this vitamin during their early years to develop properly but the adult requirements are not definitely known. Sources of vitamin D are ergosterol activated by ultraviolet light (or by electrons or sunshine), fish-liver oils, and milk enriched with activated ergosterol. Bread and cereals are also enriched with this vitamin. The commercial preparations are in the forms of emulsions, tablets, capsules, tonics, malt preparations, and concentrates from the fish-liver oils. Rosenberg says that vitamins of the E group, or "alpha-, beta-, and gamma-tocopherols, are all synthesized according to the same principle. Alkylated hydroquinone is reacted with phytyl halide in the presence of a catalyst to form in one reaction, the desired chroman derivative" (5). Alpha-tocopherol is more active than beta: or gamma-tocopherol. They have definite antioxidant properties which prevent
auto-oxidation of fats and rancidity resulting therefrom. They are stable to heat, acids, and alkalies, but are destroyed by the oxidizing action of ferric chloride and silver nitrate. Although vitamin E is prepared synthetically, it is also extracted from wheat germ oil, a natural source. Human requirements have not been definitely established, but a deficiency results in failure to reproduce, in muscular weakness, and in degenerative diseases of the nervous system. Vitamin K is a substituted derivative of naphthoquinone. It is the antihemorrhagic factor, and the synthetic vitamin is called menadione. Many factors possessing vitamin K activity have been developed. The synthesis is inexpensive and the menadione is used commercially. Most of the K vitamins are fat- and oil-soluble but the few water-soluble ones are used for intravenous administration. It maintains a normal prothrombin level in the blood and is used to treat obstructive jaundice and to prevent postoperative bleeding. This vitamin is used extensively for emergency operations near a battle front and injections of vitamin K a t such critical times have proved very valuable to the future recovery and health of the patient. The water-soluble vitamins of the B complex and vitamin C have nearly all been synthesized and are contributing greatly to supplement national nutrition. The only vitamin containing sulfur, thiamin or vitamin B1, is a thiazole-pyrimidine compound made synthetically and sold as thiamin chloride. It is quite stable but is not stored in the body. It is destroyed by heating in an alkaline solution. In the "Nutritional Charts" published by the H. J. Heinz Company, we find that this vitamin "promotes growth, stimulates appetite, aids digestion and assimilation," is "related to carbohydrate and fat metabolism," and is "essential for the normal condition and functioning of the nerve tissue" (4). Slight deficiencies result in weakness, slow heartbeat, loss in weight, cardiovascular and digestive disturbances, poor appetite, and impaired reproductive functioning. It acts as a coenzyme to oxidize pyruvic acid from carbohydrate metabolism and utilization in the body. Vitamin B, is called the energy and morale vitamin because there is a direct relation between the vitamin requirements and energy output. Any increased activity requires more of this vitamin, and i t boosts morale by eliminating emotional strain consciousness. Certain nervous disorders, as constant fearfulness, short tempers, poor memory, tearfulness, and easily hurt feelings, caused by vitamin B1 deficiencies, are cured in a very short time by thiamin injection. Its use in treating metallic poisoning is very important for the armed forces and civilians in war zones. Riboflavin, or vitamin Bz, is synthesized by various methods. A few of the starting materials are orthoxylene, a by-product of the petroleum industry, dribose from natural sources or synthesis, and alloxan obtained from the oxidation of uric or barbituric acid.
Crystals are yellow in color, soluble in water and alcohol forming green-fluorescent solutions when neutral, but are insoluble in fat solvents. The flavins are stable to heat, air, and oxygen but are sensitive to alkalies and light. Riboflavin is necessary for cell respiration, repair of nerve tissues, and normal growth and health, and it lengthens the span of life. Deficiency symptoms -ariboflavinosis-include skin changes of theilosis, ocular defects such as cataract and eyelids adhering together, lesions a t the comers of the mouth, shiny lips, digestive disturbances, loss of hair, lack of vigor, and dimness of vision. Priorities for vitamins B1 and Ba have been obtained, so that neither civilians nor the armed forces will be without these essential nutrients. These two vitamins are sold in both concentrated and synthetic forms. Nicotiuic acid, niacin, or the antipellagra factor, is prepared synthetically by the oxidation of nicotine, or of beta-picoline, or by synthesis from pyridine. The white crystals are soluble in hot water and alcohol, and in alkali hydroxide and carbonate solutions, but are insoluble in ether. It has a bitter taste and is a constituent of coenzymes which transfer hydrogen in cellular respiration and which are important in glycolysis. It promotes growth and health, and maintains the normal function of the skin and gastrointestinal tract. The symptoms of pellagra, resulting from a deficiency of nicotinic acid are glossitis and dermatitis. However, there are many more subclinical cases which show the early nonspecific symptoms of mental depression, stupor, dizziness, trembling of the head, loss of memory, copfusion, soreness of mouth, indigestion, nausea, constipation, loss of weight, and nervous disturbances. These patients may be treated for the symptoms with nicotinic acid successfully before any degenerative changes of the nerve tissue have taken place. Nicotiuic acid also cures Vincent's infection when i t is caused by a pellagra condition, relieves nausea, vomiting, and headaches of intensive sulfanilamide therapy, and prevents high tone deafness and extreme sensitiveness to heat and cold. Vitamin Be or pyridoxin is a pyridine derivative from ethoxyacetylacetone. It is quite stable as a white colorless powder, but in solutions, as the pH increases, the stability is decreased. It is destroyed by light and is soluble in water, but not in acetone. It is synthesized according to Rosenberg by "building up the pyridine nucleus from small aliphatic molecules and by partial degradation of a higher molecular compound as isoquinoline, to form the pyridine derivative of the constitution of vitamin BE" (6). The functions of this vitamin in the body are not clearly understood, but it seems to be essential for the utilization of fatty acids and production of enzymes involved in muscular metabolism. Those with residual symptoms after treatment with the other B vitamins are frequently relieved by injections of vitamin BE,showing
that clinical diseases often occur from complex deficiencies. Panthothenic acid, commonly called the "filtrate factor," seems to he curing a malady in the British Army characterized by fatigue, breathlessness, fainting spells, and disturhances of the pulse rate, due to the sensitivity of the adrenal glands whose proper fuuctioning is controlled by this vitamin. It has been made synthetically and is available as the calcium or sodium salt. Para-aminobenzoic acid seems to have some vitamin activity and has been used to treat gray or white hair, occasionally restoring the natural color. The effects of this vitamin do not seem to he toxic, hut it may cause high blood pressure, and a counteraction to the curative effect of the sulfa drugs. Synthetic methods of preparing vitamin C have been most economical for some time. Various methods have been used and the similiarity of its structure to the rnonosaccbaride sugars have made possible its synthesis starting from a variety of different carbohydrates. Vitamin C is oxidized rapidly by iron and copper, and is sensitive to alkalies and to cooking in the presence of air. It is destroyed by. infections and industrial poisons and is lost by perspiration. This vitamin favors good tooth development, is essential for normal conditions of endothelial cells, glandular functions, and tissue respiration, stimulates growth, and improves the appetite. Mild deficiency symptoms are indicated by enlarged and weak joints, headache, low resistance to infection, weakness, restlessness, and digestive disturbances. The synthetic vitamin has been used to treat diseases caused by viruses, to heal wounds and fractures, prevent benzene and toluene poisoning, and to help prevent heat prostration in war plants and among our soldiers in the tropics. It increases resistance to hay fever and is also useful in preventing postoperative shock. We have seen that all of the vitamins are necessary for life in some degree and when these are not supplied entirely by foods, they must be obtained from synthetic
or concentrated sources. Usually for good nutrition. they are sold as mixtures of several of the vitamins. There is much danger, however, in all this knowledge. Some people might take a poly-vitamin capsule, consider i t their quota for the day, and neglect to eat the right foods. The vitamin concentrates merely supplement food; they do not replace it. Further, nutrition is not an exact science. New vitamins are being discovered frequently and it would be very rash tp believe that these are not as necessary for health as the ones already known and synthesized. To obtain all these unknown vitamins, we must eat the right protective foods and avoid all deficiencies. Altogether, there are about 36 known elements necessary for health. These include a dozen well-recognized vitamins, about 10 amino-acids, and sugar, fat, water, and minerals. Swallowing a couple of vitamin capsules daily does not discharge our duty to our bodies, for all these essential elements must fit together in a physiological mosaic. A well-balanced diet plus vitamin capsules for known deficiencies will insure our getting both the known and the unknown vitamin values. Thus, while our Government is calling for an allout production scheme, let us who know the importance of vitamins in our physical, mental, and moral life pledge ourselves to an all-out campaign for spreading this essential knowledge among our fellow citizens. By so doing, we shall be participating, to a very vital extent, not only in the war-effort proper, but also in the uphuilding and preservation of the health of a great people in a great nation, the United States of America. LITERATURE CITED
(1) ANONYMOUS, "Food is also power," Fortune, 24,102, (August. 10At\
11th Ed., H. J. Heinz Company. Pitts-
(6) Ibid.. p. 352. (7) WILDER,"Nutritional problems as related to national defense, Am. I.Digestive Diseases Nutrition, 243 (1941).
