Clue from animals

As an intern at Cleveland's Lakeside Hospital in 1930, Spies lost his first patient-an alcoholic victim of pellagra. He set about proving that pellagra was the result of a diet deficiency, showed that when victims failed to recover after a good diet had been prescribed, it was because they were so soremouthed that they did not eat their food. When he force-fed them or injected food elements, they got better. Dr. Spies proved, too, that there was no essential difference between the North's "alcoholic pellagra" and the South's "endemic pellagra." He did this first by feeding up Skid Row derelicts at the same time as he allowed them as much corn liquor as they could drink; their pellagra cleared, showing that it had been caused not by alcohol but by the absence of essential food factors. At Birmingham's big Hillman Hospital, Nutritionist Spies worked seemingly miraculous cures by diet alone.

When other researchers showed that nicotinic acid or niacin (one of the B vitamins) was effective against an animal disease resembling pellagra, Dr. Spies seized on the clue, soon proved that simply adding niacin to the diet would go far to cure many cases. (It has since been shown that an amino acid, tryptophane, found in protein foods, is also essential in pellagra prevention.) But Experimenter Spies was convinced that where was one vitamin deficiency, there were likely to be others. He advocated supplements of several vitamins, was sharply criticized for "shotgun" treatment, has been fully vindicated by later findings.

Magic through vitamins

Dr. Spies did much to prove the effectiveness of folic acid, another vitamin, in treating several forms of anemia, including early cases of pernicious anemia. Next, at the University of Havana's Calixto Garcia Hospital, he gave folic acid to victims of tropical sprue, a wasting, debilitating deficiency disease of which anemia is one symptom.

EFFECTS OF MALNUTRITION AND UNDERNUTRITION ON NERVOUS SYSTEM [Reprinted from the Journal of the American Medical Association, June 7, 1958, vol. 167] We all know that mental illness is a major medical problem. I wish to discuss briefly with you some of the effects of malnutrition and undernutrition on the nervous system. Think of the loss of creativeness and productivity caused by this type of illness alone! Who can estimate its cost in terms of human misery? In the past mental illness has been considered a social, moral, or legal problem. To me, the medical profession has the responsibility of treating patients who are mentally diseased, and of preventing mental illness. As physicians, we all know that mental disorders may be an alteration of social behavior, an abnormal emotional response, a neurosis, or a psychosis. The patient may be slightly incapacitated or he may be stricken with a major psychosis that makes hospitalization necessary. It is well to remember that mental disorders are prevalent wherever human beings exist.

Some of the custodial institutions for mental diseases are doing better and better work, but I sometimes wonder if others should not be called "containers of sick people" or "storehouses of sick people." At any rate, the problem is great. Ever since insane asylums have existed, the pellagrin has been pushed into them. These patients were not recognized as pellagrins. Usually the diagnosis was "psychogenic" psychosis. They may have been mistaken for a "schizophrenic," a "manic depressive," or some other classified type of psychosis. Having trained myself more as a nutritionist than as a psychiatrist, I was more impressed by the prolonged dietary deficiency of these patients than by their psychic alteration. Eventually my associates and I found that a lack of niacin in their diets allowed the mental symptoms to arise. After its administration, these symptoms disappeared. Thus we showed that the relief of one particular kind of undernutrition or malnutrition could produce complete relief of mental symptoms. Until this time pellagra was viewed as a mental illness practically incurable. Thanks to the recommendation by the American physician of widespread use of niacin, the disease has practically disappeared.

My associates and I are now in the process of making a 20-year appraisal of niacin as a therapeutic agent. An effect on the second generation is already apparent and can be visualized by means of the following brief case history of a mother and her daughter.

Fig. 20.-Comparative intake of nutrients before and after therapy with prednisolone and aspirin in patient with rheumatoid arthritis. Asterisk indicates allowance recommended by Council on Foods and Nutrition, National Research Council.

"CASE 11.-The mother was born in north central Alabama and was of AngloSaxon stock. She married a hard-working young man who also was of AngloSaxon extraction, and they were in good circumstances until the "depression" closed the coal mines in 1929. The husband said, "When the mine shut down, I was thrown out of work." From that time on the diet consisted of corn bread, "fat back," syrup, and occasionally beans or an egg. The wife began losing body weight, and after the birth of each child she found herself weaker and weaker. In 1933 she began having "pellagracy" each spring. This "breaking out" of the skin appeared on her ankles and forearms and each year it was associated with "nervous crying spells." Her husband said that in 1936 she suddenly "went right out of her mind," and in February of that year she was committed to a mental institution.

"Four months after the mother's admission, the above-mentioned child was born. It is this child, literally born in a mental hospital, whom I would like to tell you about now. The mother, who was treated with niacin and a better diet, took this child home, and at an early age this child did some of the housework and, when two younger children were born, helped with them. In time she went to high school, where she was an excellent student, and her teacher stated, 'She is talented and very responsible.' She graduated from high school and also graduated from the university, where she won a number of competitive scholarships.

"Comment: In summary, certainly the mother could not have been released from the institution without treatment, and it is doubtful that she could have worked hard and continued to have children if she had not had treatment from time to time in her home. But, even more impressive to me is the fact that a

baby born in a mental institution was able, through the efforts of her mother and, later, of herself, to win competitive scholarships."

The older physicians among you, of course, are well acquainted with the severe mental symptoms of pellagra that manifest themselves in various types of psychoses. Perhaps the most common is that in which loss of memory, disorientation, confusion, and confabulation are predominant. In some types excitement, mania, depression, and delirium predominate. In our experience a paranoid condition is common in pellagrins. These patients, acting on their paranoied delusions, are more active than other pellagrins with psychoses.

After we had learned how to correct the baffling brain changes associated with the severe mental illness of pellagra, we began to grapple with the problem of how to relieve people who had early symptoms only. Soon we learned that many persons who had prolonged dietary deprivation suffered from what was called "hysteria," "anxiety," "extreme nervousness," or "depression." These people disliked bright lights, bright colors, noises, odors once tolerated, and foods once relished. They described themselves as being "jittery," "nervous," "restless," "fractious," and "tense." They stated that they constantly expected something terrible to happen. Still others complained of a poor memory, a memory so poor that they could not remember even what happened 10 minutes before. The patients with the milder afflictions tended to become worse as time went on, and many of them developed personality disorganization.

It is not my intention to delve deeply into why these people could not satisfy their longing for inward peace. I could not accept the concept that their brains were irreparably damaged; it seemed that the cells were waiting listlessly and would function again at full efficiency when we gave them the required nutrients. To make a long story short, we showed that not only niacin was necessary for the integrity of the nervous system but thiamine too. In samples of blood entering and leaving the brain, my associates and I observed a profound alteration in the content of glucose and lactic acid. By studying the oxygen utilization and the lactic acid production, we learned that in patients with vitamin B1 deficiency and with mental symptoms, the cerebral metabolism was diminished by 60 percent. These observations afforded a basis for the explanation of our clinical demonstration that thiamine relieved the mental symptoms in a syndrome complex which we termed the initial nervous syndrome. This syndrome can now be prevented with administration of thiamine and niacin. Other vitamins, such as pyridoxine, folic acid, and vitamin B12 under certain circumstances may be useful in correcting symptoms arising from the nervous system. Today it is with prevention that you and I, as physicians, are primarily concerned. Our group long ago learned that the emotional disorders of older people can sometimes be overcome or relieved through the science of nutrition. So many of the older patients have an initial complaint of mental fatigue. They learn that by renewed effort they can adjust, but the process of compensation worries them and anxieties and depression may develop. They feel they are no longer needed, and many of these people have no incentive for living. They resist changes and their habits become fixed. In many the personality becomes disorganized or rigid and the judgment poor. They lise insight and accept flattery hungrily. Some of them let reality slip away. All too often they confuse manliness and sexual ability. They may develop insomnia and later may become disoriented as to time, place, and, finally, person. It is in this manner that aging brings to them accumulated emotional trauma. All too often the patients have a diagnosis of cerebral arteriosclerosis with psychosis, using age as the only criterion. In trying to aid these people, we assume that their personality is the result of their hereditary factors and their experiences, and that their incapacitation, whether due to a mild neurotic disorder or to a major psychosis, is not necessarily irreversible. Whatever their permanent cerebral incapacity may be remains to be established, but the physician must not accept it without trying to do something for the patient.

Whether among the old or the young, symptoms arise from damaged tissues. In general, we stress that the processes of protection or of repair will be impeded in tissues that are nutritionally deficient. Mere duration of life is not enough. From time to time we have given you examples of the cells being damaged but not being finished. Give them what they need and they will muster strength and come back. We do not have enough information, of course, to know all they need. The science of nutrition has only scratched the surface, but it has made some progress toward a real solution of mental illnesses.

We know that many nutrients are necessary for the integrity of the nervous system. Yet many persons with anxiety and tension states do not have their

neuroses relieved by application of any or all of the nutrients now known. Accordingly, it seemed imperative that we study the so-called tranquilizers or ataractic drugs from the viewpoint of their effect on nutrition. This study is still under way, but we can say that there is, under certain circumstances, a loss of nutrients when these drugs are used and that the safest and best way of using them generally is to be certain that there is a platform of solid nutritional therapy instituted to protect the nervous system. The tranquilizing drugs certainly are an effective aid in managing severely disturbed, hospitalized psychotics, but special attention should be given to the nutrition of these patients because some of them can be helped by nutritive methods. In the past 20 years we have relieved many persons of symptoms arising from the nervous system with synthetic vitamins and a good diet. Yet these persons had no clinical evidence on which a definite diagnosis of deficiency disease could be made. On several occasions I have talked with Dr. John T. Ferguson, who is studying this aspect intensively, particularly in older people. It occurred to me that in our clinic we could be of most service in working with the milder afflictions.

The great majority of people with nutritive failure and "functional" mental disorders respond promptly and completely to adequate nutritional therapy, but there are some who have anxiety states that cannot be corrected entirely by nutritive therapy alone and it is with those people that this particular study is concerned. Conversely, some "functional" mental symptoms arising from nutritive disorders are not corrected adequately by giving the tranquilizers alone that is to say, vitamin therapy does not replace tranquilizers and tranquilizers do not replace vitamin therapy, but, when indicated, they should be used properly together for the benefit of the patient. Obviously we could not study all the tranquilizers so we chose meprobamate (Miltown, Equanil) because it is well tolerated, orally effective, and suited for prolonged therapy. The following brief case history is illustrative of what can be done by the judicious use of vitamin therapy and a mild tranquilizer.

"CASE 12.-A 49-year-old white man was first brought to the Nutrition Clinic of the Hillman Hospital in 1940 complaining of weakness, weight loss, photophobia, soreness of the mouth and tongue, pain and burning of the legs and feet, forgetfulness, and depression. Physical examination showed a man with nutritive failure. He had pellagrous glossitis, great dilatation of the conjunctival vessels associated with photophobia and lacrimation, excruciating tenderness in the nerve trunks of his legs, and hyperactive Achilles and patellar reflexes. His diet for many years was composed chiefly of refined carbohydrates and fats. He rarely ate protein in the form of meat, milk, or eggs. In a period of some 10 years he lost 25 lb. (11.3 kg.) in body weight. He was worse in the spring and fall of the year, and, although his course was not steadily downhill, his symptoms were somewhat more severe with each recurrence. Because of the severe pain in his feet and legs and his sleeplessness, he was given an injection of thiamine. Within 6 hours the pain had disappeared and that night he slept better than he had for a long time. We then decided to give him sterile saline solution as a placebo. The pain in his feet and legs returned within 48 hours and it was not relieved by saline solution. Without his knowledge the saline solution was replaced with thiamine, 10 mg. parenterally twice a day for a week. Again the pain was promptly relieved and he was able to sleep. For the following month he was given by mouth 10 mg. of thiamine daily and 50 mg. of niacin 10 times a day. Within 48 hours after this therapy was started his pellagrous glossitis disappeared, his appetite increased, and his forgetfulness and depression were relieved. The symptoms arising from his eyes were not relieved, and we decided to give him injections of riboflavin, 10 mg. twice a day for a week. The dilatation of the conjunctival vessels, the lacrimation, and the photophobia began to decrease on the second day of therapy, and by the 7th day the eye symptoms were greatly relieved. This patient's diet improved, but it has not always been completely adequate and he has required treatment from time to time. In the fall of 1957 he had influenza, and since then has complained of sleeplessness and a 'sick stomach.' Thiamine or niacin gave him no relief. It was decided to give him meprobamate, 200 mg. every 12 hours. After 5 days he volunteered that he was sleeping much better, and he no longer complained of having a 'sick stomach.' In the 2 months that he has been on this therapy he has had no recurrence of these symptoms."

It is important, as can be seen by this case history, to realize that the mere fact a person has nutritional deficiency does not mean that he cannot have other types of disorders also.

SUMMARY AND CONCLUSIONS

I have discussed with you a few of the many advances which have been made in nutrition in recent years. You have seen that what patients eat has much to do with their health and with their recovery from ill health. Primary or secondary nutritional disorders produce or complicate all the problems of the sick. I have stressed that we should be concerned with the prevention and with the earlier stages of disease when the disturbances are almost imperceptible and that we should not wait until these disturbances bring tremendous burdens and stark tragedies.

In the beginning man's main concern was the obtaining of food. He did not know that bodily functions are impaired when the cells and tissues of the body are deprived of essential nutrients. Of necessity, our ancestors had to obtain all their vitamins and essential nutrients as they were produced by nature. We have learned that, when fruits, vegetables, eggs, milk, fish, meat and other foods are not available in adequate amounts, or for any reason are not satisfactory, we must recommend methods of maintaining tissue integrity. We have shown how this may be done by supplementing what foods are available with certain synthetics and food concentrates. This means that the goal we are seeking is to devise methods of achieving biochemical independence for people. To do this, we know that excellent nutrition is basic, that disease is chemical in its origin, that the body cells can fight back to an amazing degree, and that our tissues, when properly replenished, can come into their own again. A number of examples are reported of how this works in actual practice. Above all, we must realize that, as physicians, we are properly the guardians of the health and nutrition of our patients, and it is for us to prevent or treat disease so as to increase their vigor, strength, and happiness.

[The studies in nutrition were done at the Nutrition Clinic, Hillman Hospital, Birmingham, Ala., at the Department of Nutrition and Metabolism, Northwestern University Medical School, Chicago, at the Hospital Mimiya, Santurce, Puerto Rico, and at the General Calixto García Hospital, Havana, Cuba.

[This paper is based to a considerable degree on concrete data obtained by the associates of the author working in Alabama, Illinois, Cuba, and Puerto Rico.]

REFERENCES

1. Spies, T. D.: Rehabilitation Through Better Nutrition, University of Cincinnati Studies in Nutrition at Hillman Hospital, Birmingham, Ala., Philadelphia, W. B. Saunders Company, 1947.

2. Spies, T. D.; Hightower, D. P.; and Hubbard, L. H.: Some Recent Advances in Vitamin Therapy, J. A. M. A. 115:292–297 (July 27) 1940. Spies, T. D.: Diagnosis and Principles of Treatment of Dietary Deficiency Diseases, Texas J. Med. 38:427-431 (Nov.) 1942.

3. Spies, T. D.; Bean, W. B.; and Stone, R. E.: Treatment of Subclinical and Classic Pellagra: Use of Nicotinic Acid, Nicotinic Acid Amide and Sodium Nicotinate, with Special Reference to Vasodilator Action and Effect on Mental Symptoms, J. A. M. A. 111:584-592 (Aug. 13) 1938. Spies, T. D.: Degenerative Diseases with Nutritional Interrelationships, South. M. J. 46:238-247 (March) 1953. Nutrition and Disease, T. D. Spies, editor, Postgrad. Med. 17:1-96 (March) 1955.

4. Mann, A. W.; Dreizen, S.; Pyle, S. I.; and Spies, T. D.: Red Graph and Wetzel Grid as Methods of Determining Symmetry of Status and Progress During Growth, J. Pediat. 32:137-150 (Feb.) 1948.

5. (a) Spies, T. D., and Stone, R. E.: Pituitary Adrenocorticotropic Hormone (ACTH) as Tool of Clinical and Laboratory Research, Lancet 1:11-14 (Jan. 7) 1950. (b) Stone, R. E., and Spies, T. D.: Further Observations on Cortisone and ACTH as Therapeutic Agents, South M. J. 45:885-896 (Oct.) 1952. (c) Spies, T. D.; Stone, R. E.; and Spies, H. A., Jr.: Metacortandracin and Delta 1 DehydroHydrocortisone in Rheumatoid Arthritis, GP 12:73-78 (July) 1955. (d) Spies, T. D., and others: Prednisone and Prednisolone as Therapeutic Agents: Progress Report on Their Integration into General Medical Practice, J. A. M. A. 159:645652 (Oct. 15) 1955.

6. (a) Spies, T. D.: Influence of Nutritional Processes on Aging, South. M. J. 50:216-225 (Feb.) 1957. (b) Reference 5d.

7. Spies, T. D.; Aging, C. D.; Gelperin, J.; and Bean, W. B.: Mental Symptoms of Pellegra : Their Relief with Nicotinic Acid, Am. J. M. Sc. 196:461-475 (Oct.) 1938.