Treatment of Schizophrenia

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Treatment of Schizophrenia

Introduction

Early in January 1995, a 24-year old female patient was in my office with her parents. Her parents were cheerful, the patient was exuberant. She was normal by my criteria. She told me of her plans to attend university at Simon Fraser University. I had first seen her 10 months earlier. She had been schizophrenic for four years and was on heavy doses of drugs including one of the recent ones so highly touted. Her psychiatrists had informed her and her family that she would never recover, but that she might stabilize on her tranquilizers by the time she reached age 30.

What is it worth to save a human from the fate of the chronically tranquilized psychotic, barely able to get by to stabilize? I urge all physicians to reward themselves and their patients by witnessing these recoveries. Do not wait for their psychiatrists. They are still "avant guard" as of 30 years ago. Do it yourself.

I have been practicing nutritional medicine since 1951, when I first began to treat schizophrenic patients with large doses of vitamin B-3 and vitamin C. Dr. Osmond and I were directed toward the use of these two vitamins by the hypothesis we had developed about the cause of schizophrenia. We thought that a main biochemical problem with the schizophrenic body was an abnormal diversion of adrenaline into adrenochrome. Adrenochrome is an hallucinogen( 1) which has an inhibitory effect on transmission at the synapse. In 1952 the idea that adrenochrome was present in the body was resisted strongly, but recently adrenolutin, the first major derivative from adrenochrome has been proven to be present in the body.( 2, 3)

The chemistry of adrenalin and adrenochrome suggested that the formation of the oxidation product could be inhibited by using nicotinic acid which is a methyl acceptor and ascorbic acid which is an antioxidant. Removing methyl acceptors from the body's pool of methyl groups would decrease the formation of adrenalin from noradrenalin, and adding vitamin C would decrease the rate of oxidation of adrenalin into adrenochrome. We thought this would be a good way to begin our therapeutic trials since vitamins even then were known to be very safe and could be taken in large doses.

We began to treat schizophrenic patients with 3 and more grams of vitamin B-3 (nicotinic acid or nicotinamide) and with ascorbic acid 3 to over 20 grams per day. I sometimes hear from or see patients that were started on the program many years ago. During July 1993 a man called my office for information about my current regimen. He said that I had treated him in Regina, Saskatchewan, at the Munro Wing (about 1953), that he had recovered, had completed his masters degree and had just retired from his profession. He was still taking the same vitamins. I can not remember him, but he was either one of the early patients, our pilot study or else was one of the patients who participated in the first double blind controlled experiment we ran 40 years ago.

Over the next 15 years, twelve physicians explored the various aspects of megavitamin therapy. We began to incorporate other vitamins such as pyridoxine, folic acid and thiamin into specific regimens for different psychiatric and physical conditions. We also became much more aware of the importance of nutrition. We had originally looked upon the vitamins as if they were drugs which could be used in isolation from food and nutrition, but it soon became apparent that they were supplements, i.e. added to the best possible basic diets. Gradually interest spread to the use of minerals in optimum doses especially copper, zinc and manganese, and later to the use of the amine acids such as tryptophan. Ecological principles were introduced into orthomolecular psychiatry by Marshall Mandell and William Philpott. A few years after Linus Pauling published his classic paper in Science, entitled "Orthomolecular Psychiatry", we began to use this word as an accurate description of what we were doing.

Nutritional medicine became orthomolecular when the first nutrient was recognized and made available for human therapeutics. The practice is at least 100 years old even though the word was first proposed by Linus Pauling in 1968.( 4) In 1949 Dr. Pauling published his paper on sickle cell anemia which he characterized as a molecular disease.( 5)

Vitamins were used only to prevent classical deficiency diseases such as beri, scurvy, pellagra and rickets. The vitamin paradigm was described by the following statements: ( 1) vitamins were needed in very small quantities in order to prevent deficiency diseases, enshrined by the recommended daily allowances (RDA); ( 2) these quantities were available in a well balanced diet which therefore did not need to be supplemented; ( 3) any dose above that would not be therapeutic for anything but would be a waste of money since the extra amount could not yield any additional good health and could be toxic. The underpinnings of this paradigm were weak to begin with, and became even less substantial when pellagrologists in the mid-30's showed that the prevention of a resurgence of symptoms in chronic pellagrins required 600 mg of niacin (vitamin B-3) daily. To prevent pellagra in the first place less than 20 mg daily is needed. This is the first example of using megadoses of any vitamin for preventing disease.

We studied vitamin B-3 for treating acute schizophrenic patients in four double blind controlled experiments beginning in 1951.( 3) In Saskatchewan we studied the therapeutic effect of vitamin B-3 for acute schizophrenic patients.( 6) We concluded that adding this vitamin in doses of 3 grams daily to the current best treatment program, doubled the two-year recovery rate. For many years psychiatry has maintained that about one-third of schizophrenic patients who become sick for the first time and have not been sick for a long time, about one-third will recover even with no treatment. This is known as the spontaneous recovery rate. I think this estimate is wrong because it is based on the number of patients readmitted to hospital and not upon the real recovery rate. I have seen many patients who had been admitted once to a psychiatric hospital and who never reappeared there. Their psychosis did not become as severe and they were able to stay out of hospital, but they were not well. They remained chronically depressed, occasionally paranoid, almost always in some difficulty. They were no longer having obvious hallucinations but no one could have described them as well. In my opinion the natural or spontaneous recovery rate is closer to 10 percent.

With the use of vitamin B-3 I have continued to see similar and even better recovery rates as the program has become more sophisticated and comprehensive. Our double blind experiments have become the standard way of examining the therapeutic efficacy of treatments even though they should not be the gold standard in research since they do not solve the basic problem, i.e. to remove bias from the investigation and to increase the ability to judge efficacy. There are many treatments which double-blinds have shown to be ineffective, which on the contrary have been very effective. For example l-dopa in the treatment of Parkinsonism, and many treatments shown by double-blinds to be effective which have little clinical therapeutic advantage. But double blind trials are preferred by editors, by investigators, and by governments, since they promise to replace clinical judgment by a Chi Sq number, and remove the need to think and to observe carefully. They are loved most by investigators with lots of money and little imagination.

The Treatment

I no longer treat schizophrenia with just one vitamin. The complete treatment deals with optimum nutrition, with the correct supplements in optimum dosages, with drugs as they are needed and with the type of psychotherapy every physician owes every patient.

1) The Diet

There are two main elements in dietary treatment. The first is to determine whether the patient is allergic to or has toxic reactions to foods. A good food history will provide clues, but in the end the only certain test is the elimination diet. Foods suspected of causing a problem are eliminated for one or two weeks. If at the end of this period the patient is better, that shows that this allergy was a factor. The test is completed by reintroducing that food which will reproduce the earlier symptoms. This is simple for people with few food allergies, as is usually the case with children who have one or two major food allergies, usually milk and sugar. Adults may have many more and for them special elimination diets may have to be used.

The second element is the elimination of all additives, especially the simple sugars. On the average about 125 pounds of simple sugars are eaten by each person each year. This figure is obtained by dividing the total sugar consumption by the number of people including infants. This means that over half the population uses more than 125 pounds. Many adults consume close to 200 pounds per person. The other additives are present in smaller quantities, perhaps 5 pounds per person, but they are much more potent and include any of the large list of chemicals allowed in our foods. They are there for cosmetic reasons and to enhance stability over time. They do not maintain or improve the nutritional quality of these foods.

2) The Supplements Vitamins

All the vitamins are safe when used in the dosages recommended by orthomolecular physicians. They are very safe even in doses much larger than these, but there is no point in taking more than is needed. Water soluble vitamins are safer because they are not stored in the body to the same degree as the fat soluble vitamins. The few fat soluble vitamins are vitamins A, D-3 and E. As a general rule it is wiser to take slightly more vitamin than is required because they are so safe and this ensures that all the tissues are provided with enough. The body is not stressed by taking slightly more, as it is by taking slightly less. If there is a deficiency, some reactions in the body will have to be slowed or halted and vitamin stores will be depleted making the situation even worse. More does not slow down metabolism, less does.

Niacin and Niacinamide (also called nicotinic acid and nicotinamide respectively; both are covered by the term vitamin B-3).(7)

Pellagra, the vitamin B-3 deficiency disease, is rare in industrialized countries, but subclinical states of pellagra are a lot more common than nutritionists have recognized. The four descriptive terms for pellagra are dermatitis, diarrhea, dementia and finally death, for it is a terminal disease. This vitamin is the one used most consistently by orthomolecular physicians. In Saskatchewan we examined its role in treating schizophrenic patients over 40 years ago. It is a water soluble vitamin and safe in the following dose ranges.

(A) Niacin -- Up to 9 grams daily. Usually less than 6 grams is needed and the most frequent dose is 1-1/2 to 3 grams daily. The maximum dose can be determined by increasing the dose until the person becomes nauseated. As soon as this happens the dose must be reduced. The nauseant dose varies enormously from 3 to over 30 grams daily. The dose varies with the condition being treated. To lower cholesterol levels the dose range is 1-1/2 to 9 grams daily. For schizophrenia it may need to be higher. There is a definite dose response curve. Patients who have shown little response to 3 grams may respond very quickly to 6 grams. It is advisable to start with lower doses and gradually increase them depending upon the response.

When first taken it causes a pronounced flush which starts in the forehead and works its way down the body. This is accompanied by itching and reddening of the skin. It may last up to three hours and occasionally longer than that. Every time another dose is taken thereafter there is less flush and in most cases after several weeks there is very little or no flushing. The degree of flushing depends upon the condition of the patient. As a rule alcoholics, elderly people, patients with cardiovascular problems and schizophrenics flush the least. I have seen many patients who did not start flushing until after they had been taking this vitamin for several years. This usually coincided with a sudden improvement in their clinical condition.

The flushing (vasodilatation) may be minimized by the following measures: ( 1) start with small doses such as 100 mg after each meal and gradually increase these as the patient becomes adjusted to the flush; ( 2) always take the vitamin after a meal, on a full stomach; ( 3) do not take it with a hot drink such as tea or coffee -- hot drinks increase the rate of absorption in the stomach and increases the intensity of the flush; ( 4) take one aspirin each day for three or four days before starting the niacin -- it will not be needed after that; ( 5) take an antihistamine one hour before taking the niacin; ( 6) use niacin esters such as inositol niacinate -- there is very little flush with this preparation; (7) use slow release niacin -- these preparations are not as safe as the pure niacin and there have been a few dangerous reactions to this form; I have not seen any undesirable reactions in Canada to any of the slow-release preparations. However it appears that it is best for the nia cin to be released in the stomach into an acid medium rather than into the small intestine into an alkaline medium. I suspect that the further down the gastrointestinal tract it is released, the greater is the chance for undesirable reactions. I recommend that niacin in above gram doses be taken under medical supervision. Fortunately niacin is now recognized as one of the best substances for lowering cholesterol levels and most physicians will be familiar with it.

(B) Niacinamide -- This form of vitamin B-3 has a narrower dose range. Many fewer people can tolerate more than 6 grams daily before getting nausea. The most frequent dose is 3 grams daily. The decrease in tolerance for niacinamide is a disadvantage since many patients need more than 6 grams. If this is the case one can use smaller doses of both forms. Thus if 9 grams of total B-3 is needed, one can use 4-1/2 grams of each form. Each form will be below the dose which causes nausea but the total dose will be 9 grams.

I prefer to use niacinamide for young people who often cannot tolerate the niacin flush or for people who do not want to flush for cosmetic reasons. It might be embarrassing to flush in a social or business setting. Having both forms greatly increases the versatility of this vitamin as one can switch from one to the other depending upon the response. The indications are the same except that niacinamide does not lower cholesterol and probably does not have the same beneficial cardiovascular effects.

Pyridoxine, Vitamin B-6

This is the second most frequent member of the B vitamins used by orthomolecular therapists. At first it was used empirically. Clinical studies by Dr. A. Cott and Dr. B. Rimland had shown that patients treated with this vitamin responded better to treatment. Later Dr. C C. Pfeiffer and his colleagues at the Brain Bio Center, Princeton, demonstrated the need for high doses of this vitamin was caused by the presence of large amounts of kryptopyrole (kp) in the urine and/or by the presence of easily seen clinical symptoms and signs. Kryptopyrole was originally discovered in my laboratory about 30 years ago when we were looking for the schizophrenic biochemical factor that would lead to better diagnosis and treatment. We called it the mauve factor because it colored mauve when it was developed on the paper chromatogram. Kryptopyrole binds with zinc and with pyridoxine producing a double deficiency. Pyridoxine given in large enough doses will lower the amount of kp in the urine and w ill at the same time hasten the therapeutic effect of the regimen. This urine test is easily done in any hospital or private laboratory. If the test is not available the clinical examination of the patient will indicate when more vitamin B-6 is needed. One examines the patient for white chalky areas in the nails, stretch marks on the body, changes in the skin, increase in symptoms in the premenstrual phase and psychological changes.

For patients suffering from infantile autism the most important vitamin is vitamin B-6 (Rimland(8)). For people who are well or nearly well and who wish to ensure they will have enough I recommend 50 to 100 mg daily. For specific indications I recommend between 100 and 500 mg daily. Larger doses have been used but they are seldom needed. In children it may be necessary to also use magnesium to prevent the pyridoxine from activating the child.

There are very few side effects. The ones that do occur are minor and transient. Much has been made of the few patients collected from several medical schools who took between 2000 and 6000 mg per day. The paper describing these results was inadequate because it did not describe whether they were taking any other nutrients and what type of diet they were on. These patients developed a peripheral neuropathy which cleared after a year. But based on this report the idea became current that vitamin B-6 was toxic. Marks wrote, "It has been claimed that high doses of pyridoxine can lead to liver damage, interference with the normal functions of riboflavin and a dependency state. With the possible exception of the dependency states these suggestions are not substantiated by scientific data. The dependency states were very transient."

Ascorbic Acid (Vitamin C)

Many physicians had been using megadoses of this vitamin for many years, but little attention was given to it until Dr. Linus Pauling popularized it with his book, Vitamin C and the Common Cold.(10) Dr. I. Stone had aroused Dr. Pauling's interest.(11)

Every human suffers from subclinical scurvy, from a deficiency of ascorbic acid. We can not make any in our bodies, and the amount present in even the best possible diet will not provide more than 100 mg per day. This amount is totally inadequate for optimum health. There is therefore no need to ask the question, "Do I need any vitamin C?" The only question is how much is needed. There are many clues in nature. Of these the best is the amount of vitamin C which animals make in their body normally and also under severe stress; animals are able to convert glucose into vitamin C. They make much more than we take in from our food. Thus a goat, weighing about as much as a man, will make 14 grams per day. Apparently all animals that make vitamin C make about the same amount per kg of body weight.

Since we lost the capability of making vitamin C about 25 million years ago, our bodies have had to adapt to chronic deficiency after we moved from a food supply that did provide adequate amounts of vitamin C. But the cost of this adaptation is very high. We are still paying the price, but we no longer have to since synthetic ascorbic acid is very cheap and every person could take ample quantities to replace what nature took away from us. We are not as sick as if we had scurvy, but this is small consolation since scurvy is a terminal disease and I do not think we should be content with being so close to this terminal disease.

The oral dose ranges from 0 to 75 grams each day. Very few can tolerate those extremely high doses because it exceeds the laxative dose. The majority of people can take up to 12 grams per day. However it is best to think in terms of the optimum tolerable dose which each person must determine for themselves. When more vitamin C is taken than that individual can absorb from the gastrointestinal tract, it causes increased formation of gas and the bowel contents become very fluid. If the dose greatly exceeds this level diarrhea will develop.

The ideal dose has optimum functions in the body without causing any effect on bowel except to help regulate it. It is a very good laxative. Since at least one-third of the population over 65 is constipated, it would seem to me to be wise for all elderly people to control this problem not only by consuming enough fiber but also by taking enough vitamin C. This is done by starting with doses of 3 to 6 grams each day and gradually increasing it until the sublaxative dose is reached. Then the dose is decreased to just below this level. If the laxative level is 20 grams, the optimum oral level will be around 18 grams.

Dr. R. Cathcart discovered and first reported that the more the body needs the vitamin, the more it can tolerate. I have observed the same as have almost all orthomolecular physicians. My own optimum dose has ranged between 3 and 30 grams daily depending on my state of health. If a lot more is needed it is possible to train the body to accept more. Some AIDS cases in Australia have been trained to take 200 grams daily. However, if the higher doses can not be reached, it may be necessary to take intravenous vitamin C. When given in IV drip up to 200 grams can be given over several hours without any gastrointestinal effect.

Vitamin C is a weak organic acid, comparable to lemon juice. Compared to the strong acid present in the stomach the addition of any amount of ascorbic acid makes a minor contribution to the stomach fluid acidity. However a few do not like the sour taste. For this reason it is fortunate that the salts of ascorbic acid are available. They are sodium ascorbate, potassium ascorbate, calcium ascorbate, etc. A few preparations on the market contain a variety of these salts of vitamin C. They are called mineral ascorbates. They do represent an improvement over the straight ascorbic acid which is never present in nature as the pure acid, as it is in tablets, but is associated with other nutrients. I have found a very small number of people, fewer than twenty seen over the past 30 years, who cannot tolerate any amount of vitamin C. They have developed an allergy or idiosyncrasy to either the synthetic vitamin C or to some Of the other ingredients of the preparations. They might try prep arations made from other sugar sources. The common vitamin C is made from corn syrup. It is preferable to take the vitamin several times per day to decrease the amount lost in the urine.

Opponents of the use of vitamin C claim that taking more than a few milligrams per day is useless since the vitamin C is excreted into the urine. They cynically refer to the urine rich in vitamin C. This, of course, is a foolish argument that only those ignorant of how vitamin C is absorbed and excreted could use. It is, however, better to enrich the environment with vitamin C than with antibiotics and other drugs which most physicians do without compunction. They ignore the fact that in most cases enough of any therapeutic compound must be given before it can be therapeutic, and that this means allowing a major part to appear in the urine. If a person is given 50 grams per day of penicillin to save his life, most of that also appears in the urine. With vitamin C it has been shown that the more that is taken into the body, the greater the amount which is retained and used by the body. In our early research we found we could inject chronic schizophrenics with 90 grams of vitamin C and could find none in the urine. If the dose is I gram, a fraction of that will be retained. If the dose if 10 grams, many grams will be excreted but conversely many grams will be retained. To increase the retention the dose must be increased.

Mineral Supplements

Copper and Zinc

There is an inverse ratio between copper and zinc levels in the blood. It is thus best to measure both when testing for adequacy. Because of the almost ubiquitous use of copper plumbing, copper deficiency tends to be quite rare in most areas, whereas copper excess is more common. I have found that the blood copper levels increase with age beyond age 40, and that the rate of increase is dependent upon the degree of memory disturbance. Elderly senile patients have much more copper relative to an absolute level and relative to zinc.

Low zinc levels will cause changes in sense of taste, which if extreme can be life threatening. Patients simply stop eating because the food tastes so awful. It is also associated with some cases of schizophrenia, and with children with learning and behavioral disorders. A combination of zinc and vitamin B-6 deficiency may cause changes in the skin, hair and nails including white areas in the body of the nail, stretch marks, as well as PMS and psychiatric changes.

I have not found any cases of copper deficiency but advise my patients not to take multimineral preparations if they contain more than one mg of copper. To supplement with zinc I use any of the common preparations which usually provide about 30 to 50 of zinc daily. Sometimes it may have to be given in solution as the zinc sulfate solution, usually 10%. Pharmacists can easily make up these solutions.

Linus Pauling's book, How To Live Longer and Feel Better(12) is one of the best books which describes orthomolecular treatment. For physicians I have prepared a different type of outline.(13)

Xenobiotic Treatment

By the time I see the schizophrenic patients they have already been placed on a number of drugs including tranquilizers and antidepressants. Often combined treatment is essential. I use the drugs to achieve rapid control, and the orthomolecular component for recovery. When patients are well the drugs are slowly removed. Some will require very small doses of medication, usually not enough to make it impossible for them to be well. On tranquilizers alone no one recovers even though their symptoms are relieved. I have yet to see one patient on tranquilizers alone who is practicing medicine or law, or piloting a plane.

Results of Treatment

Early Cases -- The sooner treatment is started the better are the results. With my colleagues I have published a large number of studies including copious case histories. We have described the results of four double blind controlled experiments. These were the first ever done in psychiatry and probably the first in North America in medicine.(14)

Based upon four double blind controlled therapeutic trials and upon clinical experience since 1951 on over 5000 schizophrenic patients, I expect that 90% will be well after one year of treatment. Most of the readers of this journal are physicians. They will be interested in knowing that physicians can also become schizophrenic, and when they do and are treated with drugs only, about 15% become well enough to practice unassisted by their wives who are nurses. I am personally familiar with and have treated some 17 young patients who became schizophrenic. They were treated with orthomolecular methods, recovered, went to college, became physicians and psychiatrists and are well this day. One became president of a very large psychiatric association without any of the members, most of them opposed to vitamins, knowing he had been so treated. One is a research psychiatrist. One is chairman of a large university clinical department, and the rest are practicing medicine and psychiatry. M y definition of well includes being free of symptoms and signs, getting on well with the family and community and paying income tax.

Chronic Schizophrenia -- It takes a lot longer and much more patience to help these patients become well. I have under my care about 500 chronic patients. Recently I re-examined a sample of 27, selected more or less at random as they kept coming in to be seen again. Some I see every year or two, a few more often. They had been sick on average 7 years before they came to see me, having failed every standard treatment. They have remained on the program at least ten years. Of the 27, 17 are well, the rest much better, none are worse. One example is a woman who set her house on fire during a psychotic rage. She now operates her own business and supervises 14 workers. Another example is a man who failed treatment in Toronto for several years, drifted to Victoria, lived on the streets for several months. He recovered and earned a B.A. at a local university.

Conclusion

My greatest regret is that schizophrenics have been deprived of a chance to recover, i.e. have been condemned to a lifetime of disability. The costs to the patient and their families have been immense. The cost to the community is over 2 million dollars over the lifetime of their disease. The psychiatric community has persuaded itself that this work I have described has not been repeated. There have been a few studies which had not duplicated the protocal orthomolecular physicians have used, and they have failed. Every investigator who has repeated our work has confirmed these results.

References
(1.) Hoffer, A & Osmond, H: The Hallucinogens. Academic Press, New York, 1967.

(2.) Dhalla, K.S., Ganguly, P.K., Rupp. B., Beamish, R.E. & Dhalla, N.S. Mol Cell Biochem 87:85 -- 92, 1989.

(3.) Dhalla, N.S., Yates, J.C., Naimark, B., Dhalla, K.S., Beamish, R.E. & Ostadal, B. Cardiotoxicity of Catecholamines and Related Agents. Cardiovascular Toxicology. Second Edition Edited by Daniel Acosta, Jr, Raven Press, Ltd. New York 1992.

(4.) Pauling, L. Orthomolecular Psychiatry: 160, 265 271, 1968.

(5.) Pauling, L. Itano,H.A. Singer, S.J. et al: Sickle cell anemia, a molecular disease. Science 110, 5643 -- 548, 1949.

(6.) Hoffer A, Osmond H, Callbeck MJ & Kahan I: Treatment of Schizophrenia with Nicotinic Acid and Nicotinamide. J Clin Exper Psychopathol 18:131-158, 1957.

Hoffer A, & Osmond, H: The Chemical Basis of Clinical Psychiatry. C. C. Thomas, Springfield, IL, 1960.

Hoffer, A: Niacin Therapy in Psychiatry. C. C. Thomas, Springfield, IL, 1962.

Osmond, H & Hoffer, A: Massive Niacin Treatment in Schizophrenia. Review of a Nine-Year Study. Lancet 1:316-320, 1963.

Hoffer A, & Osmond H: Treatment of Schizophrenia with Nicotinic Acid -- A Ten Year Follow-Up. Acta Psychiat Scand 40:171-189, 1964.

Hoffer, A & Osmond H: How To Live With Schizophrenia. University Books, New York, NY, 1966. Also published by Johnson, London, 1966. Written by Fannie Kahan. New and Revised Ed. Citadel Press, New York, N.Y. 1992

Hoffer, A: Use of Nicotinic Acid and/or Nicotinamide in High Doses to treat Schizophrenia. Can J Psychiatric Nursing 76:5-6, 1966.

Hoffer, A: Safety, Side Effects and Relative Lack of Toxicity of Nicotinic acid and Nicotinamide. Schizophrenia 1:78-87, 1969.

(7.) Hoffer, A:Vitamin B-3 (Niacin). Keats Pub, New Canaan CT, 1984.

Hoffer, A:Vitamin B-3 (Niacin) Update. New Roles For a Key Nutrient in Diabetes, Cancer, Heart Disease and Other Major Health Problems. Keats Pub, Inc. New Canaan, Conn. 1990.

Hoffer, A. Niacin, Coronary Disease and Longevity. J Orthomolecular Medicine 4:211-220, 1989.

(8.) Rimland, B. Callaway, E. & Dreyfus, P. The effect of high doses of vitamin B-6 on autistic children; a double blind cross-over study. Amer J of Psychiatry 135: 472475, 1978.

(9.) Marks, J. Vitamin Safety. Vitamin Information Status Paper, F. Hoffman La Roche & Co. Basle 1989.

(10.) Pauling, L.Vitamin C and the Common Cold, W.H. Freeman and Co. San Francisco, 1970

(11.) Stone, I. The Heating Factor, Vitamin C Against Disease. Grosset and Dunlap, New York, 1972

(12.) Pauling, Linus. How To Live Longer and Feel Better. W.H. Freeman and Co, New York, 1986.

(13.) Hoffer, A: Orthomolecular Medicine for Physicians. Keats Pub, New Canaan, CT, 1989.

(14.) Hoffer, A, Osmond, H, Callbeck MJ & Kahan I: Treatment of Schizophrenia with Nicotinic Acid and Nicotinamide. J Clin Exper Psychopathol 18:131-158, 1957.

Osmond, H & Hoffer, A: Massive Niacin Treatment in Schizophrenia. Review of a Nine-Year Study. Lancet 1:316-320, 1963.

Hoffer, A & Osmond, H: Treatment of Schizophrenia with Nicotinic Acid -- A Ten Year Follow-Up. Acta Psychiat Scand 40:171-189, 1964.

Hoffer, A & Osmond, H: How To Live With Schizophrenia. University Books, New York, NY, 1966. Also published by Johnson, London, 1966. Written by Fannie Kahan. New and Revised Ed. Citadel Press, New York, N.Y. 1992.

Hoffer, A: The Effect of Nicotinic Acid on the Frequency and Duration of Re-Hospitalization of Schizophrenic Patients; A Controlled Comparison Study. Int J Neuropsychiatry 2:234-240, 1966.

Hoffer, A: Treatment of Schizophrenia with a Therapeutic Program Based Upon Nicotinic Acid as the Main Variable. Molecular Basis of Some Aspects of Mental Activity, Vol II. Ed. O Walaas, Academic Press, New York, 1967.

Hoffer, A: Megavitamin B-3 Therapy for Schizophrenia. Can Psychiatric Assn J 16:499-504, 1971. Hoffer, A,: Chronic Schizophrenic Patients Treated Ten Years Or More. J. Orthomolecular Medicine Vol 9, 7-37, 1994.

Townsend Letter for Doctors & Patients.

~~~~~~~~

By A. Hoffer

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