Vitamin B-3 and Schizophrenia


Many schizophrenic patients or their families call me seeking an orthomolecular physician, or preferably, psychiatrist. I refer them to the closest physician, often practising hundreds of miles from their home. Many are helped. Some are not, and when they call me back I learn that the physician has done a fine job of advising them, but in almost every case has not given them high enough doses of vitamin B-3. This is confirmed by the few patients who arrive in my office from the United States. For many, all that is needed is to increase the dose to the amount I have been recommending - going back now at least 50 years. This is described in my new book[ 1] and latest outline of the treatment program.[ 2]

I remain surprised at the reluctance of my colleagues to use the proper doses. With schizophrenia there is a clear dose response and if the dose is below the therapeutic level, even if only one gram below, there will be little response. I have seen my patients on 3 grams per day for months show no response, but after doubling that dose to 2 grams afar each of three meals there was a sudden and marked improvement.

I think the reason is that there is the pervasive idea in medicine that niacin, and to a lesser degree niacinamide, is liver toxic. I will discount the mythology that some doctors adhere to that it causes kidney damage etc. Where has the notion come from that it is liver toxic? Once it hit the textbooks every new edition and every new book simply repeats the old idea without re-examining the data upon which it was first based.

Over fifty years ago toxicity trials on rats with niacin showed that the LD50 was about 4.5 grams per kilogram of rat. For a 60 kilogram human this means that it is nearly half a pound per person per day. Of course this quantity is simply impossible to ingest, would cause severe nausea and vomiting, and probably would be toxic for many. One of my young female schizophrenic patients in a fit of anger swallowed the whole bottle of niacin, 200 tablets, 500 milligrams each. She had a sore stomach for three days. But these extraordinarily high, dangerous doses are much higher than the recommended dosage which usually are under 10 grams per day, most often between 3 and 6 grams daily. These are the recommended doses for niacin to lower cholesterol levels, to lower triglyceride levels, to lower lipoprotein A and to elevate HDL. When the rats were sacrificed they were found to have fatty livers, i.e. about 10% of their livers were fat. About this time the methyl deficiency syndrome was popula r. Fatty livers are characteristic of this syndrome.

About ten years later, my colleague in showing that niacin lowered cholesterol, Professor R. Altchul MD, Chairman Department of Anatomy, University of Saskatchewan at Saskatoon, repeated the 1945 rat-niacin-toxicity studies and found that in his experiment no fatty livers were found. I asked him why the difference. He replied that in 1945 almost all laboratory rat colonies were infected with viruses. It was soon known that niacin combines with methyl groups. It is one of the few good methyl acceptors in the body. Therefore it made sense to look upon niacin as a potential cause of fatty livers because it could bind to many methyl groups and thus induce the deposits of fat into the liver. Later on, when the liver enzyme tests became more common, it was found that in some patients taking niacin, these test results were elevated. This was considered a forerunner of liver damage and was a major worry for many physicians, especially those who did not like niacin anyway. Other physicians, wh o used it for restoring normal blood lipid levels, were much less concerned although they were aware of the possibility, and often they would run liver function tests before and after.

The combination of theory and the increase in liver function test values combined with the belief that any increase in these values indicates liver damage, keeps alive the suspicion that niacin is dangerous and must be given only in small amounts. As happens so often, hypothesis and reality are altogether different. Clinical observations are the important facts, not conjectures based on these hypotheses, no matter how well-founded they appear to be, for it often turns out that these hypotheses are wrong and should be revised in view of the clinical data.

The causal relationship between niacin therapy and liver damage was examined by the most knowledgeable physician in the world. Dr. William B. Parsons Jr. was the first physician to study our prior claim that niacin lowered cholesterol levels. He has studied it ever since, since 1956. He was a senior resident at the Mayo Clinic, Rochester, and started a substantial number of patients with hypercholesterolemia on niacin. His results confirmed ours. The first two papers he published with his colleagues firmly established niacin's value and eventually led to niacin being the first vitamin to be approved by the FDA to be used in mega doses. This liberated niacin for other indications as well. Later Bill Parsons was medical director of Armour and Company whose product is Nicobid. He still practices medicine. His many papers describing the results culminated in his recent excellent book.[ 3]

Dr. Parsons was fully aware of the hypothesis that niacin could be liver-toxic. After his first 18 patients had been on the niacin for one year, liver biopsies were done on each one and they were all normal. After two years a few patients showed some abnormality in these tests. But these were caused by various slow-release preparations then being studied. But two weeks after these substances were omitted the liver function tests were normal. Later, he found the results were normal after one week, and finally he found that when these preparations were replaced by plain niacin without any washout period the results were normal one week later. Normally, when liver is damaged as with alcohol cirrhosis or liver damage from chemicals, it is considered fortunate if the results are normal in six months. These results convinced Bill Parsons that the abnormal results represented changes in liver function rather than in anatomic liver changes. This was the first indication that abnormal tests do not necessarily mean damage to hepatic cells with recognizable microscopic changes. Since then the FDA has recognized many substances which may cause minor changes in hepatic function tests with no clinical significance. They are examples of induced microsomal enzyme activity.

Further, the Coronary Drug project provided the next demonstration of niacin's safety. In this study 1100 post-coronary men received niacin for five to eight years. Dr. Paul Canner, head statistician for this study, told Bill Parsons that there were no abnormalities which could be attributed to niacin. Niacin was the only substance which increased longevity by two years and decreased the death rate by 11%. Bill concluded that minor elevations in enzyme tests reflecting liver function are a normal part of niacin therapy and are not a reason to discontinue treatment. If the enzyme results exceed two to three times the upper limit of normal, the changes are significant and require discontinuation of niacin, resuming later at a lower dosage. Bill further recommends a liver test be done after the correct dose has been found. The test can be done with annual examinations. In my opinion doing these liver function tests may be more protective to the physician than to the patient. I advise phy sicians who refer to me that if they wish to do the test they discontinue the niacin for five days. By then the enhancing effect of niacin on liver function enzymes is gone. Is there any positive value in the enhanced activity of these enzymes? No one has examined this possibility.

Finally, Bill Parsons, in searching the literature, found only 18 cases with varying degree of liver problems. Two were serious and irreversible. He added, "Not bad for a drug used for more than 40 years, with more widespread use in recent years, much of it as a result of the NCEP guidelines of 1988 and 1993."

I have given niacin to more than 5,000 patients since 1952. I can recall a handful of cases of jaundice which promptly cleared when the niacin was discontinued. In one case when the niacin was stopped the schizophrenia came back. I resumed the niacin and the jaundice did not recur. This suggests that the few cases of jaundice in patients taking niacin have to be examined very seriously to determine what other factors were causal. Maybe the jaundice was coincidental. There are no double blind controlled studies showing a connection. Plain ordinary niacin is effective and non-toxic. Some sustained release preparations are not quite as safe. I have seen no Canadian reports of any toxicity from the sustained release preparation available here. Inositol niacinate, as far as I know, does not elevate liver function test values.

Some clinicians avoid the increase in liver function tests by starting their patients on low doses and gradually increasing them. In almost all cases, elevated values will return to normal with continued use.

If you are going to treat schizophrenic patients effectively, please use the correct dose. Too low doses are more dangerous to the patient than the correct dose. Anything under 1.5 grams daily is probably futile, but this is a good starting-level. As the dose increases watch for nausea, and if this is not controlled (and is rare), vomiting. Children will not tell you they are nauseated. They simply lose their appetite. When these symptoms do appear, the niacin is stopped for a day or two and resumed at a lower level. If the nauseant dose is too low for either form of vitamin B-3, one can use both together. Thus, if the nauseant dose is 2 grams daily one can give the correct 3 grams dose of vitamin B-3 by using 500 milligrams of each three times daily. Children will tolerate these doses as well as adults.[ 4] David Hawkins, many years ago, suggested that the sub-nauseant dose of niacin is the optimum dose in the same way that, according to Robert Cathcart, the sub-laxative dose of ascorbic acid is the optimum dose. Usually the sub-nauseant dose is much higher for niacin than it is for niacinamide. I do not know what it is for inositol niacinate.

I think there is little difference in effectiveness of the three current forms. I think if there is a difference it favors plain niacin, followed by inositol niacinate and lastly niacinamide. The vasodilater reaction, the flush, appears to have some therapeutic value, especially in cases of chronic fatigue syndrome where vasodilation of capillaries is helpful.

Here is another anecdote of a long term followup using vitamin B-3. I received a letter from a man who started out by writing "I am one of your successes." He was a very disturbed high school dropout in 1971, suffering from schizophrenia. I saw him over a one-and-a-half year period. He completed high school, was the graduating class valedictorian. He is happily married (1999) with three children. He is a writer, a producer of television shows, and he is contemplating making a movie of his own recovery and the role I played in it.

He meets my definition of recovery: ( 1) Free of symptoms and signs, ( 2) Getting on well with family, ( 3) Getting on well with the community, and ( 4) Paying income tax. His recovery saved his province $2 million over his lifetime, the cost of schizophrenic patients to the community, whether untreated, or treated with tranquilizers only. If any reader knows the details of any schizophrenic patient who has shown the same degree of recovery, of wellness, please write to me. I am starting a collection of tranquilizer recoveries where orthomolecular therapy was not used. I know of one case so far.


A. Hoffer MD, PhD, FRCP(C), Suite 3 - 2727 Quadra Street, Victoria, BC V8T 4E5, Canada

250-386-8756/Fax 250-386-5828

1. Hoffer A: Vitamin B-3 and Schizophrenia: Discovery, Recovery. Controversy. Quarry Press, Kingston, ON, 1999.

2. Hoffer A: Orthomolecular Treatment For Schizophrenia. Keats, 4255 West Touhy Avenue, Lincolnwood IL 60646-1975, 1999.

3. Parsons WB Jr: Cholesterol Control Without Diet: The Niacin Solution. Lilac Press, Scottsdale AZ, 1998.

4. Hoffer A: Dr Hoffer's ABC of Natural Nutrition for Children. Quarry Press, Kingston ON, 1999.

Vitamin B3 and Liver Toxicity


This is to inform you that I have reviewed Dr. Abram Hoffer's draft paper, entitled Vitamin B-3 and Schizophrenia. This paper focuses mainly upon the alleged liver toxicity of Niacin (one of the forms of vitamin B3) and refutes the case against such toxicity.

I am a Family Doctor who has been in practice since 1970, and have had as part of my practice Orthomolecular Medicine since 1974. Since 1976 I have given papers at many international meetings, and have had published over a hundred items, scientific papers, editorials and other articles.

I am able to inform you that I have administered Niacin to several hundred patients over the past 26 years, not as many as Dr. Hoffer. I used the Niacin as therapy for patients with Schizophrenia, cardiovascular disease, and as an aid in the therapy of cancer. However, my experience reflects the evidence cited by Dr. Hoffer.

I have seen only one case of a patient apparently developing jaundice while taking Niacin. This was a patient in her 70's who was suffering from circulatory problems. She was also malnourished. Because of this last I also prescribed a potent multivitamin product. Some weeks later her skin turned yellow and she began passing yellow urine. She was admitted to our local hospital on my behalf by another doctor. Testing of her liver function showed some abnormalities of liver enzymes but far from those which could account for the apparent jaundice. Specifically, her serum bilirubin was in the near normal range. I then realised that the yellow urine was due to the Riboflavin in the multivitamin product. Stopping all the vitamins resulted in a complete clearance of the yellow colour of her skin. Her liver function tests returned to normal within a few days. Unfortunately she could not be persuaded to resume taking the Niacin, and she died within the year of complications of her circulatory p roblems.

Dr. Hoffer has not mentioned another specific indication for the use of Niacin.

Until the coming of the angiotensin converting enzyme (ACE) inhibitors, without exception, all patients developing cardiac failure died within five years no matter how aggressively they were treated conventionally (diuretics and Digoxin). Long before the advent of the ACE inhibitors I had a patient in his early 80's who developed cardiac failure. I treated him conventionally but he deteriorated quite rapidly. I offered him Niacin 1000 mg three times per day after meals, feeling that he had nothing to lose, and that its effects on his circulation might slow down his deterioration. In fact, within a matter of weeks his shortness of breath and anginal chest pains on exertion became very much better. He resumed his chosen, active lifestyle for about six years. Then he began deteriorating again. He chose to try to increase the dose of Niacin but this did not help. He died quite suddenly at the age of 91, eight years after starting to take the Niacin. He showed no sign of liver toxicity in all those years despite being a former alcoholic. Niacin does increase uric acid levels in those patients prone to gout but it does not cause gout, nor have I been able to find any cases in the medical literature which I have seen of kidney damage caused by uric acid in patients taking Niacin. In diabetic patients the blood glucose does go up if Niacin is taken but the most feared complications of diabetes are those to the small blood vessels (causing myocardial infarcts, strokes, blindness, kidney failure, and gangrene of the lower limbs), which Niacin helps to prevent.

One final word about the issue of Niacin versus the statin drugs - Niacin is far more cost effective than the statins. Depending on the particular statin drug, the cost to prevent one heart attack ranges between $50,000 and $135,000. In other words no patient taking a statin drug can be promised any benefit at all apart from a lowering of the cholesterol level, which means nothing. The cost of Niacin to prevent one heart attack is, by contrast, a matter of a few hundred dollars even though its cholesterol lowering effect is not as strong as the statins. In other words, the individual patient taking Niacin can be promised benefit, and the benefit continues for years even after the patient stops taking it.

Erik T. Paterson, MB, ChB, DObstRCOG, FBIS, 12-1,000, Northwest Boulevard, Creston, BC V0B 1G6 Canada

250-428-7887 / Fax 250-428-7171


By A. Hoffer

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