| Vitamin B-3: Niacin and Its
Amide by A. Hoffer, M.D., Ph.D.
Victoria, British Columbia, Canada
The first water soluble vitamins were numbered in
sequence according to priority of discovery. But after their chemical
structure was determined they were given scientific names. The
third one to be discovered was the anti-pellagra vitamin before
it was shown to be niacin. But the use of the number B-3 did not
stay in the literature very long. It was replaced by nicotinic
acid and its amide (also known medically as niacin and its amide).
The name was changed to remove the similarity to nicotine, a poison.
The term vitamin B-3 was reintroduced by my friend
Bill W., co-founder of Alcoholics Anonymous, (Bill Wilson). We
met in New York in 1960. Humphry Osmond and I introduced him to
the concept of mega vitamin therapy. We described the results
we had seen with our schizophrenic patients, some of whom were
also alcoholic. We also told him about its many other properties.
It was therapeutic for arthritis, for some cases of senility and
it lowered cholesterol levels. Bill was very curious about it
and began to take niacin, 3 g daily. Within a few weeks fatigue
and depression which had plagued him for years were gone. He gave
it to 30 of his close friends in AA and persuaded them to try
it. Within 6 months he was convinced that it would be very helpful
to alcoholics. Of the thirty, 10 were free of anxiety, tension
and depression in one month. Another 10 were well in two months.
He decided that the chemical or medical terms for this vitamin
were not appropriate. He wanted to persuade members of AA, especially
the doctors in AA, that this would be a useful addition to treatment
and he needed a term that could be more readily popularized. He
asked me the names that had been used. I told him it was originally
known as vitamin B-3. This was the term Bill wanted. In his first
report to physicians in AA he called it "The Vitamin B-3 Therapy."
Thousands of copies of this extraordinary pamphlet were distributed.
Eventually the name came back and today even the most conservative
medical journals are using the term vitamin B-3. Bill became unpopular
with the members of the board of AA International. The medical
members who had been appointed by Bill, felt that he had no business
messing about with treatment using vitamins. They also "knew"
vitamin B-3 could not be therapeutic as Bill had found it to be.
For this reason Bill provided information to the medical members
of AA outside of the National Board, distributing three of his
amazing pamphlets. They are now not readily available.
Vitamin B-3 exists as the amide in nature, in nicotinamide
adenine dinucleotide (NAD). Pure nicotinamide and niacin are synthetics.
Niacin was known as a chemical for about 100 years before it was
recognized to be vitamin B-3. It is made from nicotine, a poison
produced in the tobacco plant to protect itself against its predators,
but in the wonderful economy of nature which does not waste any
structures, when the nicotine is simplified by cracking open one
of the rings, it becomes the immensely valuable vitamin B-3.
Vitamin B-3 is made in the body from the amino acid
tryptophan. On the average 1 mg of vitamin B-3 is made from 60
mg of tryptophan, about 1.5% Since it is made in the body it does
not meet the definition of a vitamin; these are defined as substances
that can not be made. It should have been classified with the
amino acids, but long usage of the term vitamin has given it permanent
status as a vitamin. The 1.5% conversion rate is a compromise
based upon the conversion of tryptophan to N-methyl nicotinamide
and its metabolites in human subjects. I suspect that one day
in the far distant future none of the tryptophan will be converted
into vitamin B-3 and it then will truly be a vitamin. According
to Horwitt,1 the amount converted is not inflexible but varies
with patients and conditions. For example, women pregnant in their
last three months convert tryptophan to niacin metabolites three
times as efficiently as in non-pregnant females. Also there is
evidence that contraceptive steroids, estrogens, stimulate tryptophan
oxygenase, the enzyme that converts the tryptophan into niacin.
This observation raises some interesting speculations.
Women, on average, live longer then men. It has been shown for
men that giving them niacin increases their longevity.2 Is the
increased longevity in women the result of greater conversion
of tryptophan into niacin under the stimulus of their increase
in estrogen production? Does the same phenomenon explain the decrease
in the incidence of coronary disease in women?
The best-known vitamin deficiency disease is pellagra.
More accurately it is a tryptophan deficiency disease since tryptophan
alone can cure the early stages. Pellagra was endemic in the southern
U.S.A. until the beginning of the last world war. It can be described
by the four D's: dermatitis, diarrhea, dementia and death. The
dementia is a late stage phenomenon. In the early stages it resembles
much more the schizophrenias, and can only with difficulty be
distinguished from it. The only certain method used by early pellagrologists
was to give their patients in the mental hospitals small amounts
of nicotinic acid. If they recovered they diagnosed them pellagra,
if they did not they diagnosed them schizophrenia. This was good
for some of their patients but was not good for psychiatry since
it prevented any continuing interest in working with the vitamin
for their patients who did not recover fast, but who might have
done so had they given them a lot more for a much longer period
of time, the way we started doing this in Saskatchewan. I consider
it one of the schizophrenic syndromes.
Indications:
I have been involved in establishing two of the
major uses for vitamin B-3, apart from its role in preventing
and treating pellagra. These are its action in lowering high cholesterol
levels3 and in elevating high density lipoprotein cholesterol
levels (HDL), and its therapeutic role in the schizophrenias and
other psychiatric conditions. It has been found helpful for many
other diseases or conditions. These are psychiatric disorders
including children with learning and behavioral disorders, the
addictions including alcoholism and drug addiction, the schizophrenias,
some of the senile states.
Its efficacy for a large number of both mental and
physical conditions is an advantage to patients and to their doctors
who use the vitamin, but is difficult to accept by the medical
profession raised on the belief that there must be one drug for
each disease, and that when any substance appears to be too effective
for many conditions, it must be due entirely to its placebo effect,
something like the old snake oils. I have thought about this for
a long time and have within the past year become convinced that
this vitamin is so versatile because it moderates or relieves
the body of the pernicious effect of chronic stress. It therefore
frees the body to carry on its routine function of repairing itself
more efficiently. The current excitement in medicine is the recognition
that hyperoxidation, the formation of free radicals, is one of
the basic damaging processes in the body. These hyperexcited molecules
destroy molecules and damage tissues at the cellular level and
at the tissue level. All living tissue which depends on oxygen
for respiration has to protect itself against these free radicals.
Plants use one type of antioxidants and animals use another type.
Fortunately there is a wide overlap and the same antioxidants
such as vitamin C are used by both plants and animals. There is
growing recognition that the system adrenaline -> adrenochrome
plays a major role in the reactions to stress. I have elaborated
this in a further report for this journal.4
The catecholamines, of which adrenalin is the best
known example, and the aminochromes, of which adrenochrome is
the best known example, are intimately involved in stress reactions.
Therefore to moderate the influence of stress or to negate it,
one must use compounds which prevent these substances from damaging
the body. Vitamin B-3 is a specific antidote to adrenalin, and
the antioxidants such as vitamin C, Vitamin E, beta carotene,
selenium and others protect the body against the effect of the
free radicals by removing them more rapidly from the body. Any
disease or condition which is stress related ought therefore to
respond to the combined use of vitamin B-3 and these antioxidants
provided they are all given in optimum doses, whether small or
large as in orthomolecular therapy. I will therefore list briefly
the many indications for the use of vitamin B-3. For each condition
I will describe one case to illustrate the therapeutic response.
For each condition I can refer to hundreds and thousands
of case histories and have already in the literature described
many of them in detail.5
Psychiatric
1) The Schizophrenias. I have reviewed this for
this journal.6
2) Children with Learning and/or Behavioral Disorders.
In 1960 seven year-old Bruce came to see me with his father. Bruce
had been diagnosed as mentally retarded. He could not read, could
not concentrate, and was developing serious behavioral problems
such as cutting school without his parents' knowledge. He was
being prepared for special classes for the retarded. He excreted
large amounts of kryptopyrrole, the first child to be tested.
I started him on nicotinamide, one gram tid. Within four months
he was well. He graduated from high school, is now married, has
been fully employed and has been paying income tax. He is one
case out of about 1500 I have seen since 1960. Current treatment
is more complicated as described in this Journal.7
3) Organic Confusional States, non-Alzheimers forms
of dementia, electroconvulsive therapy-induced memory disturbances.
In 1954 I observed how nicotinic acid relieved a severe case of
post ECT amnesia in one month. Since then I have routinely given
it in conjunction with ECT to markedly decrease the memory disturbance
that may occur during and after this treatment. I would never
give any patient ECT without the concomitant use of nicotinic
acid. It is very helpful, especially in cardiovascular-induced
forms of dementia as it reverses sludging of the red blood cell
and permits proper oxygenation of the cells of the body. For further
information see Niacin Therapy in Psychiatry.8 In September 1992,
Mr. C., 76 years-old, requested help with his memory. He was terribly
absentminded. If he decided to do something, by the time he arrived
where he wanted to do it he had forgotten what it was he wanted
to do. His short-term memory was very poor and his long-term memory
was beginning to be affected. I started him on a comprehensive
vitamin program including niacinamide 1.5 G daily. Within a month
he began to improve. I added niacin to his program. By February
1993 he was normal. April 26, 1993, he told me he had been so
well he had concluded he no longer needed any niacin and decreased
the dose from 3.0 G to 1.5 G daily. He remained on the rest of
the program. Soon he noted that his short term memory was failing
him again. I advised him to stay on the full dose the rest of
his life.
4) An antidote against d-LSD,9,10 and against adrenochrome.5
5) Alcoholism. Bill W. conducted the first clinical
trial of the use of nicotinic for treating members of Alcoholics
Anonymous.11 He found that 20 out of thirty subjects were relieved
of their anxiety, tension and fatigue in two months of taking
this vitamin, 1 G tid. I found it very useful in treating patients
who were both alcoholic and schizophrenic. The first large trial
was conducted by David Hawkins who reported a better than 90%
recovery rate on about 90 patients. Since then it has been used
by many physicians who treat alcoholics. Dr. Russell Smith in
Detroit has reported the largest series of patients.12
Physical
1. Cardiovascular Of the two major findings
made by my research group in Saskatchewan, the nicotinic acid-cholesterol
connection is well known and nicotinic acid is used worldwide
as an economical, effective and safe compound for lowering cholesterol
and elevating high density cholesterol. As a result of my interest
in nicotinic acid, Altschul, Hoffer and Stephen3 discovered that
this vitamin, given in gram doses per day, lowered cholesterol
levels. Since then it was found it also elevates high density
lipoprotein cholesterol thus bringing the ratio of total over
HDL to below 5.
In the National Coronary Study, Canner2 showed that
nicotinic acid decreased mortality and prolonged life. Between
1966 and 1975, five drugs used to lower cholesterol levels were
compared to placebo in 8341 men, ages 30 to 64, who had suffered
a myocardial infarction at least three months before entering
the study. About 6000 were alive at the end of the study. Nine
years later, only niacin had decreased the death rate significantly
from all causes. Mortality decreased 11% and longevity increased
by two years. The death rate from cancer was also decreased. This
was a very fortunate finding because it led to the approval by
the FDA of this vitamin in mega doses for cholesterol problems
and opened up the use of this vitamin in large doses for other
conditions as well. This occurred at a time when the FDA was doing
its best not to recognize the value of megavitamin therapy. Its
position has not altered over the past four decades.
Our finding opened up the second major wave of interest
in vitamins. The first wave started around 1900 when it was shown
that these compounds were very effective in small doses in curing
vitamin deficiency diseases and in preventing their occurrence.
This was the preventive phase of vitamin use. The second wave
recognized that they have therapeutic properties not directly
related to vitamin deficiency diseases but may have to be used
in large doses. This was the second or present wave wherein vitamins
are used in therapy for more than deficiency diseases. Our discovery
that nicotinic acid was an hypocholesterolemic compound is credited
as the first paper to initiate the second wave and paved the way
for orthomolecular medicine which came along several years later.
Arthritis
2. I first observed the beneficial effects
of vitamin B-3 in 1953 and 1954. I was then exploring the potential
benefits and side effects from this vitamin. Several of the patients
who were given this vitamin would report after several months
that their arthritis was better. At first this was a surprise
since in the psychiatric history I had taken I had not asked about
joint pain. This report of improvement happened so often I could
not ignore it. A few years later I discovered that Prof. W. Kaufmann
had studied the use of this vitamin for the arthritides before
1950 and had published two books describing his remarkable results.13
Since that time this vitamin has been a very important component
of the orthomolecular regimen for treating arthritis.
The following case illustrates both the response
which can occur and the complexity of the orthomolecular regimen.
Patients who are early into their arthritis respond much more
effectively and are not left with residual disability.
K.V. came to my office April 15, 1982. She was in
a wheelchair pushed by her husband. He was exhausted, depressed,
and she was one of the sickest patients I have ever seen. She
weighed under 90 pounds. She sat in the chair on her ankles which
were crossed beneath her body because she was not able to straighten
them out. Her arms were held in front of her, close to her body,
and her fingers were permanently deformed and claw-like. She told
me she had been deeply depressed for many years because of the
severe pain and her major impairment. As she was being wheeled
into my office I saw how ill she was and immediately concluded
there was nothing I could do for her, and had to decide how I
could let her know without sending her even deeper into despair.
However I changed my mind when she suddenly said, "Dr. Hoffer,
I know no one can ever cure me but if you could only help me with
my pain. The pain in my back is unbearable. I just want to get
rid of the pain in my back." I realized then she had a lot of
determination and inner strength and that it was worthwhile to
try and help her. She began to suffer from severe pain in her
joints in 1952. In 1957 it was diagnosed as arthritis. Until 1962
her condition fluctuated and then she had to go into a wheelchair
some part of the day. She was still able to walk although not
for long until 1967. In 1969 she depended on the wheelchair most
of the time, and by 1973 she was there permanently. For awhile
she was able to propel herself with her feet. After that she was
permanently dependent on help. For the three years before she
saw me she had gotten some home care but most of the care was
provided by her husband. He had retired from his job when I first
saw them. He provided the nursing care equivalent to four nurses
on 8 hour shifts including holiday time. He had to carry her to
the bathroom, bathe her, cook and feed her. He was as exhausted
as she was but he was able to carry on.
She was severely deformed, especially her hands,
suffered continuous pain, worse in her arms, and hips and her
back. Her ankles were badly swollen and she had to wear pressure
bandages. Her muscles also were very painful most of the day.
She was able to feed herself and to crochet with her few useful
fingers, but it must have been extremely difficult. She was not
able to write nor type which she used to do with a pencil. A few
months earlier she had been suicidal. On top of this severe pain
and discomfort she had no appetite, was not hungry and a full
meal would nauseate her. Her skin was dry, she had patches of
eczema, and she had white areas in her nails. I advised her to
eliminate sugar, potatoes, tomatoes and peppers, (about 10% of
arthritics have allergic reactions to the solanine family of plants).
She was to add niacinamide 500 mg four times daily (following
the work of W. Kaufman), ascorbic acid 500 mg four times daily
(as an anti-stress nutrient and for subclinical scurvy), pyridoxine
250 mg per day (found to have anti-arthritic properties by Dr.
J. Ellis), zinc sulfate 220 mg per day (the white areas in her
nails indicated she was deficient in zinc), flaxseed oil 2 tablespoons
and codliver oil 1 tablespoon per day (her skin condition indicated
she had a deficiency of omega 3 essential fatty acids). The detailed
treatment of arthritis and the references are described in my
book.14
One month later a new couple came into my room.
Her husband was smiling, relaxed and cheerful as he pushed his
wife in in her chair. She was sitting with her legs dangling down,
smiling as well. I immediately knew that she was a lot better.
I began to ask her about her various symptoms she had had previously.
After a few minutes she impatiently broke in to say, "Dr. Hoffer,
the pain in my back is all gone." She no longer bled from her
bowel, she no longer bruised all over her body, she was more comfortable,
the pain in her back was easily controlled with aspirin and was
gone from her hips, (it had not helped before). She was cheerful
and laughed in my office. Her heart was regular at last. I added
inositol niacinate 500 mg four times daily to her program. She
came back June 17, 1982, and had improved even more. She was able
to pull herself up from the prone position on her bed for the
first time in 15 years, and she was free of depression. I increased
her ascorbic acid to 1 gram four times daily and added vitamin
E 800 IU. Because she had shown such dramatic improvement I advised
her she need no longer come to see me.
September 1, 1982, she called me on the telephone.
I asked her how she was getting along. She said she was making
even more progress. I then asked her how had she been able to
get to the phone. She replied she was able to get around alone
in her chair. Then she added she had not called for herself but
for her husband. He had been suffering from a cold for a few days,
she was nursing him, and she wanted some advice for him.
After another visit October 28, 1983, I wrote to
her doctor "Today Mrs. K.V. reported she had stayed on the whole
vitamin program very rigorously for 18 months, but since that
time had slacked off somewhat. She is regaining a lot of her muscle
strength, can now sit in her wheelchair without difficulty, can
also wheel herself around in her wheelchair but, of course, can
not do anything useful with her hands because her fingers are
so awful. She would like to become more independent and perhaps
could do so if something could be done about her fingers and also
about her hip. I am delighted she has arranged to see a plastic
surgeon to see if something can be done to get her hand mobilized
once more. I have asked her to continue with the vitamins but
because she had difficulty taking so many pills she will take
a preparation called Multijet which is available from Portland
and contains all the vitamins and minerals and can be dissolved
in juice. She will also take inositol niacinate 3 grams daily."
I saw her again March 24, 1988. About 4 of her vertebra
had collapsed and she was suffering more pain which was alleviated
by Darvon. It had not been possible to treat her hands surgically.
She had been able to eat by herself until six months before this
last visit. She had been taking small amounts of vitamins. She
was able to use a motorized chair. She had been depressed. I wrote
to her doctor, "She had gone off the total vitamin program about
two or three years ago. It is very difficult for her to swallow
and I can understand her reluctance to carry on with this. I have
therefore suggested that she take a minimal program which would
include inositol niacinate 3 grams daily, ascorbic acid 1 gram
three times, linseed oil 2 capsules and cod liver oil 2 capsules.
Her spirits are good and I think she is coming along considering
the severe deterioration of her body as a result of the arthritis
over the past few decades." She was last seen by her doctor in
the fall of 1989. Her husband was referred. I saw him May 18,
1982. He complained of headaches and a sense of pressure about
his head present for three years. This followed a series of light
strokes. I advised him to take niacin 3 grams daily plus other
vitamins including vitamin C. By September 1983 he was well and
when seen last March 24, 1988 was still normal.
Juvenile Diabetes
3. Dr. Robert Elliot, Professor of Child
Health Research at University of Auckland Medical School is testing
40,000 five-year old children for the presence of specific antibodies
that indicate diabetes will develop. Those who have the antibodies
will be given nicotinamide. This will prevent the development
of diabetes in most the children who are vulnerable. According
to the Rotarian for March 1993 this project began 8 years ago
and has 3200 relatives in the study. Of these, 182 had antibodies
and 76 were given nicotinamide. Only 5 have become diabetic compared
to 37 that would have been expected. Since 1988 over 20,100 school
children have been tested. None have become diabetic compared
to 47 from the untested comparable group. A similar study is underway
in London, Ontario.
Cancer
4. Recent findings have shown that vitamin
B-3 does have anti-cancer properties. This was discussed at a
meeting in Texas in 1987, Jacobson and Jacobson.15 The topic of
this international conference was "Niacin, Nutrition, ADP-Ribosylation
and Cancer," and was the 8th conference of this series.
Niacin, niacinamide and nicotinamide adenine dinucleotide
(NAD) are interconvertable via a pyridine nucleotide cycle. NAD,
the coenzyme, is hydrolyzed or split into niacinamide and adenosine
dinucleotide phosphate (ADP-ribose). Niacinamide is converted
into niacin, which in turn is once more built into NAD. The enzyme
which splits ADP is known as poly (ADP-ribose) polymerase, or
poly (ADP) synthetase, or poly (ADP-ribose) transferase.
Poly (ADP-ribose) polymerase is activated when strands
of deoxyribonucleic acid (DNA) are broken. The enzyme transfers
NAD to the ADP-ribose polymer, binding it onto a number of proteins.
The poly (ADP-ribose) activated by DNA breaks helps repair the
breaks by unwinding the nucleosomal structure of damaged chromatids.
It also may increase the activity of DNA ligase. This enzyme cuts
damaged ends off strands of DNA and increases the cell's capacity
to repair itself. Damage caused by any carcinogenic factor, radiation,
chemicals, is thus to a degree neutralized or counteracted.
Jacobson and Jacobson, conference organizers, hypothesized
that niacin prevents cancer. They treated two groups of human
cells with carcinogens. The group given adequate niacin developed
tumors at a rate only 10% of the rate in the group deficient in
niacin. Dr. M. Jacobson is quoted as saying, "We know that diet
is a major risk factor, that diet has both beneficial and detrimental
components. What we cannot assess at this point is the optimal
amount of niacin in the diet... The fact that we don't have pellagra
does not mean we are getting enough niacin to confer resistance
to cancer." About 20 mg per day of niacin will prevent pellagra
in people who are not chronic pellagrins. The latter may require
25 times as much niacin to remain free of pellagra.
Vitamin B-3 may increase the therapeutic efficacy
of anti-cancer treatment. In mice, niacinamide increased the toxicity
of irradiation against tumors. The combination of normobaric carbogen
with nicotinamide could be an effective method of enhancing tumour
radiosensitivity in clinical radiotherapy where hypoxia limits
the outcome of treatment. Chaplin, Horsman and Aoki16 found that
nicotinamide was the best drug for increasing radiosensitivity
compared to a series of analogues. The vitamin worked because
it enhanced blood flow to the tumor. Nicotinamide also enhanced
the effect of chemotherapy. They suggested that niacin may offer
some cardioprotection during long-term adriamycin chemotherapy.
Further evidence that vitamin B-3 is involved in
cancer is the report by Nakagawa, Miyazaki, Okui, Kato, Moriyama
and Fujimura17 that in animals there is a direct relationship
between the activity of nicotinamide methyl transferase and the
presence of cancer. Measuring the amount of N-methyl nicotinamide
was used to measure the activity of the enzyme. In other words,
in animals with cancer there is increased destruction of nicotinamide,
thus making less available for the pyridine nucleotide cycle.
This finding applied to all tumors except the solid tumors, Lewis
lung carcinoma and melanoma B-16.
Gerson18 treated a series of cancer patients with
special diets and with some nutrients including niacin 50 mg 8
to 10 times per day, dicalcium phosphate with vitamin D, vitamins
A and D, and liver injections. He found that all the cancer cases
were benefitted in that they became healthier and in many cases
the tumors regressed. In a subsequent report Gerson elaborated
on his diet. He now emphasized a high potassium over sodium diet,
ascorbic acid, niacin, brewers yeast and lugols iodine. Right
after the war there was no ready supply of vitamins as there is
today. I would consider the use of these nutrients in combination
very original and enterprising. Dr. Gerson was the first physician
to emphasize the use of multivitamins and some multiminerals.
More details are in Hoffer.19 Additional evidence that vitamin
B-3 is therapeutic for cancer arises from the National Coronary
Study, Canner.2
Concentration Camp Survivors
5. In 1960 I planned to study the efffect
of nicotinic acid on a large number of aging people living in
a sheltered home. A new one had been built. I approached the director
of this home, Mr. George Porteous. I arranged to meet him and
told him what I would like to do and why. I gave him an outline
of its properties, its side effects and why I thought it might
be helpful. Mr. Porteous agreed and we started this investigation.
A short while after my first contact Mr. Porteous came to my office
at University Hospital. He wanted to take nicotinic acid himself,
he told me, so that he could discuss the reaction more intelligently
with people living in his institution. He wanted to know if it
would be safe to do so.
That fall he came again to talk to me and this time
he said he wanted to tell me what had happened to him. Then I
discovered he had been with the Canadian troops who had sailed
to Hong Kong in 1940, had been promptly captured by the Japanese
and had survived 44 months in one of their notorious prisoner
of war camps. Twenty-five percent of the Canadian soldiers died
in these camps. They suffered from severe malnutrition from starvation
and nutrient deficiency. They suffered from beri beri, pellagra,
scurvy, infectious diseases, and brutality from the guards.
Porteous, a physical education instructor, had been
fit weighing about 190 pounds when he got there. When he returned
home he weighed only 2/3rds of that. On the way home in a hospital
ship the soldiers were fed and given extra vitamins in the form
of rice polishings. There were few vitamins available then in
tablets or capsules. He seemingly recovered but had remained very
ill. He suffered from both psychological and physical symptoms.
He was anxious, fearful and slightly paranoid. Thus, he could
never be comfortable sitting in a room unless he sat facing the
door. This must have arisen from the fear of the guards. Physically
he had severe arthritis. He could not raise his arms above his
shoulders. He suffered from heat and cold sensitivity. In the
morning he needed his wife's help in getting out of bed and to
get started for the day. He had severe insomina. For this he was
given barbiturates in the evening and to help awaken him in the
morning, he was given amphetamines. Later I read the growing literature
on the Hong Kong veterans and there is no doubt they were severely
and permanently damaged. They suffered from a high death rate
due to heart disease, crippling arthritis, blindness and a host
of other conditions.
Having outlined his background he then told me that
two weeks after he started to take nicotinic acid, 1 gram after
each meal, he was normal. He was able to raise his arms to their
full extension, and he was free of all the symptoms which had
plagued him for so long. When I began to prepare my report20 I
obtained his Veterans Administration Chart. It came to me in two
cardboard boxes and weighed over ten pounds, but over 95% of it
was accumulated before he started on the vitamin. For the ten
years after he started on the vitamin there was very little additional
material. One could judge the efficacy of the vitamin by weighing
the chart paper before and after he started on it. Porteous remained
well as long as he stayed on the vitamin until his death when
he was Lieutenant Governor of Saskatchewan. In 1962, after having
been well for two years, he went on a holiday to the mountains
with his son and he forgot to take his nicotinic acid with him.
By the time he returned home almost the entire symptomatology
had returned.
Porteous was enthusiastic about nicotinic acid and
began to tell all his friends about it. He told his doctor. His
doctor cautioned him that he might damage his liver. Porteous
replied that if it meant he could stay as well as he was until
he died from a liver ailment he would still not go off it. His
doctor became an enthusiast as well and within a few years had
started over 300 of his patients on the vitamin. He never saw
any examples of liver disease from nicotinic acid.
I have treated over 20 prisoners from Japanese camps
and from European concentration camps since then with equally
good results. I estimated that one year in these camps was equivalent
to 4 years of aging, i.e. four years in camp would age a prisoner
the equivalent of 16 years of normal living.
George Porteous wanted every prisoner of war from
the eastern camps treated as he had been. He was not successful
in persuading the Government of Canada that nicotinic acid would
be very helpful so he turned to fellow prisoners, both in Canada
(Hong Kong Veterans) and to American Ex-Prisoners of War. These
American veterans suffered just as much as had the Canadian soldiers
since they were treated in exactly the same abysmal way. The ones
who started on the vitamin showed the same response. Recently
one of these soldiers, a retired officer, wrote to me after being
on nicotinic acid 20 years that he felt great, owed it to the
vitamin and that when his arteries were examined during a simple
operation they were completely normal. He wrote, "About two years
ago, I was hit, was bleeding down the neck. The MDs took the opportunity
to repair me. They said the arteries under the ears look like
they had never been used."
There is an important lesson from the experiences
of these veterans and their response to megadoses of nicotinic
acid. This is that every human exposed to severe stress and malnutrition
for a long enough period of time will develop a permanent need
for large amounts of this vitamin and perhaps for several others.
This is happening on a large scale in Africa where the combination
of starvation, malnutriton and brutality is reproducing the conditions
suffered by the veterans. Those who survive will be permanently
damaged biochemically, and will remain a burden to themselves
and to the community where they live. Will society have the good
sense to help them recover by making this vitamin available to
them in optimum doses?
Doses
The optimum dose range is not as wide as it is for
ascorbic acid, but it is wide enough to require different recommendations
for different classes of diseases. As is always the case with
nutrients, each individual must determine their own optimum level.
With nicotinic acid this is done by increasing the dose until
the flush (vasodilation) is gone, or is so slight it is not a
problem. One can start with as low a dose as 100 mg taken three
times each day after meals and gradually increase it. I usually
start with 500 mg each dose and often will start with 1 gram per
dose especially for cases of arthritis, for schizophrenics, for
alcoholics and for a few elderly patients. However, with elderly
patients it is better to start small and work it up slowly. No
person should be given nicotinic acid without explaining to them
that they will have a flush which will vary in intensity from
none to very severe. If this is explained carefully, and if they
are told that in time the flush will not be a problem, they will
not mind. The flush may remain too intense for a few patients
and the nicotinic acid may have to be replaced by a slow release
preparation or by some of the esters, for example, inositol niacinate.
The latter is a very good preparation with very little flush and
most find it very acceptable even when they were not able to accept
the nicotinic acid itself. It is rather expensive but with quantity
production the price might come down. The flush starts in the
forehead with a warning tingle. Then it intensifies. The rate
of the development of the flush depends upon so many factors it
is impossible to predict what course it will follow. The following
factors decrease the intensity of the flush, a cold meal, taking
it after a meal, taking aspirin before, using an antihistamine
in advance. The following factors make the flush more intense,
a hot meal, a hot drink, an empty stomach, chewing the tablets
and the rate at which the tablets break down in liquid. From the
forehead and face the flush travels down the rest of the body,
usually stopping somewhere in the chest but may extend to the
toes. With continued use the flush gradually recedes and eventually
may be only a tingling sensation in the forehead. If the person
stops taking the vitamin for a day or more the sequence of flushing
will be re-experienced. Some people never do flush and a few only
begin to flush after several years of taking the vitamin. With
nicotinamide there should be no flushing but I have found that
about 2% will flush. This may be due to rapid conversion of the
nicotinamide to nicotinic acid in the body.
When the dose is too high for both forms of the
vitamin the patients will suffer from nausea at first, and then
if the dose is not reduced it will lead to vomiting. These side
effects may be used to determine what is the optimum dose. When
they do occur the dose is reduced until it is just below the nausea
level. With children the first indication may be loss of appetite.
If this does occur the vitamin must be stopped for a few days
and then may be resumed at a lower level. Very few can take more
than 6 grams per day of the nicotinamide. With nicotinic acid
it is possible to go much higher. Many schizophrenics have taken
up to 30 grams per day with no difficulty. The dose will alter
over time and if on a dose where there were no problems, they
may develop in time. Usually this indicates that the patient is
getting better and does not need as much.
I have divided all patients who might benefit from
vitamin B-3 into the following categories.
Category 1.
These are people who are well or nearly well, and
have no obvious disease. They are interested in maintaining their
good health or in improving it. They may be under increased stress.
The optimum dose range varies between 0.5 to 3 grams daily. The
same doses apply to nicotinamide.
Category 2.
Everyone under physiological stress, such as pregnancy
and lactation, suffering from acute illness such as the common
cold or flu, or other diseases that do not threaten death. All
the psychiatric syndromes are included in this group including
the schizophrenias and the senile states. It also includes the
very large group of people with high blood cholesterol levels
or low HDL when it is desired to restore these blood values to
normal. The dose range is 1 gram to 10 grams daily. For nicotinamide
the range is 11/2 G to 6 G. Nicotinamide does not affect cholesterol
levels.
Side Effects
Here are Dr. John Marks' conclusions.21
"A tingling or flushing sensation in the skin after
relatively large doses (in excess of 75 mg) of nicotinic acid
is a rather common phenomenon. It is the result of dilation of
the blood vessels that is one of the natural actions of nicotinic
acid and one for which it is used therapeutically. Whether this
should therefore be regarded as a true adverse reaction is a moot
point. The reaction clears regularly after about 20 minutes and
is not harmful to the individual. It is very rare for this reaction
to occur at less than three times the RDA, even in very sensitive
individuals. In most people much larger quantities are required.
The related substance nicotinamide only very rarely produces this
reaction and in consequence this is the form generally used for
vitamin supplementation.
"Doses of 200 mg to 10 g daily of the acid have
been used therapeutically to lower blood cholesterol levels under
medical control for periods of up to 10 years or more and though
some reactions have occurred at these very high dosages, they
have rapidly responded to cessation of therapy, and have often
cleared even when therapy has been continued.
"In isolated cases, transient liver disorders, rashes,
dry skin and excessive pigmentation have been seen. The tolerance
to glucose has been reduced in diabetics and patients with peptic
ulcers have experienced increased pain. No serious reaction have
been reported however even in these high doses. The available
evidence suggests that 100 times the RDA is safe (about 100 mg)."
Dr. Marks is cautious about recommending that doses
of 100 mg are safe. In my opinion, based upon 40 years of experience
with this vitamin the dose ranges I have recommended above are
safe. However with the higher doses medical supervision is necessary.
Jaundice is very rare. Fewer that ten cases have been reported
in the medical literature. I have seen none in ten years. When
jaundice dose occur it is usually an obstructive type and clears
when the vitamin is discontinued. I have been able to get schizophrenic
patients back on nicotinic acid after the jaundice cleared and
it did not recur.
Four serious cases have been reported, all involving
a sustained release preparation. Mullin, Greenson & Mitchell (1989)22
reported that a 44 year-old man was treated with crystalline nicotinic
acid, 6 grams daily, and after 16 months was normal. He then began
to take a sustained-release preparation, same dose. Within three
days he developed nausea, vomiting, abdominal pain, dark urine.
He had severe hepatic failure and required a liver transplant.
Henkin, Johnson & Segrest found three patients who developed hepatitis
with sustained release nicotinic acid. When this was replaced
with crystalline nicotinic acid there was no recurrent liver damage.23
Since jaundice in people who have not been taking
nicotinic acid is fairly common it is possible there is a random
association. The liver function tests may indicate there is a
problem when in fact there is not. Nicotinic acid should be stopped
for five days before the liver function tests are given. One patient
who had no problem with nicotinic acid for lowering cholesterol
switched to the slow release preparations and became ill. When
he resumed the original nicotinic acid he was well again with
no further evidence of liver dysfunction. I have not seen any
cases reported anywhere else. I have described much more fully
the side effects of this vitamin elsewhere.24
Inositol hexaniacinate is an ester of inositol and
nicotinic acid. Each inositol molecule contains six nicotinic
acid molecules. This ester is broken down slowly in the body.
It is as effective as nicotinic acid and is almost free of side
effects. There is very little flushing, gastrointestinal distress
and other uncommon side effects. Inositol, considered one of the
lesser important B vitamins, does have a function in the body
as a messenger molecule and may add something to the therapeutic
properties of the nicotinic acid.
Conclusion
Vitamin B-3 is a very effective nutrient in treating
a large number of psychiatric and medical diseases but its beneficial
effect is enhanced when the rest of the orthomolecular program
is included. The combination of vitamin B-3 and the antioxidant
nutrients is a great anti-stress program.
Correspondence:
A. Hoffer, M.D., Ph.D.
Suite 3 - 2727 Quadra St.
Victoria, British Columbia V8T 4E5
CANADA
Ph: 604-386-8756
Fax: 604-386-5828
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