ArticlePDF Available

Supplemental Niacinamide Mitigates Anxiety Symptoms: Three Case Reports



The purpose of this report is to high- light the potential of niacinamide for the treatment of anxiety disorders. Three pa- tients were prescribed large pharmacologi- cal doses of niacinamide (2,000-2,500 mg per day). Each of the patients had consid- erable relief from their anxiety when regu- larly using niacinamide. The possible bio- chemical reasons for niacinamide's effec- tiveness might be related to the correction of subclinical pellagra, the correction of an underlying vitamin B3 dependency disorder, its benzodiazepine-like effects, its ability to raise serotonin levels, or its ability to modify the metabolism of blood lactate (lactic acid). Adverse effects did not occur with these doses, but nausea and vomiting can occur when doses as high as 6,000 mg per day are used. These positive case reports suggest that niacinamide might be helpful for the treatment of anxiety disorders. How- ever, definitive proof requires properly con- ducted randomized controlled trials to as- sess niacinamide's actual therapeutic effects and adverse effects profile.
The purpose of this report is to high-
light the potential of niacinamide for the
treatment of anxiety disorders. Three pa-
tients were prescribed large pharmacologi-
cal doses of niacinamide (2,000-2,500 mg
per day). Each of the patients had consid-
erable relief from their anxiety when regu-
larly using niacinamide. The possible bio-
chemical reasons for niacinamides effec-
tiveness might be related to the correction
of subclinical pellagra, the correction of an
underlying vitamin B
dependency disorder,
its benzodiazepine-like effects, its ability to
raise serotonin levels, or its ability to modify
the metabolism of blood lactate (lactic
acid). Adverse effects did not occur with
these doses, but nausea and vomiting can
occur when doses as high as 6,000 mg per
day are used. These positive case reports
suggest that niacinamide might be helpful
for the treatment of anxiety disorders. How-
ever, definitive proof requires properly con-
ducted randomized controlled trials to as-
sess niacinamides actual therapeutic effects
and adverse effects profile.
Anxiety disorders are very prevalent
conditions treated by primary care provid-
ers. In a recent survey of 2,316 randomly
selected patients (aged eighteen-years and
older) seen by general practitioners, 42.5%
of all patients had evidence of a threshold/
subthreshold psychiatric disorder.
In the
same survey, anxiety disorders were found
in 19% of all patients. In a survey of 88
outpatients in an internal medicine clinic,
30% of patients had mixed anxiety features,
33% had generalized anxiety symptoms, al-
most half reported obsessive-compulsive
personality symptoms, and about one-quar-
ter had marked levels of worry.
The investi-
gators concluded that anxiety disorders are
more common in primary care settings than
what had been previously reported.
Anxiety disorders are classified into
various categories such as obsessive-com-
pulsive disorder (OCD), panic disorder
(PD), social phobia/social anxiety disorder
(SAD), and generalized anxiety disorder
(GAD). This report will not differentiate the
various categories of anxiety disorders as
described in the Diagnostic and Statistical
Manual of Mental Disorders.
their high prevalence, it is paramount that
effective treatments are offered to patients
due to the obvious suffering that accom-
panies anxiety disorders. Heart racing,
muscular tension, sweating, flushing, nerv-
ousness, constant worry, and panic char-
acterize some of the debilitating symptoms
of anxiety disorders. It is unfortunate that
many patients seeking standard (main-
stream) treatment for anxiety disorders
remain untreated and underdiagnosed
many years after their initial diagnoses,
leading to unremitting impairment in func-
tional status and quality of life.
I evaluate and treat patients every day
suffering from unremitting anxiety symp-
toms. In my efforts to mitigate their anxiety,
I have been prescribing the amide of niacin
(nicotinic acid) known as niacinamide (nico-
tinamide). Both niacin and niacinamide are
commonly referred to as vitamin B
. The bio-
chemistry of vitamin B
is well known in that
it is involved in some two hundred enzymatic
reactions, mostly including dehydrogenases
within the human body. Its active forms or
its coenzymes are both nicotinamide adenine
dinucleotide (NAD) and nicotinamide ad-
enine dinucleotide phosphate (NADP).
Supplemental Niacinamide Mitigates Anxiety
Symptoms: Three Case Reports
Jonathan E. Prousky, N.D., FRSH
1. Chief Naturopathic Medical Officer, Associate Dean of
Clinical Education & Associate Professor of Clinical Nutri-
tion, The Canadian College of Naturopathic Medicine, 1255
Sheppard Avenue East, Toronto, ON Toronto, M2K 1E2.
Journal of Orthomolecular Medicine Vol. 20, No. 3, 2005
Vitamin B
can be absorbed directly from
the stomach, but most of its absorption
occurs within the small intestine. The
liver contains the most concentrated
amounts of the nicotinamide coenzymes,
but all metabolically active tissues re-
quire these vital metabolic products.
The most common uses of nicotina-
mide and niacin are for the treatment of
pellagra. Pellagra is a disease caused by a
cellular deficiency of the nicotinamide
coenzymes due to inadequate dietary
supply of tryptophan and vitamin B
either niacin or nicotinamide). Diarrhea,
dermatitis and dementia characterize
this deficiency disease. Although is it not
usually fatal, when the three Ds are
present, death can occur. The adult in-
take of vitamin B
necessary to prevent
pellagra is 20 mg per day. The body can
manufacture approximately 1 mg of ni-
acin equivalents from 60 mg of tryp-
tophan obtained mostly from dietary
protein sources. This in vivo conversion
makes it rather difficult to develop frank
pellagra in affluent, industrialized coun-
tries. Rare forms of pellagra, however, do
occur. Pellagra has been found among
patients with anorexia nervosa,
and from taking anticonvulsant
Here, I report on three cases where
the use of large pharmacological doses of
nicotinamide considerably improved the
symptoms of anxiety.
In each of the
cases frank symptoms of pellagra were
absent, even though neuropsychiatric
and gastrointestinal manifestations were
present. Niacinamides therapeutic
mechanism of action was likely related
to the correction of subclinical pellagra,
the correction of an underlying vitamin
dependency disorder, its benzo-
diazepine-like effects, its ability to in-
crease the production of serotonin, or its
ability to modify the metabolism of blood
lactate (lactic acid).
Case #1
An 11-year-old female first presented
to my office on November 10, 2003. Her
chief complaints were nervousness, anxi-
ety and excessive worrying. The onset of
her symptoms occurred when her father
tragically died in September of 2003. The
patient reported anxiety when she had to
sit for examinations and when she was
around her classmates. The most concern-
ing symptom was her fear of being kid-
napped, which was instigated by a well
publicized kidnapping of a young Asian girl
in the city where she lives. She also reported
having approximately two panic attacks
each month since September for which she
had learned to deal with them byleaving
the situation to get air.” Other symptoms
that were reported included some facial
acne, frequent blushing, stomachaches, and
sweatiness. Her past medical history was
unremarkable, except for asthma that was
diagnosed approximately one year earlier.
The asthma was not a concern since her
symptoms were reported to be mild with
the rare use of an inhaler as needed. Apart
from the inhaler, she was on no other medi-
cations at the time of the visit. A complete
physical examination was performed and
all findings were within normal limits. The
only notable sign was some acne along her
cheeks and chin. She was diagnosed with
PD, with some elements of social phobia.
She was prescribed a daily multiple vita-
min/mineral preparation, 25 mg of zinc,
100 mg of pyridoxine, 400 of magnesium,
and 500 mg of niacinamide twice daily.
A follow-up appointment occurred on
December 13, 2003. The patient reported a
slight improvement with her anxiety. She
did not like taking all the supplements and
agreed to continue with just the multiple
vitamin/mineral preparation, zinc, and ni-
acinamide. She also agreed to increase the
dose of niacinamide to 1000 mg twice daily.
No side effects were reported.
A second follow-up occurred on Feb-
ruary 7, 2004. The patient, now 12 years old,
Supplemental Niacinamide Mitigates Anxiety Symptoms: Three Case Reports
reported a striking improvement with her
anxiety. She did not always take her pills
daily, but was happy with the results. Her
panic attacks completely stopped and her
acne was much improved as well.
In a recent email from the patient, she
reported to be taking only the 1,000 mg of ni-
acinamide twice daily. Her anxiety remained
much improved and was no longer interfering
with her ability to engage in a regular life.
Case #2
A 28-year-old female came to my pri-
vate practice with a chief complaint of GAD
on May 10, 2004. She had been struggling
with this anxiety disorder for the past
twelve years. She is a high school teacher
and noted that her anxiety was more pro-
nounced during the academic year. Her
anxiety was worse in the morning with
symptoms of frequent muscular tension,
the passing of flatus, and chest pain. She
reported a fear of smelling when she needed
to expel gas. The anxiety also made it dif-
ficult for her to concentrate and focus on
things. When she experienced anxiety
symptoms she would feel the need to iso-
late herself from others. The same isolat-
ing need would also occur when she sim-
ply thought about possibly feeling nervous
and expelling gas. She also reported fears
of embarrassment and worried about be-
ing criticized from others. She had been on
paroxetine for one year but had not noticed
any improvement. She reported feeling de-
pressed due to the anxiety and would get
apathetic when her anxiety was at its worst.
Baths, lying in bed, walking, and exercis-
ing helped to slightly reduce her anxiety.
She was unable to correlate any of her
symptoms with foods. This patient also had
a history of thrombocytopenia for the past
five years for which she was being regularly
monitored by her family physician. She did
report easy bruising but did not have any
history of widespread bruising and bleed-
ing. The rest of her past medical history was
Physical examination revealed a well
nourished woman with normal vital signs.
All her systems were within normal limits.
She was subsequently diagnosed with GAD
with some social phobia, and thrombocyto-
penia. Lab tests were requisitioned and she
was prescribed niacinamide at an initial
dose of 500 mg three times daily for three
days, and then was instructed to increase it
to 1,000 mg every morning, 500 mg at lunch,
and 1,000 mg at dinner. She was also pre-
scribed 5-hydroxytryptophan (5-HTP) at a
dose of 100 mg twice daily for her mild de-
pression, and 2,000 mg of vitamin C to be
taken daily for the thrombocytopenia.
The patient had a follow-up appoint-
ment on May 31, 2004. She had difficulty
swallowing the niacinamide pills due to
their bitter taste. Despite this, she was tak-
ing the recommended dose of 2,500 mg per
day. Her anxiety was much improved and
she experienced only three minor panic
attacks since the initial visit. Prior to the
treatment her anxiety was chronic, occur-
ring daily, with the sensation or need to
pass gas. The patient continued to com-
plain of depression, which she felt was more
pronounced prior to menses. Her complete
blood count was normal, except that her
platelets were low at a value of 79 (refer-
ence range, 150-400 x 10
/L). The patient
was unsure if the treatments were working
due her time away from teaching. We
agreed that she would discontinue all pre-
scribed treatments except for the vitamin
C until June 14, 2004. After this date, the
patient would resume the 5-HTP, niacina-
mide, take 250 mg of vitamin B
, and 400
mg of magnesium. The vitamin B
magnesium were prescribed for the pre-
menstrual symptoms of depression.
On June 4, 2004, I received an urgent
telephone call from the patient. Since dis-
continuing the prescribed treatments on
June 1, her anxiety symptoms returned
promptly and she had difficulty function-
ing. She agreed to resume only the niaci-
namide tablets.
Journal of Orthomolecular Medicine Vol. 20, No. 3, 2005
On July 2, 2004, the patient emailed me
with an update. She discontinued all the pre-
scribed treatments except for the niacina-
mide. She found her anxiety and depression
to be much relieved due to being at home and
not teaching during the summer months.
When she felt anxiety she would take niaci-
namide and it would help. In her words, “I
take the niacinamide and I’m fine afterwards.
Case #3
A 42-year-old female first presented to
my private practice on May 16, 2004, for
chief complaints of constipation and anxi-
ety. About three weeks ago her father had
been diagnosed with advanced carcinoma
of the stomach. For three days following his
diagnosis the patient experienced very soft
stools once or twice daily. For her entire life
she had been constipated, requiring regu-
lar laxatives in order to have a daily bowel
movement. The patient reported additional
gastrointestinal symptoms of bloating, gas,
and right-sided abdominal pain. She had
taken fiber therapy in the past but had
never stayed on it long enough to see the
benefits. She was not concerned about the
constipation since she had been having at
least one-to-two soft stools per day.
Since her father’s diagnosis she had
been feeling very anxious with symptoms
of shakiness, light-headedness, numbness
of the extremities, and balance problems.
Her medical doctor had her do a twenty-
four-hour holter monitor and the results
were normal. She was unable to correlate
her anxiety with feelings of hunger. In the
past, she would have the same kind of anxi-
ety symptoms when stressful events oc-
curred. Her medical doctor felt that the
patient’s anxiety was related to hyperven-
tilation. On physical examination, the pa-
tient was well nourished, slightly over-
weight, with normal blood pressure and
normal heart sounds. All other systems
were within normal limits. Even though her
mother currently has heart disease, the rest
of her family history was unremarkable. She
was diagnosed with panic attacks, dyspep-
sia (possible irritable bowel syndrome), and
mild obesity. She was advised to continue
with her liquid multiple vitamin/mineral
preparation, take 500 mg of niacinamide three
times each day for two days, and was told to
increase the dose to 1,000 mg twice daily. Two
capsules of lactobacillus acidophilus were
prescribed every morning upon rising.
A follow-up visit occurred on May 26,
2004. The patient felt a little better during
the first week on niacinamide. However, she
felt jittery and related this to her father’s
grim prognosis. Her sleep was unaffected,
even though she did wake-up once each
night to go to the bathroom. Overall, she
felt much more under control. She was
advised to increase the niacinamide to
1,000 mg three times each day.
On July 12, 2004, she came in for an-
other visit. She cut back on the niacinamide
since she felt that it caused her to have feel-
ings of not being present. Instead of 3,000
mg daily she lowered the dose to 2,000 mg
per day. Her constipation was not a prob-
lem and she was having one bowel move-
ment daily. Her anxiety was much im-
proved on this dose and the previous shaki-
ness had completely resolved. In fact, she
had not experienced any episodes of shaki-
ness since the last visit. She was told to
continue the prescribed treatments and to
take a B-complex vitamin preparation and
1 mg of folic acid each day.
Subclinical Pellagra
These three case reports and an addi-
tional case report by this author,
strate that niacinamide is capable of reduc-
ing symptoms of anxiety. All the patients
responded favourably to large pharmaco-
logical doses of niacinamide (2,000-2,500
mg per day or as needed). These amounts
were much greater than the amounts of
vitamin B
or protein (containing tryp-
tophan) that would be necessary to prevent
full-blown pellagra. The initial symptoms
of pellagra tend to involve the gastro-
Supplemental Niacinamide Mitigates Anxiety Symptoms: Three Case Reports
intestinal system, which are known to pre-
cede the dermatological ones.
In these
three patients, the gastrointestinal symp-
toms formed part of their clinical presen-
tation. It was impossible to determine if
these symptoms preceded their anxieties or
neuropsychiatric symptoms. In case #3, the
patient reported a long-standing history of
constipation many years before the onset
of acute anxiety. In the other two cases, the
patients had anxiety symptoms with mild
gastro-intestinal manifestations. The pa-
tient in case#1 had stomachaches when she
felt anxious, and in case #2 the patient
passed gas when she experienced anxiety.
It appears that these patients did have
pellagra-like symptoms primarily involving
the neuropsychiatric system. One of the ear-
liest reports describing the psychological
patterning of central nervous system impair-
ments due to an inadequate supply of niaci-
namide came from the work of Kaufman.
He used the term “aniacinamidosis,” to de-
note a deficiency state that could not be
ameliorated by dietary modifications, but
required daily pharmacological doses (150-
350 mg) of niacinamide to reverse its clini-
cal manifestations. Table 1, (below) de-
scribes some of the psychological symp-
toms associated with aniacinamidosis.
Some of the symptoms listed in Table 1 are
similar to the symptoms exhibited by the
patients in these case reports.
Green, in his paper on subclinical pel-
lagra, noted that mental symptoms oc-
curred in patients without frank deficiency
of vitamin B
Similarly, Hoffer reported
that the earliest symptoms of pellagra in
its subclinical form manifest as modern
mood disorders (e.g., anxiety, depression,
fatigue, and vague somatic complaints)
followed by the development of other
It is evident that subclinical
pellagra can present with symptoms prima-
rily affecting the neuropsychiatric system,
yet the reasons for its genesis remain un-
• He has not felt himself for weeks or years.
• Feels tense; cant relax.
• Is impatient and irritable.
• Frequently has unwarranted anxieties.
• Worries about unimportant things and cant seem to shake worries.
• Has the feeling of impending trouble.
• Not sure of his knowledge or abilities.
• Has uncertainties as to what the future will hold for him.
• Has lost his former interest in work, family, friends.
• Adjusts poorly to ordinary life situations.
• Lacks initiative.
• Not cooperative.
• Routine duties become particularly burdensome.
• Delays making decisions.
• Shuns and fears unfamiliar people, ideas, situations.
Frequently wishes to be alone, to get away from everyone.
• Is unhappy, frequently without apparent cause.
• Frequently thinks that something is seriously wrong with him.
• Can’t sleep right.
Table 1. Adult pattern of psychological symptoms in aniacinamidosis.
Journal of Orthomolecular Medicine Vol. 20, No. 3, 2005
known. One possible explanation might
involve a phenomenon known as a local-
ized cerebral deficiency disease. Pauling
discussed the possibility of having grossly
diminished cerebrospinal fluid (CSF) con-
centrations of a vital substance while its
concentration in the blood and lymph re-
main essentially normal.
This localized
cerebral deficiency, according to Pauling,
might occur from decreased rates of trans-
fer (i.e., decreased permeability) of the vi-
tal substance across the blood-brain bar-
rier, an increased rate of destruction of the
vital substance within the CSF, or from
some other unknown factor.
If the serum
and CSF were to be examined for micronu-
trient status, extreme perturbations be-
tween these compartments might demon-
strate the presence of a localized cerebral
deficiency. For example, in a study involv-
ing 49 patients with organic mental disor-
ders, deficient CSF levels of vitamin B
pg/mL) were found in 30 of the patients.
When the serum levels of vitamin B
tested, normal values (200-800 pg/mL)
were found in 45 of them, indicating a
marked difference between both compart-
ments. Given that serum levels of vitamin
can be normal yet deficient in the CSF,
other micronutrients (such as vitamin B
might follow a similar pattern of deficiency
if the CSF and serum were to be respec-
tively analyzed. The correction of subclini-
cal pellagra might be one of the reasons for
niacinamide’s effectiveness. Conversely, we
need to understand the role of localized
cerebral deficiency of niacinamide, includ-
ing niacinamides metabolism with the CSF,
before this diagnosis can be given the con-
firmation it requires.
Vitamin B
Dependency as a Result of
Enzymatic Defects
The patients’ positive responses to ni-
acinamide suggest that this vitamin might
have corrected an underlying vitamin B
dependency disorder. A vitamin B
ency denotes an increased metabolic need
for the vitamin. Its cause is unknown, but
it has been purported to result from a com-
bination of malnutrition and long-term en-
vironmental-genetic stresses that disrupts
the in vivo conversion of dietary tryptophan
into a sufficient amount of vitamin B
Over time, this disruption would impair all
the biochemical processes dependent on a
constant supply of the nicotinamide
coenzymes. In order to sustain adequate
health, it would be necessary to obtain a
daily intake of vitamin B
in amounts far
greater than what could be accomplished
from dietary sources alone.
This is not so
unreasonable since many enzyme systems
within the body require large pharmacologi-
cal doses of vitamins to remedy defects in
the synthesis of vital metabolic products to
sustain adequate health. Pauling reported
that, “…mental disease is for the most part
caused by abnormal reaction rates, as de-
termined by genetic constitution and diet,
and by abnormal molecular concentrations
of essential substances”.
He described how
megavitamin therapy would be necessary for
the optimal treatment of mental disease
since the saturating capacity would be much
greater for defective enzymes that have di-
minished combining capacity for their re-
spective substrates. In other words, an en-
zyme-catalyzed reaction could be corrected
by pharmacologically increasing the concen-
tration of its substrate when high doses of a
particular micronutrient are provided.
Paulings ideas were later confirmed by
Abbey who found various B-vitamin de-
pendent enzymopathies in 12 patients with
All of Abbeys patients re-
quired 200-500 mg of the various B-com-
plex factors in order to resolve both the as-
sociated enzymatic defects and symptoms
of their anxiety and panic. In a more recent
report, the need for large pharmacological
doses of micronutrients were deemed nec-
essary as a means to increase coenzyme
concentrations and to correct defective
enzymatic activity in some 50 human ge-
netic diseases.
Certainly, there must be a
Supplemental Niacinamide Mitigates Anxiety Symptoms: Three Case Reports
certain percentage of patients that would
be responsive to large pharmacological
doses of vitamin B
to correct both the dis-
ordered biochemistry and the resulting neu-
ropsychiatric manifestations; presumably,
the result of defective enzymatic activity.
Benzodiazepine-like Properties
Additional reasons for niacinamides ef-
fectiveness likely have to do with its
benzodiazepine-like effects. In a previous re-
view of the literature by Hoffer, both niacin
and niacinamide were shown to have some
sedative activity, and were able to potentiate
the action of sedatives, anticonvulsant
medications and certain tranquilizers.
In a
recent case report by this author, a review of
the literature was undertaken to determine
the biological mechanism for niacinamides
anxiolytic effects.
Table 2 (p.174) summa-
rizes this data.
It appears that niacinamide
has therapeutic effects comparable to the
benzodiazepines. Its therapeutic effects are
probably not related to it acting as a ligand
for the benzodiazepine receptor, although it
acts centrally and might have a weak bind-
ing affinity for the benzodiazepine receptor.
Both the benzodiazepines and niacinamide
exert similar anxiolytic effects through the
modulation of neurotransmitters commonly
unbalanced in anxiety.
Niacinamide might also be helpful when
weaning patients off their benzodiazepine
medications. Benzodiazepine withdrawal
symptoms include tinnitus, involuntary
movements, paresthesias, perceptual
changes and confusion. Twenty-eight pa-
tients who had been abusing flunitrazepam
for at least six months were abruptly taken
off the drug.
The patients were randomly
assigned to receive intravenous nicotinic
acid (xantinol nicotinate; 3 g in 1,500 mL of
10% glucose per day over the first 48 hours,
followed by 1.5 g over the following 48 hours)
or placebo (glucose solution alone). Al-
though blinding was not specified, patients
who received xantinol nicotinate had signifi-
cantly fewer withdrawal symptoms than
those who received placebo. These results
suggest that intravenous administration of
xantinol nicotinate can reduce withdrawal
symptoms in patients withdrawing from
flunitrazepam. Even though intravenous
xantinol nicotinate would achieve higher
blood concentrations than oral niacinamide,
both nutrients are forms of vitamin B
, and
therefore, the parenteral and oral methods
might similarly help to withdraw patients
from their benzodiazepine medications.
Serotonin Synthesis
Another biochemical reason for niaci-
namide’s anxiolytic effects might have to do
with the vital role that it has upon the syn-
thesis of serotonin. For example, in a patient
with anorexia nervosa an insufficient sup-
ply of vitamin B
or protein resulted in re-
duced urinary levels of the serotonin break-
down product, 5-hydroxy-indolacetic acid
The authors of this report pos-
tulated that a deficiency of vitamin B
duced the feedback inhibition upon the
kynurenine pathway, resulting in more tryp-
tophan being diverted to the kynurenine
pathway, making less substrate available for
the synthesis of serotonin. By contrast, the
use of pharmacological doses of vitamin B
can increase the production of serotonin.
In a rat study, the administration of 20 mg
of niacin resulted in increased levels of 5-
HIAA and decreased levels of xanthurenic
acid via the kynurenine pathway.
pharmacological doses of niacinamide (or
any other form of vitamin B
) would increase
the production of serotonin, by diverting
more tryptophan to become substrate for
serotonin synthesis. Niacinamides therapeu-
tic ability to increase serotonin production
might explain why it was successful in re-
ducing the anxiety symptoms of the three
Modulation of Blood Lactate (lactic acid)
The final biochemical reason for niaci-
namide’s favourable effect might have to do
with its ability to modulate the metabolism
Journal of Orthomolecular Medicine Vol. 20, No. 3, 2005
of blood lactate (lactic acid). Before this
therapeutic mechanism is explained, it is
necessary to review some of the studies
that have explored the relationship be-
tween lactic acid and anxiety. This re-
search will demonstrate a consistent link
between PD and lactate provocation.
In a single-blind study using sodium
Table 2. Biochemical data summarizing niacinamides benzodiazepine-like effects.
Niacinamide modulated spinal cord activity, and had anticonflict, an-
ticonvulsant, muscle relaxing and hypnotic effects. The potency of ni-
acinamide was found to be equivalent to a highly potent benzodiazepine.
Niacinamide had a low affinity to the benzodiazepine-binding site in
the mammalian brain. This low affinity may have been the result of the
binding assay used, or it may have been a reflection that more than one
binding-site existed by which niacinamide exerted its benzodiazepine-
like properties.
Niacinamide antagonized the effects of diazepam, therefore interacting
with the benzodiazepine receptor in vivo. However, niacinamide did not
mimic the benzodiazepine properties of diazepam when tested with
the rat head-turning model. Niacinamide probably does have
benzodiazepine-like properties at different benzodiazepine receptor sites
in the CNS, but its effects are unrelated to the actions of gamma-
aminobutyric acid (GABA).
Niacinamide had a qualitatively similar effect to that of diazepam. It was
concluded that niacinamide exerted its effects by influencing the turnover
of serotonin, noradrenaline (norepinephrine), dopamine and GABA in those
areas of the brain thought to be unbalanced in anxiety.
Niacinamide could possibly be a competitive antagonist for the
benzodiazepine receptor since it prevented the binding of kynurenine
to the benzodiazepine receptor. It was further postulated that this ac-
tion was more likely of central origin than peripheral origin. It could
not be determined if niacinamides action was indeed related to its
occupation of the benzodiazepine receptor.
Niacinamide was structurally dissimilar to the benzodiazepine receptors.
Niacinamide did not act as a specific ligand for the benzodiazepine
receptor, but instead had a weak binding affinity for the receptor.
Niacinamide and its analogs possessed properties similar to
benzodiazepines at various zones of the cerebral cortex by influencing
the GABA-ergic system.
Supplemental Niacinamide Mitigates Anxiety Symptoms: Three Case Reports
lactate infusions, 11 out of 15 patients with
PD had panic attacks with the lactate.
15 control subjects did not experience
panic attacks during the infusions. Even
though no biochemical abnormalities were
seen between the groups, it was hypoth-
esized that the treatment group had an
increased baseline arousal level causing
them to be more susceptible to panic at-
tacks. In another study, 72% of the treat-
ment group (n=43) developed panic attacks
with intravenous sodium lactate infu-
The treatment group was com-
prised of patients with either PD, or agora-
phobia with panic attacks. In the control
group (n=20) none of the participants de-
veloped panic attacks with the infusions.
There was increased activity of the central
noradrenergic system in most of the pa-
tients in the treatment group who experi-
enced panic attacks. A similar study involv-
ing 43 subjects having PD or agoraphobia
with panic attacks were administered in-
fusions of sodium lactate.
Thirty-one of
the subjects panicked in response to the
infusions, whereas none of the 20 subjects
in the control group had any panic attacks.
It was concluded that the lactate-induced
panic attacks were associated with height-
ened central noradrenergic activity and hy-
perventilation. It now appears that the lac-
tate-induced panic response involves angi-
otensin-II, which interfaces with the
basolateral nucleus of the amygdala (BLA)
and the autonomic nervous system in the
generation of anxiety disorders.
All of the patients in the case reports
experienced frequent panic attacks in ad-
dition to their other anxiety symptoms.
Lactate sensitivity or an increased respon-
siveness to lactate might have caused some
of their anxiety symptoms. Only one of the
patients (case #3) appeared to have hyper-
ventilation as part of her clinical presenta-
tion. All of them had a therapeutic response
to niacinamide demonstrating its ability to
reduce panic attacks. Abbey suggested that
an insufficient supply of NAD would inhibit
the conversion of lactate back to pyruvate,
which would contribute to a high lactate-
to-pyruvate ratio and therefore to anxiety.
In 3 out of 12 patients, Abbey found defi-
cient levels of urinary N
mide (indicating deficient intake of niaci-
namide) normalized when large pharma-
cological doses of B-complex vitamins
were provided, to which she conjectured
that an excess of NAD was required to
drive the conversion of lactate to pyruvate.
Buist also hypothesized that anxiety neu-
rosis is associated with elevated blood lac-
tate and an increased lactate-to-pyruvate
ratio to which effective treatment requires
increasing niacin status (i.e., increasing
NAD levels) through supplementation.
The formation of lactate by the en-
zyme, lactate dehydrogenase, is the final
product of anaerobic glycolysis in
eukaryotic cells. Niacinamide supple-
mentation might result in an increased
conversion of lactate to pyruvate, thus re-
versing the equilibrium of the pyruvate
to lactate reaction. For example, when a
patient with MELAS (mitochondrial en-
cephalopathy, myopathy, lactic acidosis,
and stroke-like episodes) syndrome was
treated with 1,000 mg of niacinamide
four times daily, large reductions (50% or
more) in blood lactate and pyruvate con-
centrations occurred by the third day of
Large pharmacological doses
of niacinamide appear to be capable of
reducing blood lactate and pyruvate con-
centrations. Patients with panic attacks
likely have a greater demand placed upon
anaerobic glycolysis due to the rapidity
or shallowness of breathing that so often
accompanies their anxiety attacks.
Therefore, a greater amount of NAD ob-
tained by means of niacinamide supple-
mentation might help the tissues of the
body, including the central nervous sys-
tem, to readily oxidize lactate (obtained
from the blood) to pyruvate, and conse-
quently mitigate panic attacks, and hy-
perventilation (if present).
Journal of Orthomolecular Medicine Vol. 20, No. 3, 2005
Prescribing Instructions
In terms of proper dosing, most pa-
tients require a minimum of 2,000-4,500 mg
per day to achieve therapeutic results.
These dosages were derived from the work
of Hoffer, who recommended 1,500-6,000
mg of niacinamide per day for all patients
with psychiatric syndromes.
Patients usu-
ally experience relief of their symptoms
within one month of taking the medication
(personal observation). The three patients
tolerated the large pharmacological doses
of niacinamide very well. Only one patient
needed to reduce her dose from 3,000 mg
per day to 2,000 mg per day due to feelings
of not being present (perhaps derealiza-
tion). The 28-year-old patient had problems
swallowing the niacinamide tablets. For
this reason, it might be necessary to switch
some patients to capsules or powder forms
of niacinamide.
Large pharmacological doses of niaci-
namide (1,500-6,000 mg per day) have been
safely used in children and adolescents for
extended periods of time without any ad-
verse side effects or complications such as
clinical hepatitis.
The most common
side effect with niacinamide is sedation,
but dry mouth and nausea have been the
most common side effects that I have ob-
served among some my patients. There has
been one case report linking large pharma-
cological doses of niacinamide (9 g per day)
to hepatic toxicity.
The patient in the cited
report had no evidence of clinical hepatitis
when taking 2,000-3,000 mg per day of ni-
acinamide, but did develop clinical hepati-
tis when the dose was increased to 9,000
mg daily. All clinical abnormalities did re-
vert to normal once the niacinamide was
discontinued. I never exceed 6,000 mg per
day of niacinamide since most patients
will develop nausea and sometimes vom-
iting on this dose.
There is hardly any
need to go above 4,500 mg per day when
treating anxiety. If nausea does occur, de-
creasing the dose by 1,000 mg usually cor-
rects the problem.
Large pharmacological doses of niaci-
namide were effective in relieving the symp-
toms of anxiety in these three patients. Even
though niacinamides mechanisms of action
have not been substantiated from control-
led clinical trials, this agent does appear to
have a wide spectrum of beneficial effects
upon anxiety disorders. It is imperative that
properly designed randomized controlled
trials are developed in order to identify ni-
acinamides therapeutic effects and adverse
effects profile. A head-to-head placebo-con-
trolled trial of niacinamide and a benzo-
diazepine medication also seems to be wor-
thy of consideration.
Clinical trials of niacinamide as an
agent that mitigates symptoms of anxiety
are warranted by the following:
1. the clinical observation from these three
case reports and an additional one
onstrate that niacinamide reduces symp-
toms of anxiety;
2. biochemical data showing niacinamide
to have both benzodiazepine-like proper-
ties and the ability to increase serotonin
3. by comparison, mainstream anti-anxiety
medications similarly interface with the
benzodiazepine and serotonergic systems;
4. niacinamide has other possible bio-
chemical properties (corrects subclini-
cal pellagra, corrects vitamin B
ency, and favorably modulates blood lac-
tate) that may perhaps make it a more
effective agent than current contempo-
rary medications for the treatment of
anxiety disorders;
5. the relative absence of negative side ef-
fects when large pharmacological doses of
niacinamide are used;
6. the wide availability of inexpensive ni-
Written consent was obtained from
these patients or their guardians for publi-
cation of this report.
Supplemental Niacinamide Mitigates Anxiety Symptoms: Three Case Reports
1. Ansseau M, Dierick M, Buntinkx F, et al: High
prevalence of mental disorders in primary care.
J Affect Disord, 2004;78:49-55.
2. Sansone RA, Hendricks CM, Gaither GA,
Reddington A: Prevalence of anxiety symptoms
among a sample of outpatients in an internal
medicine clinic: a pilot study. Depress Anxiety,
2004; 19: 133-136.
3. Diagnostic and Statistical Manual of Mental Disor-
ders. Fourth Edition, Text Revision. Washing-
ton, DC: American Psychiatric Association;
4. Colman SS, Brod M, Potter LP, Buesching DP,
Rowland CR: Cross-sectional 7-year follow-up
of anxiety in primary care patients. Depress
Anxiety, 2004; 19: 105-111.
5. Prousky JE: Pellagra may be a rare secondary
complication of anorexia nervosa: a systematic
review of the literature. Altern Med Rev, 2003;
8: 180-185.
6. Hawn LJ, Guldan GJ, Chillag SC, Klein L: A case
of pellagra and a South Carolina history of the
disorder. J S C Med Assoc, 2003;99:220-223.
7. Prasad PVS, Babu A, Paul EK, Balasubramaniyan
S: Myxoedema pellagraa report of two cases.
J Assoc Physicians India, 2003;51:421-422.
8. Wallengren J, Thelin I: Pellagra-like skin lesions
associated with Wernickes encephalopathy in
a heavy wine drinker. Acta Derm Venereol, 2002;
82: 152-154.
9. Pitsavas S, Andreou C, Bascialla F, Bozikas VP,
Karavatos A: Pellagra encephalopathy follow-
ing B-complex vitamin treatment without ni-
acin. Int J Psychiatry Med, 2004; 34: 91-95.
10. Kertesz SG: Pellagra in 2 homeless men. Mayo
Clin Proc, 2001; 76: 315-318.
11. Lyon VB, Fairley JA: Anticonvulsant-induced
pellagra. J Am Acad Dermatol, 2002;46:597-599.
12. Kaur S, Goraya JS, Thami GP, Kanwar AJ: Pella-
grous dermatitis induced by phenytoin. Pediatr
Dermatol, 2002;19:93.
13. The case reports, the analysis pertaining to ni-
acinamides benzodiazepine-like effects, some
of the discussion, and the prescribing informa-
tion have been previously published in Prousky
JE: Orthomolecular treatment of anxiety dis-
orders. Townsend Lett Doctors Patients, 2005
[in press]. Written permission was obtained
from the publisher for the reproduced mate-
rial contained in this report.
14. Prousky JE: Niacinamides potent role in allevi-
ating anxiety with its benzodiazepine-like
properties: a case report. J Orthomol Med, 2004;
19: 104-110.
15. Hegyi J, Schwartz RA, Hegyi V: Pellagra: der-
matitis, dementia, and diarrhea. Int J Dermatol,
16. Kaufman W: The Common Form of Niacin
Amide Deficiency Disease: Aniacinamidosis.
Bridgeport, CT: Yale University Press; 1943.
17. Green RG: Subclinical pellagra among peniten-
tiary inmates. J Orthomol Psychiat, 1976; 5: 68-
18. Hoffer A: Vitamin B
dependency: chronic pel-
lagra. Townsend Lett Doctors Patients, 2000;
207: 66-73.
19. Pauling L: Orthomolecular psychiatry. Varying
the concentrations of substances normally
present in the human body may control men-
tal disease. Science, 1968;160:265-271.
20. van Tiggelen CJM, Peperkamp JPC, Tertoolen
JFW: Vitamin B12 levels of cerebrospinal fluid
in patients with organic mental disorders. J
Orthomol Psychiat, 1983;12:305-311.
21. Hoffer A: Vitamin B3: niacin and its amide.
Tow nsend Lett Doctors Patients, 1995; 147: 30-
22. Abbey LC: Agoraphobia. J Orthomol Psychiat,
1982; 11: 243-259.
23. Ames BN, Elson-Schwab I, Silver EA: High-dose
vitamin therapy stimulates variant enzymes
with decreased coenzyme binding (increased
Km): relevance to genetic diseases and
polymorphisms. Am J Clin Nutr, 2002; 75: 616-
24. Hoffer A: Nicotinic acid and niacinamide as
sedatives. Niacin Therapy In Psychiatry.
Springfield: Charles C Thomas; 1962:24-31.
25. Möhler H, Polc C, Cumin R, Pieri L, Kettler R:
Nicotinamide is a brain constituent with
benzodiazepine-like actions. Nature, 1979; 278:
26. Slater P, Longman DA: Effects of diazepam and
muscimol on GABA-mediated neurotrans-
mission: interactions with inosine and nicoti-
namide. Life Sci, 1979; 25: 1963-1967.
27. Kennedy B, Leonard BE: Similarity between the
action of nicotinamide and diazepam on neu-
rotransmitter metabolism in the rat. Biochem
Soc Trans, 1980; 8: 59-60.
28. Lapin IP: Nicotinamide, inosine and hypoxan-
thine, putative endogenous ligands of the
benzodiazepine receptor, opposite to diazepam
are much more effective against kynurenine-
induced seizures than against pentylenetetra-
zol-induced seizures. Pharmacol Biochem
Behav, 1981; 14: 589-593.
29. Markin RS, Murray WJ: Searching for the en-
dogenous benzodiazepine using the graph theo-
retical approach. Pharm Res, 1988;5:408-412.
30. Akhundov RA, Dzhafarova SA, Aliev AN: The
search for new anticonvulsant agents based on
nicotinamide. Eksp Klin Farmakol, 1992;55:27-29.
Journal of Orthomolecular Medicine Vol. 20, No. 3, 2005
31. Vescovi PP, Gerra G, Ippolito L, et al: Nicotinic
acid effectiveness in the treatment of
benzodiazepine withdrawal. Curr Ther Res,
1987; 41: 1017-1021.
32. Judd LE, Poskitt BL: Pellagra in a patient with an
eating disorder. Br J Dermatol, 1991;125:71-72.
33. Gedye A: Hypothesized treatment for migraine
using low doses of tryptophan, niacin, calcium,
caffeine, and acetylsalicylic acid. Med Hypoth-
eses, 2001;56:91-94.
34. Shibata Y, Nishimoto Y, Takeuchi F, Tatsuma Y:
Tryptophan metabolism in various nutritive con-
ditions. Acta Vitamin Enzymol, 1973; 29: 190-193.
35. Den Boer JA, Westenberg HG, Klompmakers AA,
van Lint LE: Behavioral biochemical and neu-
roendocrine concomitants of lactate-induced
panic anxiety. Biol Psychiatry, 1989; 26: 612-622.
36. Leibowitz MR, Gorman JM, Fyer A, et al: Possi-
ble mechanisms for lactate’s induction of panic.
Am J Psychiatry, 1986;143:495-502.
37. Leibowitz MR, Gorman JM, Fyer AJ, et al: Lac-
tate provocation of panic attacks. II. Biochemi-
cal and physiological findings. Arch Gen Psy-
chiatry, 1985; 42: 709-719.
38. Shekhar A, Sajdyk TJ, Gehlert DR, Rainnie DG:
The amygdala, panic disorder, and cardiovascu-
lar reponses. Ann N Y Acad Sci, 2003;985:308-325.
39. Buist RA: Anxiety neurosis: the lactate con-
nection. Int Clin Nutr Rev, 1985;5:1-4.
40. Majamaa K, Rusanen H, Remes AM, Pyhtinen
J, Hassinen IE: Increase of blood NAD+ and at-
tenuation of lactacidemia during nicotinamide
treatment of a patient with MELAS syndrome.
Life Sci, 1996;58:691-699.
41. Hoffer A: Vitamin B
dependent child. Schizo-
phrenia, 1971;3:107-113.
42. Hoffer A: Dr. Hoffers ABC of Natural Nutrition for
Children. Kingston, ON: Quarry Press Inc; 1999.
43. Werbach MR: Adverse effects of nutritional sup-
plements. Foundations of Nutritional Medicine.
Tarzanna: Third Line Press, Inc; 1997:133-160.
44. Winter SL, Boyer JL: Hepatic toxicity from large
doses of vitamin B
(nicotinamide). N Engl J
Med, 1973;289:1180-1182.
... Butyrate is able to increase the serotonin and BDNF synthesis, components associated with the reduction of stress and anxiety levels and cognition improvement [46,47]. Niacinamide and valine have been reported as precursors of serotonin [48][49][50]. Tyrosine and phenylalanine act in the catecholamines synthesis. This group of neurotransmitters contribute to the decrease of stress, anxiety and depression and enhance cognitive performance and memory formation [51,52]. ...
... Hypoxanthine also participates in the recovery process of purines degraded by energy metabolism [55][56][57]. Moreover, lysine, acetate, adenosine, choline, fumarate, leucine, isoleucine, niacinamide, succinate and valine act in the formation of ATP in the citric acid cycle [48,49,58]. Beyond that, butyrate decreases the expression of the IL-1 proinflammatory cytokine [59]. ...
... Activation: Mukai, Kishi, Matsuda, & Iwata, 2014;Carlomagno, Unfer, Buffo, & D'Ambrosio, 2011;Nierenberg et al, 2006;Chengappa et al, 2000;Elizur, Kofman, & Belmaker, 1995 Decreased reward-seeking behavior : Gelber, Levine, & Belmaker, 2001;Fux, Benjamin, & Belmaker, 1999Sedation: Palatnik, Frolov, Fux., & Benjamin, 2001Benjamin et al, 1995 Suggested daily dose: 2-25 g Activation: Thompson & Proctor, 1953;Washburne, 1950 Altered sense perception : Hoffer, 1994;Osmond & Hoffer, 1962;Hoffer & Callbeck, 1962;Hoffer, Osmond, Callbeck, & Kahan, 1957;Gregory, 1952;Sydenstricker & Cleckley, 1941 Enhanced cognition : Hoffer, 1974;Hoffer, 1962;Gregory, 1952;Sydenstricker & Cleckley, 1941 Psychomotor slowing: Kunin, 1976 Sedation: Thompson & Proctor, 1953 Suggested daily dose: 75-4,500 mg Niacinamide Activation: Chouinard, Young, Annable, & Sourkes, 1979;Chouinard, Young, Annable, & Sourkes, 1977;MacSweeney, 1975 Altered sense perception : Hoffer, 1994;Hoffer, Osmond, Callbeck, & Kahan, 1957Enhanced cognition: Brenner, 1982Hoffer, 1971Psychomotor slowing: Brenner, 1982Hoffer, 1971 Sedation: Prousky, 2005;Prousky 2004;Wright, 1992 Suggested daily dose: 1,000-6,000 mg Lerner, Kaptsan, Miodownik, & Kotler, 1999;Lerner & Liberman, 1998;Brenner, 1982Sedation: Kashanian, Mazinani, & Jalalmanesh, 2007Wyatt, Dimmock, & Jones, 2000 Suggested daily dose: 50-1,200 mg (adults); 0.6 mg/kg or up to 100 mg (children); 200 mg (adolescents) ...
Full-text available
The author presents the perspective that orthomolecular treatments possess psychoactive effects that result in potentially desirable physiological changes (e.g., sedation, psychomotor slowing, activation, and/or altered sense perception). The psychoactive effects of a broad range of commonly-recommended orthomolecular interventions are listed. This perspective can be integrated into a more expansive understanding of how orthomolecular interventions work, without claiming specific biochemical alterations. Lastly, several key advantages are delineated to support the use of orthomolecular interventions for their psychoactive effects.
... There is definitely a significant therapeutic role that vitamin B 3 could play (mostly, niacin) if it was part of the mainstream approach to treating alcohol withdrawal delirium, and even as a putative treatment to curb drinking behaviour. At the very least, niacin offers individuals with AUD the opportunity to feel more mentally stable, likely from the correction of either niacin insufficiency or deficiency (if the alcohol consumption is significant and prolonged) and/or from the anti-tension, anti-anxiety 23,24 and antidepressant 25 effects that the vitamin possesses. Even though smaller doses have been used successfully for alcohol withdrawal delirium, I believe that the optimal doses of niacin as advocated by Hoffer, i.e., one gram three times daily with meals, should be the therapeutic dose prescribed to all individuals that have AUD, and even to individuals that present to hospitals or medical facilities with alcohol intoxication. ...
Full-text available
The consequences of excessive and prolonged use of alcohol leads to mild-to-severe forms of pellagra (i.e., some combination of diarrhea, dermatitis, dementia, and possibly death). The author describes the work of many notable individuals who reported on the clinical effectiveness of vitamin B 3 treatment for compulsive drinking behaviour, alcohol withdrawal delirium, and for improving sobriety. There is definitely a significant therapeutic role that vitamin B 3 could play (mostly, niacin) if it was part of the mainstream approach to treating alcoholism and its related complications.
... According to the formula for dose translation based on the body surface area (human equivalent dose (mg/kg) ¼ animal dose (mg/kg) £ animal km factor/human km factor) (38) , the human equivalent doses are about 13 and 52 mg/kg, respectively, which equals to approximately 780 and 3000 mg niacin for a 60 kg person, respectively. These doses are within the range used in the treatment or prevention of some human disorders, such as hyperlipidaemia (39) , type 1 diabetes (40) and anxiety symptoms (41) . Thus, there is the possibility that such levels of niacin exposure may occur in some pregnant women, although this may be rare. ...
Full-text available
Recent evidence shows that excess nicotinamide can cause epigenetic changes in developing rats. The aim of the present study was to investigate the effects of maternal nicotinamide supplementation on the fetus. Female rats were randomised into four groups fed a standard chow diet (control group) or diets supplemented with 1 g/kg of nicotinamide (low-dose group), 4 g/kg of nicotinamide (high-dose group) or 4 g/kg of nicotinamide plus 2 g/kg of betaine (betaine group) for 14-16 d before mating and throughout the study. Fetal tissue samples were collected on the 20th day of pregnancy. Compared with the control group, the high-dose group had a higher fetal death rate, and the average fetal body weight was higher in the low-dose group but lower in the high-dose group. Nicotinamide supplementation led to a decrease in placental and fetal hepatic genomic DNA methylation and genomic uracil contents (a factor modifying DNA for diversity) in the placenta and fetal liver and brain, which could be completely or partially prevented by betaine. Moreover, nicotinamide supplementation induced tissue-specific alterations in the mRNA expression of the genes encoding nicotinamide N-methyltransferase, DNA methyltransferase 1, catalase and tumour protein p53 in the placenta and fetal liver. High-dose nicotinamide supplementation increased fetal hepatic α-fetoprotein mRNA level, which was prevented by betaine supplementation. It is concluded that maternal nicotinamide supplementation can induce changes in fetal epigenetic modification and DNA base composition. The present study raises the concern that maternal nicotinamide supplementation may play a role in the development of epigenetic-related diseases in the offspring.
Physical activity has been considered an important non-medication intervention to preserve mnemonic processes during aging. However, how resistance exercise promotes such benefits remains unclear. A possible hypothesis is that brain-metabolic changes of regions responsible for memory consolidation is affected by muscular training. Therefore, we analyzed the memory, axiety and the metabolomic of aged male Wistar rats (19-20 months old in the 1st day of experiment) submitted to a 12-week resistance exercise protocol (EX, n = 11) or which remained without physical exercise (CTL, n = 13). Barnes maze, elevated plus maze and inhibitory avoidance tests were used to assess the animals' behaviour. The metabolomic profile was identified by nuclear magnetic resonance spectrometry. EX group had better performance in the tests of learning and spatial memory in Barnes maze, and an increase of short and long-term aversive memories formation in inhibitory avoidance. In addition, the exercised animals showed a greater amount of metabolites, such as 4-aminobutyrate, acetate, butyrate, choline, fumarate, glycerol, glycine, histidine, hypoxanthine, isoleucine, leucine, lysine, niacinamide, phenylalanine, succinate, tyrosine, valine and a reduction of ascorbate and aspartate compared to the control animals. These data indicate that the improvement in learning and memory of aged rats submitted to resistance exercise program is associated by changes in the hippocampal metabolomic profile.
Full-text available
A vitamin dependency occurs when there is a defect in the binding of the vitamin-related coenzyme to its apoenzyme. The only way to correct a vitamin dependency is to obtain daily amounts much greater than recom-mended dietary allowances. I believe that the most common vitamin dependency among patients with mental illnesses is vitamin B 3 . These three cases involve members of the same family. Each case improved clinically upon taking megadoses (500-1500mg/day) of the vitamin. A fourth member of this fam-ily has schizophrenia. This is significant since recent postmortem biopsies of brain tissues have shown defects in the ability of schizophrenic patients to generate adequate amounts of vitamin B 3 coenzymes from tryptophan. Families share similar genet-ics and environmental factors, and thus this family likely shares varying degrees of the ability to synthesize adequate amounts of vitamin B 3 coenzymes. If schizophrenic genes are common among the entire human population, then the majority of people will suffer from slight-to-severe defects in this biosynthetic pathway. Introduction The 16th edition of The Merck Man-ual of Diagnosis and Therapy defines a vitamin dependency as that which relates to "coenzyme function and results from an apoenzyme abnormality that can be overcome by administration of doses of the appropriate vitamin that are many times the recommended dietary allow-ance (RDA)."
Obsessive Compulsive Disorder (OCD) affects 0.5-2% of young people many of whom are resistant to conventional treatments. This case study describes an 18-year-old male with OCD who first underwent cognitive behavioral therapy (CBT) for a 1-year period with a modest response (his OCD had shifted from severe to moderate). Within a year, his anxiety had deteriorated back to the severe range and he now had major depression. He then entered an ABAB design trial using a nutritional formula consisting mainly of minerals and vitamins (together, known as micronutrients). After 8 weeks on the formula, his mood was stabilized, his anxiety reduced, and his obsessions were in remission. The treatment was then discontinued for 8 weeks, during which time his obsessions and anxiety worsened and his mood dropped. Reintroduction of the formula again improved the symptoms. This case illustrates the importance of considering the effect micronutrients have on mental illness.
Full-text available
Anxiety disorders are extremely debilitating and are the most common psychiatric disorders in the United States. Such patients have greater chances of developing other medical illnesses such as chronic obstructive pulmonary disease, diabetes and hypertension. The underlying anxiety that exists in these patients also tends to prolong the course of any additional medical illnesses that they may develop. The conventional approach to severe anxiety involves pharmacotherapy with benzodiazepines, selective serotonin re-uptake inhibitors (SSRIs), or other medications such as buspirone, imipramine or trazodone. A case report demonstrated that the use of 2500mg of niacinamide (nicotinamide) per day ameliorated severe anxiety in a 34-year-old male patient. It appears that niacinamide has therapeutic properties similar to the benzodiazepines. However, the therapeutic effects of niacinamide likely have little to do with it acting as a ligand for the benzodiazepine receptor. Niacinamide might exert its effects through its modulation of neuro-transmitters that are commonly unbalanced in those areas of the brain associated with anxiety. Niacinamide might also reduce anxiety by shunting more tryptophan toward the production of serotonin and/or by simply correcting a vitamin B3 dependency. The use of niacinamide for extended periods of time appears to be safe, but megadoses can cause sedation, nausea and vomiting. More case reports, research and rigorous controlled trials are needed to properly evaluate niacinamide's therapeutic effectiveness, safety and mechanisms of action for the treatment of anxiety.
Physical and psychological dependence on benzodiazepine that induce withdrawal syndrome after abrupt interruption of the drug are well known. Specific withdrawal symptoms have also been evaluated after discontinuation of therapeutic doses of benzodiazepines. Purines, nicotinamide, and other molecules have been considered antianxiety endogenous ligands of benzodiazepine receptors. The aim of our study was to evaluate the effectiveness of nicotinic acid (xantinol nicotinate) in decreasing the severity of benzodiazepine withdrawal. Twenty-eight flunitrazepam abusers (at the dose of 8 to 10 mg daily) were studied. Eighteen patients (group A), randomly selected, were treated with xantinol nicotinate after abrupt discontinuation of the anxiolytic drug; the other ten patients (group B) were treated with glucose solution only. The group A (treated with xantinol nicotinate) showed significantly lower frequency and severity of withdrawal symptoms than group B treated with placebo. These data suggest that nicotinic acid or nicotinamide may be considered endogenous ligands for benzodiazepine receptors in the human brain.
Assayed vitamin B12 levels in serum and CSF in samples from 23 dementia patients (aged 60–85 yrs), 16 organic affective syndrome patients (aged 30–60 yrs), 10 postnatal depression patients (aged 25–40 yrs), and 12 normal controls (aged 25–50 yrs). Normal serum levels correlated with normal levels in CSF in controls. In the postnatal depression group, serum levels were below normal, reportedly the level found in patients with untreated pernicious anemia. Of the remaining group of 45 Ss, all had a normal serum level, while 26 Ss appeared to have an abnormally low level of B12 in CSF. Six weeks of hydrocobalamine medication increased the abnormally low pretreatment levels in CSF to levels far higher than in the controls. Results suggest that a potentially treatable condition of vitamin B12 deficiency can be overlooked in a significant proportion of patients with organic mental disorder when determination of CSF vitamin B12 is not included in the assessment. (22 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Pellagra defines systemic disease as resulting from a marked cellular deficiency of niacin. It is characterized by 4 “D’s”: diarrhea, dermatitis, dementia, and death. Diagnosis of pellagra is difficult in the absence of the skin lesions, and is often facilitated by the presence of characteristic ones. The dermatitis begins as an erythema. Acute pellagra resembles sunburn in its first stages, but tanning occurs more slowly than typically in sunburn. Exacerbation follows re-exposure to sunlight. In this work we review the findings of this once mysterious disorder, one that still challenges clinicians world-wide.
BENZODIAZEPINES are a group of drugs with wide therapeutic application as anxiolytics, hypnotics, anticonvulsants and muscle relaxants. To exert their therapeutic and pharmacological effects, they apparently interact with a brain-specific benzodiazepine receptor characterised by a high-affinity binding site for this group of compounds1,2. In analogy to the identification of morphine receptors in the brain and the subsequent isolation of opioid peptides, the discovery of the benzodiazepine receptor prompted the search for an endogenous brain constituent, which physiologically may display benzodiazepine-like actions3. We describe here the isolation and benzodiazepine-like actions of nicotinamide, a compound which might exert these actions in the brain physiologically.
Inosine and nicotinamide have been proposed as endogenous ligands for the brain benzodiazepine receptor. An method for detecting drugs with GABA-mimetic properties was used to examine the effects of inosine, nicotinamide and diazepam in the rat globus pallidus. Inosine and nicotinamide completely prevented the GABA-mimetic action of diazepam but neither compound alone had any GABA-like activity. These findings suggest that inosine and nicotinamide are able to antagonize but are not able to mimic the GABA-like actions of diazepam at the benzodiazepine receptor.
In phenylalanine administered rat, tryptophan chiefly metabolized to xanthurenic acid and in nicotinic acid administration to 5-hydroxy indole acetic acid mainly. MAO reaction inhibited by quinoline compound and the inhibition of kynurenine aminotransferase activity through the injection of epinephrine or serotonin were observed. And also the induction of tryptophanpyrrolase in starvation was discussed.