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Vitamin B3 for depression: Case report and review of the literature

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While on parental leave during November 2009, my clinical shift was spearheaded by one of my colleagues who recommended fairly significant doses of inositol hexaniacinate to treat a patient's depression. In January 2010, the patient returned for a visit on my clinical shift, and much to my surprise her long-standing depression had resolved. As a result, I conducted a search for articles describing the use of vitamin B3 for depression. Six articles were found to meet the inclusion criteria and were included in this review. There is evidence that niacin and niacinamide (in combination with tryptophan) might be effective for the treatment of depression. Hypothetical reasons for niacin's effectiveness include its vasodilatory properties, while the mechanisms responsible for the effectiveness of niacinamide involve its ability to inhibit tryptophan pyrrolase and possibly protect neurons from damage. The side effect profiles of niacin and the niacinamide-tryptophan combination are also discussed. Even though the mechanisms of action for niacin and niacinamide have not been substantiated from well conducted controlled clinical trials, these forms of vitamin B3 appear to have beneficial effects upon depression. It is imperative that properly designed controlled trials are developed in order to determine the true therapeutic effects and adverse effect profile of both preparations of vitamin B3 for depression.
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Review Article
JOM Volume 25, Number 3, 2010 137
Vitamin B3 for Depression: Case Report
and Review of the Literature
Jonathan E. Prousky, ND, MSc1,2
1 Chief Naturopathic Medical Ocer, Professor, Canadian College of Naturopathic Medicine, 1255 Sheppard
Avenue East, Toronto, Ontario, M2K 1E2, Tel: 416-498-1255 ext. 235, email: jprousky@ccnm.edu
2 Editor, Journal of Orthomolecular Medicine, email: editor@orthomed.org
Introduction
e most commonly cited uses of vi-
tamin B3 (niacin/nicotinic acid and niacin-
amide/nicotinamide) are for the treatment
of pellagra. Pellagra is a disease caused by a
cellular deficiency of the nicotinamide coen-
zymes due to inadequate dietary supply of
tryptophan and vitamin B3. Diarrhea, der-
matitis and dementia characterize this de-
ficiency disease. Although is it not usually
fatal, when the 3 Ds are present death can
occur. e adult intake of vitamin B3 nec-
essary to prevent pellagra is around 20 mg
per day. e body can manufacture approxi-
mately 1 mg of niacin equivalents from 60
mg of tryptophan obtained mostly from di-
Abstract While on parental leave during November 2009, my clinical shift was spearheaded by
one of my colleagues who recommended fairly significant doses of inositol hexaniacinate to treat a
patient’s depression. In January 2010, the patient returned for a visit on my clinical shift, and much
to my surprise her long-standing depression had resolved. As a result, I conducted a search for articles
describing the use of vitamin B3 for depression. Six articles were found to meet the inclusion criteria
and were included in this review. ere is evidence that niacin and niacinamide (in combination
with tryptophan) might be effective for the treatment of depression. Hypothetical reasons for niacin’s
effectiveness include its vasodilatory properties, while the mechanisms responsible for the effective-
ness of niacinamide involve its ability to inhibit tryptophan pyrrolase and possibly protect neurons
from damage. e side effect profiles of niacin and the niacinamide-tryptophan combination are
also discussed. Even though the mechanisms of action for niacin and niacinamide have not been
substantiated from well conducted controlled clinical trials, these forms of vitamin B3 appear to have
beneficial effects upon depression. It is imperative that properly designed controlled trials are devel-
oped in order to determine the true therapeutic effects and adverse effect profile of both preparations
of vitamin B3 for depression.
etary protein. is in vivo conversion makes
it rather difficult to develop frank pellagra in
affluent, industrialized countries where food
supply is seldom scarce unless there are miti-
gating factors like disease (anorexia nervosa,
hypothyroidism, and alcoholism),1-6 medica-
tion-induced nutrient depletion (the use of
anticonvulsants),7,8 or from a lack of food in-
take (homelessness and undernutrition).9,10
While it is not common practice to use
vitamin B3 for medical reasons unless pellagra
has been identified, orthomolecular practi-
tioners have been using vitamin B3 therapeu-
tically for more than 50 years to treat numer-
ous neuropsychiatric conditions. One of the
first publications documenting the need for
Prousky.indd 137 9/2/10 11:43:23 AM
Journal of Orthomolecular Medicine Vol 25, No. 3, 2010
138
vitamin B3 occurred in the early 1940s when
the late Dr. William Kaufman of Connecti-
cut detailed its use as a treatment for a syn-
drome that he termed, “aniacinamidosis.”11
Kaufman’s description of aniacinamidosis
is practically indistinguishable from the
modern clinical presentations of anxiety and
mood disorders (Table 1, below). e treat-
ment of this syndrome could not be amelio-
rated by dietary modifications, but required
between 150-350 mg of niacinamide each
day to reverse its clinical manifestations.11
One decade later, Dr. Abram Hoffer of
Regina, Saskatchewan, along with his team
of investigators, conducted a total of six
double-blind, randomized controlled clini-
cal trials involving schizophrenic patients
from 1953-1960. ese trials demonstrated
that vitamin B3 doubled the recovery rate
of acute schizophrenic patients, and also re-
duced patients’ reliance upon the health care
system.12 ese studies did not, however,
show a favorable response among chronic
schizophrenic patients who were ill longer
than one year. When Hoffer reviewed this
problem more substantially, he discovered
that the treatment duration was not long
enough to have produced adequate results.
Chronic patients required vitamin treatment
for five or more years in order to derive ob-
servable benefits.13-15
From the 1950s until Hoffer’s death in
2009, he elucidated numerous additional
therapeutic uses of vitamin B3 for the treat-
ment of various neuropsychiatric condi-
tions. Some of Hoffers reports included
those involving children with learning and
behavioral issues,16,17 dementia of both the
Alzheimer’s and non-Alzheimer’s type,18-20
Huntington’s disease,21-23 and the starvation-
stress syndrome (similar to post-traumatic
stress disorder).24 While Hoffer was prolific
in his writings about the therapeutic uses of
vitamin B3 and other nutrients, he did not
author (to my knowledge) a single report
documenting the merits of vitamin B3 for
the treatment of depression. He merely al-
luded to it when discussing the psychiatric
Table 1. Psychiatric Manifestations of Aniacinamidosis
• Has not felt “like himself” for weeks or years
• Feels tense; can’t relax
• Is impatient and irritable
• Frequently has unwarranted anxieties
• Worries about unimportant things and can’t seem to shake worries
• Has the feeling of impending trouble
• Not sure of his knowledge or abilities
• Has uncertainties about what the future will hold for him
• Has lost his former interest in work, family, and 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
Prousky.indd 138 9/2/10 11:43:24 AM
139
Vitamin B3 for Depression: Case Report and Review of the Literature
and somatic complications of having a de-
pendency on vitamin B3. He did, however,
report on the relationship between chronic
allergies and depression, and the need for
allergy treatment as an effective antidepres-
sant strategy.25,26
Like Hoffer, I have not considered vi-
tamin B3 to be an effective antidepressant
and have typically prescribed other treat-
ments, such as omega-3 essential fatty acids,
5-hydroxytryptophan, tyrosine, Rhodiola,
and St. Johns wort extract to augment mood.
While on parental leave during November
2009, my clinical shift was spearheaded by
one of my colleagues who recommended
fairly significant doses of no-flush niacin to
treat a patient’s depression. In January 2010,
the patient returned for a visit on my clini-
cal shift, and much to my surprise her long-
standing depression had resolved.
Case Presentation
e patient was a 47-year-old female that
presented to the Robert Schad Naturopathic
Clinic on October 21, 2009. She had a 27
year history of both anxiety and depression.
When she was 20 years old she moved away
from her home due to the stress imposed by
her mother’s bipolar disorder. As a result, the
patient became depressed, which was further
complicated by the challenges of taking care of
her teenage sister. e patient referred to this
as her “subclinical” depression that had lasted
her entire adult life. Her father had mental
health issues of his own, for he had depression
and was a heavy social drinker. e patient re-
ported suicidal thoughts on and off since being
depressed. She also tried numerous antidepres-
sant medications and found them to be ineffec-
tive while also having the unfortunate side ef-
fect of increasing suicidality. She was currently
taking 0.5 mg of lorazepam daily and 7.5 mg
of zopiclone at bedtime to help with sleep. Her
affect was depressed and flat. Her diagnosis
was consistent with dysthymic disorder. On
October 28, she returned for a second visit and
was prescribed 3,000 mg of no-flush niacin
(inositol hexaniacinate/hexanicotinate), 300
mg of gamma-amino butyric acid (GABA),
and a probiotic to improve overall health.
On November 24, the patient returned for
a third visit. With the 3,000 mg of no-flush
niacin, she felt better overall, more calm, more
balanced, and reported no anxiety attacks
as well. Her affect was normal and she even
smiled during the intake. e no-flush niacin
was increased to 6,000 mg in divided doses
daily. On January 5, 2010, she returned for a
fourth visit and was on my clinical rotation.
She reported an absence of depression. ere
was even a marked improvement in her pre-
menstrual depression that apparently plagued
her as well. As of the latest entry in her chart,
dated March 22, 2010, her depression (dys-
thymic disorder) was noted to be in clinical
remission presumed to be the result of the
no-flush niacin. While it cannot be ascer-
tained if the GABA and probiotic helped
in reducing this patient’s depression, the pa-
tient did attribute her mood improvement to
the no-flush niacin.
Review of the Literature
While this case is not very compelling, it
did make me consider the possible antidepres-
sant effects that vitamin B3 might possess. As a
result, I conducted a search for articles describ-
ing the use of vitamin B3 for depression. To be
included in my final review the articles had to
(1) report on the use of vitamin B3 for depres-
sion either alone or in combination with other
medicines; and (2) describe the method of vita-
min B3 administration. A total of eight potential
eligible articles were screened. One article was
excluded because it was not possible for me to
obtain.27 A second article was excluded28 be-
cause it merely summarized a more descriptive
article that was included in the final review.29 Six
articles were found to meet the inclusion crite-
ria and were included in this review.29-34 Table 2,
(pp 6-8) displays the characteristics of the stud-
ies included in this review.
Discussion
e results of this review indicate that
vitamin B3 may have a therapeutic effect on
depression. e quality of the evidence at
this point, however, is only hypothesis gen-
erating, and randomized trials are required
to determine the clinical implications of this
Prousky.indd 139 9/2/10 11:43:24 AM
Journal of Orthomolecular Medicine Vol 25, No. 3, 2010
140
novel treatment.
ere are several important limitations
to consider in the interpretation of this re-
view. I was unable to find any randomized or
high quality controlled trials assessing vita-
min B3 by itself or in combination with other
medications for the treatment of depression.
I cannot determine to what extent publica-
tion bias has on the results of this review. I
am unable to draw clinical inferences on the
results of the included studies as they were of
low quality and have a low level of external
generalizability. Despite these limitations, I
attempted to conduct an exhaustive search
and included all reports of relevance.
Given these limitations, it is still impor-
tant to comment on the biochemical and
physiological mechanisms that might ac-
count for some of the positive results report-
ed in Table 2. For the studies in which niacin
was used alone30 and in combination with
phenobarbital,32 the mechanism believed to
produce its antidepressant benefits was ce-
rebral vasodilatation. Niacin causes periph-
eral vasodilatation and cutaneous flushing
by inducing the production of prostaglandin
D2 (PGD2) in the skin, leading to a marked
increase of its metabolite, 9α, 11β-PGF, in
the plasma.35 When niacin is administered
orally in amounts of 500 mg or topically via
a 6-inch patch of 10-1 M aqueous methylni-
cotinate on the forearm, PGD2 is markedly
released in the skin and its metabolite ap-
pears in high amounts in the plasma.35,36 It
is not known if PGD2 causes vasodilatation
of the intracranial arteries, but niacin’s abil-
ity to abort acute migraine headaches sug-
gests that this might be what is occurring.37
Old reports cited by Bicknell and Prescott,38
demonstrate that niacin does indeed cause
vasodilatation of the cerebral and spinal ves-
sels, and that intravenous administration in-
creases the rate of intracranial blood flow in
human beings for 20-60 minutes without any
significant change in blood pressure. Other
published data pertaining to niacin’s effects
on cerebral vasodilatation has been equivo-
cal. In one study, subjects having various
diseases (e.g., pernicious anemia, congestive
heart failure, hysteria, diabetes, and hyper-
tensive vascular disease) were administered
intravenous niacin (300-800 mg in 200-300
ml of saline over 20-25 minutes) and nu-
merous measurements were obtained, such
as arterial pressures, blood oxygen contents,
glucose, cerebral oxygen utilization, cerebral
glucose utilization, and cerebrovascular re-
sistance.39 e results of this study failed to
find any effect upon cerebral vasodilatation
by the intravenous administration of niacin.
In an animal study using anesthetized cats,
intravenous injection of niacin (0.5 ml/kg)
caused a short-term increase in both cerebral
blood flow and in arterial blood pressure in
venous vessels of the head, but this was fol-
lowed by a lowering of these parameters.40 In
a study assessing cerebral blood flow in ba-
boons under anesthesia using single photon
emission computed tomography (SPECT)
of the brain, a combination of niacin and
pentifylline increased cerebral blood flow
compared to the control baseline (p<0.01).41
In another study of similar design, the ce-
rebral blood flow was increased above that
of the control when a combination of pen-
tyifylline and niacin were administered to
baboons.42 e increase in cerebral perfusion
that resulted from the pentyifylline-niacin
combination was 2.31 ± 0.19 versus 1.79 ±
0.13 for the control. Based on the results of
these reports, it appears that intravenously-
administered niacin might increase cerebral
blood flow, but more studies are warranted.
Unfortunately, there have no reports exam-
ining the effects of orally-administered nia-
cin upon cerebral blood flow in human or
animal subjects.
If intravenous and oral niacin do in-
crease cerebral blood flow, this therapeutic
benefit might be important since there are
studies that have documented reduced ce-
rebral blood flow in depressed patients and
improved cerebral blood flow following
treatment. Presumably, increasing brain per-
fusion would benefit depression. In a study
of patients with late-life depression (55 years
of age or older), reduced cerebral blood flow
was increased in certain brain areas follow-
ing a mean of 13.7 weeks of pharmacothera-
py.43 Specifically, reduced cerebral blood flow
Prousky.indd 140 9/2/10 11:43:25 AM
141
Vitamin B3 for Depression: Case Report and Review of the Literature
increased (improved) in the left dorsolateral
prefrontal cortex to precentral areas and in
the right parieto-occipital regions. In anoth-
er study, patients with refractory depressive
disorder had alterations in regional perfusion
in specific brain areas (decreased activity of
the bilateral prefrontal areas) that differed
from patients having non-refractory depres-
sive disorder.44 A more compelling study
evaluated cerebrovascular reactivity (CVR)
following a dilatory stimulus (acetazol-
amide) in a healthy control group and a de-
pressed group of patients.45 CVR reflects the
compensatory dilatory capacity of cerebral
arterioles to a dilatory stimulus, and is a vital
mechanism that enables constant cerebral
blood flow. e group of acutely depressed
patients had a more significant reduction in
their CVR values compared to healthy con-
trols. On follow-up 21 months later when
the depressed patients had received treat-
ment and were in remission, their CVR had
significantly improved, whereas the CVR
values of the control group remained un-
changed. Another study demonstrated that
81.48% of patients with depressive disor-
ders had reduced cerebral blood perfusion as
measured by SPECT.46 In a study evaluating
CVR in 16 patients with unipolar depres-
sion, their CVR was reduced during the de-
pressive phase of their illness, and increased
in most of the depressed patients when in
remission.47 Based on the data cited here, it
appears that depression is marked by reduced
cerebral blood flow and that improvement is
characterized by increased (or normalized)
cerebral blood flow. ese findings suggest
that niacin might hypothetically have the
capacity to increase cerebral blood flow and
therefore assist in ameliorating depression.
Another biochemical mechanism that
might account for the antidepressant ben-
efits of vitamin B3 involves the use of niacin-
amide in combination with tryptophan.29,33,34
Niacinamide functions as an inhibitor of the
liver enzyme, tryptophan pyrrolase, which
prevents the metabolism of tryptophan by
the kynurenine pathway.29 When trypto-
phan is administered in combination with
niacinamide, more tryptophan enters into
the brain.48 is would have the therapeu-
tic benefit of increasing the production of
5-hydroxytryptophan, and subsequently
increasing the production of the serotonin
neurotransmitter. is makes the niacin-
amide-tryptophan combination a thera-
peutically attractive intervention for the
treatment of depression. Niacinamide also
provides protection against neuronal and
vascular injury.49 While the mechanisms that
account for these unique therapeutic proper-
ties are very complex and require further de-
lineation, niacinamide might provide some
antidepressant benefit by reducing neuronal
damage because it protects against anoxia
and nitric oxide cytodegeneration.49 Niacin-
amide also alters tryptophan metabolism to
increase serotonin synthesis while limiting
the formation of kynurenines.” Kynurenine
production or the induction of indoleamine
2,3 –dioxygenase (a.k.a., tryptophan pyrro-
lase) has been linked to mental depression
as well as apoptotic, neurotoxic, and pro-
oxidative effects, and upregulation of induc-
ible nitric oxide synthase, phospholipase A2,
arachidonic acid, prostaglandins, 5-lipoxy-
genase, and the leukotriene cascade.50 In
patients with major depression or in animal
models of depression, significant increases in
the production of pro-inflammatory cytok-
ines have been reported, leading to an over-
production of glucocorticoids, free radicals
and oxidants, which adversely affects glial
cell functions and damages neurons in the
brain.51 Other data has shown depression
to be associated with neuroinflammation52
and cell-mediated immune activation.53 Pre-
cisely how niacinamide would interface and/
or limit neuroinflammation and neuronal
injury requires more study, but published
data suggests that it might be very useful.
Whether or not niacinamide’s neurotrophic
mechanisms have any direct antidepressant
benefits also requires further study. I can-
not, therefore, rule-out the possibility that
niacinamide alone possesses antidepressant
effects.
With respect to dosing, it makes sense
to use niacin alone or in combination with
antidepressant medications. Since cutane-
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Journal of Orthomolecular Medicine Vol 25, No. 3, 2010
142
Table 2. Summary of Articles Demonstrating Vitamin B3’s Eectiveness for the
Treatment of Depression
Ref Condition n Protocol Outcome Type of Study
30 Various types
of depression
Various types
of depression
No benet was obser ved
Case Series
Case Series
Case Series
15
16
All patients were given nia-
cin as an adjunct to psycho-
therapy. Intravenous niacin
(300-400 mg) was given to
10 patients, followed by oral
niacin. Five other patients
were given niacin orally and
never did receive an initial
intravenous dose. All patients
received gradually increasing
doses of niacin before meals
until they reached 900 mg
daily, but one patient reached
2,500 mg daily. All patients
were maintained on their
maximum daily dose for 7-10
days, and then the dose was
gradually tapered. The aver-
age duration of niacin treat-
ment varied from 2-6 weeks.
14 of the 15 patients ex-
hibited subjective and
objective improvement
following the use of nia-
cin in conjunction with
psychotherapy.
31
32
Eleven patients were given
450-600 mg of niacin daily for
the rst week, then 900 mg
daily for 2 weeks in divided
doses. Treatment was then
terminated abruptly. Five pa-
tients were given identical-
looking placebo pills and no
niacin in the same manner to
the patients that were given
niacin. Nightly sedatives were
also prescribed to patients
when necessary.
Patients with
a mixture of
depressive
and anxiety
symptoms
100 Patients were given a com-
bination of niacin and phe-
nobarbital in tablet form or
elixir. Each tablet or 5cc of
the elixir contained 100 mg
of niacin and 8 mg of pheno-
barbital. All patients received
increasing daily dosages of
the combination until 900
mg of niacin and 72 mg of
phenobarbital was reached
47.2% of patients re-
ported denite improve-
ment; 34.0% reported
some improvement;
13.2% reported no im-
provement; and 5.4%
discontinued treatment.
Prousky.indd 142 9/2/10 11:43:25 AM
143
Vitamin B3 for Depression: Case Report and Review of the Literature
Table 2. Summary of Articles Demonstrating Vitamin B3’s Eectiveness for the
Treatment of Depression
Ref Condition n Protocol Outcome Type of Study
on day 15. From day 16 to day
21, daily doses of the combi-
nation were reduced to 450
mg of niacin and 36 mg of
phenobarbital. Presumably,
the combination was discon-
tinued after day 21.
33 Unipolar
depression
27
11
Patients randomly assigned
to 2 groups: group 1 received
2 electroconvulsive therapy
(ECT) treatments unilater-
ally weekly with a minimum
of 8; group 2 received 3 g of L-
tryptophan and 1 g of niacin-
amide daily. Thirteen patients
in group 1 completed the trial,
while 12 patients in group 2
completed the trial. The Beck
self-rating scale for depression
was used the day before the
trial began, and then on days
3, 7, 10, 14, 17, 21, 24, and 28.
The mean baseline Beck score
for group 1 was 25.6, and the
mean baseline Beck score for
group 2 was 24.4.
Group 2 improved more
than group 1 on day 10
(Beck scores: group 1,
16.8 and group 2, 15.2).
By day 21, the results
achieved statistical sig-
nicance (Beck scores:
group 1, 8.8 and group
2, 3.7; p<0.05). Scores
for each group on day 28
were almost identical.
Human pilot
open-label
trial
29 Newly
admitted
depressed
patients with
primary
aective
disorder
Patients received tryptophan-
niacinamide combination for
four weeks. Patients were giv-
en 2 g L-tryptophan and 0.5 g
niacinamide during week 1,
and then gradually increased
to 6 g L-tryptophan and 1.5
g of niacinamide at the start
of week 3. All patients re-
ceived diazepam if needed
for insomnia or agitation. The
mental status of patients was
scored before treatment, and
on days 7, 14, 21, and 28, on
a modied Hamilton Depres-
sion Rating Scale, and a Clini-
cal Global Impression Scale of
Severity of Depression (CGI).
In addition, the Beck Depres-
sion Inventory was completed
at the same intervals.
Human pilot
open-label
trial
There were statistically
signicant improvements
(i.e., reductions) in the
mean scores of all pa-
tients among all the in-
ventories used (p<0.01).
The mean Hamilton score
went from a 33.7 on day
0 to a 20.5 on day 28. The
Beck score went from
a 33.1 on day 0 to 20.9
on day 28. The CGI went
from a 7.2 on day 0 to
a 4.5 on day 28. On the
basis of percentage im-
provement on the Ham-
ilton scale, there were 3
marked-responders (50%
or more), 4 moderate-re-
sponders (25-49%), and 4
non-responders (< 25%).
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Journal of Orthomolecular Medicine Vol 25, No. 3, 2010
144
Table 2. Summary of Articles Demonstrating Vitamin B3’s Eectiveness for the
Treatment of Depression
Ref Condition n Protocol Outcome Type of Study
34 Newly
admitted
severely
depressed
patients
25 All medications were admin-
istered under double-blind
conditions for a period of
4 weeks. Eight patients re-
ceived the tryptophan-nia-
cinamide combination for 4
weeks. They were given 2 g
L-tryptophan and 0.5 g nia-
cinamide during week 1, and
then gradually increased to 6
g L-tryptophan and 1.5 g of ni-
acinamide at the start of week
3. Eight patients were given a
single dose at bedtime of 75
mg of imipramine for week
1, which was increased to
225 mg at the start of week
3. Nine patients were given
the tryptophan-niacinamide-
imipramine combination us-
ing the same daily dosages
described above. Throughout
the study, the tryptophan-
niacinamide group received
imipramine placebo and the
imipramine group received
tryptophan placebo and
niacinamide. All patients re-
ceived diazepam if needed
for insomnia or agitation. The
mental status of patients was
scored before treatment, and
on days 7, 14, 21, and 28, on
a modied Hamilton Depres-
sion Rating Scale, and a CGI
of Severity of Depression. In
addition, the Beck Depres-
sion Inventory was com-
pleted on the specied days.
Superior results oc-
curred among patients
in the imipramine group
and in the tryptophan-
niacinamide-imip-
ramine group. However,
if bipolar patients were
excluded from the anal-
ysis (n=7), than there
were no dierences in
the therapeutic ecacy
of the 3 treatments
in unipolar patients.
Controlled study
Prousky.indd 144 9/2/10 11:43:26 AM
145
Vitamin B3 for Depression: Case Report and Review of the Literature
ous flushing is an important aspect to the
putative therapeutic benefits of niacin, the
daily dose should be low enough so that
flushing is not significantly lessened. e
daily dose should also be kept low since 900
mg was the dose most often used (except in
one patient whose daily dose was 2,500 mg)
in the cited studies. I speculate that there
might be a relationship between the cuta-
neous flushing (peripheral vasodilatation)
induced by niacin and cerebral vasodilata-
tion. When niacin is administered at 1,000
mg (or more) three times daily, the cutane-
ous flushing is dramatically reduced after
the first few days of use by depleting PGD2
and other metabolites in the skin. erefore,
lower daily doses of niacin would presum-
ably be more therapeutic than daily doses
that deplete PGD2 and other metabolites
in the skin. I recommend that patient’s take
100-300 mg of niacin about 15-20 minutes
before meals three times daily. A patient’s
tolerance (or intolerance) to niacin’s cutane-
ous effects might require dose adjustments.
Preparations that produce no flushing, such
as inositol hexaniacinate or niacinamide, or
those that significantly lessen the flushing,
such as timed-, sustained-, or slow-release
preparations, would presumably be less ef-
fective than niacin at increasing cerebral
blood flow. A 28-42 day trial seems appro-
priate since this approximates the duration
of niacin treatment that was reported to be
beneficial in the cited studies. If niacin does
indeed benefit a patient, it might be neces-
sary to prolong treatment for 4-6 months
or several years depending on a patient’s
stability and functional capacities. Side ef-
fects such as headache, nausea, and/or vom-
iting are possible and patients should be
informed that they are usually temporary.
Transaminases are unlikely to increase from
daily doses of niacin below 1,000 mg. A
baseline measurement should be obtained
and transaminase levels should be moni-
tored every six months until treatment is
discontinued.
When treating depression with niaci-
namide, it should be used in combination
with tryptophan. In studies that used this
combination, the niacinamide-tryptophan
was administered twice daily and away from
food. Taking this combination in the morn-
ing and prior to bed is an effective dosing
strategy. e initial dose of this combination
should be 500 mg of niacinamide and 1,000
mg of tryptophan twice daily, which should
be doubled over several weeks of use. e
daily dose of tryptophan does not need to
exceed 4,000 mg and the daily dose of nia-
cinamide does not need to exceed 1,500 mg
to obtain an effective antidepressant effect.
Doses of tryptophan above 4,000 mg are
unlikely to provide additional benefit for
unipolar depression, but for bipolar depres-
sion the daily dose of tryptophan should
exceed 4,000 mg to be effective.34 Older
adult patients do not need as much niaci-
namide as do younger adult patients since
they have less tryptophan pyrrolase activi-
ty.29 For older patients the daily amount of
niacinamide does not need to exceed 1,000
mg, but for younger adult patients the dai-
ly amount might need to exceed 1,500 mg
to enable the accumulation of free plasma
tryptophan in the blood and consequently
increase cerebral serotonin.29 Trying this
combination for 28 days seems appropri-
ate since this approximates the duration of
treatment that was reported in the cited
studies. Consideration to increase treat-
ment duration should be discussed with
patients that have a positive treatment re-
sponse, for it can take 4-6 months of treat-
ment or even years before there is clinical-
ly significant improvement in a patient’s
stability and functional capacities. Side ef-
fects from this combination are usually not
severe, but patients can experience mild
rigidity, mild tremor, dry mouth, constipa-
tion, nausea, vomiting, dizziness, fainting,
anorexia, heartburn, and increased thirst.
A rare side effect is serotonin syndrome
(due to the tryptophan), which can be
severe. Transaminases are unlikely to in-
crease from daily doses of niacinamide at
or below 1500 mg. I do recommend base-
line transaminase measurements and then
monitoring the levels every six months un-
til treatment is discontinued.
Prousky.indd 145 9/2/10 11:43:27 AM
Journal of Orthomolecular Medicine Vol 25, No. 3, 2010
146
Conclusion
Even though vitamin B3s mechanisms
of action have not been substantiated from
rigorous controlled clinical trials, it does ap-
pear to have beneficial effects upon depres-
sion. Oral niacin is believed to increase ce-
rebral blood flow and decrease depression.
Intravenous niacin has some supportive data
demonstrating that it might increase cere-
bral blood flow, but data on oral niacin and
cerebral hemodynamics is lacking. Niacin-
amide in combination with tryptophan has
more robust data demonstrating an effec-
tive antidepressant response among patients
with unipolar depression. e niacinamide-
tryptophan combination increases serotonin
levels within the brain, but niacinamide by
itself might possess antidepressant effects. It
is imperative that properly designed and well
conducted controlled trials are developed in
order to determine the true therapeutic ef-
fects and adverse effect profile of niacin and
niacinamide for depression.
Acknowledgements
Written consent was obtained from this
patient for publication of this report.
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... A review study reported that oral niacin may enhance cerebral blood flow, resulting in a reduction in depression. An effective antidepressant response among patients with unipolar depression treated with the niacinamide-tryptophan combination, suggests increased serotonin levels in the brain (Prousky, 2010). Washburne reported that 15 patients with various types of depression were given vitamin B3 orally (around 900 mg daily) and intravenously (300-400 mg) for 2-6 weeks. ...
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