JOM Volume 26, Number 4, 2011 Review Article 163

Treating Dementia with Vitamin B3

and NADH

Jonathan E. Prousky, ND, MSc1,2

1
Chief Naturopathic Medical Officer, 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

Abstract Dementia affects approximately 5 million people in the United States, and about 475,000
elderly Canadians. Dementia is a debilitating and often progressive illness. The most common type
of dementia is Alzheimer’s disease, followed by vascular types. There is a need to investigate novel
treatments because the current crop of medications have limited value. Niacin might be a worthwhile
treatment to consider. Research has shown that the risks of incident AD increase when patients have
insufficient intakes of niacin from diet or medical conditions that precipitate niacin deficiency. Clini-
cal reports have documented therapeutic benefits when patients receive optimum daily doses of niacin.
Preliminary trials evaluating the reduced form of nicotinamide adenine dinucleotide (NADH) found
it a safe and effective treatment for AD. At present, research evaluating the therapeutic applications of
niacin and/or NADH for dementia is at a standstill. However, niacinamide is being evaluated in a
clinical trial to determine if it is safe and beneficial for patients with AD. Hopefully, the forthcoming
results will encourage researchers and clinicians to study niacinamide further, and revisit the therapeu-
tic potential of vitamin B3 as a safe and an effective treatment for dementia.

Introduction functions, including language, motor skills,

Among elderly patients, Alzheimer’s judgment, orientation ability, and, most
disease (AD) is the most common type of notably, memory. Patients eventually lose
dementia, followed by vascular types. World- themselves in the disease, unable to remem-
wide, more than 30 million people suffer ber even vestiges of the lives they once lived.
from AD. In the United States, AD affects The cognitive declines of AD are asso-
approximately 5 million people.1 About ciated with problems in the cerebral cortex
475,000 elderly Canadians have dementia, including the formation of senile plaques,
with the majority of cases being attributed to neurofibrillary tangles, and granulovascular
AD.2 Experts predict that the number of pa- degeneration of neurons.3 Various risk fac-
tients afflicted with dementia in Canada will tors have been implicated in the suscepti-
increase to 778,000 by the year 2031.2 The bility to AD. These include advancing age,
burden that this disease will place on health family history, apolipoprotein E epsilon 4
care systems is staggering when you consider genotype, obesity, insulin resistance, vascular
that the elderly constitute the fastest growing factors, dyslipidemia, hypertension, inflam-
population in all industrialized countries.1 matory markers and Down syndrome.1
Dementia is a debilitating and often The medical treatment of AD uses ace-
progressive illness characterized by intellec- tylcholinesterase inhibitors or n-methyl-d-
tual decline and the loss of higher cognitive aspartic acid glutamate receptor antagonists,

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 164 Journal of Orthomolecular Medicine Vol 26, No 4, 2011

with the former treatment having only weak participants were reported to have pellagra
evidence of benefit on cognitive function.4 (i.e., diarrhoea, dermatitis, dementia, and
Clearly there is a need to investigate other shortly thereafter, death), some participants
treatments because the current crop of med- who demonstrated mental and cognitive de-
ications have limited value in mitigating the clines may not have met the recommended
progression and symptoms of dementia, most dietary allowance for niacin (14 mg for adult
notably, AD. In this article, I will summarize females and 16 mg for adult males6). Some
and comment on: (1) research linking a re- of the study participants may have had sub-
duction in the incidence of AD with high clinical pellagra.
dietary intakes of vitamin B3; (2) the merits The mental signs of mild niacin deficien-
of using niacin or the reduced form of nico- cy (a.k.a., pellagra sine pellagra) often occur
tinamide adenine dinucleotide (NADH) as in the absence of any dermatologic, mucous
treatments for dementia; and (3) current re- membrane, or gastrointestinal symptoms.7,8
search investigating the safety and efficacy of The researchers did not acknowledge that
niacinamide as a treatment for AD. niacin deficiency can lead to symptoms of
AD, and thereby play a role in the patho-
Preventing AD with Vitamin B3 genesis of AD. Decades ago Aring and Spies
Research has shown a relationship be- reported that neurasthenic symptoms in 225
tween dietary niacin and the development of mild pellagrins were ameliorated by taking
AD.5 A total of 3,718 participants aged 65 300 to 600 mg of niacin every day for 1-12
years and older underwent at least two clini- days (3-6 pills, with each pill providing 100
cal assessments and provided dietary data for mg of niacin).8 The neurasthenic symptoms
analyses over a median of 5.5 years. In this reversed by niacin appeared long before any
large, prospective study, dietary niacin defi- other manifestations of the disease. These
ciencies were associated with incident AD included fatigue, insomnia, anorexia, vertigo,
and cognitive decline. Niacin intake from burning sensations in various parts of the
foods was inversely associated with AD body, numbness, palpitation, nervousness, a
(p for trend = 0.002). A higher food intake feeling of unrest and anxiety, headache, for-
of niacin was associated with a slower annual getfulness, apprehension, and distractibil-
rate of cognitive decline. Specifically, an in- ity. These niacin-deficiency manifestations
creased food intake of niacin slowed the an- could easily be confused with prodromal
nual cognitive decline by 0.019 standardized symptoms of AD, and, if left untreated, they
units per natural log increase in intake (mg), could become severe enough for a diagnosis
which was statistically significant (p=0.05). of AD. The dementia of pellagra looks much
The participants in intake quintiles 2-4 had a like AD since its clinical presentation, while
statistically significant 70% reduction in risk varied, includes aggression, apathy, confu-
compared to participants in the lowest quin- sion, depression, disorientation, hallucina-
tile (median niacin intake 12.6 mg/day). The tions, insomnia, psychosis, and seizures.9
participants in the highest quintile (median Low dietary intakes of niacin would not
niacin intake 22.4 mg/day) had an 80% sta- entirely account for the increased incidence
tistically significant reduction in risk. of AD among the study participants. Many
These researchers did not provide any participants had varying intakes of alcohol
robust explanations as to why diagnoses of and cigarette consumption, as well as the
AD increased among participants with low presence of diabetes and/or cardiovascu-
dietary intakes of niacin but they did note lar disease. These and other possible factors
that the level of dietary niacin associated could have increased the participants’ vulner-
with pellagra (8.8 mg of niacin equivalents ability to niacin deficiency during the study
per 2000 kilocalories) was lower than the period (Table 1, opposite).7
range of intake for the lowest quintile (13.2- Above all, this study demonstrates that
27 mg per day). While none of the study insufficient intake of niacin from diet or

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 Treating Dementia with Vitamin B3 and NADH 165

Table 1. Possible causes of niacin deficiency

Precipitating Factors Explanations

Inadequate amount of niacin in diet Inability to procure an adequate diet (e.g., socioeco-
nomic reasons), or choosing a nutritionally unbal-
anced diet (e.g., due to ignorance, individual prefer-
ence, or lack of advice about nutrition)

Interference with ingestion Functional and organic conditions leading to an-

orexia or vomiting, gastrointestinal disease, psychi-
atric disorders (e.g., psychoneuroses, both organic
and functional psychoses, and addiction to alcohol
or other drugs), neurological and traumatic disorders
that interfere with self-feeding, and oral diseases
(e.g., sore mouth, or loss of teeth)

Interference with bio-synthesis Inadequate intake of tryptophan, ingestion of

structurally similar compounds that would inhibit the
formation of niacin by substrate competition (e.g.,
maize), and destruction of intestinal bacteria (e.g.,
bowel “sterilizing” antibiotics)

Interference with absorption Absence of normal digestive secretions (e.g., achlo-

rhydria and obstructive jaundice), intestinal hypermotility
(e.g., various types of diarrhoea), reduction in absorptive
surface (e.g., disease or surgical removal of the gastrointes-
tinal tract), and medications (e.g., mineral oil)

Interference with utilization Problems with cellular metabolism (e.g., alcohol,

general anaesthesia, and metabolic disorders such
as hypothyroidism or diabetes), specific inactivation
(e.g., sulphonamides exert an anti-vitamin effect by
substrate competition with para-aminobenzioc acid,
corn, and isoniazid)

Interference with storage Any condition causing impairment of liver function would
interfere with the amount of niacin retained in the body

Increased excretion or loss Elevated metabolic rate (e.g., hyperthyroidism), periods

of rapid growth, pregnancy and lactation, pyrexia from
any cause, any condition requiring increased muscular
activity, and specific treatments (e.g., high carbohy-
drate diets, insulin, thyroid medication, and overuse of
stimulants (such as caffeine or amphetamines)

Increased nutritive requirements Urinary loss (e.g., renal disease, and diabetes), or
other routes (e.g., lactation, serous exudates due to
burns, and severe blood loss)

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 166 Journal of Orthomolecular Medicine Vol 26, No 4, 2011

conditions that can precipitate vitamin defi- if a patient’s psychiatric condition was due to
ciency can increase the risks of incident AD. a deficiency of niacin (i.e., an “avitaminosis”)
As more data emerges linking niacin insuf- even though the aetiology was uncertain. In a
ficiency to AD, it might be prudent to create discussion following their paper, other clini-
public health programmes to promote niacin cians remarked that the therapeutic value of
consumption from foods or increase niacin niacin could not necessarily be attributed to
fortification. Such measures could protect the correction of a vitamin deficiency. They
more of the population from mental and reported that niacin might have helped some
cognitive decline, and reduce the incidence patients as a result of its physiological effects
of dementia. upon cerebral circulation, and/or as a result of
its ability to facilitate carbohydrate metabo-
Treating Dementia with Niacin lism within the brain.
Subsets of patients with early or even In 1952, Gregory administered large
established dementia appear to require large doses of niacin orally (300 mg three times
daily doses of niacin to reverse and/or slow daily) and intravenously (100 mg/day) to 54
the progress of their disease. In 1941, Syden- patients having organic psychoses of senil-
stricker and Cleckley were two of the first ity immediately following their admission
clinicians to report impressive benefits from to a private mental hospital.11 During their
oral and intravenous niacin administration in hospital stays, patients were also given a nu-
29 patients with stuporous or active psycho- tritious diet and liberal amounts of other
ses of unknown origin.10 Two-thirds of their vitamins. All patients were evaluated before
patients were in the presenile or senile age treatment and immediately following any
range with severe psychiatric symptoms of degree of improvement. The evaluations in-
a confusional nature, but none had physical cluded thorough psychiatric examinations
signs of malnutrition or pellagra. Twenty- (with particular reference to orientation,
eight patients recovered after niacin treat- memory, and secondary symptoms), as well
ment. Eight patients received oral niacin as intelligence tests. The duration of niacin
treatment, while the remaining 21 patients treatment was approximately 3-12 weeks.
received intravenous niacin or a combination Once patients became maximally improved,
of oral and intravenous niacin. The oral niacin they were placed on a maintenance dose of
prescribed to patients ranged from 75-4500 niacin (100 mg orally/day). In the group
mg daily until discharge. The intravenous of 14 patients 65 years of age and under, 8
doses of niacin ranged from 100-900 mg. patients improved dramatically following
For most patients, the intravenous admin- niacin treatment. They were able to leave the
istration continued until discharge, but for hospital, whereas the remaining 6 patients
some patients, intravenous treatments were improved symptomatically or not at all. In
stopped and replaced by oral niacin until dis- the group of 40 patients over the age of 65,
charge. Within 4 days of niacin treatment, 31 completed the course of niacin treatment.
the majority of these patients experienced Only 4 patients from the over-65 group
rapid and usually impressive improvements. improved enough to re-socialize. The au-
While the duration of niacin treatment was thor concluded that “nicotinic acid is most
unclear, estimates from the cited case reports effective in those psychoses of senility that
suggest 7-30 days or longer since some pa- are of recent, and fairly rapid, onset,” which
tients continued with the niacin treatment was reported to be of a duration less than 6
following their hospital stay. The authors months. The findings showed that the earlier
concluded that the majority of patients with niacin treatment was started, the better the
toxic psychosis or exhaustion delirium, as well prognosis, especially among patients 65 years
as those with unexplained clouding of con- of age and under. With respect to mecha-
sciousness, should be given a therapeutic trial nism of action, the author discussed several
of niacin. This was the only way to determine possibilities including: (1) the correction of

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 Treating Dementia with Vitamin B3 and NADH 167

a niacin deficiency; (2) a “saturation” effect leagues discovered that 3,000 mg/day of
in the absence of any deficiency; and/or (3) niacin improved and sometimes reversed
cerebral vasodilatation. The author also sug- dementia.12 Hoffer’s patients required large
gested that lesser amounts of niacin might daily doses of niacin to remain well (Table
delay or prevent the psychoses of senility if 2, below).
given to individuals in the presenile and se- In total, 12 of 15 elderly patients re-
nile age groups. sponded favourably to large doses of niacin.
In 1962, Dr. Abram Hoffer and his col- Table 3 (p. 168) describes the type of clinical
Table 2. Treatment response from large (3000 mg/day) doses of niacin in 15 elderly patients
fast becoming senile or with clear evidence of senile mental changes
Patient Age Diagnosis Clinical response Duration
Initials (years)

OR 62 Psychosis Recovered 4
with arteriosclerosis

JC 80 Presenile psychosis Recovered 1

HC 67 Presenile changes Recovered 6

FM 72 Normal Remains well 6

MT(f) 58 Normal Remains well 3

MT(m) 63 Normal Remains well 2

AC 79 Senile depression Recovered 1.5

LW 74 Senile psychosis Recovered 0.25

MC 70 Normal Remains normal 0.75

BB 68 Senile depression No response 0.25

GC 75 Psychosis with Marked 0.5

arteriosclerosis improvement

RR 67 Psychosis with Marked 1 month

arteriosclerosis improvement

DG 68 Psychosis with No change Not provided

arteriosclerosis

NR 77 Psychosis with No change Not provided

arteriosclerosis

HV 70 Depression Remains well 1

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 168 Journal of Orthomolecular Medicine Vol 26, No 4, 2011

Table 3. Brief clinical descriptions of the therapeutic effects of niacin in elderly patients

Case JC (Age 80): In February, 1959, this woman had a mild coronary occlusion. She
developed generalized weakness, weakness grasping with one hand, anorexia, and ataxia.
She was also nervous and had feelings of confusion and hopelessness. During April, 1959,
she began to take three grams of nicotinic acid daily. Within a few weeks, her appetite
improved and she felt stronger. By June, she was able to walk slowly but well. Mentally, she
was much improved. She still had a few episodes of nervousness preceding social events.
There was no more confusion and her memory was good. For the next year, she continued
to improve and in April, 1960, she was quite well. In May, 1960, she had influenza and later
that month she died from a coronary occlusion and secondary metastasis of a bowel carci-
noma. She had been mentally alert up to three days before dying, when she sank quietly
into her fatal coma.

Case GC (Age 75): For several months Mr. G.C. complained of violent dizzy spells, with
headaches, vomiting and general deterioration. Physically he was normal. In November,
1959, he was given nicotinic acid, three grams daily. Two months later he was much im-
proved. He had no more dizzy spells and regained his normal vigour. April 13, 1960, he ran
out of tablets. There was a rapid relapse and again he complained of headaches and dizzy
spells. Nicotinic acid tablets were sent to him and again he improved.

responses that were observed by Hoffer and cursor), other amino acids and thiamine, and
his colleagues.12 In many of these cases, pa- found them reduced in patients with AD.16
tients who responded to niacin remained im- In these three studies, dietary intakes did not
proved as long as they did not stop the vita- satisfactorily explain the findings.
min. Once they discontinued it, they relapsed Niacin might also aid dementia as a
fairly quickly, but they improved again when result of its well-established cholesterol-
they resumed the vitamin. Hoffer reasoned modifying properties (i.e., lowers low den-
that these patients had metabolic conditions; sity lipoprotein-cholesterol, increases high-
vitamin dependencies which required more density lipoprotein-cholesterol, and lowers
niacin than they obtained from their diets. triglycerides).17 Research has shown choles-
Another case reported by Hoffer in 1974 terol reduction to possibly aid in the treat-
(and mentioned in his book, Smart Nutrients) ment of dementia.18,19 While data regarding
involved his mother who was 86 years old at this relationship is emerging, some published
the time of publication (Table 4, opposite).13 reviews have shown contradictory results
From the cited clinical reports, it is ap- and even negative outcomes from cholester-
parent that niacin administration offers clin- ol-modifying medication.20,21 More studies
ical benefits irrespective of dietary intakes. are needed to determine whether cholesterol
There is likely some metabolic need for ad- modification is a reasonable and effective in-
ditional amounts of niacin among a subset of tervention for dementia.
patients who show early signs of dementia Another possibility for niacin’s effective-
or have established dementia. Two case-con- ness might involve its ability to increase cere-
trolled studies reported lower blood levels of bral blood flow due to its presumed ability to
a nicotinic acid metabolite among patients increase cerebral vasodilatation. When niacin
with dementia compared to similarly aged is administered orally in amounts of 500 mg
controls.14,15 Another study assessed plasma or topically via a 6-inch patch of 10-1 M aque-
concentrations of tryptophan (a niacin pre- ous methylnicotinate on the forearm, prosta-

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 Treating Dementia with Vitamin B3 and NADH 169

Table 4. Hoffer’s clinical description of his mother’s response to a daily dose of 3000 mg of niacin

Case CH (Age 86): In 1954…my mother, then 67 years old, was very nervous and de-
pressed and complained of severe pain in her joints, failing vision in one eye, generalized
weakness and fatigue, and severe arthritis of her hands…Her memory was beginning to
fail. It was clear that she was aging very quickly. I knew no treatment was effective but
I was by then familiar with nicotinic acid used in megadoses. I decided to start her on 3
grams per day, more or less as a placebo…To my amazement, mother was nearly well six
weeks later. Her arthritis had cleared, her fingers were straight, and Heberden’s nodes be-
gan to soften and regress. Her vision in both eyes was normal, and her tension, anxiety, and
depression were gone…Today (1974) at 86 she is physically weaker, does not hear as well,
but is mentally well…She has been taking 3 grams each day of nicotinic acid for 18 years. I
have not seen any evidence of toxicity, and there has been no progression of mental senil-
ity which was so apparent 18 years ago.

glandin D2 (PGD2) is markedly released in rebral blood flow and in arterial blood pres-
the skin and high amounts of its metabolite sure in venous vessels of the head, but this
appear in the plasma.22,23 It is not known if was followed by a lowering of these parame-
PGD2 causes vasodilatation of the intracra- ters.27 In a study assessing cerebral blood flow
nial blood vessels, but niacin’s ability to abort in baboons under anaesthesia using single
acute migraine headaches suggests that this photon emission computed tomography of
might be occurring.24 the brain, a combination of niacin and pen-
Old reports cited by Bicknell and tifylline increased cerebral blood flow com-
Prescott,25 indicated that niacin causes vaso- pared to the control baseline (p<0.01).28 In
dilatation of the cerebral and spinal vessels. another study of similar design, the cerebral
They also noted that intravenous niacin ad- blood flow was increased above that of the
ministration increases the rate of intracranial control when a combination of pentyifylline
blood flow in human beings for 20-60 min- and niacin were administered to baboons.29
utes without any significant change in blood The increase in cerebral perfusion (denoted
pressure. Other published data pertaining to as an increase in R-value) was +29 % from
niacin’s effects on cerebral vasodilatation has the pentyifylline-niacin combination (2.31 ±
been equivocal. In one study, subjects hav- 0.19) compared to the control (1.79 ± 0.13).
ing various diseases (e.g., pernicious anemia, Based on these reports, it appears that
congestive heart failure, hysteria, diabetes, intravenously-administered niacin might
and hypertensive vascular disease) were giv- increase cerebral blood flow. More intra-
en intravenous niacin (300-800 mg in 200- venous niacin studies are warranted. Al-
300 mL of saline over 20-25 minutes). Nu- though no reports examine the effects of
merous measurements were obtained, such orally-administered niacin upon cerebral
as arterial pressures, blood oxygen contents, blood flow in human or animal subjects, nia-
glucose, cerebral oxygen utilization, cerebral cin could be increasing cerebral blood flow
glucose utilization, and cerebrovascular re- since it has been shown to abort acute mi-
sistance.26 The results of this study failed to graine headaches presumably by vasodilata-
find any effect upon cerebral vasodilatation tion of the intracranial blood vessels.24 This
by the intravenous administration of niacin. potential mechanism of action is important.
In an animal study using anesthetized Data demonstrate that as dementias of the
cats, intravenous injection of niacin (0.5 mL/ Alzheimer and vascular types progress, ce-
kg) caused a short-term increase in both ce- rebral blood flow and metabolism become

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 170 Journal of Orthomolecular Medicine Vol 26, No 4, 2011

functionally low.30 The severity of demen- inflammatory cytokine known as S100.35

tia symptoms have been correlated to de- IL-1 promotes the synthesis of beta-amy-
viations in cerebral blood flow and metabo- loid precursor protein (β-APP) in neurons,
lism.30 A more recent study found marked and promotes β-APP outside the cell where
cerebral blood flow reductions in the frontal it forms plaques.35 A preliminary study us-
(p=0.001) and parietal (p=0.001) cortices in ing rats found that slow-release niacin, or a
both vascular dementia and AD, when com- combination of slow-release niacin and sim-
pared to aged-matched cognitively normal vastatin, were able to reduce axonal damage
controls.31 Since orally-administered niacin and increase axonal density by decreasing the
benefits some patients, its therapeutic prop- expression of amyloid precursor protein.36
erties might facilitate cerebral vasodilatation While this study is very preliminary, these re-
and increase cerebral blood flow. sults suggest that supplemental niacin might
Niacin might also benefit patients with offset the production of amyloid plaques,
dementia as a result of its ability to stimulate which are perhaps the most important histo-
cellular metabolism. The brain is almost en- pathological markers in AD. Amyloid plaques
tirely dependent on the metabolism of glu- also occur within the brain when ischemia is
cose by oxidative processes. In a decades-old present,36 which suggests that supplemental
study, patients with organic brain syndromes niacin might lessen axonal damage associ-
(mean age: 68 years) had their cerebral blood ated with vascular types of dementia as well.
flows evaluated.32 Clinical deterioration and Table 5, (opposite) summarizes niacin’s pur-
functional decompensation was associated ported mechanisms of action in the treat-
with a worsening in cerebral and oxidative ment of AD and vascular types of dementia.
metabolism, and a resultant shift to anaero-
bic glycolysis. Significantly heightened ce- Treating Dementia with NADH
rebral metabolic rates of lactate were con- NADH is a coenzyme in all living cells,
sidered a causal quantitative factor in the including the brain. As a component of the
pathogenesis, manifestation, and severity of electron transport chain, it plays a central role
organic brain syndromes. in intracellular energy production. NADH
An insufficient supply of nicotinamide is also believed to increase the synthesis of
adenine dinucleotide (NAD) is known to the neurotransmitters dopamine and norepi-
inhibit the conversion of lactate to pyruvate, nephrine in the brain.
and contribute to a high lactate-to-pyruvate In an open-label pilot trial involving 17
ratio.33 Therapeutic doses of niacin might di- AD patients taking 10 mg of NADH 30-
minish the shift in anaerobic glycolysis (and minutes before their first meal for 8 to 12
lower lactate levels) as a result of niacin’s abil- weeks, all patients had demonstrable cogni-
ity to increase the synthesis of NAD.34 The tive improvements (as per favorable changes
increased synthesis of NAD might drive the in their mini-mental state exams and global
conversion of lactate to pyruvate, enhance ox- deterioration scales).37 No side effects were
idative processes within the brain, and miti- associated with the NADH treatment. Some
gate cerebral metabolic disturbances associ- patients took NADH for more than one year.
ated with increased cerebral lactate levels. They also reported no side effects.
Yet another potential mechanism might Following the pilot trial, 25 patients with
explain how niacin benefits some patients mild to moderate dementia of the Alzheimer,
with dementia. Niacin might reduce axonal vascular, and fronto-temporal types received
damage and increase axonal density. Re- 10 mg of NADH daily in addition to their
search has shown that neuronal damage in cholinomimetic medication.38 Nineteen of
the brains of patients with AD leads to acti- the 25 patients completed this 3-month
vation of brain immune cells – microglia and open-label trial. The results showed no evi-
astrocytes – and stimulates them to produce dence of benefit (as per established psycho-
interleukin-1 (IL-1) and a soluble astrocyte metric tests), so the authors concluded that

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 Treating Dementia with Vitamin B3 and NADH 171

NADH is unlikely to enhance cognitive and visual-construction ability (p=0.038),

ability and could not treat dementia. with a trend toward improved abstract ver-
The most recent trial, published in 2004, bal reasoning (p=0.08). No differences were
was favorable.39 In this randomized, place- found between the AD patients and placebo
bo-controlled, matched-pairs, double-blind, group in measures of attention, memory, or
6-month clinical study, patients with prob- clinician ratings of dementia severity.
able AD (n = 26) were randomized to re- The rationale for using NADH as a
ceive either NADH (10 mg/day) or placebo. treatment for dementia comes from several
At the conclusion of the trial, AD patients sources of evidence which suggest that this
who received the NADH treatment had no treatment can reverse some of the defects as-
evidence of further cognitive deterioration. sociated with AD (Table 6, below).40 Clearly
Their dementia rating scales showed im- more studies are needed. The initial dosage
proved scores compared to the AD patients of NADH should be 10 mg/day about 30-
in the placebo group (p<0.05). Specifically, minutes prior to a meal. The label or package
the NADH treatment was associated with insert must state that the particular NADH
significantly better verbal fluency (p=0.019) product is stabilized; otherwise, it will be de-

Table 5. Niacin’s purported mechanisms of action in the treatment of AD and vascular types
of dementia
t
3FTPMWFT
NFUBCPMJD
EFQFOEFODZ
CZ
SFQMFUJOH
FO[ZNF
DPGBDUPST

t
.PEJmFT
MJQJE
MFWFMT
JF
UIF
DIPMFTUFSPM
QSPmMF

t
*ODSFBTFT
DFSFCSBM
CMPPE
nPX
WJB
WBTPEJMBUBUJPO

t
4UJNVMBUFT
DFMMVMBS
NFUBCPMJTN
CZ
JODSFBTJOH
UIF
QSPEVDUJPO
PG
OJDPUJOBNJEF
BEFOJOF


dinucleotide

t
3FEVDFT
BYPOBM
EBNBHF
BOE
JODSFBTFT
BYPOBM
EFOTJUZ
CZ
EFDSFBTJOH
UIF
FYQSFTTJPO
PG


amyloid precursor protein

Table 6. NADH’s purported mechanisms of action in the treatment of AD

AD Defects reported in the scientific literature NADH’s biochemical effect

Dopaminergic neurotransmitter Increases dopamine production by

system dysfunction regenerating tetrahydrobiopterin, an
essential cofactor in tyrosine
hydroxylase

Increased oxidative stress Repletes antioxidant level

Reduced activity of enzymes (i.e., NADH Reverses oxidative phosphorylation

ubiquinone oxidoreductase and NADH diaphorase) defects
important for energy metabolism in the brain

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 172 Journal of Orthomolecular Medicine Vol 26, No 4, 2011

graded by the hydrochloric acid in the stom- Conclusion

ach and rendered ineffective. Numerous clinical reports have shown
that patients with dementia can benefit from
Current Research niacin supplementation. Niacin can also help
At present, research evaluating the ther- to prevent the incidence of AD. This makes
apeutic applications of niacin and/or NADH niacin therapy a clinically-plausible inter-
for dementia is at a standstill. However, nia- vention which merits further study. One
cinamide is being evaluated in a clinical trial open-label and one small randomized con-
to determine if it is safe and beneficial for trolled trial have shown NADH to benefit
patients with AD.41 Patients will be random- patients with AD, but no substantive clini-
ized to treatment or placebo groups. Those cal trials have been done to confirm these
given niacinamide will take 1,500 mg twice preliminary findings. Only niacinamide
daily for 24 weeks. The results of this study is currently being investigated as a treat-
should be available within the next year. The ment for AD. Hopefully, the forthcoming
rationale for using niacinamide is that it can results will be positive and encourage re-
prevent nerve cell degeneration in animal searchers and clinicians to review the lit-
models of various neurodegenerative diseases erature and perform additional research to
(e.g., amyotrophic lateral sclerosis, Hunting- verify the benefits of vitamin B3 therapy for
ton’s disease, and Parkinson’s disease).42-44 In treating dementia, develop dosage recom-
addition, niacinamide was shown to markedly mendations and revise clinical guidelines.
improve learning and memory in transgenic
mice that develop AD. Treatment with the Acknowledgements
vitamin also resulted in decreased accumula- I thank Mr. Bob Sealey for his helpful
tion and increased stabilization of tau, a pro- editing suggestions and input on the con-
tein that accumulates excessively in AD.45 tents of this paper.
The earliest report showing that niacin-
amide can assist in dementia was written by Competing Interests
Foster, in 1949, after he gave niacinamide to The author is a consultant for Veeva Inc.,
40 patients with toxic psychosis (considered a company that develops and sells natural
an organic reaction accompanied by mem- health products with a strong focus on stress,
ory defect, disorientation, and other mental anxiety, sleep and overall mental health well-
deficits).46 Twenty-three of the 40 patients ness. Veeva Inc. has not seen this manuscript
were over the age of 60. Foster concluded nor do they have any knowledge of it.
that niacinamide therapy should be com-
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