- the supervitamin body and mind energizer
by James South MA
NADH is the abbreviation used for Nicotinamide Adenine Dinucleotide, one of the
most important coenzymes in the human brain and body.
A coenzyme is the active, or
working form of a vitamin. NADH is the reduced (electron- energy rich) coenzyme
form of vitamin B3, while NAD is the oxidized (burned) coenzyme form of B3.
NAD and NADH are converted into
each other in numerous different metabolic activities. In some metabolic
reactions it is NAD which is the needed catalyst, with NADH a useful by-product,
in other reactions the situation is reversed.
NAD and NADH also serve to
activate various enzymes, NAD for example, activates alcohol dehydrogenase and
acetaldehyde dehydrogenase that are the two enzymes needed to detoxify the
alcohol we drink into carbon dioxide and water.
NADH is the first of five enzyme
complexes of the electron transport chain, where much of the ATP bioenergy that
runs every biological process of our lives is formed.
NADH its vital chemical role
As already noted, NAD(H) is the
coenzyme or active form of vitamin B3. The chemistry of NAD(H) is some of the
most complex in the human body. NAD(H) is necessary to oxidize (burn) all
foodstuffs (fats, sugars, amino-acids) into ATP bioenergy. There are three
interlinked energy production cycles: the glycolytic (sugar burning) and
Krebsí citric acid cycles (aminos and fats are "burned" through the
Krebsí cycle), and the electron transport side chain.
A glycolytic cycle
"waste" end product- pyruvic acid- helps power the Krebsí cycle,
while electron "sparks" released from the step by step slow
"burning" that occurs in the Krebsí cycle provide the fuel used by
the electron transport side chain to generate much of the ATP bioenergy that literally powers our life.
NAD(H) is involved in all of these different cycles, as well as in the
conversion of the pyruvate end product of the glycolytic cycle into the
beginning fuel of the Krebsí citric acid cycle. It is NADH, which captures the
electron "sparks" thrown off during Krebsí cycle oxidation and
shuttles them to the electron transport side chain energy production cycle.
Each unit of NADH is capable of
generating three units of ATP energy. In a very real sense, NADH is the
"energy of life" coenzyme.
NAD(H) is a relatively large and
complex molecule, as coenzymes go. It is vitamin B3 (niacinamide) combined with
a ribose (5-carbon sugar), a phosphate group and an adenine nucleotide (a DNA
component). NAD(H) can be made in the liver and other cells from vitamin B3.
It can also be made from the
amino acid L-Tryptophan at the "expensive" ratio of 60mg tryptophan
for 1mg B3. Taking in exogenous (from outside the body) B3 or NAD(H) may spare
the scarce amino acid tryptophan, which is the least plentiful amino in any
normal diet. Tryptophan is the precursor of one of the most important
antidepressant neurotransmitters, serotonin.
NADHís role in Parkinsonís
J.D. and W. Birkmayer of the
Birkmayer Institute have pioneered the clinical use of NADH only in the last
decade for Parkinson Therapy, Vienna, Austria.
The Birkmayersí are the first
to develop a stable and absorbable oral tablet form of NADH. They have also
conducted groundbreaking research on the use of NADH in Parkinsonís disease,
depression, Alzheimerís dementia and fatigue.
In a series of scientific papers
published between 1989 and 1993 the Birkmayers have related their clinical
success with NADH in Parkinsonís, as well as provided supporting biochemical
experiments and rationale for their success with NADH.
Parkinsonís disease, one of the
most common neurological diseases of aging, involves the gradual and even more
severe destruction of the dopamine using neurons, in a brain region called the
substantia nigra. Parkinsonís involves movement disorders, speech
difficulties, depression and cognitive dysfunction.
The traditional medical therapy
for Parkinsonís is L-dopa, the amino acid precursor of dopamine. However, this
therapy has serious drawbacks. After a period of use, even higher L-dopa doses
are required, and these eventually cause severe side effects. In addition the
dopamine formed through L-dopa therapy is prone to auto-oxidation to free
radical forms that eventually "burn out" what few dopaminergic neurons
(Parkinsonís disease begins
when the substantia nigra neuron population has dropped to 20-30% of normal).
Dopamine is usually made inside
the neurons that use it through a two step process. The amino acid tyrosine is
first converted to L-dopa through an enzyme called tyrosine hydroxylase.
L-dopa is then converted to dopamine. Research has shown that it is
the activity of tyrosine hydroxylase, which is the rate-limiting controller of dopamine synthesis,
and tyrosine hydroxylase activity is considerably lower in Parkinsonís patients than healthy
Research has also shown that
giving Parkinsonís disease patients L-dopa diminishes their already weak tyrosine hydroxylase
activity, thus further limiting their own L-dopa production and increasing the
need for L-dopa supplements in an ever worsening vicious spiral.
The Birkmayers discovered that
the coenzyme that activates tyrosine hydroxylase - tetrahydrobiopterin (H4BP) is reduced 50% in the
brains of Parkinsonís patients compared to age matched healthy controls. They
further discovered that NADH activates the enzyme, which helps produce H4BP.
Cell culture studies showed that
NADH could elevate tetrahydrobiopterin production, tyrosine hydroxylase activity and dopamine production.
The Birkmayers thus decided to
try a therapy that might increase the brainís own production of dopamine,
rather than suppress it as L-dopa therapy eventually does.
The Birkmayersí treated a group
of 885 patients with NADH, 415 with intravenous (IV) NADH and 470 with oral NADH
(Acta Neurol Scanda, 1993, PP 32-35).
Both groups showed overall good
response to treatment, especially in motor improvements, walking, pushing,
posture and speech. They also noted cognitive and emotional improvements in some
patients, and surprisingly, the improvement figures for both IV and oral NADH
were almost identical, and the maximum total improvement was actually shown by
oral NADH users.
The Birkmayers also found
increased urinary excretion of dopamine metabolites in the patients, indicating
there was an actual NADH induced increase in dopamine production. They also were
able to reduce and even eliminate other anti-Parkinson medications in some
NADH and its anti-depressant
Based on their success with NADH
treatment of Parkinsonís patients, the Birkmayers decided to try NADH as an
antidepressant in 205 depressed patients. There are multiple theoretical
rationales for such use.
NADH increases brain dopamine and
noradrenaline using brain cells use dopamine to make noradrenaline.
It is generally accepted that
dopamine and/ or noradrenaline are frequently diminished in the brains of
depressed patients, and drugs that raise brain dopamine/ noradrenaline levels
will frequently end depression. In addition, through NADHís sparing of
tryptophan (discussed earlier in this article), more tryptophan would be left to
end up as brain serotonin, another neuro-transmitter frequently reduced in
depressives, and when drugs or tryptophan supplements raise brain serotonin,
this frequently halts depression.
Lastly, it should be noted that
the human brain must produce and use 20% of the bodyís total ATP bioenergy,
and PET scans of the brains of depressed and demented people frequently show
reduced brain energy production. Thus, through its multiple roles in producing
ATP energy, NADH might be expected to literally energize the brain, and
depression may be in part the mental/ emotional direct experience of the
brainís lowered energy status.
Not surprisingly therefore, the
Birkmayers reported in their 1992 paper in New Trends in Clinical
Pharmacology, a beneficial effect in 93% of the NADH treated depressed
As with their Parkinsonís
patients, the Birkmayers found that NADH tended to induce serious improvement
more in younger (less than 65 years old) than older patients. Their
Parkinsonís studies also showed shorter duration illness patients to benefit
more than longer duration patients.
NADH and Alzheimerís disease
Because many Parkinsonís
patients exhibit dementia as well as neurotransmitter problems, while many
Alzheimerís patients exhibit neuromotor dysfunction as well as dementia, the
Birkmayers next tried oral NADH on 17 Alzheimerís dementia (AD) patients
(unpublished paper). These patients ranged from mildly to severely demented. The
results were nothing short of astounding! Not only did NADH halt the progression
of Alzheimerís disease, it significantly reversed the cognitive and behavioral
problems, even in the worst cases.
The NADH therapy was even able to
restore some patients from being virtual "vegetables" to a semblance
of normalcy. The Birkmayers also did before and after urinary analyses of
dopamine and noradrenaline metabolites and found evidence indicating
significantly improved brain dopamine/ noradrenaline activity. While deficits in
the function of acetylcholine neurons is the more well known pathology of
Alzheimerís dementia, studies have also shown seriously diminished dopamine/
noradrenaline nerve activity in Alzheimerís dementia.
In several patients NADH was
halted briefly to determine if the improvements would last without it. After
several weeks absence of NADH (after a yearís NADH treatment), deterioration
began. Once again, NADH was started, and the previous improvements were
brain formula Raise your IQ
NADH a possible fatigue fighter?
In June 1997 W. Birkmayer was to
announce the details of a successful trial using NADH to combat fatigue at a Las
Vegas health convention. I was unable to get the details at the time of writing
However, given the
multi-dimensional roles of NADH in all aspects of human cellular ATP production,
favorable results with NADH in fatigue situations is hardly surprising.
NADH doses and uses
The standard dosage of NADH has
been 10mg, taken with water 30 minutes before breakfast.
Animal studies suggest 1000mg per
kilogram of body weight (70,000mg for a 154 pound human!) to be a tolerable
dosage, so aside from the expense, there is no reason not to experiment with
higher doses should 10mg not suffice to bring a hoped for benefit.
Those wishing to use NADH in
Parkinsonís cases might do well to accompany it with tyrosine and deprenyl.
Those wishing to try NADH for
depression might add DLPA, tyrosine and/ or tryptophan or 5-hydroxy-tryptophan.
Those wishing to try NADH for
Alzheimerís dementia might include acetyl-L-carnitine and DMAE or
centrophenoxine (Lucidril) with NADH.
In serious fatigue situations,
B-complex vitamins, alpha-lipoic acid, CoQ10 or Idebenone and magnesium would be
synergistic with NADH.
In situations involving chronic
alcoholism, however the cellular NAD/ NADH ratio is already detrimentally skewed
in favor of NADH, so NADH would not be appropriate.
Given the routine interconversions in all cells
between niacin, niacinamide (2 forms of vitamin B3), NAD and NADH, as well as
B3ís sparing effect on tryptophan, it may be useful to add small (50-100mg)
doses of vitamin B3 to any NADH regimen