A text about Niacin:
TOURETTE SYNDROME, ALLERGY
AND THE B6 DEPENDENCY STATE
I have my Bachelor's degree in Biology, specializing in Medical
Technology, and in graduate school, I took graduate courses in
biochemistry. I work as a medical technologist performing and
verifying clinical laboratory tests in Chemistry, Hematology and
Blood Bank at Mt.Carmel East Medical Center in Columbus, Ohio.
I do not have TS but my son, Jason (13 yrs old) has TS with OCD.
ADD has not been formally diagnosed, although he has problems
with organization, distractibility, and the ability to switch gears.
My son has had allergies since he was a baby. He
is sensitive to red dye #40 with tired splitting headaches which
make him scream until he is exhausted and sleeps. This, of course,
hasn't happened in several years since he has avoided the dye.
He also is allergic to sulfa, molds, dust, grass, trees, and most airborn
allergens. He has been on the vitamins below for 1.5 months and the
teachers
have said that he is a different kid. Medications that he had been
on made him progressively worse, and so we made a personal decision
to discontinue meds altogether. He now is motivated in school,
concentrates
and finishes his work, and is less disruptive with his tics in class. At
home he still has his tics and compulsions, but they are shorter lived
and occur less often. He has had a set back this week due to a new
semester with a new schedule, plus a very moldy, rainy few days. We
gave him a little extra calcium-magnesium and one extra vitamin B3.
He said that this gave him relief from his symptoms (he has never
said this before with anything else).
I solidified my theory on the premise that Jason
is probably mildly vitamin B6 dependent. He was either born requiring
high amounts of B6, and/or B6 antagonists attacked early in his first year
of life. B6 antagonists are hydrazines (plant growth regulators,
tartrazine,
etc), DOPA found in certain beans, penicillinamine, antioxidants in
petroleum, many drugs including penicillin, erythromycin, phenobarbital,
tetracycline, corticosteroids, sulfamethoxazole, etc. Amino acids began
building up in his system, from decreased transamination, etc.
Serotonin became decreased from tryptophan not being able to
be utilized. Allergies developed (which is in association with low B6),
I believe allergy produces swings in histamine levels which causes
a constant fluctuation in neurotransmitters capable of producing mood
swings and rages. The conservation of vitamin B6 (when not abundantly
available) causes it to be used by the prevailing neurotransmitter system
at any given time, leaving other neurotransmitter systems less than
optimally functional. Histamine receptors have been found to trigger
dopamine receptors directly.
Histamine is also a neurotransmitter affected by deficient vitamin B6.
Its
receptor sites are probably increased to compensate. Kinins released
into the body's tissues in response to immune complexes can damage
the blood brain barrier, thus altering the sensitivity of brain cells to
acetylcholine, serotonin, dopamine, histamine, epineprine and
norepineprine.
I found that L-dopa doesn't readily form dopamine in B6 deficiency,
so probably dopamine is reduced causing an increase in
dopamine receptor sites along with an increase the norepinephrine
and epinephrine (which are formed from dopamine) receptors sites.
These increased receptor sites make the nerves more excitable and
false transmitters or true neurotransmitters can set them off with
explosive qualities. These false transmitters can
be phenolic substances, such as food additives, drugs, etc.
The enzyme, phenol sulfotransferase (PST), detoxifies and eliminates
phenolics (drugs, food additives, serotonin, dopamine (to name a few).
In the brain, sulfation is used while glucuronidation prevails elsewhere.
Cysteine requires B6 to enzymatically release sulfur for sulfation of
these phenols by PST. Considering this, the neurotransmitters would
would be conserved to a certain extent (their sulfation and elimination
would be slowed down). ADD may happen when these false transmitters
create background "noise", and if there is a real message to get through
via other neurons, it is masked. When a true message is fired, it may
have too strong of a signal, creating a strong impulsion, which can lead
to the development of a tic or compulsion if the impulsion is acted upon
and repeated creating a sort of conditioned reflex network of nerves.
Mental, motor, and vocal tics can develop this way.
According to my_ Biochemistry_ by Lehninger textbook
from my graduate student in Biology days, tryptophan is broken down
in Vitamin B3 deficiency to make nicotinic acid. Tryptophan is
found in meat and is plentiful, if you are a meat eater. Tryptophan
is the precursor for serotonin. I also looked up Vitamin B3 and
how it could be connected to the issues of allergy
and serotonin defiency in the brain. I found that Vitamin B3 is used
to make NAD, NADP, which are coenzymes used in making
histamine and serotonin (to name a few), and are essential in
oxidative-reductive cellular metabolism. The B3 is needed due to
tryptophan's inability to be broken down to nicotinic acid without
adequate B6.
So, if Vitamins B3 and B6 are being used for histamine production, then
serotonin production suffers. Tryptophan then must be used in
a higher frequency to make nicotinic acid. In Vitamin B6
deficiency, this cannot happen, because the enzyme kynurinase,
that catalyzes the cleavage of 3 hydroxykynurine
(an intermediate in tryptophan catabolism),
contains pyridoxal phosphate (an active coenzyme form of Vitamin B6).
In Vitamin B6 deficiency, large amounts of L-kynurenine are excreted
in the urine, because of its high plasma levels.
This is described in "Elevated plasma kynurenine in
Tourette syndrome", _Molecular & Chemical Neuropathology_21(1):
55-60,1994 Jan. Kynurenine itself is metabolised to other
substances, several of which are known to have effects on
neurones. (per a research study done at University College
London Medical School Harlow, England by Sheila L. Handley,
BPharm, Ph.D. 1994) Large amounts of tryptophan which is broken down
to ineffectively try to produce nicotinic acid reduces the amount of
serotonin produced. Ineffective tryptophan utilization
also uses alot of oxygen with tryptophan 2,3-dioxygenase.
Low serotonin levels could cause obsessive compulsive behaviour,
depression, and other mood related disorders.
B6 is also required for the decarboxylase step of
serotonin, histamine, and catecholamine pathways in the brain.
In low B6, conservation takes place, so that B6 is used for fewer
enzymes. When allergy strikes, the production of histamine causes
a further imbalance of neurotransmitters, causing serotonin and/or
catecholamine production to be further depleted.
Sherry A Rogers, M.D., a specialist in environmental medicine,
reports that all of the TS cases she has seen have a least one
nutrient deficiency, and usually several. And she notes that all
of these patients have hidden mold, dust, chemical and food
sensitivities. ("Tourette Syndrome", _Health Counselor_, Vol.7, No.4)
Acetylcholine is produced by acetyl CoA and choline.
The choline is supplied through lecithin in Jason's supplements.
In vitamin B6 deficiency, acetyl CoA would be made by
fatty acid oxidation. So acetycholine could be functional
with an adequate supply of fatty acids (evening primrose oil or flax
oil might be useful).
Acetylcholine could be in shorter supply in the parasympathetic
system (relaxation) due to overuse in the sympathetic system where
norepinephrine usually rules. The parasympathetic nervous system would
need to have more acetylcholine in TS and associated disorders, it seems.
Relaxation through the parasympathetic nervous system (which uses
acetylcholine), where the heart rate is slowed, the blood pressure is
lowered, the food is digested well, etc. is difficult in TS.
Acetylcholine is probably overactive in the sympathetic autonomic
nervous system, trying to stimulate the low supply of catecholamines,
which would be decreased due to B6 deficiency/dependency.
The receptors sites for catecholamines would be hyperexcitable
and increased in number. The net usage of catecholamines could
be normal to decreased due to increased stimulation by acetylcholine,
depending on the availability of B6 in the body, and the conservation by
low
sulfation by PST.
Conditions of emotional stress are known to produce more ticcing in TS.
In short term stress, norepineprine, dopamine, and epineprine should
be able to be produced by the conservation tactics of the body, but in
long term stress, these would be exhausted, especially when another
B6 dependent system is triggered. Likewise, the same would happen
when histamine and serotonin are produced in short term and long term
allergy. But as you might expect, the short term conditions
would be explosive events with all of those increased receptor sites!
Acetylcholine is also involved in the contraction of
voluntary muscle cells and many other motor nerves, which are
in heavy use in TS. Many people with TS are helped by
exercise, where cardiac output and increased body temperature
over a period of time inhibit the sympathetic nervous system. It
may also help to clear toxic waste, such as kynurenine.
Adequate water intake would be required to catabolize
acetylcholine by cholinesterase. In my opinion
acetylcholine is needed in B6 deficiency/dependency to run
the nervous system. Fatty acids are essential to its success
in this situation. Fatty acids require NADPH2, and NADH2
for their synthesis, and thus Vitamin B3. Water is also an utmost
requirement in keeping acetylcholine from becoming a continuous
firecracker. Jason has a water bottle close by most times and
drinks tons of water. Water has always calmed him down. It may
also dilute the kynurenine, excess amino acids and promote their
excretion.
If you look at the material written on the Canadian Mennonite families
that
have been studied with
Tourette's disorder, you will see a high frequency of autoimmune and rare
conditions. These findings are consistent with what one can expect with
other
Tourette's patients. For example, there is a high frequency of allergic
conditions.
My informal survey of TS and allergy results from the online TS support
group are:
With a total of 25 respondents with TS:
96% have allergies (24 out of 25)
56% have mold allergies
72% have obsessive complulsive traits (18 out of 25)
67% of those with obsessive compulsive traits
have mold allergies
3 respondents thought they may have mold allergies, but
weren't sure
52% have pollen allergies (ragweed, grass, tree, etc)
56% of those with obsessive compulsive traits have pollen
allergy
48 % have animal allergies (cats, dogs, horse)
39% of those with obsessive compulsive traits have animal
allergies
40% have dust allergy
39% of those with obsessive compulsive traits have dust
allergy
20% have penicillin allergy
28 % of those with obsessive compulsive traits have
penicillin allergy
20 % have miscellaneous allergies
11% of those with obsessive compulsive traits have
miscellaneous allergies
16 % have food allergies
22 % of those with obsessive complulsive traits have
food allergies
8% have sulfa allergy
11% of those with obsessive compulsive traits have
sulfa allergy
