Vitamine B6 deficiency and future for POIS?

[Daveman]

This thread starts with a quote made by Starsky on the XN thread. It belongs to that thread, but I felt that it will also be a good base for resolving many "Brain Fog Issues" that don't seem to be covered by the autoimmune theory.

To me it seems like a very exciting scenario.

It's quite technical, but deciphering should be very interesting.

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

[B_Daniel]

Starsky,

You are much smarter than me.  I understood bits of that, like that a B3 or B6 deficiency can be causing all sorts of harm to my serotonin levels and more.  But I didn't really come away from reading all that with a plan.  Do you recommend I take a tryptophan or B6 supplement?  I've taken some of those pills in the past and have never felt better from it.  Maybe I wasn't paying close enough attention to my body, but i know at least it's not the magic cure i'd ideally like.  But Starsky, what's your take-away from all that?  Should I be taking a b6 supplement?

[Daveman]

Hi B_Daniel,

It sounds interesting, although as you say pretty technical. I think there's a lot of information here that needs to be processed, to see how it relates to the whole chain in a POIS cause somewhere.

This explains for instance how B3 and B6 could be related to some of the POIS symptoms, but doesn't necesarily indicate why we may be deficient or where exactly in the chain our system might be broken.

For instance, for the moment we are more directed towards "correcting" or raising the B3 levels before "O". It works, but we aren't sure why. I'm not sure what we know (through member experience) as far as B6. Have we tried it and it hadn't worked? Why didn't it work? Is it important to take it at a certain hour? Is our system "broken" at a point that unties the relationship between B6 and B3, or makes it irrelevant?

Lots to check into, but answers should be out there.

I've been in POIS so no energy to start taking it apart. But I'm going to reread the post and see if there are some GOOD things we can start looking up or even testing!!

[Daveman]

I gave this post another read, and got to about half way!!

But from what I can see, it goes a long way to explaining many POIS symptoms including brain-fog depression and ADD.

It points to a tremendous chain of weaknesses that can result from B6 definciency.

It seems there may be an outright B6 definciency or a high B6 dependancy, when B6 can't be utilized fully.

One of the deficiencies that can result is B3 which is produced from B6. And to make up for the B3 defiency, a precursor of serotonine and histamines is overused, producing low levels of serononine especially when allergies are present needing histamines.

So by taking B3, it seems we free up the precursor allowing the histamine production without letting the the serotonine levels drop.

So I hope that is a slightly easier reading description, as it could relate to POIS. There's still more in there that I can;t get my head around right now.

Anyone else want to take a stab?

[0002ppdnuos]

Hadn't Daniel in another thread tried Hidroxil which contains B1, B6, and B12?
It worked for him.

[Observer]

Hadn't Daniel in another thread tried Hidroxil which contains B1, B6, and B12?
It worked for him.

After taking a more profound look to the text that Starsky provides us, i think that it´s very logic that B-6 is working.

Then, in Daniel´s case, the extra-B-6 would allow more tryptophan to be transformed into niacin, and niacin will produce the extra-histamine against the allergic reaction(It will explain why when i had the skin prick test after taking the niacin, i showed reaction but i did not develop any POIS symptoms.)  and at the same time, it could cope with a normal serotonin production - thus no symptoms are produced.

Maybe, when we are taking niacin we are not preventing the allergic reaction of POIS, but its effects.

[Observer]

Another point is that i realized that what i was eating was directly related to my POIS symptoms. Food with high Glucemic Index would cause a "hell" on my mind and my cognitive function (BUT ONLY WHILE IN POIS, not out of POIS). Brain fog/cognitive impairment will dramatically spike after taking this kind of foods- like red meat, sugar, desserts, msg, alcohol -.

It has been discussed here that some of us could be "Hypoglicemic" while in POIS.  I feel compelled to share this text with you:

What is happening?

Two possible reasons behind brain fog with respect to hormones can be hypo-glycaemia (...)

Insulin is a hormone responsible for moving glucose out of the blood stream into tissues where it is either used as energy or stored as fat.

Foods that are rapidly converted into glucose are known as high glycaemic index (GI) foods and when we eat them they increase sugar levels in the blood.

Insulin is secreted by the pancreas in response to these high GI foods and also to coffee, cigarettes and alcohol.

In some individuals, this high insulin level brings about a rapid drop in blood glucose levels, resulting in a drop in energy.

Other symptoms of this drop in sugar levels can be headaches, palpitations, fuzzy thinking, feeling anxious, or a sudden desire for another “quick fix” of sugar or coffee.

This is known as “hypoglycaemia”, or low blood sugar levels. Mid-afternoon is a classic time to experience these symptoms, but they can also occur if you haven’t eaten for a while, or have recently eaten a high GI “hit” like lollies.
Source: http://www.superliving.com.au/health/mental-health/science-and-research/how-hormones-can-affect-brain-fog

Looking for more answers i found this, Vitamin B-3 and Vitamin B-6 play a very important role in avoiding Hypoglycaemia:

Niacin (a B vitamin) works to metabolize carbohydrates in the body. Another important one to take is vitamin B6. Vitamin B6 helps to metabolize glucose (blood sugar) and stabilize glucose levels. You can find a good combination of the B vitamins to take in one tablet.

Read more: How to Treat Hypoglycemia With Vitamins | eHow.com http://www.ehow.com/how_2122693_treat-hypoglycemia-vitamins.html#ixzz1wr7rUlYY

Just more food for thought,

Regards.

[0002ppdnuos]

You guys are amazing researchers. 

[Observer]

Perhaps in POIS, The niacin in our body cannot lower and adjust the glucose levels - because it is occupied with allergic response and there is simply not enough -, and then a massive insuline response is activated thus causing hypo-glycaemia.

Then Vitamin B-6 should work turning the carbohydrates into glucose when the sugar blood levels are low(hypo-glycaemia), but if we are deficient on B-6 this could not happen properly, and POIS cognitive symptoms are increased.

Again,in my case, this only happens in POIS, and not out of POIS.

I don´t know if what i am saying makes any sense(i am trying to achieve it   ), i hope more people jumps into these reflections.

My sources:
http://www.ehow.com/about_5030650_effect-niacin-glucose-levels.html
http://www.livestrong.com/article/510258-what-are-the-effects-of-vitamin-b6-on-sugar-levels/

[0002ppdnuos]

My brewer's yeast had just arrived.
I'd try it tomorrow morning.
It contains lots of B6 and other B-complex.
I couldn't take B-complex pill.
It somehow worsened my POIS symptoms.

[Nightingale]

I do think this is a next step in the pathology of POIS.  I am thinking about putting together a post for reddit at /r/askscience/

There are many biologists/nutritionists that frequent that subreddit.  If you feel like helping, please write a sentence or two that can help summarize and condense our question into something easy to read

[Observer]

I do think this is a next step in the pathology of POIS.  I am thinking about putting together a post for reddit at /r/askscience/

There are many biologists/nutritionists that frequent that subreddit.  If you feel like helping, please write a sentence or two that can help summarize and condense our question into something easy to read

Nightingale, count me on this one for helping with it, you should ask for it on the NSF too.

[Daveman]

I do think this is a next step in the pathology of POIS.  I am thinking about putting together a post for reddit at /r/askscience/

There are many biologists/nutritionists that frequent that subreddit.  If you feel like helping, please write a sentence or two that can help summarize and condense our question into something easy to read

Great idea. I barely have time to write my name right now though, but can lend a hand once it’s posted.

We  need to take this reference and adapt it such that it fits our particular case though, considering that this reference represents a different albeit similar syndrome.

For instance, what effect does orgasm have that triggers the reaction or deficit? Is it a deficit or is it a lack of capability to utilize substances? Does the histamine release during orgasm stimulate the imbalance? Do we release MORE histamines than the average? Does some autoimmune response require more histamine?

It seems that extra niacin in the bloodstream ONLY DURING ORGASM is what contributes to the “magic”. Niacin before or after don’t contribute.

There’s a “magic process” that happens just at orgasm that is capable of utilizing niacin (B vitimins).

Those are some questions and thoughts.

Great idea and go for it!

[Nightingale]

Got it.  I'll post in NSF tomorrow with some of my own ideas and drum up some more...!

[vetrofragile79]

I tried some of the b group vitamin supplement but did not enhance the effect of niacin. Niacin causes me pain in the shins, this happens to you?

[Daveman]

Pain in the shins. That's a new one for me!

How long does it last? Just during the flush or for a while after?

[Nightingale]

Acetylcholine is produced by acetyl CoA and choline.
The choline is supplied through lecithin in Jason's supplements.

Acetylcholine seems to be a major player in this boy's symptoms, and maybe ours.  Lecithin supplementation sounds like a good thing to try, in conjunction with fatty acid supplementation.  The vitimin B6 deficiency seems to cause major increases in neurotransmitter receptors, and might lead to a burnout of transmitters that Acetylcholine seems to help make.  I am going to look into it more, and pick up Lecithin tomorrow.

On a personal note, I think this might explain something I've suffered heavily from, and almost killed myself over: severe reactions to medications taken for deperession, bipolar, and schizo-affective disorder (schizophrenia-like symptoms).  I had a little cry reading this material, because I saw an explanation for my problems.  I hope to be seeing a research-focused neurologist soon, and I will be armed with this man's findings!  Really gives me hope 

[Daveman]

I’m enthused by the activity in this direction. The process is complicated, especially if one is not a neurobiologist, so the more of us helping out with the interpretations the better.

Like you Nightingale, this path gives me some hope. That emotion that you felt at the possibilities is what will drive us to beat this thing.

Let us know what you find and don’t give up until we all have a chance to evaluate what might be going on.

[Starsky]

Did someone else tried B6 megadoses?

[Stef]

You guys are amazing researchers. 

AGREED!!!!!!   You men NEVER cease to amaze me!!!!!

Stef