RE: Re: Amy Yasko - MTHFR and CBS deplete B12 ?

August 21, 2006

Jill,

I know that with tryptophan it is possible to decrease SSRI dosages while

gradually increasing trypto. Do you suppose it might make it all easier using

trypto while withdrawing? Worth a thought.All the best,

Adrienne

Re: Amy Yasko - MTHFR and CBS deplete B12 ?

Let me refine this a little. Without going back to my notes at the

moment, there was another mutation with that MTHFR SNP that could be

fixed with low folate--that was the only combo that was significant.

And easily fixed.

That's not having read the journal article yet, and not looking back

at my notes. And it would be nice of course to do a few more such

studies if one could to be sure.

In preparation for embarking on Yasko sometime in Sept when I get my

results back, I am still tapering off my sleeping pill. I'm using a

really cool water titration method which allows me to be very precise

even though its powder in a capsule; but the taper is still AWFUL. I

feel HORRIBLE. Being impatient, and stoical, and mad about the whole

thing (I never would be at this dose if not for my crazy building's

insane or should I say obscene demolition) I've decided that since the

withdrawal is already somewhat hellish, I might as well speed it up.

I'm going to go down 2 milligrams every few days. If I'm really

feeling bad I may not post much. I may just have to rest a lot while

doing this. I figure however that to be on a drug like this is nuts if

I'm going to be trying to restore pathways in my body. So this is

really step one of my journey.

> > > >

> > > > Hi,

> > > > I'm reading through the messages on www.autismanswer.com. One

> > thing she

> > > > says is that the MTHFR C6777T SNP and the CBS SNP upregulation

> > will

> > > > deplete B12.

> > > > For those of you studying this info, does this make sense ? I

> > can't

> > > > quite grasp why this would occur.

> > > >

> > >

> >

>

This list is intended for patients to share personal experiences with each

other, not to give medical advice. If you are interested in any treatment

discussed here, please consult your doctor.

August 21, 2006

HI Rich,

So I am confused. I am on step one and Yasko recomends subligual

cyanocobalamine B 12 and sublingual hydroxycobalamine B12. Of course what I have

on hand is methycobalamin. I am CBS upregulated with MTHFR (A1298C) +/-. Can I

take the methylcobalamin now without distrubing things????

Also I don't understand the front way around or the long way around. Can you

explain what cycle she is talking about???? Which genes are affected by this???

How do I figure out what I need to do for myself???

As always, thank you for your help,

Janet

rvankonynen <richvank@...> wrote:

Hi, .

If she is speaking of the methyl form of B12, I think I can understand

that. First, the forward MTHFR SNP to which you refer will slow the

production of 5-methyl tetrahydrofolate from 5,10 methylene

tetrahydrofolate. Since 5-methyl THF is needed to supply methyl

groups to remethylate B12, a deficiency there would tend to lower the

supply of methyl B12.

With regard to the CBS upregulation SNPs, I think the idea there is

that this upregulation will raise the production of cysteine, and

higher cysteine causes the flow to be diverted through the cysteine

dioxygenase enzyme down to sulfoxidation, rather than through

glutamate cysteine ligase, to make glutathione. So glutathione will

go low. Low glutathione will lower the production of methyl B12 from

either cyano B12 or hydroxo B12, because it, together with SAMe, is

needed to make those conversions.

Rich

>

> Hi,

> I'm reading through the messages on www.autismanswer.com. One thing

she

> says is that the MTHFR C6777T SNP and the CBS SNP upregulation will

> deplete B12.

> For those of you studying this info, does this make sense ? I can't

> quite grasp why this would occur.

>

August 21, 2006

Hot baths, a heating pad, rest, and a good attitude. I was trying to

'talk' to my body last night and will try to do so more. Letting it

know it needs to start making gaba.

Jill,

That all sounds good. While your are communicating with you, see what feedback

you may hear. I don't understand; if it's gaba you need, why not take some?

Adrienne

August 21, 2006

Hi Jill,

Thanks for the explaination.

I was not clear if this may also be a problem from taking GABA(for sleep).

Will the brain have worse problems if you want to stop Gaba too?

Thanks,

Sue T

jill1313 <jenbooks13@...> wrote:

It is temazepam. From my reading, it seems that though all the benzos

are similar, some bind more tightly to receptors, and have shorter

half-lives. The most difficult to get off, for that reason,

apparently, are klonipin and xanax. The equivalence is strange, too. 6

milligrams of xanax equals 120 milligrams of valium. 30 milligrams of

temazepam equals 15 milligrams of valium. So milligram amounts fool

unsuspecting patients and maybe doctors, I suspect. They might think,

" I'm only on 2 milligrams of this drug " and not realize its power. And

the short half life can be a problem in withdrawal apparently.

I suspect there is a kind of crossover line for every individual,

where the dose gets to a level that causes the body to really

significantly shut down its own production.

I also suspect that the gaba receptors change structure slightly to

accomodate the drug when there is a lot of it around, and may even

develop a greater affinity for that drug than natural gaba.

I also read that the drugs are stored in fatty tissue and release over

many months from the fat.

These all could be reasons it could be hard to get off. Your body has

to realize what's going on and make its own. Your receptors have to

change shape back to 'normal'. All kinds of shifts have to occur to

get you back to where you were.

>

> > In preparation for embarking on Yasko sometime in Sept when I get

> my

> > results back, I am still tapering off my sleeping pill. I'm using a

> > really cool water titration method which allows me to be very

> precise

> > even though its powder in a capsule; but the taper is still AWFUL.

> I

> > feel HORRIBLE. Being impatient, and stoical, and mad about the

> whole

> > thing (I never would be at this dose if not for my crazy building's

> > insane or should I say obscene demolition) I've decided that since

> the

> > withdrawal is already somewhat hellish, I might as well speed it

> up.

> > I'm going to go down 2 milligrams every few days. If I'm really

> > feeling bad I may not post much. I may just have to rest a lot

> while

> > doing this. I figure however that to be on a drug like this is

> nuts if

> > I'm going to be trying to restore pathways in my body. So this is

> > really step one of my journey.

>

August 22, 2006

Please direct me to the paper that discusses the reduced folate SNP.

Also, is this discussed in her talk at the April DAN! Conference ?

Re: Amy Yasko - MTHFR and CBS deplete B12 ?

Its exactly as you say. She said that the one concern was the low

folate with that SNP but that the enzyme recovered beautifully when

you restored the folate.

And I think it would be unlikely, given our whole hypothesis here,

that CFS would have significantly different variations than autism.

You're either very right about this or very wrong . Let's hope

you're very right as so much work is being done on methylation stuff

for the autistic kids.

>

August 22, 2006

HI Rich,

Thanks for clearing that up for me. But I am still a bit confused because when

I see her talk about TMG, she says " no more than what is in the multiple for CBS

up regulation. " I will try the methy B-12 as all my COMT's are +/- and pay

attention to how I feel.

I think timing is important, so when do I add in the phosphatidyl serine,

phosphatidy choline and do I add in more TMG???

As always, thank you for your help,

Janet

rvankonynen <richvank@...> wrote:

>

> HI Rich,

>

> So I am confused. I am on step one and Yasko recomends subligual

cyanocobalamine B 12 and sublingual hydroxycobalamine B12. Of course

what I have on hand is methycobalamin. I am CBS upregulated with

MTHFR (A1298C) +/-. Can I take the methylcobalamin now without

distrubing things????

***You could try it, and see if you experience mood swings. If you

do, then switching to the non-methylated forms of B12 may help. I

think Dr. Yasko recommended them in your case because you have COMT

SNPs, and that can cause you to have too many methyl groups

available, because they are not being used by COMT as fast as normal.

>

> Also I don't understand the front way around or the long way

around. Can you explain what cycle she is talking about???? Which

genes are affected by this??? How do I figure out what I need to do

for myself???

***There are two pathways that go from homocysteine to methionine.

One of them requires B12 and 5-methyl tetrahydrofolate. I think she

calls this the long way, because more is required to get it going,

and it takes longer to do that.

***The short way uses trimethylglycine or phosphatidly choline,

phosphatidylserine or phosphatidylethanolamine. In people who have

the CBS upregulation, as you do, she recommends using the short way

first, because you can get it going faster. Then she recommends

building up what's necessary to get the long way going, so that you

can switch to that later on by adding DMG to shut down the short

way. But you have to build up folate and B12 before you can make

that switch, and it takes some time to do that.

>

> As always, thank you for your help,

>

> Janet

***You're welcome.

***Rich

August 22, 2006

Hi and Janet,

I believe Dr. Yasko suggests to use Methyl B12 if you are COMT--, which I am.

Once in a while depending on the rest of the genetics she runs she will allow

Methyl B12 with a COMT+-, but I have never seen her suggest it at all for

COMT++.

Thats pretty much the bottom line as far as I know.

Best wishes,

Sue T

riversinger48 <sfriedl@...> wrote:

>

> HI Rich,

>

> So I am confused. I am on step one and Yasko recomends subligual

cyanocobalamine B 12 and sublingual hydroxycobalamine B12. Of course

what I have on hand is methycobalamin. I am CBS upregulated with MTHFR

(A1298C) +/-. Can I take the methylcobalamin now without distrubing

things????

>

Janet, I have been studying this some for a friend on Yasko's site.

From what I understand, using the methyl B12 before the CBS problem is

corrected can increase ammonia problems. You might try searching for

Methyl B12 and Ammonia, and see if anything comes up.

Once your ammonia is under control, and other CBS issues are

corrected, then methyl B12 and other methyl donors are added in slowly.

Hope this helps.

August 23, 2006

Hi Rich and Janet,

I have a general comment about using hydroxycobalamine. I read

Pangborns section on B12 in the Autism: Effective Biomedical treatments

book and it says that glutathione is needed to make Mb12 out of

hydroxycobalamine. I know Dr. Yasko recommends hydroxyB12 for those

with extra methyl groups, but I'm wondering if this would be effective

if one is low in glutathione ?

-

Re: Amy Yasko - MTHFR and CBS deplete B12 ?

>

> HI Rich,

>

> So I am confused. I am on step one and Yasko recomends subligual

cyanocobalamine B 12 and sublingual hydroxycobalamine B12. Of course

what I have on hand is methycobalamin. I am CBS upregulated with

MTHFR (A1298C) +/-. Can I take the methylcobalamin now without

distrubing things????

***You could try it, and see if you experience mood swings. If you

do, then switching to the non-methylated forms of B12 may help. I

think Dr. Yasko recommended them in your case because you have COMT

SNPs, and that can cause you to have too many methyl groups

available, because they are not being used by COMT as fast as normal.

>

> Also I don't understand the front way around or the long way

around. Can you explain what cycle she is talking about???? Which

genes are affected by this??? How do I figure out what I need to do

for myself???

***There are two pathways that go from homocysteine to methionine.

One of them requires B12 and 5-methyl tetrahydrofolate. I think she

calls this the long way, because more is required to get it going,

and it takes longer to do that.

***The short way uses trimethylglycine or phosphatidly choline,

phosphatidylserine or phosphatidylethanolamine. In people who have

the CBS upregulation, as you do, she recommends using the short way

first, because you can get it going faster. Then she recommends

building up what's necessary to get the long way going, so that you

can switch to that later on by adding DMG to shut down the short

way. But you have to build up folate and B12 before you can make

that switch, and it takes some time to do that.

>

> As always, thank you for your help,

>

> Janet

***You're welcome.

***Rich

August 27, 2006

Rich,

I understand that some people might need less rather than more methyl donors,

but doesn't the hydroxy form convert into the methyl in the body anyhow? I mean,

does the need to make the conversion mean a significant decrease in available

methyl.

Is it then, a question of taking every advatage possible, no matter how small?

Adrienne

Re: Amy Yasko - MTHFR and CBS deplete B12 ?

and I think that's why Dr. Yasko

recommends hydroxocobalamin for these people.

Rich

.

August 27, 2006

Hi Rich,

Here is what is said in the Autism : Effective Biomedical Treatments

about B12

- It is stored in the lysozymes of cells as hydroxocobalamin;

in this form, cobalt is at the +3 oxidation state

- hydroxycobalamin (OHCbl) is secreted from the lysosomes and

combined with GSH, forming glutathionylcobalamin (GSCbl) in the cytosol

of cells

- GSCbl can then stay in the cytosol where cobalamin +2 or b12

is delivered to the methionine synthase (MS) complex, or it can enter a

mitrochondrian where it is processed further into adenosylcobalamin

- The MS complex exists in 2 forms; one with 3 enzyme assisting

domains and one with 4 domains.

- The liver contains the 4 domain version

- Consider the 4 domain MS

o Suppose MS needs a new Cbl because its old one is ruined beyond

repair

o When GSCbl arrives at MS, it gets reduced to Cbl+1 by the MS

reductase ; glutathione departs the scene

o Then the SAM binding domain of MS methylates Cbl+1 to make

methylcobalamin, MeCbl+2

o When homocysteine arrives at MS, the active site catalyzes the

transfer of the methyl group from MeCbl+2 to Hcy forming Met.

Cobalamin is left, bound to its domain on MS as Cbl+1. From then on ,

5-MeTHF delivers methyls to the Cbl domain of MS, and those methyls are

used to make Met from Hcy

o The process of methyl transfer repeats until , by accident or

design, Cbl+1 gets oxidized to Cbl+2.

o As Cbl+2 it can't accept a methyl from 5-MeTHF

o The oxidation occurs after Cbl has given away its methyl and

before it gets a new one from 5-MeTHF.

o Oxidized Cbl can be rescued by the MS reductase part of the

enzyme. Cbl+2 can be reduced back to Cbl+1, methylated once by SAM from

the SAM binding domain and it's ready to go again

So, it does seem that in order for hydroxycobalamin to be used in the MS

enzyme, glutathione is involved.

Re: Amy Yasko - MTHFR and CBS deplete B12 ?

Hi, .

I may have answered this before. Sorry, I lose track sometimes.

I think the answer here can be found in Professor Deth's talks. He

notes that the methionine synthase enzyme can be booted back up

either by getting a new methyl B12 molecule, having it regenerated

by getting a methyl group via methionine synthase reductase from 5-

methyl tetrahydrofolate, or having it regenerated by SAMe. In the

case of people who don't use as many methyl groups as normal for the

COMT reactions, because they have a slow COMT, then I think there

can be more SAMe available, and I think that's why Dr. Yasko

recommends hydroxocobalamin for these people.

Rich

>

> Hi Rich and Janet,

>

> I have a general comment about using hydroxycobalamine. I read

> Pangborns section on B12 in the Autism: Effective Biomedical

treatments

> book and it says that glutathione is needed to make Mb12 out of

> hydroxycobalamine. I know Dr. Yasko recommends hydroxyB12 for

those

> with extra methyl groups, but I'm wondering if this would be

effective

> if one is low in glutathione ?

>

> -

>

August 29, 2006

Injections of hydroxycobalamine was, after the whole concept of supplements in

general, the best single thing that ever happened to me since contracting this

disorder. I didn't make any real headway until it started bringing my mind back.

Nothing like being able to think when you are needing to take care of yourself.

They were out once and I switched to methyl, and maybe, just maybe it was a

little different. Definitely not worth the extra price. B12 did a zillion times

more for me than whey ever did- and I gave that a real, consistent try. Various

brands.

Adrienne

Re: Amy Yasko - MTHFR and CBS deplete B12 ?

Hi, .

Thanks for your persistence on this issue. In response, I did my

homework on it more thoroughly. I listened to three of Dr. Deth's

talks again, reread the part of the Pangborn and Baker book that you

cited, and looked up the original paper on methionine synthase

reductase (which happens to be from Canada)!

Well, now I agree with you. I don't see how hydroxocobalamin can be

used by methionine synthase without glutathione to reduce the cobalt

ion from its +3 state to its +2 state. Once it's in the +2 state,

then methionine synthase reductase, with the help of NADPH and SAMe,

can produce methylcobalamin.

So how does Dr. Yasko get good results using hydroxocobalamin? The

only thing I can think of is that there must still be enough

glutathione to supply what's needed. Of course, there should also

be a boot-strapping process going on over time, because as the

methylation cycle operation is restored, there should be more

production of glutathione.

In view of this, I guess I would lean toward using methylcobalamin

unless problems arise from too many methyl groups. I think you

asked how this could be a problem. The only thing I can think of is

the socalled law of mass action in chemistry. If a larger

concentration of reactants for a reaction is supplied, the reaction

rate will increase. It may be that you would get too many

methylation reactions, and that would throw some of the biochemistry

off balance. That's the only thing I can think of. I think I will

have a lot of questions to ask Dr. Yasko come late October!

Rich

>

> Hi Rich,

>

> Here is what is said in the Autism : Effective Biomedical

Treatments

> about B12

>

> - It is stored in the lysozymes of cells as

hydroxocobalamin;

> in this form, cobalt is at the +3 oxidation state

>

> - hydroxycobalamin (OHCbl) is secreted from the lysosomes

and

> combined with GSH, forming glutathionylcobalamin (GSCbl) in the

cytosol

> of cells

>

> - GSCbl can then stay in the cytosol where cobalamin +2

or b12

> is delivered to the methionine synthase (MS) complex, or it can

enter a

> mitrochondrian where it is processed further into adenosylcobalamin

>

> - The MS complex exists in 2 forms; one with 3 enzyme

assisting

> domains and one with 4 domains.

>

> - The liver contains the 4 domain version

>

> - Consider the 4 domain MS

>

> o Suppose MS needs a new Cbl because its old one is ruined

beyond

> repair

>

> o When GSCbl arrives at MS, it gets reduced to Cbl+1 by the

MS

> reductase ; glutathione departs the scene

>

> o Then the SAM binding domain of MS methylates Cbl+1 to make

> methylcobalamin, MeCbl+2

>

> o When homocysteine arrives at MS, the active site

catalyzes the

> transfer of the methyl group from MeCbl+2 to Hcy forming Met.

> Cobalamin is left, bound to its domain on MS as Cbl+1. From then

on ,

> 5-MeTHF delivers methyls to the Cbl domain of MS, and those

methyls are

> used to make Met from Hcy

>

> o The process of methyl transfer repeats until , by

accident or

> design, Cbl+1 gets oxidized to Cbl+2.

>

> o As Cbl+2 it can't accept a methyl from 5-MeTHF

>

> o The oxidation occurs after Cbl has given away its methyl

and

> before it gets a new one from 5-MeTHF.

>

> o Oxidized Cbl can be rescued by the MS reductase part of

the

> enzyme. Cbl+2 can be reduced back to Cbl+1, methylated once by

SAM from

> the SAM binding domain and it's ready to go again

> So, it does seem that in order for hydroxycobalamin to be used in

the MS

> enzyme, glutathione is involved.

>

August 29, 2006

I remembered you had a good experience with hydroxyl B12 and so did

Doris. So I'm wondering if it is doing something other than what Dr.

Yasko is trying to do ie. Reactivate the methylation cycle. I know

Pall recommends it to scavenge nitric oxide.

How often do you take it and how much does it cost you ?

Re: Re: Amy Yasko - MTHFR and CBS deplete

B12 ?

Injections of hydroxycobalamine was, after the whole concept of

supplements in general, the best single thing that ever happened to me

since contracting this disorder. I didn't make any real headway until it

started bringing my mind back. Nothing like being able to think when you

are needing to take care of yourself.

They were out once and I switched to methyl, and maybe, just maybe it

was a little different. Definitely not worth the extra price. B12 did a

zillion times more for me than whey ever did- and I gave that a real,

consistent try. Various brands.

Adrienne

August 29, 2006

On Aug 29, 2006, at 4:29 PM, wrote:

> I remembered you had a good experience with hydroxyl B12 and so did

> Doris. So I'm wondering if it is doing something other than what Dr.

> Yasko is trying to do ie. Reactivate the methylation cycle. I know

> Pall recommends it to scavenge nitric oxide.

I've also had great success with injecting methyl B12. Great stuff. I

love having a brain again.

Sara

August 29, 2006

Hi Sara -

Would love to have my brain again too. What is your source for the

methyl B12 shots?

Thanks -

Colin

Mercuria wrote:

>

> On Aug 29, 2006, at 4:29 PM, wrote:

>

> > I remembered you had a good experience with hydroxyl B12 and so did

> > Doris. So I'm wondering if it is doing something other than what Dr.

> > Yasko is trying to do ie. Reactivate the methylation cycle. I know

> > Pall recommends it to scavenge nitric oxide.

>

> I've also had great success with injecting methyl B12. Great stuff. I

> love having a brain again.

>

> Sara

>

August 29, 2006

On Aug 29, 2006, at 5:04 PM, Colin Green wrote:

> Hi Sara -

>

> Would love to have my brain again too. What is your source for the

> methyl B12 shots?

I get mine under an Rx from FFC. The MB12 is in a cocktail with

glutathione and AMP, which I get every other day.

Sara

August 29, 2006

Sara, what is FFC? thanks, joanee

Mercuria wrote:

>On Aug 29, 2006, at 5:04 PM, Colin Green wrote:

>

>>Hi Sara -

>>

>>Would love to have my brain again too. What is your source for the

>>methyl B12 shots?

>>

>

>I get mine under an Rx from FFC. The MB12 is in a cocktail with

>glutathione and AMP, which I get every other day.

>

>Sara

>

August 29, 2006

On Aug 29, 2006, at 6:00 PM, Joanee Webb wrote:

Fibro and Fatigue Center -- a national network of clinics

specializing in FM and CFS/ME.

<www.fibroandfatigue.com>

Sara

August 29, 2006

I take it erratically. Lately feeling more need since I have been taxing my

brain much more. Several times a week.

It is tricky; if I don't take it in time, then my memory starts to fail and

then it is hard to remember to take it and several days may go by before I force

myself to remember. Sometimes I just feel real resistant about sticking myself.

Or something. Haven't done that in awhile.

I take 2 cc's at a time. I used to take it mid afternoon when I was clearest

and minded the shot least. Now I can manage the shot early.

I pay somewhere around $60 bucks for a vial, maybe less? It is my very good

friend. I have no idea what it is doing biochemically of course, but starting it

was the beginning of my way back up.

Adrienne

Re: Re: Amy Yasko - MTHFR and CBS deplete

B12 ?

Injections of hydroxycobalamine was, after the whole concept of

supplements in general, the best single thing that ever happened to me

since contracting this disorder. I didn't make any real headway until it

started bringing my mind back. Nothing like being able to think when you

are needing to take care of yourself.

They were out once and I switched to methyl, and maybe, just maybe it

was a little different. Definitely not worth the extra price. B12 did a

zillion times more for me than whey ever did- and I gave that a real,

consistent try. Various brands.