How do I know if CBS is "expressed"?

[Star-Anise]

@anxiousguy
re: Deplin - I believe that Deplin is methylfolate. not folate or folinic acid. It's the methylated form of folate.
Deplin I believe comes in 7.5 - 15 mg doses. When I started my initial dosing was around 10mcg per day or less (considerably less than 7.5mg). Any more would cause ++anxiety or fatigue. My body seems to respond that way. Mild overdose = anxiety, major overdose = incredible fatigue, lol
My point was that from my readings some people find that they may do okay on that dose (Deplin) originally, but decompensate & need to drastically reduce the dose due to negative symptoms.
With respect to hydroxy- I have only used the sublinguals and I would just cut them in pieces. I started with a rapid dissolve under tongue & now tend to keep wedged between gum & side of mouth so can slowly dissolve over 1-3 hours.
I have never used drops, but I have heard of people diluting them.
S

 

[anxiousguy]

@Star-Anise

Thanks. Still a little confused.

L-methylfolate is what is called for for much of my situation in nutrachacker.

What is the difference b/w methylfolate, folate and folinic acid?

I am confused by the methylcobalamin, hydroxycobalamin, etc and all the folates.

You need b12 and folate correct? Is it then just a matter of SNPs? Do all the folates and b12s "do" the same thing and you just need to choose the correct based on which won't give you adverse effects due to your snps?

Thanks again

 

[Star-Anise]

@Star-Anise

Thanks. Still a little confused.

L-methylfolate is what is called for for much of my situation in nutrachacker.

What is the difference b/w methylfolate, folate and folinic acid?

I am confused by the methylcobalamin, hydroxycobalamin, etc and all the folates.

You need b12 and folate correct? Is it then just a matter of SNPs? Do all the folates and b12s "do" the same thing and you just need to choose the correct based on which won't give you adverse effects due to your snps?

Thanks again

@anxiousguy
hey there, just do a quick google, you'll see that folate, which is mostly from food forms. Whereas folinic acid, & methylfolate is a more bio-available form. Our bodies have to convert food forms of folate into methylfolate & folinic acid (I did read once however that folinic acid is found in food too), which comprises big problems for those that cannot do so.
I did a quick google & found this that explains essentially this:
http://autismcanada.org/treatments/biomed/folicacid.html

You need b12 and folate correct? Is it then just a matter of SNPs? Do all the folates and b12s "do" the same thing and you just need to choose the correct based on which won't give you adverse effects due to your snps?

Yes we need both folate and b12 to survive. Our snps indicate potential areas where normal processing of folate and b12 are interrupted. No not all the folate and b12s do the same thing. They have various different functions. I'm not familiar with all of their functions. The main one I know is that methyl-b12 is critical for the methyl cycle, and adenosyl-B12 seems to be more connected to mitochondrial function.
Have you read Yasko's work? It may help answer some of your questions. Some of her stuff around the less common mutations is controversial, & not universally accepted, but I think her stuff on folate & B12 is pretty well accepted. You can download her book here: http://www.dramyyasko.com/wp-content/files_flutter/1327512160_9_1_1_8_pdf_02_file.pdf
Hope that helps & all the best,
S

 

[ahmo]

@anxiousguy Deplin is a HUGE dose for you to start with. I was on .5mg for a long time, then made my way up to 1.5. But I didn't balance w/ MB12, and got reactions which I thought were 'detox', but I now understand to have been due to this imbalance.

Here a pr member has summarized Freddd's Protocol. There are, however, some corrections to be made to this list, which I’ve indicated by striking through the original, and added a bracket to the potassium info. You may need to start the folate at less than 800 mcg.

http://forums.phoenixrising.me/index.php?threads/b-12-the-hidden-story.142/page-141#post-390845

Freddd’s Protocol – Getting Started... as I understand it and in my own words. 9/27/13

Assuming you already have the basics like Vitamin B Complex, C, D, calcium, magnesium, zinc and omega 3s in your supplements routine, start by testing:


1. 1 capsule of L-carnitine fumarate on an empty stomach (available in about 400 – 800 mg capsules)
If there are no new negative start up symptoms (like feeling super hyped & wired) keep
taking it every day.
If there are new negative start up symptoms (like feeling super hyped & wired), you’ll need to titrate up gradually until you’re comfortable with 1 capsule/day. That may mean taking 1/10 of a capsule. As your body gets use to having this long missing nutrient, you’ll gradually increase (titrate up) your daily amount to 1/5 capsule, then 1/2 a capsule etc. until you’re doing 1 capsule daily. You can take days or weeks to do this titrating. Don’t rush your body. When your body is use to 1 capsule of L-carnitine fumerate per day, continue that and start:

2. 1 Enzymatic Therapy B12 Infusion (1,000 mcg MeB12) after breakfast, placing the tablet
between upper lip and gum, for as long as it takes to dissolve. When your body is settled with
this, start:

3. 1 Solgar Folate (800 mcg Metafolin) with breakfast
If there are no new start up symptoms (new headaches, rashes, irritabilities, anxieties,
depressions, joint pains, muscle pains, insomnia, continue with this amount daily.
If there are new negative start up symptoms (new headaches, rashes, irritabilities,
anxieties, depressions, joint pains, muscle pains, insomnia) you’ll need to titrate up gradually until you’re comfortable with 1 capsule/day. Then continue the Folate and start:

4. [Country Life Active B-12 Dibencozide] [no longer preferred brand; instead, Anabol Naturals] (3,000 mcg AdB12), after breakfast, 3 X week, placing the tablet between upper lip and gum, for as long as it takes to dissolve.

5. Potassium (99 mg tablets) [You may need more K+; Potassium Gluconate powder or Potassium citrate allow you to easily take higher doses. Tablets are only allowed to be 99mg to avoid stomach problems] taken with a glass of water, as needed, anytime during the introduction of the previous 4 supplements, if new nausea, itching, heart palpitations, weakness, muscle spasms or cramps start happening. For some, several potassium tablets may be needed, several times a day.

As you progress in this protocol, go to the following web site. good layout
http://howirecovered.com/active-b12-therapy-faq/
There Eric provides well organized information that can save you from trying to find your way through the voluminous information on Phoenix Rising. It will help you understand Active B12 therapy and methylation

.


Here's a comprehensive look at the folate and B12 types from Freddd, which discusses the different types of folate and B12.
THE COMPLETE METHYLATION REVIEW Freddd Feb 2013
http://forums.phoenixrising.me/index.php?threads/the-stages-of-methylation-and-healing.21725/

And here's a compilation from phoenixrising member Eric, as FAQ for B12 protocol:
http://howirecovered.com/active-b12-therapy-faq/

 

[Critterina]

I only have a minute, but my alarms when off when i thought I saw you starting the B12 before the methylfolate. Didn't have time to read Star's post. But methylfolate before B12, ok?

 

[SOC]

I am not ill or sick other than anxiety/depression/ocd.

Everytime I read/research or deal with this stuff I end up in a panic attack/have a depressive episode.

Just a thought -- if you're not ill other than anxiety/depression/ocd perhaps focusing so much in your diet and genetics is causing you more stress than benefit. Perhaps you would benefit from letting go of most of your reading and research since it's aggravating your condition, not helping it.

I know everyone here wants to help, but it sounds to me like all we're doing is overloading you and overwhelming your ability to cope.

Pick one simple strategy such as the one amho linked above ( http://forums.phoenixrising.me/inde...h-three-supplements.18369/page-16#post-433283) do ONLY that, stick to it for several months without reading/researching or changing things. Don't let your anxiety and ocd drive you into overloading yourself with this and ignoring other important parts of your life. It seems only to be making your condition worse, and you sure don't need that.

 

[anxiousguy]

@ahmo

What I meant to say, was should I split up a deplin since I already have a full year supply or just buy something else?

The only thing I am taking now is D3 and cod liver oil.

Starting to read Fredd's protocol does starts to give me a panic attack just like reading anything on Yasko's board does. A ton of tests and more supplements. Some people have suggested not worrying about B complex right now. I am getting C, Calcium, Magnesium, and zinc bloodwork done.

I absolutely CANNOT do all of this balancing and tons of supplements. Take this and balance with that etc. I can't afford to spend all of the money and hours a day on all of this. I would just abandon all of this if I weren't concerned about homocysteine and all of that.

@Critterina caledonia was suggesting starting and stabilizing b12, then adding methylfolate

@SOC

i agree with you. I just want to abandon all of this. The GABA, lavendar and everything else my naturopath/mthfr doc gave me didn't work. It seems that what everyone has said in the past is that the methylation is what is going to help me feel better and NOT be a bandaid.

I am attaching all my snps info. What folate/b12 should i be taking and what doses/types? What is the simplest start to methylation that I can do?

I am also waiting to talk to my dr. I am not sure if I need another mthfr doctor. Before 23andme came back, he wanted me to take a 1/4 of my 15mg Deplin and a b complex with 1000mcg of b12 (not shots or sublingual)
http://www.metabolicmaintenance.com/product/B-Complex/vitamins_minerals

I don't know if he knows what he is talking about , or if I should find another mthfr doctor. Someone else said that they would be concerned about methyl trapping/overmethylation and he wasn't concerned.

Thanks

 

[anxiousguy]

@Star-Anise
@SOC
@Critterina
@ahmo

Nutrahacker says about my CBS
This is a very small up-regulation, and should not result in sulfur or ammonia problems.

I have the sulfur strips on the way, so I will test for that, but can I start folate/b12?

Is folapro and hydroxy ok? should i have anything on hand besides niacin? where should i start and how quickly should i go up?

 

[ahmo]

Deplin is 7.5 mg? So, if you wanted to "start low and go slow", which might mean as low as .5 mg, you'd want about 1/14 of a tab. (never trust my math!). You probably can't slice it, but you could crush the tab. Or, dissolve it in water, take small sip, but I don't know if it will dissolve, or how you'd calculate this.

For me, hydroxy never worked. But you might have better luck. I guess the immediate question is whether it will be effective enough for you to be able to take the folate w/o creating more anxiety.

I can absolutely understand that reading this stuff creates a panic attack. I know that well. I don't think he's advocating tests, I don't test, just watch symptoms. But howirecovered FAQ is a lot easier to comprehend. B complex you can probably wait to start. The one your doc is recommending w/ B12 is probably not going to give you that B12, it's just not absorbed well when swallowed.

I totally understand your frustration. Fortunately/unfortunately, I can't work, so that leaves me time to read this material, and I've been doing so for about a year and a half. Which means I can pretty much manage my process, and have answers to the difficulties I've experienced, like sulfur and histamine. But I'm not equipped for any in-depth answers. Caledonia is good at this.

Kraken has just posted a question re p5p (active B6), mentioning that it helps w/ homocysteine. I'd forgotten that. Did I link the pyroluria questionnaire? It's a simple thing, if you score high, you might find that p5p and the other associated minerals help. I'll link you to further info if you need it. Pyroluria was discovered before gene testing. My hunch is that it probably pertains especially to certain methylation defects. http:www.hputest.nlevaag.htm

 

[anxiousguy]

@ahmo

I was taking the 15mg Deplin before I knew anything about any of this - as per shrink

How would i know if hydroxyb12 was "working"

I took b6 daily to the point where my levels were high, but my homocysteine stayed high.

I don't think I can't take methylcobalamin due to my snps(comt). That leaves hydroxy as my only option as I understood.

Thanks

 

[ahmo]

oh. Then it's not pushing your anxiety. That, I think, would be the primary reason to make sure you've got B12 coverage. Well, anxiety and the other items on the long list of symptoms. So hydroxy seems to be the way to go. Sorry, I'm at the limit of my knowledge here.

 

[Star-Anise]

@ahmo

I was taking the 15mg Deplin before I knew anything about any of this - as per shrink

How would i know if hydroxyb12 was "working"

I took b6 daily to the point where my levels were high, but my homocysteine stayed high.

I don't think I can't take methylcobalamin due to my snps(comt). That leaves hydroxy as my only option as I understood.

Thanks

@anxiousguy
symptom watching is the only mechanism that we have to ensure that things are working that I know about. Like @ahmo however, I'm reaching my knowledge limits as well. If you are looking for more definite testing I'm sure there is stuff out there. I know that many people get methylation panels done. This might help you more so pinpoint the exact methylation blockages if you have them. snps (genetics) only speak to potential; there really is a chance that these snps are not expressed for you, or just partially. If you supplement @ therapeutic doses for a significant period of time & do not notice improvements or deterioration then for myself I would hypothesize that it isn't helping, & likely would discontinue the supplement. I like to keep my regimen as streamlined as possible, because I crash quite easily so I like to be able to pinpoint why effectively. If you were taking Deplin & were relatively stable before (without increase in negative symptoms) then I would look at adding some kind of B12 to that regimen. Some people do not experience problems until they try to take methylfolate and B12 at once. It is possible that you need both due to your genetics, but you are going to have to experiment to see what form of B12 you can tolerate, and how much. You likely need some methylB12, but you could be sensitive to it. If I were you, I would try the Deplin, if you did okay on it before, then try it again. I would wait a week a that dose (this time frame is arbitrary, but I tend to use it for myself), then I would attempt to introduce a low dose of hydroxy-B12, and see what happens. Please note this is just advice, and based on my limited experience with my own issues and a handful of others. But basically at a certain point you may just have to try something. For me, my negative response will be either increased anxiety or fatigue.
Hope that helps, S

 

[anxiousguy]

I did get the sulfate strips and started them today. They are very hard to read. (I work in a pool store and tests strips are famously unreliable/subjective/hard to read). I think it was b/w <800 <1200. Is that high? What am I looking for?

@Star-Anise @ahmo @Critterina

 

[Critterina]

I did get the sulfate strips and started them today. They are very hard to read. (I work in a pool store and tests strips are famously unreliable/subjective/hard to read). I think it was b/w <800 <1200. Is that high? What am I looking for?

@Star-Anise @ahmo @Critterina

I found they were hard to read, too! The hardest part is waiting 2 minutes. I don't usually keep a second-hand watch in my bathroom. What I did was lay the strip agains the vial and scoot it over to where it looked like it was between the closest colors.
Is it high? well, I think that depends a lot on what you eat. I think Yasko likes it between 400-800. But if you eat something with a lot of sulfur (eggs, cruciferous veggies) and then you get rid of it like you should, it may be high for a reading or two. I did a lot of readings (3x/day) for a few days then sort of lost interest. Did it once a week. If it was high, I did it a second time a few hours later. It was an expensive experiment. I didn't learn much.

 

[ahmo]

It was an expensive experiment. I didn't learn much.

same here. and yes, v hard to read.

 

[Star-Anise]

I did get the sulfate strips and started them today. They are very hard to read. (I work in a pool store and tests strips are famously unreliable/subjective/hard to read). I think it was b/w <800 <1200. Is that high? What am I looking for?

@Star-Anise @ahmo @Critterina

Hey there, I actually have never used them, lol. I just use my symptoms as a guide. Cheers, S.

 

[whodathunkit]

Kraken has just posted a question re p5p (active B6), mentioning that it helps w/ homocysteine. I'd forgotten that. Did I link the pyroluria questionnaire? It's a simple thing, if you score high, you might find that p5p and the other associated minerals help. I'll link you to further info if you need it. Pyroluria was discovered before gene testing. My hunch is that it probably pertains especially to certain methylation defects. http:www.hputest.nlevaag.htm

Hey @ahmo, the link doesn't work. Can you repost?

 

[ahmo]

Looks like there was one character missing. http://www.hputest.nl/evraag.htm

This one is "What is HPU?" http://www.hputest.nl/ewhat.htm

And this is a protocol from Dr. Klinghardt, one of the experts on HPU, working w/ autism:
http://www.klinghardtacademy.com/images/stories/powerpoints/hpu 2009.pdf

I was just watching Ben Lynch's vid re MTHFR. It's a good, fairly technical presentation, goes through the diagrams, joins all the pieces. It's the first of 2. I notice he has more recent presentation, I'll check them out tomorrow. At about 46" he talks a bit about CBS, tho not so much, but in the context of the whole cycle. One of the things he mentions is the need for choline, which presumably you're getting from eggs. Don't know if this sort of thing is of interest to you.
http://www.youtube.com/watch?feature=player_detailpage&v=-lCQp0KkSB4

And there's another simplified presentation of methylation pathway. I've found it helpful to trying to understand this, you'll find a break-down of the different parts of the cycle, w/ analogies to community recycling.
http://www.autismnti.com/yourbodyschemistry.html

 

[alex3619]

On genes being a problem if expressed: this is a misleading issue. If you have the gene, then somewhere in your body it is probably expressed. In most cases (but not always) that means everyone will have it. The issue with expression is that not every gene is expressed in every tissue. The combination of genes expressed, and genes silenced, are what make a tissue function unique. So CBS would be expressed in a specific range of tissues. I haven't looked it up, but I would think the liver would be a major place to find it expressed.

A range of tissue subtypes will have it expressed, and a range wont. Further, without getting into specific snps, if you have two different versions of the gene it will only be partially expressed, and if you have two it will be fully expressed.

Sex-linked genes, should that come up at some point, are different. Its possible to have only one copy expressed, which will vary area by area in the body in females, and will be constant in males.

 

[alex3619]

http://www.ncbi.nlm.nih.gov/pubmed/9466825

Arch Biochem Biophys. 1998 Feb 1;350(1):95-103.
Identification and tissue distribution of human cystathionine beta-synthase mRNA isoforms.
Bao L1, Vlcek C, Paces V, Kraus JP.

Abstract

Cystathionine beta-synthase (CBS) catalyzes the irreversible, serine-dependent conversion of homocysteine to cystathionine via a transsulfuration pathway. CBS deficiency not only is the leading cause of homocystinuria, an inherited genetic disorder, but may contribute to cardiovascular disease as well. We isolated three new isoforms of human CBS mRNA from a human liver cDNA library. We designate these CBS mRNAs as CBS 3, CBS 4, and CBS 5, and the CBS mRNAs reported previously by Kraus et al. (1993) (Hum. Mol. Genet. 2, 1933-1938) and Kruger and Cox (1994) (Proc. Natl. Acad. Sci. USA 91, 6614-6618) as CBS 1 and CBS 2, respectively. Sequence analyses show that the only difference among the five CBS mRNAs is at the beginning of the 5'-untranslated region. Tissue distribution studies reveal that liver and pancreas have the highest amounts of CBS mRNAs. CBS mRNA is present in all regions of the brain tested. We also report the differential distribution of CBS mRNA isoforms in tissues, showing that pancreas contains all five CBS isoforms and the liver has four CBS mRNA isoforms, CBS 1-4. The kidney contains only CBS 1 and CBS 2. In human fetal tissues, CBS 2 is present in the liver and kidney. PCR-based quantitative analyses of CBS mRNA isoforms in human liver demonstrate that CBS 1 and CBS 2 are the major species, with CBS 2 being more abundant, while CBS 3-5 are the minor species. Furthermore, results from our human liver cDNA screening and primer extension experiments show that each of the five CBS transcripts begins with a different exon, suggesting that CBS gene transcription might be regulated by more than one promoter.

PMID:9466825

[ My bolding highlights tissues in which CBS is active.] So its primarily expressed in the liver and pancreas, but also the kidneys and brain.