New, Inexpensive CBS Ammonia Fix

[kel88]

@aaron_c in my multi is P5P! Total 35mg .. But i read that b6 or P5P speed up the CBS mutation and P5P is sort of sulfur containing or something??

@ahmo my own doctor ( paul van meerendonk, he works together with Dr. de meirleir ) disribet me the hydroxy because of brainfog! He also said that you get brainfog from high ammonia ...

 

[aaron_c]

@ahmo: The ammonia and B6 link is not new, but I am glad it has clicked for you! In addition to being used by CBS, B6 is necessary for any transamination reaction, which includes reactions where we break down amino acids for energy, producing ammonia as a byproduct. So CBS is not the only link between B6 and ammonia.

In terms of sulfur: Ahmo, I think we have had a conversation about some b-vitamin containing sulfur, but when I looked into it I found that the sulfur was not donated, and just got excreted as a whole vitamin. Thiamine has a sulfur that remains part of the thiamine molecule, perhaps we were talking about that?

@kel88: B6 can increase our load of (toxic) sulfites through increasing the action of CBS. CBS is the rate-limiting enzyme for cysteine synthesis (a sulfur-containing amino acid), among (I think) other things. Rich Van K theorized that the inflammation in ME causes much of our cysteine to become cystine, which is two cysteines attached to one another. The process of recycling this back to cysteine produces sulfite. So generally, I think sulfur problems in ME is not that our CBS enzymes are working too hard, but that cysteine is oxidized too quickly. However, taking B6 and getting our CBS enzyme to work at a relatively normal speed can cause us to produce more sulfites--perhaps a great deal more--than a healthy person with a CBS enzyme working at the same pace.

Another thing to mention is that CBS activity is ultimately limited by how much methionine we have available. My current understanding is that as we run out of methionine, CBS slows down regardless of if we have the C699T mutation or not, and regardless of if we have a moderate or a megadose of B6 in our bodies at the time. So yes, B6 can increase toxic sulfites--but only up to a point. For myself, I found that as I increase my dose of B6, the optimum dose for sulfite support (molybdenum) levels off well before the optimum dose for ammonia support does.

I am also interested in your use of hydroxycobalamin injections to protect you from ammonia toxicity. I start to feel ill if my B12 is in some degree of balance with my methylfolate, particularly as I take larger doses of B12...but that was with methylB12. I am curious how much one can use hydroxycobalamin to protect from ammonia toxicity. Do you find that it stops working after you take so much of it? Or does it always fix the issue?

 

[ahmo]

B6 is necessary for any transamination reaction, which includes reactions where we break down amino acids for energy, producing ammonia as a byproduct. So CBS is not the only link between B6 and ammonia.

we have had a conversation about some b-vitamin containing sulfur, but when I looked into it I found that the sulfur was not donated, and just got excreted as a whole vitamin

Rich Van K theorized that the inflammation in ME causes much of our cysteine to become cystine, which is two cysteines attached to one another. The process of recycling this back to cysteine produces sulfite. So generally, I think sulfur problems in ME is not that our CBS enzymes are working too hard, but that cysteine is oxidized too quickly. However, taking B6 and getting our CBS enzyme to work at a relatively normal speed can cause us to produce more sulfites--perhaps a great deal more--than a healthy person with a CBS enzyme working at the same pace.

as I increase my dose of B6, the optimum dose for sulfite support (molybdenum) levels off well before the optimum dose for ammonia support does.

Thanks so much for clarifying and repeating this information. I've followed your lead, and have been taking 1200mcg molybd/day for a few weeks. My body again rejected P5P the last couple nights. Then I checked my B complex, and realized that I'm still getting 25mg/day with that! So something has shifted, whether it's good or bad bacteria making B6 in my gut, or the body now has a lesser need, I don't know. Having finally gotten that my B6 has been pushing my ammonia, implemented Pall's antioxidant suggestions and engaged as well with a Candida protocol, in case that's a source, I 'm ready to stop my intense search to identify these mechanisms. You've been a great help.

 

[kel88]

Hmm for me its difficult to understand.
I have to take P5P because of pyrroluria. But my body doenst want it anymore i got so much pain from the B6 or P5P. Do anybody know what to do?

I will take also moly 1000mcg and try yucca and twice a week b12 injections hydroxo.
Aaron i take the injections for years now and it works great. Now not so much but thats because ivo got other issieus now

Are you both also becomming more and more ill in those years? Of is it stable?
I hope that i can try kuvan for BH4 and ammonia support...i think that would help me the most...

Why are you both take B6 when you cant handle it? Why dont you stop then with b6??

Amho i read a post about wich probiotic for histamine intoleranz, can you look id i did buy a good one (sorry off topic) i think i have mast cell disorder because the MTHFR 1298C (homo) and MAO mutation pffff my sickness becomes more and more terrible

 

[ahmo]

@kel88 I started P5P for pyroluria. It made a huge positive difference in my mental state within 5 days. My body is either producing it now in gut, or now needs less.

I commented on your probiotic on that thread.

 

[kel88]

Ahmo i also get a huge diffrents in mood ... Now i have to stop because of the neuropatic pain and poisend feeling and histamine reactions i get sooooo depressed and got back my fructose intoleranz... ( i dont like )

 

[aaron_c]

@kel88 : I think it is the same for me--B6 allows me to feel things, including happiness. Thus, I prefer to take a lot of it if I can.

Do you know what is preventing the hydroxycobalamin from helping now?

Since I began educating myself about methylation--Rich Van Konynenburg's work, among others--I have begun to feel better. But whatever the base problem is, I have yet to fix that. I have been sick for nine years now. In terms of a cure (ie you take it for a while, and then feel all better, and do not have to keep taking it), my understanding is that the methylation stuff usually works best for those who have been sick the shortest period of time.

Good luck with the Kuvan, I think it should work well, assuming you can reduce it to a low enough dose. I got a headache when my BH4 dose was too high, and the highest dose I used was 25 mg per day, spread out. I see that the dose recommended for kuvan is 10mg/kg/day, so you might have some issues reducing the dose. Although you could always grind it up. Will your healthcare pay for it? If so, I am quite jealous.

If kuvan doesn't pan out, I imagine there is someone else in europe selling tetrahydrobiopterin--I believe the BH4 we get in the states has to be shipped from europe.

And finally, if cost is an issue, you could try the aforementioned malic acid capsules or cooked and cooled potato starch, both of which have worked at least to some degree for me.

 

[kel88]

Aaron its weird right that we all want to take a high dose B6 but out bodys protesting! I found w lot of sick people in holland also MS patients who also had a high level of B6, but didnt took any multi or something! There is some issue about absorbing the B6 of P5P. If some dokter could find out what the problem is than there a much dissease that will be do better i think..

Die you try kuvan as well? Of did you take 10 pills from amy yasko? Expensive right..: i dont know if my docter would desribe me kuvan ( i dont think so but in going to try!!) and dont know if my ensurance does pay..: but ii hope so! Some people are very enthousiast about BH4 and some people wont they say that you will crashe if you dont treed the CBS mutation first ...?

Why dont you take the BH4 anymore? And how much P5P do you take? And are you on a dieet ( loslw sulfur or protein or something?)

 

[kel88]

@aaron_c was rich van konijnenburg from holland? Because he"s got a holloands name

 

[Valentijn]

@aaron_c was rich van konijnenburg from holland? Because he"s got a holloands name

No, he was American ... but of Dutch heritage

 

[kel88]

Ahhh nice to know Valentijn

 

[aaron_c]

Aaron its weird right that we all want to take a high dose B6 but out bodys protesting! I found w lot of sick people in holland also MS patients who also had a high level of B6, but didnt took any multi or something! There is some issue about absorbing the B6 of P5P. If some dokter could find out what the problem is than there a much dissease that will be do better i think..

I am a little confused. I didn't mention this, but I am under the impression that the reason many of us appear to be deficient in B6, meaning that we need to take supplements, is that activation of B6 requires phosphorylation--the donation of a phosphate molecule from...I think ATP, but in any case something that we won't have very much of because our mitochondria aren't working well. I am not aware of a problem with absorption or transport of B6, have you heard this?

I think the reason that our bodies are protesting from too much B6 is that it causes us to produce more ammonia, which we cannot handle. Others might disagree, but I do not think we have a good understanding of how this happens. One problem it seems to create is a decrease in BH4...I think relative to BH2.

Are you saying that you know MS patients who take B6, but no other b-vitamins?

Die you try kuvan as well? Of did you take 10 pills from amy yasko? Expensive right..: i dont know if my docter would desribe me kuvan ( i dont think so but in going to try!!) and dont know if my ensurance does pay..: but ii hope so! Some people are very enthousiast about BH4 and some people wont they say that you will crashe if you dont treed the CBS mutation first ...?

I took tetrahydrobiopterin from living well today international, not Kuvan, which I believe is basically BH4 with something added to the molecule to make it more stable. And ya, it was expensive, which is the main reason I am not taking it any longer. Also, I found that the much cheaper alternatives worked just as well, if not better.

I am a little confused about your last sentence. As far as I am concerned, taking BH4 directly treats "CBS dysfunction," although as I said before, I think that molybdenum is also needed.

And how much P5P do you take? And are you on a dieet ( loslw sulfur or protein or something?)

When I was taking the cooked and cooled potato starch, I had 75-100 mg of PLP daily (I write PLP to differentiate it from pendose-5-phosphate, which can also be abbreviated P5P). I seem to have become sensitive to potato starch, however, so now I am back to malic acid. I am starting with a dose of about 20 mg PLP daily, but it might end up lower or higher, I am not sure.

Since I started taking 1500 mcg of molybdenum per day, I have not had any restrictions on sulfur intake.

While taking the potato starch, I also had no restrictions on protein intake. The last time I took malic acid as my main way of dealing with ammonia, I severely limited protein. I basically had oatmeal with fat and fruit for breakfast and dinner, and a hamburger for lunch, the hamburger being my only high-protein food. This was not ideal, but if I had more protein, I started to get "ammonia issues." I am not sure if this time will be different or not.

 

[Gondwanaland]

I am a little confused. I didn't mention this, but I am under the impression that the reason many of us appear to be deficient in B6, meaning that we need to take supplements, is that activation of B6 requires phosphorylation--the donation of a phosphate molecule from...I think ATP, but in any case something that we won't have very much of because our mitochondria aren't working well.

That is an interesting perspective. It just makes me think that lack of dream recall is a good indicator that B6 isn't being activated.
I have been having a recurrent dream when I need to get up to urinate (the more urine = the more ammonia converted to urea). I am riding a tall monocycle in the middle of traffic and the last resource of my brain to make me wake up is that I loose balance and before I hit the ground I wake up.

Also, I found that the much cheaper alternatives worked just as well, if not better.

What are they?

I think that molybdenum is also needed.

Coincidentally it raises uric acid

(I write PLP to differentiate it from pendose-5-phosphate, which can also be abbreviated P5P

What is a commercial form of PLP?

I seem to have become sensitive to potato starch

I can't tolerate the tiniest doses of that, and malic acid defnetly triggers my salicylate intolerance (increase urination, tinnitus, thick skin around nails, itchy back, strong teeth grinding the whole night - I took 75mg of malic acid with 15mg of magnesium oxide).

I think that one of the reasons I keep having trouble with uric acid is lead

 

[aaron_c]

@Gondwanaland: Unfortunately (for you), the cheaper alternatives to BH4 I was referring to are malic acid and cooked-and-cooled potato starch.

Yes, molybdenum raises uric acid, which might be an issue for some people. For myself, it seems not to matter terribly--unless I take an inosine supplement, that is.

I get my PLP from Life Extension. They accurately name it pyridoxal-5-phosphate, which is what PLP, or P5P stands for.

I am sorry about the lead...but on the other hand, if it is true, it would be a big step forward to clear that out. I don't think any of us can hope to recover significantly while we still harbor toxins like that.

 

[kel88]

Gondwanaland offtopic i see that you also have much mutations... Also the MTHFR A1298C homozygoot.
How do you feel? I mean how sick are you? Bedridden or do you work....?
And you also have CBS mutation ... Ive got almost only homozygoot mutations only much the same...

And i see the mutation DAO do you also have Mast cell disease? And what do you take for it?

@aaron_c thanks for youre explanasion again! That of the B6 makes sensce.
But not only in ME patients but also in parkinson and MS and maybe more ( lupus and sarcoidose?)
If doctors can solve this problem i think we would much better...

Does BH4 solve CBS upregulation? I read everywhere that supplemantion with bh4 ( kuvan) without treathing CBS first ( sulfur free dieeet) will give much more problems, but i dont understand why...
I think when i take bh4 it will lowers my ammonia and boost serotonine dopamine and produce NOO.. .? ( whats NOO..?)

I found something intressting only difficult to understand but maybe you understand it the association about B6 and moly and sulfur...

Wich moly do you take? And 1500mcg right?

I am taking 1000 moly since yesterday and 3 pills yucca daily and it looks like its going a little bit better with me.
The cold feelings in feets en legs are still the same but the neutopatic pain in back feets and hands are much less..
I think because of the yucca (ammonia).
Why does not anybody takes yucca? I read it kills the gut bacteria that cause ammonia...

 

[Gondwanaland]

Unfortunately (for you), the cheaper alternatives to BH4 I was referring to are malic acid and cooked-and-cooled potato starch.

at least I can eat potato salad with no issues - let's see what happens if I eat it everyday Perhaps the reason I am still doing fairly well despite all my +/+ SNPs is due to the fact that I ate cooked-and-cooled rice and potatoes my whole life My husband is CBS+/+ and is under sulfur overload right now due to abx and just bought a bag of potato chips, the cat also craves it

I get my PLP from Life Extension. They accurately name it pyridoxal-5-phosphate, which is what PLP, or P5P stands for.

Then I was under the wrong impression that PLP and P5P are different things

I am sorry about the lead...but on the other hand, if it is true, it would be a big step forward to clear that out. I don't think any of us can hope to recover significantly while we still harbor toxins like that.

I guess I will have to seal all the wall paint cracks with adhesive tape after all. I can't chelate since I still have amalgams.

How do you feel? I mean how sick are you? Bedridden or do you work....?

No, not bedridden, but desperate to regain my health and life back.

And you also have CBS mutation

Only one heterozygous. It doesn't affect my dietary sulfur intake, but I have to watch for supplements and antibiotics. My husband has one homozygous CBS SNP and has to restrict some high sulfur foods like garlic and onions, otherwise he gets severe brainfog and diarrhea. At least now we know why.

And i see the mutation DAO do you also have Mast cell disease? And what do you take for it?

I don't have mast cell disease. Usually magnesium oxide supplementation relieves my intolerances. Sodium bicarbonate footbaths also help.

Why does not anybody takes yucca?

I tried it last week for the 1st time, just a tiny bit. THe following day I woke up with urticaria in my belly. Not sure it Yucca was the culprit or something I ate...

Edit: I will give Yucca to DH

Edit II: He is the one with heavy histamine issues

 

[kel88]

You guys, i found a very interesting post about P5P.
Now i know why its the only thing thats helped me and others and autism.
I have to take the neuropathy for granted.
and now i now why i have to take more P5P for the same effect. When you read a post at the link on facebook, you see that someone post that when you take methylfolaat you need MORE p5p. everybody stops with high dose methylfolaat because they dont now that they also have to take p5p...

so i think thats why the Dr Klinkhardt protocoll work so good to almost everybody who have MTHFR issues!

http://mthfralliance.com/2014/02/03/why-b6-is-the-queen-b/

https://www.facebook.com/mthfralliance1/posts/530029950446740

@aaron_c @ahmo @Gondwanaland

 

[ahmo]

@kel88 I had to reduce my P5P a couple months ago. I realized it was creating ammonia or peroxynitrite, I can't distinguish which. But I was having high ammonia symptoms. I'd been taking 33mg P5P + 25mg in a B Complex. When I first started P5P about 2.5 years ago, I started at 33mg, went up to about 3x that, and then returned to 33mg. I did this through self-testing, would not have been aware of ammonia symptoms at that time. I don't know what's shifted in my body that's meant I now need less.

 

[aaron_c]

I had not heard that B6-dependent enzymes are inhibited by oxidative stress. Interesting.

 

[Gondwanaland]

Someone post under another topic that Ray Peat says serotonin has the same effect as ammonia. I thnik both B2 and B6 increase serotonin, isn't that right?