CBS / Ammonia / Glutathione

Mary

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Hi @Methyl Head - thank you for all of this! I have been crashed today, I don't have the brain power to attempt to digest it (physical and mental exertion make me crash), but when I am feeling better and have energy to spare, I'll go over it in more detail. I looked at it very quickly tonight and some seems to fit and some doesn't, but again that was a very quick scan.

Hope you have a good holiday :star:
 

Methyl Head

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My pleasure Mary and thank you! Sounds good, I look forward to hearing what's relevant and I hope some of it is applicable! Take care of yourself and enjoy the holiday!
 

Learner1

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@Methyl Head
A caution... just because you have certain SNPs does not mean you will for sure be high or low in nutrients. It greatly depends in environmental.factors, including diet, toxins, infections, mitochondrial health, and other factors.

It is far wiser to do a test like a Genova Diagnostics NutrEval, and then adjust one's protocol accordingly.

My body needs over 4.5g glycine and 400mg P5P (B6) daily to make glutathione, etc. If I were to.listen to your advice, it would get me in a great deal.of trouble.

Additionally, taking arginine is problematic as it promotes herpes famiky viruses, which many of us have. Instead, like @Mary I've found that ornithine aspartate and citrulline are useful in reducing ammonia and promoting sleep.

Yasko and Heartfixer were useful in my early learning about methylation, but there is much more to be learned to support a body with ME/CFS. It's more than just feeding the SNPs.
 

Methyl Head

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@Learner1 - I definitely agree, health is different for everyone so your body probably doesn't need what his or hers might/might not. I wouldn't suggest most of what I did for someone who had already gone through this/had an entirely different list of SNPs or other limiting factors but I was talking about early stage CBS protocol stuff here specifically and I didn't speak on glutathione production because I don't know where he is in his journey yet, however with >800 reading on sulfur urine tests I assumed he'd need to deplete ammonia and sulfites before anything else occurred which is standard as is avoiding glycinate (for the time being) in early stage CBS. I never said don't do something, I made a point to say be careful because it may very well work for him and that's great if it does, I provided an alternate source of magnesium if glycinate aggravated him because I thought it would be important for him to know before just going for it.

Every methylation case is absolutely different depending on where someone lives (types of toxins, diet norms, tooth fillings, sun exposure, infections and other extenuating circumstances etc) how advanced their case is, combinations of certain SNPs, what stage you're in as far as treatment is concerned and like you said cellular health. 400 mg P-5-P would be pyroluria dosage levels but for someone with early stage and unaddressed CBS that would only add to their toxicity (I know it's a hottly debated subject on whether it's real or not but I'm curious to know if you take high dose zinc and pyro co-factors)! also what have you tested for?
 
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Learner1

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your body probably doesn't need what his or hers might/might not. I wouldn't suggest most of what I did for someone who had already gone through this/had an entirely different list of SNPs or other limiting factors
It would be helpful if you made that clear.

However, my SNPs are quite similar, and the advice you gave woukd be a disaster for me, due to environmental factors that have changed my biochemistry.
I didn't speak on glutathione production because I don't know where he is in his journey yet
Numerous studies have found significant oxidative and nitrosative stress in ME/CFS patients, where depletion of glutathione is a problem.

Excess sulfur can be addressed with binders and attention to the transsulfuration pathway, by adding B1 and molybdenum.
CBS is a SNP in a gene. There's no "early stage."
I provided an alternate source of magnesium if glycinate aggravated him because I thought it would be important for him to know before just going for it.
Glycine is essential for glutathione production. If glutathione production is "aggravating," one should ask why. One big reason can be mobilization of toxins. Avoiding glycine is not usually the answer.
Every methylation case is absolutely different depending on where someone lives (types of toxins, diet norms, tooth fillings, sun exposure, infections and other extenuating circumstances etc) how advanced their case is, combinations of certain SNPs, what stage you're in as far as treatment is concerned and like you said cellular health.
Exactly. Also, we have other genes that may be impacting our need for various nutrients.

. 400 mg P-5-P would be pyroluria dosage levels but for someone with early stage and unaddressed CBS that would only add to their toxicity (I know it's a hottly debated subject on whether it's real or not but I'm curious to know if you take high dose zinc and pyro co-factors)! also what have you tested for?
I didn't recommend that dose for anyone else, I was just making a point that advising on doses can be tricky. I am on that dose due to B6 being deficient on successive tests as I slowly increased the dose. B6 is used, not only in methylation and glutathione production, but also in heme production and in sphingolipid production for healthy cell and mitochondrial membranes, another area that has been found to be challenged in ME/CFS patients.

Doing a Genova Diagnostics NutrEval every 9-12 months has proved very useful in putting together my protocol, under the care of excellent functional medicine doctors, rather than getting advice over the internet, which might give me well-intentioned but bad advice. I've also done OAT, Spectracell, and various LabCorp tests (amino panel, minerals, homocysteine) which have been helpful, too.
 
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So I am new to this and don't really understand methylation. I do know that my sulfur pathway is impaired and I cannot convert sulfur to sulfates. I also have hydrogen sulfide sibo so i cannot take epsom salt baths (I get headaches) I just ordered glucosamine/chrondroitin sulfate but I think ingesting it will aggravate the sulfide bacteria. I'm going to go on a Parasite protocol which is one of my root cause and a low histamine diet. And take PC.

Has anyone had success taking PC who has Sulfur intolerance? I read that you're not supposed to but also read it will heal the mitochondria. I also read no glycine with sulfur intolerance but I'm thinking if I can't do the epsom salt baths I have to fix the methylation block, correct? And the glycine will do that. I am taking magnesium glycinate with good results. I am new and very sick. Any help would be appreciated!
 
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Methyl Head

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@Learner1 - dbose is the person I was originally responding to and I didn't suggest you do or follow any of what I said. Furthermore, I'm an advocate for getting tested and understanding what's going on, with that in mind, I specifically chose the things I suggested because they are low risk and won't harm him/her if they choose to take them because I understand the damage that can be done without a clear picture of where this person is in recovery (with the exception of arginine but I made a note to be careful with this as well if you look at the initial post because of BH4).

If the advice isn't relevant and useful to you then kindly disregard. I don't know if you actually have CBS but I'm sure you know there are stages to treating and clearing the transsulfuration pathway if it is a problem. If you have a high urine sulfate reading you may qualify for this approach as the transsulfuration pathway has to be cleared first before moving on to any other methylation treatment. If you don't solve this problem first, you're not only flushing all the Mcbl, P-5-P and MTHF down the drain you're also causing yourself damage because your good nutrients will convert to ammonia and sulfites then release into the body which will make things worse in the long run/raise taurine and further exacerbate glutathione production issues because they share the same pathway. With that in mind, there is a stage type approach to methylation when CBS is involved, and early on in treating this problem especially, because certain things will only aggravate symptoms. Here is a link that justifies my views.

http://resqua.com/702188759/what-does-a-cbs-gene-mutation-mean

This way of thinking is not only valid, it's been designed by Dr. Amy Yasko and it's been confirmed in the link above. I'm not saying this will work for everyone but I can say that it worked for me when I first tested for and found CBS, I was very sick and it took me a while to clear everything before I could handle other supplements, and my sulfate readings were about the same as dbose's. I understand the body needs sulfur and the same goes for glycine, it's about timing though, like I stated in my first response to dbose, be careful and really feel what works for you because you might not be ready for some things yet.
 
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Wow that link is super helpful! Thanks! What is a lipid donor? It says I should limit them. I take PC. Would that constitiute a lipid donor?
 
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In the link she also said magnesium flushes can reduce ammonia. I can't find info on that. Do you know what type of magnesium and how much? Never mind. I just found it. Take magnesium citrate for bowels.
 

Methyl Head

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@calexis6666
Bona Fide Lipid Donors would be:
-Lipoceutical EDTA
-Lipoceutical glutathione
-High doses of essential fatty acids (EFAs)
-CoQ10
-Alpha Lipoic Acid (ALA)
-Idebenone

PC is a methyl donor and a type of lipid but it's amphiphilic, so it's both hydrophobic and hydrophilic (emulsifier), polar, contains a phosphorus group and makes up the bilayer of cell membranes which control the in/outflow of most thing traversing our cells as opposed to lipid donors which are only hydrophobic and can be burned as energy (meaning that instead of leaving a standard metabolic trace like burning mono- di- triglycerides would it's recycled in autophagy but that's complicated and a bit over my head/cutting edge science). Phospholipid replacement is not only helpful for ME/CFS it's also used in moderate/high doses after the intial clearing of the transsulfuration pathway and can stimulate BHMT function because choline can be broken down into TMG, I'd say it's safe as long as you know your urine sulfate/ammonia status.
 
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The Hansa Center treat lyme patients with something called Neuro-Antitox to eliminate the extra ammonia produced by lyme. Reducing the ammonia is the first step before treating lyme and co infections. Once the ammonia is reduced the treatments do not cause herxing. This is explained in their book.
 
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@calexis6666
Bona Fide Lipid Donors would be:
-Lipoceutical EDTA
-Lipoceutical glutathione
-High doses of essential fatty acids (EFAs)
-CoQ10
-Alpha Lipoic Acid (ALA)
-Idebenone

PC is a methyl donor and a type of lipid but it's amphiphilic, so it's both hydrophobic and hydrophilic (emulsifier), polar, contains a phosphorus group and makes up the bilayer of cell membranes which control the in/outflow of most thing traversing our cells as opposed to lipid donors which are only hydrophobic and can be burned as energy (meaning that instead of leaving a standard metabolic trace like burning mono- di- triglycerides would it's recycled in autophagy but that's complicated and a bit over my head/cutting edge science). Phospholipid replacement is not only helpful for ME/CFS it's also used in moderate/high doses after the intial clearing of the transsulfuration pathway and can stimulate BHMT function because choline can be broken down into TMG, I'd say it's safe as long as you know your urine sulfate/ammonia status.
Thank you! Yea I got some way to go clearing the ammnoia before I can take it. I tried a couple of days ago and the pressure headache came back.
 
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The Hansa Center treat lyme patients with something called Neuro-Antitox to eliminate the extra ammonia produced by lyme. Reducing the ammonia is the first step before treating lyme and co infections. Once the ammonia is reduced the treatments do not cause herxing. This is explained in their book.
Actually I"m taking this. It is helping a lot. Right away I notice more clear headedness.
 

Methyl Head

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Thank you! Yea I got some way to go clearing the ammnoia before I can take it. I tried a couple of days ago and the pressure headache came back.
@calexis6666 Those headaches are the worst, I found that Ornithine and Chlorophyll helped with that for me. Keep in mind that if you have those headaches it can be a sign of PH problems as well (considering that free radicals generally cause this to begin with and when you can't get rid of them it's worse), especially if you have muscle soreness accompanying. I say this because it's highly common for those with moderate 5- Oxoprolinase deficiency (genetic glutathione deficiency) to experience these symptoms along with Anion GAP/metabolic acidosis and light/moderate hemolytic anemia. For the sake of reference (albeit a clinically understudied subject and complex issue to study because other SNPs affect the conditions behavior and activation) we can use 5- Oxoprolinase as a map for the potential issues associated with the CBS SNP if indeed we are under producing Glutathione.

Now, it's much easier for guys to figure this out through a simple CMP or blood testing because our iron should stay fairly stable and if we are experiencing anemia without internal bleeding it should signal a problem and then it's easier to gauge how severe/what the problem is once other tests are run, especially if MCV is normal and no other blood issues are indicated. For ladies though, iron storage changes and this might not be so cut and dry so the other option would be to do a UAA or urinalysis with a NutraEval Genova to see what's going on as it would save you a lot of trouble, time and experimentation. If you choose to experiment with making some glutathione without testing try turmeric/curcumin (if you suspect gut issues or autoimmunity I'd use curcumin because you don't need black pepper to activate curcuminoids unlike turmeric) or a 2:1 ratio of glutamine and glycine (<800 urine sulfate suggested, but if you feel like you have a ton of cysteine which can cause pressure headaches by the way then go for it, if glutamine bothers you, wait until later for the aminos) low dose P-5-P and R-5-P with magnesium glycinate can help too.

It's also possible that whenever you take PC the body is breaking it down into TMG thereby stimulating BHMT function and bypassing potential MTR/MTRR defects and now that the methylation block up stream from CBS is gone your body can't clear what's being sent fast enough, if you think that's the case try zinc along with PC. If that doesn't work check COMT and VDR taq status to determine your tolerance for methyl groups, you might be overstimulating with PC if you are a slow burner of dopamine, just a couple ideas to address those headaches, happy hunting!

https://rarediseases.org/rare-diseases/glutathione-synthetase-deficiency/
http://www.heartfixer.com/AMRI-Nutrigenomics.htm (glutamine sensitivity - BHMT activity)
 
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Thanks for your help! Glycine/glutamine gives me headaches as well as PC. I feel the Ornithine and Yucca is helping the most. I cannot do Turmeric due to Sulfur/Salycilate intolerance. No herbs. I am now more consistent with diet so I'm sure everything will get better as gut and liver heals.
 
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@calexis6666 Those headaches are the worst, I found that Ornithine and Chlorophyll helped with that for me. Keep in mind that if you have those headaches it can be a sign of PH problems as well (considering that free radicals generally cause this to begin with and when you can't get rid of them it's worse), especially if you have muscle soreness accompanying. I say this because it's highly common for those with moderate 5- Oxoprolinase deficiency (genetic glutathione deficiency) to experience these symptoms along with Anion GAP/metabolic acidosis and light/moderate hemolytic anemia. For the sake of reference (albeit a clinically understudied subject and complex issue to study because other SNPs affect the conditions behavior and activation) we can use 5- Oxoprolinase as a map for the potential issues associated with the CBS SNP if indeed we are under producing Glutathione.

Now, it's much easier for guys to figure this out through a simple CMP or blood testing because our iron should stay fairly stable and if we are experiencing anemia without internal bleeding it should signal a problem and then it's easier to gauge how severe/what the problem is once other tests are run, especially if MCV is normal and no other blood issues are indicated. For ladies though, iron storage changes and this might not be so cut and dry so the other option would be to do a UAA or urinalysis with a NutraEval Genova to see what's going on as it would save you a lot of trouble, time and experimentation. If you choose to experiment with making some glutathione without testing try turmeric/curcumin (if you suspect gut issues or autoimmunity I'd use curcumin because you don't need black pepper to activate curcuminoids unlike turmeric) or a 2:1 ratio of glutamine and glycine (<800 urine sulfate suggested, but if you feel like you have a ton of cysteine which can cause pressure headaches by the way then go for it, if glutamine bothers you, wait until later for the aminos) low dose P-5-P and R-5-P with magnesium glycinate can help too.

It's also possible that whenever you take PC the body is breaking it down into TMG thereby stimulating BHMT function and bypassing potential MTR/MTRR defects and now that the methylation block up stream from CBS is gone your body can't clear what's being sent fast enough, if you think that's the case try zinc along with PC. If that doesn't work check COMT and VDR taq status to determine your tolerance for methyl groups, you might be overstimulating with PC if you are a slow burner of dopamine, just a couple ideas to address those headaches, happy hunting!

https://rarediseases.org/rare-diseases/glutathione-synthetase-deficiency/
http://www.heartfixer.com/AMRI-Nutrigenomics.htm (glutamine sensitivity - BHMT activity)
methyl head, I have a CBS mutation but on my Spectracell test my gluathione was high/normal. How is that possible? I cannot tolerate ANY b vitamins nor magnesium glycinate/glycine.
 
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@calexis6666 Those headaches are the worst, I found that Ornithine and Chlorophyll helped with that for me. Keep in mind that if you have those headaches it can be a sign of PH problems as well (considering that free radicals generally cause this to begin with and when you can't get rid of them it's worse), especially if you have muscle soreness accompanying. I say this because it's highly common for those with moderate 5- Oxoprolinase deficiency (genetic glutathione deficiency) to experience these symptoms along with Anion GAP/metabolic acidosis and light/moderate hemolytic anemia. For the sake of reference (albeit a clinically understudied subject and complex issue to study because other SNPs affect the conditions behavior and activation) we can use 5- Oxoprolinase as a map for the potential issues associated with the CBS SNP if indeed we are under producing Glutathione.

Now, it's much easier for guys to figure this out through a simple CMP or blood testing because our iron should stay fairly stable and if we are experiencing anemia without internal bleeding it should signal a problem and then it's easier to gauge how severe/what the problem is once other tests are run, especially if MCV is normal and no other blood issues are indicated. For ladies though, iron storage changes and this might not be so cut and dry so the other option would be to do a UAA or urinalysis with a NutraEval Genova to see what's going on as it would save you a lot of trouble, time and experimentation. If you choose to experiment with making some glutathione without testing try turmeric/curcumin (if you suspect gut issues or autoimmunity I'd use curcumin because you don't need black pepper to activate curcuminoids unlike turmeric) or a 2:1 ratio of glutamine and glycine (<800 urine sulfate suggested, but if you feel like you have a ton of cysteine which can cause pressure headaches by the way then go for it, if glutamine bothers you, wait until later for the aminos) low dose P-5-P and R-5-P with magnesium glycinate can help too.

It's also possible that whenever you take PC the body is breaking it down into TMG thereby stimulating BHMT function and bypassing potential MTR/MTRR defects and now that the methylation block up stream from CBS is gone your body can't clear what's being sent fast enough, if you think that's the case try zinc along with PC. If that doesn't work check COMT and VDR taq status to determine your tolerance for methyl groups, you might be overstimulating with PC if you are a slow burner of dopamine, just a couple ideas to address those headaches, happy hunting!

https://rarediseases.org/rare-diseases/glutathione-synthetase-deficiency/
http://www.heartfixer.com/AMRI-Nutrigenomics.htm (glutamine sensitivity - BHMT activity)
I just got my MTHFR test back and it came back negative as far as mutations. It said if you are having mathylation issues it could be zinc deficiency (which I know I have) The COMT test came back balanced dopamine. No issues. So even if my COMT and MTHFR are fine, i seem to be having these problems anyways. I am getting the Nutreveal test in Feb so I'll have more information then.
 
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I just got my MTHFR test back and it came back negative as far as mutations. It said if you are having mathylation issues it could be zinc deficiency (which I know I have) The COMT test came back balanced dopamine. No issues. So even if my COMT and MTHFR are fine, i seem to be having these problems anyways. I am getting the Nutreveal test in Feb so I'll have more information then.
The COMT test came back Balanced GA/Valmet
 

Methyl Head

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The COMT test came back Balanced GA/Valmet
@calexis6666 - That's very interesting indeed, did you get your Vitamin D Receptors (VDR taq) NOS, SUOX and CYP7A1 CYP7B1 and other liver pathways done too? I need more information before I can really make an informed opinion but since you say you can't handles b's or glycine this could be a couple of different things: Normal dopamine could mean you're COMT -/- and VDR taq +/- or +/+, or you have a diet rich in bioflavinoids, bioflavinoids can slow down COMT and stop you from using dopamine too quickly, but without VDR status I can't confidently say. I'd also be interested to know if you're vegan or on a plant based diet low in sulfur already. That would explain a lot as well. Normal/high glutathione could be related to deficiencies in other antioxidants, (Zinc, Vitamin C and Vitamin E come to mind off the top of my head) and since you've confirmed zinc as a problem that makes sense. I'm curious about your dopamine though, what type of b12 are you using?
 
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Hi Methyl Head, thank you for helping me.

VDR BSM TT: +/+
VDR TAQ GG: +/+
COMT P199P: -/-
COMT V158 AG: +/-
NOS : -/-
CYPA1 and B1: +/-

SUOX isn't on the test . Is there another name for it? Is it methylation related?

Well I'm on a diet low in thiols. I still eat small amounts of meat. . I have a hard time with plant based due to adrenal burnout and pre diabetes. I just started IF and I'm planning on eating green juices for lunch and for dinner and ONLY beef broth as far as animal protein. I was vegan for a few weeks and I kept binging on carbs and made my gut worse. I think the broth will be fine. My blood ammonia level is 24.