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HELP: Has anyone been able to resolve their CBS upregulation problems?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by dannybex, Oct 30, 2011.

  1. dannybex

    dannybex Senior Member

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    Hi Anne,

    Good to hear from you -- it's been a while! I guess moly-b is not part of my protocol until the copper issue is addressed -- even though it showed up low on my test. Iron was also very, very low, but she said it could also be biounavailable, so said not to take any. Just eat red meat once or twice a week.

    I really do think I need some moly-b -- but it does reduce copper, so I guess I need some copper to increase cereuloplasmin levels first.

    Thanks Anne!

    d.
  2. dannybex

    dannybex Senior Member

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    Hi again Rydra,

    Yasko is also treating adults as well as kids. Perhaps more kids than adults, but I agree -- her take on magnesium sulfate (and sulfate itself) just doesn't make sense. And other researchers seem to totally disagree with her on that.

    d.
  3. rydra_wong

    rydra_wong Guest

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    Dan

    I have been treating 10 cats at my place and 2 at my Dad's with flea products plus spraying both houses weekly and it is making my protocol for banishing what to me is "PMS-forever" (for I have had these symptoms every PMS when my hormones would dip) not work. I looked into the products only to the extent that I saw the words "androgen receptor blocker" and decided that right there was my problem because I cannot function without DHEA which sounds like it is being blocked. Which makes me more like you, if you are not taking DHEA/hormones.

    So based on what someone here said and just a few minutes of search (I have no real time these days) I decided to beef up my magnesium and take extra
    P5P and TMG. In so doing I discovered I was taking 100mg P5P tablets (I forgot I had raised my dose -- I had thought I would not be able to handle it but I wanted the extra P5P because it saves your kidneys and B6 does not), and since it did not bother me I kept it up (it's just a click at iherb, I usually just "get the same" as last time). I was taking 50mg for over a year. The 100 makes no discernable difference, it is just a safety feature.

    PMS (that is my genes w/o hormones to assist) make me tense and every day the tension builds a little more until my chest feels like it will burst, muscles and joints hurt, yada, yada. I even found my blood pressure went up again (a clear sign the DHEA was not working) and I starting waking up shaking with low blood sugar (another clear sign).

    I had bought the 300mg adrenal glandular from Nutricology during allergy season when my adrenals bottomed out temporarily and I put it back into service. Here is what I took to banish low blood sugar, and tension. My blood pressure only went up the one day -- I got that in hand too.

    300mg P5P spread out over the day
    1600mcg methylfolate
    3g. TMG
    600mg adrenal glandular spread out over the afternoon when blood sugar started going low
    1g. cal/mag (I was just careful to take the full dose, plus I added a huge greens sald and drank mint decaf tea)

    plus my usual stuff - in particular
    75mg DHEA (divided dose)
    30mg pregnenolone
    Thorne Basic B 2x/day (all active B's - I never take any inactive B's)
    1 Jarrow mB12 sublingual
    high dose antiocidants, etc.

    It banished the tension. I did however also notice in the last few days, that I am starting to get optic nerve swelling in one side of my brain again since I have been exposed to androgen receptor blockers for a month or so now. I priorly identified that as caused by hyperthyroid caused by too much iodine, but as I am not taking iodine, it is now true hyperthyroid from lack of copper...so the androgen ..blocker is making it difficult for me to absorb copper. I decided to eat a can of little shellfish as they are high in zinc, copper, and betaine. Those in my family with these health issues eat can of little fishies. No one else in the family does. So far it blunted the optic nerve swelling but did not make it go away. It made me feel like I'm glowing with health but still have something emitting oxidants in my brain (I may up my antioxidants further -- I did take an extra selenium).

    I don't know if you suffer from tension due to CBS. The above may drain it if you do (you only have some of the same genetics as me though). I do not believe the DHEA was doing that much for me because of the androgen...blockers. But the extra adrenal glandulars picked up where they started failing and kept my blood sugar stable. (Do you ever think one thing and type/say something else??? I saw a website of jokes called "scumbag brain' that comes to mind...for light humor look here: http://memegenerator.net/Scumbag-Brain)

    Lots of magnesium will help you get rid of as much ammonia as you have BH4 to pair with it. As long as you are not eating a high protein diet, you should have BH4 available. (I have 3 genes that cause low BH4 and I am able to manage it, so take heart on that. I would be able to handle 80g of protein and you should not eat more than that as it leads to cancer anyway. (How many grams do you eat every day?)).

    Do not discount the calcium! Some doctors were finding that a 3x(daily requirement) dose of calcium/day would tremendously help PMS and I used that for the major portion of my life to good effect. (Of course I have the VDR mutation and I now take 7000 mg D/day so I'm not sure which thing it was that the calcium helped). Of course, some people make stones. I don't know enough about the chemistry of stone formers to provide any help there.

    So when someone here said there is no reason for cal/mag to help except to make the symptoms less gruesome, I have to say "less gruesome" is quite a lot of help.

    ---

    When you say you have problems with B6, do you mean you also have a problem with P5P?

    I always go way out of my way to avoid chemicals and drugs of any kind. For instance, I would not buy canned fishies that are smoked or that are stored in anything but water. I eat stuff like Steamer's tv dinners and throw out the sauce. I eat naked food. I do not eat even processed cheese -- I could not eat cheese at all for 6 months until I discovered DHEA and that allowd me to eat something as salty as cheese. But aside from the salt I never woudl eat fake cheese -- only real stuff. I buy organic whenever I can. I won't even eat any chocolate but Dove because they all contain a preservative called PGPR in them now and I don't want it! Dove is theonly one that doesn't. When my head hurts from tension from flea products I will not take aspirin because it interferes with absorption of something I need -- I am thinking copper, but maybe more minerals than that. I wil apply DMSO for any pain or tension, even headaches, and it works. If you cannot tolerate P5P, the first thing I would ask is what drugs, medicines, and chemicals are you being exposed to? Because we both have CBS mutations so you should be able to tolerate P5P I am thinking.

    Best
    Rydra
  4. rydra_wong

    rydra_wong Guest

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    Dan,

    Some papers regarding TMG and CBS:

    Vitamin B-6 is a cofactor for CBS, and 50% of subjects with homocystinuria are responsive to vitamin B-6 therapy. ... betaine... improves clinical symptoms, reduces homocysteine, and increases plasma methionine, serine, and cysteine concentrations (208221). ...Betaine treatment in children significantly lowers homocysteine in cerebrospinal fluid and raises serine and SAM concentrations (222). Studies on MTHFR deficiency (223230) showed that betaine improves homocysteine remethylation, lowers plasma homocysteine, normalizes very low plasma methionine, elevates SAM, and leads to clinical improvement. A defect in cobalamin-C (vitamin B-12) activation results in methylmalonic acidemia and homocystinuria, and treatment with cobalamin, folate, or vitamin B-6 does not completely correct the biochemical defect. Addition of betaine leads to normalized homocysteine and clinical improvement (231234).

    In mice with moderate homocysteinemia caused by a disruption in the CBS gene, betaine supplementation decreases homocysteine, increases liver betaine, and increases BHMT activity in both heterozygous and wild types (252).

    CBS contains heme (so iron status likely affects it):
    http://www.nature.com/emboj/journal/v20/n15/abs/7593888a.html
    Cystathionine -synthase (CBS) is a unique heme- containing enzyme that catalyzes a P5P-dependent condensation of serine and homocysteine to give cystathionine.

    The heme part may not be correctable:http://www.sciencedirect.com/science/article/pii/S0002929707610623
    ... All five cbs mutations formed substantially more aggregates than did the wild-type CBS, and no aggregates contained heme. These data suggest that abnormal folding, impaired heme binding,...may be common mechanisms in CBS deficiency.

    Never fear, TMG does the trick if you do not respond tp P5P:http://journals.lww.com/geneticsinm...ne__beta__synthase_deficiency__Effects.3.aspx
    Betaine improves metabolic control in B6-nonresponsive patients with homocystinuria after optimum dietary control.

    CBS is susceptible to oxidants (but Yasko reported that). One such study with peroxynitrite: http://www.sciencedirect.com/science/article/pii/S0003986109002860
    So anti-oxidants are extremely important if you have the CBS mutation!

    Here's an interesting study showing some other possibilities for help in the future for some CBS mutations through agents that cause proper folding of the CBS enzyme. Also interesting statement here is that yeast with CBS CANNOT GROW in a cysteine-free medium. As in with CBS, cysteine becomes a serious dietary need: http://www.sciencedirect.com/science/article/pii/S1096719207001369
    ...mutations in the cystathionine beta-synthase (CBS) gene, ...are responsible for CBS deficiency, the most common inherited disorder in sulfur metabolism. Expression of human mutant CBS proteins in Saccharomyces cerevisiae reveals that most disease causing mutations severely inhibit enzyme activity and cannot support growth of yeast on cysteine-free media. Here, we show that the osmolyte chemical chaperones glycerol, trimethylamine-N-oxide, dimethylsulfoxide, proline or sorbitol, when added to yeast media, allows growth on cysteine-free media and causes increased enzyme activity from ...other mutant CBS proteins. ...This effect is not specific to yeast,...our data show that chemical chaperones present during the initial folding process can facilitate proper folding of several mutant CBS proteins and suggest it may be possible to treat some inborn errors of metabolism with agents that enhance proper protein folding.

    I ran across this interesting study - nothing to do with CBS exactly, but it shows a list of antioxidants that prevented rise of homocysteine in aging (normal) rats - we'd have to figure out what the dose woul be for people and see where we stack up on our supplementation regimes (I thought I read once that all CFS have lowered production of DHEA-S): http://www.sciencedirect.com/science/article/pii/S0304394010010128
    The study has shown that in aged (2224 months) rat brains an elevation of homocysteine level (42%) and a decrease in dehydroepiandrosterone sulphate (DHEA-S) content (32%) occur compared to those in the brains of young rats (46 months). Such changes in the brain levels of homocysteine and DHEA-S in aged rats are prevented, when the diet daily of the rats is supplemented with a combination of antioxidants (N-acetyl cysteine 50 mg, ?-lipoic acid 3 mg and ?-tocopherol 1.5 mg each per 100 g of body weight) starting ...The brain content of reduced glutathione is also decreased in aged rats as compared to that in young ones and the phenomenon can again be prevented completely by the same regimen of antioxidant supplementation. ...

    http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2010.06606.x/full
    This study is interesting because it brings something new into the mix: apparently CBS makes H2S which is one of 3 gasses modulating the H-P-A axis. Hmm, it says here H2S is made in brain which would contradict a previous study saying the CBS pathway does not exist in brain (I'll haveto track that down). Basically it says H2S calms down the inflammation hyper response of the HPA (lack of which which is probably what burned out your adrenals). I am going to try and see if DMSO seems to affect this (I will have to buy a new bottle). I don't know if that sulfur can combine to form H2S, but if so -- an adrenal protection bonanza there. It does deflate inflammation noticeably (like fast enough that you can see it happen).

    The above paper is of further interest because it says: "CBS activity in the brain is calcium/calmodulin-dependent".

    For that assertion, here is the paper cited: http://www.ncbi.nlm.nih.gov/pubmed/... 5 Nov from 10-12 GMT for monthly maintenance
    New roles for cysteine and transsulfuration enzymes: production of H2S, a neuromodulator and smooth muscle relaxant.
    Dominy JE, Stipanuk MH.

    And re: calcium/calmodulin, I also find this: http://www.ncbi.nlm.nih.gov/pubmed/12213817
    A novel enhancing mechanism for hydrogen sulfide-producing activity of cystathionine beta-synthase.
    Eto K, Kimura H.
    CBS (3 regulatory domains activated by p5p, SAMe and redox [13])

    HEY - BINGO YOURSELF HERE -- NOTE THAT TESTOSTERONE INDUCES CBS ACTIVITY (so it is not just estrogen that positively affects the methyl cycle!) see below

    CBS activity is induced by SAMe (via enzyme stabilisation) [14], testosterone [15], vitamin D [16], and by neuronal Ca2+/calmodulin [17,18]. CBS is modulated via redox (fe(III) & CO) [13,19] and notably inhibited by peroxynitrite [20[/B]
    H2S is produced from cysteine by cystathionine beta-synthase (CBS) in the brain and functions as a neuromodulator. Although the production of H2S is regulated by Ca2+ and calmodulin in response to neuronal excitation, little is known about the molecular mechanism for the regulation in CBS activity. ...

    Wiki says of calmodulin: CaM mediates processes such as inflammation, metabolism, apoptosis, smooth muscle contraction, intracellular movement, short-term and long-term memory, nerve growth and the immune response. ...Many of the proteins that CaM binds are unable to bind calcium themselves, and as such use CaM as a calcium sensor and signal transducer. ...CaM can bind up to four calcium ions, and can undergo post-translational modifications, such as phosphorylation, acetylation, methylation and proteolytic cleavage, each of which has potential to modulate its actions. Calmodulin can also bind to edema factor toxin from the anthrax bacteria.

    SO I did a little search of Vitamin D since you say you have the Vitamin D receptor defects as I do and I found this:
    http://www.clinsci.org/cs/120/0099/1200099.pdf
    ...vitamin D...up-regulates expression of metallothionein, a free radical scavenger protein with photoprotective properties [120].
    (I take 7000 mg D/day)
    The enzymes of the transsulfuration pathway also have the capacity to catalyze the desulfhydration of cysteine. Recent studies demonstrate a role of the transsulfuration enzymes, cystathionine gamma-lyase and cystathionine beta-synthase, in catalyzing the desulfhydration of cysteine in brain and smooth muscle. The H2S produced from cysteine functions as a neuromodulator and smooth muscle relaxant. In glutamatergic neurons, the production of H2S by cystathionine beta-synthase enhances N-methyl-D-aspartate (NMDA) receptor-mediated currents. In smooth muscle cells, H2S produced by cystathionine gamma-lyase enhances the outward flux of potassium by opening potassium channels, leading to hyperpolarization of membrane potential and smooth muscle relaxation.

    I see there is already a CFS site that knows about the effect of calmodulin, If you are not aware of it you may want to take a look: http://bb-cfs.blogspot.com/2010/07/methylation-pathway-regulation.html

    I'm sorry I don't have the kind of time I've had in the past to go over studies. I think the above is useful for someone who doesn't know much about CBS (like me), not so sure about you. I just followed Fredd's protocol and got my homocysteine perfect and figured the gene was therefore not a problem since I could do it.

    Regards,
    Rydra
  5. lampkld2

    lampkld2

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    This is all talking about upregulating CBS which is not what we want... I think we want to downregulate it....
    soulfeast likes this.
  6. aquariusgirl

    aquariusgirl Senior Member

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    i think richvank already posted something that showed low VIt D levels downregulate it....so probably not a problem for a lot of us.
  7. lampkld2

    lampkld2

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    Yea but low vitamin d puts us at risk for a lot of other things that are not so good.

    So we are stuck between a rock and a hard place.

    Apparently they are working on some drugs for down syndrome that downregulate CBS.

    Anyone know anything about this? Anyone know any CBS downregulators?
  8. rydra_wong

    rydra_wong Guest

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    Lampkld2 said:

    This is all talking about upregulating CBS which is not what we want... I think we want to downregulate it....

    Please do not just suck up what anyone says to you, doctor or no. I have two CBS +/+ and +/- genetic defects and Yasko says this is supposed to require me to DOWNregulate CBS.

    But I tested my homocysteine and it was HIGH, not low. That means I need to UPregulate CBS!

    And please do not EVER think you are between "a rock and a hard place" because you need Vitamin D no matter what. I did not know my genes when I started taking 50,000 mg Vitamin D/week. And if I had, I would have taken it anyway. I think if you get the whole protocol in place some things will UPregulate and some DOWNregulate and you need a homocysteine test to see what you need to do next.

    If homocysteine > 6.3, then you need to UPregulate CBS.
    If homocysteine < 6.3, then yu need to DOWNregulate CBS.

    All I know is that with heavy antioxidant use and use of things like Olive Leaf extract to kill pathogens and a good vitamin regime (but not yet Fredd's protocol) my homocysteine was HIGH (despite CBS). With Fredd's protocol, it is ON THE MONEY.

    Untill you get your homocysteine measured, you don't know what OTHER FACTORS besides your genes are affecting CBS. You really do not know if you need to up or down regulate!

    (P.S> My ammonia is on th emoney too -- I know I can eat at least 80 grams of protien a day and any more than that is unhealthy anyway).
  9. dannybex

    dannybex Senior Member

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    Hey Lampkid,

    Glad to see you're hanging in there. It's tough I know, but trust yourself to know you can get through this.

    All this CBS 'upregulation' stuff is very confusing, but from what I've been able to gather over the last couple weeks, most researchers tend to DISAGREE with Yasko when it comes to her conclusions re the CBS issue. She says to avoid sulfate, others say sulfate is CRUCIAL, and sulfur foods are also important.

    More information can be found on the 'trying low oxalates' yahoo group. There are two long messages from Susan Owens, who spoke with a lot of researchers who had published papers on the CBS enzyme, and ALL of them disagreed with her conclusions. I don't think I'm allowed to copy and paste anything, but will just paraphrase one part:

    Rosemary Waring (one of the leading researchers) apparently told Owens that if the amount of ammonia produced by that pathway was a problem for the body to handle, then you have far more serious issues than Yasko was talking about.

    Waring, Jon Pangborn, Susan Owens, and one unidentified researcher disagree with Yasko on this issue, and some have wondered why she hasn't published any research?

    I'm beat. Will be back in a few days...hope this helps a little. Hopefully Rich will chime in.

    Dan

    p.s. I've also read studies where Jill James calls CBS 'upregulation' an 'adaptive' situation. Suggesting it's not permanent, but adapting to perhaps metals, other toxins???
  10. rydra_wong

    rydra_wong Guest

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    Again, what are your homocysteine numbers?
    I would not even think of not taking a vitally needed vitamin like D. If I truly needed to DOWNregulate, the first thing I would do is make sure that my system was free of toxins (maybe get chelated), and pathogens (I use herbals like olive leaf extract (but this is a vasodilator and if you have low blood pressure this one won't work for you), oil of oregano, astralagus, etc to kill pathogens).

    Here's the best strategy IMHO -- get rid of all the things that affect the methyl cycle (any bit of it) that you know are bad, put a reasonable protocol in place,then test homocysteine. See if that didn't take care o most of the problem. (In other words get rid of the bad stuff before ever considering getting rid of the healthy things).
  11. rydra_wong

    rydra_wong Guest

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    I know this gene is scarey. But it can be solved -- I DID IT.
  12. Joopiter76

    Joopiter76 Senior Member

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    I can confirm that Yasko is right with the sulfate and sulfite issues. As I got very bad from many things I know understand what the reasons are. I can barely stand any sulfate, even those in bottled water. therefore I have to drink tap water which has low sulfate levels. Vegetables with sulfur are very bad for me. So thats it.
  13. dannybex

    dannybex Senior Member

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  14. rydra_wong

    rydra_wong Guest

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  15. Valentijn

    Valentijn Activity Level: 3

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    We do appreciate your input, Rydra. But it's important to remember that ME/CFS is a very complicated disease. Even when there are some similar genetic factors, there may be other factors that vary widely from one patient to another, such as other genetic factors and infections.

    You also need to keep in mind that a lot of people with ME/CFS have had "answers" thrown at them from every side for years, which is both confusing and overwhelming, especially when dealing with brain fog. You need to accept that 1) you may not be "right", 2) what's right for you isn't right for everyone, and 3) you can't force people to adopt your views, even if they are 100% correct.

    Believing and insisting that you know what's best for others is not healthy for yourself, and is not helpful for others. Richvank and others have a good reputation on this forum because they present the data and their theories, and clearly distinguish between the two, and give explanations and advice when it's asked for or it seems warranted. They don't insist that we do things their way if we want to improve, and they don't imply that failing to listen to them equates to a stubborn desire to remain ill.

    I think you have some helpful information and theories, and I hope that you can continue to share them in a respectful manner.
    juniemarie and Jenny like this.
  16. rydra_wong

    rydra_wong Guest

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    Valentijn
    It is frustrating trying to communicate and being ignored out of turn without discussion, and seemingly just for having achieved most of what the entire topic is supposed to be searching for. I think you are assuming I don't know what it's like, but maybe I know more about what those things are like than you think (not saying that I know what it's like exactly for you, but don't assume I am clueless, please).

    I do know about brain fog - I have had stretches lifelong in which I could not make my brain wake up -- when I was younger it was due to severe anemia, undiagnosed because my family just assumed everyone is healthy and anyone sick was just being 'difficult'. I treated at the time with 20 cups of coffee a day (until I was 30 and passed out and finally got diagnosed, but thereafter had a lifelong struggle with recurring symptoms). When I got to be 48 I started having month-long stretches of being unable to wake my brain up and coffee was only a marginal help. Then I had high blood pressure diagnosed and have not had serious problems with brain fog since then. (I have every single day of my life without fail taken 12-25 vitamin pills a day to achieve this, and after age 50 have progressed to 42).

    However, I had a 9 month stretch of something almost worse -- hyerthyroid so bad it felt like a belt sander to my brain and sounded like the buzzing of a hornet's nest in my skull. From lifelong experience I feel doctors can never help me, so despite that I could not concentrate I had to solve that problem myself. I could only skim studies to ascertain whether they might be of some practical benefit but I could not really retain from one sentence to the next so all I could do is sequester likely-seeming papers, print them out, and later go over them slowly with a highlighter. And the re-review the highlighted stuff to see if it really added up to anything or was just interesting. Yes, I could still reason, but only with a memory of 1 sentence, so very hard to find the way.

    I don't like talking about the past, nor about sickness. It does not mean I don't experience it or sympathasize with others. Frankly talking about my own illnesses makes me depressed and I like to focus on happy things, and nothing makes me happier than learnng something new (it is better than sex!).

    I look at things differently that most, never follow the crowd, and miss the blind alleys that the crowd falls into (maybe find some of my own). Seems like the fresh point of view could be mutually beneficial.

    Apparently I do not communicate well - I do not understand where I go wrong in communication - but I find I am often ignored when in fact I had said something that took the problem out of the landscape of Kansas and into Oz. I find that distressing, it makes me feel invisible.

    Rydra

    I did not mean to distress Dan. I like Dan.
  17. shannah

    shannah Senior Member

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    Posting for your information.


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  18. rydra_wong

    rydra_wong Guest

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    BiancaS said:
    For the ammonia, I have ordered yucca and I am also using some drops which bind Ammonia in the gut. Working full speed on gut dysbiosis and the intercellular acidosis. Additionally, I am trying to get some prescription BH4 to refill the tank.
    Molybdenum will be the challenge and I am planning on taking a daily dose of 1000 mcg per day for the next 2-3 months and then retest levels. B6 is a challenge, since I have KPU and I need P5P, but not too much, so I do not overdrive the CBS and end up with Ammonia again..
    Apparently, low Moly is also responsible for the messed up copper/zinc ratios, according to Yasko.
    Zink - some people with KPU in the german Forum also experience strange symptoms after taking zink. The hypothesis there is that for some reason it is supposed to block the krebst cycle and activate the glutamate receptors. These people usually scale back zink and start with a very nlow dose, slowly working it up.
    -------------------

    I understand you actually had ammonia tested and do have high ammonia (this is not just theory). There are two things I can think of that can cause that:

    (1) You might want to check your magnesium levels because you need magnesium to eliminate ammonia. I dont take any yucca or charcoal product and have no problems with ammonia despite 3 genes that cause low BH4. I take 1g. of magnesium / day and I eat 60 g. of protein/day (but I tested my serum ammonia levels at 80 g/day and was fine at that level too).
    (2) Could it be possible that you were on a high protein (Atkind-like) diet before this diagnosis? I believe (and I can find papers if necessary) that a high protein diet (such as Atkins) can cause ammonia buildup even in genetically healthy people due to magnesium depletion by excessive ammonia from excessive protein intake.

    It is possible with CBS to have no ammonia issues. I do not know what else I do that may affect ammonia. Except I think getting the methyl cycle to work in general would take the load off the CBS genes and lower it in that way.

    I have high Moly and borderline low copper. So, not so sure about Yasko there. However my hair analysis showed low copper, unlike yours (although I understand that high hair copper may not mean high copper load). I understood from reviewing studies last year (so not new studies) that there is no serum or cerruloplasim or other way to measure copper status that has any validityand the scientific community has called for researchers to develop a reliable test. (If such a test came out just recently I dont know about it). High serum copper indicates inflammation, which surely the average CFS person has. (It kindof tells you nothing you don't already know).

    I dont have inflammation myself and believed I escaped that due to high antioxidant intake. (Anytime I feel any sort of inflammation I also take extra antioxidants until the symptoms go away)

    Did you know that zinc inhibits/prevents copper uptake and copper is a cofactor of methionine synthase. (This means that low copper causes all the same neuropathies and symptoms as low B12).

    Some things to consider:
    Are the people you are referencing taking 5-methylfolate to get past that? If not, having less places to go, homocysteine would naturally go down the CBS path more, producing more ammonia.
    What amount of magnesium were they taking (needed to eliminate ammonia)?
    What amount of protein were they eating were they making a large demand on their system?
    If ammonia is allowed to accumulate, it will depolarize the magnesium gates of the NMDA receptors, which is what causes glutamate toxicity.
    There are studies that show that estrogen protects against ammonia depolarizing the NMDA receptors and causing glutamate tocicity.

    (I take DHEA which converts to some level of estrogen which protects me from it. If I do not take the DHEA I also have gotton glutamate toxicity (thought I would die from it once due to msg)).

    I am interested in how the BH4 works for youhow expensive it is, whether it was hard to get your doctor to prescribe it, and how you felt (or your labs showed) different while taking it?

    Lastly, you say you can barely tolerate B6. But I can take any amount of P5P without difficulty despite the two CBS genetic defects. So maybe there is some other reason than the genetics for why you cant tolerate it. (I am sure the genetics figures in but it is possible to get around that bit).

    Rydra
  19. rydra_wong

    rydra_wong Guest

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    Dunningblue said some very interesting things:
    Interestingly, my headaches and brain fog did decrease substantially with molybdenum.
    The doctor at the heartfixer site says that carnitine will help bind up ammonia.


    This is should be posted on a things that work site with a sticky that does not roll away!

    A warning though is that molybdenum greatly interferes with copper absorption and low copper seems to be more serious than low molybdenum (although both are serious). Anyone with both shortages might want to study that maybe taking them at different times of day is all that is needed, not sure. (I am high in molybdenum despite have two CBS genes mutated).

    Epsom salts can get around a molybdenum shortage for awhile by providing magnesium and pre-made sulfates so the body can excrete toxins (which could have a negative impact on the methyl cycle). Obviously does not get rid of sulfites though.

    Using Freddds protocol, I make plenty of carnitine and do not need to supplement it. I regard normal carnitine and normal homocysteine as objective signs that Freddd's protocol is working for me. Fredds protocol is NOT just methylation supplements it is quite extensive. Sometimes one thinks one knows what supplements are helping and one is only partially right. (For instance I did not know Vitamin D helped CBS and did not list that I take 7000 mg/day. Fredd also says you may need to take his whole protocol including all the peripheral vitamins for it to work. Something to consider. I do know people who have tried very hard to get it to work and had to supplement carnitine anyway. I am only suggesting taking a good look at the protocol and making sure you aren't ignoring large chunks of it because it doesn't look like it applies.

    Rydra
  20. lampkld2

    lampkld2

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    Thanks for all your input guys.

    Rydra-

    Hmmm interesting. My Homocystine is also slightly high at 10.8 but my urine sulfate was high and my plasma Ammonia was like 54 (which is just slightly over the top of the ref range, but my Doc wants to get it retested at a hospital lab since it rises at room temp).

    I'm not sure it is that simplistic. I need 5-mthf really badly, as I react very well to it, but My homocystine is only slight high . I think my homcystine would be higher but CBS is sucking up some. I think to reduce homocystine simply to CBS would be wrong and be too much of a leap as there are other factors involved raising and lowering it. Does that make sense? I'm have some trouble writing right now.

    Danny-

    Thank you... its been tough But I feel like I'm narrowing in on things.

    How are you? did you ever figure out the metal issues?

    Yes CBS stuff is confusing....so.... I do have possibly high plasma ammonia.. what does that mean? My mbd was low on hair and my urine sulfate was moderately elevated.

    I will check out the low oxoalate group.

    Not sure what to do if I have to cut out animal protein... Can't have whey and most vegetable protiens have lots of glutamic acid.

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