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CBS and cofactors. Are CBS+ low in B6?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by sregan, Jun 20, 2013.

  1. sregan

    sregan Senior Member

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    Yasko mentions those with CBS mutations have an "open door" draining methylation toward transulfuration.

    That open door also requires B6 (or P5P/PLP depending on which diagram you look at).

    Wondering if people that are CBS+, especially if they have good methylation or taking SMP supps, might be prone to B6 deficiency?


    [​IMG]
  2. juniemarie

    juniemarie Senior Member

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    Glad you brought this up because I have read CBS- no b6 at all, CBS - no P5P, CBS - only P5P Kinda confusing
  3. sregan

    sregan Senior Member

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    Found This Article

    Guy says this:

    "Elevated B6 on an OAT test - B6 may also be elevated during CBS up-regulations"

    Doesn't make sense to me if CBS is an open door and needs B6 as a cofactor. Seems it would eat up all B6 it could find. Unless those can't convert B6 to P5P?
  4. sregan

    sregan Senior Member

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    Heartfixer has this on his page:

    "We need B6 for many activities but B6 drives the CBS enzyme; therefore supplement with the P5P form of B6 as opposed to B6 if possible."

    I have seen plenty of diagrams that show PLP or P5P as the Transulfuration catalyst so I'm not sure if I believe P5P is ok where B6 is not for CBS+

    From this link
  5. sregan

    sregan Senior Member

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    another from remedy spot

    "My son reacts badly to most (if not all B vits), however testing shows he is deficient inmost of them. *There is info in Rosemary Warings research on sulphation re: p5p.If there is a sulphation problem p5p is needed but you will negative reactions unless given with correct ratio of mg. *Kirkman do a P5p with mg glycinate in correct ratio.
    If there is a CBS upregulation (which my son has severe verson of) p5p will increase this problem. *We manage by giving a very small dose (just 5mg * - around 1/10 cap) of the kirkman p5p with mg). *This small amount really does make a difference - he has seizures without it. *If I increase it he reacts badly.
    P5P is needed along with active folate (folinic acid) and B12 for methylation."
  6. dannybex

    dannybex Senior Member

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    From Andy Cutler (in the context of heavy metal issues like mercury):

    "
    Nothing you hear on the web from 'alternative' sources about CBS relates to
    reality. Ignore all of it. Much of it is dangerously wrong and if you actually
    believe it you will hurt yourself a lot. It is all so random and unrelated to
    reality there isn't any way to work through it and 'explain what part of it
    makes sense,' because none of it does."
  7. Jarod

    Jarod Senior Member

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    I am high in b6 and that has been measured with blood work. If I get too much, I get really wired but in weird way. p5p is more tolerable but not sure if I need P5P or not.

    I still haven't done my homework on methylation yet.
  8. sregan

    sregan Senior Member

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    Danny,

    I can't agree with "Ignore all of it", I respect Cutler as an authority on Metal chelation but he doesn't know everything to be making blanket statements like that. If he knows that much of it is dangerously wrong then he should be able to tell us why and give us the proper info on CBS.
    Star-Anise likes this.
  9. dannybex

    dannybex Senior Member

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    I understand. I can't speak for him, but I think he's probably talked about it before, and is just getting sick of it. Susan Owens, Rosemary Waring, etc., also disagree with her interpretations.
  10. sregan

    sregan Senior Member

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    Jarrod, you are CBS C699T +/+ (I'm just +/-), from my reading CBS is like the fly in the ointment. If you don't have CBS+ it seems things will be much easier, you just take your B12 and Mfolate and you're good. CBS+ is like an open door to the transulfuration path (which requires B6). The logic goes if you increase methylation you increase what can potentially go through that door. There are some products of transulfuration (ammonia, sulfites) that you may have too much of and need to deal with. (see this link about that)

    Yasko mentions:



    I would say the best route is after your genetic test results come back you can have certain tests run, based on your mutations, to see if those mutaitons are being expressed (High ammonia, sulfate for CBS+ for example) these test can eliminate a lot of guesswork.

    Based on mutations and test results then you can formulate your strategy for diet and supplements, etc...
    Jarod likes this.
  11. caledonia

    caledonia

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    My Nutreval test showed a pretty high need for B6 (#2 after B2). I have CBS C699T +/-, needed to go through a CBS protocol before tolerating methylacobalamin, etc.

    Prior to knowing much about methyation, I tried a Thorne B Complex which had a high amount of B6. I could only tolerate 1/8 of one pill. It didn't seem to do anything for me.

    Now I'm taking Yasko's B Complex, which is low in B6. I can tolerate a whole pill, which means I'm getting a lot more B2 and the other B's which I so desperately require. I'm starting to get several positive results.

    Yasko's has 7.5mg of B6. I'm also getting a similarly small amount in my Thorne multi (3mg) and Yasko multi (4mg).

    In this case, less is more.
    ukxmrv likes this.
  12. Jarod

    Jarod Senior Member

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    Thanks sregan.


    Interesting about this up-regulation stuff. I don't want to get off topic, but have an interesting experience that might relate to what you and Dannybex are talking about and will post a blog about it.

    This draining stuff is something I don't understand.

    In my situation it seems more like a stomach infection that prevents me from tolerating the sulfur supplements.
  13. triffid113

    triffid113 Day of the Square Peg

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    Do not believe everything Yasko says. She is the front line of research - meaning she has to make guesses before actually knowing and research is not supporting her guesses as regards to CBS.

    I have CBS C699T +/+ and CBS A360A +/- and it does NOT cause me low homocysteine. Unsupplemented I have high homocysteine. So (1) in real life we have multiple polymorphisms and they interact with each other so you cannot know what the total effect willl be w/o testing...the gene test merely tells you what to test for. (2) Yasko is testing CHILDREN who have a higher need for folate as folate is needed for cell division and they are growing. So what she finds in children may not apply to adults at all. (3) the study she uses only shows less than a 3% difference between homocysteine levels despite CBS polymorphism (not terribly significant).

    That said, I have many genetic defects and I find I need DHEA 75mg plus 50mg P5P OR DHEA 50mg and 100mg P5P to avoid anxiety. P5P is needed to make Gaba, dopamine, and serotonin. DHEA is part of the hormone chain that effects gene expression. idk what gene combos cause me to need this but it works for me as part of an overall methylation startegy (as in I take a good B complex and TMG and potassium and D and antioxidants as well). I take P5P because P5P inhibits/prevents glycation and protects the kidneys, unlike B6. Also too much B6 causes neuropathy whereas I have never read any such thing about P5P. I have a policy of only taking active supplements and the body does not use B6, it uses P5P. There is logically a speed limit in converting B6 to P5P (and some people cannot convert) and I would guess that is the source of the problem with too much B6. The reason you see PLP and P5P on biochemistry charts is because that is what is actually biochemically what is used. Also I have no issue with too much or too little B6 on OATS test.

    Here is a cogent rebuttal of Yasko regarding CBS: http://onibasu.com/archives/am/218588.html
    CBS Upregulation, Myth or Reality?
    By Mark London

    Upregulation of the CBS enzyme via two genetic polymorphisms has been
    theorized to be possibly detrimental for some conditions, based on the
    work by Dr. Amy Yasko in autism. These two polymorphisms were studied
    in 2000, and in that study, the Post Methionine Load (PML) test was
    used to determine the effects of different CBS polymorphism genotypes.
    That loading test can detect subtle defects in the transsulfuration
    pathway, which is the metabolic process that is affected by the CBS
    enzyme. The polymorphism with the greatest effect, as shown by the
    PML test, was found to be 699CàT (Y233Y). People with the TT (+/+)
    genotype of that polymorphism, and to a lesser degree CT (-/+),
    produce lower levels of homocysteine levels in response to the PML
    test, when compared with the CC (-/-) genotype. Lower homocysteine
    levels from that test infers greater CBS activity. By the way, none
    of these genotypes are rare. About 40% of the population has CC, 40%
    has CT, and 20% have TT. Thus, all the genotypes of this polymorphism
    are quite common. The study also looked at the CBS polymorphism
    1080CàT (A360A), but that was found to have less a significant effect.
    The TT genotype of that polymorphism only showed a significant
    decrease in homocysteine in the PML test, if 2 other polymorphisms
    were also excluded. Thus, 699TT seems to have the most significant
    affect on CBS activity.

    On the other hand, a similar study in 2003 on these polymoprhisms did
    not show a significant difference in homocysteine levels due to the
    different genotypes, in response to the PML test. One difference with
    this new study is that it was done on a different ethnic group, which
    is sometimes a factor in genetic studies. Also, while the mean age
    was the same in both studies, this new study had a much smaller range
    of ages, and did not include anyone younger than about 40 years old.
    This might be a factor, since CBS activity is known to decrease as a
    person gets older.

    Even more interestingly, is that a study on pregnant women in 2003
    surprisingly showed an increase in basal homocysteine levels from the
    TT genotype, the same genotype that had the lowest homocysteine level
    in the 2000 study. This study did not give any possible reason for
    this result.

    In any event, even in studies which showed increased CBS activity
    effects from the TT genotype, such as the one from 2000, and a more
    recent one from 2007, only small changes in homocysteine levels were
    observed. For example, in the latest study, which used a very large
    population of 10000, the basal homocysteine levels only differed by
    2.7%, between the TT genotype, which has the highest CBS activity,
    compared to the CC genotype, which has the lowest CBS activity.

    This minor decrease in homocysteine levels is in contrast to that
    which is seen in Down's syndrome, where CBS upregulation is definitely
    known to occur. In one study on Down's syndrome children, basal
    homocysteine levels were reduced by 25%, and plasma levels of
    cystathionine, which is produced by the transsulfuration pathway, was
    increased by 3.8 fold.

    On the other hand, a later study on Down's syndrome adults did not
    show decreased homocysteine levels. This surprising result was
    theorized to be due to the fact that adults have a much lower
    requirement for folic acid. When folic acid was given to the Down's
    syndrome children, their homocysteine levels rose significantly.

    Thus, age may become a factor when considering the effects from CBS
    upregulation. Dr. Yasko claims that these CBS polymorphisms can have
    significant effects for autistic children. Even if that claim is
    true, it is possible that it only has relevancy for children. Also,
    the claim may have no relevancy for other conditions, due to the fact
    that autism has many other metabolic disturbances that are not found
    in other conditions.

    It's also been claimed that increased urinary taurine and ammonia can
    help diagnose CBS upregulation. While it's true that CBS upregulation
    can cause increased taurine and ammonia production, there's no
    evidence that this increased production can be detected by measuring
    their urinary levels.

    Urinary taurine is an unreliable test for CBS upregulation, due to
    fact that urinary taurine is dependent on many factors, including age,
    genetics, gender, renal function, clinical conditions, and especially
    dietary intake. Thus, even though a study on Down's syndrome found a
    significant increase in plasma taurine, another study on Down's
    syndrome found that urinary taurine levels were normal. Urinary
    inorganic sulfur was also not significantly different, which doesn't
    confirm Dr. Yasko's prediction of excess sulfur byproducts from CBS
    upregulation .On the other hand, urinary thiosulfate was
    significantly increased. Thiosulfate is a metabolite of hydrogen
    sulfide, and CBS is one of only three enzymes known to be able to
    produce hydrogen sulfide. Thus, significant CBS upregulation was
    likely occurring, even though urinary taurine and sulfur levels were
    normal.

    Urinary ammonia is an even less reliable method for testing for CBS
    upregulation. This is because most of the ammonia (NH4+) in urine is
    produced by the kidneys for ph regulation. The ammonia that is
    produced elsewhere in the body, is usually detoxified by being
    converted to urea, which is then excreted. This process mainly occurs
    in the liver, and the liver is quite capable of handling the large
    amount of ammonia that is produced in the body, which occurs due to
    the metabolization of amino acids. The liver has to be able to do
    this, because the nervous system can only tolerate very low levels of
    ammonia. Excess ammonia, i.e., hyperammonia, only usually occurs
    either when liver functioning has been greatly reduced, or where a
    genetic defect in the urea cycle exists. Only by testing serum
    ammonia, can such a condition be diagnosed.

    In conclusion, the medical literature states that these CBS
    polymorphisms have only very mild effects on CBS activity. And even
    if there is significant CBS upregulation, there is no evidence that it
    can significantly cause any negative effects, such as overproduction
    of ammonia. Furthermore, the medical literature doesn't support the
    claim that elevated levels of urinary ammonia or taurine is indicative
    of CBS upregulation.

    Dr. Yasko claims that CBS upregulation can lead to "a lack of
    glutathione." However, while glutathione is reduced in Down's
    syndrome, medical researchers do not believe that this is due to the
    CBS upregulation. Instead, they believe it is due to the
    overexpression of the superoxide dismutase (SOD) gene, which also
    occurs in Down's syndrome: "The reduced plasma glutathione observed in
    the children with DS most likely reflects an adaptive antioxidant
    response to chronic oxidative stress, resulting from SOD
    overexpression." This conclusion is possibly confirmed by a lab study
    on CBS overexpression in mice, where even though homocysteine levels
    were significantly reduced by the CBS upregulation, gluathione levels
    were unchanged.

    Thus, while some of the aspects of Dr. Yasko's treatment plan may have
    usefulness, there is no support that CBS upregulation can have any
    negative effects.
    sregan and Mercy like this.
  14. Jarod

    Jarod Senior Member

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    Hi triffid,

    I've noticed that some people seem to respond well to glycine, and others do not. Do you know if you respond well to supplementing glycine? I can't tolerate it, I forget why exactly. It may increase excitoxicity in myself, but not sure.

    How about excitoxicity? you have excitoxicity issues by any chance?

    Every have luck with NAC?

    Thx.
    Jarod
  15. triffid113

    triffid113 Day of the Square Peg

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    ok, here is the scoop. I did a bit of research into NMDA receptors - I cannot remember what terminology I searched on offhand just now, but I found that estrogen protects the magnesium gate ion from being stripped from the NMDA receptors and thus prevents influx of calcium which is the basis of excitotoxicity. I would have never figured out for myself that I was deathly sensitive to MSG because of being female and protected at times of high estrogen but I had a bf figure it out for me one time that I almost died from MSG. I could NOT relax any muscle for 24 hours and could have had a heart attack. It felt life threatening. But I did not go to hospital I would not have known what to say - I would have just said "it's me being me - the random horrific health I am cursed with" and as usual docs would not have had a clue. Now I take DHEA and it protects me from excitotoxicity ALL the time. Dunno if it does so by virtue of the estrogen in makes or if DHEA itself helps (as it turns out for instance that it is the DHEA, not the estrogen, that corrects my blood pressure).

    I think I ran across other things that help but I don't recall what. You guys on Atkins-like diets (isn't that essentially Paleo) can be subject to this because the byproduct of protein breakdown is ammonia which takes magnesium to be excreted. The more ammonia you generate the more magnesium you need...or else your body strips it from the NMDA receptors.
    helen1 and Jarod like this.
  16. triffid113

    triffid113 Day of the Square Peg

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    More specifically I have never supplemented glycine. Don't know why I would?

    I want to thank y'all for raising the possibility that brain fog and headache may be caused by excitotoxicity. I take so many pills I often forget some of the reasons I am taking them. So for years I have said I am taking DHEA for my blood pressure and to prevent a forever panic attack. However I forgot that I am also taking it to prevent excitotoxicity (hmm, I wonder if panic is related to excitotoxicity...is this redundant? To me it feels different tho). I have thought of excitotoxicity as the muscle clenching, can't unclench whole body problem I had after eating at a Chinee restaurant known for using heavy MSG and never considered anything lesser as potentially being also excitotoxicity.

    Well now I am wondering about this nasty weird thing that happened to me (one of my random tsunamis of bad health that lasted 2 days). I have been trying to dial down my DHEA dose...I take 75mg, which puts me in the range of those taking it for depression, tho in my case it is panic. I have long wanted to dial down to a normal 50mg but I get panic symptoms back. I had read that B6 (P5P) treats panic and I tried it and it worked so I dialed down my DHEA to 50mg. I forgot about excitotoxicity. I also have a problem of schlepiness in the morning before taking my DHEA and sometimes this results in me going awhile before I take it. So, my fault, and yet it is SCHLEPINESS' fault, grrr. So 2 days ago I took all my pills together but not until an hour or so after lunch, and my pills caused severe edema, brain pain, brain fog, and I thought - oh my bp must be high in my head. Now after listening to discussions here I wonder if it is because my DHEA got so low that it did not protect me from excitotoxicity in time because it was not digested prior to other supplements and food. (Although it was not the MSG whole body effect I had before so I don't know). The other possibility is that I an iodine sensitive and today I caught myself mistaking the thyrocsin bottle for my B complex (they look the same). Usually when I take thyrocsin I pay close attention to whether I am tolerating the iodine...I never take it first thing before other supplements. Iodine causes brain tinnitis / buzzing and headache in me. Yesterday I had edema also -- not sure which possibility could have caused that.

    But I just read something REAL interesting about potassium suplementation which is a whole nother topc so I will put it in a following post as this is important.
  17. triffid113

    triffid113 Day of the Square Peg

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    Important stuff about POTASSIUM:

    From Iron Man Magazine Feb 2013 article on potassium:

    (1) Low carb diets have a diuretic effect that causes excretion of otassium and sodium and the potassium loss causes muscle weakness and fatigue. Supplementing potassium AT THE RIGHT TIME can make those side-effects vanish.

    So...what this "the right time"?

    (2) Taking isolated potassium supplements can lead to the release of adrenal hormone ALDOSTERONE. (!!!) Aldosterone conserves sodium while promoting excretion of potassium. This causes water retention. {Hell, THIS CAUSES HIGH BLOOD PRESSURE!] The water retention requires them to get more potassium which should be taken in food or via a supplement taken WITH MEALS.

    (3) Potassium has a relationship with other minerals. It works with sodium in controlling fluid in cells. Magnesium is needed to retain potassium in cells.

    (4) Potassium plays a role in helping to restore depleted glycogen. Muscle glycogen is the primary fuel of muscles.

    The article follows with all sorts of horrific near death and death cases of body builders getting too much or too little potassium...(so beware).
  18. triffid113

    triffid113 Day of the Square Peg

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    I have problems with glycogen storage which is why rhodiola has helped me in the past (it increases glycogen storage). I have severe problems with blood pressure and I wonder if that potassium dysregulation might be the source of my glycogen problems. I have a lifelong problem that I need to avoid sweating (I always assumed because of the mineral loss) or I get very sick. (I had heatstroke 3x before I figured that out). I do go in saunas but can only tolerate 10 minutes or it feels UN-healthful. This is the first I have ever heard about any timing issue taking potassium but I SURE do not want it to cause raised aldosterone - my b.p. cannot handle it. In fact I am wondering if some of my random edema issues could all trace back to potassium - even how it is supplemented.

    fyi this ties back a bit to CBS as I have wondered if my glycogen issues are related to CBS in the past as Yasko makes some mention of that. My panic attacks are actually glycogen issues...in my 40's I called them "undeserved low blood sugar attacks" and I would have to eat after every stressors (every time I got cut off in traffic I could not stop shaking until I ate, for example, and I live in an urban area where being cut off is the norm). I searched for an adrenal assist as the adrenal tells the liver to break down glycogen. I found rhodiola and it worked - studies prove it raises glycogen. After 50 it was no longer enough. After my hysterectomy I has "undeserved low blood sugar" forever. There is NO DIFFERENCE between panic attack symptoms and low blood sugar symptoms except whether or not sugar fixes it. So I was forced to start calling it panic attack. I knew it had to do with my hormones so I found DHEA right away and it cleared me up in 15 MINUTES. I could feel it working like going through a funhouse mirror as it sorted me out and then I was fine. So...anything to do with CBS? Or is it the fact that I am ACE +/+ as well as NOS +/- and - I forget which other gene of mine causes high b.p. and thus POTASSIUM LOSS and thus GLYCOGEN problems. I'll have to ask my doc if the 3rd gene that causes it is CBS.
  19. Jarod

    Jarod Senior Member

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    Hiya,

    I've noticed people mention they benefit from glycine on here in the past. It is also sometimes suggested as a supplement that can may help with repairing the stomach. Not in my case, I tend to favor NAC. I'm wondering if one may benefit from one or the other based on some kind of individual situation?

    Glycine is also an ingredient for making glutathione.

    Excitoxcity can be caused by all kinds of foods and stuff. Dr Blaylock has a video(in the first 30 mins) that discusses excitoxicity in POST #12 HERE.
  20. Jarod

    Jarod Senior Member

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    I believe eliminating caffine can be most beneficial in controlling excitoxicity and balancing electrolytes, vitamins, minerals etc.

    I just can't seem to absorb much stuff when drinking caffine and get all kind of other issues like frequent urination or weak shut off. I tend to be highly excitoxic. Maybe it is a potential CBS upregulation thing with dysfnctional cysteine exchange from these various antiporters and other receptors like the EAAT3 maybe?? I haven't done all the homework on the yasko stuff, but this draining thing is something I can't comprehend.

    I'm wondering if the CBS draining thing may actually be more of a higher requirement for cysteine, but that is just speculation based on futzing around with NAC and ALA.

    I wondering is my intolerance in my to those sulfur prodcuts now might be related to a stomach infection of leaky gut?

    I tend to be adrenal fatigued, mental fatigued and cognitive dysfunction more than the imobilizing physcial fatigue. However, I do know what being bed bound is like and do get PENE.

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