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Sulfite/sulfate ratio and overcoming the problem

Discussion in 'General Treatment' started by Kimsie, Sep 20, 2014.

  1. Kimsie

    Kimsie Senior Member

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    I posted about 8 or 9 months ago about how I was giving certain vitamins to my sons, who have depression and schizophrenia. I have now completely revised my ideas about what is causing their problems, and I think it might be involved in the cause of many other illnesses, including chronic fatigue. I had mentioned once how my son with depression, who I will call D, had experienced extreme fatigue for over a year until we started giving him high doses of methylfolate. Then over a period of several months he became depressed. My son with schizophrenia responded well for about 4-6 weeks to the supplements, and then he relapsed. I have finally figured out why he relapsed.

    I have a partially new paradigm about how these illnesses are caused. I think I have found one piece of the puzzle that pulls together many other pieces of the puzzle into one comprehensible whole, if I am right in my ideas. This is rather technical, but I know that a lot of you have studied the TCA cycle and I saw there was a good thread about the problems with low sulfate earlier in the year, and this relates to that. I have written a somewhat more scholarly paper about this that I am still revising that has citations if anyone wants to see it. So here is my hypothesis, I have put the most relevant statements in bold so that people who don’t want to wade through the whole thing can just read the bold parts.

    Human Endogenous Retrovirus (HERV) can be activated by various stressors. In the case of my two sons, they both had mono at the time their illnesses started, and I believe that EBV activated the HERV. I have come to the conclusion that this retrovirus inhibits either sulfite oxidase itself, or the molybdenum cofactor, either of which will raise the sulfite/sulfate ratio. The high sulfite/sulfate ratio can interfere with many processes in the body, including but not limited to sulfation, phenol sulfur-transferase and enzymes which use sulfate as a cofactor, such as aconitase, one of the enzymes in the TCA (citric acid) cycle. There are so many enzymes which are affected by sulfur in the body and many of them could be candidate for inhibition by a high sulfite/sulfate level, directly or indirectly. Which symptoms a person has depends on environmental and genetic factors of the individual.

    A high cysteine/sulfate ratio has been found in many chronic illnesses, such as CFS, migraine headaches, multiple sclerosis, depression and fibromyalgia (Moss and Waring,"The Plasma Cysteine/Sulphate Ratio: A Possible ClinicalBiomarker" This is a great article and the PDF is available online). I think that this high cystine/sulfate ratio is caused by inhibition of sulfite oxidase.

    Sulfite oxidase is in the mitochondria and interacts with cytochrome c in the the electron transport chain, part of the energy producing pathways in the mitochondria, which depends on iron-sulfur clusters for electron transport, is inhibited. Since folate is involved in the synthesis or repair of iron-sulfur clusters, large doses of folate improve the function of the electron transport chain, leading to less fatigue in people who are experiencing fatigue due to inhibition of the iron-sulfur clusters in the electron transport chain.

    The electron transport chain (ETC) takes the H (proton) off of NADH, returning it to NAD. If the electron transport chain is inhibited, NADH can build up in the mitochondrial matrix, leading to inhibition of the alpha-ketoglutarate dehydrogenase enzyme, which changes alpha-ketoglutarate into succinyl-CoA, and truncates, or shortens, the TCA cycle. These low levels of succinyl-CoA are a huge problem, which I will explain below. The TCA cycle enzymes are activated by low ATP, the energy unit of the body, so when a person has fatigue from low ATP, the low ATP overcomes the NADH inhibition and the full TCA cycle creates sufficient succinyl-CoA.

    Succinyl-CoA is combined in a reaction with glycine, an amino acid, as part of the process of making heme. Heme is required for complex IV in the ETC, and also for sulfite oxidase. Heme is also required to make catalase, an enzyme which changes hydrogen peroxide (H2O2) to O2 and water. High H2O2 can cause many problems: it is involved in signaling the release of dopamine, and it produces free radicals. Catalase is also needed for the dopamine beta-hydroxylase reaction which changes dopamine to norepinephrine. Dopamine beta-hydroxylase has been found to lose more than 90% of its activity without catalase. This can lead to high dopamine and low norepinephrine, causing depression in some people. This is why while D had great fatigue he was not depressed, and when folate made his fatigue go away, he became depressed after his reserves of nor-epinephrine became depleted.

    We have found that the pyruvate dehydrogenase complex, which changes pyruvate into acetyl CoA to feed into the TCA cycle, is affected, because taking coconut oil, which produces ketones for acetyl CoA production to bypass this enzyme helps relieve symptoms, until molybdenum levels are depleted. We have found that supplementing to bypass these problems drains molybdenum. When we tested our son who has schizophrenia, who I will call S, his RBC molybdenum levels were extremely low after he had relapsed. It is interesting to note that D’s levels were somewhat high, but he didn’t get permanent improvement until we started giving him molybdenum every day. I guess that there is a constant turnover of sulfite oxidase that drains the molybdenum or requires high molybdenum levels to partially overcome the effects of the inhibition when you are taking supplements to keep the TCA cycle moving when sulfite oxidase is inhibited in this way. But molybdenum alone does not fix the problem.

    Niacin or niacinamide (B3) is required in large doses (250-1000 mg 3X a day) in order for the body to make enough NAD to lower the NADH/NAD ratio and lower inhibition of alpha-ketoglutarate dehydrogenase. This is just my hypothesis, I am not saying that there are studies to prove it. But I can say that this protocol absolutely does not work without the high B3.

    We have found that B6 is also required. If someone has problems taking B6, they may find that they tolerate it better when they have sufficient B3 and folate (3-5 mg per day) to support these inhibited enzymes.

    We make coconut treats out of coconut oil, vanilla, ripe banana, cocoa or carob powder and rolled oats to make taking coconut oil easy.

    Taking doses of 4-8 grams of glycine can help. Glycine does not readily cross the BBB but some of it does when you take large doses. Glycine will help make heme and catalase.

    R-lipoic acid and CoQ10 might also help some people. Lipoic acid is a cofactor for two of the TCA cycle enzymes and CoQ10 is in the ETC.

    Calcium and magnesium both have to be sufficient. If you supplement a large amount of one without the other you can run into problems.

    I am sure other enzymes are affected, but taking these supplements should help with those, too.
    A lot of this applies to heavy metals toxicity because they affect sulfur enzymes.

    I hope this is helpful. I know it is pretty confusing but hopefully you get the idea.
     
    Last edited: Sep 20, 2014
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  2. Peyt

    Peyt Senior Member

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    Do you know the genetic profile of your son? I am willing to bet he is CBS+
     
  3. Valentijn

    Valentijn WE ARE KINA

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    CBS C699T has only a tiny impact on the CBS gene and little or no relevance to sulfur metabolism.

    It's a smart bet to make though, since 55-75% of Europeans are "+" for CBS C699T. And it's pretty much guaranteed that almost everyone is "+" for at least one of Yasko's absurdly pointless CBS SNPs.

    Shall we use runes and star charts to determine the status of our methylation next?
     
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  4. Kimsie

    Kimsie Senior Member

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    Since this thread has popped up again, I would like to add that I have revised my hypothesis considerably since I first posted it so if anyone is interested in the changes they should take a look at my recent posts.

    On the subject of SNP's, I have yet to find a single SNP that I think is really relevant to my sons' illnesses, not even the MTHFR SNP's. This is because although I think the folate pathway is affected, and methylation can be affected mainly because B12 can be drained by oxidative stress, the part of the folate pathway that is the most important is NOT the part which concerns methylation. I think that the greatest improvement that people with CFS get from folate may come from the ATP producing parts of the folate pathway, which is a mixed blessing.

    I am sure that which symptoms a person gets from mitochondrial dysfunction is determined by genetics, and maybe how susceptible they are in general to mitochondrial dysfunction, but I now think that it isn't really very important to know which SNP's you have, although I keep checking various SNP's in case I might be wrong about that.
     
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  5. Peyt

    Peyt Senior Member

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    CBS C699T is not the only one... as you know there is also CBS A360A(which is the one I have)
    It's easy to disapprove the work, but what is your genetic explanation regarding sulfur metabolism?
    If not CBS, then what gene is responsible?
    I have High Sulfur and the CBS+ protocol is working for me... so before I go changing anything, I want to hear an intelligent explanation of what does impact sulfur metabolism based on your findings??
     
  6. Peyt

    Peyt Senior Member

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    Hi Kimsie,
    Have you actually ran your son's genetic profile?
     
  7. Valentijn

    Valentijn WE ARE KINA

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    I've read the research. C699T +/+ is mildly beneficial for reducing certain risks associated with elevated homocysteine. A360A and N212N have no research showing that they have any impact at all. But based on them not being involved in protein changes, it's highly unlikely that they are doing much, if anything.
    What work? Yasko reading a paper about half of a gene being lopped off in a lab yeast, and equating the results with some harmless SNPs at random?
    I don't know. Neither do you. And neither does Yasko. People's apparent problems with sulfur (self-diagnosed with industrial strips which probably don't work very well for medical use) may have a cause which has nothing at all to do with any gene.
    If it works, do it. But don't make up an explanation which has no rational or scientific foundation.
     
  8. Kimsie

    Kimsie Senior Member

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    Yes, I was posting on two sons, actually, and the one with schizophrenia had Yasko's panel done and the other had the 23andme panel. Our whole family has been tested (6 of us plus 2 of our grandchildren.)

    I know you were asking Valentijn, but I don't think a gene is directly responsible for the problems with sulfur metabolism in these illnesses. I think that the oxidative stress damages iron-sulfur clusters, and the iron-sulfur clusters are required for the assembly of the molybdenum cofactor which is used by sulfite oxidase, which is in the pathway for sulfur metabolism. Heme, which is in sulfite oxidase, may also be affected.

    This is according to my own hypothesis; there are no studies proving it directly, but the cysteine/sulfate ratio study gives some support to the idea, I think. The fact that ROS damages iron-sulfur clusters is well established and I can give references if anyone wants to see them.
     
    Last edited: Jan 12, 2015
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  9. Peyt

    Peyt Senior Member

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    First of all I have not made any explanation.. where do you see I have made an explanation?? Please look up the word explanation in your dictionary so you understand what that word means!...
    2nd, the protocol that I am using is on heartfixer and I don't like using anything from Yasko simply because she likes to sell her supplements and I stay away from any Dr. who does that...

    And I really don't care if you could not find any scientific foundation!... What's important is healing ...there are people like myself with this problem who are improving their health using different protocols. That's all that matters! If you and analitical people like you must have a scientific foundation before healing, that's your problem!

    The protocol that Kimisie is using is interesting to me because it resembles the CBS/BHMT protocol yet she has found it from a different approach... So if you don't mind, I like to have a conversation with her without you interrupting!
     
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  10. Valentijn

    Valentijn WE ARE KINA

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    Okay, you're repeating someone else's made-up explanation then. Yasko started it, and heartfixer has a bad habit of paying too much attention to Yasko and not enough attention to the research.
    Then you can stick to healing, and there's no need to create or parrot unfounded scientific explanations is if they were established science. Hypothesizing is useful, of course, but only if you understand that it is a hypothesis and not something with any scientific support thus far (and in some cases with scientific opposition).
     
  11. Peyt

    Peyt Senior Member

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    It is none of your business to tell me what to write or not write! This is an open forum!
     
  12. Kimsie

    Kimsie Senior Member

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    Hi Peyt, I think you might be overreacting a little. I agree with Valentijn that the CBS mutations are not important. She was just a bit sarcastic in her reply. I think it is helpful to have analytical people posting, I consider myself to be somewhat analytical. That said I understand her frustration with the fact that people keep bringing up the CBS mutations, because the top speed of CBS is controlled by things like how much SAMe and homocysteine there is, not by the mutations.

    You might be interested in reading my newer posts or even checking out my blog, which I have recently updated to conform with the latest version of my hypothesis. I keep trying to make my explanations easy to understand, but I think they are somewhat difficult for a lot of people to follow.
     
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  13. Valentijn

    Valentijn WE ARE KINA

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    Sure. And I can respond at some length explaining why you're wrong when you make incorrect claims :)
     
  14. Peyt

    Peyt Senior Member

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    Hi Kimsie,
    Is there a lab where I can get my cysteine/sulfate ratio study done? Is it a blood plasma test?
    Thanks
     
  15. Peyt

    Peyt Senior Member

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    Yes you can write lengthy explainations, but I will never read it :) ..
    because all your posts are the same... "there is no scientific foundation about.... " and you never actually have anything positive to report that actually helps heal... not worth reading!
     
  16. Kimsie

    Kimsie Senior Member

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    The Genova serum oxidative stress test has the cysteine/sulfate ratio on it. We have recently had blood drawn for this test, but the results are not in yet. The reference range for the Genova test is significantly higher than the reference range from the Waring study, so I would use the reference range for the Waring study, which is 0.12 as the highest normal level (it looks different in the Waring study paper because they multiplied it by 1000.) It is a blood plasma test. They also have a urine oxidative stress test so you have to specify.
     
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  17. Kimsie

    Kimsie Senior Member

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    It is my hope that this test will turn out to be an objective measure of progress towards actual wellness, since in many of these illnesses I believe that the severity of the symptoms does not always correspond directly with the amount of damage to the iron-sulfur clusters, thereby affecting the electron transport chain and energy production.
     
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  18. Jesse2233

    Jesse2233 Senior Member

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    Has anyone here tested their cysteine/sulfate on an ongoing basis and correlated it with symptoms?
     
  19. jjxx

    jjxx Senior Member

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    Brilliant! Thank you so much for putting it all together!
    I have a question: do you monitor your sons liver enzymes since the Niacin dosage involved is high?
     

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