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Thiol sensitivities, cutler and shade protocol, CBS/SOD/SUOX/BHMT?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Sam7777, Sep 9, 2015.

  1. Sam7777

    Sam7777 Senior Member

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    I'll try to highlight some points.

    • Absolutely know I was hurt by severe redistribution. 100% mercury issues.
    • Still need to get a gene testing.
    • Could be some other metals thrown in hiding, never have taken DMSA.
    • Debating on doing Cutler and Shade protocol combined, people aren't keen but my research suggests its worthwhile.
    • Initially 4 years ago I had a very bad episode with ALA at a time when I didn't understand the amalgam controversy, and that basically I guess you could view as the beginning of me being 'CFS' like in condition. I did some successful rounds of fdc in fall of 2013 but I was doing them with RLA. I tried to do an overly aggressive round again a year and a half ago this time with ALA (I got the tooth extracted in May 2013) and that knocked me hard for about 5 months, started up some small rounds in summer 2014 and just couldn't wake up to the damn alarm, couldn't handle even those doses. I've done rounds recently, and it seemed finally manageable at 5 mg with IMD and multivitamin. I've done larger RLA doses on Shade's protocol with positive reactions recently too.
    • Not impressed with ALA in the literature, but NaRLA is too $. Regular RLA is still highly rated at online vendors. ALA can work, I've been reading a lot of Cutler success blog stories, but its long and grueling.
    • ALA is a good chelator, RLA is a stellar neutraceutical, especially in high doses. ALA is the devil in high doses. ALA makes me especially feel unwell/crazy compared to RLA.
    • I may resort to doing FDC with RLA, but I'm planning on sticking to 25 mg per dose of ALA, and perhaps doing Shade's protocol on different days. I still simply don't see a justification in Cutler's issues with RLA.
    • What Shade's protocol and methylation have in common- nutrigenomics. Cutler's is a bit lacking in the area. But I still have not seen a better protocol in terms of consistent success stories.
    • Shade's IMD seems to negate a lot of the discomfort of cutler's rounds, or LA in general.
    • Triphala (clearway cofactors) and coffee enemas seem to be a big deal for me in terms of energy. Shade's theories on nrf2 seem to hold up and match the literature.
    • I'm feeling a lot more open to the notion of methylation after spending a lot of time looking at the background stories of people who had pretty bad snp combos and had done cutlers protocols.
    • A key consistent thing that has turned me away from methylation is that I don't have the sensitivities to these supplements that so many do. And since becoming interested, I've vetted it out. I've never had a noticeable positive or negative reaction to b12 and folate supplements of any type, nor to TMG and ALCAR while trying the protocols for periods.
    • But I do react to chelation disproportionately compared to many. I react to thiols in food and supplements pretty significantly. I was ready to jump on a assumption of CBS but I'm reserving hasty conclusions. I feel there's more to it.
    • Two examples of my point are here: 1 is a guy who has some pretty similar conditions to my own and to many poor responders of chelation, and he does not have CBS but he has issues with SOD and his ammonia. 2 is a pretty elaborate case for why CBS really messes up chelation (which I see some current large threads now on this, though this is all the first I'm hearing of it)
    • http://howirecovered.com/my-genetics/
    • http://www.heartfixer.com/AMRI-Nutrigenomics.htm#CBS (Cystathionine Beta Synthase) Explanation and Generic Plan of Action
    • Which led me to come up with some consideration worthy supplements (I'm not about to jump into them blindly, I have reservations once again) but it may only be ya know, manganese and molybdenum which I was terribly low in on my hair test.
    • So I guess I should ask a hypothetical. Let's say you are positive or heterozygous for some snps on these CBS/SOD/SUOX/BHMT what would you do? The heart doctor there is saying to get CBS under control before adding methylfolate and methylb12. He's worried about glutathione not helping process stuff. Which brings us back to using Chris Shade's protocol.
    • What I notice in terms of methylation support that actually seems to help me, are just huge doses of good like thorne methyl support multivitamin multimineral, its not the individual vitamins and minerals that do much for me. And this is especially noticeable with RLA.
    • But I threw together a list here of stuff that came up in some of these links that I could conceivably use to deal with these tricky snps
    • P-5-P folinic acid hydroxycobalamin boron molybdenum vitamin e, mag, c, zinc, riboflavin serine or choline basically phosphylserine PS/PC etc TMG creatine orinthine and malic acid.

    • My main goal really is to desensitize the sulfur reactions, so that I can do cutler, and do shade. But I'm coming to the conclusion after years of this bickering among protocols, that the science and literature suggest that no one is totally correct. Your snps can make your individual case very unforgiving. With such symptoms and stories it seems that methylation is always an underlying factor. I personally don't want to take any chances, so using nutrigenomics and fdc chelation in conjunction seems prudent.
     
  2. Valentijn

    Valentijn WE ARE KINA

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    The CBS and BHMT SNPs used by Yasko and others (and displayed by Genetic Genie), all have very little or no impact. They are not capable of causing problems. There is no research supporting their claims about those SNPs.
     
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  3. Sam7777

    Sam7777 Senior Member

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    It doesn't seem anyone agrees on much. . .
     
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  4. Sam7777

    Sam7777 Senior Member

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    Never mind the fact that there are people talking about it in this forum, who evidently ascribe to the notion that they have issues with sulfur and ammonia.
     
  5. Sam7777

    Sam7777 Senior Member

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    @picante see your story and the guy in the link makes more sense to me because you don't have CBS issues. Despite whatever misgivings in Yaskos research, which even the heart doctor in the link admits is speculative, I see plenty of reasons why people would still develop severe thiol and sulfite issues. I don't think you have to have CBS, though I'm suspicious that CBS probably isn't good. But the guy in the link is obviously amalgam poisoned, and you're describing that you thought the glutathione was moving metals.

    I still suspect a lot of people have metals.
     
  6. picante

    picante Senior Member

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    Which link? One of mine? I've posted many links.

    I do, too. Some of my friends here have led me to look at other things, and recently I've been exploring pyroluria and thioredoxin.

    Why pyroluria? Because according to Klinghardt
    Why thioredoxin? Because that is the thiol redox system. It's hard to find much about it here on PR. Right now I'm working my way through this article (which is like swimming upstream, with my minimal knowledge of biochem): http://ajpcell.physiology.org/content/295/4/C849#F1
     
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  7. picante

    picante Senior Member

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    Yes, the grueling part is the killer. I have not looked at chelation therapy for over 10 years now because my detox systems are not working well enough.

    For me, it was EBV that triggered my metabolic crash (in 1992). I'd had mercury in my teeth since the 1960s, but my detox systems were functioning, apparently, until after the crash.

    Yes, I think the reduced L-glutathione cream triggered some mercury redistribution symptoms, but it took a while. The glutamate toxicity symptoms appeared first. I started it April 9th and took it off and on 5 days at a time. Dropped it like a hot potato July 27th.

    Here's what I suspect: If I can get the glutathione redox system working, and the thiol redox system, I'll be able to tolerate thiols and sulfites and resume the methylation protocol. Then the mercury will detox the way it's supposed to. Peachy keen, hey? ;)

    Right now I'm thinking that the thiol redox system might be the upstream problem, and BTW, it affects glutathione recycling.
     
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  8. Sam7777

    Sam7777 Senior Member

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    I'm pretty sure this is the strong suit of Christopher Shade's arguments. He talks about thioredoxin here. Fast forward to the 52:30 mark to jump right into this part in particular

    I'm still learning about Shade and Cutler even 3 years later, its many layers deep. In fact you reminded me about thioredoxin. My theory that I speculate is that the enzyme systems are more important than supplements in conclusion. Yes you need supplements, but you need supplements that normalize all these enyzmes. Shade even says that its better to have higher GST enyzmes than it is to have high glutathione. It's kind of a principle really. It's the assembly line.

    Though I might be slightly in error, I think most of what makes Shade's approach work is the bacopa, RLA, and triphala. Well those are what expel mercury, they're not his binder IMD. That's his approach in my crude terms.
     
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  9. Sam7777

    Sam7777 Senior Member

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    http://jn.nutrition.org/content/140/9/1628.short

    "Genes analyzed by RT-PCR array showed that 4 major antioxidant enzymes in aorta [superoxide dismutase (SOD) 1, SOD2, glutathione reductase (GSR), and thioredoxin reductase 1] were upregulated in BB-fed mice. "

    It's blueberries. I mean if you want to eat a giant bowl of blueberries everyday. Penn Gillette did this when he lost his weight too, he would eat 4 boxes of blueberries for breakfast everyday. I've gotta find something cheaper though.

    Penn's diet, which was a potato vegan plant paleo sort of diet with sauna and ice bath makes me strongly suspect he had metals and pollutants and methylation, basically all the stuff he doesn't believe in lol.

    Was his diet friendlier for CBS? Well partly. It is comparable to Wahl's ordeal, but minus meat. Meat probably aggravated Penn's genes. This is what worries me about just slamming chelation. If Penn can get off 6 blood pressure meds just by cutting out so many foods and going on a diet that likely removed most allergenic compounds. . .
     
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  10. Johnmac

    Johnmac Senior Member

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    I've been on the Cutler Protocol for 3-4 years, & on methylation protocols for a couple of years.

    I've had modest but noticeable progress with chelation, & dramatic but erratic progress on the Freddd Protocol.

    (You can see my protocols & SNPs below.)

    My biggest roadblock with Cutler was massive thiol reactions - by far the worst (IMO) of anyone on the Frequent Dose Chelation forum. After half a year of incapacitation I began the Simplified Methylation Protocol, and these disappeared in a few days - never to return. The SMP didn't have methyl B12, so I surmise that the methyl-folate is what did the trick.

    I've only heard of one or two others who fixed the thiol problem this way - tho possibly few try it, as Cutler is very skeptical about methylation protocols. (Cults tend to form around illnesses & healing methods. I agree with you that no-one is totally correct. Tho I do tend to trust Cutler on ALA over RLA, as he has more science in his head on heavy metal transport than anyone, so far as I can tell.)

    Now I'm on the Freddd protocol. I am learning dosing the hard way, but the improvements are great so long as they last. Then I crash, ramp up folate & tweak down carnitine (or whatever), improve again...

    Methylfolate is also part of the Freddd Protocol, & I am able to chelate with ALA at 300 mg/dose now. I dose two-hourly - a faster way to burn through the mercury IMO.

    @stridor much improved his ability to chelate, & had big health gains, after beginning methylation therapy.

    I don't have his scientific knowledge, nor yours. I just try to find the smartest person in the room on a given subject, & do what they say. Then I tweak a lot based on what happens, or doesn't.

    For practical purposes I regard pyroluria as a separate subject, but have this year seen anxiety evaporate after beginning the zinc, B6, etc.
     
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  11. picante

    picante Senior Member

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    @Sam7777, I was out of town and then out of commission (crashed). Now I've had a chance to watch the video from about 46:00 on, and that's a lot of enzymes!

    My suspicion is getting stronger that the thioredoxin system is the upstream problem. Especially Trx Reductase.
     
  12. Violeta

    Violeta Senior Member

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    @picante , I think you're right about thioredoxin being the upstream problem for thiol issues. I have been having severe reactions to isothiocyanate, it just kept getting worse and worse. I started taking FMN about two weeks ago, and then about a week ago decided to try broccoli and cauliflower. I did get one of the symptoms I get from isothiocyanates, abdominal pain, and was trying different things to get rid of it. I was going to try clay and charcoal, but before I took them I took another dose of FMN, and voila, then pain in my abdomen subsided. I started taking more doses of FMN, even when I wake up during the night or get a headache, a full 25mg after eating broccoli and cauliflower, and I think I am getting over the problem.

    I had been taking B2 for about a year and a half now, but have noticed that the coenzymated form works much better for me. (I hope I am not incorrect about FMN being very important for thioredoxin synthesis.)

    This weekend I will try eating eggs again.

    It would be great to be able to eat vegetables again, especially after finding this link.

    Sulforaphane Suppresses Oligomerization of TLR4 in a Thiol-Dependent Manner
    http://www.jimmunol.org/content/184/1/411

    TLRs are pattern recognition receptors that detect invading microorganisms and nonmicrobial endogenous molecules to trigger immune and inflammatory responses during host defense and tissue repair. TLR activity is closely linked to the risk of many inflammatory diseases and immune disorders. Therefore, TLR signaling pathways can provide efficient therapeutic targets for chronic diseases. Sulforaphane (SFN), an isothiocyanate, has been well known for its anti-inflammatory activities. In this study, we investigated the modulation of TLR activity by SFN and the underlying mechanism. SFN suppressed ligand-induced and ligand-independent TLR4 activation because it prevented IL-1R–associated kinase-1 degradation, activation of NF-κB and IFN regulatory factor 3, and cyclooxygenase-2 expression induced by LPS or overexpression of TLR4. Receptor oligomerization, which is one of the initial and critical events of TLR4 activation, was suppressed by SFN, resulting in the downregulation of NF-κB activation. SFN formed adducts with cysteine residues in the extracellular domain of TLR4 as confirmed by liquid chromatography-tandem mass spectrometry analysis and the inhibitory effects of SFN on oligomerization and NF-κB activation were reversed by thiol donors (DTT and N-acetyl-L-cysteine). These suggest that the reactivity of SFN to sulfhydryl moiety contributes to its inhibitory activities. Blockade of TLR4 signaling by SFN resulted in the reduced production of inflammatory cytokines and the decreased dermal inflammation and edema in vivo in experimental inflammatory animal models. Collectively, our results demonstrated that SFN downregulated TLR4 signaling through the suppression of oligomerization process in a thiol-dependent manner. These present a novel mechanism for beneficial effects of SFN and a novel anti-inflammatory target in TLR4 signaling.
     
    Last edited: Sep 18, 2015
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  13. Violeta

    Violeta Senior Member

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    I can see why thioredoxin would be very helpful for the stress (pain) it had been causing throughout my body because it actually generates ROS.

    I don't yet know if the generation of ROS is extreme in my gut and vagus nerve because of a pathogen or metal, but look at this study.

    I understand this study is in regards to the lungs, but it would seem to be a universal reaction in tissue. I just need to search other studies.

    Sulforaphane Induces Antioxidative and Antiproliferative Responses by Generating Reactive Oxygen Species in Human Bronchial Epithelial BEAS-2B Cells

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3207051/
     
  14. picante

    picante Senior Member

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    How do you know your reaction is to isothiocyanate? What are you actually ingesting when you get these severe reactions?

    I am still confused about synthesis of thioredoxin itself (Trx). This book, Advanced Nutrition and Human Metabolism, says that thioredoxin reductase is a flavoprotein, and the chart on page 328 shows both riboflavin (FAD) and niacin (NADPH) involved in its [activity? synthesis? I'm not sure which].

    Clearly, the FMN is doing something for you. I'm taking R-5'-P (Douglas Labs), which is allegedly the same chemical, because I wasn't tolerating something in the sublingual FMN. But I'm now taking 1/2 cap (5 mg) 3-4 X a day, because when I take the whole cap, I get pretty uncomfortable hot flashes (no doubt it's ramping up my cellular thyroid metabolism).

    Another piece, though, is niacin. I've been gradually increasing my niacinamide supplementation since learning that niacin provides the main cofactor, NADPH, for the reduction of thiols. And FAD seems to be involved somehow in NADPH recycling (???).

    I'm tolerating an egg most days now, and a mid-sized serving of Swiss chard.
     
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  15. picante

    picante Senior Member

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    I've been on Eric's page many times. I see he attributes his ammonia overload to his +/+ NOS snps. I have the same two NOS2 mutations he does, plus another +/+ NOS2: rs 3729508 (T;T), which I looked up. I wonder whether these three are inherited as a group.

    I haven't tried taking BH4 because it's so spendy. Yucca makes me feel worse (gut discomfort), and Na-K-butyrate doesn't have a noticeable effect. Perhaps I should consider BH4, since I'm unable to do much with methylation supps at the moment. Have you taken it?
     
  16. Sam7777

    Sam7777 Senior Member

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    No, I read fairly extensively in the archives of peoples discussions here to see about BH4. I am skeptical of such an approach because it's essentially throwing an end product into the cycle (that's almost impossible to afford or obtain) without fixing the underlying reasons its low. So I am pretty convinced I have to trudge through Cutler, but am obviously trying to do everything I can to speed it up and make it more bearable, in the hopes that these sorts of snps correct themselves somewhat. Of course it is confusing comparing to people here. Almost everyone here responds to methyl b12 and methyl folate, but I don't. And I have a special history with Hg/amalgam/cutler, I AM one of the unlucky people who blasted themselves with an improper protocol and never was right again, I did do a ton of damage, basically sticking it all in my brain a fair bit. These are the individual things that make it hard to gauge. I really do think Shade is right about people having totally shut down enzyme systems, multiple enzyme systems interacting with one another, and also being affected by these kinds of snps.

    Of course, I was very surprised at just how strongly some of those people responded to BH4, at least initially, but I think that wears out over time, it balances things out some, then since the snps are still there and the root issues are still there it gets deficient again, ad naseum presumably. If I am not mistaken one thing suggested for BHMT was the TMG and malic acid. I tried malic acid but didn't respond. I might only get very mild benefits from TMG.

    I am tempted to say that even with people who don't have amalgam illness there's a compelling reason to try maybe up to a gram of RLA a day, especially after reading on it, and with Shade. I mean in terms of someone suspecting thioredoxin. Course' the risk in that is assuming you don't have amalgam illness, which is a mistake I have made. But for instance, it's well established that lipoic generally treats the damage caused by lead while not persay chelating lead much. I think that there's quite a host of things that could have the ability to smash the methylation cycle. Smashing it the way mercury does, at least to a degree. The same sort of inflammation that messes these enzymes up. There are countless persistent organic pollutants, plus cadmium, arsenic, etc. RLA is still very important for this I believe.

    I think it is really important to kind of assume that there's something latent (some pollutant) triggering significant enough inflammation to affect things. The malic acid idea made more sense because it was further upstream, and the premise is to try to get the glutathione system up by raising BH4 (the GSH GST etc enzymes specifically). But producing more glutathione doesn't even neccesarily guarentee that those enzymes are being raised.

    There is the mushroom cordyceps that is suppose to affect NO levels in the body, and I've had OK results once in the past. But I can't say the effects lasted, primarily because of my redistribution accident and Hg. With cordyceps I guess the issue is only $$, (which cheaper brands aren't too bad, typical herb, nothing compared to BH4).

    Like for instance, comparing RLA to cordyceps, I think cordyceps runs its course pretty early. Adaptogens don't just keep these biochemical changes going forever, it takes about six weeks, there are some lasting changes, but then you develop tolerance to the herb early on, and you kind of have to wait several months. But RLA is much more . . persistently pharmaceutical.
     
  17. Violeta

    Violeta Senior Member

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    I know my reactions are to isothiocyanate (sulforaphane, goitrogens) because of years of getting the same symptoms from a specific group of fruits and vegetables all in the category of goitrogens.

    So if you look up a list of goitrogens, and actually you might have to look at several lists because some lists aren't comprehensive, those are the foods that cause the problems.

    So if the sulforaphane is causing oxidative stress and I have inadequate amounts of antioxidants on hand to neutralize the oxidants, it could cause symptoms.

    Besides the FMN I have been drinking ionized water, high in hydrogen, and hydrogen neutralizes the free radicals, too. But the stomach pain was definitely relieved by the FMN.
    This study is good, I wish I could understand the whole thing. This is one sentence that seems to make sense to me, though.
    "Prior to cell death, intracellular reactive oxygen species (ROS) were generated at a high rate within a minute of commencing SFN treatment."
     
  18. Violeta

    Violeta Senior Member

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    Yes, the FMN is helping a lot. My eyes were actually worse for a couple of days, though. That happened when I started taking the B2, too, though.

    The Source Naturals R-5'-P tastes terrible, I may try Douglas Labs next. A whole cap of Douglas Labs is only 10mg?

    I should probably start trying to take some niacin, too.

    I don't understand the whole thioredoxin, thioredoxin reductase, NADPH thing either. I just keep reading and then sooner or later it breaks through.

    This paper says that selenium can be a limiting factor, too. I know I'm terribly deficient in selenium, and that might be why I was so mercury toxic. Either that, or visa versa. But I think we talked about this before.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1220815/

    PS: Good for you that you can handle eggs and swiss chard!
     
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  19. Violeta

    Violeta Senior Member

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    This is interesting. But what happens if you don't have any thioredoxin???
    http://www.ncbi.nlm.nih.gov/pubmed/15728556

    Sulforaphane induces thioredoxin through the antioxidant-responsive element and attenuates retinal light damage in mice.
     
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  20. Violeta

    Violeta Senior Member

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    NADPH keeps thioredoxin in a reductive state.
    "NADPH provides the reducing equivalents for biosynthetic reactions and the oxidation-reduction involved in protecting against the toxicity of ROS."

    Thioredoxin reduces oxygen (free radicals) by donating a hydrogen.

    Does NADPH keep thioredoxin in a reductive state with it's H?

    Maybe we are all just low in hydrogen? Would measuring your pH give a good picture. Maybe not, because I've read that if it goes on too long your pH will eventually become too alkaline. I think I also read that ammonia will be used for alkalizing when we have used up all other alkalizing options. I'm too tired to look for links right now, but thought I would get this in writing so I don't forget.
     
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