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Looking for some education around my mutations

Discussion in 'Genetic Testing and SNPs' started by goodr189, May 25, 2016.

  1. goodr189

    goodr189

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    I got the following homozygous mutations:

    • VDR Taq
    • MAO-A R297R
    • CBS C699T

    and the following heterozygous MTHFR mutations:

    • MTHFR C677T
    • MTHFR A1298C
    Can anybody lend me their brain in how to handle this cluster f***? Due to the bad combo hetero MTHFR I should have high homocysteine but since I'm homo CBS C699T it possibly lowers it?

    I have POTS and am curious to see if any of these methylation genes are to blame. I also suffer from bad anxiety and the occasional panic attacks. Recently supplementing with Vitamin-B12 and D along with staying away from Sulfur based foods (based on CBS mutation) seem to be helping a bit. What else should I do to help myself? I was looking into L-Methylfolate but my COMT mutations have me hesitant to try due to methyl donors interactions and the fact that my homocysteine may be already in balance due to my CBS mutation.

    Thanks so much.

    [​IMG]
     
  2. Valentijn

    Valentijn Senior Member

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    Those are pretty common variations, so nothing to really worry about, and certainly not a clusterfuck :p

    You can't really predict if you are or aren't compound heterozygous, with the variants on different strands (from different parents). But in either event, it's also very common to have MTHFR activity reduced. Studies have shown that a diet with a decent amount of veggies, or a normal dose of folate is sufficient to correct for any associated risk factors.

    CBS +/+ should be lowering homocysteine slightly, but it's a tiny impact compared to the common MTHFR variants. The easiest way to find out would be by having homocysteine tested, which is a pretty common test done in yearly check-ups in the US.

    No, there's no indication of those SNPs being associated with POTS.

    Again, CBS SNPs have very little impact. They are not capable of causing problems with sulfur. Though if something makes you feel better, and is safe, there's no reason not to give it a try.

    There's no known correlation between COMT variations and tolerance of methyl donors. It's merely an hypothesis which doesn't hold up in the real world, and people's reported tolerance of methyl donors often contradicts that hypothesis.
     
    Last edited: May 26, 2016
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  3. goodr189

    goodr189

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    Curious to see why you say that. When looking into CBS C699T +/+ I noticed that sulfur foods cause a lot of symptoms. Dr Amy Yasko has also indicated that this mutation causes problems with high sulfur and ammonia in the body. I am asthmatic and also allergic to sulfa drugs so I'm not sure if that is a coincidence at all. I also seem to get a lot of rashes depending on foods I eat but have not paid that close attention until my 23andme results.
     
  4. Valentijn

    Valentijn Senior Member

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    Reacting to "sulfur foods" does not have a connection to CBS C699T. Undoubtedly there are other factors which can cause such a reaction.

    It is her belief (or at least her message), but she has no basis for it.

    And billions of other people have CBS C699T, but certainly aren't asthmatic or allergic to sulfa drugs. Your reaction to sulfur is a coincidence completely unrelated to CBS C699T.
     
  5. goodr189

    goodr189

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    Thanks for the in-depth responses Valentijn. It's good to get some valuable feedback around what seems to be a lot of misinformation.
     
  6. da2020

    da2020

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    I am ++ for that CBS and my labs and symptoms all match up with the sulfur and ammonia symptoms and related methylation issues, and addressing those issues by prioritizing and addressing CBS has been HUGELY beneficial for me. I don't care if there aren't "proven" studies or if there's conflicting information out there (in what part of medicine is something 100% known and understood anyway?). What works, works. I don't need a lab rat to tell me how I feel. No one does.

    See Caledonia's guide for a helpful overview of getting started with SNPs.
     
    Last edited by a moderator: Jul 22, 2016
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  7. goodr189

    goodr189

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    Can you provide some steps you have taken to address the CBS mutation?
     
  8. alicec

    alicec Senior Member

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    You may well have problems with sulphur and ammonia - many people do - so addressing this would be beneficial. But it has nothing to do with CBS.
     
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  9. da2020

    da2020

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    Interesting opinion, but according to my doctor it has everything to do with CBS. And all my labs back that up.
     
  10. da2020

    da2020

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    Note: one of the signs of upregulated CBS is low homocysteine. Mine is extremely, dangerously low, or at least was before I started this protocol. I need to test it again soon. So that's one lab marker. I also have elevated liver enzymes and extremely elevated B6 levels and high urine sulfate that goes down fairly quickly if I don't cheat on the stuff below.. Urine sulfate definitely corresponds to feeling terrible when it's high. I don't have SUOX so I don't measure sulfite, just sulfate. At this point I don't even really need to measure it, I know what it's going to be based on how I feel. You can buy test strips on Amazon btw.

    What I do that works for me (actually makes me feel better, not just rumored to work):

    Low thiol and sulfur diet (meat doesn't count unless eaten in excess. For me that's more than 4 oz per meal (I'm 140 lbs). Meat/fish/eggs are essential for me and the only safe way to get the sulfur amino acids that phase 2 liver detox needs. Garlic is the worst for me. I also avoid onions, kale, arugula, broccoli, brussel sprouts etc. I never liked those foods and used to force myself to eat them because they were "healthy". Once I stopped eating them I felt great. Instead of those greens I eat lots of romaine lettuce, parsley, other leafy herbs, celery, cucumber, fennel etc, so I do get lots of greens.

    Avoiding sulfur amino acids in supplements (cysteine is the worst for me, including NAC, taurine is bad for me too).

    Avoiding too much B6 (I can only tolerate very little and it's added to so many things, even amino acids). Not taking any B in excess, esp not methyl Bs.

    Taking frequent breaks from supplements altogether. Simple brewers yeast and Standard Process are often my best "vitamins".

    Avoiding random sulfur things like chlorella (I've tested extremely reactionary to that for many years, it's added to many "green drink" powders).

    Taking molybdenum, zinc, manganese, selenium, iodine, magnesium (I drain minerals like crazy and need really high amounts just to have "normal" levels, I've been aware of this for many years -- it might not fix CBS upregulation so much as compensate for it, I don't know. The connection between CBS and mineral loss is interesting and increasingly speculated on. Some feel mineral repletion fixes sulfur sensitivity. For me sulfur drains minerals back out so fast it's not worth the trouble).

    Avoiding ALA, MSM and other sulfur supplements (many multi supplements add these).

    Avoiding all "liver detox" supplements (they all rely on sulfur compounds) except for LEF Liver Efficiency. I also do rounds of coffee enemas off and on. Detoxing the liver with CBS is one of the biggest challenges because most of the normal things that help the liver upregulate CBS and just make the liver more toxic.

    Avoiding Epsom salts, "trace minerals" with sulfur and any hot springs etc with sulfur.

    Eating organic as many pesticides contain sulfur type compounds. Salad bars are often sprayed with sulfite compounds too and pretty much all the prepared foods at places like Trader Joes and cheap restaurants is too.

    Taking malic acid and arginine/ornithine.

    Doing charcoal flushes along with magnesium citrate.

    Not drinking coffee and alcohol, esp wine.

    No fun, I know.


    In my opinion the easiest thing to do is stop eating thiols/sulfur (including supplements containing them) for a week and see if you feel better. That will give you your answer whether CBS is affecting you and it's cheap and easy.

    And for all those people who think it's mercury that's the cause of sulfur sensitivity, I think they have it backwards. Because CBS people are prone to losing minerals, they're prone to retaining mercury and other toxic metals in their place more than other people. So in my mind it's CBS that's actually the cause of the mercury problem. If you treat CBS by avoiding sulfur and replenishing minerals, the mercury and other toxic metals go down safely. Chelation is way too toxic for a CBS person to handle safely, and it makes everything worse by chelating out already low stores of healthy minerals too. I did Cutler protocol about 12 years ago and that was my experience.
     
  11. da2020

    da2020

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    Btw I have the same exact as these except for MTHFR C677T. I have other ones too, but these are the main ones I focus on.
     
  12. Valentijn

    Valentijn Senior Member

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    It's not an "opinion". It's been well-established by research into those SNPs, and is strongly supported by the billions of people with those CBS SNPs who lack the symptoms Yasko would associate with them.
     
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  13. alicec

    alicec Senior Member

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    It's nothing to do with my opinion.

    CBS is one gene whose SNPs have been well studied, so we have plenty of information about the effect of the various nucleotide changes on function of the enzyme. There are some SNPs which have a marked effect on the enzyme (downregulations) and are pathogenic, but CBS C699T has only a small effect (upregulation). It is characterised as a benign variant.

    We also know about the study that Yasko says is the basis for her claims about CBS C699T. It doesn't show what she says it does. She simply didn't understand the experimental situation described and drew completely erroneous conclusions.

    There is no dispute about these facts.

    You of course can believe what ever you like, but in trying to understand cause and effect and in assessing things that might be helpful for at least some of my problems, I prefer to start with what is known. I can't see the point of starting with a serious misinterpretation.
     
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  14. da2020

    da2020

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    There is a lot of conflicting information about CBS precisely because it hasn't been well studied at all. A lot of the information that is helping people is not based on published studies but on clinical experience by people like my doctor who has worked with hundreds if not thousands of patients with difficult chronic health issues for over 20 years and has a lot of experience with what helps her patients and what doesn't.

    But for you on the other hand, I definitely commend your choice to only "start with what is known." Science should have that all completely figured out really soon. Definitely don't take any risks or do anything experimental in the meantime. Stay safe!
     
    Last edited by a moderator: Jul 22, 2016
  15. Valentijn

    Valentijn Senior Member

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    All of the data is on one side - these CBS SNPs are harmless. Yasko's baseless claims stand alone on the other side. Her claims are not supported by anything at all, and even a basic comparison of allele rates between patients with sulfur issues and no issues would show that the rates of these CBS SNPs are the same for both.
     
  16. Valentijn

    Valentijn Senior Member

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    Yasko's protocols are not cheap, if using her products.

    And some of the advice centering around CBS is potentially quite harmful. For example, some recommend avoiding B6 to slow down CBS activity, which can induce a vitamin deficiency, result in raised homocysteine, and impair the creation of glutathione and the ability to properly detox the typical harmful substances which everyone encounters.

    The time frame also seems to be quite extensive, with a series of supposed problems given a order in which the right one must be attacked first for any other treatments to be effective. These rules can be quite elaborate, and seem set up to involve a lot of back-tracking and restarts.
     
  17. alicec

    alicec Senior Member

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    This is another straw person that you have created.

    No one suggested proof beyond doubt was necessary. Any plausible reason that doesn't fly in the face of basic science and just plain common sense is good enough for me to give something a go.

    In the case of some of Yasko's claims, any supporting evidence would be welcome.
     
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  18. alicec

    alicec Senior Member

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    1) I often share relevant personal experience - did so in a post this morning. When my SNPs are relevant I will discuss those too.

    I didn't bother in this discussion because I was simply trying to make a general point about a particular SNP and what it does or doesn't do. I didn't think my own experience or genetic status made any difference to that discussion and didn't want to overcomplicate the post.

    Since you think it important, I am happy to reveal that I have several CBS+/- SNPs (including C699T), several +/-BHMT SNPs, none of which amount to anything, plus one BHMT +/+ which does have a small effect. I have normal homocysteine and ammonia levels and don't have problems with thiol -containing foods.

    2) I have never claimed to have total knowledge/authority. Where I have researched SNPs, usually because I have them, I am always happy to share what I have discovered.

    With the CBS SNPs under discussion, I didn't bother to give references yet again because they have in fact been discussed over and over again on PR. Many people do know about them but I agree, I shouldn't presume that everyone reading this thread does.

    So here are a few basic references to CBS summarising what is known about it's SNPs, most particularly defining which are the pathogenic ones. There are links to the original papers.
    http://www.omim.org/entry/613381?search=cbs&highlight=cbs
    http://www.ncbi.nlm.nih.gov/clinvar?term=613381[MIM]
    http://www.ncbi.nlm.nih.gov/clinvar/variation/92426/

    The first two summarise all SNPs and their clinical effect, the third is just for C699T.

    The latter shows several interesting things - the SNP was last evaluated relatively recently (Dec 2014), its status as a benign variant is unchanged and it is a synonymous codon change - ie the nucleotide change has no effect on the amino acid sequence of the gene product.

    In other words, the enzyme produced by the variant gene is identical to the one produced by the ancestral or wildtype gene.

    This tells you immediately that the SNP doesn't amount to much.

    There are situations where a nucleotide change without protein change could make a difference - for example, the nucleotide change could destabilise the mRNA and this in turn could lead to less of the enzyme being produced. This doesn't apply to a single nucleotide change however, but rather to the effect of a number of SNPs in concert. This has never been found for CBS as far as I am aware and in any case, less enzyme would lead to less activity, not the upregulation that is claimed for this SNP.

    Alternatively, the SNP could be in linkage disequilibrium with something else and it is the something else that is having the effect. I do recall reading that this is thought to be behind the small upregulation that has sometimes been observed for this SNP. I can't lay my hand on that paper at the moment but here is a summary of the variable effects that have been observed for the SNP in a methionine loading test and the reasons the SNP does not have negative effects. It has links that you can follow if you want to read the original studies.

    And what of Yasko's claim about a 10 x upregulation? Here is an old thread (from April 2013) in which this was discussed on PR. One member tracked down the reference which Yasko said the claim was based on, plus other studies by the same authors, and reported here and here.

    Basically, Yasko completely misinterpreted the paper. The scientists had created a truncated mutant (in yeast) to study aspects of enzyme activity - it had no relationship to the SNPs Yasko was interested in.

    3) If you have a problem with OMIM or ClinVar then I'm sorry, but the difficulty lies with you, not the reference. Yes the summary is just someone's analysis but it is a quick way of gathering together information and you can read the originals if you want to. If you don't trust the report of dbkita, who once made many helpful posts on PR on many aspects of biochemistry, then I suggest again that the problem lies with you. In any case, you can read the originals yourself - they are referenced in the thread.

    4) I've never thought I needed to present my credentials in order to make posts. Nor have I demanded it of anyone else. But since you claim it is important, and more to the point, claim that I don't have any credentials, I'd better lay them out.

    I have a PhD in biochemistry and spent almost 30 years working in medical research in various university medical schools. For the last couple of years of my working life, before I retired due to ill health, a few colleagues and I set up a company to commercialise our research and conduct clinical trials in humans, using the protein that we discovered.

    I have run my own research lab, written and received research grants from national and international granting bodies, had many scientific papers published in reputable journals, presented my research to national and international scientific meetings and have supervised PhD students.

    While my greatest expertise is in protein biochemistry, because our lab was trying to understand the function of a new protein, I became familiar with a wide range of biological systems. I also became very familiar with recombinant DNA technology which I used to produce large amounts of the protein I had originally purified so laboriously from biological sources. In doing so I worked closely with geneticists and molecular biologists and gained a good working understanding of these disciplines.

    So I am well able to understand a wide variety of scientific subject matter.

    I think I can add some information or experience that might be helpful to someone else. Sometimes it is to correct misinformation. In this respect, Yasko's many erroneous claims and dubious theories would be a common source of such posts.

    These and related claims have completely distorted the SNPs discussion. People have come to believe that they have serious mutations which are the source of their health problems. While it is true that some SNPs have very serious consequences, these are relatively rare and they are not the ones that Yasko has fixated on.

    This latter group often do nothing at all, or have relatively small effects. Some combinations may indeed make a contribution to health problems but it is a contribution, not the main event and I think it is important that people understand their SNPs in a proper context

    I am certainly guilty of pointing out the errors behind Yasko's claims but I wonder why this is considered to be a problem.

    I am perfectly happy to agree to disagree with you but I do not accept your attribution of improper motives to myself and others
     
    Last edited by a moderator: Jul 22, 2016
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  19. Kina

    Kina

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    Sofa, UK
    Please note, this thread has been moderated to remove some personal attacks. Other posts have been edited/removed as they referred to posts that contained personal attacks.

    Please stick to the subject matter and avoid any personal attacks.

    Thank you.
     
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  20. mamabear72

    mamabear72

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    I too suffer from POTS and am CBS C699T +/+ & MTHFR C677T +/+

    I didn't know we should stay away from sulfur based foods. I would love to hear more about what I should avoid based on my double homozygous in CBS. Thank you kindly for you help :)






    QUOTE:

    I have POTS and am curious to see if any of these methylation genes are to blame. I also suffer from bad anxiety and the occasional panic attacks. Recently supplementing with Vitamin-B12 and D along with staying away from Sulfur based foods (based on CBS mutation) seem to be helping a bit. What else should I do to help myself? I was looking into L-Methylfolate but my COMT mutations have me hesitant to try due to methyl donors interactions and the fact that my homocysteine may be already in balance due to my CBS mutation.

    Thanks so much.
     

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