Review: 'Through the Shadowlands’ describes Julie Rehmeyer's ME/CFS Odyssey
I should note at the outset that this review is based on an audio version of the galleys and the epilogue from the finished work. Julie Rehmeyer sent me the final version as a PDF, but for some reason my text to voice software (Kurzweil) had issues with it. I understand that it is...
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Head Spinning After Genetic Test: MTHFR, COMT, CBS, etc. Help?

Discussion in 'Genetic Testing and SNPs' started by InsomniacNextDoor, Nov 23, 2017.

  1. InsomniacNextDoor

    InsomniacNextDoor

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    Hello, are any of you here dealing with similar gene variations? Having done a genetic test has been very revealing to me because I can finally connect the dots with all these things that I never considered before: sulfur, sulfates, ammonia issues, histamine, and all these paradoxical reactions I've been having with supplements. So far, pretty much all supplements and vitamins (except for Magnesium, fish oil) make me more tired and more sleepless. Molybdenum is somewhat helpful and I feel my liver working better but it causes more fatigue.

    From what I read epigenetics is quote a rabbit hole and navigating all these genetic mutations like MTHFR, CBS, COMT is extremely complicated. Not only I have to find a way to support methylation but also be careful not to aggravate all these CBS and COMT issues. My body is very sympathetic dominant and any supplements I tried before like Methyl B12, SAMe, Biotin and some others make wired and unable to sleep. The only thing I haven't tried is Methyl Folate which I'll try in very slow dosages together with B6, B12 once I recover from my recent spout of insomnia.

    My biggest priority now is to remove a few silver fillings as I read that all these gene mutations have been implicated in people storing heavy metals like mercury and copper. I was so stupid to have a doc in US talk me into this... BIG MISTAKE.

    Here's an image with my results. I'm really hoping there is someone here with similar gene variations that have learned how to navigate this well. Would be very grateful for your comments and any sense of direction. I have no docs in my country that understand these things, perhaps I'll have to consult with someone from US via Skype once I know who can be of help.

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  2. Learner1

    Learner1 Professional Patient

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    Genetics is an important piece, but environmental factors, like heavy metals and other toxins and your current nutrient status affect how you will use nutrients. Additionally, these are just a few genes, you may have others that affect how your biochemical pathways work.

    Its not just about one bad gene. Its how the entire system works together. But, from whatvyoure shown you likely do have a tendency to accumulate toxins which can impact mitochondrial function and ATP production.

    If at all possible, see if you can do a provoked urine heavy metals test yo see what you're dealing with, using EDTA and DMSA or DMPS.

    And a Genova Diagnostics NutrEval test, which will show you comprehensive nutrient status do you can build a personalized treatment plan rather than just guessing and throwing random supplements at the problem which can result in unintended consequences, which is why many folks around here think methylating nutrients don't work.

    You'll want to begin gently, working on your transsulfuration pathway, moving backwards to glutathione production, then to the methionine cycle, and finally to folate, so you can unblock the traffic jam. If you just start taking a lot of methylfolate and MB12, you'll be in trouble fast.

    You might read Amy Yasko's Pathways to Autism, Dr. Robert's Heartfixer site, and get familiar with Ben Lynch's Pathway Planner and YouTube videos. Yasko is a little outdated, but is a good place to begin getting educated, Heartfixer is very concise, and Lynch has gathered a lot of relevant research.

    Once you understand the dynamics, it is possible to manage it yourself, but you have to start with good information.

    After you get methylation going, you might also look into the Cutler protocol for do it yourself metal detox.
     
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  3. InsomniacNextDoor

    InsomniacNextDoor

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    @Learner1, thank you so much. You're so right, this is not just about few genes and this is what makes it rather overwhelming.

    Could you let me know what would provoking of urine heavy metals show me?

    I'll check out eh NutrEval test. Now that the gene test has been so revealing and explains why I reacted to methylation supps the way I did, I am a fan of testing and dialing everything in, or at least not making things much worse by guessing :)

    Yes I did read on several sites now that I must address the CBS gene first and only then go for MTHFR, so thank you for this great advice. I've already come across those three names you mentioned but didn't have the time to study all of their content as there's so much! So from what I read best way is to steer away from high sulfur foods and limit my ammonia exposure from meat and other sources? Chelated molybdenum seems to work pretty well for me (suspected CBS issues even before the genetic test) but it hits me with fatigue later so now sure, maybe I need to try even smaller doses. Maybe I'll get more answers by studying that material from Lynch and others.

    OK, if I can really figure out the methylation part my next step will be to try a gentle detox to see how I do. Thank you so much for steering me towards good info!
     
  4. alicec

    alicec Senior Member

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    First you need to seek out reliable information. Much of the so-called complexity has been created by people trying to sell supplements.

    None of those sources is reliable. In fact Yasko is responsible for starting much of the misinformation that circulates on the internet. Most of her claims for SNPs are not based on any research or are contrary to research. Only a few of the SNPs she makes claims for have actually been shown to have any effect.

    Heartfixer just repeats Yasko's mistakes. I haven't bothered to delve too deeply in Lynch's site because I have come across so many errors in the statements I have read.

    The claims for CBS are nonsense. Yasko simply misread a research paper that had nothing to do with the SNP she claims results in a massive upregulation of the gene. It doesn't. There may be a slight upregulation but even that has not been replicated. This small upregulation appears to be protective since it reduces homocysteine.

    The other CBS SNPs she makes claim about have not been shown to do anything.

    No you don't. As I have already indicated, CBS is a non-issue. Furthermore, the claims that people who are +/+ for COMT are sensitive to methyl donors has no foundation. This was simply a theory of Yasko that became self-fulling. She thought COMT +/+ might mean sensitivity to methyl groups so people with these SNPs were not given them, just in case. This soon morphed into the fact that they WERE sensitive to methyl groups and SHOULDN'T be given them - based on nothing whatsoever.

    Plenty of people have put this to the test (including myself) and found it is not so. Some COMT +/+ people have no trouble with methyl groups, some COMT -/- people do. Certainly many are sensitive to methyl groups but it has nothing to do with COMT.

    Of the SNPs you list, only the first COMT and the two MTHFR have much consequence. MTRR A66G in combination with a MTR SNP which you don't have can be significant, but +/- in isolation has very little effect.

    There is 50-50 chance that the two +/- SNPs on MTHFR could have a similar effect to +/+ (if they are on opposite strands but 23 and me don't report this so you can't know), but even if you are compound heterozygous it simply means that you have a moderate slowing of the enzyme. Many millions of people live with these SNPs and cope perfectly well. The SNPs become more significant when there is increased demand for folate such as during pregnancy. You can compensate for this with modest doses of methylfolate.

    Similarly many millions of people cope perfectly well with the COMT +/+ variant. It confers certain advantages just as the -/- variant confers different advantages.

    Magnesium is co-factor for the enzyme so ensuring you magnesium intake is adequate will help to keep the enzyme stimulated.

    There has been a great deal of discussion on PR on these and other SNPs. You can search for these. Here are several threads which list the SNPs which are actually known to have some effect. There are more if you search.

    COMT, CBS, MTHFR, MTR, MTRR
     
  5. Learner1

    Learner1 Professional Patient

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    @alicec. Lynch is extremely well-researched and has some great tools. I suggested STARTING with Yasko and Heartfixer as they give a layof the land, but I noted that they were older, and that Lynch, whose info you're not familiar with, is more comprehensive and up to date. But, plunging into his lectures without some background would be confusing.

    I also mentioned its not just about genes you have, but that TESTING for nutrient status is incredibly important as there are other genes and environmental factors which confound the picture. As Lynch says, treat the patient, not the SNPS.

    Being familiar with how the pathways work, using a tool like Lynch's Pathway Planner, understanding the tendencies the SNPs MIGHT predispose you to, and getting familiar with your nutrient status and your own tendencies over time is the key to getting methylation working well.

    My CBS does seem to be unregulated. Not sure why, but I need an incredible amount of nutrients to run my methionine cycle and get down to making glutathione. I don't care what Amy Yasko or anyone's study says - its how my body operates, and learning and testing the theories in real time has been helpful.

    I also have folate SNPs, but need a little extra folate, but not s huge amount, and though I'm homozygous COMT++ for 2 SNPs which says I should be high in dopamine and might need to beware of methylators, I've run out of dopamine, and need huge quantities of methylates and tyrosine.

    We are all unique. Its been very helpful for these people to map out these theories for us to work with. But following ANYONE else's protocol is a recipe for disaster and its why so many people on this site have so much trouble with getting methylation, an essential process working properly.

    Understanding the moving parts and testing nutrient status to see what's going on occasionally can pay dividends as you learn to control these processes and make midcourse corrections as needed and vastly improve functioning.

    Youre welcome and good luck @InsomniacNextDoor !
     
  6. alicec

    alicec Senior Member

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    I disagree. @InsomniacNextDoor has clearly started with Yasko or one of her derivatives and now has completely the wrong idea about the significance of SNPs. Not only does Yasko get the SNPs wrong but also she gets many of the pathways wrong. Much of her diagram of interlocking cycles is just plain wrong. See this post for more detail.

    Heartfixer just repeats Yasko's errors, not just in SNPs but in metabolic pathways.

    I haven't bothered much with Lynch's site but I would urge caution in just accepting what he says. I have encountered quite blatant errors. See for example this and this post as just one example. I would compare his pathway analysis with a reputable site that is not trying to sell supplements.

    I don't have any problem with testing for nutrient status - sometimes it can be very helpful. One's overall nutrient status however has little to do with SNPs - at best some of these might be making a contribution.
     
  7. Learner1

    Learner1 Professional Patient

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    We disagree.
     
  8. alicec

    alicec Senior Member

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    You think that Yasko's metabolic pathways diagrams are correct and/or what she says about SNPs?
     
  9. InsomniacNextDoor

    InsomniacNextDoor

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    For the longest time I thought I was going crazy, guys because my various experiences with supplements did not fit into any recognized disease pattern. Most methylation products make me too amped up, most liver supporting herbs and supplements keep me cooler at night but make my legs very heavy during the day, yes there's "adrenal fatigue' but not quite, yes there's CFS but not quite, yes there food sensitivities but they mainly manifest as heat or cold at night that does not allow me to sleep, sometimes there's this wired/tired thing going but I have no clue how it comes about. I can have a glass of wine or eat a raw salad in the evening and stay up most of the night. None of these things added up to me but once I learned a few things about COMT, CBS and MTHFR at least most things fell into place. I'm probably sensitive to sulfur via CBS, my CNS is in chronic sympathetic overdrive probably due to COMT, all these high histamine foods keep me up at night probably because it is not being broken down due to MTHFR and so on.

    At least some things fall into place here but by reading both of your advice I can't help but to wonder whether this pats of supporting various SNPs can lead me back to health or down some other hole that I usually find myself in by experimenting with supplements and herbs. I feel that now that I've discovered this new direction I'll study it as much as I can and experiment very gently but then what? Is it possible to recover using these supplements or are we simply shifting the body temporary into some other state that will spring back as soon as we stop the supplements? I liked Learner1's idea that I have to try a detox if I can stabilize this methylation issue and gain some stability.

    Methyl donors like Methyl B12 do give me more energy but they also keep me up at night and this is probably because of COMT (or not like alicec says) and perhaps this is why there is advice for COMT folks to avoid it. Are Yasko's other claims valid and true? I have no clue. Lynch sounds like he knows what he's talking about but then he's right there in your face with his products like Pathway Planner. I'm not about to cough up 200$ to check it out.... Are the people online that can plug my raw data into his planner for a few buks?

    So @Learner1, do you feel you're making progress? I mean do you feel you're recovering? Are these conditions with these SNP only manageable or do we have a chance to recover and go off all supplements?

    @alicec I really do appreciate a critical eye on all this as I see very few people, if any that have actually totally recovered addressing genetic issues alone. I'll try tiny doses of methylfolate once I get it and see how I do.

    I do feel like I'm constantly navigating a landmine field with all these supplements and diets. Thanks goodness QiGong is one thing that I'm, making progress with.

    I'll keep reading on both your suggested materials, there's no choice. Like you guys say, this is a big deal and I have to get educated myself and perhaps some day I'll talk to some good specialist in US who can help me dial everything in. THANK YOU!
     
  10. alicec

    alicec Senior Member

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    You believe things have fallen into place because you have accepted a narrative which, unfortunately, has little foundation.

    Many people have reported the kinds of sensitivities you describe, or variations on the theme. Some of them may indeed have a similar collection of SNPs in the genes you mention because after all, these SNPs are very common.

    Many however have quite a different combination of SNPs.

    In other words there is no evidence for any causative role for these SNPs, either for your sensitivities or for your illness in general.

    You will indeed be disappearing down a rabbit hole if you persist in believing that "treating" your SNPs will somehow cure your health problems.

    Assisting metabolic weaknesses due to particular SNPs is more like an insurance strategy. It might be wise to consider it, particularly in conditions such as ME/CFS which has widespread metabolic derangements, to ensure the weaknesses don't become limiting.
     
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  11. Learner1

    Learner1 Professional Patient

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    Yes, optimizing biochemical pathways gas been a tremendous help. It is part of getting well, though there are other factors involved.

    Taking a step back, I started learning about the biochemical pathways 9 years ago, before there was so much discussion all over the internet.

    My motivation at the time was to help my child, a star athlete, who had come home from a top college with what looked like a very serious mental illness. After consulting 22 doctors and going through 9 psychiatric medications, it became clear that psychiatry didn't have the answers.

    I finally found an excellent naturopathic doctor who practiced functional medicine. He tested and diagnosed celiac disease, multiple good allergies, a very leaky gut, malabsorption and severe nutrient deficiencies.

    Fixing these, with an emphasis on nutrients, was the key to a complete cure, and my child returned to college, majored in neuroscience, and is finishing a PhD in Nutrition at a top US school.

    Unfortunately, our family health problems didn't stop there, and with 6 family members suffering from various issues, and finding help in nutrition, we began doing the 23andme and Genova Diagnostics NutrEval tests on everyone and began to compare the nutrient test results with the SNPs and the pathways.

    I read Yasko. I read Heartfixer. I read Rich van Konynberg here on PR.

    And I found that the theories I was reading about were proven out in real time, with my family's results. Not everything matched 100%, but there was enough that did match, and I went on to read study after study on the SNPs, various health issues, and the pathways. And understand that environmental factors and other genes have impacts, too.

    I discussed what we found with our doctor, who has a good grasp of nutrigenomics and is a colleague of Lynch's. I went to Lynch's Seeking Health Conference where I saw doctor after doctor give case study after case study of nutrigenomics successes.

    At first, it was tempting to just match up SNPs with issues. But, with more experience, it became evident that its the pathways that are the focus. There are substances that each pathway needs to function, and to function optimally, there needs to be enough of each ingredient available or you'll get stuck.

    For example, even if your SNPs say you need a lot of methylB12, you need adequate cofactors like B6" B2, magnesium, potassium, trimethylglycine, and methionine to make your methionine cycle work. And then, you need adequate aminos to get to make glutathione which can tackle toxins, and then you need adequate transsulfuration pathway ingredients and adequate water, fiber and elimination processes to get rid of them. And there are substances that inhibit pathways, such as mercury, casein, pesticides, etc. so getting rid of those is important.

    Again and again, I've heard "Treat the patient, not the SNPs." And, in my family and in the many case studies, its not just SNPs and nutrients... It's infections, toxins, mold, leaky guts, etc. that change how well the pathways work, too.

    And, with 9 years of testing under our belts, we now identify symptoms like headache, fatigue, anxiety, depression, sick liver feeling, etc. and realize the tendencies ourcpatheays have, and can adjust our nutrient intake as needs to "normalize" function and make symptoms go away. For me, it usually means taking lots of MB12, TMG, and P5P, with nominal amounts of other cofactors, but adding methionine and molybdenum when under stress. One of my children need a lot of folate - but she has the MTHFR C677T SNP and thectestvof us don't.

    Understanding the the pathways empowers you to.manage your own health. And methylation is essential to mitochondrial function, DNA replication, neurotransmitter production, immune function, and Anyboyhrr essential tasks.

    I had a lot of toxicity which led to my cancer and may have led me here. Optimizing methylation supported me getting rid of toxins. Maintaining adequate B12 is essential to helping with my fatigue, and all of it helps me tremendously. I look healthy and have functioned better than I should, given how sick I am.

    But it won't kill infections, reverse my auto immune issues, or fix my dysfunctional immune system. Its a part of the solution, butvtggere are other tools in my toolbox as well.

    And, though I plan to reduce my supplements as I return to health, I will likely always need some supplementation, as my child, who is now healthy, does.

    Youre welcome! Keep reading!
     
  12. InsomniacNextDoor

    InsomniacNextDoor

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    Very possible I have fallen into that place but only in my head and I won't start experimenting until I really do all this study. These 'mystery' conditions really do have a ton of nuts and bolts and easily fit into many narratives.

    I won't be treating the SNPs, I realize this is futile but I'm really hoping that by supporting certain SMPs might improve my quality of life until I figure out how to support my health better by addressing the underlying causes. If I read you correctly, then this is what you suggesting doing anyways.
     
  13. InsomniacNextDoor

    InsomniacNextDoor

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    @Learner1 wow, thank you for being so kind and sharing this remarkable story here. Sounds like you've done everything you could as a dad and it has paid its dividends. Your experience kind of goes against elicec's critical take on treating SNPs but perhaps you didn't treat them (as you said it yourself) but looked for signals and directions on how to better support your own and your family's health. This makes good sense to me too.

    When you say you have to tweak your nutrients every so often for symptoms to go away... how did you learn all that? Merely from studying and experimenting or did you consult with someone? Also, I'm very curious... how did you collect all this toxicity? Were you exposed to high amounts of it somewhere or was it your body that had trouble flushing all of it due to impaired methylation?

    I've started consulting with a guy with similar condition as mine who says he took care of his auto-immune issues and infections with Traditional Chinese Medicine. Have you heard about Gu Syndrome? If you google it you'll come across the work of Heiner Fruehauf, who is an authority on the subject. It might be something you can look into as well.I'll try that approach before I tweak anything with methylation supplements, very curious how it goes but he says it's a long process so need to arm myself with patience.

    I'll keep studying these resources you mentioned and come back for some guidance if you don't mind. Thank you again!
     

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