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Next steps after receiving MTHFR information

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Sparrowhawk, Aug 24, 2013.

  1. Sparrowhawk

    Sparrowhawk Senior Member

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    I just received my 23andMe info last night and ran it through Genetic Genie today. My detox pathway analysis looks pretty darn good, which surprises me, but I do have some red items on the Methylation pathway analysis.

    Gene & Variation rsID Alleles Result
    COMT V158M rs4680 AA +/+
    COMT H62H rs4633 TT +/+
    COMT P199P rs769224 GG -/-
    VDR Bsm rs1544410 CT +/-
    VDR Taq rs731236 AG +/-
    MAO-A R297R rs6323 TT +/+
    ACAT1-02 rs3741049 GG -/-
    MTHFR C677T rs1801133 AG +/-
    MTHFR 03 P39P rs2066470 GG -/-
    MTHFR A1298C rs1801131 GT +/-
    MTR A2756G rs1805087 AA -/-
    MTRR A66G rs1801394 GG +/+
    MTRR H595Y rs10380 CC -/-
    MTRR K350A rs162036 AA -/-
    MTRR R415T rs2287780 CC -/-
    MTRR A664A rs1802059 GG -/-
    BHMT-02 rs567754 CT +/-
    BHMT-04 rs617219 AC +/-
    BHMT-08 rs651852 CT +/-
    AHCY-01 rs819147 CT +/-
    AHCY-02 rs819134 AG +/-
    AHCY-19 rs819171 CT +/-
    CBS C699T rs234706 AA +/+
    CBS A360A rs1801181 GG -/-
    CBS N212N rs2298758 GG -/-
    SHMT1 C1420T rs1979277 GG -/-

    I am working my way slowly through this Methylation sub-forum and am finding the amount of archived information overwhelming. I did watch the Rich VanK swedish presentation which was a great intro. I am also working my way through the links in caledonia's sig and some of the posts helping other newbies by folks like Valentijn.

    Any suggestions on next steps, or is it best to just follow the simple Rich VanK protocol and just see how it goes? Conversely if, as asserted a few times in Rich's messages, one really should be under a Dr.'s care when embarking on this, are there Dr.'s other than Yasko folks would recommend? I think Dr. Nathan was mentioned (CA Clinic, Gordon Medical, I think worked with Rich)?

    What is really fantastic about Genetic Genie if you haven't looked at it lately is they now provide interpretation of your MTHFR results, and are working on the same functionality enhancement for the Detox results. However some of it is confusing. For instance it says jump on L-methylfolate supplementation for some of the issues, then says but wait, you must address CBS first. My entire diet, due to hypoglycemia, hinges on meat and eggs, so I'm not sure I can just cut out sulfur containing foods.

    Thanks in advance.
  2. caledonia

    caledonia

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    There are things you have to do first before starting methylation supps, otherwise, you'll run into problems and have to backtrack and address them anyway. (Speaking from hard experience here.)

    One of those is CBS. If you start methyl supps and get a stress/anxiety reaction, suspect CBS. You have CBS C699T +/+, plus all the BHMTs. The BHMTs can add to CBS and even create a CBS situation when you don't have a CBS mutation. So I'm thinking you do want to check to see if this is expressed.

    I used Heartfixer's CBS protocol except I used the Free Thiol diet instead of a low sulfur diet. I didn't stop eating meat. Eggs, however, do look problematic. Shawn Bean from MTHFRsupport.com says that you can follow the diet about 80% and it will still work. So maybe you can still sneak in a few eggs from time to time.

    The other thing you need to address first is leaky gut. Otherwise, you will run into the extremely high need for potassium and/or magnesium which can become a dangerous situation. I'm still researching this, but it looks like a 4R gut rebuilding program would be the best thing for leaky gut.

    For your COMT/VDR combination, Yasko suggests hydroxy and adenosylcobalamin. (Rich's protocol uses hydroxy.)

    So to answer your question, as long as you check for CBS and leaky gut and address those first if necessary, I think Rich's protocol would be ok for you.
    Sparrowhawk likes this.
  3. Sparrowhawk

    Sparrowhawk Senior Member

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    caledonia thanks very much, very helpful.
    "
    One of those is CBS. If you start methyl supps and get a stress/anxiety reaction, suspect CBS. You have CBS C699T +/+, plus all the BHMTs. The BHMTs can add to CBS and even create a CBS situation when you don't have a CBS mutation. So I'm thinking you do want to check to see if this is expressed."

    So is the only way to check for CBS just to start methyl supps or if not what did I miss?

    Ok it looks like there is a test, from Heartfixer's website:
    CBS initiates the trans-sulfuration pathway, converting homocysteine in to cystathionine and its downstream metabolites. This is the most important Methyl Cycle defect and is present in 90% of the patients who we have tested. The CBS defect is an up regulation. CBS is operating at up to ten times its normal rate. Homocysteine and all of the upstream methyl cycle precursors will be “pulled down the CBS drain” to produce toxic levels of cystathionine metabolites. The C699T and (to a somewhat lesser extent) A360A defects are associated with CBS up regulation. Homozygotes (+/+) will be more severely affected than will be individuals heterozygous (+/-) for a CBS abnormality. We treat CBS ( +) individuals with dietary animal protein and sulfate restriction and supplements designed to neutralize ammonia and speed up clearance of sulfite/sulfate. Laboratory findings consist of an elevated urine sulfate level, a low or low normal blood homocysteine level, an elevated or high normal blood ammonia level, and positive findings of ammonia, sulfite, or sulfite upon Asyra testing"

    I'm just stunned about the sulfur thing. I eat an egg every morning, and coconut pancake with egg in, collards and such twice a day, both on the bad sulphur list, and the rest is meat and fat. Yikes, Scoobie Doo!

    I also have GI issues, reading the 4R site now, thanks.
  4. Critterina

    Critterina Senior Member

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    caledonia,
    What is leaky gut? Symptoms, labs? I was tested for every kind of bacterial overgrowth and pathogen, ova and parasites, and all negative. Can I assume I'm not leaky? What would happen if I was and started methylation? I mean, more specific than "feeling bad".
  5. Critterina

    Critterina Senior Member

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    The heartfixer website reflects the Yasko understanding of CBS. @Valentijn has read the source document and reports that the CBS "variant" that causes the 10x upregulation is a laboratory-induced artifact where they chopped off a large part of the gene, not the mutations mentioned. I haven't found a free copy of the article, or I'd read it for myself. Whatever the CBS thing is, it's probably not that drastic. And now that I've tagged Valentijn, she might just chime in with her understanding.
    I did the low-sulfur diet for a week after I got my test strips. My CBS is +/-, my sulfites were about 10 (10-25 range), and sulfates were 800-1200 at the beginning of the week, 400-800 at the end. I felt immensely better, but didn't stay on the low-sulfur diet because of it being low protein and my history of muscle wasting, and slowly got worse. So, tough as it is, the low-sulfur diet cuts out a bunch of things, so if there is a dietary component, it will probably tell you so. (My current theory is that I'm histamine intolerant, exacerbated by copper deficiency. Stay tuned next week to see if I have new theory!) :)
    Coconut pancakes? Please share the recipe! Thanks.
  6. Sparrowhawk

    Sparrowhawk Senior Member

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    Thanks Critterina that's good to hear the CBS may not be as dire as it sounds from reading the Heartfixer site. Reading the lists of foods left me wondering what in the world I would eat, as with the IBS all grains are out, with the hypoglycemia all remotely starchy or high glycemic foods are out (including carrots, yams, etc.).

    Just ordered the test strips but they'll take a week to get here. Do you have a reference page that goes into how to measure that? You have two values above, sulfates and sulfites, do they need diff test strips?

    A good description of leaky gut I found today when researching the 4R approach is here:
    http://www.thenaturalwayclinic.com/health_blog/index.php?itemid=77

    There is a test available which she mentions, but I haven't done it. I've done two complete Genova Diagnostics (merged recently with Metamatrix I believe) digestive analyses, and was ok for parasites and harmful bacteria. Some of my indictaors are off, like Ph, and I have a higher than normal number of lymphocytes -- thus lymphocitic colitis / IBS diagnosis.

    Coconut Pancakes:
    Here is the recipe, online: http://www.cheeseslave.com/coconut-flour-pancakes/

    Here is what I actually do/use. I make a batch every few days. Eat one with breakfast and one at 3-4pm with some tahini (yeah, more thoil/sulfur!):

    Ingredients:

    Eggs, preferably pastured (3) -- I use either farmer's market eggs or pastured
    coconut oil — (3 TBS) — I pre-melt this much coconut oil (Nutiva brand) in a ramekin that is set in the fry pan to warm up while I'm mixing the other ingredients
    Coconut milk (2-3 TBS) — I get the Natural Value coconut milk with no guar gum and no BPA coating in the can. They recently stopped making the organic so I just ordered 'natural' we'll see if I can tell any difference. This goes bad after about five days so I never get through an entire can...
    I don't use any sweetener. At one point I was putting a small amount of cashew butter on top but it caused bloating so I quit that.
    Sea salt (1 tsp) — I don't use any salt
    Coconut flour (3 TBS) — I use Bob's Red Mill organic coconut flour from Whole Foods.
    Optional: Baking powder, aluminum-free (1/2 tsp) -- I use this too
    Instructions:

    1. Heat cast iron skillet on a medium flame.
    2. Using a wire whisk, mix together eggs, baking powder, let sit for a minute until the baking powder puffs up
    3.. melt coconut oil in ramekin, mix coconut milk into ramekin when warm, then add and mix with whisk into eggs
    4. Continuing to whisk, add the and coconut flour until thoroughly mixed.
    I don't add any butter or coconut oil to the pan -- what is in the cakes is sufficient that they don't stick.
    4. Spoon 2-3 tablespoons of batter onto skillet making pancakes about 3-4 inches in diameter.
    The first set of two don't usually cook as well as the later ones, don't know why, maybe it's heat.
    5. Serve with whatever works for you...I have mine with another egg (softboiled)!
    Critterina likes this.
  7. Critterina

    Critterina Senior Member

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    I used a combination of the Heartfixer list and something else, maybe this low-thiol list at the bottom: http://www.livingnetwork.co.za/chelationnetwork/food/high-sulfur-sulphur-food-list/. Quinoa, amaranth, and buckwheat are not true grains, so maybe you could eat them? They are also complete protein. Veggies are celery, green beans, zucchini. Fruits (a few restrictions) and nuts (all but peanuts and Brazil nuts) are what kept me going. I can do well on a diet of pure fruit, just spaced out during the day, for about 10 days. When I'm worried about my blood sugar falling, I combine fats and proteins with my carbs and that's often enough. But then I'm not in your situation.

    Yes, they are different test strips. I bought them both because I suspected a SUOX mutation/downregulation. The fact that I have low sulfites means I probably don't, at least not enough to pay any attention to it. The key is on the metal tube that the test strips come it. The hardest part is timing the 120 s for the sulfates. I generally wet it, then lay it on the tube between the numbers I think it will be. And wait.



    Thanks. That was helpful! :)

    Well, if I had any coconut flour, I think this would be dinner! Thanks for the recipe and the interpretation!
  8. Valentijn

    Valentijn Activity Level: 3

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    I deleted -/- and results not supported by research, including CBS - you have the good version.

    Due to MTHFR C677T and A1298C your methlfolate is produced at 30% of the normal rate. You would probably benefit from methylfolate supplementation.

    MTRR indicates you might need some B12, but due to MAOA, COMT, and VDR being slow at using up methyl groups, you may tolerate hydroxoB12 better than methylB12.
    Sparrowhawk likes this.
  9. Valentijn

    Valentijn Activity Level: 3

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    CBS C699T does not result in a 10x upregulation. At most it has a minor impact, which has only been shown to be beneficial.
  10. taniaaust1

    taniaaust1 Senior Member

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    Im going to second what Valentijn said. Having both of those acts in the same manner and is just as bad as if you had a double copy of one of the MTHFR polymorphism and supplementing properly for this could really make a difference (I get a bit more endurance etc out of treating MTHFR issues). I dont know the correct way to supplement for someone who has one copy of each (with two copies of the one I have (MTHFR C677T) I need methylB12 as well as the bioactive form of folate).
  11. Sparrowhawk

    Sparrowhawk Senior Member

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    Thanks for both your responses. I am still in the initial baby steps of learning all this and every bit of guidance helps. Could I ask you to refer me to any source docs or perspective that might give me more along the lines of what you have provided above (like Heartfixer, but I assume with a different view based on your response)? I will look into the differences of methylB12 v.s hydroxoB12. Thanks again!
  12. Sparrowhawk

    Sparrowhawk Senior Member

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    The bioactive form of folate, is that the folinic acid I have seen Rich VanK mention in some of his posts? Thanks!
  13. Valentijn

    Valentijn Activity Level: 3

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    It's been discussed in detail elsewhere here. Basically Yasko makes the claim based on a paper where a huge chunk of the gene was chopped off and inserted into a bioengineered yeast.

    Normal research in humans shows health risks are actually associated with the slower version, due to increased homocysteine levels. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2366099/ shows that one T results in reduced risk, and TT results in much greater reduced risk of birth defects associated with low folate and/or high homocysteine. There's also a study showing T results in less risk of adenoma, which I can't find off-hand.

    Yasko's CBS file has a bunch of cut-and-pasted excerpts which really have nothing to do with each other. It's at http://dramyyasko.com/wp-content/uploads/2010/06/31-A1-CBS.pdf , and from what I recall, the mutant yeast paper doesn't even discuss C699T. CBS C699T isn't even a missense mutation, so doesn't even change the structure of the protein at all. The whole situation is quite weird. The full paper she's referring to is at http://hmg.oxfordjournals.org/content/10/6/635.long
    Sparrowhawk likes this.
  14. Sparrowhawk

    Sparrowhawk Senior Member

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    Thank you again! I am plowing through the posts in the genetic testing portion of the forum, which I now realize is likely a better home for this thread. For some reason I completely missed that one as I kept clicking on the one for detox and methylation, so I have my reading cut out for me today!
    Valentijn likes this.
  15. caledonia

    caledonia

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    The gut should have very small junctions (holes) in it to let vitamins into the bloodstream, but not food particles. If the gut lining gets damaged the junctions will open up somewhat larger and start to let (teeny tiny) food particles, bacteria and toxins into the bloodstream. Your body reacts to these as foreign invaders and it causes inflammation. Inflammation causes a wide range of problems in the body such as arthritis. Leaky gut also causes food intolerances and allergies.

    Various things can damage the gut lining and cause leaky gut, such as candida, h. pylori, gluten, alcohol, NSAIDs, GMOs, etc. So not always just gut bugs.

    There is a specific test for leaky gut, I think it's called an intestinal permeability test. For the test you drink two different sugars, each with different sizes molecules, one larger and one smaller. Then they measure how much of each molecule makes it to your urine. If the larger molecules are getting waylaid and not showing up in your urine, then you have leaky gut.

    The leaky gut will cause magnesium and/or potassium leaking. This is greatly exacerbated once you start methylation. It might not show up for a few months or it might show up right away, depending on how slow or fast you're doing methylation. This is the same thing as the potassium insufficiency that Freddd talks about. Supplementing with mag or potass will help in the short term, but it won't solve the problem. Nor will continuing with methylation solve the problem. It will only make things worse and worse. This is a potentially dangerous situation as you need these electrolytes to maintain your heart rhythm.

    So if you start methylation, and you're getting heart palps, and twitchy muscles or muscle cramps this is what is happening. You may also start waking up at night or feeling unrefreshed sleep because your feet or legs start twitching at night while you're sleeping.
  16. Sparrowhawk

    Sparrowhawk Senior Member

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    "So if you start methylation, and you're getting heart palps, and twitchy muscles or muscle cramps this is what is happening. You may also start waking up at night or feeling unrefreshed sleep because your feet or legs start twitching at night while you're sleeping."

    I have that all already, without methylation! Twitching all over in fact.
  17. Mimi

    Mimi Senior Member

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    Hi All,

    I've been doing higher dose s-acetyl glutathione and BH4. I have a CBS upregulation (hetero for A360A) plus a bunch of BMHT SNPs, an MTHFR, two VDRs and a double NOS. So you'd think I'd have both sulfur and ammonia problems, right? I have been very sensitive to wine and once had a bad reaction to a sulfur drug. But now I can tolerate wine and my sulfite and suflate test strips showed only negligible amounts. I attribute this largely to the BH4, but I'm sure the extra glutathione helps a lot. If anyone has any insight please let me know. I also found out I have the GHC1 SNP (single) so I make less BH4. Taking BH4 has allowed me to cut down my mood supps in half and has both strengthened and stabilized me to almost normal.
  18. Mimi

    Mimi Senior Member

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    That's in the context of taking a bunch of other stuff for pathogens, liver support, tonics and a ton of minerals. I also went through 7 rounds of DMSA (frequent low-dose) last spring. So not normal normal, but able to function more normally. I do crash, though, if I work too hard, like doing 6 loads of laundry in a day and vacuuming the entire house for fleas. I'm now working on a crash protocol - SAG (s-acetyl glutathione) by the gram really helps, as does NADH. Gonna try idebenone next.
  19. Sparrowhawk

    Sparrowhawk Senior Member

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    what is BH4?
  20. taniaaust1

    taniaaust1 Senior Member

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    Yes.
    My MTHFR specialist has me on calcium folinate (folinic acid) ie bioactive form of folic acid. I used to take regular folate before due to a specialist not realising we need an active form of folate and that didnt do a thing, this other form does help me. My specialist says I should never have been put on normal form of folic as those with this MTHFR cant use that form well.

    With one of the MTHFR issues you have at least, I know you need the methylB12 form for that as you need the methyl group. I do have an drawing of how this works with the methylB12 which my specialist copied for me, I'll find and post it here for you some time so you can understand this polymorphism better and where the methylB12 plays into it etc

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