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What can cause anxiety when taking methyl donors ?

Discussion in 'Genetic Testing and SNPs' started by Kreiss, May 8, 2014.

  1. Kreiss


    Hello everyone,

    I am MTHFR C677T homozygous. Every time I try to take a methyl donor like L-methylfolate or trimethylglycine (TMG) I get anxiety, and I am trying to find out what could be the cause.

    These are the results from 23andme:

    COMT V158M rs4680 GG -/-
    VDR Taq rs731236 AA +/+
    MAO A R297R rs6323 GT +/-
    MTHFR C677T rs1801133 AA +/+
    MTRR A66G rs1801394 AG +/-
    MTRR K350A rs162036 AG +/-
    MTRR A664A rs1802059 AG +/-

    I went to see my naturopatic Doctor today, and She told me my symptoms do not match with the results from the test, meaning people who are COMT V158M rs4680 (GG) (-/-) should tolerate the methyl donors well. She does not understand why I get anxious when I take a methyl donor. Do you have any ideas why this could be happening ?

    BTW, I take pristiq - 150 mg.

    Thanks a lot for your help.
  2. ahmo

    ahmo Senior Member

    Northcoast NSW, Australia
    @Kreiss Just a quick, superficial response. 1st, I suggest you move this question to the Glutathione/detox forum. There are a great lot of problem solvers for these issues there, @caledonia springs to mind.

    This might be happening if you are not also taking MB12 to meet the extra methyl groups. Not only the MTHFR, but the MTRR suggest you need extra B12.

    COMT, leading to mood swings, dopamine fluctuation, might be an indication for lithium orotate. I don't know the mechanism, but lithium is also useful/necessary (?) for B12 absorption.

    MAO is only heterozygous, but it might also be causing histamine problems. If so, those can cause anxiety. ahmo
  3. Martial

    Martial Senior Member

    Ventura, CA

    Your naturpath can't make blanket statements on COMT results alone, anxiety reactions are one of the most common things to happen, especially when a person is flooded with methyl donors they could not create for an extended period of time. There is no real black or white to it, everyone has different reactions and symptoms and it is a very odd and strange path to healing.

    It could be low potassium or from methyl folate, among other things, I have heard this happen from many other people for different reasons, panicky from low potassium, moody and wired feeling reeved up from too much methyl folate, or feeling like they are jumping out of their skin with L Carnatine Fumarate.. There are many different things that can happen but as long as you are treating for whats necessary it will move towards healing, just go at a pace you can handle!
  4. caledonia


    Cincinnati, OH, USA
    Technically, with COMT -/- and VDR taq +/+ methyl donors should be no issue at all. That's actually the least sensitive combination.

    You're not reporting any CBS or BHMT mutations, which could also cause anxiety with methyl donors. If you happened to have SUOX (rare but does happen - not reported on 23andme), that would be the same as having CBS, and the treatment would be the same. Might be worthwhile to test for ammonia and urine sulfate.

    So then it might be down to, what types of B12 and folate are you taking and how much. Did you start low and increase slowly? 1mcg is low - 1000mcg is not.

    There could be some kind of detox going on, or deficiencies that start up when you start methyl supps, such as potassium or other electrolytes. Could be methyl trapping caused by the wrong kinds of B12 or folate, or by the wrong amounts relative to each other.

    Maybe a possible reaction with Pristiq, not sure about that though. I would think you would get something more like a serotonin syndrome if that was the case.

    Try going through my two documents "Start Low and Go Slow" and "Roadblocks to Successful Methylation" and see if anything rings a bell. They're linked in my signature.
  5. musicchick581

    musicchick581 Senior Member

    Isn't it sulfates according to Yasko? That can prevent the methyls from working? And heavy metals like aluminum? I was worse with anxiety and weird feelings with methyls. I had to stop everything that isn't in my multivitamin so I'm on 400 mcg methyl folate split in two tablets a day, so only 200 mcg at a time. The B's are low...only 50 mcg and it probably isn't absorbed well in tablet form. My anxiety is still here but lessened. Panic attacks are still daily but lessened since stopping the other methyls and NAC. So check sulfates maybe. Mine aren't lowering for some reason though.
  6. Martial

    Martial Senior Member

    Ventura, CA
    Have you ever been tested for Pyroluria? That is one possibility and would be good to rule out, if this is the case your body is being depleted severly of zinc, and vitamin b6 while building higher levels of copper at the same time. It is an easy urine test to find out if this is an issue. The supplementation is also cheap just P5P and Zinc, however you should not treat for this unless you come back positive, the amount you would need to intake at times would be toxic for someone without the condition.

    Sometimes anxiety is just anxiety though and may take a more integrative approach, I had severe anxiety for five years before falling physically ill and was on multiple medications. I eventually weaned off all my meds and cured it completely using tips I learned from a book called "At last A Life by Paul David." It really is all you would ever need to read to recover from anxiety but believe me I was also a very severe case, so proof it can help anyone.

    There are other possibilities to like low intra cellular potassium, and Magnesium, different chronic ongoing infections like Lyme and Co infections, etc... Anxiety is a result of sensitized nerves after all, then we get those darn racing thoughts and can never shut off our minds because we feel so off. It can really become a vicious cycle from there, The attitude I learned cut it at the source by not engaging in the mind anymore and with a radical acceptance of the condition, and no longer tuning into all my different symptoms and body anymore.

    I have sensitizied nerves now as a result of lyme and other anxiety triggers like low potassium but it is only physical feelings in nature and I treat or relax through the source, before it was an intense mind trap of whats wrong with me, this doesn't feel right, panic, OMG IM DYING!! LoL I had to turn a plane around on the terminal track that was going to New York when I was 19, had an intense panic attack that lasted two and a half hours to three hours and the Fire Department came. Man no one knows what fear is like unless they have a really intense panic attack like that. I always felt like a ticking time bomb of anxiety just precipitating the next time I would have another big panic attack and got locked in a very huge cycle in fear of fear.
    Last edited: May 22, 2014
    ahmo likes this.
  7. sregan

    sregan Senior Member

    I'm just starting to experience anxiety in the mornings only the last 2 days. Not sure if I've reached some type of deficiency or what.

    I've been on SMP for about 4 weeks now and been doing pretty good with only mild symptoms so far. Anxiety is by far the most disturbing symptom. Freddd mentions it might be part of the brain (limbic system) coming back to life with the addition of the Cbls.

    Diet has been pretty much the same with the exception of eating eggs (sulfur) the day before the first morning of anxiety. Yesterday's diet was low sulfur. Did have a baked chicken stuffed with an onion but did not eat any of the onion.

    Also noticed on both mornings stool was loose and odorous. Makes me thing maybe I could be having a die-off reaction. Or possible a sulfur/food reaction.

    Here's what I've been taking for 4-5 weeks:

    Made some capsules with about 15 mg each of B1, B2, B3 about 750mcg Biotin and 50mg PABA. With about 50mg LCF and about 60-75 mcg of Folapro). Sublinguals with 1/4 Source Naturals p5p (100mg), 1/4 source naturals Pantethine (25mg), 1/4 Jarrow Glass bottle MB12, 1/8 ACBL. About 200 mg Mag-Glycinate and 200 mg of Calcium.

    Been taking about 2 99mg Potassium Glycinate during the day, have been experiencing some cramping in the calfs mostly as SMP side effects.

    Today too these sups Except the LCF. Gonna see if that helps. Would have though if it were the LCF it would have happened sooner that now though.

    Any thoughts?
  8. Critterina

    Critterina Senior Member

    Arizona, USA
    @sregan ,

    I have no idea what a Jarrow glass bottle of folapro contains, but I would guess that perhaps your folate and B12 ratios could be off.

    1. Since you have the MTRR A66G ++ and MTR A2756 +/-, adding methylB12 will really accelerate the use of methylfolate in the methyl cycle. Thus you will need more methylfolate that you did before, maybe more than you are taking (just a guess).

    2. Since you have the MTHFR A1298C +/-, the reaction that uses up methylfolate to activate biopterin (BH4) is slower than if you didn't have it. Biopterin is the enzyme that makes serotonin (from tryptophan) and dopamine (from tyrosine), the source of other neurotransmitters.

    What is the net effect? If it's less methylfolate to support the biopterin cycle, as it very well could be, that could be the source of your anxiety.

    Of course, there are probably other SNPs that affect how you use your biopterin, whether it favors dopamine or serotonin. I have similar SNPs, and when I use methylB12 and methylfolate, my tryptophan tests low but my tyrosine is normal. Is that because tryptophan is limited by diet, whereas the body can manufacture it's own tyrosine? Perhaps. I found that I need to supplement more than 500 mg tryptophan. I use 1500 mg, but haven't been retested. My mood seems better, though.
    victoriana likes this.
  9. sregan

    sregan Senior Member

    Critterina, thank you for the reply!

    That is Jarrow glass bottle "MB12". It's the Methylcobalamin in the glass bottle when Jarrow was potent.

    This go around I have been taking more MB12 than I did on previous attempts. My dosage of MB12 and MFolate are almost where they were when I started on the other SMP attempts now (200mcg). I have been much better and gone much longer on this go around than the others. My other attempts I believe I was low on MB12 and did start feeling better when I added more.

    Your interpretation of my MTRR and MTR are the opposite of what I was thinking. I thought they were telling me that I'm going to use up MB12 fast AND not recycle to well. So what I take will be gone quick.

    I do believe I am low Serotonin just based on symptoms

    I've taken my Tryptophan with a little B3 and p5p. The B3 so my body doesn't seal tryptophan to make B3. And the p5p to help the conversion to Serotonin.

    I haven't experienced the anxiety since. I haven't eaten much for anything high sulfur since and also stopped the 60 or so mg of LCF I was taking daily. I'm leaning toward the LCF but who knows. I'll have to try eggs again for breakfast to rule out sulfur
    Last edited: Jul 28, 2014

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