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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Help please? Homozygous for MTHFR C677T / COMT V158M / COMT H62H / VDR Bsm

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Lemnia, Jan 4, 2016.

  1. Lemnia


    I have been very ill for 4 years, firstly diagnosed with CFS/ME and then in 2015 I tested positive for Lyme Disease.
    I believe I have a vitamin B12 Deficiency (yet my tests constantly come back sky high) and that I have a blocked methylation pathway.

    My 23andMe results indicate I need help in this area (Genetic Genie Interpretation attached).

    I am homozygous for MTHFR C677T /
    COMT V158M / COMT H62H / VDR Bsm

    I am heterozygous for MAO-A R297R/ MTR A2756G/ MTRR A66G / CBS C699T.

    My Mother almost died 20 years ago when they failed to diagnose Pernicious Anaemia, after 9 months deteriation she collapsed and it took 17 days in hospital before they found it. My Father died of Parkinsons. I am now bedridden most days and I'm convinced there is a link here.

    I do know that with my combination of MTHFR and COMT I need to be very careful with what I take. I'm highly sensitive to most things.

    I would appreciate any advise. Too ill to work this out on my own. Does anyone know of a specialist who I can consult with via Skype or phone? (I am in the UK ).
    ANY help at all with this, I'd be most grateful !!

    Attached Files:

    pattismith likes this.
  2. chloedog


    Following - I have the same mutations as you except I'm -/- for the CBS C699T, but I am hetero for CBS A360A.
    I am new to all this so I can't comment, sorry.
  3. alicec

    alicec Senior Member

    High levels in blood could indicate that the vitamin is not being used - ie it is accumulating in blood rather than being taken up into cells.

    In my own case, I had never supplemented B12 apart from the small doses of cyanocobalamin in a multivitamin, yet blood tests for B12 were very high. The doctors who ordered the test had no comment. When I asked what high levels might mean they had no clue.

    Later I had an organic acids test (OAT), which showed that the methylmalonic acid (MMA) marker was very high. This indicates that a functional B12 deficiency is present (the enzyme processing MMA is B12 dependant. It accumulates when this enzyme is not working properly).

    As I began reading more I began to appreciate that the high serum B12 was a clue that I had not previously understood.

    Supplementation with methyl and adenosylB12 soon returned the MMA to normal levels.

    So apart from revealing frank deficiency, blood tests for B12 are not particularly helpful. A better test for B12 status would be either a blood test for MMA, or an OAT, which measures many metabolic products in urine, including MMA. It can be helpful for revealing a variety of functional metabolic defects.

    I might add that for me, an analogous situation applied to folate. I had only ever supplemented the small amounts of folic acid in a multivitamin, yet had very high blood levels. The OAT also showed a functional folate deficiency which was remedied by methylfolate.

    Regarding your SNPs, the homozygous MTHFR C677T would cause a marked slowing of the enzyme. Supplementation with methylfolate could be helpful, along with the cofactor (B2), which may help stimulate the enzyme.

    The +/+ COMT V158M would also slow the enzyme, so supplementation of its cofactor magnesium may be helpful.

    It is a myth that COMT+/+ means intolerance of methyl groups. Some people are certainly sensitive, but it is nothing to do with COMT.

    Since you say you are sensitive to many things you would be very wise to approach methylfolate and both B12s very cautiously. Start very low and build up very slowly.

    The +/- SNPs for MTR A2756G/ MTRR A66G would also slow the enzymes and hence use of B12.

    The other SNPs don't amount to much.

    There is much discussion of B12/folate protocols on PR. There are different versions and different responses. Many people have benefitted but many have found them problematic. These active vitamins can have powerful effects.

    Given your's and your parent's history, B12 could be profoundly important for you so it is worth trying. Just proceed very cautiously.
    pattismith, Helen and Valentijn like this.
  4. Lemnia


    Alicec, I am so grateful for your response. I'm so ill and no treatment I seem to trial helps. I recently returned from 3 weeks in hospital in Germany hooked up to IV 4 times a day. Still no improvement and often too sick and ill to get out of bed. Thank you for your very welcome advice you have shared here. When I first got ill 4 years ago I was convinced it had something to do with Vitamin B 12 deficiency. But like you every doctor just shrugged and had no help with why my blood tested so high for Vit B 12. They certainly wouldn't entertain that perhaps it indicated my body wasn't actually utilising the B 12 (here in the UK they are very limited in thinking outside of the box). I believe I must give this a try. May I ask you, can you please advise exactly how you would start this if you were me? I'm too poorly to research it in depth. I will start low and slow. But what do I take ? I have not taken any vitamin or mineral supplements (except magnesium which I take daily) for 2 years now. If you feel you'd rather not offer me more advice, do you know of any expert that would be willing to assist me that I could make an appointment with via Skype (there are pretty much no experts practitioners available in the UK who understand the SNPs or the B 12 issues I have). Thank you with gratitude again.
    Shabbylady121 likes this.
  5. alicec

    alicec Senior Member

    Here is a recent review of the high B12 phenomenon. B12 deficiency, as revealed by elevated MMA and homocysteine, is a common reason for it.

    A few general considerations first.

    Metabolic derangement seems to be characteristic of CFS/ME and OAT tests which people have shared on PR show a variety of metabolic blockages/slow points.

    Adding active B12s and folate can have widespread metabolic consequences, stimulating various pathways that have maybe not been functioning well. Sometimes this can be unpleasant.

    Other nutrients involved in these pathways may become limiting, causing an initial positive response to peter out, or maybe never start at all. It may be necessary to supply various nutrients as well as the B12s for optimal effect.

    Different protocols have been proposed for how best to get these active vitamins to work.

    One which has been discussed a lot is Freddd's active B12 protocol, aka the deadlock quartet (or DQ; it contains 4 elements {both B12s, methylfolate and carnitine} each of which can deadlock the effectiveness of the others if it becomes limiting).

    Here is a thread discussing it (there are plenty of others). Some PR members have written their own guides to this - eg here.

    Another approach, the Simplified Methylation Protocol, proposed by Rich Van Konynenburg, differed in suggesting hydroxyB12 might be more suitable for people with adverse reactions to the active B12s.

    There was much discussion back and forth but it appears that Rich's protocol is not much used these days.

    Some people do seem to benefit from injections of very large doses of hydroxyB12 (where the large doses do other things like scavenge NO), but Rich's protocol uses small amounts and I think in principal is different.

    Personally I don't advocate Rich's approach. I think the suggestion the hydroxy doesn't cause the same problems as the active B12s is because it is doing very little. But some people did benefit from the approach I believe.

    Anyhow, recently a thread started trying to compare Rich's approach with yet another version advocated by the scientist who runs B12 oils (transdermal B12 products). There weren't many advocates of Rich's approach but interesting things were revealed about the ideas of Greg from B12 oils.

    Essentially he differs from Freddd in saying that it is B12 plus B2 that is needed. When sufficient active B2 is available the often large amounts of folate needed in Freddd's protocol, as well as carnitine, are unnecessary - we can make our own.

    (The enzyme which recycles folate is B2 dependant, and carnitine synthesis also requires B2).

    The catch is that for some people at least, making active B2 from riboflavin has multiple stumbling blocks (eg good thyroid function, a good supply of minerals such as molybdenum, manganese, selenium as well as iodine). This might be the biggest hurdle of all in using active B12s.

    My own experience suggests that much of what Greg says is correct and his transdermal B12 products are great, but too potent a place to start for sensitive people.

    In the beginning I don't think you should count on being able to make your own methylfolate so some of that will be necessary in addition to B12 to get things going.

    If later you find yourself needing large amounts of folate then I think Greg's analysis applies - you are not making enough active B2 to recycle folate properly. You would need to concentrate on that (various ideas discussed in the thread I linked).

    I suggest you start with the sublingual approach suggested by Freddd. The basic idea is to start with a small amount to gauge response. You want an amount that you maybe notice but that is not too unpleasant. Reduce the starting amount if necessary.

    Then you want to titrate up (slowly) - ie add more until an increase makes no difference. If you are tolerating and positively responding to larger doses of the B12s, then you could consider changing to the B12 oil products (much better than a mouthful of sublinguals).

    The basics supplies to start with would be: -
    MethylB12 - Enzymatic Therapy B12 Infusion, sublingual 1 mg
    Methylfolate - Solgar Metafolin (called folate on bottle), 400 microgram tablet
    AdenosylB12 - Source Naturals Dibencozide, sublingual 10 mg.

    There are other brands but these are known to be potent and a good place to start. There is quite a bit of variability in potency, especially in B12s.

    You probably want to have on hand a potassium source - either potassium gluconate powder or potassium chloride capsules - and niacinamide.

    This is because need for potassium can increase suddenly and cause unpleasant symptoms. Greg says this shouldn't happen if B2 is working, but maybe it isn't and a bit of potassium can be a great help. If needs become very great then B2 becomes the issue to address.

    Niacinamide can have a "quenching" effect if you get overstimulated from too high a dose.

    Where you start depends on how sensitive you think you are likely to be - but maybe 1/2 or 1/4 of the MeB12 and methylfolate to start with.

    Swallow the folate and place the B12 lozenge between upper lip and gum (dissolves more slowly than under the tongue, giving better absorption). If this is ok, repeat a few hours later. If too powerful, wait a day or two and try 1/2 that dose. You might aim for 3 or 4 doses in a day.

    How quickly you increase dose depends on your response and how brave you feel.

    As the guides and the threads indicate you may get unpleasant symptoms which could indicate a need for potassium and/or folate. Sometimes it can be hard to tell which is needed. You need to experiment by adding more and seeing what symptoms respond to what. Take folate away from potassium.

    Once you are tolerating 1 or 2 mg MeB12, you might try adding in adoB12. Start with just a tiny sliver of the 10 mg lozenge.

    Given you are not supplementing anything other than magnesium, you need to consider the issue that other things might become limiting very quickly. Freddd lists a lot of basics but these can be daunting to someone who is not supplementing at all. You will need to make you own decisions about all that depending on your own problems and responses.

    The B2 issue is critical but other B vitamins will also be important and this is probably the first thing you should think of adding. A low dose B complex could be helpful - without folic acid and cyanocobalamin. I saw a thread recently canvassing good ones - you could search for that. I would seriously consider additional riboflavin (very inexpensive) and also Source Naturals sublingual Flavin Mononucletide (the first step in B2 activation). You would probably need to cut this up, it is very potent, but it can be a good way of bypassing some of the blockages in making active B2. Start with the riboflavin to gauge response, try the FMN later.

    Trace minerals could be very important. This is something you could think about a little down the track along with the other basics.

    The carnitine issue is something you can also address down the line when you have other things in place. The only way to know if supplemental carnitine is a help is to try it but be warned, it can have a powerful effect. If it does help, then according to Greg's logic, this means you still don't have B2 right. But that is for later.

    The main thing it to be alert to your own body's response and not worry too much about someone else's rules.
    Last edited: Aug 4, 2016
    Creachur, CedarHome, Skippie and 6 others like this.
  6. Lemnia


    Alicec, thank you so so much for taking the time to put all this most helpful information down. I'm very grateful indeed. I'm going to read through it all carefully and consider my next step. Thank you again.
  7. Shabbylady121


    Durham England

    I am homozygous mthfr c777t and in the uk , chronically ill and just as frustrated!
    I been ill with me for 6 years .
    2 years ago I found out I was homozygous. I tried then but I’m giving it another go .
    I’ve gone gluten free .
    1000mcg of b12 for for days then increasing so far haven’t been able to tolerate folate

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