International ME/CFS and FM Awareness Day Is On May 12, 2018
Thomas Hennessy, Jr., selected May 12th to be our international awareness day back in 1992. He knew that May 12th had also been the birthday of Florence Nightingale. She was the English army nurse who helped to found the Red Cross as well as the first school of nursing in the world.
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Discussion in 'General Treatment' started by OkRadLakPok, Nov 11, 2012.

  1. OkRadLakPok

    OkRadLakPok Senior Member

    I have the COMT++ and this interferes with my ability to take certain supplements. I am looking for others who are COMT++, too.

    It is part of the whole methylation genetics. MTHFR gene is the most well known.

    MTHFR folks do not have enough whereas COMT++ have too much.

    I am thinking about hydroxycobalalin instead of methylcobalamine, but am leery. I do take methylfolate, though I am told that TOO might make things worse. Grrrrrrrrr
  2. Steve-22


    Hi there!

    I am COMT H62H +/+ COMT V158M +/+.I've been talking about this with Freddd as I have the same problem.We have been told to take hydroxocobalamin but he says it will only cause more damage in the long run and COMT or not,we should take methylcobalamin in tiny doses and ADB12 too.

    "The COMT enzyme transfers methyl groups which inactivate the neurotransmitter dopamine. With COMT V158M + these enzymes are less active, and thus inactivate dopamine to a lesser extent. The VDR/Taq SNP also impacts overall dopamine levels. That’s why together the VDR/Taq and the COMT V158 status are key indicators of bodily levels of dopamine. The composite of the COMT V158M and the VDR/TAQ status determines the amount of methyl donors a given individual may tolerate.
    The norm, VDR /Taq—/has been associated with higher levels of dopamine. VDR /Taq +/ + represents changes in the gene typically resulting in reduced dopamine levels. The combinations and permutations of these four SNP variations cover a wide range of dopamine levels and rates of dopamine breakdown. The supplement recommendations for each composite variation take that into account.
    Understanding B12 Support

    Since COMT +/+ mutations slow the activity of the COMT enzyme, this variant slows dopamine metabolic activity, allowing dopamine levels to build. As a result, these higher levels then feed back and inhibit additional dopamine synthesis. For this reason, individuals who are COMT +/+ seem to have a reduced tolerance for methyl donors.
    COMT -/= need to supply methyl groups

    COMT +/+ = less need to supply methyl groups

    So what is the best approach to B12 use for those who are COMT +/+ as compared to those who are COMT-/-? According to published work by Dr. James Neubrander, no toxic doses of B12 have been found, and this medical finding is supported by my clinical experience. Parents report back that “the more B12, the better.” In some cases, elevated doses of B12 (50 milligrams and above) have helped to stimulate speech in formerly apraxic children. However, those who are COMT + often cannot tolerate high doses of any methylating agents. For this reason, I tend to focus more on the use of hydroxylcobalamin B12, dibencozide (adenosyl) B12, and cyanocobalamin B12 for those who are COMT +/+ and to use methylcobalamin B12 along with these other forms of B12 for those who are COMT-/-."

    Freddd says people like us should stop any form of carnitine for a few days till it fades from the system then use a combination of MB12 and ADB12 for example starting on 10 mcg and slowly titrate up to 100 mcg daily.

    Sadly this COMT homozygous mutation only makes things worse but Amy Yasko mentions that people with COMT ++ will have a faster recovery from the damage of B12 deficiency compared to non COMT.
    I haven't found any more positive side effects of having this mutation though...

    Knowing your COMT status is not enough by the way.Do you also have no mutations on VDR? Because it makes things worse.I have none for VDR.
  3. OkRadLakPok

    OkRadLakPok Senior Member

    Hi! It's good to know I am not alone in this. It seems that the MTHFR gets all the attention, but this one can really mess a person up! Good lord, the Dr who told me what to do based on the hetero MTHFR really sent me down a wrong path!!! He did not test the COMT.
    Thank you for the suggestions. I had hydroB12 in my Amazon box, but think will switch to the Ad12.....I also had cartinine, but will take that off.

    I also take Methionine and boost glutathione.....Do you know if those may be helping or hurting? It seems that we are overmethylators and thus have too little homocysteine.

    Honestly, I knew this was bad. I have had trouble for a long long time and I started to exclude foods from my diet as a kid, just out of pain instinct. AND it caused a lot of mood issues. It makes sense that it wacks dopamine, too. And all the time, Drs keep going on about serotonin. If I take Prozac, i go nuts and now I know why.

    It makes no sense to me ever to go to another Dr who does not check my genotype reports first.

    As to the VDR- It seems I am hetero for 2 of those as well as a MTHFR hetero. I am also ++ for a MTRR, too. Have you done the genetics genie to check all the methyl groups? I did it and if you want to exchange panels, we can compare. Did you get genotyped somewhere? I did 23 and Me.

    Here is the genetic genie chart you can make by dropping in your raw data.......

    This is really great. I am homo for three (2 COMTs and 1 MTRR) and hetero for several.
  4. Steve-22


    You need to know other snps before starting supplementing.
    I don't know about being over methylators.I've been reading about it,hope you don't mind if I post it here.


    Elevated serotonin - not true
    Elevated dopamine - true
    Elevated norepinephrine -true
    High religiosity - true
    High artistic/musical ability - true
    Self injury - not true
    Auditory hallucinations - not sure
    Absence of seasonal inhalant allergies - true
    Frequent dry eyes - true
    Multitude of chemical sensitivities - not sure
    Multitude of food sensitivities - not sure
    High anxiety evident to all - true
    Low libido - not true
    Obsessions but not compulsions - not sure
    Paranoia - true
    Underachievement as child - true
    Heavy body hair - TRUE
    Hyperactivity - not sure
    Nervous legs - true
    Grandiosity - TRUE
    Respond well to b12 but avoid SAM-e, inositol, methionine TMG and DMG (1)
    Treatment revolves around folic acid, niacin, B12, and a high protein diet. (2)
    Depression - true
    Despair - true
    Panic attacks - true
    Upper body pain - not sure
    Head pain - not sure
    Nervous - true
    Low salivary - not true
    Low tears - not sure
    High pain tolerance - not sure
    Low motivation - true
    “space cadet” - not sure
    Learning disabilities - true
    Intolerance to SSRI drugs - true
    Low perspiration - true

    Now let's see the under methylation ones:


    Depression - true
    High salivary flow - not sure
    High tear flow - not sure
    Never dry eyes - not true
    Good tolerance of cold - not true
    Poor tolerance of heat - true
    Unexplained nausea - not true
    Hyperactivity - not sure
    Frequent colds and flu - true
    Phobias - true
    Highly motivated - not true
    Hard driving personality - true
    Poor pain tolerance - not sure
    Joint pain - not true
    Joint swelling - not true
    Joint stiffness - true
    Excess perspiration - not true
    Addictive tendencies - true
    bipolar disorder - not sure
    OCD - true
    Schizophrenia - not true
    Insomnia - true
    Muscle pains - true
    Abundant or excess saliva in mouth - true
    Obsessive compulsive - true
    Slenderness -
    Do worse on b12 and folates (4)
    Shopping/gambling disorders - true
    Oppositional –defiant - very true
    Seasonal depression - true
    Inhalant allergies - true
    Frequent headaches, - true
    Perfectionism - TRUE,MY WORST SYMPTOM
    Competitiveness - TRUE
    Asthma - not sure,possibly
    Vasomotor rhinitis - not sure
    Allergic skin disorders - not sure
    Pruritis - TRUE
    Excess stomach acid - not sure
    Fatigue - true
    High libido - true
    Sparse body hair - not sure
    Elevated absolute basophils - not sure
    Extreme internal anxiety despite outwardly calm - true
    Delusion thinking rather than hallucinations - true
    Respond well to SAM-e, methionine, avoid folic acid (1)
    Anorexia/bulimia - not true
    Low serotonin - true
    Low dopamine - not true
    Low norepinephrine - not true
    Psychosis - true
    Prone to hives - not sure
    High motivation - not true

    Are you similar to me? I have no idea about my methylation whether it's under or over.Or maybe I could tell you with the use of simple logic just don't ask me things like this,I blame it on the brain fog.
  5. anon105x


    Hey all, apologies for bringing up an old thread - this subject seems to be important and very related to my quality of life and ability to focus / do tasks, but I don't quite have the comprehension to put all the data on it together into actionable advice. Please, can anyone help? I have the following:

    • COMT V158M rs4680 AA +/+
    • COMT H62H rs4633 TT +/+
    • COMT P199P rs769224 GG -/-
    • VDR Bsm rs1544410 CT +/-
    • VDR Taq rs731236 AG +/-
    • MTHFR A1298C rs1801131 GT +/-
    From my basic understanding of the research I've gone through (First 20 pages of the results on both Google and DuckDuckGo), this means that:

    • A combination of V158M and H62H ++ means high Dopamine, not broken down fast enough.
    • VDR Taq +/- seems to slightly counteract high Dopamine? Clinically observed, but not studied.
    Symptom-wise, I do horrible with warm weather (hate anything over 75, literally makes me nauseous), low motivation, high anxiety, borderline anhedonia (unable to feel much). And now the questions I'm unable to answer despite all this:
    • Does this mean I'm an "over-methylator"?
    • What be done to bring down Dopamine/Nor-epinephrine?
    • What be done to "increase" COMT production/activity? is this even possible?
    Any other input is welcomed. I've been looking at this for years and haven't been able to improve the situation.
  6. alicec

    alicec Senior Member

    There's a thread on COMT that you may find interesting here.

    COMT V158M +/+ definitely results in a slower enzyme. Magnesium is a co-factor for this enzyme. Supplementation may help to stimulate a sluggish enzyme.

    It is a myth that COMT +/+ means you cannot tolerate methyl groups.

    I have this and several other COMT+/+ SNPs and I doubt too that it means that dopamine is necessarily high. I wish I had more dopamine. To me it feels like the negative feedback control is trigger happy and as soon as dopamine starts to rise, it kicks in and switches everything off. Most of the time I feel like I haven't enough dopamine.

    The other two COMT SNPs you list have very little effect.

    In general combinations of COMT SNPs can be more important than single SNPs. Some of these are discussed in the other thread.

    The VDR SNPs have little effect.

    The symptoms you describe are very common in CFS. Possibly COMT may be making a small contribution but it is not the cause.
    Valentijn likes this.

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