COMT++

[OkRadLakPok]

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

 

[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.

 

[OkRadLakPok]

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 NAC.......to 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.......

http://geneticgenie.org/methylation-analysis/

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

 

[Steve-22]

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 NAC.......to 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.......

http://geneticgenie.org/methylation-analysis/

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

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.

OVER METHYLATORS

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:

UNDER METHYLATORS

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.

 

[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.

 

[alicec]

Any other input is welcomed

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.

 

[npeden]

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.

 

[npeden]

Hi, after a long while.

I won't go into more than the COMT++ V158/H62H. And I hope this helps someone.

I have struggled with these SNPs a long while and have worked in epigenetics mentoring 46k online. I finally had 3 breakthroughs.

1. My oncologist who is also MTHFR but knows up until now, Medicare/Medicaid would not cover genetic issues even as I showed her evidence that my ovarian cancer could be related to COMT++ which are estrogen "driven" a better word failing me SO she trying to help me be insured and helped labeled me with homocystinuria. There is another similar disorder.

What we were after was my "bouncing" homocysteine which is in one of the diagnoses. And I was on most of the supps: b6, b12 NOT methyl and NATURAL folate so she agreed that I knew as much if not more than most hematologists.

2. Also, recognize that HOMOCYSTEINE LEVELS are now clearly recognized as causative in psychiatric disorders. I finally found a psych who now understands I am not crazy. https://www.google.com/search?q=nih...3i10i160l2.22415j0j7&sourceid=chrome&ie=UTF-8

3. THIS is my GOLDEN FIND. I found via Ben Lynch and Seeking Health Hydroxo b12 (it has a bit of cobalamin; I can handle some methyls) with FOLINIC ACID which I do not know about but BAM...for 6 months my homocysteine has tested twice at a lovely 8 in a range of 1-12.

I hope all understand that methylation and homocysteine work inversely: LOW homocysteine, dangerous for folate related cancers, would be in the below 5 range as well as create HYPERMETHYLATION.

Conversely HIGH homocysteine can lead to panic attacks and atherosclerosis and LOW methylation. For panic attacks probably caused by HYPERmethylation, I take high dose Niacin BUT the catch is that B3 RAISES HOMOCYSTEINE. It DOES stop my obsessiveness and panic and it may make you itch all over.

The blood tests needed are homocysteine which measures that AND MMA (Methylmalonic Acid) which measures folate to b12 levels/ratios. I use Quest diagnostics and they include both in one test and also have good online write-ups.

Most of all I suggest anyone who is METHYL sensitive as in COMT++ try Seeking Health Hydroxo B12 and Folinic Acid. It has changed my life.

I am not a certified anything. I do have MTHFRc677t, COMT++, and MAO-A. MEDITATION IS ESSENTIAL as COMT and MAO-A are called by some "placebo" SNPs which are often helped by "warm and fuzzy" situations. We know DNA is fluid and environmentally dependent. This is all epigenetic. Get love and comfort as best you are able.

My doctoral work was in Transformative Learning and Change and I love learning in communities like Phoenix. Stay well and I hope this helps someone and is not redundant. .