6 replies to this topic

[jwwilliams002]

Hi everyone, 

 

 I wanted to see if anyone knew about a good supplement regimen for someone with homozygous MTHFR C667T mutation and a COMT ++ mutation.   My symptoms have been pretty consistently horrid over the years including lots of depression, anxiety and panic as well as really crippling brain fog.  

 

The problem is that many of the things that help my depression will cause an increase in anxiety and things that help anxiety don't help the depression and slow me down even more.  Supplements for methylation I have tried such as methylb12, methylfolate , TMG all caused a huge spike in anxiety.  SAMe caused panic attacks but also blasted me off into some pretty serious mania followed by a crash to depression.  

 

Currently I am on 20 mg of Brintellix and the addition of this has lowered my baseline anxiety enough to allow me to try some things that help my mood that used to cause intolerable anxiety but now its not as bad.  

 

From what I have read the COMT ++ mutation will cause slowed degradation of dopamine which in turn either downregulates the receptors or acts as a negative feedback lowering PFC dopamine as the final result.   My subjective feelings of zero drive, low libido, brain fog and inability to concentrate seem to get somewhat better if I take a stimulant or tyrosine.  Other things that have helped are suniferam and pheynlpiracetam.  I feel that none of these are very long term solutions and will just further impair dopamine levels through negative feedback.   

 

I would greatly appreciate any advice or ideas on how to move forward with treating this.  

[nicklesprout]

just because you have the mutations doesn't necessarily mean you are under-methylating, from what i've read. i have the homozygous c677T mutation as well, but methylfolate/methyl b12 does nothing for me. you can take a methylation profile test to determine your SAM/SAH ratio to see what your methylation status is, but that is kind of pricey i think. 

[world33]

Hi,
 
Did you plug your 23andme.com results into nutrahacker.com (Basic report is free)? I have exactly the same mutations and I find hydroxycobalamin injections very helpful which is reccommended for rs4633 TT, rs4646312 TT, rs4680 AA. methylb12 is not reccomended for COMT++ mutations. I get a crash effect a couple of hours after taking methylb12, similar to a coffee crash. If you do not like the idea to try injections, which is the ultimate way to absorb B12, you can try Perque Activated Hydroxycobalamin B-12 Guard 100 Lozenges. The closest thing to injections according to some.
Check also if you have any CBS mutation. SAMe for example is not reccommended when you have that mutation. I find Molybdenum very helpful for the CBS mutation (rs1801181 AA).
In a nutshell try to stop methylb12 and switch to hydroxycobalamin injections (once a week, their half life is several days), address the CBS issue if any and then, only then, start methylfolate. If you take too much  methylfolate take some niacin (Vitamin B3) to limit the side effects.
In the nutrahacker report focus on Homozygous mutations with a low genotype frequencies (below 20/30%). It would not make sense that a mutation with a genotype frequency of 50% could affect negatively half the population. The MTHFR C667T Homozygous mutation affects only around 7% of the population, some COMT and CBS mutations are below 20%.
Lastly check if you are intolerant to certain food that trigger inflammation in your gut and/or brain. I eliminated wheat and dairy products and feel much better. Curcumin and quercetin are anti inflammatory.
Another thread on the C667T mutation is here http://www.longecity...th-mthfr-c677t/

Edited by world33, 15 October 2015 - 10:31 AM.

[jwwilliams002]

Thanks for this response World , 

 

I plugged my genetic data into "genetic genie" bc it was free and got a methylation report there.  I am hetero for the CBS mutation, so I am not sure how much that will effect things.  I am looking into the hydroxy b12 right now.  Can you tell me the difference you felt between the methyl b12 versus the hydroxy?   Did you get any anxiety with the hydroxy? 

[PeaceAndProsperity]

As I explained in the other thread (the MAO-A enzyme mutation thread), it's a common mutation, there's nothing to worry about.

These mutations are all common and hardly have any significance in of themselves.

Check the frequency of the mutations before you jump to any conclusions.

 

I've personally tried methyl B12 and tetrahydrofolate and none of them had any effect whatsoever, and I have the same mutations (but no anxiety or depression).

 

If you want to seriously mess with genes for fixing your problems, get a FULL genome sequence done on you from fullgenomics.com (or whatever the site is) or another site altogether. 23andme provides too little data to be useful for the money it costs.

[world33]

As I explained in the other thread (the MAO-A enzyme mutation thread), it's a common mutation, there's nothing to worry about.
These mutations are all common and hardly have any significance in of themselves.
Check the frequency of the mutations before you jump to any conclusions.
 
I've personally tried methyl B12 and tetrahydrofolate and none of them had any effect whatsoever, and I have the same mutations (but no anxiety or depression).
 
If you want to seriously mess with genes for fixing your problems, get a FULL genome sequence done on you from fullgenomics.com (or whatever the site is) or another site altogether. 23andme provides too little data to be useful for the money it costs.

 

I wish I could say the same RatherBeUnknown. The MTHFR C667T homozygous genotype frequency is about 7/10% (depending on the source) so it is not as common as you think. The CBS rs1801181 homozygous genotype frequency is about 7% as well. For me methylfolate is a life changer and I need a relatively high dosage on a daily basis to function normally. Some other people in this forum need only a limited amount thought. Everyone is different and possibly in some people genetic mutations are not expressed to a full extent or there are other genes that counteract mutations and deficiencies.
For this reason jwwilliams002 I suggest you to personally try and compare methyl b12 versus the hydroxy version because what could be better for me it could not be better for you.
You do not need a full genome sequence to understand some common methyliation issues that 23andme can provide you for 99 dollars and interpret through third party services. Nutrahacker has also a free basic version after answering a brief survey.

[Cube]

Very old post i know! I'm also homozygous for mthfr c667t and met/met comt. Have you guys come across any new info?. I'm finding it difficult to workout a good supp protocol. Most info only points to mthfr or comt. Anything worked wonders for you?. Cheers