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Please Comment on my Methylation Profile

Messages
11
Hi All,

I have only posted once here, regarding what I thought was a strange methylation experience. In summary, I had a great reaction (lots of energy, metter mood, more confidence ) to a Coenzymated B Complex (though later I noticed that it did contain some Folic Acid). I increased the dose and added Mb12, Adb12 and LCF and in a few weeks had next to no energy.

Well I have finally got my 23andme snps back and they perhaps, at least partially answer the above experience.

Methylation Profile.jpg


I only have a very basic grasp of what is going on here. But I seem not to have much of an issue metabolising Folic Acid and B12 (although I am hetro for MTHFR A1298C). My main concern is CBS and BHMT conspiring against me. I guess when I increased Metafolin and MB12 I was converting more and more Homocysteine into cystathionine down the trans-sulfurtion pathway? In doing so creating more Ammonia and perhaps depleting BH4.

COMT doesn't look good. It again I think conspires against me along with MAO. This might help to explain my persistent mood issues. COMT in isolation would suggest high Dopamine as it is involved with the breakdown of this neurotransmitter amongst others. However, I have extremely low drive and motivation, this would suggest low Dopamine. I guess the ammonia created by my CBS +/- snp is using up BH4 so I am perhaps not making enough Dopamine in the first place (i.e. COMT doesn't have enough Dopamine to break down even if it wasn't mutated!).

I believe I should tackle the CBS mutation first. I am confused here as I don't seem to have a problem with sulfur, I'm ok with onions, garlic and NAC. I feel good on taurine, I do well on B6 and P-5-P. The only thing I didn't seem to react well to MSM.

Anyway, I might have all this wrong and I would appreciate someone with more knowledge and a clearer brain to have a look and make comment.

Many thanks in advance for any help you can provide.
 

TheChosenOne

Senior Member
Messages
209
VDR Taq also contributes to dopamine. So a mutation there lowers dopamine.
I have COMT +/+ like you with VDR Taq +/+, which should cancel each other out to some extend. The problem is that I'm very anxious from time to time which suggests high dopamine.
CBS +/- shouldn't be a problem. There are a number of posts on this forum that state that CBS mutations are overrated.
Low motivation can be part of mood swings, hence high dopamine.
You might wanna try phosphatidylcholine/serine to fix the BHMT shortcut.
If you are anxious or have mood swings, you can try niacinamide (B3).
Always start with low doses, since you have COMT +/+ so have to be careful with methyl donors.
 

Sherpa

Ex-workaholic adrenaline junkie
Messages
699
Location
USA
You don't have any genetic defects on this report associated with B12 deficiency and folate. You may not need to supplement it.

The main ones you might want to treat are MAO A and COMT.

The only one I have experience treating is MAO A R297R. This requires a working thyroid and B2. I had a low thyroid & a B2 deficiency and needed to correct those to feel much better.
 
Messages
11
Thanks you all very much for your replies. Thanks for putting my mind at rest regarding CBS.

@JaimeS - I had a quick look at your blog JaimeS and had to close it down for more careful read tonight (it looks like a serious piece of work).


@TheChosenOne - I now understand why I am sensitve to methyl donors (COMT +/+), however, I react well to TMG which I believe is one of the most powerful donors, but I guess that is helping overcome my BHMT limitations? Interesting that phosphatidylcholine/serine fixes the BHMT, I have some NT factor on order so I will carefully monitor the results.

I am much more relaxed after taking some B3 (mostly Niacin or Nicotinic Acid), I guess this suggests over-methylation?

@Sherpa - Interesting about your experience with MAO A R297R. I have slightly low thyroid, it has always intrgued me that I do well on Iodine, Selenium and Tyrosine (all needed in the manufacture of thyroid hormones I believe). I also fin the B2 reference interesting. When I had the postive experience with the active B Complex, it wore off over a few weeks when I increased my MFolate and Mb12. I then considered what else in the supplement caused the effect and my conclusion was B2. It is a supplement that I have neglected in the past and have many of the B2 deficiency symptoms.

I have a hard time figuring out if I am low or high in Dopamine. I mostly have low Dopamine symptoms of low motivation, drive, etc. But I am anxious which lties in the high Dopamine. As you can see my gene mutations provide arguements for boh low and high.

Thanks again for your help.
 

TheChosenOne

Senior Member
Messages
209
@TheChosenOne - I now understand why I am sensitve to methyl donors (COMT +/+), however, I react well to TMG which I believe is one of the most powerful donors, but I guess that is helping overcome my BHMT limitations? Interesting that phosphatidylcholine/serine fixes the BHMT, I have some NT factor on order so I will carefully monitor the results.
That's correct. TMG also assists with liver detoxification. Most people on this forum have slow liver phase 2. I haven't tried TMG myself yet, so I have no idea how it improves things. I'd suggest to keep using it if it benefits you.

I am much more relaxed after taking some B3 (mostly Niacin or Nicotinic Acid), I guess this suggests over-methylation?
Yes. The problem is that B3 slows down methylation. This might not be a problem for you.

Edit: Some people argue that you should take DMG to counter the shortcut in favor of the full methylation cycle. Can someone confirm this?
 
Last edited:

MAF14

Senior Member
Messages
195
Thanks you all very much for your replies. Thanks for putting my mind at rest regarding CBS.

@JaimeS - I had a quick look at your blog JaimeS and had to close it down for more careful read tonight (it looks like a serious piece of work).


@TheChosenOne - I now understand why I am sensitve to methyl donors (COMT +/+), however, I react well to TMG which I believe is one of the most powerful donors, but I guess that is helping overcome my BHMT limitations? Interesting that phosphatidylcholine/serine fixes the BHMT, I have some NT factor on order so I will carefully monitor the results.

I am much more relaxed after taking some B3 (mostly Niacin or Nicotinic Acid), I guess this suggests over-methylation?

@Sherpa - Interesting about your experience with MAO A R297R. I have slightly low thyroid, it has always intrgued me that I do well on Iodine, Selenium and Tyrosine (all needed in the manufacture of thyroid hormones I believe). I also fin the B2 reference interesting. When I had the postive experience with the active B Complex, it wore off over a few weeks when I increased my MFolate and Mb12. I then considered what else in the supplement caused the effect and my conclusion was B2. It is a supplement that I have neglected in the past and have many of the B2 deficiency symptoms.

I have a hard time figuring out if I am low or high in Dopamine. I mostly have low Dopamine symptoms of low motivation, drive, etc. But I am anxious which lties in the high Dopamine. As you can see my gene mutations provide arguements for boh low and high.

Thanks again for your help.

What do you mean by sensitive to methyldonors? What side effects do you experience if any?
 
Messages
11
After a week or so of feeling more energetic, happier and clear headed I started to lose that feeling. It was replaced with low energy and even lower mood.
Now things have settled down a bit, I can reflect and say that Metafolin and Mb12 make me uncomfortably edgy and tense. Going forward my strategy is to go with hydroxy12 and Adb12 as my main sources of B12 and a 'start low go slow' philosophy for B9.
 
Messages
7
Wow, you have the same homozygous mutations I have, except I also have MTRR A66G. I just ordered some hydroxyB12 because after adding methylB12, I have been having the worst mood swings and anxiety today. I'm also going to try folinic acid instead of methylfolate to see if that cuts down on overmethylation while I try to increase.
 
Messages
11
Wow, you have the same homozygous mutations I have, except I also have MTRR A66G. I just ordered some hydroxyB12 because after adding methylB12, I have been having the worst mood swings and anxiety today. I'm also going to try folinic acid instead of methylfolate to see if that cuts down on overmethylation while I try to increase.

Hi dulcinea,
It would be worth updating each other on progress given our similar snps. I am going on holiday shortly (sadly bringing lots of methylation reading with me!) so I might not be able to post for a week or so, but after that I will update my experiences as I appreciate others doing so. I am currently grappling with the question "Is my anxiety due to overmethylation or undermethylation with COMT/MAO/VDR snps?". I'm actually leaning towards overmethylation. I'm not sure if this can be tested for, homocysteine could be a guide, but my CBS mutation could skew that.
More reading I think!
 
Messages
1
Hey guys I have been told that red and purple colored fruits/veggies are metabolized via COMT and I am trying to free up as much COMT as I can since I have double homozygous COMT mutations and I'm sensitive to all methyl donors. I actually don't have red or purple in my normal diet but there is lots of cinnamon. Anyone know if cinnamon counts for red in this instance? or is it brown? I can't tell!! lol any input is much appreciated :)