Looking for some MTHFR help

[tommyboyo]

Hi all, I have had a few blood results back, hoping to find someone who might be able to help me interpret them.

I’m apoe 3/4, homozygous for MTHFR c677T and I eat a low carb/keto diet. I generally feel fine but never particularly sharp, mentally, also my memory is pretty bad. I certainly don’t get any mental clarity boosts that people fasting/on keto talk about.

Anyway, I’m trying to work out whether I’m methylating properly or not. I have had quite a few general health blood tests (cholesterol is very high, liver function normal etc) but the ones I want to share are:

- Active B12: Very high at 280 pmol/L
- Serum Folate: Normal at 45 nmol/L
- Homocysteine: Normal at 7 µmol/L

I read that with MTHFR you are often B12 deficient, so my result is the opposite of that i.e. no problem, but I read conflicting sources that say if it’s really high it suggests you can’t use it properly, so you do have problems. The homocysteine level is encouraging but does anyone have any views? I can share any other lab results or gene variants if people want.

Grateful for any expert advice!

[TheresaB]

Our wiki has a very good article on methylation. https://wiki.apoe4.info/wiki/Methylation

[Plumster]

Are you taking a B12 supplement and if so, what kind (cyanocobalamin, methylcobalamin, etc) and how much? When you get tested, do you stop taking the vitamin for several days? The most accurate B12 test is methylmalonic acid (MMA). My standard lab test for B12 always comes back as high, even out of range, but when I did mma last year, it showed I was "borderline." Use a sublingual lozenge B12--preferably methyl B12 if you can tolerate it--since we don't always absorb it well in the gut.

[babl]

Hi tommyboyo -- your labs and MTHFR issue look very similar to mine. I'm also homozygous for MTHFR c677T and have been trying out different approaches for the past year. My blood labs have also consistently show my B12 levels as being extremely high (even higher than yours). I recently started going to a Functional Medicine doctor and she's been very helpful in explaining this to me. Essentially, she tells me my B12 levels are high because my body isn't able to utilize it properly, which would go along with my MTHFR issue.

Prior to seeing this new doc, I had been taking one of the B12 supplements from Seeking Health (the "B12 with L-5-MTHF"). I was wondering if this might be why my B12 levels were so high. The form of B12 in that one contains 80% as methylcobalamin and 20% as adenosylcobalamin. My doc suspected that the methylcobalamin might be harder for my body to use, so she had me switch to the "Hydrox-Adeno B12", which has B12 in the form of 50% as hydroxocobalamin and 50% as adenosylcobalamin. I'll be taking another blood test this summer to see if this has helped.

She also discovered that I have a COMT mutation, which might also be affecting my methylation pathway. About 6 weeks ago she put me on a new (to me) supplement -- TMG (trimethylglycine). I have been extremely surprised at how much my mental clarity has improved! It's really very significant. I don't know if this is due to the addition of just this one supplement, or if (more likely) it's a combination of a few different strategies, including the addition of betaine HCL and pepsin to help with digestion of proteins (my blood work showed that I was not digesting proteins very well).

[Josiah]

I also have extremely high B12. Is there such a thing as a MTHFR coach I could hire to help sort out my problem?

[slacker]

I also have extremely high B12. Is there such a thing as a MTHFR coach I could hire to help sort out my problem?

If you haven't checked out the wiki methylation chapter, that would be a good place to start. It's linked 3 posts above yours in this thread. The wiki chapter is full of science, references, and how to. It also links to Chris Masterjohn's work. This could be your virtual MTHFR coach.

[Josiah]

If you haven't checked out the wiki methylation chapter, that would be a good place to start. It's linked 3 posts above yours in this thread. The wiki chapter is full of science, references, and how to. It also links to Chris Masterjohn's work. This could be your virtual MTHFR coach.

I'm struggling as hard as I can to keep up with Recode for which I have a coach. I'm just not up to doing a deep dive into this. MTHFR seems like an ideal subject for which a specialized health coach would work much like the Bredesen coaches.

[tinamalone]

[She also discovered that I have a COMT mutation, which might also be affecting my methylation pathway. About 6 weeks ago she put me on a new (to me) supplement -- TMG (trimethylglycine). I have been extremely surprised at how much my mental clarity has improved! It's really very significant. I don't know if this is due to the addition of just this one supplement, or if (more likely) it's a combination of a few different strategies, including the addition of betaine HCL and pepsin to help with digestion of proteins (my blood work showed that I was not digesting proteins very well).[/quote]

Hi, babl, from a fellow COMT mutant! I am Met/Met. Do you know if you are Met/Met or Val/Val? I also take the TMG. I wanted to let you know that I have been taking the adenosylcobalamin form of B12 from Seeking Health and my B12 came back high also. I chose that form as my COMT (Met/Met) mutation can cause me to get overmethylated using the methyl form. My primary care physician recommended going to every other day. But, I am his first "known" APOE4 and he is learning right along with me. I am grateful he is so willing.

I am compound heterozygous A1298C and C677T MTHFR.

The interplay of APOE4, MTHFR and COMT is interesting and still such a mystery to me.

[mike]

She also discovered that I have a COMT mutation, which might also be affecting my methylation pathway. About 6 weeks ago she put me on a new (to me) supplement -- TMG (trimethylglycine). I have been extremely surprised at how much my mental clarity has improved! It's really very significant. I don't know if this is due to the addition of just this one supplement, or if (more likely) it's a combination of a few different strategies, including the addition of betaine HCL and pepsin to help with digestion of proteins (my blood work showed that I was not digesting proteins very well).

Hi, babl, from a fellow COMT mutant! I am Met/Met. Do you know if you are Met/Met or Val/Val? I also take the TMG. I wanted to let you know that I have been taking the adenosylcobalamin form of B12 from Seeking Health and my B12 came back high also. I chose that form as my COMT (Met/Met) mutation can cause me to get overmethylated using the methyl form. My primary care physician recommended going to every other day. But, I am his first "known" APOE4 and he is learning right along with me. I am grateful he is so willing.

I am compound heterozygous A1298C and C677T MTHFR.

The interplay of APOE4, MTHFR and COMT is interesting and still such a mystery to me.

Tina, I fixed your quote, so babl will get notified...

[babl]

Hi, babl, from a fellow COMT mutant! I am Met/Met. Do you know if you are Met/Met or Val/Val? I also take the TMG. I wanted to let you know that I have been taking the adenosylcobalamin form of B12 from Seeking Health and my B12 came back high also. I chose that form as my COMT (Met/Met) mutation can cause me to get overmethylated using the methyl form. My primary care physician recommended going to every other day. But, I am his first "known" APOE4 and he is learning right along with me. I am grateful he is so willing.

I am compound heterozygous A1298C and C677T MTHFR.

Hi Tina,
So true - it IS fascinating how all of these factors are at play in so many different ways! I just checked my reports to see what COMT I am. The Met/Met or Val/Val terminology is not familiar to me, but I think I found something to explain it. I was surprised to find that I'm actually -/- (Val/Val?) for all of the COMT genes. My doc had me do the Dutch Test which showed that the COMT link in my methylation cycle was not doing it's job very well. She suggested taking supplemental B6 as well as the TMG to give it some support. The test also showed that I was not digesting proteins very well despite my diet being pretty high in protein, so she also has me taking some digestive enzymes and betaine HCL with pepsin with every protein meal I eat. The only other thing she's targeting for me right now is the high cortisol levels the test showed, so for that she added in L-theanine and GABA. I've been taking these new supplements for about 6 weeks now and I'm so pleased with how much better I'm feeling, particularly my mental clarity.

As for MTHFR, I'm homozygous for the c677T one.