methylation problems: M12 and A12 not working?

[Hindi1989]

So I ran my DNA test results using nutrahacker and genetic genie, and as I suspected, it showed ++ for MTR A2756G, MTRR A66G. It also shows that I'm ++ for SOD2 and CYP1A2, and BHMT-02, and few other +- snps.

I'm not sure about the others but MTR and MTRR would indicate lack of m12 correct? My blood tests also show significantly higher levels of homocysteine. So i went ahead and took 4 mg Enzymatic Therapy m12 and around 2mg of Country Life Dibencozide a12. I also took some Metafolin maybe 400mcg. Well, nothing happened. Quite disappointed as I was hoping it would help me with some mental clarity and maybe even give me some energy. I just don't understand why it didn't work. Am i missing something? is there any other deficiencies that I need to look into?
I placed them both under my upper lip for as long as possible (maybe 20-40 mins).

FYI, I'm also taking 1.5mg of NAG which helps with brain Fog.

 

[Eastman]

@Hindi1989

Have you seen any progress since your post?

If you follow Freddd's methylation protocol, you would know that he considers adenosylcobalamin and carnitine as very important too, but there are plenty of other cofactors that may also need supplementing.

You would need either lab tests or a closer look at symptoms to narrow down the list of additional supplements that might be needed.

 

[Learner1]

Eastman's advice to do lab testing is excellent. You have lots of genes and environmental factors that could muddle the picture. Labs and symptoms tell you where you are and provide guidance on where you need to go.

 

[Hindi1989]

Thanks for the replies @Learner1 and @Eastman

Lab testing isn't always easy as I live in a developing country and if the tests are available it's rather expensive and generally insurance doesn't cover many of theses tests. I also don't have the money or ability to try as many supplements as possible though I'm sure there are some supplements that will help me. NAG has had a noticeable effect in terms of reducing brain fog but there is still long way to go.

A lot of my symptoms are quite fitting inefficient methylation so I'm quite confident that my situation will improve if I can figure why these two, A12 and M12 aren't working.

What are the necessary factors in b12 functioning? And what could prevent b12 from being effective? What are the most likely supplements that could address this?

I would love @Freddd or anyone else who has experience in methylation to pitch in, it would be great! Thanks

 

[Learner1]

Freddd has a very unique set of genes, so following his approach may very well backfire on you.

Work backwards.

You need to have elimination working well. Happy microbiome, lots of fiber and water. Then, you need adequate B1 and molybdenum to make transsulfuration work.

Then, ensure you have adequate B6 and aminos, particularly glycine, glutamine and NAC to make glutathione.

Then, you add B12. Most people and I share your SNPs do fine with MB12. Maybe AB12. Not cyanocobalamin. You also need will need sufficient magnesium, potassium, b2 and B6..these all get the methionine cycle going. Maybe some TMG or methionine.

Then you add 5-MTHF and or folinic acid.

If you start in reverse adding folate and B12 first, you may mobilize some toxin that you can't get rid of since you didn't start with getting glutathione and elimination giing, and you will have bad symptoms and think methylation doesn't work.

So, if you start doing this and have nasty symptoms, headache, mood swings, intestinal discomfort, liver or kidney pain its because your methylation protocol isn't customized to your genes and level of toxicity.

That is why I recommend testing. Its a lot better than guessing or copying from someone who is not you. But, if you are patient and systematic, it can be done. The key is figuring out the right ratios of the various co factors then ramping up.the level.

 

[Hindi1989]

Thanks for the replies guys.

My question remains unanswered: why is M12 and A12 totally ineffective? Are there conditions and lack of supplements which will render them totally ineffective? I eat a healthy diet and the blood tests which I have done don't show any deficiencies. What could be the reason that even 8mg M12 makes no noticeable difference? I have take most of the supplements that @Learner1 has recommended so I don't know why it's not working. I have not tested for the V.Bs except b9 and 12 which were normal though I had very high homocysteine. I am clearly lacking b12 as indicated by the snps but taking M12 isn't changing anything.

Here are some of the persistent symptoms which are b12 or b9 related - 1) I can't stand erect without waving like a plant on was wavy day, terrible brain fog, tinnitus, sleep issues, lack of dreams, bump into things, mouth sores, blurry vision at times, cold hands and feet as many people have mentioned it got better on methylation. Any many more.

Also, please note that I cannot do much in terms of testing or experimenting with many supplements as I just don't have the money or its not available in my country. If we can hone in on something particular I can definitely try it.

Thanks alot,

 

[Busson]

I'm not sure about the others but MTR and MTRR would indicate lack of m12 correct? My blood tests also show significantly higher levels of homocysteine.

So i went ahead and took 4 mg Enzymatic Therapy m12 and around 2mg of Country Life Dibencozide a12. I also took some Metafolin maybe 400mcg

@Hindi1989 MTR/MTRR defects might mean the methionine synthase reaction is impaired. MS recieves methyl groups from the folate cycle and, with the help of mB12, passes them to the methionine cycle where they reduce homocysteine by converting it into methionine. You can best see this by Googling for a diagram.

Perhaps consider lots more folate. The dibencozide B12 does not have a role in this part of the system. You may want to look into something called the "methyl trap" which might cause resistance to mB12 and folate unless high doses are used which may answer your question.

There are various approaches to reduce homocysteine and fixing possible mB12/folate problems is just one. Others find TMG can help by bypassing the MS reaction.

On the other hand, some people with a problem in a pathway called the "transulfuration" take vitamin B6 and might add zinc to reduce raised homocysteine.

Your raised homocysteine is telling and if it gives clincially significant symptoms then perhaps you might want to explore homocystinuria/homocysteinemia with a doctor.