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What is your understanding of the methylation cycle trap or blockage?

Pyrrhus

Senior Member
Messages
4,172
Location
U.S., Earth
I have no idea, but if someone can explain this, like you would explain to a child, I'd be grateful:
https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-020-00960-z

That paper is discussed here:
https://forums.phoenixrising.me/thr...emic-dysfunctions-helliwell-et-al-2020.81953/

It talks about possible epigenetic changes in blood cells:
Epigenetics:
The field of epigenetics looks at types of modifications that a cell makes to its DNA, without changing the coding for genes. Such modifications may increase the translation of certain genes or may inhibit the translations of certain genes, changing the programming of a cell. One of these types of modifications is called DNA methylation.

DNA Methylation:
The chemical process of methylation simply refers to the addition of a "methyl group" to a given molecule, such as DNA. A "methyl group" contains one carbon atom and three hydrogen atoms. In the methylation of DNA, a methyl group is added to a specific location on the DNA, which generally inhibits the translation of that section of DNA into RNA. When a gene's translation is inhibited, there will be fewer copies of that gene's RNA found in the cell.

While it is theoretically possible that a low blood concentration of the main methyl donor S-Adenosyl-Methionine (AdoMet or SAMe) will lead to reduced DNA methylation, widespread reduced DNA methylation was not noted in the paper you mention.

Hope this helps.
 

Methyl90

Senior Member
Messages
274
Insisting on vitamin B12 won't free you from the folate trap. Only large doses of methylfolate can do this, better sublingually or injected because oral absorption is very poor. (I'm doing various experiments but still can't figure out the half-life if done injected or sublingually.)
 
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29
Stumbled acrossed this thread ... Isn’t the only way to free yourself from methyl trap taking more b12? Since that is the factor that has ended?
 
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29
Well, I take 6000 mcg folate and 5000 mcg mb12. When I try to increase folate to 7000 I hit a wall (old me/cfs symptoms returning fast and hard). The only thing that relieves it is taking 1000 mcg more b12. The ”methyl trap” disappears while I’m holding the sublingual in my mouth.

That must be a true methyl trap situation that TMG can’t resolve?

Freddd always stated that more b12 didn’t increase the need for more folate but in my case taking more b12 always increase the need for more folate immediately.
 

Pyrrhus

Senior Member
Messages
4,172
Location
U.S., Earth
Well, I take 6000 mcg folate and 5000 mcg mb12. When I try to increase folate to 7000 I hit a wall (old me/cfs symptoms returning fast and hard).

Many people here on Phoenix Rising have reported very strange, very negative reactions from megadoses of folate. (doses much higher than the standard 400mcg per day)

Since I don't know of any research on such megadoses of folate, I personally would be wary of such mega-doses.

Although mega-doses of B vitamins are generally seen to be harmless, as the body easily excretes the excess vitamins, there may well be exceptions.

I hope this helps.
 
Messages
29
Thanks for input. Well, I started at 200 mcg folate but reach folate deficency (the donut folate theory) almost immediately. So I titrate all the way up. I would love to take less folate but the deficency symptoms hit.
 

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
Well, I take 6000 mcg folate and 5000 mcg mb12. When I try to increase folate to 7000 I hit a wall (old me/cfs symptoms returning fast and hard). The only thing that relieves it is taking 1000 mcg more b12. The ”methyl trap” disappears while I’m holding the sublingual in my mouth.

That must be a true methyl trap situation that TMG can’t resolve?

Freddd always stated that more b12 didn’t increase the need for more folate but in my case taking more b12 always increase the need for more folate immediately.
Folate does not act in a vacuum - for the benefits of the folate cycle to be realized, other nutrients are necessary beyond vitamin B12, including minerals like magnesium, potassium, zinc, and molybdenum, other B vitamins like B1, B2, and B6, and aminos like Sistine, glutamine, and glycine. Have you done testing to ensure that you have all of these so that you can use your folate? 🤔
 

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
Thanks for input. Well, I started at 200 mcg folate but reach folate deficency (the donut folate theory) almost immediately. So I titrate all the way up. I would love to take less folate but the deficency symptoms hit.
Because you probably ran out of some necessary cofactor... Think of making an angel food cake that requires 12 eggs, flour, sugar, etc. And you add the flour and sugar, But only have five eggs... How do you think the cake's going to turn out?
 
Messages
29
Learner1: If I add more folate I get out of the donut hole and symptoms improve within an hour. That makes me think that it’s the folate that was missing. But of course, could be a cofactor too.
 
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29
Learner1: Here are my gene testing:
COMT V158M rs4680 GG -/-
COMT H62H rs4633 CC -/-
COMT P199P rs769224 GG -/-
VDR Bsm rs1544410 CC -/-
VDR Taq rs731236 AA +/+
MAO-A R297R rs6323 GT +/-

ACAT1-02 rs3741049 GG -/-
MTHFR C677T rs1801133 AG +/-
MTHFR 03 P39P rs2066470 GG -/-
MTHFR A1298C rs1801131 GT +/-
MTR A2756G rs1805087 AA -/-
MTRR A66G rs1801394 AG +/-
MTRR H595Y rs10380 __ no call
MTRR K350A rs162036 AA -/-
MTRR R415T rs2287780 __ no call
MTRR A664A rs1802059 AG +/-
BHMT-02 rs567754 CT +/-

BHMT-04 rs617219 __ no call
BHMT-08 rs651852 CT +/-
AHCY-01 rs819147 TT -/-
AHCY-02 rs819134 __ no call
AHCY-19 rs819171 TT -/-
CBS C699T rs234706 GG -/-
CBS A360A rs1801181 GG -/-
CBS N212N rs2298758 __ no call
SHMT1 C1420T rs1979277 __ no call
 
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11
My experience with a partial methylation block I found really intriguing. I had been taking sublingual methylcobalamin for months or even a couple of years.

I then slowly added Methylfolate. When I reached 6.4 mg of methylfolate a day, it felt like somebody flipped a switch and turned my body on.

My energy was much, much higher and I could think clearer. I really thought I had found the cause of my ME/CFS. Unfortunately this slowly faded over several weeks.

I think I was still getting benefits but they weren't anywhere near what they were when what I assume was a partial methylation block, opened up. I still take Methylcobalamin and Methylfolate now, because it does help some with energy, detoxification and other things.

I think I may have a methylation block -happened accidentally while doing the ElementalDiet. Do you know how to reverse it?
 

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
I think I may have a methylation block -happened accidentally while doing the ElementalDiet. Do you know how to reverse it?

I took 25-50 mcgs of methylfolate every 3 days and slowly worked up to 6.4 mg a day. I was already taking methycobalamin, so I didn't need to add that in.

It's my understanding that both methycobalamin and methylfolate work together, so it's important to take both to open up the methylation cycle. There are other co-factors that are needed as well, but I'm less familiar with what they are.

I was already taking a good multivitamin and many other supplements, so I had the co-factors covered.

The reason I took the methyfolate every 3 days was because I couldn't tolerate taking even 25 mcgs a day. As I said in my post you quoted, when I reached 6.4 mg a day of methylfolate, my methylation cycle opened up.
 
Messages
11
I took 25-50 mcgs of methylfolate every 3 days and slowly worked up to 6.4 mg a day. I was already taking methycobalamin, so I didn't need to add that in.

It's my understanding that both methycobalamin and methylfolate work together, so it's important to take both to open up the methylation cycle. There are other co-factors that are needed as well, but I'm less familiar with what they are.

I was already taking a good multivitamin and many other supplements, so I had the co-factors covered.

The reason I took the methyfolate every 3 days was because I couldn't tolerate taking even 25 mcgs a day. As I said in my post you quoted, when I reached 6.4 mg a day of methylfolate, my methylation cycle opened up.

Gotcha. Thank you for the reply.
 
Messages
11
I took 25-50 mcgs of methylfolate every 3 days and slowly worked up to 6.4 mg a day. I was already taking methycobalamin, so I didn't need to add that in.

It's my understanding that both methycobalamin and methylfolate work together, so it's important to take both to open up the methylation cycle. There are other co-factors that are needed as well, but I'm less familiar with what they are.

I was already taking a good multivitamin and many other supplements, so I had the co-factors covered.

The reason I took the methyfolate every 3 days was because I couldn't tolerate taking even 25 mcgs a day. As I said in my post you quoted, when I reached 6.4 mg a day of methylfolate, my methylation cycle opened up.
One more thing. I was only taking 50mcg of mfolate and 10mcg of mb12 in a diet shake for 2 weeks. Could this have possibly put me in a trap?