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August 6, 2012 at 4:32 pm #3063
I am so confused with all the conflicting info. on what to take with MTHFR mutations. I’ve read to take folic acid, not to take folic acid, to take methylfolate, to take b12, not to take b12, to take methylated b 12 (which I can’t find), so I am very confused. What is methyl trapping? What are the symptoms of it and why is it such a bad thing?
thank you!August 17, 2012 at 9:36 pm #3187
I started looking for Dr. Ben’s explanation of methyl trapping when you first posted, but I didn’t find it right away. And then there was a wildfire near my house, and I was evacuated for one night, but fortunately the fire stayed 600 ft. away from my house thanks to a firebreak. But that was a wake-up call that I needed to get off the computer and get some outside stuff done, so I’ve just recently gotten back to this forum. Hope you see this.
Dr. Ben explained methyl trapping in a September 19, 2011 comment to Jill at http://mthfr.net/mthfr-mutations-help-wanted/2011/09/09/. Here is his comment:
Your comment inspired me to dig further and I believe I found the connection – or at least one of them – or more than one:
Methyl trapping does not occur if one takes – and absorbs – both folate and vitamin B12. Methyl trapping happens when people take folic acid only and not the active form of vitamin B12 (methylcobalamin).
What happens in methyl trapping is a methyl group (CH3) is moved from 5-MTHF to vitamin B12 via an enzymatic process called methionine synthetase.
The issue is the enzyme methionine synthetase requires vitamin B12 (cobalamin) in order to function.
If methionine synthetase doesn’t have adequate vitamin B12 to function, the methyl groups created by 5-MTHF do not create methylcobalamin.
If cobalamin cannot accept the methyl group from 5-MTHF, 5-MTHF accumulates, is trapped and THF doesn’t get regenerated.
What is supposed to happen is methylcobalamin donates its methyl group to homocysteine to convert homocysteine to methionine – a major requirement for methylation. Thus, the methyl group found on 5-MTHF is no longer trapped as it has been given to methionine.
(Only thing else required for methionine to assist with methylation is the addition of ATP and magnesium.)
What is THF used for?
THF helps make purines and to process histidine.
High levels of histidine have the ability to create high levels of …histamine.
Histidine, without THF, doesn’t break down to FIGLU.
FIGLU is then further broken down into what is a problem for those with bipolar: Glutamate.
So, having said all this, you can understand what happens if you take high levels of active 5-MTHF and methylcobalamin:
You will process histidine more effectively thereby lowering your histamine levels. This is excellent.
The problem is you will suddenly begin processing histidine very effectively thereby increasing your levels of glutamate.
Glutamate is often elevated in those with bipolar.
This begs the question then – what breaks down glutamate?
The glutamate dehydrogenase enzyme breaks down glutamate.
What is required for the glutamate dehydrogenase enzyme to process glutamate?
Niacin enables the glutamate dehydrogenase to process glutamate.
My opinion here is many of those with histadelia have MTHFR mutations – or at least I believe those with MTHFR mutations is what is contributing to histadelia.
Why do I think that?
Because those with histadelia have high levels of folate. I bet those with histadelia also have high levels of histidine.
High levels of folate occur because folate is unable to proceed through the MTHFR enzyme and become methylated to 5-MTHF.
If something is unable to be processed, it builds up in the body. This shows up on the lab testing as ‘elevated folate’.
What they should be testing are levels of 5-MTHF.
I bet the levels of 5-MTHF are low.
Because if folate becomes methylated and lead to 5-MTHF, the methyl group gets donated to homocysteine changing it to methionine (in the presence of B12).
If methionine is formed, then S-Adenosyl methionine can be made from methionine and ATP via the methionine adenosyltransferase enzyme.
In order for the methionine adenosyltransferase enzyme to work, ATP and magnesium are required. If magnesium is deficient, then the reaction does not move forward.
What is S-Adenosyl methionine?
Remember what I said above:
Histidine break down requires THF which comes indirectly from folic acid via the synthesis of methionine.
That said, if folic acid is able to get ‘through’ the MTHFR defect, not only will homocysteine levels drop, but so will histidine levels.
If histidine levels drop, histamine levels should drop also.
But…histidine converts to glutamate.
But you now know that glutamate is broken down by an enzyme using niacin.
That is a pretty crucial step and nutrient for those with bipolar.
Will SAMe lower your homocysteine levels without making you manic?
One study showed SAMe induced mania in a patient
I can see this happening because a methyl group from SAMe will be donated to folic acid and bypass the MTHFR cycle perhaps and also increase levels of glutamate from histidine.
If those with bipolar take niacin (vitamin B3) along with 5-MTHF, B12, TMG and B6, will the mania not occur?
Biochemistry shows this possible. Is it clinically? According to those who practice functional and orthomolecular medicine – yes.
I think if the authors knew about MTHFR, they would have a real solid paper.
On another note:
You are absolutely right that those who are toxic (and we all are) and begin taking nutrients which increase methylation are susceptible to detox reactions.
This is why I suggest people to order the methylation profile to see what it is looking like – along with a full history by your doctor. Start slowly and work up.
If there is any block in the methylation process or detoxification pathways, the detox reactions will occur.
Dr BenAugust 17, 2012 at 9:37 pm #3188
Methylated B12 is methylcobalamin, which should be taken in a sublingual form.August 17, 2012 at 9:46 pm #3189
I’m new too, Emily and have making myself nuts reading and listening to tapes, etc. It is very very confusing (and I am a nurse). I finally asked a question about what to take on the other website “Seeking Health” where you can purchase products. The answer that i received that I “assume” was from the doctor was to take the sub-lingual product. It combines 8000mcg of metafolin with Vit B-12. The email said to start with 1/4 tablet and increase based on tolerance. I hope this helps. I’m going to start next week. Good luck.August 18, 2012 at 3:41 pm #3196
Thanks Lynn for your detailed explanation. I’ve missed you! I’m glad you are OK. Dr. Ben should hire you to help him with this forum. There has been many unanswered posts since you where away. Welcome back. I knew that methyl trapping meant that folate couldn’t be used without methyl b12, and would build up in the body, and basically not work, but wouldn’t be able to explain many details, or what would happen, so thank you again.August 19, 2012 at 7:46 am #3207
Thanks for your kind words Dolores.August 20, 2012 at 2:01 pm #3220
It all seems so hopelessly complicated; how can one ever really figure out what to take and in what amounts?August 21, 2012 at 12:50 am #3228
One step at a time Peter… one supplement at a time, start low and work up. Dr Ben has given his ideas on which order elsewhere on the site. But also, don’t rely on just taking pills – so much is about lifestyle. The supplements enhance output of toxins, but if you can also reduce inputs then you are tackling it from both angles.August 27, 2012 at 1:29 am #3265
Patti- which product was that?
Thanks!August 9, 2013 at 3:46 pm #376745
So if I take a 1000mcg of sublingual methylcobalamin and then try to support it with my multivitamin by Thorne Basic Nutrients lll, which contains all the right forms of B vitamins and has the methylfolate which is needed when taking methylcobalamin, but it also contains vit c which is said to cancel out the methylfolate so does this mean I need to take a separate methylfolate as well or will it be fine? Also is the abd12 in the multivitamin sufficient or do I need that too?