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Worried about my ratio of methylfolate to MB12--any insight?

Messages
52
I'm on all the stuff in @Freddd 's protocol, pretty much (including the brands he uses). However, my ratio of MB12 to MFolate has gotten really weird, and I'm worried that I'm misinterpreting my symptoms and making some wrong choices.

I'm taking only 1mg of MB12 per day (although it takes almost 2 hours for it to dissolve), and maybe 5mg of Dibencozide total per week, so, less than 1 mg of that per day. BUT, I've gotten up to 12mg of methylfolate per day.

I kept increasing because I keep getting scaly, itchy skin patches on my face, which will then clear up if I increase the folate. I went through a couple of rounds of that, and it seemed to be steady for awhile at the 12 mg dose. However, they are back again, although this time they are at my hairline, when before they were around my eyes. Also, my scalp has gotten itchy and irritated all along the hairline. So, I'm thinking maybe I need to up my folate AGAIN, but I'm already at a very high dose of that while at a fairly low dose of B12s!

Does this seem okay to you all? Or am I improperly attributing the epithelial issues to lack of folate, but it is really something else? What would drive my need for so much folate, when I'm not taking that much b12?

I'm heterozygous on the MTHFR SNPs, so I would expect to have some extra need for folate, but that much more? It's making me nervous. Does the fact that I'm COMT++ have something to do with it?

Can these type of skin issues be due to lack of potassium? I'm not having any of my usual signs of potassium deficiency, which are twitching eyelid and increased heart rate. However, I did decrease my potassium intake over the past week because I didn't seem to need so much of it based on my usual symptoms. Also, if I overdose on the potassium I get a little farty, which is my warning to back off.

Is it possibly a sign that I'm not taking enough B12? I don't actually know what the signs of too little B12 are. Also, based on my COMT SNPs it was suggested to me to switch from MB12 to Hydroxy B12, which I haven't done yet. Basically, I am confused, lol!

EDIT: Hmmm, I just realized that I've been a bit low on the NT Factors (I've been taking that instead of the lecithin). I just keep forgetting to take it. So, some days I'm getting the dose, and other days I'm not. Could this contribute to my issues?

EDITED again: I've been doing methylation for a year, just fyi
 
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ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
@Soporificat If you're eating green veggies, it's possible that the vegetable folate, which is folinic form, might be blocking your Mfolate, hence you're getting deficiency symptoms. This happened to me. I'd gotten up to 30mg folate, and still getting sx. I found that Fred had referred to this phenomenon, saying he limits his veg intake. When I quit my cooked veg, my methylation cycle took off. I was in the midst of detox, and it became out of control. When the whole system settled down, after some days with no folate, and no deficiency symptoms, I reduced my dose from 250 mg to 15 mg, and B12 from 30mg to 20mg.

I'm currently about to eliminate my remaining green veg, about 6 leaves of lettuce, to see if this is also the cause of s current patch of eczema that won't go away..:(

I don't think this is likely low K+. I can't remember whether this tendency is for MTHFR or COMT. cheers, ahmo
 

boo85

Senior Member
Messages
178
@Soporificat I'm currently about to eliminate my remaining green veg, about 6 leaves of lettuce, to see if this is also the cause of s current patch of eczema that won't go away..:(

I've also had an eczema flair-up on my hands in the past two weeks. Is that a symptom of methylation block from low folate?
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
It's possible, as it's skin/epithelial. Earlier my eczema was related to sulfur and histamine intolerances. It's pretty individiual how our symptoms manifest. Fred has some long lists of symptoms, look in the Guide linked to my signature for more info. I've just not been able to account for this patch over the past couple weeks, so I'm seeing if folate is the answer.
 

stridor

Senior Member
Messages
873
Location
Powassan, Ontario
I have never had enough money to find out how much mfolate I would need if I swallowed it. I have to open the caps and pour them into the buccal pouch. I doubt that I am the only one who has difficulty absorbing this. (also problems with Vit D, iron, B2).
I suspect that a % of people here taking mega-doses of folate are in the same boat. 13 mg is close to the 15 mg found in Deplin, Your getting there but it is not alarming yet IMO.

Foliculitis and psoriasis improved a lot with the removal of amalgams and tx for mercury. Furthermore, persistent skin problems improved more with addition of probiotics. Problems in my gut along with all that entails (not to be confused with entrails) can still give me flair-ups. Vitamin A was also very helpful and it is about the only change directed by my 23 results as I was already on mB12 and mfolate.
Coconut oil keeps the eczema at bay. As far as I know, I have not had any for many months. I apply coconut oil after showers to the areas where historically I have had problems. It's magic for me. brad
 
Messages
52
@ahmo -- ok, I'll try cutting out my green vegetables. I don't like green vegetables anyway, lol! I suppose beans are bad, too, since they have an enormous amount of folate?. I'm a little confused by the difference between folate and folinic acid. Oh, btw, I love the guide that you wrote up. Thank you for sharing that with everyone.

@stridor -- yes, my levels are just under the Deplin full dose, so that is why I've been comfortable sitting at that dose for about 6 months. I have friends who only take Deplin (not for ME/CFS; for depression). What suddenly has started to worry me was reading on another thread about concerns over mega-doses of methylfolate causing the deactivation of folate receptors! Creating a vicious cycle where you have to take increasing level of methylfolate just to get a reasonable dose. It also has struck me as odd that I take so little MB12 (relatively speaking), and then to suddenly think I need to crank up the methylfolate even more -- well, it is just overall making me feel uneasy. I'm doubting my choices.

Yes, amalgam removal is in my future, for sure. Other than that I think my gut is in unusually good shape for an ME patient.
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
Update: 48 hrs. after excluding my remaining green veggies, my eczema has nearly gone. It seemed to be so after 24 hrs, but I didn't want to report prematurely. And again, as with the first time I found this association, it seems to have also removed a burden on my adrenals. Some slight indicators of adrenal stress have also disappeared.

I'm going to try Brad's suggestion for buccal Mfolate with my next dose, in a few hours. I'd love to reduce not only my costs, but whatever strain high dose Mfolate might be placing on my adrenals.:balloons:

Re folate/folinic: My understanding is that the body has to convert folinic to folate, and some of us can't do that. Check the folate section in the Guide, I think there's some info there. I have no memory, so can't tell you definitively.;)
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
@stridor THANK YOU for this tip on taking folate via buccal.:love: My first dose like this felt like rocket fuel! My sense is that what I was experiencing was a histamine rush from the 'over-methylation'. It calmed after I took my anti-hist supps. I'm omitting my PM dose, which means today I'm taking 10 instead of 15mg. Will see how this goes in the next days. Happy Happy!:woot:
 
Messages
233
I'm a little confused by the difference between folate and folinic acid.
@Soporificat - There are multiple forms of folate. Some graphics to clear the confusion: here and here.

Dietary folate is Dihydrofolate, which still needs to convert to L-methylfolate and can be hindered by MTHF polymorphisms. Rich Van K. proposed Freddd might have an MTHFS polymorphism (separate from MTHFR) causing issues with both folinic and vegetable folate.

The calcium salt form of L-methylfolate is used in Metafolin, Deplin, and Douglas Labs L-5-MTHF. The glucosamine salt form Quatrefolic is used in Seeking Health L-5-MTHF. Some "bad" folates here.



What suddenly has started to worry me was reading on another thread about concerns over mega-doses of methylfolate causing the deactivation of folate receptors!
Caledonia linked an article which states an overdose of L-methylfolate can cause excess folic acid to pile up, which can burn out receptors. Stephen Stahl, MD, PhD on CNS Spectrums stated L-methylfolate precursors can compete because they bind on folate receptors, preventing L-methylfolate from reaching the brain. So, competition between folic acid and L-methylfolate can cause issues.
 
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Avalon

Senior Member
Messages
112
Location
Oxford, England
Over many years prior to starting methylation I have had intermittent facial rashes around the hair line, jaw line and itchy parts of my face. I noted that on the methylation protocol after introducing mfolate (taking 500mcg mb12 prior) that I would get facial rashes and itching, when I reduced or stopped, the rashes went away or reduced in severity. I'm thinking of moving to use hydroxy b12 with initially folinic acid then followed by mfolate as proposed by Rich's protocol.
 

liverock

Senior Member
Messages
748
Location
UK
I'm on all the stuff in @Freddd 's protocol, pretty much (including the brands he uses). However, my ratio of MB12 to MFolate has gotten really weird, and I'm worried that I'm misinterpreting my symptoms and making some wrong choices.

I'm taking only 1mg of MB12 per day (although it takes almost 2 hours for it to dissolve), and maybe 5mg of Dibencozide total per week, so, less than 1 mg of that per day. BUT, I've gotten up to 12mg of methylfolate per day.

I kept increasing because I keep getting scaly, itchy skin patches on my face, which will then clear up if I increase the folate. I went through a couple of rounds of that, and it seemed to be steady for awhile at the 12 mg dose. However, they are back again, although this time they are at my hairline, when before they were around my eyes. Also, my scalp has gotten itchy and irritated all along the hairline. So, I'm thinking maybe I need to up my folate AGAIN, but I'm already at a very high dose of that while at a fairly low dose of B12s!

Does this seem okay to you all? Or am I improperly attributing the epithelial issues to lack of folate, but it is really something else? What would drive my need for so much folate, when I'm not taking that much b12?

I'm heterozygous on the MTHFR SNPs, so I would expect to have some extra need for folate, but that much more? It's making me nervous. Does the fact that I'm COMT++ have something to do with it?

Can these type of skin issues be due to lack of potassium? I'm not having any of my usual signs of potassium deficiency, which are twitching eyelid and increased heart rate. However, I did decrease my potassium intake over the past week because I didn't seem to need so much of it based on my usual symptoms. Also, if I overdose on the potassium I get a little farty, which is my warning to back off.

Is it possibly a sign that I'm not taking enough B12? I don't actually know what the signs of too little B12 are. Also, based on my COMT SNPs it was suggested to me to switch from MB12 to Hydroxy B12, which I haven't done yet. Basically, I am confused, lol!

The symptoms sound like 'methyl trapping' caused by too little Mb12.

Normally Mb12 and methylfolate form into methyl groups that then eventually form methionine. With too low Mb12 the folate not used eventually gets spilled into the blood and starts to build up. This causes the body's cells to signal low folate symptoms whilst having high folate blood levels. Taking extra folate can make the problem worse as it will cause an increase in folate blood levels whilst increasing the 'methyl trapping.'
This causes a 'methylation cycle block' which is the reason your not needing potassium as your not forming new cells.

Another problem you have with Mb12 is the MTRR++ mutation which will cause low recycling of Mb12 which is necessary to move the folate/methionine part of the cycle.

Having a high blood folate/ B12 ratio can also cause a lot of health problems if not remedied.

Try increasing Mb12 in steps and monitor symptoms and you may also need to cut back on folate. Starting up too quickly from a methylation block can sometimes cause an increase in 'roller coaster' symptoms.

With COMT++ mutations you may also be better eventually trying Hydroxy B12.
 
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Messages
52
The symptoms sound like 'methyl trapping' caused by too little Mb12.

Normally Mb12 and methylfolate form into methyl groups that then eventually form methionine. With too low Mb12 the folate not used eventually gets spilled into the blood and starts to build up. This causes the body's cells to signal low folate symptoms whilst having high folate blood levels. Taking extra folate can make the problem worse as it will cause an increase in folate blood levels whilst increasing the 'methyl trapping.'
This causes a 'methylation cycle block' which is the reason your not needing potassium as your not forming new cells.

Another problem you have with Mb12 is the MTRR++ mutation which will cause low recycling of Mb12 which is necessary to move the folate/methionine part of the cycle.

Having a high blood folate/ B12 ratio can also cause a lot of health problems if not remedied.

Try increasing Mb12 in steps and monitor symptoms and you may also need to cut back on folate. Starting up too quickly from a methylation block can sometimes cause an increase in 'roller coaster' symptoms.

With COMT++ mutations you may also be better eventually trying Hydroxy B12.

Thank you so much! This makes a lot of sense. I didn't know that about the MTRR ++ mutation. Awesome! I will start titrating tomorrow (today I've already screwed up my dosing schedule due to other things). I was thinking about making the move to Hydroxy b12. There are surprisingly few sources to get it from, and so many people have dismissed it as worthless that I wasn't sure if it was worth the hassle.
 
Messages
52
@Soporificat - There are multiple forms of folate. Some graphics to clear the confusion: here and here.

Dietary folate is Dihydrofolate, which still needs to convert to L-methylfolate and can be hindered by MTHF polymorphisms. Rich Van K. proposed Freddd might have an MTHFS polymorphism (separate from MTHFR) causing issues with both folinic and vegetable folate.

The calcium salt form of L-methylfolate is used in Metafolin, Deplin, and Douglas Labs L-5-MTHF. The glucosamine salt form Quatrefolic is used in Seeking Health L-5-MTHF. Some "bad" folates here.




Caledonia linked an article which states an overdose of L-methylfolate can cause excess folic acid to pile up, which can burn out receptors. Stephen Stahl, MD, PhD on CNS Spectrums stated L-methylfolate precursors can compete because they bind on folate receptors, preventing L-methylfolate from reaching the brain. So, competition between folic acid and L-methylfolate can cause issues.

Ah, ok, what was confusing me was that some people are referring to Dihydrofolate as folinic acid. But, I was only aware of folinic acid as a man-made substance, not the dietary folate. So, there is only one type of folate in food, which is dihydrofolate?

OK, so the folic acid is the thing causing the burn-out, not the L-methylfolate. So, if you have no sources of folic acid (no folic acids supps, no folic-enriched bread, etc...) then there won't be issues? I mean, aside from having too many methyl donors if you are COMT++ (which I am, but so far any problems I have have been dealt with through TMG).
 

liverock

Senior Member
Messages
748
Location
UK
Thank you so much! This makes a lot of sense. I didn't know that about the MTRR ++ mutation. Awesome! I will start titrating tomorrow (today I've already screwed up my dosing schedule due to other things). I was thinking about making the move to Hydroxy b12. There are surprisingly few sources to get it from, and so many people have dismissed it as worthless that I wasn't sure if it was worth the hassle.

This site will explain all parts of the Methylation Cycle including MTRR and suggested remedies for mutations.

http://www.heartfixer.com/AMRI-Outcomes-Non-CV-Autism-Methyl Cycle.htm#MTRR: Methionine Synthase Reductase

With the MTRR mutation reducing methylation, if you have been using TMG, this bypasses MTRR using the 'short cut BHMT pathway.' and increases methylation. As you increase B12 the MTRR should work better and If this happens and you are still taking TMG the resulting increase in methyl groups could cause COMT to be overwhelmed. I would get ready to cut down on TMG (which is a methyl donor) as you increase B12 before methyl levels get too high.

Looking at the MTRR diagram will make this clearer)


image008.jpg



 
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Messages
52
This site will explain all parts of the Methylation Cycle including MTRR and suggested remedies for mutations.

http://www.heartfixer.com/AMRI-Outcomes-Non-CV-Autism-Methyl Cycle.htm#MTRR: Methionine Synthase Reductase

With the MTRR mutation reducing methylation, if you have been using TMG, this bypasses MTRR using the 'short cut BHMT pathway.' and increases methylation. As you increase B12 the MTRR should work better and If this happens and you are still taking TMG the resulting increase in methyl groups could cause COMT to be overwhelmed. I would get ready to cut down on TMG (which is a methyl donor) as you increase B12 before methyl levels get too high.

Looking at the MTRR diagram will make this clearer)

image008.jpg

Thank you for the clear advice, Liverock. I look at diagrams like the above and I can't make sense of them. But, I went on the site and the level of info is AMAZING!
 
Messages
233
@liverock - Brilliant explanation!


Soporificat said:
So, there is only one type of folate in food, which is dihydrofolate?
@Soporificat - Good question! From what I understand, foods can have different types, amounts, and percentages of folates. Folate in food can be processed by the intestines/liver to dihydrofolate. So dihydrofolate or dietary folate in the graphics is a derivative. Dbkita linked an older article here. More posts here, here, and here. Freddd also talked about how his grandfather was given a stew, made with liver extract which contained L-methylfolate, here.

You will probably learn more about folates than you ever originally wanted to know. I would work on genetics first as that is going to help your situation more (and help save the brain).


Soporificat said:
OK, so the folic acid is the thing causing the burn-out, not the L-methylfolate. So, if you have no sources of folic acid (no folic acids supps, no folic-enriched bread, etc...) then there won't be issues?
For the interaction with L-methylfolate, yes. Any precursor can compete with L-methylfolate, but I do not know if the same "burn out" effect occurs with anything other than folic acid.
 
Messages
52
@liverock - Brilliant explanation!



@Soporificat - Good question! From what I understand, foods can have different types, amounts, and percentages of folates. Folate in food can be processed by the intestines/liver to dihydrofolate. So dihydrofolate or dietary folate in the graphics is a derivative. Dbkita linked an older article here. More posts here, here, and here. Freddd also talked about how his grandfather was given a stew, made with liver extract which contained L-methylfolate, here.

You will probably learn more about folates than you ever originally wanted to know. I would work on genetics first as that is going to help your situation more (and help save the brain).



For the interaction with L-methylfolate, yes. Any precursor can compete with L-methylfolate, but I do not know if the same "burn out" effect occurs with anything other than folic acid.

Aha! So helpful, thank you! If there are different types of folates in food, that might explain why people like Freddd and Ahmo have a problem with green vegetables, yet make no mention of similar problems with legumes, which are very high in folate. It sounds like the type of folate that might be in broccoli, for example, might be different from the type in lentils. That was the part that was really puzzling me.

Thanks for the clarification about folic acid and "burn-out." I'm not worried about it now because I get zero folic acid in my diet, and haven't had any for the past 3 years.

OK, so I'm really trying to understand the SNPs thing, but as I trace through my various SNPs it seems like some of them cancel each other out (which is good, of course) and some seem unclear, particularly the ones that are +/-. If I have SNPs that are +/- do I treat them as if they are somewhere in between ++ and -- in terms of their effect and the treatment for them? For example, I know that is mostly true of the MTHFR ones, but is that the case for all of them?