What is Methyl Trapping ?

[Branston]

I have kept seeing this term being used and suggestions that it is very bad, and I am trying to understand what it means.
At its .... is it a problem that occurs if you need mB12 and mFolate, but start taking the Folate without having first taken mB12 for a while.?
Are there symptoms that are caused by Methyl trapping?
Could someone please explain.
Thanks

 

[Xara]

I have kept seeing this term being used and suggestions that it is very bad, and I am trying to understand what it means.
At its .... is it a problem that occurs if you need mB12 and mFolate, but start taking the Folate without having first taken mB12 for a while.?
Are there symptoms that are caused by Methyl trapping?
Could someone please explain.
Thanks

Hi Branston,
Here I am again.

As far as I know:
Methyl trap = methyl folate trap = folate trap.

In simple words, and again as far as I know:
In the body THF is formed into methylfolate. Methylfolate needs to get rid of its methyl groups to become THF again.
THF is used for several things. Methylfolate is being used for one thing: to work together with B12 and form methionine out of homocysteine . While doing that methylfolate loses its methyl groups.

If there's no B12, methylfolate can not be turned into THF again, because it can not get rid of its methyl groups. So there's no nice circle anymore, but a dead end. The methylfolate starts building up. It's trapped. When it's trapped it starts going from the cells to the blood plasma.

Continue to take folates and no B12 and simply more folates are turned into methylfolate while none is turned back into THF, so serum folate rises while the intracellular folate concentration is going down.
Meanwhile not enough methionine is being made, and homocysteine is building up, both causing all sorts of problems. In other words: the methylation cycle is blocked thanks to no B12.
That may cause many, many different problems, amongst them irreversible neurological damage and anaemia.

When confronted with anaemia some doctors think it's because of lack of folates and they prescribe folic acid. You can see that won't work, the methylfolate has no partner to work with, so the extra folate won't change the amount of methionine being made, and the harm being done to the body continues.

Now in my explanation above I used 'no B12'. That is not realistic, I think, most of the time there is some B12. But when you do not have enough B12 you have a partial methylation block.

So always make sure there's enough B12 before adding folates. You have to keep that methylfolate busy. When it starts being idle, whistling and looking at the ceiling, you're in for trouble.

If I am wrong, I hope someone will correct me.

 

[Freddd]

Rich gives a very good desribtion of it somewhere that could be found. Basically the "methyltrap" (hypothesis for 30 years or so) occurs when there is not enough MeCbl for the methylfolate in the cell to complete it's function and it is kicked out of the cell, causing distinctive folate deficiency symptoms instead of the MeCbl deficiency symptoms that would be expected. It is a more severe level of methylation block than the partial methylation block.

 

[Branston]

Thank you, chaps. So the answer is to make sure you start with the MB12 and be on that for a while before adding in the Folate.
Freddd, what are 'distinctive folate deficiency ' symptoms that would help you differentiate from B12 deficiency?

 

[Freddd]

Hi Branston,

Generally both cause a very overlapping set of symptoms but onset is different. So folate deficiencies/insufficiencies can happen suddenly and b12 take longer.


Group 3 - Induced and/or Paradoxical Folate deficiency or insufficiency
Headache, Increased malaise, Fatigue,IBS – Diarrhea alternating with constipation, IBS –Normal alternating with constipation, IBS – Steady diarrhea, IBS – Diarrhea alternating with normal, Stomach ache, Uneasy digestive tract, increased hypersensitive responses , Skin rashes, Increased acne, Skin peeling around fingernails, Skin cracking and peeling at fingertips, Angular Cheilitis, Canker sores, Coated tongue, Runny nose, Increased allergies, Increased Multiple Chemical Sensitivities, Increased asthma, rapidly increasing Generalized inflammation in body, Increased Inflammation pain in muscles, Increased Inflammation pain in joints, Achy muscles, Flu like symptoms, Depression, Less sociable, Impaired planning and logic, Brain fog, Low energy, Light headedness, Sluggishness, Forgetfulness, Confusion, Difficulty walking, Behavioral disorders, Dementia, Reduced sense of taste, Increase irritability, Loss of reflexes, Fevers, Old symptoms returning, Heart palpitations, Bleeding easily.

For instance, with methyltrap a lot of these symptoms can come on in a day or five. With low b12 it can take 6 months or more. Partial methylation block starts with 1 or 2 symptoms very quickly and may add more or get worse or may not. For me I get things like angular cheilitis, scalp and face acne type lesions withing 2-3 days, IBS in 5 days and peeling and cracking skin on my fingertips in 2-3 weeks, but that starts changing right away but takes a while to become obvious. It takes practice to recognize the changing symptoms.

 

[Freddd]

Thank you, chaps. So the answer is to make sure you start with the MB12 and be on that for a while before adding in the Folate.
Freddd, what are 'distinctive folate deficiency ' symptoms that would help you differentiate from B12 deficiency?

Hi Branston,

I see nothing at all wrong with adding the folate from the start. Otherwise you just have cause of symptoms swapping back and forth. To heal you need the l-methyylfolate and MeCbl hitting the cells at the same time. If you take the folate 30-60 minutes before a sublingual, absorbtion and retention appears better, usually a small improvemnt, but then thats what I have done for 10 years, after the big ones are in place.It became a matter of gaining another few percentage points of improvement over and over again.

 

[Branston]

Hi Branston,

I see nothing at all wrong with adding the folate from the start. Otherwise you just have cause of symptoms swapping back and forth. To heal you need the l-methyylfolate and MeCbl hitting the cells at the same time. If you take the folate 30-60 minutes before a sublingual, absorbtion and retention appears better, usually a small improvemnt, but then thats what I have done for 10 years, after the big ones are in place.It became a matter of gaining another few percentage points of improvement over and over again.

But if you take the Folate without the mB12 you can be in big trouble ?
A friend of mine was given 5MTHF 800mcg by her ND last week. She took one dose and ended up in the Emergency Dept with pounding/racing heart.
My own doctor told me this week that she took one dose of 5MTHF and felt so awful that she hasn't touched it since.
Both of these people have MTHFR C677T +/-

 

[Freddd]

But if you take the Folate without the mB12 you can be in big trouble ?
A friend of mine was given 5MTHF 800mcg by her ND last week. She took one dose and ended up in the Emergency Dept with pounding/racing heart.
My own doctor told me this week that she took one dose of 5MTHF and felt so awful that she hasn't touched it since.
Both of these people have MTHFR C677T +/-

Some people start the folate days or weeks before. It only take 5 minutes for the MeCbl to start spreading throughout the body with a sublingual. Taking one dose and feeling awful can be for all sorts of reasons. Without knowing what else and all sorts of details it is impossible to even make a reasoned guess. Take them together. Swallow a l-methylfolate and put the MeCbl AND AdoCbl under you lips. That way you are NOT doing that. The particular genetic info is useless here. It just doesn't matter. The horrid symptoms can be methyltrap which can hit in minutes and hard and/or paradocical folate deficiency and/or low potassium. Those don't depend on genes. They can happen to anybody depending upon the exact details of their situation. Methyltrap is the fastest hardest hitting but can take from an hour to a day to hit.

Timing is important. Combinations are important. Both examples given didn't do appropriate timing or combinations and predictably failed.

 

[ahmo]

Hi Branston,

Generally both cause a very overlapping set of symptoms but onset is different. So folate deficiencies/insufficiencies can happen suddenly and b12 take longer.


Group 3 - Induced and/or Paradoxical Folate deficiency or insufficiency
Headache, Increased malaise, Fatigue,IBS – Diarrhea alternating with constipation, IBS –Normal alternating with constipation, IBS – Steady diarrhea, IBS – Diarrhea alternating with normal, Stomach ache, Uneasy digestive tract, increased hypersensitive responses , Skin rashes, Increased acne, Skin peeling around fingernails, Skin cracking and peeling at fingertips, Angular Cheilitis, Canker sores, Coated tongue, Runny nose, Increased allergies, Increased Multiple Chemical Sensitivities, Increased asthma, rapidly increasing Generalized inflammation in body, Increased Inflammation pain in muscles, Increased Inflammation pain in joints, Achy muscles, Flu like symptoms, Depression, Less sociable, Impaired planning and logic, Brain fog, Low energy, Light headedness, Sluggishness, Forgetfulness, Confusion, Difficulty walking, Behavioral disorders, Dementia, Reduced sense of taste, Increase irritability, Loss of reflexes, Fevers, Old symptoms returning, Heart palpitations, Bleeding easily.

For instance, with methyltrap a lot of these symptoms can come on in a day or five. With low b12 it can take 6 months or more. Partial methylation block starts with 1 or 2 symptoms very quickly and may add more or get worse or may not. For me I get things like angular cheilitis, scalp and face acne type lesions withing 2-3 days, IBS in 5 days and peeling and cracking skin on my fingertips in 2-3 weeks, but that starts changing right away but takes a while to become obvious. It takes practice to recognize the changing symptoms.

Hi Fredd. I think I've been experiencing methyl trapping, and have now caught it.

During the past 6 months I spent many hours reading posts between you and Rich and others, trying to muster enough comprehension to continue. I began MTHF and methyl B12 about 5 months ago. I also started TMG, p5p, r5p, biotin, plus high doses of Se, Molybd, zinc.

Carnitine fumarate lingered in my mind, but when I went looking for references, I came away believing it to be not the best source. So I tried the ALCAR I had on hand, w/ no results, and self-testing negative. Then I tried carnitine bitartrate, no effect and negative testing. So I ordered carnitine fumarate. WOW! Perseverance furthers! I felt this almost immediately. Brighter, better overall feeling, no sense of racing. A great addition.

I soon upped my methylfolate to 3/day. I'm not sure what I read that prompted me to up it. Anyway, it seemed fine. Until over the last weeks I've had an unremitting rash. Histamine responses are one of my primary concerns. I've eliminated histamines from my diet, and have a v minimal GAPS diet, so I can tell if there's a reaction to any specific food. And I take anti-histamine supps recommended by Yasko, quercetin and butterbur. Still, even adding a 2nd butterbur, rash continued. Also, increasing lesions on scalp. Reading these threads, I decided to cut the methylfolate. I reduced to 1 instead of 3. My itching has decreased (this is just in one day). I hope this is the source of it.

Actually, this also happened when I upped my B12 to 4/day (methylB12, Jarrow) a month or 2 ago. I then reduced to 1, the reaction stopped. Over the last 2 weeks I've gone up to 2/day.

I've been very cautious implementing the protocol, as I also have a sulphur intolerance and wanted to make sure I didn't run into problems. I haven't eaten any thiol-rich foods for 5 months, my sulfate urine readings are next to lowest on the sticks, said to be acceptable. I'm awaiting my Metametrix urine results (comprehensive & toxic/nautral metals) before adding in Yasko's RNA formulas.

One of the benefits I saw on the methyl protocol was hair regrowth on my arms. I'd been looking at my arms for months, seeing the pigment changes and trying to understand what I was looking at. What I didn't see was that there was no hair on my arms. Zip. I was reading a thread of people talking about hair loss and it finally twigged that I was hairless on my arms, nearly so on legs. Now, after about 4 months on protocol, hair is regrowing. I've added other things during this time, as listed above, + lithium. Maybe there was some influence from these. Maybe being sulfur-free helped. I can only assume the methylfolate and B12 had an influence.

My condition is slowly improving. When I added the carnitine fumarate I wrote on a forum post that I felt perilously close to resolving my ME/CFS, it felt so good. And yet, the greatest gains have been in my interiority. My mind has settled, anxiety decreased, clarity increased. (Especially from the TMG, p5p, lithium.) My physical gains have been real, I can do my gentle exercise more frequently, more vigorously. But I can't do much of anything beyond my limited computer use and reading. I don't know whether the next gains are dependent upon methylation or treating the SNPs. I'll begin Dibencoplex when it arrives, probably this week. In any case I'm very grateful for all that you and the community have done to clarify and problem-solve this piece of the puzzle. ahmo

 

[Freddd]

Hi Fredd. I think I've been experiencing methyl trapping, and have now caught it.

During the past 6 months I spent many hours reading posts between you and Rich and others, trying to muster enough comprehension to continue. I began MTHF and methyl B12 about 5 months ago. I also started TMG, p5p, r5p, biotin, plus high doses of Se, Molybd, zinc.

Carnitine fumarate lingered in my mind, but when I went looking for references, I came away believing it to be not the best source. So I tried the ALCAR I had on hand, w/ no results, and self-testing negative. Then I tried carnitine bitartrate, no effect and negative testing. So I ordered carnitine fumarate. WOW! Perseverance furthers! I felt this almost immediately. Brighter, better overall feeling, no sense of racing. A great addition.

I soon upped my methylfolate to 3/day. I'm not sure what I read that prompted me to up it. Anyway, it seemed fine. Until over the last weeks I've had an unremitting rash. Histamine responses are one of my primary concerns. I've eliminated histamines from my diet, and have a v minimal GAPS diet, so I can tell if there's a reaction to any specific food. And I take anti-histamine supps recommended by Yasko, quercetin and butterbur. Still, even adding a 2nd butterbur, rash continued. Also, increasing lesions on scalp. Reading these threads, I decided to cut the methylfolate. I reduced to 1 instead of 3. My itching has decreased (this is just in one day). I hope this is the source of it.

Actually, this also happened when I upped my B12 to 4/day (methylB12, Jarrow) a month or 2 ago. I then reduced to 1, the reaction stopped. Over the last 2 weeks I've gone up to 2/day.

I've been very cautious implementing the protocol, as I also have a sulphur intolerance and wanted to make sure I didn't run into problems. I haven't eaten any thiol-rich foods for 5 months, my sulfate urine readings are next to lowest on the sticks, said to be acceptable. I'm awaiting my Metametrix urine results (comprehensive & toxic/nautral metals) before adding in Yasko's RNA formulas.

One of the benefits I saw on the methyl protocol was hair regrowth on my arms. I'd been looking at my arms for months, seeing the pigment changes and trying to understand what I was looking at. What I didn't see was that there was no hair on my arms. Zip. I was reading a thread of people talking about hair loss and it finally twigged that I was hairless on my arms, nearly so on legs. Now, after about 4 months on protocol, hair is regrowing. I've added other things during this time, as listed above, + lithium. Maybe there was some influence from these. Maybe being sulfur-free helped. I can only assume the methylfolate and B12 had an influence.

My condition is slowly improving. When I added the carnitine fumarate I wrote on a forum post that I felt perilously close to resolving my ME/CFS, it felt so good. And yet, the greatest gains have been in my interiority. My mind has settled, anxiety decreased, clarity increased. (Especially from the TMG, p5p, lithium.) My physical gains have been real, I can do my gentle exercise more frequently, more vigorously. But I can't do much of anything beyond my limited computer use and reading. I don't know whether the next gains are dependent upon methylation or treating the SNPs. In any case I'm very grateful for all that you and the community have done to clarify and problem-solve this piece of the puzzle. ahmo

Hi Ahmo,


So I ordered carnitine fumarate. WOW!

Excellent. Right here you have put your finger precisely on the one of the mysteries. Why does LCF work so much totally better than any other form for most people and yet ALCAR is superior for a few? Why does ALCAR get all the attention and preference by everybody else? Why can't our bodies synthecize the l-carnitine fumarate as it is "supposed" to do? This could be at the root of mitochondrial failure for who knows how many of us. It might lead to genes or some kind of defect even lower down the chain. My opinion is that this could be as big in understanding CFS/FMS/Parkinson's/ALS/SACD/MS/autism as the folate polymorhisms.

My legs were slick for 20 years and surprised me by regrowing hair, not as much, not as dark.

After things level off with the LCF you might want to consider rebalancing. Try more l-mehtylfolate and see if and how it makes a difference. You may find that it is now limiting other things. Watch for increased donut hole paradoxical folate insufficiency symptoms. Also potassium may change again. LCF may turn on a whole lot of healing, mitochondria and cell formation. It made a huge difference for me on exercise capacity and rate of adapting..

 

[ahmo]

Excellent. Today's the second day w/ lower folate, and the rash has disappeared. After reading your comment re the mysteries of carnitine, I (rashly!) tested myself for carnitine and have added a second 250mg cap at night, tonight's the second. Now I'll just hang in before doing anything else. Thanks Freddd.

 

[Freddd]

Excellent. Today's the second day w/ lower folate, and the rash has disappeared. After reading your comment re the mysteries of carnitine, I (rashly!) tested myself for carnitine and have added a second 250mg cap at night, tonight's the second. Now I'll just hang in before doing anything else. Thanks Freddd.

"WOW" type responses need so time to for the healing and biochemical responses to occur and to see what changes and what remains. Be in good health.

 

[Lotus97]

I've been studying some of Rich's more recent posts about the methyl trap. It seems that due to peroxynitrite, folate levels don't actually rise for people with ME/CFS.

If the methyl trap mechanism were operating alone, it's true that the serum folate would rise. However, in ME/CFS, the serum folates are observed to be low. Prof. Marty Pall has convinced me that this is due to peroxynitrite reacting with methylfolate and breaking it down. There is published evidence for this reaction.

It is known that normally after vitamin B12 is absorbed by the gut, it is transported in the blood to the body’s cells, bound to the carrier transcobalamin. After entering the cells, the B12 normally passes through an intracellular processing pathway, which produces the appropriate amounts of the two active coenzyme forms of B12 needed by the cells, i.e. adenosylcobalamin and methylcobalamin.

Adenosylcobalamin acts as a coenzyme in the mitochondrial methylmalonate pathway, which feeds certain substances into the Krebs cycle to be used as fuel for making ATP. These substances are isoleucine, valine, threonine, methionine, the side-chain of cholesterol, and odd-chain fatty acids.

Methylcobalamin acts in the cytosol as a coenzyme for the methionine synthase reaction, which links the methylation cycle with the folate metabolism and also helps to govern the flow into the transsulfuration pathway, which feeds the synthesis of glutathione, among other reactions.

One of the key parts of the intracellular processing pathway for vitamin B12 is called the CblC complementation group. This group normally binds cobalamin in order to carry on its processing. The strength of this binding, called the affinity, depends strongly on the presence of glutathione. A recent study by Jeong and Kim (2011, PMID: 21821010) using bovine CblC and cyanocobalamin, found that glutathione, which is normally present in the cells, raised this affinity by a factor of over one hundred.

In ME/CFS, we have found that glutathione becomes depleted. That being the case, we can expect the affinity of CblC for cobalamin to drop considerably. The effect of this would be to lower the rate of production of both adenosylcobalamin and methylcobalamin. The effect of lowering adenosylcobalamin is to decrease the fuel supply to the Krebs cycle and hence to lower the rate of production of ATP. The effect of lowering methylcobalamin is to partially block the methionine synthase reaction, lowering the methylation capacity, and draining the methylation cycle and disrupting the sulfur metabolism in general. The methyl trap mechanism then continues to convert other forms of folate into methylfolate, and this is partly catabolized by reaction with peroxynitrite which forms as a result of the glutathione depletion. The folates thus become depleted, and a chronic vicious circle mechanism is set up.

Now, consider what happens when a high dosage of B12 is injected, as in the treatment discovered by Lapp and Cheney. When the dosage is high enough, the low affinity of the CblC complementation group for cobalamin is overcome, so that the rates of production of adenosylcobalamin and methylcobalamin are able to come up, perhaps even to normal levels. I suggest that this affinity problem is the reason for the need for such a high dosage of B12 to obtain a therapeutic effect.

The added adenosylcobalamin would support the methylmalonate pathway, and more fuel would be supplied to the Krebs cycle, which would raise the rate of production of ATP. I suggest that this is what causes ME/CFS patients to experience a boost in energy, stamina or well-being on the high-dose injected B12 treatment. This is particularly significant in ME/CFS, because carbohydrate and fat metabolism is hindered due to the effect of glutathione depletion on the aconitase reaction, early in the Krebs cycle. Note also that deficiencies in some of the B-complex vitamins can interfere with obtaining this benefit, because they are also needed by the methylmalonate pathway.

However, I suggest that even though methylcobalamin production would also rise, the partial block of the methionine synthase reaction would remain if B12 alone is given, and this is the reason for the limited benefit of that treatment. The reason why B12 treatment alone will not correct the partial block in methionine synthase is that there is insufficient methylfolate available to feed this reaction. The reason for that, as Prof. Martin Pall has pointed out, is that the level of methylfolate has been lowered by reaction with peroxynitrite. Peroxynitrite has risen because of the state of oxidative stress that ensues when glutathione is depleted.

If methylfolate is added in addition to adding high-dosage B12, the partial block of methionine synthase can be lifted, which can then break the vicious circle mechanism that holds glutathione down. Over time, as glutathione rises, the affinity of CblC for cobalamin will also rise, and supplementation of high-dosage B12 will no longer be necessary. Likewise, peroxynitrite will drop as glutathione is restored, so that supplementation of methylfolate will no longer be necessary, either.

Rich explains the study about glutathione and cobalamin in more detail here

O.K., in 2011 a paper was published by two researchers in Korea, Jeong and Kim. The abstract is pasted below.
The research they report was actually done on a bovine (cow) B12-processing complementation group and cyanocobalamin. However, the human complementation group is very similar, and I suspect that the results will also be similar for other forms of B12 than cyanocobalamin.

They studied the CblC complementation group. This is part of the B12 processing pathway that is found inside all cells. When a form of B12 comes into a cell from the blood by the usual transcobalamin route, it is bound to CblC, and its beta ligand (cyano-, methyl-, or adenosyl-) is removed. Then it is sent on to be converted back to methylcobalamin or adenosylcobalamin as needed by the cell.

In order for this processing to happen, the CblC complementation group must first bind the B12 form. The strength of binding is called the affinity (Kd), and it is measured in concentration units. The higher the affinity, the lower the Kd. It turns out that the bare CblC complex has a relatively low affinity for B12, compared to the concentration of B12 in the cells, and this would be unfavorable for the necessary binding, and would tend to lower the reaction rate.

What these researchers found is that normally glutathione binds to CblC, and in doing so, it increases the affinity of CblC for B12. And it does so by a whopping amount--over a factor of a hundred!!

Turning this around, if glutathione becomes depleted, as in ME/CFS and autism, the affinity of CblC for B12 is going to drop substantially. I suggest that the glutathione depletion, combined with its major effect on this affinity, is the reason the B12 dosage must be so high in treating ME/CFS and autism.

Best regards,

Rich


Biochem Biophys Res Commun. 2011 Aug 26;412(2):360-5. Epub 2011 Jul 29.

Glutathione increases the binding affinity of a bovine B?? trafficking chaperone bCblC for vitamin B??.

Jeong J, Kim J.

School of Biotechnology, Yeungnam University, 214-1 Dae-dong, Gyeongsan-si, Gyeongsangbuk-do 712-749, Republic of Korea.

Abstract

Intracellular B(12) metabolism involves a B(12) trafficking chaperone CblC that is well conserved in mammals including human. The protein CblC is known to bind cyanocobalamin (CNCbl, vitamin B(12)) inducing the base-off transition and convert it into an intermediate that can be used in enzyme cofactor synthesis. The binding affinity of human CblC for CNCbl was determined to be K(d)=?6-16 ?M, which is relatively low considering sub-micromolar B(12) concentrations (0.03-0.7 ?M) in normal cells. In the current study, we discovered that the base-off transition of CNCbl upon binding to bCblC, a bovine homolog of human CblC, is facilitated in the presence of reduced form of glutathione (GSH). In addition, GSH dramatically increases the binding affinity for CNCbl lowering the K(d) from 27.1 0.2 to 0.24 0.09 ?M. The effect of GSH is due to conformational change of bCblC upon binding with GSH, which was indicated by limited proteolysis and urea-induced equilibrium denaturation of the protein. The results of this study suggest that GSH positively modulates bCblC by increasing the binding affinity for CNCbl, which would enhance functional efficiency of the protein.

Copyright 2011. Published by Elsevier Inc.

PMID: 21821010

 

[TomS]

Freddd, how do you know whether you have methyl trapping or donut hole deficiency? How do you know the difference if the symptoms are the same?

I've been on the protocol for about 2 weeks now and had some improvements at the very beginning followed by some setbacks. I started out with all the basic vitamins/minerals (twice a day: vitA, p5p, Jarrow B-Right, C, D ,E ,fish oil, borage oil, Mg, Ca, Zn) plus very low titrations of mB12 (Enzymatic Therapy - I started with 0.25mg per day) and aB12 (Source Naturals - I started with a crumb).

I'm at 1mg mB12 (1 pill of Enzymatic Therapy spread out over 4 intakes) and about 2.5mg aB12 (a quarter of a Source Natural spread out over 2 intakes) sublingual per day right now. I started with very little methylfolate (Solgar - first day was 400mcg, then worked my way up to 2400mcg) and had some improvements. My brain fog cleared, dreams returned and my skin got better (I have rashes on both arms).

After initial improvements, it got to a point where I was taking the same amount of mB12/aB12/methylfolate for a day or two and my symptoms got worse all of a sudden. I assumed it was the paradoxical folate deficiency where too little methylfolate triggers more healing than it can sustain and jacked up my methylfolate. I'm at 8,000mcg per day now (staggered over 5 intakes, 3 of which are with food, 2 without).

While my brainfog hasn't returned and I still have vivid dreams, my skin seems to have stopped recovering (and actually got a bit worse) despite the higher methylfolate intake. I am making the switch from Jarrow B-Right to Pure Encapsulation B-Complex tomorrow to rule out residual Folic Acid, but am not sure as to what to make of my symptoms. I am scared of taking even more methylfolate to get out of what I think might be a donut hole deficiency, because I think there is a possiblity that I am wrong and this is actually methyl-trapping. I am still taking 1mg mB12 and about 2.5mg aB12. Is this too little? Is it even possible to fall in the methyl trap with this amount of B12 in the system?

I appreciate any thoughts you or anybody else might have.

-Tom

 

[Freddd]

Freddd, how do you know whether you have methyl trapping or donut hole deficiency? How do you know the difference if the symptoms are the same?

I've been on the protocol for about 2 weeks now and had some improvements at the very beginning followed by some setbacks. I started out with all the basic vitamins/minerals (twice a day: vitA, p5p, Jarrow B-Right, C, D ,E ,fish oil, borage oil, Mg, Ca, Zn) plus very low titrations of mB12 (Enzymatic Therapy - I started with 0.25mg per day) and aB12 (Source Naturals - I started with a crumb).

I'm at 1mg mB12 (1 pill of Enzymatic Therapy spread out over 4 intakes) and about 2.5mg aB12 (a quarter of a Source Natural spread out over 2 intakes) sublingual per day right now. I started with very little methylfolate (Solgar - first day was 400mcg, then worked my way up to 2400mcg) and had some improvements. My brain fog cleared, dreams returned and my skin got better (I have rashes on both arms).

After initial improvements, it got to a point where I was taking the same amount of mB12/aB12/methylfolate for a day or two and my symptoms got worse all of a sudden. I assumed it was the paradoxical folate deficiency where too little methylfolate triggers more healing than it can sustain and jacked up my methylfolate. I'm at 8,000mcg per day now (staggered over 5 intakes, 3 of which are with food, 2 without).

While my brainfog hasn't returned and I still have vivid dreams, my skin seems to have stopped recovering (and actually got a bit worse) despite the higher methylfolate intake. I am making the switch from Jarrow B-Right to Pure Encapsulation B-Complex tomorrow to rule out residual Folic Acid, but am not sure as to what to make of my symptoms. I am scared of taking even more methylfolate to get out of what I think might be a donut hole deficiency, because I think there is a possiblity that I am wrong and this is actually methyl-trapping. I am still taking 1mg mB12 and about 2.5mg aB12. Is this too little? Is it even possible to fall in the methyl trap with this amount of B12 in the system?

I appreciate any thoughts you or anybody else might have.

-Tom

Hi Tom,

In my experience, methyltrap hits like a ton of bricks. I had FMS for perhaps 10 years. Then one morning I woke up terribly sick with 100 more symptoms taking shape over the first week. That was the combination of methyltrap and partial ATP block based on what has occurred since then.

Paradoxical folate insufficiency, including donut hole, is much slow and gentler onset. It usually creeps up on you. It dfoen't have as many symptoms and it doesn't hit like a ton of bricks.

You are taking plenty of b12 for most healing and certainly enough to keep you out of methyltrap. One of the cautions that comes up now is to be careful of B2 amounts. It can cause what looks like a really severe donut hole folate insufficiency as well as very low potassium which is difficult to correct. For some people relatively too much biotin can overdrive the ATP end of things much as too much B2 appears to overdrive part of the methylation cycle or something of the sort.

Also, NAC and/or glutathione can cause the same set of methyltrap symptoms regardless of how much b12 and folate one takes confusing the issue to no end.

 

[TomS]

Thanks for your insight, Freddd. I was particularly nervous about whether or not I had enough mB12 and aB12.

Since my last post I upped my methylfolate intake and I almost don't dare to say it out loud, but the rashes seem to be dying down a bit. I read some good stuff about 5-MTHF from Metabolic Maintenance and decided to give it a try. I know it's not Metafolin, but it seems to be working for me right now. I am currently taking 5mg three times a day (breakfast, lunch, dinner) and a dose of Solgar (1600mcg) twice a day between my meals. With the metafolin from the B complex from Pure Encapsulations (twice a day) that puts me at a total of 19mg of 5-MTHF/Metafolin per day.

I have slightly increased my mB12 intake to 1.25mg (0.25mg five times a day with each 5-MTHF or Metafolin intake) and kept the 2.5mg of aB12 (I'm splitting it into two doses and taking it around 30 minutes after the Metafolin that I take in between meals).

I have about 730mg of potassium (potassium chloride powder from NOW) in the mornings and take 16 potassium gluconate pills throughout the day (99mg of K each). The rest of my intake remains as described in my previous post. On second thought, my improvements could also be attributed to the fact that I switched from Jarrow B-Right to the folic acid-free B complex from Pure Encapsulations. Who knows..

I'm being this specific about what I take in case somebody is having similar symptoms and would like to try and replicate the effect.

I read your post about the B2 on the other thread. I'm sorry this has thrown you off balance the way it did. To me this goes to show how murky these waters really are that we're all navigating in. I don't get any B2 except for what's in the B complex. I vaguely remember taking B2 separately about half a year ago, but I couldn't tell you what my reaction was since I wasn't exactly stable at the time and while I do remember my skin got worse this could also have been due to a bunch of other things I was doing wrong at the time. I'm definitely not going to up my B2 now that I seem to be stabilizing a bit.

I'm also trying to stay away from NAC and glutathione thanks to your repeated warnings on this forum. Thanks so much for putting all this work into this. I have been on a quest of my own to find out about the relationship between the B vitamins and my condition for the last seven years, but never had the stamina or clarity of thought to be able to experiment in a systematic manner the way you did. So, thank you.

[Edit]
This is where I read about the 5-MTHF from Metabolic Maintenance. It's a blog by a girl who relies on Deplin for depressions, but then discovers Metabolic Maintenance and it seems to have a similarly positive effect on her (check the comments section of this post):
http://confessionsofabpgirl.blogspo...lfolate-prescription.html?zx=b56e82a9e435415a

 

[pamrr]

Hi Branston,

Generally both cause a very overlapping set of symptoms but onset is different. So folate deficiencies/insufficiencies can happen suddenly and b12 take longer.


Group 3 - Induced and/or Paradoxical Folate deficiency or insufficiency
Headache, Increased malaise, Fatigue,IBS – Diarrhea alternating with constipation, IBS –Normal alternating with constipation, IBS – Steady diarrhea, IBS – Diarrhea alternating with normal, Stomach ache, Uneasy digestive tract, increased hypersensitive responses , Skin rashes, Increased acne, Skin peeling around fingernails, Skin cracking and peeling at fingertips, Angular Cheilitis, Canker sores, Coated tongue, Runny nose, Increased allergies, Increased Multiple Chemical Sensitivities, Increased asthma, rapidly increasing Generalized inflammation in body, Increased Inflammation pain in muscles, Increased Inflammation pain in joints, Achy muscles, Flu like symptoms, Depression, Less sociable, Impaired planning and logic, Brain fog, Low energy, Light headedness, Sluggishness, Forgetfulness, Confusion, Difficulty walking, Behavioral disorders, Dementia, Reduced sense of taste, Increase irritability, Loss of reflexes, Fevers, Old symptoms returning, Heart palpitations, Bleeding easily.

For instance, with methyltrap a lot of these symptoms can come on in a day or five. With low b12 it can take 6 months or more. Partial methylation block starts with 1 or 2 symptoms very quickly and may add more or get worse or may not. For me I get things like angular cheilitis, scalp and face acne type lesions withing 2-3 days, IBS in 5 days and peeling and cracking skin on my fingertips in 2-3 weeks, but that starts changing right away but takes a while to become obvious. It takes practice to recognize the changing symptoms.

Hi Freddd, this is an ultra-late question/hijack, but, regarding this "Group 3 - Induced and/or Paradoxical Folate deficiency or insufficiency" I have a couple of questions:

1. Could air hunger (clear, healthy lungs - no asthma) be a symptom here?

2. Could one have this deficiency or insufficiency and have only a few symptoms but not others?

If yes to either, and if you even see this reply, I could start a new thread...more questions.

pamrr

 

[Sea]

If you want to get someone's attention specifically pamrr tag them like this pamrr Freddd

 

[pamrr]

Thanksfor the tip.

 

[surfbaby]

Hi Fredd. I think I've been experiencing methyl trapping, and have now caught it.

During the past 6 months I spent many hours reading posts between you and Rich and others, trying to muster enough comprehension to continue. I began MTHF and methyl B12 about 5 months ago. I also started TMG, p5p, r5p, biotin, plus high doses of Se, Molybd, zinc.

Carnitine fumarate lingered in my mind, but when I went looking for references, I came away believing it to be not the best source. So I tried the ALCAR I had on hand, w/ no results, and self-testing negative. Then I tried carnitine bitartrate, no effect and negative testing. So I ordered carnitine fumarate. WOW! Perseverance furthers! I felt this almost immediately. Brighter, better overall feeling, no sense of racing. A great addition.

I soon upped my methylfolate to 3/day. I'm not sure what I read that prompted me to up it. Anyway, it seemed fine. Until over the last weeks I've had an unremitting rash. Histamine responses are one of my primary concerns. I've eliminated histamines from my diet, and have a v minimal GAPS diet, so I can tell if there's a reaction to any specific food. And I take anti-histamine supps recommended by Yasko, quercetin and butterbur. Still, even adding a 2nd butterbur, rash continued. Also, increasing lesions on scalp. Reading these threads, I decided to cut the methylfolate. I reduced to 1 instead of 3. My itching has decreased (this is just in one day). I hope this is the source of it.

Actually, this also happened when I upped my B12 to 4/day (methylB12, Jarrow) a month or 2 ago. I then reduced to 1, the reaction stopped. Over the last 2 weeks I've gone up to 2/day.

I've been very cautious implementing the protocol, as I also have a sulphur intolerance and wanted to make sure I didn't run into problems. I haven't eaten any thiol-rich foods for 5 months, my sulfate urine readings are next to lowest on the sticks, said to be acceptable. I'm awaiting my Metametrix urine results (comprehensive & toxic/nautral metals) before adding in Yasko's RNA formulas.

One of the benefits I saw on the methyl protocol was hair regrowth on my arms. I'd been looking at my arms for months, seeing the pigment changes and trying to understand what I was looking at. What I didn't see was that there was no hair on my arms. Zip. I was reading a thread of people talking about hair loss and it finally twigged that I was hairless on my arms, nearly so on legs. Now, after about 4 months on protocol, hair is regrowing. I've added other things during this time, as listed above, + lithium. Maybe there was some influence from these. Maybe being sulfur-free helped. I can only assume the methylfolate and B12 had an influence.

My condition is slowly improving. When I added the carnitine fumarate I wrote on a forum post that I felt perilously close to resolving my ME/CFS, it felt so good. And yet, the greatest gains have been in my interiority. My mind has settled, anxiety decreased, clarity increased. (Especially from the TMG, p5p, lithium.) My physical gains have been real, I can do my gentle exercise more frequently, more vigorously. But I can't do much of anything beyond my limited computer use and reading. I don't know whether the next gains are dependent upon methylation or treating the SNPs. I'll begin Dibencoplex when it arrives, probably this week. In any case I'm very grateful for all that you and the community have done to clarify and problem-solve this piece of the puzzle. ahmo

@ahmo I am writing to you on this thread, because I wanted to refresh your memory about your post from Feb. 2013 to this thread called "What Is Methyl Trapping ?" I don't know if I've gone about doing this properly, but this is a 1-page thread that actually touched on several things we've already discussed, as well as something new I wanted to ask you (which pertains to your post). Will ask you about the other things next time (which pertain to Fred's posts to someone else), because too tired now.

The new thing, is what's been going on with me for the past week as I've been increasing both my MF and MB12 again. I started FP a month ago at 1/4 tablets, and have increased slowly by 1/4 tablets every week or so. I've been doing my MF/MB12 3x/day for now, but planning to eventually increase to 4x/day when I can fine-tune my schedule. On Wed., 11/4, I increased to 3/4 tablet Solgar 400 mcg MF (300 mcg 3x/day = 900 mcg/day) and 3/4 ENZY MB12 1,000 mcg (750 mcg 3x/day = 2,250 mcg/day). I am also taking 1/8 capsule LCF 1-2x/day (still deciding whether to switch to ALCAR), and 1/4-1/2 Country Life AdB12 3,000 mcg 1-2x/week (waiting for Source Naturals AdB12 order because can't tolerate taste/smell of Anabol).

On Sat., 11/7, I decided to increase a little more, starting with my 2nd dose of the day, because I noticed my angular chellitis starting to flare, and Fred has that on his Group 3 symptoms list for more MF. I also decided to increase MB12 just to get them both up to 1 tablet 3x/day. After only one dose of the increase, I started getting really fatigued and foggy. Even taking two more 1/8 capsules of LCF in the afternoon didn't help. A few hours later, I noticed numbness and tingling in the bottoms of both feet, pain in feet/ankles, and leg weakness. This scared me a little, because it reminded me of the symptoms I had 10 years ago when I had the severe B12 deficiency I told you about. It's hard to distinguish, but sometimes those are also the same symptoms you briefly get when you're recovering from B12 deficiency.

I was confused about whether this was methyltrapping or donut hole paradoxical folate deficiency, or just having to get the right ratio between MF and MB12. For the 3rd (last) dose of the day, I decided to decrease MF back to 1/2 tablet but keep MB12 at the new 1 tablet dose. Almost immediately, I had more energy/clarity for a while, and by morning the feet/leg issues had subsided. However this morning my angular chellitis started to split open, and my diarrhea, which started even before doing FP and had finally begun subsiding yesterday, also got worse at 2am! (I was already in a cycle of several weeks of diarrhea possibly from trying glutathione before I heard about FP.) So this morning I decided to go back to the 3/4 MF dose I was at before increasing yesterday, but keep the MB12 at 1 tablet, hopefully for more energy. I didn't want to decrease MF too much, because I think it helped my angular chellitis and diarrhea. This morning I felt a little better, but already starting to feel tired/foggy.

Anyway, that brought me to this thread, and reading your Feb. 2013 post. You said after decreasing your MF from 3/day to 1/day, in just one day it reduced the itching of lesions on your scalp. In your 2nd post, you said on the second day with lower MF your rash disappeared. Usually Fred says to increase MF for skin stuff, but it seemed to be the opposite in your case. Maybe that's the difference between paradoxical folate deficiency and just taking too much? You also mentioned having to go up and down on your MB12 dose too before finding the right one. I have a lot of skin and hair loss issues like you, and one of your other posts about blood blisters in your mouth was the first time I ever heard of anyone else having them! Also IBS, and when I have time I'm going to write you about your probiotic posts, tho I'm on a good one already.

Anyway I wonder if you have any insights on what I should do? The fact that I'm already feeling so tired right now makes me wonder if I should cut back further on MF to 1/2 tablet, because that made me feel better last night. On the other side of the coin, I think increasing MF to 3/4 tablet last week was helping my diarrhea for the first time in over a month and my angular chellitis, both of which flared this morning after decreasing to 1/2 MF last night (or was it because I increased to 1 MB12?) Also the tingling is starting to return a little, in my hands too now. I have seen things turn around quickly with just one or two slight dose changes, but I don't know which to change. I was thinking of either staying where I am now (3/4 MF and 1 MB12) or going back to the 1 tablet each that I tried to do yesterday, and riding out this fatigue/tingling and seeing if it doesn't improve by tomorrow. However the return of the tingling is making me wonder if I should go back to 3/4 MB12 also. Do you think my body just needs to adapt to the stronger dose, or needs to go back to 1/2 tablet each where I was earlier this week. I didn't feel that great all the time then either, but I have had glimpses of improvement through this process, but sometimes have had to suffer a little before feeling better. I can't afford to go down the rabbit hole for too long, because I have the market and major cooking mid-week. I really appreciate any input you might have on this!