Burned out folate receptors - why you need high dose methylfolate?

[caledonia]

I just saw this info contained in an MTHFRsupport.com fact sheet. I put the relevant part in bold.
http://www.mthfrsupport.com/mthfr-facts/

Many doctors are giving high doses of L-Methylfolate. When should they consider lower dosages?

When folate levels are not extremely low. Many people have done well on just 400mcg-800mcg of folate daily along with a folate (not folic) rich diet. Giving too much L-methylfolate to certain individuals can cause a back up in high folic acid levels for the folate that they are not utilizing. Unmetabolized folic acid is one of the risk factors in colorectal cancer. Excess folic acid (not folate) can then burn out folate receptors. High levels of L-methylfolate can put a burden on people with COMT V158M and H62H expressing who have a hard time breaking down epinephrine. Methyl donors like L-methylfolate can elevate epinephrine and lead to anxiety and panic attacks in individuals with COMT V158M and H62H expressing.

Thoughts?

@ahmo

 

[PeterPositive]

I don't understand what it means that high dose folate supplementation can cause a backup in high folic acid levels. What is it supposed to mean?

 

[Sea]

Evidence?

 

[Leopardtail]

I don't understand what it means that high dose folate supplementation can cause a backup in high folic acid levels. What is it supposed to mean?

This stuff is fairly basic folate metabolism. If cells are unable to use methyl-folate it oxidises until it becomes folic acid. Folic acid is hard to convert back to MethylFolate, it blocks access to transporters that allow 5-MTHF in, and being an acid, too much can oxidise=burn tissue.

With most B-vitamins, there is risk of toxicity at high doses.

 

[Snowdrop]

I have only the most rudimentary understanding of biochemistry but when I first started methylation I did so with the idea of using hydroxoB12. I thought first that it would mop up some of the cyanide that had to be floating around from all the fortified food (CB12) I ate and also that it would smooth out (control) methylation by the HB12 splitting off the hydrogen and picking up the methyl from the Mfolate.

I felt better when I was taking the hydroxoB12 but that doesn't necessarily mean it was working better since I understand that there is supposed to be some discomfort when healing (a little more than I can deal with).
Sorry if this is a tangent from the intention of the thread.

 

[Leopardtail]

I have only the most rudimentary understanding of biochemistry but when I first started methylation I did so with the idea of using hydroxoB12. I thought first that it would mop up some of the cyanide that had to be floating around from all the fortified food (CB12) I ate and also that it would smooth out (control) methylation by the HB12 splitting off the hydrogen and picking up the methyl from the Mfolate.

I felt better when I was taking the hydroxoB12 but that doesn't necessarily mean it was working better since I understand that there is supposed to be some discomfort when healing (a little more than I can deal with).
Sorry if this is a tangent from the intention of the thread.

Hyroxo-B12 is better at various detox functions - it's the only form of B12 effective for dealing with excess nitric oxide or peroxy-nitrate, as you point out it also binds mercury. So far as Mercury goes, Freddd leads me to understand there is controversy over whether methyl- or hydroxy-B12 is better.

 

[caledonia]

This stuff is fairly basic folate metabolism. If cells are unable to use methyl-folate it oxidises until it becomes folic acid. Folic acid is hard to convert back to MethylFolate, it blocks access to transporters that allow 5-MTHF in, and being an acid, too much can oxidise=burn tissue.

With most B-vitamins, there is risk of toxicity at high doses.

I looked this up and it's true:

folic acid = oxidized methylfolate

oxidized methylfolate = folic acid

=-=-==-=--=

MTHFRsupport says too much methylfolate (in certain people?) creates folic acid. Woah.

I was thinking they were referring to people who had taken prior folic acid supplementation.

So by taking too much methylfolate (in certain people), you can create the very thing you're trying to avoid.

The next question is, who are these certain type of people? Does this have anything to do with FOLR mutations (FOLR = folate receptor).

 

[PeterPositive]

Thanks everyone for adding some clarifications.
I am still scratching my head since the original excerpt doesn't define "too much" and "certain people", leaving the statement open to almost any interpretation.

Is a few thousand mcg too much or are we talking about Deplin-like doses?

I suppose a good way to avoid the problem is keeping an eye on the oxidized folate levels. My levels of folic acid for example have never gone down even after 1 year of stopping any direct supplementation. This is likely to explain why, part of the methylfolate I am taking goes back to oxidized form...

 

[Sea]

This stuff is fairly basic folate metabolism. If cells are unable to use methyl-folate it oxidises until it becomes folic acid. Folic acid is hard to convert back to MethylFolate, it blocks access to transporters that allow 5-MTHF in, and being an acid, too much can oxidise=burn tissue.

With most B-vitamins, there is risk of toxicity at high doses.

Folic Acid is an oxidised synthetic version of folate. The only source of it is supplementation. Our bodies do not make folic acid.

http://www.aacc.org/publications/cln/archive/2011/january/Pages/FolateMetabolismFigure.aspx

 

[Sea]

I suppose a good way to avoid the problem is keeping an eye on the oxidized folate levels. My levels of folic acid for example have never gone down even after 1 year of stopping any direct supplementation. This is likely to explain why, part of the methylfolate I am taking goes back to oxidized form...

If your body is not efficient at converting Folic Acid to Methylfolate that would explain why your levels are still high after stopping any supplementation. Unmetabolised Folic Acid can stay in your system for a long time. The methylfolate you are taking does not turn into Folic Acid

 

[adreno]

I looked this up and it's true:

folic acid = oxidized methylfolate

oxidized methylfolate = folic acid

Can we see some scientifically valid references, when discussing this? If not, this thread is just meaningless talk.

 

[PeterPositive]

Folic Acid is an oxidised synthetic version of folate. The only source of it is supplementation. Our bodies do not make folic acid.

http://www.aacc.org/publications/cln/archive/2011/january/Pages/FolateMetabolismFigure.aspx

This is what I always thought, but now I am confused

If your body is not efficient at converting Folic Acid to Methylfolate that would explain why your levels are still high after stopping any supplementation. Unmetabilised Folic Acid can stay in your system for a long time. The methylfolate you are taking does not turn into Folic Acid

That's the question... I have never heard of this before. I've watched an entire 8 hour methylation webinar with Dr.Lynch and this never came up even though a specific section was dedicated to unmetabolized folic acid.

In any case my levels of folic acid have been the same for over a year. They don't budge. Which would make sense with what you say. It could be "floating in there", without any use.

@Leopardtail
I am not a chemist or an expert in folate metabolism but I suppose that oxidation is not an on/off switch, meaning that you don't jump from 5-CH3-THF up to folic acid (C19H19N7O6) in one step... just like the reverse is true.

So I am still very confused...

 

[Jarod]

I do better with 4800 mcg a day of methylfolate and don't even have the MTHFR mutation. For whatever that is worth.

 

[Leopardtail]

This is what I always thought, but now I am confused


That's the question... I have never heard of this before. I've watched an entire 8 hour methylation webinar with Dr.Lynch and this never came up even though a specific section was dedicated to unmetabolized folic acid.

In any case my levels of folic acid have been the same for over a year. They don't budge. Which would make sense with what you say. It could be "floating in there", without any use.

@Leopardtail
I am not a chemist or an expert in folate metabolism but I suppose that oxidation is not an on/off switch, meaning that you don't jump from 5-CH3-THF up to folic acid (C19H19N7O6) in one step... just like the reverse is true.

So I am still very confused...

This stood is only half understood by the people who study it, I needed nearly six months to half understand it.

Folate Metabolism is complex. Your body does not have an enzyme that converts 5-MTHF to folic acid, nor does it happen in one step. What Dr Lynch is referring to is Folate your body reacting with other chemicals (free radicals), that's different your body doing it. If you are in America one issue is they add Folic to flour. I had high folic acid but low folate, despite high B12 and never having supplemented Folic.

The two possibilities are your cells aren't absorbing it, or you have an issue converting it to active folate.

They key point you need to take home is that 400mcg is enough 5-MTHF for most people, 800mcg is the max and should not be exceeded unless an expert medic tells you to do it.

Have you ever had a full folate panel done? I found the one from vitamin diagnostics useful

 

[Leopardtail]

Folic Acid is an oxidised synthetic version of folate. The only source of it is supplementation. Our bodies do not make folic acid.

http://www.aacc.org/publications/cln/archive/2011/january/Pages/FolateMetabolismFigure.aspx

Our bodies have no enzyme to do this but dihydrofolate in large amounts can be oxidised by free radicals, also with too much active folate, your body won't use Folic. The enzymes feature allosteric inhibition, & osmotic action requires less of a metabolite in cells than outside in the absence of an active transporter.

 

[PeterPositive]

Have you ever had a full folate panel done? I found the one from vitamin diagnostics useful

Yes, I have and I have low level of all forms of folate with the exclusion of folic acid, which I have taken as a supplement for around 1 year, which would explain it. I live in Italy and we don't have fortified foods like you have in the US.

Also I have the C677T double mutation of the MTHFR gene, which makes me a slow folate converter.

Do you have any article references for this process of conversion / oxidation back into folic acid?

 

[Leopardtail]

This is what I always thought, but now I am confused


That's the question... I have never heard of this before. I've watched an entire 8 hour methylation webinar with Dr.Lynch and this never came up even though a specific section was dedicated to unmetabolized folic acid.

In any case my levels of folic acid have been the same for over a year. They don't budge. Which would make sense with what you say. It could be "floating in there", without any use.

@Leopardtail
I am not a chemist or an expert in folate metabolism but I suppose that oxidation is not an on/off switch, meaning that you don't jump from 5-CH3-THF up to folic acid (C19H19N7O6) in one step... just like the reverse is true.

So I am still very confused...

Converting folate requires active forms of B3, have you ever checked that?

 

[Leopardtail]

I looked this up and it's true:

folic acid = oxidized methylfolate

oxidized methylfolate = folic acid

=-=-==-=--=

MTHFRsupport says too much methylfolate (in certain people?) creates folic acid. Woah.

I was thinking they were referring to people who had taken prior folic acid supplementation.

So by taking too much methylfolate (in certain people), you can create the very thing you're trying to avoid.

The next question is, who are these certain type of people? Does this have anything to do with FOLR mutations (FOLR = folate receptor).

yep, you got it... It's worth bearing in mind that Dr lynch is the expert on folic acid. He places the entries into PubMed for folic/folate related research, hence has knowledge of stuff we can't see.

 

[Leopardtail]

Can we see some scientifically valid references, when discussing this? If not, this thread is just meaningless talk.

It's meant to be some basic info, if you want more details your best bet is MTHFR.net. It's search engine is awful though, so it' takes persistence.

I will at a later time be writing a paper on this complete with references, but right now it's #3 on my to do list. I am hoping somebody beats me to it.

 

[PeterPositive]

Converting folate requires active forms of B3, have you ever checked that?

Yes, actually B2 and B3 in their active forms.

MTHFR contains a bound flavincofactor and uses NAD(P)H as the reducing agent.

http://en.wikipedia.org/wiki/Methylenetetrahydrofolate_reductase