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

[Leopardtail]

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?

It's from about 1 year ago that I was reading up on this stuff, if I remember where, I will gladly post. Your mutation makes that a side issue.

If you have double 677T then you are very likely to need 5-MTHF, Dr Lynch has an excellent tabulation of what;'s needed.
I would start with Methyl-B12 @500mcg, then MethylFolate @200mcg (note Lynch recommends first B12, then Folate)
I personally would avoid folic acid where you can.
If that does not do the trick increase B-12 @1mg + Folate @400mcg.

I would not do anything about Glutathione until that stabilises.

Let us know what you decide and how you get on.

Leo

 

[PeterPositive]

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.

According to the simple folate cycle digram posted by @Sea, 5-MTHF (Metafolin) donates its methyl group to B12 (making methyl-B12) and goes back to THF.

DHF, instead, is a step higher in that cycle and if what you're saying is correct (oxidized DHF can become folic acid), then it would seem that a high consumption of dietary folate (DHF) is more risky than supplementing 5-MTHF.

Again, I am not an expert, all I could do is reading as much technical info as possible about folate cycle, methyl-trap, methylation cycle etc... I've never encountered this particular claim, which to me seems quite a big deal if correct. I am kind of surprised that no one (especially the expert methylation docs) have ever mentioned this.

Additionally I wonder why products like Deplin are not regarded as being dangerous in this sense.

Here dr. Ben Lynch talks about methylfolate toxicity:
http://mthfr.net/methylfolate-taking-too-much-a-problem/2012/01/08/

Here's another review of high dose 5-MTHF
http://cdn.neiglobal.com/content/blog/l-methylfolate.pdf

 

[Leopardtail]

According to the simple folate cycle digram posted by @Sea, 5-MTHF (Metafolin) donates its methyl group to B12 (making methyl-B12) and goes back to THF.

DHF, instead, is a step higher in that cycle and if what you're saying is correct (oxidized DHF can become folic acid), then it would seem that a high consumption of dietary folate (DHF) is more risky than supplementing 5-MTHF.

Again, I am not an expert, all I could do is reading as much technical info as possible about folate cycle, methyl-trap, methylation cycle etc... I've never encountered this particular claim, which to me seems quite a big deal if correct. I am kind of surprised that no one (especially the expert methylation docs) have ever mentioned this.

Additionally I wonder why products like Deplin are not regarded as being dangerous in this sense.

Here dr. Ben Lynch talks about methylfolate toxicity:
http://mthfr.net/methylfolate-taking-too-much-a-problem/2012/01/08/

Here's another review of high dose 5-MTHF
http://cdn.neiglobal.com/content/blog/l-methylfolate.pdf

Peter,

if you have double 677T your body has marked difficulty converting folates to 5-MTHF and that is what you need to supplement.
The SNP changes things completely.

If you have a normal Mediterranean diet (lots of leafy greens) you will have ample dietary folate in the other forms.

Leo

 

[PeterPositive]

Peter,

if you have double 677T your body has marked difficulty converting folates to 5-MTHF and that is what you need to supplement.
The SNP changes things completely.

If you have a normal Mediterranean diet (lots of leafy greens) you will have ample dietary folate.

Leo

Sure, thanks for your response. But my questions were more generic and regarding the claim in the opening post that you seem to find straightforward. A lot of people here take what might be considered high doses of methylfolate, in the thousands of mcgs, and probably some might be worried about the possibility to end up with elevated folic acid, which is what they are trying to avoid in the first place.

It would be great to see the scientific references for such claim and understand in which cases this is more likely to occur.

Cheers

 

[caledonia]

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

Good point. I'm going to see if I can get some clarification from MTHFRsupport on this statement.

 

[Sea]

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.

It may well be that our body utilises methylfolate in preference to Folic Acid, but those who have no trouble converting should not have high levels of Folic Acid unless they have been supplementing Folic Acid or supplementing methylfolate while not being careful to limit intake of Folic Acid from fortified foods.

I agree that it is possible that methylfolate supplementation may create a backlog of Folic Acid but the Folic Acid does not come from the methylfolate. It comes from supplementation or fortified foods.

For those who cannot convert efficiently obviously it would be better if they were never exposed to Folic Acid at all.

Once a person has high Folic Acid levels I don't know whether they would be better off avoiding folate and Folic Acid altogether for a while (since they do have some capacity to convert). This would however leave them deficient in folate for a period of time. Perhaps an intermittent schedule of methylfolate supplementation would be best. The research doesn't have these answers yet.

 

[Leopardtail]

It may well be that our body utilises methylfolate in preference to Folic Acid, but those who have no trouble converting should not have high levels of Folic Acid unless they have been supplementing Folic Acid or supplementing methylfolate while not being careful to limit intake of Folic Acid from fortified foods.

I agree that it is possible that methylfolate supplementation may create a backlog of Folic Acid but the Folic Acid does not come from the methylfolate. It comes from supplementation or fortified foods.

For those who cannot convert efficiently obviously it would be better if they were never exposed to Folic Acid at all.

Once a person has high Folic Acid levels I don't know whether they would be better off avoiding folate and Folic Acid altogether for a while (since they do have some capacity to convert). This would however leave them deficient in folate for a period of time. Perhaps an intermittent schedule of methylfolate supplementation would be best. The research doesn't have these answers yet.

If you observe Peter's post above, he falls into the group that has that trouble. Specifically conversion of MethylleneTetraHydroFolate to 5-MethylTetraHydroFolate. With such an issue surely less 5-mthf more often would yield lower build up of UTMF due to less short term excess?

On this point: "but the Folic Acid does not come from the methylfolate." you are diasagreeing with an authority on MethylFolate - evidence please?

Re the high folic - lynch does not advise avoidance of methyl-B9, however he is anti high doses in general.

 

[Sea]

On this point: "but the Folic Acid does not come from the methylfolate." you are diasagreeing with an authority on MethylFolate - evidence please?

I am not disagreeing with any authority. Folic Acid is a synthetic human invention.

 

[Leopardtail]

I am not disagreeing with any authority. Folic Acid is a synthetic human invention.

If you read the earlier post, you are disagreeing with an Authority (Lynch).

I suspect you misunderstood me here. High oxidative stress, combined with high dihydrofolate can create folic through oxidative stress with no need for a catalyst. This is what lynch discusses. This would not occur with natural folate consumption. Better read it direct from the horses mouth than me continue.

 

[Leopardtail]

Sure, thanks for your response. But my questions were more generic and regarding the claim in the opening post that you seem to find straightforward. A lot of people here take what might be considered high doses of methylfolate, in the thousands of mcgs, and probably some might be worried about the possibility to end up with elevated folic acid, which is what they are trying to avoid in the first place.

It would be great to see the scientific references for such claim and understand in which cases this is more likely to occur.

Cheers

Processing Folates requires ATP, my experience has been that those patients who deal with ATP first have few such problems. Methyl supps produce Methionine, but it takes three 'ATP equivalents' to convert it to SAM (which does the work).

Personally having read Lynch's work and corresponded with him those high doses cause me concern that these high doses mask another problem & raise risk.

Right now I am working on Cystine, so can't look that up for you,

perhaps asking Lynch directly might be best?

 

[Sea]

If you read the earlier post, you are disagreeing with an Authority (Lynch).

No I am not.

I suspect you misunderstood me here. High oxidative stress, combined with high dihydrofolate can create folic through oxidative stress with no need for a catalyst. This is what lynch discusses. This would not occur with natural folate consumption. Better read it direct from the horses mouth than me continue.

You keep saying methylfolate that is not used turns into Folic Acid. It does not. And Lynch does not say that it does, at least not in any reference on this thread.

"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." (Lynch)
This is not saying the methylfolate creates Folic Acid. It is saying it creates a backlog because the Folic Acid that is there can't be used.

 

[Leopardtail]

Peter,

if you type unmetabolised folic acid into pubmed. It will give several papers showing why folic is not a good idea. Not cover the burning out issue though...

I vaguely remember Dr Lynch discussing Folic competing with Folates for absorption by cells hence 'receptors' or 'transporters' might well be good to search for.

 

[adreno]

On this point: "but the Folic Acid does not come from the methylfolate." you are diasagreeing with an authority on MethylFolate - evidence please?

No, you are the one making the claim (that unused methylfolate turns into folic acid). The burden of evidence is on the person making the claim.

I have not seen any references to this, nor have I seen Lynch claim this.

 

[adreno]

Peter,

if you type unmetabolised folic acid into pubmed. It will give several papers showing why folic is not a good idea. Not cover the burning out issue though...

I vaguely remember Dr Lynch discussing Folic competing with Folates for absorption by cells hence 'receptors' or 'transporters' might well be good to search for.

This has got nothing to do with the question at hand. No one here is claiming that folic acid is a good idea, or that it doesn't compete for folate absorption.

 

[Little Bluestem]

Processing Folates requires ATP, my experience has been that those patients who deal with ATP first have few such problems. Methyl supps produce Methionine, but it takes three 'ATP equivalents' to convert it to SAM (which does the work).

I thought that unblocking the methylation cycle was supposed to deal with ATP. If it does not, then what does?

 

[acrosstheveil]

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/



Thoughts?

@ahmo

yes, i experienced this while trying to increase my methylfolalte dosage. In the end, I had to resort back to a low dose. like 2.4 mg a day.

 

[Leopardtail]

I thought that unblocking the methylation cycle was supposed to deal with ATP. If it does not, then what does?

It is thought that unblocking the methyl cycle and improving Glutathione protects energy generation - RVK's original thesis. But that thesis was done on patients who had first taken ATP supplements.
It helps a bit with ATP, but it's primary effect is to get various enzymes working and allow genes to bed switched on and off.

I have never seen any evidence that it comes close to ribose, coq10 etc for ATP improvements. From simple logic though creating SAM destroys an ATP molecules such that it cannot be 'recharged' meaning you don't get ADP. That means making it is the equivalent of at least three ADP->ATP conversions. That makes Methylation much more dependant on ATP than vice versa.

The way in which people get symptoms of over methylation when they add carnitine is the nearest thing to 'hard evidence' available now.

This one is a bit like knowing that metal falling on your head hurts, knowing gravity pulls metal down, so deciding standing under metal would not be smart. It's a common sense thing.

 

[PeterPositive]

"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." (Lynch)
This is not saying the methylfolate creates Folic Acid. It is saying it creates a backlog because the Folic Acid that is there can't be used.

This statement still doesn't make sense to me What is exactly the cause of the backlog? Methylfolate? Why? Isn't the backlog supposed to be unmetabolized folic acid?

If so the problem is that the body's enzymes can't process folic acid. Methylfolate supplementation seems irrelevant to this problem.

If DHF can indeed oxidize and become folic acid (pteroylglutamic acid) then that's a different story... people like myself with C677T double mutation should be wary of eating too many dietary folate.

 

[Sea]

This statement still doesn't make sense to me What is exactly the cause of the backlog? Methylfolate? Why? Isn't the backlog supposed to be unmetabolized folic acid?

If so the problem is that the body's enzymes can't process folic acid. Methylfolate supplementation seems irrelevant to this problem.

If DHF can indeed oxidize and become folic acid (pteroylglutamic acid) then that's a different story... people like myself with C677T double mutation should be wary of eating too many dietary folate.

In a person who cannot process Folic Acid efficiently unmetabolised Folic Acid builds up. If you avoid all supplementation and dietary folate (not that this is necessarily a good thing) some of the Folic Acid will be converted. A homozygous C677T operates at about 30% of normal in this conversion process.

If you supplement with methylfolate your body will use that preferentially and the unmetabolised Folic Acid will remain. If you don't avoid Folic Acid while supplementing methylfolate Folic Acid will build up.

 

[Leopardtail]

This statement still doesn't make sense to me What is exactly the cause of the backlog? Methylfolate? Why? Isn't the backlog supposed to be unmetabolized folic acid?

If so the problem is that the body's enzymes can't process folic acid. Methylfolate supplementation seems irrelevant to this problem.

If DHF can indeed oxidize and become folic acid (pteroylglutamic acid) then that's a different story... people like myself with C677T double mutation should be wary of eating too many dietary folate.

The issues Dr Lynch talks about occur with high doses of Folate, small amounts seem unlikely to do this. In the article you reference Lynch talks about quite high doses of 5-MTHF.

Enzymes (often) do only as much work as they need to. They are designed to use resource efficiently. If there is loads of tetrahydro- the enzyme that converts folic to it slows down. Hence lots of folate means folic builds up because its not used.