Sign the White House Petition to end Mandatory Flour Fortification with Folic Acid

[Ripley]

I see lots of stuff about folate and methylation on PR, indeed, but I have never figured out what the reason is to think is has anything to do with ME other than somebody once had a theory about it.

Ah.. I see. So, because you haven't figured it out, the theory must be dismissed or not talked about. That makes a lot of sense.

Keep in mind that this thread was literally posted in the, "'Detox: Methylation; B12; Glutathione; Chelation" forum. Like it or not, the discussion is relevant to methylation, period.

 

[Jonathan Edwards]

I am not dismissing anything. I am here to learn. But I hear nothing whatever about methylation at scientific meetings on ME and I have not yet come across any evidence for it being relevant to ME despite the vast amount of discussion. If you can explain what the evidence is that would be great. All I have come across is a theory by Dr van Konynenburg that did not sound very plausible on general epidemiological grounds.

 

[Ripley]

Sorry, but it's right.

You are deliberately confusing the issue (much like the FDA does).

Read this explanation:

Folic Acid vs. Folate: Part I

The terms “folate” and “folic acid” are often used interchangeably but they are not one and the same. Folates are members of the B vitamin family (referring to various tetrahydrofolate derivatives) naturally occurring in foods, mainly leafy green vegetables. Folic acid, on the other hand, is a fully oxidized, synthetic compound (pteroylmonoglutamic acid), used in dietary supplements and in food fortification. The important difference to note is that folic acid does not occur naturally.

While you are technically correct that folic acid is a kind of folate, the author of the petition is obviously referring to natural folates. Even the Wikipedia article on the subject highlights this distinction in the food industry:

Wikipedia: Folic Acid

The term folate in the food industry often refers to "the natural occurring form of folic acid"...All the biological functions of folic acid are performed by tetrahydrofolate and other derivatives. Their biological availability to the body depends upon dihydrofolate reductase action in the liver. This action is unusually slow in humans, being less than 2% of that in rats. Moreover, in contrast to rats, an almost-5-fold variation in the activity of this enzyme exists between humans.[10] Due to this low activity, it has been suggested this limits the conversion of folic acid into its biologically active forms "when folic acid is consumed at levels higher than the Tolerable Upper Intake Level (1 mg/d for adults)."

Said in slightly more understandable terms:

The little known (but crucial) difference between folate and folic acid

The form of folate that can enter the main folate metabolic cycle is tetrahydrofolate (THF). (2) Unlike natural folates, which are metabolized to THF in the mucosa of the small intestine, folic acid undergoes initial reduction and methylation in the liver, where conversion to the THF form requires dihydrofolate reductase. The low activity of this enzyme in the human liver, combined with a high intake of folic acid, may result in unnatural levels of unmetabolized folic acid entering the systemic circulation.

 

[Ripley]

I am not dismissing anything. I am here to learn. But I hear nothing whatever about methylation at scientific meetings on ME and I have not yet come across any evidence for it being relevant to ME despite the vast amount of discussion. If you can explain what the evidence is that would be great. All I have come across is a theory by Dr van Konynenburg that did not sound very plausible on general epidemiological grounds.

I see. Well, you would have to ask @Fredd and others for more details. I'm afraid I would butcher their research. You may want to start a new thread, since your question is really about questioning the role of the entire methylation cycle in ME/CFS, but I suppose talking about it here is fine if more people learn about the petition that way.

I would point out that @Fredd 's treatment plan (which vehemently tries to avoid folic acid) seems to help people here, so I would think it must be related somehow.

 

[Jonathan Edwards]

You are deliberately confusing the issue (much like the FDA does).

Read this explanation:

While you are technically correct that folic acid is a kind of folate, the author of the petition is obviously referring to natural folates. Even the Wikipedia article on the subject highlights this distinction in the food industry:

Said in slightly more understandable terms:

Yes but I am a scientist with a biochemical training. When I see someone writing a petition with a basic mistake like this (from the point of view of a biochemist) I am likely to be unimpressed. The first citation you give is from a magazine for people who sell supplements as far as I can see. The third one also seems to be a commercial supplement site. These are hardly authoritative. Wikipedia can be good but it tends to be taken over by enthusiasts in this sort of situation. 'Folates' in the plural is not folate either - it is a generic term for related compounds.

I prefer to go with the word usage of the sort of scientific papers quoted above than that of an industry designed to put a gloss on things.

 

[Ripley]

Yes but I am a scientist with a biochemical training.

Excellent. Then perhaps you can make sense of this (Free Download):

British Journal of Nutrition: Folic Acid under scrutiny (2007)

Note the obvious fact that "folic acid" would not be "under scrutiny" if it was identical to naturally occurring folates.

 

[Jonathan Edwards]

I see. Well, you would have to ask @Fredd and others for more details. I'm afraid I would butcher their research. You may want to start a new thread, since your question is really about questioning the role of the entire methylation cycle in ME/CFS, but I suppose talking about it here is fine if more people learn about the petition that way.

I would point out that @Fredd 's treatment plan (which vehemently tries to avoid folic acid) seems to help people here, so I would think it must be related somehow.

I am not asking for details. Just some basic idea why PWME are interested in folates. I found a piece on Cort Johnson's Health Rising from last summer and basically it says that there is no evidence to support RvK's suggestion. It was just a speculation. In the whole article there is actually no explanation for why folates should be relevant to ME. Lots of treatment plans seem to help people - I am afraid that proves nothing.

 

[Ripley]

I am not asking for details. Just some basic idea why PWME are interested in folates. I found a piece on Cort Johnson's Health Rising from last summer and basically it says that there is no evidence to support RvK's suggestion. It was just a speculation.

I'm afraid you're asking the wrong person (I don't have ME/CFS). I simply posted this in the "'Detox: Methylation; B12; Glutathione; Chelation" forum because it is relevant to that topic, period.

In the whole article there is actually no explanation for why folates should be relevant to ME. Lots of treatment plans seem to help people - I am afraid that proves nothing.

Oy vey. This is the "'Detox: Methylation; B12; Glutathione; Chelation" forum. If you feel the "'Detox: Methylation; B12; Glutathione; Chelation" forum is too speculative to be part of PR, you ought to take it up with the moderators. This specific thread does not require any more explanation than any other thread in this area of the forum.

 

[Jonathan Edwards]

I'm afraid you're asking the wrong person (I don't have ME/CFS). I simply posted this in the "'Detox: Methylation; B12; Glutathione; Chelation" forum because it is relevant to that topic, period.

Oy vey. This is the "'Detox: Methylation; B12; Glutathione; Chelation" forum. If you feel the "'Detox: Methylation; B12; Glutathione; Chelation" forum is too speculative to be part of PR, you ought to take it up with the moderators. This specific thread does not require any more explanation than any other thread in this area of the forum.

So are you saying that you have not even tried to find out why PWME are interested in folates - which seemed to be what you were chiding me for doing?

I have nothing against speculation, and in fact welcome it and do it myself, and I don't think it is the business of the moderators. What I do find it hard to see is what concerns about folic acid giving people cancer has to do with ME. At least this ought to be a forum about the relevance of methylation to ME, shouldn't it? And nobody seems to know what that is!

 

[Jonathan Edwards]

Excellent. Then perhaps you can make sense of this (Free Download):

British Journal of Nutrition: Folic Acid under scrutiny (2007)

Note the obvious fact that "folic acid" would not be "under scrutiny" if it was identical to naturally occurring folates.

It makes perfect sense. Naturally occurring 'folates' in the plural is understood to be generic. But I note that the author tries very hard to pin the blame on folic acid and distinguish it from folates for almost all the paper. The near the end she quotes studies in which cancer is linked to blood levels of 'folate' or 'folate intake'. If she means folic acid then presumably she agrees with me that the two are interchangeable. If she means folates that suggests that the risk of cancer has nothing to do with folic acid per se - it is an effect of folates in general. So I can make sense of it but as a result find there are some rabbits loose in this story - in fact something of a Watership Down!

 

[Ripley]

So are you saying that you have not even tried to find out why PWME are interested in folates - which seemed to be what you were chiding me for doing?

I'm chiding you for taking up the relevancy of an entire PR sub-forum, based on an extremely broad health issue ('Detox: Methylation; B12; Glutathione; Chelation), within the context of this thread. You are literally high-jacking this thread.

At least this ought to be a forum about the relevance of methylation to ME, shouldn't it? And nobody seems to know what that is!

Absolutely. Why don't you start a new thread about it.

 

[adreno]

At least this ought to be a forum about the relevance of methylation to ME, shouldn't it? And nobody seems to know what that is!

It's hard to prove relevance to something we don't know what is (ME). However the methylation cycle has long been speculated to be involved in ME. If you want to know what it is, you can read Rich Vanks work.

There is evidence that people with MTHFR mutations cannot convert folic acid to its active form, methylfolate. That is basically why folic acid is undesirable (for everyone, not just PWMEs).

 

[Hip]

I do get the impression that the methylation protocol, when discussed on this forum, often descends into pseudoscience.

This is not to say that methylation does not help some ME/CFS patients; however, no other protocol used by ME/CFS patients gets into this highly ornate Nth degree discussion on how, when a ME/CFS patient has found no benefit from methylation, there may be blockages or obstacles to it working.

When the methylation protocol does not help, it's not just a simple case of accepting that methylation was not useful for the patient; if it did not help, then there is this idea that if the patient could just make some cunning adjustments to their protocol, it would suddenly begin to work.

With other ME/CFS protocols or treatments (such oxymatrine, inosine, Valcyte, low-dose naltrexone), patients may try them, and if they are found not to work for them, that is that, and a patient will move on to another protocol to try out.

But not so with the methylation protocol. If that does not work, patients then get involved in all this ornate speculation about methylation blockages or obstacles, which sound like very science-like, but I am not aware of any empirical evidence supporting the idea that methylation can be blocked by one of the "cogs" getting stuck in the machinery of methylation.

What's worse, although there is no empirical evidence for overcoming these blockages that I have come across — and not even any decent anecdotal evidence (I don't know anyone on this forum who has overcome these mythical blockages) — people on will often talk about all this Nth degree discussion on methylation blockages as if were fact.

When you present as a fact something that at best is highly speculative, that is pseudoscience.

 

[Jonathan Edwards]

That was pretty much my take, Hip. Well put.

 

[Jonathan Edwards]

It's hard to prove relevance to something we don't know what is (ME). However the methylation cycle has long been speculated to be involved in ME. If you want to know what it is, you can read Rich Vanks work.

There is evidence that people with MTHFR mutations cannot convert folic acid to its active form, methylfolate. That is basically why folic acid is undesirable (for everyone, not just PWMEs).

I am very ready to be shown layers of complexity that I have missed with these mechanisms, Adreno, and I like to tease things out until I get the full picture, but I do find this one confusing.

You say it is hard to prove relevance to ME, but we know what ME is - it is whatever is making life miserable for a whole lot of people with PEM and brain fog and OI and all that. I don't really buy that as a reason for not knowing the relevance. The reason seems to me more that nobody is quite sure what the hypothesis is that needs testing.

My understanding is that MTHFR mutations are very common in the general population so they don't seem to be too much of a problem for metabolism per se. If people with these mutations cannot convert folic acid to reduced folates then why is folic acid undesirable? Surely it would just be useless. I cannot see how it can stimulate cancer cells to divide unless it DOES get converted to the reduced forms since the unreduced form is inactive. I don't get it. I guess my question is whether anyone gets it or is it all a muddle.

 

[deleder2k]

I see lots of stuff about folate and methylation on PR, indeed, but I have never figured out what the reason is to think is has anything to do with ME other than somebody once had a theory about it.

Thank you for raising an interesting question. It was time that someone did. As I see it the theory about methylation issues leading to or maintain ME is without any basis in reality.

 

[sregan]

What's worse, although there is no empirical evidence for overcoming these blockages that I have come across — and not even any decent anecdotal evidence (I don't know anyone on this forum who has overcome these mythical blockages) — people on will often talk about all this Nth degree discussion on methylation blockages as if were fact.

When you present as a fact something that at best is highly speculative, that is pseudoscience.

It's anectodotal which is the past has been mostly relegated to "home remedies" but with the internet it has some real substance behind it. With thousands of clinical trial subjects. I think it's dismissive to call it pseudo-science.

Most people here don't have any other options because science doesn't know what's wrong with them. But scientific studies are referenced all the time. So we don't disregard science but not waiting for it at the same time.

And I don't see anyone here saying that methylation is the one key fits all treatment for ME. But some people are having tremendous success with it to the point of complete remission. That cannot be ignored.

 

[Hip]

It's anectodotal which is the past has been mostly relegated to "home remedies" but with the internet it has some real substance behind it.

It's not even anecdotal. Can you point me to any ME/CFS patient who tried the standard Rich Van Konynenburg methylation protocol and observed no benefit, but then by making some cunning adjustments to their methylation protocol to get one of these mythical blocked methylation "cogs" running, suddenly found that methylation brought noticeable benefits.

I am not saying methylation is pseudoscience; but this idea that if you keep tinkering with a methylation protocol that does not work for you, you will somehow be able to overcome these mythical methylation blockages; that seems to be pseudoscience.

Most people here don't have any other options because science doesn't know what's wrong with them.

There are other options. For example, Dr Jay Goldstein provided this list of drugs which he found often had benefits for his ME/CFS patients. You might be better advised to devote your time and energy to trying some of these, or some of the other protocols for ME/CFS, rather than getting bogged down in all this tinkering a with a methylation protocol that does not work for you.

 

[sregan]

I am not saying methylation is pseudoscience; but this idea that if you keep tinkering with a methylation protocol that does not work for you, you will somehow be able to overcome these mythical methylation blockages; that seems to be pseudoscience.

Or anecdotal because others have made adjustments and made progress. The protocol is not set in stone or even that mature. It's a work in progress which is why you are seeing many making adjustments and doing better. I would hate to see someone who could have been helped stop because they didn't take enough Zinc.

Maybe in a year when a more formal protocol is established with all proper cofactors and dosage ranges. Then if it works great if not move on to another possible cause/treatment.

 

[adreno]

If people with these mutations cannot convert folic acid to reduced folates then why is folic acid undesirable? Surely it would just be useless. I cannot see how it can stimulate cancer cells to divide unless it DOES get converted to the reduced forms since the unreduced form is inactive. I don't get it. I guess my question is whether anyone gets it or is it all a muddle.

In the blog post by Lynch already linked to you in this thread, several examples of why folic acid is undesirable are given.

This science is in its very infancy now, and we don't have all the answers. But the hypothesis seems to be that the inactive folic acid blocks active folate through binding to transporters and receptors, thereby contributing to a functional folate deficiency.