• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of, and finding treatments for, complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia, long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

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

DanME

Senior Member
Messages
289
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.

It is true! Where is the evidence? To this very point the Methylation theory by RvK is just that...a theory. To prove it, we would need placebo controlled, blinded and randomised trials, but they were never conducted. I don't know a single one. And besides that, which of the dozen of slightly different protocols is the right one? We would need even more controlled trials to differ their effectiveness. Anecdotal success stories, a huge amount of discussion and a pile of theories are no replacement for conducting real scientific studies.
 

Ripley

Senior Member
Messages
402
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.


Well, one theory the excess folic acid floating around the body blooms candida—candida can metabolize folic acid, and candida has been linked to cancer (i.e. most cancer patients have rampant candida). Since nobody can easily explain how candida causes cancer, you'll just call that "pseudoscience," of course, so I'm hesitant to mention it.

Does anyone here believe that candida plays a role in ME/CFS? I'll bet more than a few do.

At any rate, does it even matter what the mechanism is? The point is that even a double blind, placebo controlled randomized trial of 1021 men and women carried out over a 10 year period showed that, “Folic acid was associated with higher risks of having 3 or more adenomas and of noncolorectal cancers."
http://www.ncbi.nlm.nih.gov/pubmed/17551129

If controlled medical trials can't easily explain the mechanism, do you just ignore the problem? Or do you feed the offending supplement to millions of Americans who don't need it?

Folic acid fortification is intended to prevent rare NTD birth defects that ONLY affected 0.05% of US births before fortification began. Meanwhile, the majority of the population has difficulty utilizing that supplement. It's a ridiculous policy that should be ended.

And frankly, it's
such a dumb policy that I'm surprised more people haven't filled out the petition yet. That's too bad, since the few people who probably understand the bad science behind this policy blunder are here on this forum!
 
Last edited:

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
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.

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.

Methylation protocol has gotten me from off the bed to now some days now not lying down through the day. My life-long insomnia has resolved, my cognition is incomparably better. I initially tried Rich VanK's SMP, but no amount of tweaking made it work for me. When I switched to Freddd's Protocol, I started having results. When I finally became brave enough to really increase my levels of Methylfolate, I really started to feel better.

I've also discovered that I'm one of those that has problems with folinic acid. It never worked as a supplement for me in Rich's SMP. And eventually I found that green vegetables, which are sources of folinic form, block Methylfoate for me, and cause adrenal stress. This seems to be related to MTHFR, I've read. My experiences are anecdotal. But they are my experiences, in my body. Folate and fixing the methylation cycle has returned me to the land of the living.
 

Ripley

Senior Member
Messages
402
Last edited:

sregan

Senior Member
Messages
703
Location
Southeast
Why are we doing this? What is the point. There are differing views going on. Everyone can have their viewpoint (like politics, religion, whatever) and we can go about our business. This is the B12/Methylation forum for people to discuss these theories. If you can do nothing but shoot them down I would ask why do you feel the need? It's not your job to educate us and not our job to enlighten you.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
If you can do nothing but shoot them down I would ask why do you feel the need? It's not your job to educate us and not our job to enlighten you.

Because that is how science works - by shooting down the ideas that do not quite add up. If the idea is to talk scientific theories about ME then there isn't much point unless one take the scientific approach. Biochemistry is like chess, very complicated and very predictable if you follow all the complexities. If a theory predicts something that sounds right (like your knight takes a bishop) that is no good if it also predicts something that does not add up (like then his queen can take your rook). What I see on these sites on methylation is a muddle of ideas that look good at first glance and then make no sense at all. If folic acid blocks the enzyme then it should be a good anti-cancer drug and lots of babies should have had horrible malformations when they first added it to Mother's Pride. The numbers don't work as far as I can see.

Why are we doing this? What is the point.

For me the point is trying to figure out what the hell is going on in ME and the way a scientist does that is not to pick something that looks trendy but to systematically knock down all the options that do not work and see what is left. It is a painful process if you have a favourite theory but if you don't have a favourite theory it works very well in my experience.

I realise full well that I sound patronising. But you get like that if dealing with half baked stuff on the net. Someone said that now we have the net we have more evidence. But what we have is more people pushing a line because it suits them - often financially. We have oceans of junk ideas and every time you Google you are being conned by the marketing people who know exactly what adverts to flash up on your particular screen.

Perhaps more specifically the point for me is to try to persuade my colleagues that PWME have a real illness and are not weirdos who think they have a non-existent disease due to viruses or strange metabolic defects that scientists have wilfully ignored. As part of that it helps me to try to find out if any if these theories actually make sense and so far the methylation idea seems to me to be a complete muddle that generates contradictory predictions at every turn.
 

Sidereal

Senior Member
Messages
4,856
Methylation hypotheses of ME/CFS make no sense to me but that could just be my limited knowledge/understanding.

What I do see in these discussions is people taking huge supraphysiologic doses of reduced forms of folate and methylated B12 and sometimes improving on some fronts but also causing new problems to emerge like psychiatric symptoms and low potassium. Many people also report reactions that sound like increased glutamate/excitotoxicity and inflammation but these are often interpreted as "detox" or "start up reactions" or "CBS/sulfur issues" and the person is encouraged to continue supplementation, add more supplements, up the dose...

Any form of folate supplementation dramatically worsens my condition, by the way.

That said, problems with folic acid utilisation in those of us with DHFR and MTHFR SNPs are real. Folic acid supplementation is also bad for those who have a B12 deficiency (but don't know about it so are not supplementing B12) due to methyl trapping.

Some have even hypothesised that one of the factors driving the autism epidemic is folic acid fortification of foods reducing the incidence of neural tube defects but instead resulting in those pregnancies that would otherwise have been spontaneously aborted coming to full term and giving rise to neurodevelopmental disorders.

I think women planning to become pregnant should supplement vitamins if they and their doctors think this is indicated instead of the government getting to shove folic acid down everyone's throat.
 

adreno

PR activist
Messages
4,841
If folic acid blocks the enzyme then it should be a good anti-cancer drug
Wrong again, Professor. It's not natural folates that increase cancer risk, it's unmetabolized folic acid:

Also, concerns have been raised about the potentially untoward effects of unmetabolized synthetic folic acid with regard to cancer, depression, and cognitive impairment. With all these concerns, early data suggest supplementation with l-methylfolate rather than folic acid may mitigate these risks.


More on MTHFR mutations:

Genetic variations (polymorphisms) are common within the human genome and, in some cases, can result in the production of proteins with altered biologic activity. Several such polymorphisms have been identified in the genes encoding proteins involved in folate metabolism. As noted, metabolic processes requiring methyl group donations are regulated by the enzyme MTHFR. In the United States, up to approximately 60% of the population are intermediate metabolizers of folate or heterozygous for genetic polymorphism of the MTHFR enzyme,8 whereas up to 25% of certain populations are homozygous for these genetic variations.5 In varying degrees, these polymorphisms impair the conversion of folate to its active form, l-methylfolate. For example, individuals who are poor metabolizers of folate are homozygous for the common variant MTHFR 677C->T genotype and show approximately 30% of the enzyme activity found in those with the wild-type (CC) variant, whereas heterozygotes for the same genetic polymorphism have around 65% of wild-type enzyme activity.9 With another variant, MTHFR 1298A->C, homozygous individuals can display catalytic activity of the enzyme that is reduced to 68% of the wild-type activity.10

Based on the high prevalence of MTHFR genetic polymorphisms in the general population and concerns about reduced enzymatic activity and, therefore, less biologically available l-methylfolate, newer research in this area has focused on supplementation with l-methylfolate rather than folic acid as a means of preventing folate-related pathology.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218540/
 
Messages
18
Any form of folate supplementation dramatically worsens my condition, by the way.

It is complex and interrelated, a quote from a difficult paper: (2013)

"The vitamin folate is required for methionine homeostasis in all organisms. In addition to its role in protein synthesis, methionine is the precursor to S-adenosyl-methionine (SAM), which is used in myriad cellular methylation reactions, including all histone methylation reactions.

Folate, methionine, and SAM have essential functions in cells unrelated to histone methylation—for instance, folate is necessary for synthesis of purines (Rébora et al. 2005), methionine is crucial for all protein synthesis, and methylation via SAM is required for rRNA maturation (Tollervey et al. 1991). In principle, if a nutritional deficiency were to compromise one of these other functions before affecting histone methylation, the cell would likely die of the nutritional deficiency without histone methylation levels being perturbed. Thus, the results in this study implied the existence of a metabolic triage mechanism in which the less essential metabolic functions of folate, methionine, and SAM in histone methylation were compromised so that SAM levels could be maintained for essential functions, similar to the triage mechanism proposed by Ames (2006)."
 

Jonathan Edwards

"Gibberish"
Messages
5,256
Wrong again, Professor. It's not natural folates that increase cancer risk, it's unmetabolized folic acid:

And the evidence for that, Adreno? There is one study on folic acid administration in prostate cancer that is not statistically significant if you analyse the data carefully. The theory is that the effect is from unmetabolised folate but I don't know of any evidence. And my original statement seems to stand. Methotrexate is an anti-cancer drug that blocks this enzyme if I remember rightly. And we routinely use folic acid to OFFSET the unwanted effects of methotrexate. It doesn't figure.
 

Ripley

Senior Member
Messages
402
And the evidence for that, Adreno? There is one study on folic acid administration in prostate cancer that is not statistically significant if you analyse the data carefully. The theory is that the effect is from unmetabolised folate but I don't know of any evidence. And my original statement seems to stand. Methotrexate is an anti-cancer drug that blocks this enzyme if I remember rightly. And we routinely use folic acid to OFFSET the unwanted effects of methotrexate. It doesn't figure.

Some mechanisms are explored in this paper:

http://www.ncbi.nlm.nih.gov/pubmed/21135116

And again, it seems you've forgotten but the evidence and hypotheses suggest a dual role for folic acid in cancer. Yet another study:

http://www.ncbi.nlm.nih.gov/pubmed/17063929
 

DanME

Senior Member
Messages
289
Of course, you are ignoring the glaring logical fallacy you are making in those statements.

On one hand, you feel the need to ignore evidence and dismiss results you can't explain (in the name of science!), while at the same time being completely unable to explain ME itself. One could just as easily dismiss ME with the exact same arguments you've just made. And lord knows people have done just that.

Good job, sir. You've just dismissed yourself.

(And once again, I'll remind you that you continue to hi-jack this thread.)

There is no logical fallacy. To the contrary. Prof Edwards didn't ignore any evidence, because there isn't any. The burden of proof is on you, not on him. And the proof must be supported by serious scientific methods and standards. You could study cells and see, if they show any enzymatic or genetic abnormalities. But even if they do, you still have to try your treatment scheme in a carefully thought out placebo controlled trial and see if it really works.

Also he doesn't have to explain ME, if the cause is not known yet. And it is totally not. This is the honest approach to a problem. You don't know, if your theories are correct until you proof them.

It's not hi jacking or derailing the thread, if someone comments on the topic, even if he (or she) has another opinion about it. Maybe people want to point out, that it's not wise to sign the petition or that the petition has its flaws.
 

JPV

ɹǝqɯǝɯ ɹoıuǝs
Messages
858
I am completely against putting supplements into the food and water supply. If I want to introduce such things into my body I want to be the one who decides what it is and in what quantities.

The government has become so corrupted, due to the influence of corporate interests, that it can no longer be trusted to oversee policies such as this.

I can't fathom why anyone would defend such a practice unless they were totally misguided or had some sort of vested interest.
 
Last edited:

JPV

ɹǝqɯǝɯ ɹoıuǝs
Messages
858
Maybe people want to point out, that it's not wise to sign the petition or that the petition has its flaws.

What flaw is there in not wanting supplements to be put into our food supply? Why on earth should the food and water supply be used as a vehicle to administer drugs and supplements?

If some people feel so strongly about the need to ingest such supplements they can do so by purchasing them separately. If I don't want to ingest them, I shouldn't be forced to do so against my will because of what I see as flawed science (based on old inaccurate studies) or possible conflicts of interest.
 
Last edited:

Hip

Senior Member
Messages
17,865
Methylation protocol has gotten me from off the bed to now some days now not lying down through the day. My life-long insomnia has resolved, my cognition is incomparably better. I initially tried Rich VanK's SMP, but no amount of tweaking made it work for me. When I switched to Freddd's Protocol, I started having results. When I finally became brave enough to really increase my levels of Methylfolate, I really started to feel better.

So you found Rich VanK's SMP did nothing, but when you switched to Freddd's protocol it worked? Interesting. I guess that is a least one example of someone who did benefit from tinkering with their methylation / B12 / folate regimen (though given all the tinkering people do with these protocols, you'd hope for more than just one success story).

I'd just like to examine your success in a little more detail:

Rich Van Konynenburg's simplified methylation protocol consists of the following daily supplements:
Vitamin B12 hydroxocobalamin 2000 mcg sublingual
L-5-methyltetrahydrofolate 200 mcg
Folinic acid 200 mcg
Lecithin 1200 mg
Plus a multivitamin / multimineral tablet

Freddd's protocol consists of the following daily supplements:
Vitamin B12 methylcobalamin 5000 mg sublingual
Vitamin B12 adenosylcobalamin 3000 mg sublingual
Metafolin (calcium-L-methylfolate) 800 mcg
B vitamin complex
Omega 3 fish oil
Potassium
Plus other add-ons such as zinc, calcium, magnesium, vitamins A, D, E and C

The main differences between these two protocols seems to be:
• a different form of B12
• a slightly different form of methylfolate (Rich's L-5-methyltetrahydrofolate versus Freddd's calcium-L-methylfolate)
• the lack of folinic acid in Freddd's protocol

Perhaps as you have suggested, ahmo, it the lack of folinic acid which played the crucial role in improving your ME/CFS on switching to Freddd's protocol.


I've also discovered that I'm one of those that has problems with folinic acid. It never worked as a supplement for me in Rich's SMP. And eventually I found that green vegetables, which are sources of folinic form, block Methylfoate for me

Did you also stop eating green leafy vegetables when you switched to Freddd's protocol, in order to cut out eating the folinic acid from this food source? In other words, did you do both Freddd's protocol and elimination of green vegetables at the same time?

And did you ever take even higher doses of folinic acid, and observe your symptoms worsening when you did?


Regarding folinic acid blocking the action of methylfolate: this article indicates the precursors of methylfolate can occupy the folate transporters, preventing methylfolate from being transported into the brain:
Although high doses of folic acid can be administered orally, the precursors of MTHF may compete with MTHF for entry into brain by binding to folate transport receptors, limiting the amount of MTHF that can enter the brain (Figure 4B).

Rich Van Konynenburg said here that:
It's true that folinic acid competes for absorption and transport into cells with methylfolate. However, it also offers advantages in that in most people it is able to support other folate reactions, while methylfolate cannot do so until it reacts with homocysteine to produce tetrahydrofolate. This is the reaction that is partially blocked in ME/CFS, and it takes some months to get it up to normal operation with this protocol.

Someone posted here that:
According to references I’ve read, the form of folates in leafy greens is mostly folinic acid and some methylfolate. Some CFS people find that the folinic acid in leafy greens makes them folate deficient, because it competes with the active folate L-5-MTHF. They need to take an extra methylfolate pill just before eating leafy greens, and limit how many greens they eat, otherwise they go into folate deficiency.
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
@Hip
Did you also stop eating green leafy vegetables when you switched to Freddd's protocol, in order to cut out eating the folinic acid from this food source? In other words, did you do both Freddd's protocol and elimination of green vegetables at the same time?

No. I was juicing lettuce and eating cooked zucchini. My folate deficiency symptoms continued on, even when I was on very high doses. Then I became aware that I was having adrenal stress. I looked up zucchini, and only found a reference that it's good for pregnant women, as a source of folate. So I concluded this was a problem for me. I don't think I even recalled Fred's info re folinic at that time. In fact, it was only later, when I started searching the forums that I saw his statements.

I was engaged in a detox protocol at the time. I stopped the zucchini, which at that time was about 2 medium/day. And my detox was thrown into high gear. It was all I could do to ride the process out. I assumed that it was because the cooked veg had been keeping things in check. But in fact, once I removed the high folinic veg, my methylation kicked in like a bucking bronco. I stopped all Mfolate for several days, with no deficiency symptoms, unheard of in my past experience. And when I eventually resumed, it was at 1/2 the dosage I'd been on. I stayed on that dosage for some months, until reading about sublingual use. Once I started taking folate sublingually, I needed only 1/3 of what I'd been using since. I'd been up to 30mg when eating green veg; dropped to 15mg without the greens; and now use 5mg sublingually.

I've found that at least for now, avoiding green veggies altogether is best for me. My most recent attempt was a small handful of pea sprouts. I had adrenal signs appear overnight. I'm certainly hoping that maybe completing my current Candida and proteolytic enzyme regimen, or after that a 3-day fast to reset immune system, might make a shift. But I'm no longer so hopeful for that result. There's clearly a certain level of brokenness in my methylation cycle. Maybe this represents one of the several ME's that Jonathan Edwards postulated some months back.

Both of the key elements in Rich's SMP, HydroxyB12 and Folinic were unhelpful for me. I tried them over a couple years, before I was using the forums. And I tried again once I'd corrected my diet and was ready to get serious about methylation. Rich's injunctions about Fred's unique genetics and need for high doses made me very fearful to try. But clearly the other wasn't working.

Furthermore, The additional components of Fred's Deadlock Quartet, AdenoB12 and L-Carnitine Fumarate, performed as Fred said they would. I tried 3 other forms of carnitine before the fumarate. In part, this was because I'd been using 2 different forms in the past, and so had some on hand. But really, it was due to the fact that as many hours as I spent reading the info re Freddd's Protocol, looking again and again for the correct form, my brain was still so impaired that I just couldn't focus and retain the information long enough. I ended up thinking LCF was the wrong form, when, as he predicted, when I took it there was an almost immediate brightening. That's what led to me compiling so many notes, which I then consolidated into a Guide, so that others wouldn't have to spend quite so many hours searching.

I know there's a group of people here who've been having good results. Maybe they weren't attracted to a thread about a petition regarding govt regulations of folic acid. There's a very long thread, ActiveB12...something or other. There's another entitled something re High Methylfolate users, which has a real-time account of the detox drama I mention above.. Someone could create a poll thread re methylation.
 

Hip

Senior Member
Messages
17,865
@Ripley
If you are supporting this petition, the onus of proof is indeed on you and those who started the petition. You and they need to be diligent enough to spend time surveying the scientific literature, to see if there is any evidence to back up the assertion that folic acid fortification of food leads to increased cancer rates.

From my brief survey (see below), there is no strong evidence for this.



In the petition it says: "the FDA mandated that all enriched wheat flour was to be fortified with folic acid. This unilateral decision has turned into one of the worst health fiasco's in the history of our country."

One of the worst health fiasco's in the history of our country? That is a very strong statement, so I would expect to see scientific backing for it. But there is none provided. No scientific analysis; no facts and figures; no references; just emotive statements.

Where is the diligence here?



Looking at some studies, meta-analyses and literature reviews on the folic acid–cancer connection, the evidence for folic acid causing cancer is weak:

This study looked at cancer rates over a 5 year period for 50,000 people from several countries, where some were taking a folic acid supplement and others a placebo. There was a slight increase in cancer incidence, but this did not reach statistical significance, meaning it could have been just due to chance.

This systematic review and meta-analysis of 10 RCT studies found a borderline significant increase in frequency of overall cancer in the folic acid group compared to controls. Prostate cancer was the only cancer type found to be increased after folic acid supplementation.

This study found that those with the MTHFR 677C-->T polymorphism are at higher risk from colorectal cancer when folic acid is low, and that additional studies are required in order to determine whether folic acid supplementation may be a useful agent in preventing colorectal cancer.

However, this later study found no evidence that folic acid is effective in the prevention of colorectal adenomas or colorectal cancer for any population.

This study found that higher folate intake can be a protective factor against lung cancer, though in a marginal manner.

This review concluded that low folate status is a risk factor for cancer and cardiovascular disease. However, it also said that; "recent folate intervention trials raise concern about possible adverse effects of folate supplementation and suggest that too much folate in inopportune settings may be potentially harmful in individuals at higher risk for cardiovascular disease and cancer."

This study was very interesting, as it proposes a 'dual-modulator' role for folate in colorectal cancer, in which moderate dietary increases initiated before the establishment of neoplastic foci have a protective influence, whereas excessive intake or increased intake once early lesions are established increases tumorigenesis.
 
Last edited:

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
PS: It was on a GAPS forum that I learned I should pursue methylation. There were mostly mums with autistic kids. Methylation issues seems to be one of the things PWME have in common w/ autism. Or maybe, the thing. I don't know.