Help! I can't take folate without terrible over-methylation symptoms and need it for pre-pregnancy

[Jonathan Edwards]

@barbc56

I was addressing this quote specifically

not disputing that some supplements can be harmful to some people. I know that they can. And FWIW, I agree with you to a great extent about basing supplement intake on DNA tests. IMO symptoms are a better guide to supplement intake, if you can monitor yourself well.

But I stand by my contention that a lack of evidence means exactly that: that there is a lack of evidence. Further, and most importantly, a lack of evidence regarding the efficacy of a therapy in no way implies the therapy has no therapeutic value for a given subset of people. It just means it hasn't been investigated.

When speaking of evidence we are trying to deal in known sureties, not conjectural possibilities such as "But you don't know, the opposite could be true."

You can use that argument to sell anything. If there is no indication of benefit on average then presumably as many people get worse as better - which doesn't seem a very good argument for trying something you do not like or need.

The placebo effect is very strong. Human beings like taking stuff. That is why they were taking stuff for thousands of years before anybody discovered anything that was actually useful (mostly around about 1950). And why take something as a tablet when there is plenty in ordinary food? It makes no sense to me.

 

[dannybex]

No, I think it would be completely irrelevant to be honest. This sounds like pseudophysiology to me.

Documented low blood volume in an ME/CFS patient who is pregnant would be 'completely irrelevant'?

And low blood volume is 'pseudophysiology'? Dr. Bell found it to be extremely common, almost a biomarker in his experience dealing with patients for over thirty years, as have other many other ME/CFS doctors.

If you don't believe the experts, then you might consider asking some of the patients on this forum low blood volume is real or not.

 

[PeterPositive]

You can use that argument to sell anything. If there is no indication of benefit on average then presumably as many people get worse as better - which doesn't seem a very good argument for trying something you do not like or need.

The placebo effect is very strong. Human beings like taking stuff. That is why they were taking stuff for thousands of years before anybody discovered anything that was actually useful (mostly around about 1950). And why take something as a tablet when there is plenty in ordinary food? It makes no sense to me.

This is also a generalization that is not very useful.
A lot of people from this forum have experienced clear benefits from so called "methylation supplements" that were not able to obtain from any other "tablet". (I am one of those)

We're not talking about subtle, non repeatable effects. It makes the difference from lying in bed unable to get out and being able to function again to a certain level. And when interrupted the situation declines again.

It's pretty difficult to argue in favor of a "post hoc propter hoc" effect when the experiment can be repeated with the same results.

I agree that this, in the grand scheme of things, may not have clinical relevance for those purely interested in statistics, yet for a significant amount of people it does make a difference. This disconnect, sometimes, is what makes patients frustrated with their physicians, imo.

 

[Jonathan Edwards]

Documented low blood volume in an ME/CFS patient who is pregnant would be 'completely irrelevant'?

And low blood volume is 'pseudophysiology'? Dr. Bell found it to be extremely common, almost a biomarker in his experience dealing with patients for over thirty years, as have other many other ME/CFS doctors.

If you don't believe the experts, then you might consider asking some of the patients on this forum low blood volume is real or not.

If these are experts why is nothing published on this? Self-appointed experts are eveywhere in science and medicine. And anyway, I am not disputing that ME patients may have low blood volume. What I am disputing is that this has any relevance to taking folate. If you lose blood suddenly having folate around is no help. There is no gradual blood loss in pregnancy. And folate will not increase your red cell mass if that is dysregulated at a low level. There is a complete logical disconnection between the two - called pseudoscience.

 

[Jonathan Edwards]

This is also a generalization that is not very useful.
A lot of people from this forum have experienced clear benefits from so called "methylation supplements" that were not able to obtain from any other "tablet". (I am one of those)

We're not talking about subtle, non repeatable effects. It makes the difference from lying in bed unable to get out and being able to function again to a certain level. And when interrupted the situation declines again.

It's pretty difficult to argue in favor of a "post hoc propter hoc" effect when the experiment can be repeated with the same results.

I agree that this, in the grand scheme of things, may not have clinical relevance for those purely interested in statistics, yet for a significant amount of people it does make a difference. This disconnect, sometimes, is what makes patients frustrated with their physicians, imo.

I don't buy that as a basis for giving other people advice.
If these supplements have these useful effects then all the people recommending them need to do is take a small group of patients (maybe 20) who report benefit and do a blinded crossover trial against placebo for that group. It would cost more or less nothing to do. Tapering dosage could be included as a safeguard. If any body recommending these treatments really thought they worked they could easily do such a trial. And there would be no issue of the result 'just being statistical' because the subjects would all be supposedly responders.

And the fact is that none of these supplement pushers do trials like this -presumably because they know they will show their supplements do not even work on the people who think they do - otherwise they could publish the results and make vast amounts more money as true experts in the field.

I don't think any body here has any business recommending vitamins to someone wanting to know the right medical approach to getting pregnant. It has nothing whatever to do with ME. They just need basic medical advice from a primary care physician with a special interest in obstetrics.

 

[PeterPositive]

I don't buy that as a basis for giving other people advice.

I don't think generalizations will work either.
We're talking about non prescription dietary supplements that are freely available on the market. Why people should not be allowed to talk about them or give basic suggestions based on their experience?

Similarly one should never give basic dietary suggestions to anyone unless he has the necessary academic credentials. Seems to me an extreme position to maintain.

It goes without saying that the bottomline for anyone coming to this website is that medical advice is the preferred route, especially in presence of complex health issues. It also seems that the vast majority of suggestions from users in this forum come with this disclaimer.

I agree that this "methylation/23andMe" craze has become ridiculous and too many people have been taken for a ride by self appointed experts.

I think this website offers both sides of the story and lately I've seen more healthy criticism directed to the most vocal proponents of methylation as a cure-all system. (Yasko etc...)

Other people like Dr Ben Lynch are pretty honest in their work and don't claim that methylation protocols are the key to solving ME, CFS and whatnot.

If these supplements have these useful effects then all the people recommending them need to do is take a small group of patients (maybe 20) who report benefit and do a blinded crossover trial against placebo for that group. It would cost more or less nothing to do.

This is quite funny... You realize you're asking ME patients to suddenly become medical researchers and run on their own resources a blinded crossover trial against placebo for 20 people? .

Come on, let's be serious for a moment. Methylation supplements such as B complex vitamins and some minerals are well documented for their effects on energy production and cognition. This is not even controversial.

It doesn't come as a surprise that people taking high dose of active cobalamin, for example, report improved mental functions and less fatigue.

 

[Valentijn]

Genetically, it looks like B12 is a bigger issue for you (two MTRR mutations).

It's the mutations which are relevant, not the number of them. MTRR A664A +/+ (AA) is actually a mild up-regulation, which should be beneficial. MTRR A66G can be a substantial down-regulation, but only if homozygous or compound heterozygous. Hence those MTRR variations are looking completely harmless.

 

[Valentijn]

It is not without reason. While it probably is true that eating a good diet is the best advice, in Australia it is a standard medical recommendation for women to take a folic acid supplement pre-conception and to continue throughout pregnancy. It probably doesn't make sense now that so many of our foods are fortified anyway, but Josephine is just following the latest medical "wisdom" in believing she needs to take it.

It's recommended for routine use in women (not just pre-natal) because so many pregnancies are not closely planned, and might not even be detected for several months. But pre-pregnancy, I don't think folate is of any particular use regarding eventual defects in the fetus. Though it's certainly easy to see how the official advice becomes confusing.

 

[Valentijn]

We're talking about non prescription dietary supplements that are freely available on the market. Why people should not be allowed to talk about them or give basic suggestions based on their experience?

Over the years I've seen several people here experience something similar to psychosis while trying out various methylation protocols. They then take some B3 or whatever, and things calm down after a few days, but that's not the sort of risk that makes any sense to take during pregnancy. Many more struggle with potassium balance.

Any supplementing during the pregnancy should be 100% about the pregnancy. If someone feels that they want to experiment with high doses of vitamins or other substances which have a somewhat unknown (largely unresearched) effect and side-effects, then the sensible option is to delay the pregnancy. Trying to mix two medical concepts like methylation and pregnancy, in the absence of a sound evidence base, would be risking too much.

Personally I wouldn't opt to take anything stronger than a prenatal vitamin while pregnant, if I could possibly avoid it. If there is no folate deficiency, no B12 deficiency, and no elevation of homocysteine, there is no reason to take above-average doses of either substance.

 

[PeterPositive]

Over the years I've seen several people here experience something similar to psychosis while trying out various methylation protocols. They then take some B3 or whatever, and things calm down after a few days, but that's not the sort of risk that makes any sense to take during pregnancy. Many more struggle with potassium balance.

I agree. But thesis of @Jonathan Edwards is that nutritional supplements are generally placebo. That's were my disagreement lies.

Any supplementing during the pregnancy should be 100% about the pregnancy. If someone feels that they want to experiment with high doses of vitamins or other substances which have a somewhat unknown (largely unresearched) effect and side-effects, then the sensible option is to delay the pregnancy. Trying to mix two medical concepts like methylation and pregnancy, in the absence of a sound evidence base, would be risking too much.

I agree with this too, but the opening post is asking for folic acid usage for pre-pregnancy. This is not an outlandish request as it is found in the guidelines of most national associations of gynecologists/obstetricians of the world.

cheers

 

[barbc56]

Come on, let's be serious for a moment. Methylation supplements such as B complex vitamins and some minerals are well documented for their effects on energy production and cognition. This is not even controversial

Citations?

Barb

 

[PeterPositive]

Citations?

Any nutrition manual.

 

[Jonathan Edwards]

This is quite funny... You realize you're asking ME patients to suddenly become medical researchers and run on their own resources a blinded crossover trial against placebo for 20 people? .

Come on, let's be serious for a moment. Methylation supplements such as B complex vitamins and some minerals are well documented for their effects on energy production and cognition. This is not even controversial.

It doesn't come as a surprise that people taking high dose of active cobalamin, for example, report improved mental functions and less fatigue.

I wasn't actually suggesting that patients did the trial - I was suggesting the 'naturopaths' or whatever they call themselves who make money out of this stuff should do trials.

Yes, let's be serious. Where is the evidence for methylation supplements having any effect on energy production or cognition in people who have adequate dietary intake? That would be highly controversial to my mind.

It does not come as a surprise that people taking cobalamin report feeling better. It has been used as a 'medical sounding' placebo since long before I qualified. When I was a student if we did not know what to do with a patient we gave them a jab of B12 to make them think they were getting some treatment.

 

[barbc56]

Any nutrition manual.

Which one of the numerous nutrition manuals, written by many authors who have different theories about what good nutrition includes?

 

[PeterPositive]

Which one of the numerous nutrition manuals, written by many authors who have different theories about what good nutrition includes?

I am sorry I don't understand your question.
Would you agree that we have a pretty accurate understanding of the fundamental functions of the essential elements of nutrition, such as mineral and vitamins?

You seem to be suggesting that there is controversy regarding the function of these nutrients.

 

[PeterPositive]

I wasn't actually suggesting that patients did the trial - I was suggesting the 'naturopaths' or whatever they call themselves who make money out of this stuff should do trials.

Sorry, it was not clear to me. I agree with that.

Yes, let's be serious. Where is the evidence for methylation supplements having any effect on energy production or cognition in people who have adequate dietary intake? That would be highly controversial to my mind.

Exactly my point, let's avoid generalizations and try to be specific.

Who knows if people who have had significant improvements from methylation supplements did have adequate dietary intake. Many ill people may not have a proper diet or digestion, or they may be intolerant to entire families of foods.

Also how exactly do we establish proper nutritional status? Not all standard lab test can provide a satisfactory picture of the dietary intake.

It does not come as a surprise that people taking cobalamin report feeling better. It has been used as a 'medical sounding' placebo since long before I qualified. When I was a student if we did not know what to do with a patient we gave them a jab of B12 to make them think they were getting some treatment.

But then any pill would do, regardless of it containing actual cobalamin or just some sugar. Also this is another generalization that won't take us anywhere.

People who have reported improvements with specific supplements have typically tried bucketloads of them, all promising on paper and none providing a result that comes closer.
Also the placebo effect is neither long lasting nor stable since "placebo" is basically another way for saying that the highs and lows of an illness are erroneously associated post-hoc with the intake of specific remedies.

When the positive effects of a supplement are repeatable and pretty much stable there must be something else going on.

 

[Sherpa]

@josephinegolightly The most common reason people overreact to methylfolate is having the MAO R297R mutation combined with B2 deficiency (and / or thyroid dysfunction)

• The most common reason for people to respond poorly to methylfolate is vitamin B2 deficiency.
• Lack of B2 in combination with MAO +/+ means that your ability to turn off your neuronal stimulus is greatly reduced, thus leading to 'apparent' over-stimulation of nerves
• MAO requires a metabolite of B2 called FAD to be present when the enzyme is synthesized.
• It normally takes 2-4 weeks of regular B2 supplementation (e.g. 5mg or more, 3x daily) to normalize activity of MAO. This is provided that you have normal thyroid function.

Be aware that starting up methylation when MAO A is still not functioning well can cause reactions that are quite similar to the side effects of MAO inhibitor drugs, and that are also confusingly similar to the symptoms of low potassium and/ or B12 deficiency. I experienced dry mouth, sudden awakening at night (insomnia), muscle jerking, tingling in arms and legs. I found these symptoms resolved with continued B2 supplementation.


Here is how I fixed my MAO A R297R mutation problem by addressing my B2 levels - after I did that taking methylfolate was no problem.

p.s. Jigsaw SRT Time Released magnesium tablets (with methylfolate) are a very gentle way to take methylfolate for senstitive people.

 

[whodathunkit]

You can use that argument to sell anything.

Perhaps. But I think there's a stronger case to be made for the fact that you can also fallaciously dismiss everything with this argument.

there seems to be no good evidence for it having anything to do with ME/CFS

Since we seem to be using the same kinds of sloppy rhetorical tactics I guess we'll just have to agree to disagree, Doc.

No, I think it would be completely irrelevant to be honest. This sounds like pseudophysiology to me.

P.S. This type of sloppy, 20th-century argument is also a convenient, easy dismissal of things we don't agree with.

I find it interesting that most of the people who are so insistent that everything be proven or have evidence to back it up are also some of the people who very quickly use these types of non-evidenced-based arguments against things when it's convenient for them.

I stand by my contention that a lack of evidence means precisely that and nothing more. We can't logically infer harm (or benefit) from something just because there is no evidence regarding it. Especially when it comes to something like methylation and its role in helping ME/CFS sufferers. There are some who have not done well on it, and others who have.

 

[dannybex]

If these are experts why is nothing published on this? Self-appointed experts are eveywhere in science and medicine. And anyway, I am not disputing that ME patients may have low blood volume.

If not, then why were you asking why nothing was 'published on this'? Bell and Streeten did publish their study as noted in my earlier link.

What I am disputing is that this has any relevance to taking folate. If you lose blood suddenly having folate around is no help. There is no gradual blood loss in pregnancy. And folate will not increase your red cell mass if that is dysregulated at a low level. There is a complete logical disconnection between the two - called pseudoscience.

In my original post, I questioned if it was wise to consider pregnancy at all if one has M.E. Nowhere did I suggest that folate supplementation would help if she got pregnant, and especially not if she suffered blood loss during pregnancy.

 

[dannybex]

Who knows if people who have had significant improvements from methylation supplements did have adequate dietary intake. Many ill people may not have a proper diet or digestion, or they may be intolerant to entire family of foods.

Exactly. One may have gut inflammation or malabsorption or intestinal permeability. Plus, they may have folate receptor autoantibodies, which have been connected with milk consumption:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715943/

Folate receptor autoantibodies are also associated with 'various pathologies during fetal and neonatal development.'

http://www.ncbi.nlm.nih.gov/pubmed/23314538