Folic Acid: Bad Idea or VERY Bad Idea and how much is too much?

[Lotus97]

Does the MTHFS polymorphism show up on the 23andme testing?

There's a thread about Folinic acid and MTHFS in the SNP forums where people are posting their MTHFS results. According to what was discussed in the thread, you might need to have a defect in both MTHFS and SHMT to have a problem with folinic acid.
http://forums.phoenixrising.me/inde...d-intolerance-request-for-genetic-data.19168/

In January, Rich asked people to share their 23andMe results for the MTHFS gene to see if we can sort out which SNP or SNPs may be detrimental in ME/CFS. I didn't see where anyone responded. (You can find your MTHFS results by going tohttps://www.23andme.com/you/explorer/ and logging in and entering "MTHFS" for the gene name.)

It's important people contribute so we can try to figure out when folinic acid should be supplemented or avoided for certain people as part of a methylation protocol.

I may be intolerant to folinic acid (seems to cause exacerbation of fatigue, irritation of taste buds) and so am providing my DNA results. We need MTHFS results from as many other people as possible, though, whether intolerant or not.

If you could also include the one SHMT result that Yasko tests for, that may be helpful also. I'm heterozygous (AG) for that SNP (SHMT1 C1420T rs1979277), and the first day I took folinic acid it helped, as might be expected, but then I seemed to gradually get worse over several days (800-1600 mcg/day).

Below are Rich's personal MTHFS results with mine next to his in parentheses (he volunteered to be the DNA "standard"). At the time Rich was tested, 23andMe only gave results for 22 SNPs. They gave 24 for me. (36 are known?) There was only one instance of a flip in homozygosity between Rich's results and mine, rs7177659, and I discuss it after:
We're not likely to be so lucky right away that rs7177659 is the "bad" SNP, but it's interesting because having the hetero version (AC) for that SNP actually seems to be "normal" (58% frequency according to openSNP) and apparently results in a 29% decrease in cardiovascular disease risk compared to the homo versions (AA/CC). (This is from a May 2012 publication: http://jn.nutrition.org/content/early/2012/05/28/jn.111.157180.abstract - I don't have access to the full text; it's not mentioned in the abstract.)

So with respect to that SNP it might be that I have a detrimental down-regulation of MTHFS and Rich has a detrimental up-regulation (or vice versa). A down-reg would cause a build up of folinic acid and thus inhibition of SHMT (and several other enzymes outside the methylation cycle as well) and create an intolerance to supplementation. An up-reg can cause an increased turnover rate and depletion of cellular folate. Note: The C allele - what Rich has two copies of - is the ancestral (wild type) allele according to the NCBI data page.

Hopefully, if enough people contribute, we can figure out which SNP(s) is/are problematic. Thanks!

You can check out the thread, but this seems to be a work in progress so your results might indicate whether you have an issue with folinic. It seems like it would be easy to test out though. If you have a tendency towards overmethylation and are familiar with the symptoms then you could take a large dose of folinic acid (along with your normal B12 and methylfolate dose) and see if that triggers the symptoms. If it does, then you're probably converting it adequately to methylfolate thereby increasing methylation. Conversely, if you have a high need for methylfolate and are familiar with the symptoms of not getting enough methylfolate then you could take folinic with methylfolate and see if folinic acid blocks methylfolate. Now I realize there might be grey area where the tests won't give a conclusive answer and the tests might take a few days or longer to see results. Especially if you have to adjust the dosage.

 

[Lotus97]

In the morning I take my methylB12. 2 days ago I tried your suggestion of sticking it under my top lip - good tip! It was 500mcg. After about 15mins I was pretty wired. Kind of like a couple of coffees wired but with the fatigue still there. It took an hour to dissolve and I felt like my eyelids were super glued open! Then later on the folinic acid which seems to amplify the methylB12 feelings. Didn't feel sleepy until the evening. Woke up with a sore throat!

As I had felt too wired, yesterday I did 1/4 methylB12, so 250mcg. Same feeling of wiredness but not quite so strong! Folinic amplified this again. Felt sleepy in the afternoon so slept and then went to bed early as still really tired. I am also suffering some leg cramp pains but not quite cramping like I'm used to. Legs feel very achy like someone is squeezing them every few seconds. This leg ache is also something that happens when I have a heavy Perrin therapy session but goes away after 24 hours. I've had it now for 3 days - I am assuming it's a potassium problem? I am also having bad dizziness problems when I bend over and nearly black out. Am tired walking up the steps and have to rest for 5 mins. The blacking out/dizziness and tired walking up steps is how I feel when I'm not in a good ME way. So it's like I've gone backwards.

I agree with Freddd about the hypokalemia/low potassium symptoms and you should definitely be supplementing with that. As far as the rest of your symptoms, it sounds like you're experiencing excitotoxicity. Taking more methylfolate is going to overdrive the methylation cycle and make your symptoms much worse and is also going to make you need even more potassium. It might even create new symptoms beyond what you're experiencing.

 

[Freddd]

There's a thread about Folinic acid and MTHFS in the SNP forums where people are posting their MTHFS results. According to what was discussed in the thread, you might need to have a defect in both MTHFS and SHMT to have a problem with folinic acid.
http://forums.phoenixrising.me/inde...d-intolerance-request-for-genetic-data.19168/

You can check out the thread, but this seems to be a work in progress so your results might indicate whether you have an issue with folinic. It seems like it would be easy to test out though. If you have a tendency towards overmethylation and are familiar with the symptoms then you could take a large dose of folinic acid (along with your normal B12 and methylfolate dose) and see if that triggers the symptoms. If it does, then you're probably converting it adequately to methylfolate thereby increasing methylation. Conversely, if you have a high need for methylfolate and are familiar with the symptoms of not getting enough methylfolate then you could take folinic with methylfolate and see if folinic acid blocks methylfolate. Now I realize there might be grey area where the tests won't give a conclusive answer and the tests might take a few days or longer to see results. Especially if you have to adjust the dosage.

Hi Lotus,

You appear to have this backwards.

large dose of folinic acid (along with your normal B12 and methylfolate dose) and see if that triggers the symptoms. If it does, then you're probably converting it adequately to methylfolate thereby increasing methylation.

A large dose of folinic acid can cause all sorts of symptoms because it blocks l-methylfolate causing paradoxical folate deficiency. Folinic acid in any dose is NOT predictive of l-methylfolate.

 

[UM MAN]

Does the MTHFS polymorphism show up on the 23andme testing?

Yup, 24 of them.

 

[Lotus97]

Hi Lotus,

You appear to have this backwards.

large dose of folinic acid (along with your normal B12 and methylfolate dose) and see if that triggers the symptoms. If it does, then you're probably converting it adequately to methylfolate thereby increasing methylation.

A large dose of folinic acid can cause all sorts of symptoms because it blocks l-methylfolate causing paradoxical folate deficiency. Folinic acid in any dose is NOT predictive of l-methylfolate.

I understand you're speaking from your own experience, but other than Nandixon I have yet to come across anyone else with paradoxical folate deficiency. There was no one in that 7+ page thread you created about paradoxical folate deficiency that had that. Don't get me wrong, I'm absolutely positive there are a couple other people here that have problems with folinic acid. Maybe some of them will even come to your defense in this thread. But you seem to tell just about everyone (including me) that they have paradoxical folate deficiency when the symptoms you list could be from so many different things...You don't have folinic acid in your protocol and most of the people following Rich's protocol you tell that to seem to be simply overmethylating/overdriving the methylation cycle. Considering there's a study showing large doses benefited the vast majority of CFS patients seems pretty convincing to me.
http://www.natural-holistic-health.com/cd19-blood-test-and-chronic-fatigue-syndrome/
As a result the team used a drug, Leucovorin, a folinic acid derivative, for several months. They found that 81% of the patients reported improvement within two months. Unfortunately, at the conclusion of the study the researchers didn’t perform a cytometry measurement that would have given insight into the clinical efficacy of the drug leaving them only with the functional reports of improvement.
Folinic acid co-enzymes are responsible for several important metabolic functions. These include the formation of DNA and RNA, the formation of heme protein in hemoglobin, formation of amino acids and the formation of glutathione.

 

[Victronix]

Folinic acid co-enzymes are responsible for several important metabolic functions.

Are there functions that methylfolate doesn't work for, that folinic acid does work for?

I can see supplementing methylfolate, since it can cross the blood brain barrier and seems to be the least work for the body to access. But then if you need folinic acid, shouldn't that be in the same foods as folate (I'm assuming, since their chemical structure is so similar)?

 

[Freddd]

I understand you're speaking from your own experience, but other than Nandixon I have yet to come across anyone else with paradoxical folate deficiency. There was no one in that 7+ page thread you created about paradoxical folate deficiency that had that. Don't get me wrong, I'm absolutely positive there are a couple other people here that have problems with folinic acid. Maybe some of them will even come to your defense in this thread. But you seem to tell just about everyone (including me) that they have paradoxical folate deficiency when the symptoms you list could be from so many different things...You don't have folinic acid in your protocol and most of the people following Rich's protocol you tell that to seem to be simply overmethylating/overdriving the methylation cycle. Considering there's a study showing large doses benefited the vast majority of CFS patients seems pretty convincing to me.
http://www.natural-holistic-health.com/cd19-blood-test-and-chronic-fatigue-syndrome/
As a result the team used a drug, Leucovorin, a folinic acid derivative, for several months. They found that 81% of the patients reported improvement within two months. Unfortunately, at the conclusion of the study the researchers didn’t perform a cytometry measurement that would have given insight into the clinical efficacy of the drug leaving them only with the functional reports of improvement.
Folinic acid co-enzymes are responsible for several important metabolic functions. These include the formation of DNA and RNA, the formation of heme protein in hemoglobin, formation of amino acids and the formation of glutathione.

Lotus,

You know you can test my hypothesis any time you like on yourself. I have no idea how many people may demonstrate one variety or another, perhaps it is at least the 19% that didn't get benefit in that one study. However, to the person involved it is everything. Now, as the paradoxical folate insufficiency/deficiency hypothesis can be tested in a couple of days to a week or so to most people's satisfactions, by actually trying large enough doses to cause the insufficiency symptoms to start fade and the other hypotheses takes months or years to get through the so-called "detox", game theory would suggest that a person actually try it as defined and KNOW within a week before trying the multi year hypothesis. Instead of knowing for sure by testing, you appear to want people to play guessing games as you are. You know, some people just want to get better and they don't really care who's idea it might be. You need a little history. The paradoxical folate deficiency came about because of so many people right here having it in such an amazingly profuse density. I suggested that the incredible incidence of "detox: indicated to me that people were doing something HERE to cause it. It appears to be caused by the combination of supplements. Four years later it still looks like the supplement choice and quantities causes the vast degree of problem. The only thing that has changed in 4 years is that the people that use the low potassium and folate insufficiency hypothesis generally have considerable improvement and move on and start dealing with secondary and tertiary problems instead of still struggling to get methylation working and not be perpetually in "detox".

Don't get me wrong, I'm absolutely positive there are a couple other people here that have problems with folinic acid. Maybe some of them will even come to your defense in this thread.


LOL

 

[Freddd]

Folinic acid co-enzymes are responsible for several important metabolic functions.

Are there functions that methylfolate doesn't work for, that folinic acid does work for?

I can see supplementing methylfolate, since it can cross the blood brain barrier and seems to be the least work for the body to access. But then if you need folinic acid, shouldn't that be in the same foods as folate (I'm assuming, since their chemical structure is so similar)?

Hi Victronix,


Are there functions that methylfolate doesn't work for, that folinic acid does work for?


Emphatically NO! in humans.

And I would add:
Are there functions that folinic acid doesn't work for, that methylfolate does work for?

And the answer is emphatically YES! in humans


But then if you need folinic acid, shouldn't that be in the same foods as folate (I'm assuming, since their chemical structure is so similar

Methylfolate is the form eaten in meat and works for everybody in all functions.