Could it be folate?

[PhoenX]

The protocolls of Rich and Freddd seem to work for some people, but as far as I see, most of them aren't fully healed yet. I think I found out why.

During my research I came across the MTHFR polymorphism and I wondered if most of us have it. This polymorphism hinders the conversion from folic acid to 5-methyltetrahydrofolate(Metafolin, 5-MTHF). I also found studies about Folate receptor antibodies. So there are at least two conditions that result in low 5-MTHF.

There is a product called Deplin, which is a high dose of Metafolin. It is marketed as a treatment against depression. It seems to do a great job. There are many enthusiastic articles about it on the net:
http://www.drugs.com/comments/l-methylfolate/

Both Rich and Freddd suggest the use of Metafolin(5-methyltetrahydrofolic acid), but it's a small dosage in comparison to Deplin. So I wondered if a higher dosage might help.

There is a guy called Dr. Smith who claims to treats CFS/ME successfully with Deplin and Methyl B12:
http://www.youtube.com/watch?v=3KylT1Muvq8

Watch the video, you might be quite familiar with this theory

I also found a thread from Karin:
http://www.mecfsforums.com/index.php/topic,7009.0.html
high dosages of folinic acid seem to help her.

They found a study about folinic acid(5-MTHF precursor)which supports this hypothesis:

A remarkable 81% of CFS patients experienced subjective improvement of their symptoms after treatment with folinic acid (CAS 58-05-9, leucovorin). The findings provide unprecedented evidence that CFS frequently is a folinic acid responsive clinical entity...
http://www.ncbi.nlm.nih.gov/pubmed/16889122#

yboldt14 takes 45mg of Deplin - which is a LOT - and it seems to work for him:
http://forums.bettermedicine.com/sh...agnosed.?p=298013&highlight=Deplin#post298013
http://forums.bettermedicine.com/sh...agnosed.?p=298390&highlight=deplin#post298390

Karin and yboldt14 seem to have a problem with folate auto-antibodies.

I started taking a high dose of Metafolin(15mg) for a few days and I definetly made improvements. My brain fog improved, my depressive mood is gone and I feel less fatigue. I feel quite happy at the moment.

I don't want to promise too much, but it seems to help. The Van Konynenburg Hypothesis(thats how I call it ) made sense to me right at the beginning.
Since yesterday I feel emotions, which I haven't felt for a long time

Thank you Rich for leading me to this point!

 

[PhoenX]

Ohh I forgot:
I found a cheaper product than deplin:
http://www.iherb.com/Metabolic-Maintenance-5-MTHF-L-Methylfolate-10-mg-90-Capsules/38360?at=0

I haven't found a high dose 5-MTHF product in europe and folinic acid is rare and pretty expensive.
So I asked vitaminsuk.com if they could import the Metabolic Maintenence, but they already have it! You probably have to mail them. They have a great service. I wrote them twice and they answered on the same day - it was sunday!

I haven't tried this product yet. I'm using lots of 800mcg Solgar tablets.

 

[MaxQ]

Are there any repercussions of taking a high dose Metafolin?

 

[PhoenX]

Honestly, I don't know. Karin wrote about startup reactions from folinic acid(a 5-MTHF precursor). She recommends to start at a lower dosage. I also started with a lower dosage and haven't noticed any startup reactions yet. I also take two 5mg jarrows Methyl-B12 and Pure encapsulations B Complex plus.

From the deplin site:
Is Deplin safe? Can it cause side effects?
The L-methylfolate found in Deplin is Generally Recognized as a Safe (G.R.A.S.). L-methylfolate found in Deplin is a form of folate that is naturally used in the body. In trials, the side effects reported for Deplin were similar to the side effects reported with placebo (sugar pill). Deplin has not been found to be associated with weight gain, insomnia or sexual dysfunction.2,3

Deplin package insert:
http://www.deplin.com/wp-content/uploads/Deplin_PI.pdf

I found a video from metabolic maintenance about 5-MTHF:
http://www.youtube.com/watch?v=2PNRvkig-y4

 

[L'engle]

I think Freddd has reported taking up to 8000mcg a day of metafolin, if I'm not mistaken. (Apologies Freddd if I am mistaken in this!) I've taken maybe 3200mcg in a day myself, and didn't personally have side effects. Some people have trouble taking very much though.

 

[PhoenX]

I think Freddd has reported taking up to 8000mcg a day of metafolin, if I'm not mistaken. (Apologies Freddd if I am mistaken in this!) I've taken maybe 3200mcg in a day myself, and didn't personally have side effects. Some people have trouble taking very much though.

Yes, I also read that Freddd takes 8mg.

Do you know if these people took sufficient B12?
Karin wrote:

But in any case, for anyone tempted to try, make sure you have plenty of B12 available prior to starting, in order to avoid the folate trap phenomenon (http://www.dach-liga-homocystein.org/EN/Fachinfo/folsaeure/falle.htm).

 

[L'engle]

I'm not sure how much anyone else takes. I take 45mg of methyl b12 sublingual a day, but recently only 1800mcg of methylfolate. I may start taking more methyl folate, to see if it had more cumulative effect.

 

[globalpilot]

Thank you so much for bringing this issue up. I Have had this on my to do list since I heard Cindy Schneider (I think it was her) speak of it at the fall 2010 dan! conference. I just didn't know where to go with the info.

She links the problem to paraoxinase activity - which I have had tested - and my activity was very low.

So you are taking 15mg a day ? The product you refered to at iherb is 10mg/pill. Are you splitting the pills.

COngratulations on your improvements and thanks again for posting!

 

[Jenny]

The protocolls of Rich and Freddd seem to work for some people, but as far as I see, most of them aren't fully healed yet. I think I found out why.

During my research I came across the MTHFR polymorphism and I wondered if most of us have it. This polymorphism hinders the conversion from folic acid to 5-methyltetrahydrofolate(Metafolin, 5-MTHF). I also found studies about Folate receptor antibodies. So there are at least two conditions that result in low 5-MTHF.

There is a product called Deplin, which is a high dose of Metafolin. It is marketed as a treatment against depression. It seems to do a great job. There are many enthusiastic articles about it on the net:
http://www.drugs.com/comments/l-methylfolate/

Both Rich and Freddd suggest the use of Metafolin(5-methyltetrahydrofolic acid), but it's a small dosage in comparison to Deplin. So I wondered if a higher dosage might help.

There is a guy called Dr. Smith who claims to treats CFS/ME successfully with Deplin and Methyl B12:
http://www.youtube.com/watch?v=3KylT1Muvq8

Watch the video, you might be quite familiar with this theory

I also found a thread from Karin:
http://www.mecfsforums.com/index.php/topic,7009.0.html
high dosages of folinic acid seem to help her.

They found a study about folinic acid(5-MTHF precursor)which supports this hypothesis:


yboldt14 takes 45mg of Deplin - which is a LOT - and it seems to work for him:
http://forums.bettermedicine.com/sh...agnosed.?p=298013&highlight=Deplin#post298013
http://forums.bettermedicine.com/sh...agnosed.?p=298390&highlight=deplin#post298390

Karin and yboldt14 seem to have a problem with folate auto-antibodies.

I started taking a high dose of Metafolin(15mg) for a few days and I definetly made improvements. My brain fog improved, my depressive mood is gone and I feel less fatigue. I feel quite happy at the moment.

I don't want to promise too much, but it seems to help. The Van Konynenburg Hypothesis(thats the way I call it ) made sense to me right at the beginning.
Since yesterday I feel emotions, which I haven't felt for a long time

Thank you Rich for leading me to this point!

Thanks Phoenx - it's interesting that one of the studies you mention links folinic supplementation to B cell deficiency and EBV. May therefore be a link to the effectiveness of Rituximab treatment in some way.

Clinical activity of folinic acid in patients with chronic fatigue syndrome.
Lundell K, Qazi S, Eddy L, Uckun FM.
Source
Parker Hughes Institute and Parker Hughes Clinics, St. Paul, MN 55113, USA.
Abstract
A high incidence of severe B-cell immunodeficiency and chronic reactivated Epstein-Barr virus (EBV) infection in patients with chronic fatigue syndrome (CFS) is reported herein. Of the 58 patients evaluated, 100% had evidence of prior EBV exposure and 72% had evidence for reactivated EBV infection. Notably, 94% of CFS patients had B-cell immunodeficiency with a marked depletion of their CD19+IgM+ mature B-lymphocyte population. A remarkable 81% of CFS patients experienced subjective improvement of their symptoms after treatment with folinic acid (CAS 58-05-9, leucovorin). The findings provide unprecedented evidence that CFS frequently is a folinic acid responsive clinical entity accompanied by B-cell immunodeficiency and inappropriate antibody responses to EBV.

PMID: 16889122 [PubMed - indexed for MEDLINE]
Publication Types, MeSH Terms, Substance

 

[PhoenX]

Thank you so much for bringing this issue up. I Have had this on my to do list since I heard Cindy Schneider (I think it was her) speak of it at the fall 2010 dan! conference. I just didn't know where to go with the info.

She links the problem to paraoxinase activity - which I have had tested - and my activity was very low.

So you are taking 15mg a day ? The product you refered to at iherb is 10mg/pill. Are you splitting the pills.

COngratulations on your improvements and thanks again for posting!

I haven't tried the Metabolic Maintainence product yet, but I will buy it. I'm taking 18(3x6) Solgar 800mcg tablets so far. Karin takes 25mg of folinic acid a day and she suggests to split it.

I started this whole thing 5 days ago. So I can't tell if this is really the last piece to the cure, but I thought I bring it up, so we can try this together.

My two older brothers also have health problems. One has problems with his teeth and suffers from obsessive compulsive disorder(OCD) and the other one suffers from anxiety, gastritis and reflux. I suffer from from fatigue, zero libido, brainfog, allergies, gastritis, reflux, etc. I think we all suffer from inflammation to some degree.

I wondered if we share the same underlying issues and found out, that OCD and teeth problems are associated with oxidative stress. I began to search for people who found a treatment against OCD and found an article where someone said, that Deplin helped him alot with OCD. This got me into this whole thing.

Here is a video about inflammation and the MTHFR polymorphism:
http://www.youtube.com/watch?v=4ob41QNUSgM

 

[Adster]

Are there any repercussions of taking a high dose Metafolin?

I've seen it mentioned that there have been concerns about high doses of folate increasing rate of growth or risk of colon cancer. It looks like newer studies have disproved that fear.

 

[richvank]

Hi, PhoenX.

I appreciate hearing about experiments like yours. I don't think we yet have a good understanding about how to optimize methylation treatment for each person.
And
It's true that some good results have been reported from taking high dosages of folates alone. And for many years, some of the doctors have been injections high-dose vitamin B12 and have found that to be helpful. However, I still think that combining active folates with high-dose B12 will work better for most PWMEs, because both are needed by the enzyme that is partially blocked, based on lab testing. If B12 is included, the dosage of folates needed appears to be much less.

I realize that lab testing is not feasible for everyone, but it is very helpful in interpreting what is going on if some tests can be run before and after trying various treatments for a while. The most helpful combination is a methylation pathways panel from the European Laboratory of Nutrients or the Health Diagnostics and Research Institute in the U.S. and a fairly complete amino acids panel, preferably in the blood plasma, such as the Metametrix 40 plasma amino acids profile.

Best regards,

Rich

 

[aquariusgirl]

Sigh, I wish we could figure this out. I took 10mg of methyl b12 the other day, plus 800 mcg of folapro & later that day I got a terrible burning sensation in the back right side of my brain. it took 8 aspirin & 2 OSR to extinguish the pain.

I've had similar nasty experiences with nebulised b12 + glutathione...a terrible, localised, burning sensation in the brain that is very hard to get rid of.

Anyone else get this?

The other issue I run into is excitotixicty .... once I supplement above a certain threshold.
IT's a bummer, because b12, folate and sam-e really help my brain.

I'm hoping that once I get my viral and metals load down, it will be less complicated and I can supplement this stuff w/out running into problems.

 

[Adster]

....

I'm hoping that once I get my viral and metals load down, it will be less complicated and I can supplement this stuff w/out running into problems....

It could be metals. I have issues with excitotoxicty, and struggle to take anything in a meaningful dose. NAC is amazing for a few days then I crash bigtime. A round of chelation with DMSA generally gets me back to baseline. I had mercury exposure as a kid.

 

[Gloria H]

I recently started the metafolin form of folate. But has anyone tried Quatrefolic, a folate form made available in 2010? If anybody has experience with it for CFS, I'd be very interested to hear of it. Here are a couple links:
http://www.gnosis-bio.com/quatrefolic.php
https://www.swansonvitamins.com/SWU533/ItemDetail
http://www.iherb.com/Doctor-s-Best-Best-Fully-Active-Folate-Featuring-Quatrefolic-400-mcg-90-Veggie-Caps/38067?at=1
http://www.webwire.com/ViewPressRel.asp?aId=138022
Blessings to you!

 

[PhoenX]

I can increase the growth of colon cancer apparently.

Could you refer to your source?
I couln't find it.

 

[Adster]

I should be clearer, I'll edit my post, I've seen it mentioned that there are concerns that it(and/or any other high dose of folate) may increase growth rate or risk of colon cancer http://depression.emedtv.com/deplin/deplin-warnings-and-precautions.html http://cebp.aacrjournals.org/content/16/7/1325.abstract . I'm fairly sure Rich has mentioned it before. That said, I think there are newer studies disproving it. So, probably nothing to worry about.

Rich mentions it here http://forums.phoenixrising.me/show...uot-ddtox-quot&p=167992&viewfull=1#post167992 but in reference to folic acid, not metafolin.

 

[PhoenX]

I should be clearer, I'll edit my post, I've seen it mentioned that there are concerns that it(and/or any other high dose of folate) may increase growth rate or risk of colon cancer http://depression.emedtv.com/deplin/deplin-warnings-and-precautions.html http://cebp.aacrjournals.org/content/16/7/1325.abstract . I'm fairly sure Rich has mentioned it before. That said, I think there are newer studies disproving it. So, probably nothing to worry about.

Rich mentions it here http://forums.phoenixrising.me/show...uot-ddtox-quot&p=167992&viewfull=1#post167992 but in reference to folic acid, not metafolin.

It's good that you have a critical attitude. It's important to question this! I believe, that regardless of the drug, there are always risks involved. We don't understand our bodies and the drugs sufficiently enough.

"Large doses of folic acid may accelerate the growth of colon tumors. It is unknown if Deplin, which contains an active form of folic acid, has the same effect on colon tumors. If you have cancer of the colon, talk to your healthcare provider before taking Deplin. "

We should keep that in mind! But both of your sources refer to folic acid, a precursor of folinic acid and 5-MTHF. Neither Freddd nor Rich suggest taking folic acid.

My assumption was that I have not enough 5-MTHF. If this is true there would be more risk of getting cancer from not doing anything. Of course I can't say for sure that 5-MTHF is my problem, so there is risk involved.

One possible explanation for the increase of cancer might be the folate trap:
http://www.dach-liga-homocystein.org/EN/Fachinfo/folsaeure/falle.htm
If the people don't have sufficent B12, the methylation cycle breaks. For this reason I suggest taking Methyl B12 in addition to 5-MTHF.

Interestingly I found sources that indicate that the opposite is true. According to this 5-MTHF decreases risks of getting colon cancer:

...These data suggest that dietary methyl supply is particularly critical among MTHFR val/val individuals. When dietary methyl supply is high, MTHFR val/val individuals may be at reduced risk of colorectal cancer probably because higher levels of 5,10-methylenetetrahydrofolate may prevent imbalances of nucleotide pools during DNA synthesis. In contrast, when 5-methyltetrahydrofolate is depleted by alcohol consumption, val/val individuals may be less able to compensate, leading to potentially oncogenic alterations in DNA methylation.
http://cancerres.aacrjournals.org/content/56/21/4862.short

As far as I understand this, 5-MTHF and folinic acid raise 5,10-methylenetetrahydrofolate which is part of the folate cycle and it might be important in the treatment of colon cancer.

There are more sources indicating that:
http://clincancerres.aacrjournals.org/content/9/5/1611.short

and

Wikipedia:
Levomefolic acid(5-MTHF) has been proposed for treatment of cardiovascular disease[1][2] and advanced cancers such as breast and colorectal cancers."

The question is, is depleted 5-methyltetrahydrofolate our problem?

 

[PhoenX]

...
I realize that lab testing is not feasible for everyone, but it is very helpful in interpreting what is going on if some tests can be run before and after trying various treatments for a while. The most helpful combination is a methylation pathways panel from the European Laboratory of Nutrients or the Health Diagnostics and Research Institute in the U.S. and a fairly complete amino acids panel, preferably in the blood plasma, such as the Metametrix 40 plasma amino acids profile.

I would like to do that. I commited to do everything in my power to solve my problem, but I'm a student and it is in our nature to lack money

Therefore i can't afford tests at the moment. I need new glasses. I hardly see anything at the blackboard...

 

[richvank]

I would like to do that. I commited to do everything in my power to solve my problem, but I'm a student and it is in our nature to lack money

Therefore i can't afford tests at the moment. I need new glasses. I hardly see anything at the blackboard...

Hi, PhoenX.

I certainly understand. Glasses have to come first!

Best regards,

Rich