Could it be folate?

[richvank]

Hi, Adster and PhoenX.

I think the situation with folate and cancer is that if you don't have cancer to start with, keeping your folate and B12 levels up will help your methylation cycle to properly methylate DNA and that will help to prevent cancers from developing. On the other hand, if you already have cancer, adding folate may make it worse, because cancer cells have a higher demand for folate than do normal cells. The reason seems to be that folate is necessary for making new DNA, and the cancer cells need to make a lot of that because they rapidly proliferate to form new cancer cells, and the old ones don't die.

I think this is somewhat similar to the situation with testosterone in men and estrogen in women. If they don't have cancer, it can be beneficial to supplement these if they are low. However, certain types of prostate cancer proliferate faster if given testosterone, and certain types of breast cancer do the same if given estrogen, so if the cancer is already present, it can be best to avoid these and even lower their levels in the body.

Folic acid is still not a form of folate that I would recommend. It is an unnatural, oxidized form, and there is some evidence that it suppresses the activity of the natural killer cells if it builds up in the blood. It will build up in some people because they have inherited a slow form of the enzyme DHFR (dihydrofolate reductase), which is needed to chemically reduce folic acid so that it can be used by the body.

Folic acid also competes with the active, natural forms of folate for absorption from the gut into the blood and from the blood into the cells. Since the active forms are what are needed in treating ME/CFS, I think it makes sense to minimize the amount of folic acid that is coming in, to enable the active ones to get into the cells better.

Best regards,

Rich

 

[rydra_wong]

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

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.

!

PhoenX I am very interested in this even though I don't have CFS because according to an AHA study, methylfolate is supposed to cure my hypertension but it doesn't (I cure it with DHEA). That led me to think maybe my methyl cycle is working because everything is going down the BHMT pathway to make SAMe (and there is no BHMT pathway in the brain). So I also had on my todo list to experiment with higher doses of methylfolate.

But, what I find confusing in your note is that you talked about folinic acid and its benefits but what YOU TOOK was METHYLFOLATE. These are not the same. Can you clarify? Also, if you know it, how much of what kind of folate is in that drug that Yboldt takes? And how much are you taking? (I'd like to try the dose that works for you to see if it does anything for me...I can't try until the weekend because I will have to go off DHEA and that will be gruesome if the methylfolate does not work for me).

Thanks
Rydra

 

[rydra_wong]

Good answer, Rich.

 

[rydra_wong]

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, but Fredd had severe reactions to FOLINIC acid. He takes METHYLfolate. It seems this thread is using the two interchangeably and I would like to be clear on which is which? Thanks.
(I don't have reactions to either folate, but not sure either really does anything for me either...it could be the 2g. TMG I take that is working for me)

Regards,
Rydra

 

[globalpilot]

DOes anyone know about the testing done by someone named Quadros ? How to contact them ? The cost ? The meaning of the results ?

 

[Adster]

Hi, Adster and PhoenX.

.... Since the active forms are what are needed in treating ME/CFS, I think it makes sense to minimize the amount of folic acid that is coming in, to enable the active ones to get into the cells better.

Best regards,

Rich

Is there enough in fortified bread etc to cause problems?

Thanks Rich.

 

[Joopiter76]

Folinic acid helps to restore BH4 whis may be the way it works. when you supplement high doses of foic acid it superseeds methylfolate because transporters in the cell cant decide very good between those two very similar moleculs. So this may be the reason why methyl-folate does not cause cancer and high folic acid is controversial. although there are some studies that show that a high normal blood level of folic acid is associated with lower cancer rates.

anypne with histamine issues should be very careful with folates. I think folinic acid is tolerated best in such cases.

 

[richvank]

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

Hi, PhoenX.

Thanks for posting the url for Dr. Smith's video. I watched it. I had heard about his treatment in the past from others, but had not contacted him. I decided to send him the info about the seminar in Sweden. He looked at the slides, and seems to have gotten very excited.
Based on the wonderful things he wrote about my presentation, I would say that we are very much on the same page! Thanks for posting this.
Little by little, we are forming a network of clinicians who are believers in methylation treatment, and that should have a multiplier effect as they talk to other physicians. Dr. Smith is actually a dentist, but seems to get involved in treating some non-dental disorders as well.

Best regards,

Rich

 

[PhoenX]

Yes, but Fredd had severe reactions to FOLINIC acid. He takes METHYLfolate. It seems this thread is using the two interchangeably and I would like to be clear on which is which? Thanks.
(I don't have reactions to either folate, but not sure either really does anything for me either...it could be the 2g. TMG I take that is working for me)

Regards,
Rydra

Hi Rydra,

Thanks for raising this question, I'm also interested in this. The only one who really knows this stuff is Rich. I'm not an expert. Let's try to solve this puzzle together.

Maybe this helps. Watch this video at 1:50:
http://www.youtube.com/watch?v=4ob41QNUSgM

That's the way I see it:
5-MTHF(=Methylfolate/5-methyltetrahydrofolic acid =the drug metafolin ) is part of the folate cycle and folinic acid is a precursor. Folinic acid is converted to 5,10-Methylenetetrahydrofolate which is converted to 5-MTHF. The folate cycle needs 5-MTHF to work properly.

In red you see the MTHFR enzyme which is needed to make the conversion to 5-MTHF. This is the point where many people have genetic problems. They can't convert that much. For this reason I assumed, that folinic acid is not the right choice, if someone has the MTHFR polymorphism. I don't know if I have it, I just thought I could avoid this problem by taking 5-MTHF directly.

Maybe Freddd has a MTHFR polymorphism or he can't convert folinic acid to 5,10-methylenetetrahydrofolate. I don't know how the body reacts to this. I think this is something that we have to find out in the course of this thread.

Karin takes 25mg of folinic acid a day. A study used 0,5mg/kg - 1mg/kg of folinic acid(which was too much for Karin). In this study 81% reported subjective improvement.

At the moment I take 15mg of 5-MTHF. This wasn't a scientific decision. Deplin has 15mg and I thought I could try this dose without doing any harm. If you are taking Solgar Metafolin 800mcg you need 18 tablets a day to get this high dose!

I read that Yboldt arrived at 45mg Deplin which would be 56 Solgar tablets! I don't know him, I just found his post.

How much did you take?

 

[richvank]

Is there enough in fortified bread etc to cause problems?

Thanks Rich.

Hi, Adster.

In the U.S. since 1996, flour has been fortified with folic acid at a level of 1.2 milligrams (1200 micrograms) of folic acid per kilogram of flour. How much folic acid a person gets will of course depend on how much grain the person eats. A study by the CDC showed that this fortification led to an average increase of 190 micrograms of folic acid per day, so it is a significant amount on the average. Generally speaking, people with ME/CFS are not able to use carbs as fuel very well because of a partial block of aconitase in the Krebs cycle, so minimizing the intake of bread is probably a good idea for most PWMEs/PWCs, and that will keep the folic acid intake down.

Best regards,

Rich

 

[PhoenX]

Half life of 5-MTHF and dosing

Today I did some research in relation to the dose of 5-MTHF. My question is:
What if a large subset of people with depression has a folate deficiency[1], could it be, that 15mg of Deplin might not be enough folate for many people?

...measured across depressive subtypes, low folate appears to predominate in melancholic depression, and anorexia and weight loss are common features of this type.
[1] Fava M, Borus JS, Alpert JE, et al: Folate, B12, and homocysteine in major depressive disorder. Am J Psychiatr. In press.

Deplin is often prescribed along with an antidepressant. The antidepressant inhibts the reuptake of neurotransmitters like serotonin, norepinephrine and dopamine thus raising their availability, which improves symptoms.
My question is, is this just an artifical accumulation of neurotransmitters through antidepressants which improves some symptoms while the underlying folate deficiency still exists?

This source is quite interesting:
http://cdn.neiglobal.com/content/blog/l-methylfolate.pdf

Doses up to 90 mg/day of methylfolate (45 mg l-methylfolate) have been studied without any additional adverse events
L-methylfolate is generally regarded as safe
A toxic dose of l-methylfolate is not known at this time

Looks as if 15 mg are far from being an issue.

About the half-life of 5-MTHF:

Mean elimination half-life approximately 3 hours for d,l-methylfolate

I think it's probably the best to take 5-MTHF several times throughout the day.

 

[rydra_wong]

PhoeniX, I tried 5 pills of 800mcg at most. I knew Fredd trid some huge number but to me that is half a bottle! To put this in perspective, I get my vitamins from iherb and if I took that many pills I would have to go without for while until new ones came. I figured it was unsustainable. But I did not realise there was a drug form of the vitamin (is it a drug or is it a vitamin?) where in I could get the high dose in a single pill.

The thing is that your later post says it only persists for 3 hours and I need something that lasts for 12 hours or more to be safe with my blood pressure so DHEA is safe for me in that regard. Interestingly, anyone who takes a dose greater than 50mg DHEA is taking a dose known to work for DEPRESSION. (I believe that is the only thing high dose DHEA was tested in, at least when I started it). I would rather actually fix the actual problem as DHEA is obviously just a way around some problem. But it has to be a way that I am not running out of pills (or efficacy every few hours). I definitely have neurological issues which are treated with it fyi. But I can't say how bad they'd get because the very day I got them I ran to the health food store and started sucking down DHEA. (Cleared up panic in minutes for me). I always think that if you work around a problem that will get you by for awhile, but it is better to solve it because until you figure out the problem you don't know all the repercussions it may cause.

Thanks for the link. I can't watch it now, I'm late to go feed my cats. But your post is EXTREMELY INTERESTING. Thank you!

Regards,
Rydra

 

[rydra_wong]

Hi, Adster.

In the U.S. since 1996, flour has been fortified with folic acid at a level of 1.2 milligrams (1200 micrograms) of folic acid per kilogram of flour. How much folic acid a person gets will of course depend on how much grain the person eats. A study by the CDC showed that this fortification led to an average increase of 190 micrograms of folic acid per day, so it is a significant amount on the average. Generally speaking, people with ME/CFS are not able to use carbs as fuel very well because of a partial block of aconitase in the Krebs cycle, so minimizing the intake of bread is probably a good idea for most PWMEs/PWCs, and that will keep the folic acid intake down.

Best regards,

Rich

I should also mention that Life Extension wrote up a huge spread on something very radical their doctors noticed...they found that ALL THEIR PATIENTS HAD TO DO to have normal blood pressure was AVOID ALL WHEAT. (I did wonder what sort of folate was in wheat). Is there any way to get ahold of non-folic-acid fortified wheat products? Do you know if it is added to the wheat or to the baked goods? In other words, if we buy bread makers and make our own bread, will it have folic acid in it from the wheat we buy?

I had heard that the practice of adding folates to bread products has saved many lives, however hard it makes life for me. Sigh

Thanks for the informative post!
Rydra
This is also very interesting.

 

[PhoenX]

...
The thing is that your later post says it only persists for 3 hours and I need something that lasts for 12 hours or more to be safe with my blood pressure so DHEA is safe for me in that regard.

In this case folinic might be the better choice, which has a half life of 6,2 hours according to wikipedia. Half life is the period of time it takes for the amount of a substance undergoing decay to decrease by half. With folinic acid you could have two half life periods within 12 hours.

You have the MTHFR A1298C +/- polymorphism which reduces the MTHFR enzyme activity to about 50-60%[1].

I wrote you a message. I'm interested in your current protocol.

PhoenX

[1] A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity.
Weisberg I, Tran P, Christensen B, Sibani S, Rozen R.
http://www.ncbi.nlm.nih.gov/pubmed/9719624

 

[richvank]

Hi, PhoenX.

I think the half-lives you are citing from Wikipedia refer to the levels in the blood plasma. I think the folates are transported into the tissue cells with these half-lives, not lost from the body.

This use of the term half-life is not the same as the way it is used in some other contexts, such as in radioactive decay.

Best regards,

Rich

 

[PhoenX]

Hi, PhoenX.

I think the half-lives you are citing from Wikipedia refer to the levels in the blood plasma. I think the folates are transported into the tissue cells with these half-lives, not lost from the body.

This use of the term half-life is not the same as the way it is used in some other contexts, such as in radioactive decay.

Best regards,

Rich

Thanks for the information!

I think I chose the wrong field of study

 

[rydra_wong]

I don't have my mouse and I am crippled w/o one so this is just a quick note. I had to apply flea control medicine (Advantage II) to my 10 cats yesteday and it is an androgen receptor blocker (DHEA blocker) so today has benn horrible....I am so irrirtable I want to shed my skin and anything that touches me is excrusiating, and I am having brain swelling all over (not judt right side which iodine causes for me). So I decided to try your 6 methylfolates since my DHEA wasn't doing what it should for me. I got busy with something else then started to notice an efervesence in my brain, like it has been rubbed with Vicks Vaporub. It wasn't extremely pronounced but it was noticeable and it made me stop what I was doing and try to figure out if I had taken a high dose omega=3 today? (Because in my life I have found 9g omega-3 causes brain effervescence as does a high dose choline (don't remember that dose))/ I had not takn any extra omega-3 but I remem,bered I had taken the folate. So I took 6 more and it is a definite glow. I still have a headache -- it has not counteracted the flea medicine completely but it is making my brain happier -- increasing circulatoon, although it feels more like VENTILATION. Pls excuse the typos - I am going to take and extra 6 to make 18...I discovered I have a bottle in reserve so I won't run short.

I don't know about thehalf life of anything but DHEA - it is 10 hours (DHEA is in your system 20 hours). If I let my DHEA go to zero at night, then I am too schleppy in the morning to get going. Also if I let it go to 0, then the rise in testosterone when I take it makes me horny (don't laugh!). Th efirst time I took it (starting from subzero) the rise in testosterone made be break out for 1-2 days. But if I keep it in my system all the time, these problems don't happen. My protocol is at the thread herein "Fredd's protocol" or whatever started by Idie. It's sort of Fredd's with a gigantic wrapper. I have to keep a detailed list for my doctor (Yasko's protocol for me is longer but I am fearless about methyls (unlike her) and I tested to prove I didn't need some of the other things like yucca and charcoal.

I'll get in tomorrow and tell you the results of taking 18 folates. Thanks for poking into this and sharing!
Regards,
Rydra

 

[rwac]

Is there any way to get ahold of non-folic-acid fortified wheat products? Do you know if it is added to the wheat or to the baked goods? In other words, if we buy bread makers and make our own bread, will it have folic acid in it from the wheat we buy?

Look for organic bread/wheat, it doesn't have added folic acid.

 

[PhoenX]

...
My protocol is at the thread herein "Fredd's protocol" or whatever started by Idie. It's sort of Fredd's with a gigantic wrapper. I have to keep a detailed list for my doctor (Yasko's protocol for me is longer but I am fearless about methyls (unlike her) and I tested to prove I didn't need some of the other things like yucca and charcoal.

I'll get in tomorrow and tell you the results of taking 18 folates. Thanks for poking into this and sharing!
Regards,
Rydra

Even though this thread is about folate, I don't think that the answer is that easy. I gave this thread this challenging title, because so many people seem to take low doses of folate and I wanted to give them an impulse to try something different. I believe that most of us do not take enough folate, but each of us has to do an individual protocol. Genotyping as well as knowledge about the methylation cycle can help us.

I racked my brain about your case and couldn't sleep until 3 AM
I think I learned a lot from it. Here is my hypothesis:

...
Methyl B-12 (1 sublingual)
Brand: Jarrow Dose: 5000mcg Sublingual
Reason: Methylation, Methylation in Brain
Notes: 2 were no more effective than 1 for me

P-5-P (Coenzymated B-6) (1 pill)
Brand: Source Naturals Dose: 100mg Tabs
Reason: Kidney Protect, Lower Homocysteine
Notes: 50mg worked as well, but this is kidney protective so since I can tolerate it, more is better. Shortness of breath when I ran out of this (but could have been iron shortage as welllow ferritin but Hemoglobin level fine).

TMG (2 pills)
Brand: Now Foods Dose 1000mg Tabs (2x/day)
Reason: Methylation. Those who get the most TMG through diet get 2g/day.
Notes: Can cause nausea (only if taken with adrenal supplement for me)
...

My assumption is, that you suffer from high blood pressure because of high cortisol and DHEA helps you to deal with it. I hypothesize that cortisol is correlated with homocysteine[1] which seems to be your major problem, since you have the CBS C699T +/+ as well as the CBS A360A +/- polymorphism. This leads to drastically reduced CBS enzyme activity.

Watch this:

[2]

The CBS enzyme activity is reduced which in turn accumulates homocysteine, because you can't get rid of it. The problem is that homocysteine is toxic. There is evidence that homocysteine plays a role in hypertension[3].

The question is, how do we get rid of it?

I suggest the following:
Let's take a look again at the graphic [2]. B6 and Zn is also involved in the activity of CBS. I suggest to double your B6(P-5-P) supplementation to 200mg. This can help the CBS enzyme to convert more homocysteine.

I also suggest a high dose of 5-MTHF and more of the B12 5000mcg subliminals. You wrote, that more than one B12 doesn't give you any additional effect. Maybe this was due to low folate. Together they may convert more homocysteine.

I suggest a higher dose of TMG/Betaine up to 6mg. I think this could help you a lot.

If you take another look at the graphic [2], you will see that in the end methionine is converted to homocysteine.
Therefore I suggest lowering methionine in your food:
I read that it is in cows milk, regular formula, meat, fish, cheese, eggs, Regular flour, dried beans, nuts, and peanut butter.

Since you have this CBS bottle neck you will have problems to get sufficient cysteine. It's probably a good idea to raise it through NAC supplementation.

I searched for the upper limit of TMG and I found this protocol. It seems that I wasn't the first one with this idea
http://www.lef.org/protocols/heart_circulatory/homocysteine_reduction_02.htm

I'm pretty shure that this will help you! I think the reduction of methionine in your food is a very important part!

__________________________
[1]Serum Homocysteine: Relationship with Circulating Levels of Cortisol and Ascorbate
Jos F. Cascalheiraa, Mnica C. Parreiraa, Andreza N. Viegasa, Maria C. Fariab, Fernanda C. Dominguesa
http://content.karger.com/produktedb/produkte.asp?doi=158636

[2]http://www.ebm.rsmjournals.com/content/229/10/988/F1.large.jpg

[3]SERUM HOMOCYSTEINE CONCENTRATIONS IN PATIENTS WITH HYPERTENSION
Alina Atif, Muhammad Atif Rizvi, Shoaib Tauheed, Irum Aamir, Farrukh Majeed,
Khalid Siddiqui, Sadaf Khan
http://www.pps.org.pk/PJP/4-1/Alina.pdf

 

[globalpilot]

I read through Karins thread and she tested positive for autoantibodies to the folate receptors through Quadroz and high supplementation helps her.

I've been thinking about antibodies and wondering if autoantibodies would occur mainly due to increased cell death. I say this because cell proteins are generally inside the cell and the ones outside the cell would be within the fatty membrane. And antibodies bind to substances in plasma. So high autoantibodies may mean there is increased cell death and the cell contents are spilling into the blood causing antibodies to bind to them. I''m guessing high folinic would still help b/c it would saturate the remaining cells that are not damaged.

I'd be interested in anyones thoughts (especially you Rich!)

GlobalPilot