1. Patients launch $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
Nitric oxide and its possible implication in ME/CFS (Part 2 of 2)
Andrew Gladman explores the current and historic hypotheses relating to nitric oxide problems in ME/CFS. This second article in a 2-Part series puts nitric oxide under the microscope and explores what it is, what it does and why it is so frequently discussed in the world of ME/CFS....
Discuss the article on the Forums.

Study: Folinic acid beneficial to 81% of CFS patients...plus biomarker?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by dannybex, Feb 8, 2013.

  1. dannybex

    dannybex Senior Member

    Messages:
    2,283
    Likes:
    584
    Seattle
  2. caledonia

    caledonia

    Messages:
    3,039
    Likes:
    1,712
    Cincinnati, OH, USA
    This is yet another thing related to methylation. You fix methylation and these things should improve.
     
  3. dannybex

    dannybex Senior Member

    Messages:
    2,283
    Likes:
    584
    Seattle
    That's why I posted it in the methylation section. :)

    I found this study 2-3 months after starting folinic, based on the results from Jill Jame's study with autistic kids. It's helped me considerably (along with a small dose of methylfolate), plus TMG and small doses of mb-12 and ad-b12, but don't need the b12's every day.

    Thanks Caledonia. :)
     
  4. alex3619

    alex3619 Senior Member

    Messages:
    7,723
    Likes:
    12,640
    Logan, Queensland, Australia
    The B cell marker: this is the third time something like this has come up, but the first time I think a percentage of any kind was put to it.
     
  5. Dreambirdie

    Dreambirdie work in progress

    Messages:
    5,129
    Likes:
    3,399
    N. California
    This sounds good to me. But what is the difference btwn folinic acid and methyl folate? They are both active forms of folate--right? SO how do you know which is best/better for you?
     
    South likes this.
  6. dannybex

    dannybex Senior Member

    Messages:
    2,283
    Likes:
    584
    Seattle
    That's a difficult question to answer. On another thread I mentioned to Freddd that it seems like folinic -- because it can be a precursor to methylfolate -- that perhaps the fact that it needs to be broken down in some way, thus slowing down the "creation" of methylfolate, makes it easier to tolerate than methylfolate -- at least for some?

    Rich, in some post somewhere (?) described it as a 'buffered' form of folate.

    Hope that helps.
     
  7. Little Bluestem

    Little Bluestem Senescent on the Illinois prairie, USA

    Messages:
    2,693
    Likes:
    2,026
    Midwest, USA
    I have this about folinic acid from Rich in my notes. I do not know the originating thread.
     
    dannybex likes this.
  8. dbkita

    dbkita Senior Member

    Messages:
    655
    Likes:
    281
    These are all good points but it is not clear to me why a healthy diet with lots of vegetable folates won't handle the THF side of things for most of us unless we have some significant folate cycle genetic defects.
     
  9. juniemarie

    juniemarie Senior Member

    Messages:
    303
    Likes:
    82
    Albuquerque
    Has anyone done the CD19 lgM test? I dont remember ever seeing it talked about on this forum?
     
  10. Timaca

    Timaca Senior Member

    Messages:
    420
    Likes:
    75
    I have had lots of CD19 run (as part of a lymphocyte subset panel). My CD4s and CD19s are below the reference range. The CD19 is WAY low. I don't think I've had the CD19+IgM+ test run......

    Best,
     
  11. juniemarie

    juniemarie Senior Member

    Messages:
    303
    Likes:
    82
    Albuquerque
    What is the CFS communities thinking about this test? A true bio marker or another false alarm?
     
  12. Lotus97

    Lotus97 Senior Member

    Messages:
    2,015
    Likes:
    423
    United States
    This is from Rich. He says that folinic serves other useful purposes besides just converting to methylfolate. He also explains what happens when taking too much methylfolate with a high dose of b12

    I actually prefer including both folinic acid and 5-MTHF. 5-MTHF is the form needed by methionine synthase, which is the enzyme with the partial block. Many people's cells are able to convert folinic acid to 5-MTHF well, but many others have inherited genetic polymorphisms that slow this conversion down considerably. The polymorphisms in the MTHFR enzyme are a good example, and these are very prevalent in the population.

    Folinic acid is helpful for a couple of reasons. One is that it is very versatile, in that it can be converted to other forms of folate, which are needed to make DNA, RNA, and purines in general. Another factor is that folinic acid is polyglutamated when it is inside the cells, and this can help to lower the amount of free glutamate, which is an excitotoxin. Excitotoxicity is a problem in CFS, and it is often exacerbated when methylation cycle treatment is entered upon.

    [The reason] I don't recommend [a high dose of] Methylfolate when it is combined with several milligrams of methyl B12 is that this combination takes control of the rate of the methionine synthase enzyme away from the cells and drives it too fast. The result is that too much of the homocysteine is converted to methionine, and there is not enough left to flow into the transsulfuration pathway to support synthesis of glutathione and other sulfur-containing substances that the cells need.

    The result is that the methylation cycle gets going well, but glutathione does not come up, as it needs to do for full recovery. There are excess methyl groups produced because of overdriving the methylation cycle. These are shunted off to the folate metabolism by sarcosine, which is produced by the glycine N-methyltransferase reaction, and then they come back to the methylation cycle via methylfolate. It's sort of like a futile cycle, like a squirrel in a rotating cage.

    This is not just based on biochemical theory, though it is supported by that. It is based on lab tests that people who have been on this regimen have sent me.

    For most PWMEs, this does not work very well in the long run. In Freddd's own case, because of the genetic variations that he apparently has in the CblC complementation group and in MTHFS (not to be confused with MTHFR), it is necessary for him to use a high dosage of methyl B12 to overcome the CblC problem, and it is necessary for him to use a high dosage of methylfolate to feed his folate metabolism, since he cannot use folinic acid or folic acid. (I'm not sure why he cannot use folic acid. Perhaps he has a polymorphism in the DHFR enzyme, also). Freddd cannot tolerate raising glutathione, because it binds cobalamin to form glutathionylcobalamin, and his version of the CblC complementation group is not able to retrieve cobalamin from glutathionylcobalamin. As far as I can tell, this is a rare genetic variation. Most PWMEs are depleted in glutathione, and this is responsible for a large number of the symptoms.

    There may be other PWMEs who have one or more of these genetic issues as well, since Freddd reports that there are some others who respond to these supplements in the same way he does, but most do not seem to have them, based on our clinical study and anecdotal reports from quite a few PWMEs.

    He also has explained this to Freddd (on multiple occasions) why he has a problem with folinic acid, but says that this is rare

    Hi, Freddd.

    As I've suggested, I suspect that you have what appears to be a rare deficiency in the enzyme MTHFS (methenyltrahydrofolate synthetase) which is the enzyme that normally converts folinic acid to methenyltetrahydrofolate, from which it can normally be converted to other forms of folate, including 5L-methyltetrahydrofolate. I think that explains why your body is not able to use folinic acid, and in fact why it blocks your folate metabolism, as folinic acid is known to inhibit the SHMT reaction, which is the main reaction that converts THF to 5,10-methylene tetrahydrofolate, which in turn can be converted to 5L-methyltetrahydrofolate.
     
    dannybex likes this.
  13. Lotus97

    Lotus97 Senior Member

    Messages:
    2,015
    Likes:
    423
    United States
    Does anyone know if vitamin C blocks folinic acid absorption like it does for methylfolate?
     
  14. lampkld2

    lampkld2

    Messages:
    65
    Likes:
    3
    Dannybex,

    I recall that you, like myself, was having some neuropathy issues likely autoimmune and or inflammation related after going on a methylation protocol.

    How did you resolve this? Methylation supps helped me very much, but I am scared to go back on. Ever since that episode, I have been having relapsing and remitting parasthesia and fasiculations as I can literally feel my nerves attacked.
     
  15. dannybex

    dannybex Senior Member

    Messages:
    2,283
    Likes:
    584
    Seattle
    Hi Lampkid,

    Good to see you're still around. I can't say that I've "resolved" my methylation issues, but I'm handling the supplements much better. What works for one person may not work for another, or may affect them negatively, but for myself, because I had/have similar genetic issues, I decided to follow the supplementation that was used in this study:

    http://ajcn.nutrition.org/content/80/6/1611.full

    So I'm currently taking 800 mcgs of folinic, twice a day, plus 750 mgs of TMG (a methyl donor) 3 times a day, plus 200-400 mcgs of methylfolate once a day. I take them with meals.

    I've also had the fasciculations and parathesias come and go, but in my case, because my vitamin D level was so low, and my dietary calcium was so low, I increased both (plus a little magnesium/boron), and that seems to be helping the twitching and tingling. Taurine also seems to help with electrolyte balance and magnesium absorption -- and is calming, at least for me. I'm taking a few other things as well, but those are the main ones.

    Best of luck,

    Dan
     
  16. dannybex

    dannybex Senior Member

    Messages:
    2,283
    Likes:
    584
    Seattle
    I didn't know it blocks methylfolate -- I had heard that it can block methyl-b12 if taken within an hour or so...???
     
  17. dbkita

    dbkita Senior Member

    Messages:
    655
    Likes:
    281
    I don't know about folinic acid. but vitamin C co-administered destabilizes L-5mthf in the gut. The time window is about 20-30 minutes. So it is easy to hold off on that orange juice or vitamin C tablet. I ironically discovered this the hard way and then verified it on the Internet. Ironically my Mom who I got to take FolaPro some time ago was taking it with 1 gram of vitamin C every day. When she learned from me about the vitamin C issues, she initially just nonchalantly shifted the vitamin C to the afternoon .... and within a day or two basically flipped out since suddenly she was absorbing much more.

    You can find discussions of this on other forums including mthfr.net. There was a research paper talking about this that I read once, but my bookmarks folder is so huge and disorganized that it might as well be buried in the Triassic period, sorry.
     
    dannybex likes this.
  18. dannybex

    dannybex Senior Member

    Messages:
    2,283
    Likes:
    584
    Seattle
    I'm glad to hear I'm not the only one with an overloaded bookmarks folder... :)

    Thanks for the info.
     
  19. dannybex

    dannybex Senior Member

    Messages:
    2,283
    Likes:
    584
    Seattle
    I don't know Junemarie. But if it was found in 94% of patients in this study, I would hope that more studies are planned.

    (Sorry for the late replies...eyes have been bugging me lately, but are a little better the last few days...)
     
  20. Freddd

    Freddd Senior Member

    Messages:
    4,579
    Likes:
    958
    Salt Lake City
    HI Dan,

    I haven't read the study yet. Let's put it this way, L-methylfolate is the major type we need for every cell reproducing transaction. With enough MeCbl it can perform ALL functions. When there isn't enough, folinic acid may be a workaround in one transaction, perhaps like HyCbl being the incomplete workaround for inflammation compared to AdoCbl. In any case L-methylfolate is mandatory, folinic acid can be used for one transaction. For folinic acid or any folinate it requires an enzyme and ATP (ATP requires AdoCbl, L-carnitine fumarate,methyl groups, MeCbl, l-methylfolate). What it comes down to is even if a person is genetically able to use folinic acid, it's required conversion to l-methylfolate requires some minimum amount of each of the Deadlock Quartet to be present already. It isn't self booting.

    When a person doesn't get as much l-methylfolate as is required by the body some things don't get it and insufficiency symptoms develop. The first symptoms to develop are usually in the fast dividing epithelial cells; acne, angular cheilitis, IBS, asthma but for some it is mood first or other things on the folate insufficiency/deficiency list. Unblocking the partial methylation block starts the demand for l-methylfolate. Coming out of methyltrap, which is just as sudden as going in, starts demand for l-methylfolate.


    Group 3 - Induced and/or Paradoxical Folate deficiency or insufficiency

    IBS – Steady diarrhea, IBS – Diarrhea alternating with normal, Stomach ache, Uneasy digestive tract, increased hypersensitive responses , Skin rashes, Increased acne, Skin peeling around fingernails, Skin cracking and peeling at fingertips, Angular Cheilitis, Canker sores, Coated tongue, Runny nose, Increased allergies, Increased Multiple Chemical Sensitivities, Increased asthma, rapidly increasing Generalized inflammation in body, Increased Inflammation pain in muscles, Increased Inflammation pain in joints, Achy muscles, Flu like symptoms, Depression, Less sociable, Impaired planning and logic, Brain fog, Low energy, Light headedness, Sluggishness, Forgetfulness, Confusion, Difficulty walking, Behavioral disorders, Dementia, Reduced sense of taste, Increase irritability, Loss of reflexes, Fevers, Old symptoms returning, Heart palpitations, Bleeding easily.

    Increased l-methylfolate relieves these symptoms. Getting rid of folinic acid may relieve these tissues or allow a smaller amoint of methylfolate to relieve them, for whatever reason(s).
     
    dannybex likes this.

See more popular forum discussions.

Share This Page