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!
The ePatient Revolution
Ryan Prior shares his experience and his thoughts from attending the Stanford Medicine X Conference as he contemplates the rising of the ePatient Revolution ...
Discuss the article on the Forums.

Simplified Methylation Protocol Revised as of Today

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by richvank, Mar 30, 2011.

  1. richvank

    richvank Senior Member

    Messages:
    2,717
    Likes:
    758
    Hi, leela.

    Please see the other posts I have made on this thread. I wish I could be more definitive. I think Freddd and I do agree that it's best to avoid folic acid, but we have different views on the other supplements. I'm attempting to work from known biochemistry, and Freddd is working from experiences of himself and others. I don't think either of us has all the answers (yet!).

    When you were injecting methyl B12 subQ, were you taking any form of folate simultaneously?

    Best regards,

    Rich
     
  2. ukme

    ukme Senior Member

    Messages:
    169
    Likes:
    8
    try vitaminuk.com
     
  3. Jenny

    Jenny Senior Member

    Messages:
    1,233
    Likes:
    200
    London
    Thanks Anne and Rich for the info on price.

    Jenny
     
  4. Rockt

    Rockt Senior Member

    Messages:
    296
    Likes:
    13

    Hi Freddd.

    Jarrow B-Right and Country Life AB12, which you had previously recommended, both contain Folic acid. Are they no longer recommended. If so, have you found replacements?
     
  5. drex13

    drex13 Senior Member

    Messages:
    186
    Likes:
    13
    Columbus, Ohio
    Thank you very much Rich, for your answer as well as all of your research. This pretty much answers my questions.:thumbsup:
     
  6. Freddd

    Freddd Senior Member

    Messages:
    4,579
    Likes:
    958
    Salt Lake City
    Hi Leela,

    I injected methylcobalamin subQ with no effect (good or bad) for some time

    I suspect that you did not get "good" mb12 for this. I find that Jarrow and Enzymatixc Therapy tablets far more reliable that the typical pharmacy prepared mb12 solution. It could be the mb12 crystals they started with. In directly comparing 5 different batches of mb12 injectable solution that they had as much variation amongst them as the various brands of sublingual tablets have; from poor to excellent. Even worse, most is exposed to way too much light in preparation and is broken down before you even get and if not immediately wrapped in foil and kept that way and the syringe wrapped in foil before drawing the injection it could be ruined on the spot. Broken down by light mb12 is hycbl.

    but I think I am still dumping mercury right now--


    I don't see how this would have anything at all to do with "no effect" at all.

    I also wonder if one choses folic vs folinic

    How about NEITHER. For me and many others they were both bad news, just slightly differently. Metafolin of whatever marketing brand, OTC or prescription is far superior. Both folic and folinic acid can cause paradoxical folate deficiency in an unknown percentage of people. One of effects of this appears to be the onset and diminishment of IBS in some people.

    I am still quite confused by the methyl/hydroxy/adenosyl conundrum

    I can understand that. There are two, and only two active in humans forms of cobalamin; adenosylb12 and methylb12. Hydroxycbl and cyanocbl both have to be converted to the active forms to do anything at all. There are many ways for this to go wrong in the most complicated absorption and distribution in the body. Many assumptions must be correct for an individual person to be able to use them. Then at best they affect up to about 33% of the the set of symptoms for 67% of people that mb12/adb12 will affect and even heal for near almost everybody, especially with Metafolin present. So hycbl/cycbl leave 2/3 of symptoms unaffected and even made worse for 2/3 of people and 100% of symptoms unaffected or made worse for 1/3 of people.

    Based on the reports of lots of people the odds are pretty good that after a year of mb12/adb12/Metafolin a substantial percentage are ready and able to start rehabilitation or are back at work already and/or are working on the comorbidities that are revealed as the multitude of other symptoms retreat. With hycbl that percentage is almost zero. They are all caught up in "detox" forever (folate deficiency for whatever reason) or any of a whole host of things but the majority of active b12 affected symptoms are still present. That hasn't changed in the 20 months I have been present here.

    Do you want to try the program that based on everything I have seen and experienced gives you a substantial chance of substantial recovery or do you want to be asking the same questions a year from now with nothing much changed? With the folate problem found the odds are even better now. I think this folate is potentially much bigger than Rich appears to think. It has the potential to explain most of what is called "detox" experienced by people taking folic or folinic acid and lack of healing progress.

    You can always do one program for 3 months and switch to the other for 3 months. If you do that switching back and forth for 2 full rounds you will most likely clearly see the difference.
     
  7. Freddd

    Freddd Senior Member

    Messages:
    4,579
    Likes:
    958
    Salt Lake City
    Hi Rockt,

    I picked up another brand of very incomplete b-complex without folic acid or any form of cobalamin and am filling in the missing components with separates. I want to see what it is like without any folic acid. I have ordered some Source Natural Dibencozide and will try it after a month without any to see if I have the usually startup effects with it. If I take the Country Life once each week or so in a larger dose, the folic acid doesn't appear to cause as much a problem if I preload with Metafolin and take it concurrently. I'm going to order the Douglas Labs Metafolin containing b-complex when I have the bucks.
     
  8. leela

    leela Slow But Hopeful

    Messages:
    2,468
    Likes:
    3,071
    Couchland, USA
    Thanks to both Rich and Freddd. Both of you have put so much hard work and energy into this approach, and to helping people sort it out. What a huge gift.
    Many, many thanks.

    To answer Rich's question, I was really (really) spotty with the folate, so this combined with Fredd's explanation of "bad" methylcbl might explain why
    SubQ methyl was doing nothing at all. I was presuming it was being hijacked somehow.
    Fredd, I didn't mean to imply the mercury dump was related to the no-effect. Bad wording on my part (in a crash right now) I meant that to say that
    while I had been taking it for some time with no effect either way, perhaps the fact that I'm dumping mercury right now might be a reason to avoid it?

    I do lean more towards the idea of "active" cobalamin, but don't want to do some bad juju with the mercury. Not sure how to determine which kind
    of mercury might be floating around currently. I stopped actively chelating it a couple of weeks ago.

    Finally, my labs show low reduced GSH, high oxidised GSH, high SAH, low SAM/SAH ratio, low adenosine,
    but when it comes to folic acid derivatives, it's low (.44) THF and low RBC folinic acid only (326--this has been low for many years.)
    What I can't suss is--does this info help me decide which supplements to take or not take? If I've got enough FA in the blood stream but not in the RBCs is this more a matter of omega 3s than folate? Or is folate a separate issue?

    I'm sorry you both must get asked the same questions over and over by so many of us addle-brained Couch Warriors; but I find it near impossible to
    cull the info I am after from the vastness of info you both have made available.
    As so many of us here might lament, I never used to be this dumb...:D
     
  9. Dreambirdie

    Dreambirdie work in progress

    Messages:
    5,130
    Likes:
    3,400
    N. California
    Hi Rich--

    Just for absolute clarification... Is it accurate for me to conclude that the Folapro (by Metagenics) is still okey dokey to take, and the Actifolate (also by Metagenics) is not?

    I still have both supplements in my cabinet, and have only taken a few tablets (total) of each... over the past 6 months. I don't want to trash them if I don't have to, but I don't want to take the "wrong" one. So I'm just checking in to make sure.

    THanks in advance for your response.
     
  10. Freddd

    Freddd Senior Member

    Messages:
    4,579
    Likes:
    958
    Salt Lake City
    I am on my way out right now when I saw this. I want to say one thing. In the two days I have been without folic or folinic acid, just Metafolin, my senses have "brightened up" considerably. Methylfolate is the only form of folate to penetrate the BBB according to the Deplin website. Something has changed in just 2 days without folic acid. ANd the IBS is gone as well with speeded up healing of the cheilitis.
     
  11. richvank

    richvank Senior Member

    Messages:
    2,717
    Likes:
    758
    Hi, Dreambirdie.

    In my opinion, it's fine to keep taking both. That protocol has helped many people. The revised version hopefully will be more convenient, with liquid and powdered supplements, and I also took the opportunity to lower the folic acid, because I don't think everyone is able to make use of it well, for genetic reasons, though some are. Also, it uses NADPH in its conversion to the active forms, and some people appear to be low in NADPH. The Vinitsky protocol uses high-dose folic acid as its only folate form, and reportedly is helpful to many people. I realize that Freddd has found folic acid to be very detrimental in his case, but it's difficult to say how widspread that problem might be, without having more information about genetic polymorphisms.

    Best regards,

    Rich
     
  12. richvank

    richvank Senior Member

    Messages:
    2,717
    Likes:
    758
    Hi, leela.

    You're welcome. These test results indicate that you have glutathione depletion and a partial methylation cycle block and that therefore methylation treatment should be of help to you.
    These results also indicate that your folate metabolism is not as depleted as in many other PWCs, but it still needs some support, and there will likely be higher demands on it when the methylation cycle begins to operate more normally. The low RBC folate indicates that the cell membranes are damaged, which is usual in ME/CFS because of the oxidative stress that is associated with glutathione depletion.

    These test results do not tell us what form or forms of folate it would be best to take. Based on the biochemistry, methylfolate directly supports the methylation cycle, and therefore my opinion is that it should be included. Freddd will likely agree with this. I also believe that it would likely be helpful to include some folinic acid, to provide support for the synthesis of DNA and RNA until the methylation cycle is running faster and is converting methylfolate into tetrahydrofolate at a higher rate. Tetrahydrofolate is the "hub" of the folate metabolism, and other folate forms can be made from it. Since yours is currently low, some folinic would probably help. Freddd will likely not agree with this, based on his personal experience, but I think this depends on each person's genetic polymorphisms. Unfortunately, we don't have data on these, or even have complete information on which ones are the important ones.

    Best regards,

    Rich
     
  13. Rockt

    Rockt Senior Member

    Messages:
    296
    Likes:
    13
    If you test low for B12, (standard blood test), is that a pretty good indication that you have a methylation block, or does it just mean you are low in B12?

    I've tested low several times, got B12 shots, brought the level back up, only to have it test low the next time.
     
  14. leela

    leela Slow But Hopeful

    Messages:
    2,468
    Likes:
    3,071
    Couchland, USA
    Thank you both again, this direct exchange is so useful.

    My last frontier is to put together a protocol that works for me. I know Freddd has mentioned he reacts really badly to glutathione supplementation, but the TD form I have is the one thing that makes me feel better within an hour when I feel really toxic and awful. So I am going to make a presumptuous leap and assume that I do not have the same polymorphisms as he. Therefore I will include folinic acid. (This is perhaps a totally unscientific conclusion.)

    My final question (sorry) is this: what about alternating methyl/hydroxo/adenosyl forms to cover all the bases? Has anyone tried this?

    In the past four years that I've been doing subQ injections I've been through cyano, methyl, and hydroxo. No noticeable difference/effect, though I ended up sticking with methyl because even the buffered form of hydroxo stung pretty badly, (and cyano just sounded like a bad idea.) My long-winded point being, perhaps if one did, say, two or three days sublingual of one form, then switched, then switched again, could that perhaps help the body, or confuse it?

    Any thoughts?
     
  15. richvank

    richvank Senior Member

    Messages:
    2,717
    Likes:
    758
    Hi, Rockt.

    Low serum B12 indicates an absolute B12 deficiency. This will result in a partial methylation cycle block at some point, but I don't know how low it has to go to cause that.

    Inability to maintain serum B12 level on a diet that contains sufficient B12 indicates that there is a problem in either absorption of B12 by the gut or transport of it in the blood by transcobalamin. Conditions such as pernicious anemia or genetic deficiency in transcobalamin would be possible causes. Gut disease such as Crohn's disease or celiac disease can also cause this, as can surgery that has removed the latter part of the small intestine. Low stomach acid can be a factor, because it is necessary to liberate B12 from protein in food before it can be boumd to intrinsic factor in the gut and absorbed.

    Best regards,

    Rich
     
  16. richvank

    richvank Senior Member

    Messages:
    2,717
    Likes:
    758

    Hi, leela.

    Some of the people on the full Yasko treatment take a variety of B12 forms, and ProHealth sells a combined one. Normally, the body is capable of absorbing all the forms of B12. Genetic variations can limit this in particular cases, however, and I guess we don't know whether that is an issue in your case.

    Best regards,

    Rich
     
  17. Freddd

    Freddd Senior Member

    Messages:
    4,579
    Likes:
    958
    Salt Lake City
    Hi Rockt,

    What exactly is "low" in b12 differs from country to county. The USA and UK use a very low "standard, 170pg/ml or so. In Japan, the low alert is at 550pg/ml and they have an Alzheimer's rate of 20% of the USA. Even at 550pg/ml a person can have hundreds of mb12/adb12 responsive symptoms. In a UK study on mb12 and neuropathies with admission by symptoms rather than test results, 63% of responsive persons would have been prevented from being in the study based on test results. The average level before treatment was over 700pg/ml with some responsive persons being over 1500pg/ml at the start.

    B12 pharmacodynamics requires a multi-compartment model;

    1. Liver
    2. Other organs
    3. CNS./CSF
    4. Muscles
    5. Blood Serum
    The difference between a serum level of 200 and 600 is about 2-4mcg contained in serum. Serum level can vary by several hundred pg/ml depending upon what a person ate for dinner. A 1mg injection or 5mg sublingual with 20% absorbed, 1mg, can cause an "instantaneous" boost of 100,000 to 200,000 pg/ml in the serum depending upon which studies one reads and assumptions made and type of mb12 and dose of b12. Some of this, a few mcg, will get parked in the mitochondria or used for various reactions or end up in organs or the liver. A very much smaller amount will end up in the CSF/CNS. In the first 30 minutes half of the original dose in serum will be filtered out by the kidneys. In the next 30 minutes another 50% of remaining. In the first 12 hours the serum level will be down to 1/64 of what it started out at. Over the next 36 hours the serum hallife averages about 12.9 hours. Over the next two weeks the excretion percentage keeps falling off until at 2 weeks it is right back to where it was before the injection and the kidneys play almost no role. At this point the liver is the main excretion route losing perhaps 5-10mcg/day, most of which is reabsorbed if everything is working correctly. If everything is not working correctly the body's entire working quantity can disappear rather quickly. Reabsorption decreasing from 99.5% to 95% changes the serum halflife from 150 days or so to 25 days or so. What the actual rate of reabsorption is depends upon how much or how little is lost by the liver. The lower the serum level over time, the less excreted and the higher the percentage reabsorbed assuming IF etc are all working correctly. The dynamics of all forms of b12 are very similar with the exception of cyanocbl; said to be even more preferred for kidney excretion. In the 20-50 minute initial serum halflife range, cyanocbl tends to be towards the 20 minute end of the range.

    If your system were working correctly you wouldn't likely be low on b12 in the first place. A person can be low on b12 because of folate deficiency regardless of how achieved. A person can have plenty of serum b12 and serum folate and still have functional b12 and folate deficiency symptoms. Further, serum level est tells one virtually nothing about CNS/CSF levels. The CNS/CSF can be deficient while the body itself is not so one can have a degnerating nervous system, mood and personality changes up to and including hallucinations, psychosis and death with perfectly normal; serum levels.

    Folic acid or folinic acid can shut down cell reproduction in hours regardless of b12 serum levels. Further, a person may have low adb12 levels at the same time as having sufficient mb12 and methylfolate for all methylation reactions needed. So low serum levels, say below 1500pg/ml could very well indicate b12 deficiency symptoms and problems galore they may or may not involve methylation.

    For people responding to mb12 who have already developed symptoms, 3 days without mb12 will typically trigger the beginning of returning symptoms. Hydroxcbl doesn't typically affect those symptoms in the first place so they can't come back since they never left.

    The injections at interval method originally developed with inactive cobalamins when b12 was very expensive works for raising MCV but doesn't work well on most other b12 deficiency symptoms. It is about the worst possible method of b12 treatment that might do anything at all.

    What are YOUR specific symptoms when methylation shuts down and how do they change when it starts up? That will give you the best indicator.
     
  18. kurt

    kurt Senior Member

    Messages:
    1,132
    Likes:
    176
    USA.Earth
    Don't know about alternating, but I have learned by experimenting that Fred and Rich are both right, at least in my case. I tried all four forms. Cyano was the weakest, it helped a little but not enough to take regularly. But I take the other three forms daily, and that makes a huge difference, I need all three of the natural forms. Tried the ProHealth B12 Extreme combo tablet, but I can not set the dosages that way. The dose/ratio that works for me, and has been working for several months now, after I worked up gradually, is: 5,000mcg mB12, 1500mcg aB12, and 1250mcg hB12. Some days I take more mB12, but do not take more than 10,000mcg total B12. And this is probably effective because I am using the more effective brands Fred recommended for mB12 (Jarrow) and aB12 (Country Life), plus hB12 as Rich recommends, but for that I am using ProHealth's hB12 (their hydroxy B12 works well and is less expensive than the other brand). Since the aB12 has folic acid, I take that in the PM, several hours apart from methylfolate. This combination, along with supporting supplements, has restored my ability to work (part-time low-stress work at home, but still, that is a vast improvement). If I stop taking the B12, I only last about 12-24 hours before major symptoms start returning.
     
    frenchmoxie likes this.
  19. leela

    leela Slow But Hopeful

    Messages:
    2,468
    Likes:
    3,071
    Couchland, USA
    Thank you, Kurt, this is so useful on so many counts. Could you remind me why it is important to take the folic acid away from the methylfolate?

    ps THis is great news that the protocol has made such an improvement! How long have you been doing it? Do you think we will have to do it forever in order to maintain any functionality gains?
     
  20. drex13

    drex13 Senior Member

    Messages:
    186
    Likes:
    13
    Columbus, Ohio
    Folic acid blocks absorption of methylfolate, causing a folate deficiency. Freddd and Rich can explain better, but that's the gist of it. There is a thread devoted to that here somewhere. It's recent.
     

See more popular forum discussions.

Share This Page