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Methylation protocol for dummies please

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by mattie, Dec 3, 2017.

  1. mattie


    The title of this thread may be contradictory. The subject is complicated. At least I think it is. But many of the forum members talk about lifting methylation blocks as if they were exchanging some cookie-dough recipe. Are you all Einsteins? Or biochemists?

    In the last 2 years I have been reading a lot on this forum and elsewhere about the various methylation protocols.
    Because of the many positive reports I have tried different recommendations. Without results or any reaction at all unfortunately.

    But frankly the more I read about this subject the more confused I get. There are so many conflicting theories and protocols and revised protocols and addendums out there. It is impossible to know where to start for newbies.
    And if you delve in to all the underlying biochemistry, genetic mutations, etc. It all gets extremely complicated and it is just way over my head.

    Yes you can just point me to one of the many threads that are already there. Believe me I have read them all. And because of reading them all it is impossible to make a well informed choice. There is just too much contradiction.

    Can anybody recommend what protocol to try, based upon the latest insights.
    What kind of B12, what form, what brand, how much. same for Folate. If nothing happens, what should be added?
    Or do I need to have tests done before this can be answered?
    Can this be done under medical supervision? Perhaps over the internet? (I am homebound).

    Or what would be a reasonable relatively safe protocol to start with?
    Last edited: Dec 3, 2017
    rodgergrummidge likes this.
  2. wonderoushope

    wonderoushope Senior Member

    I feel ya! I would like to understand the basics myself and find it rather overwhelming. So will keep a lookout for updates on this thread. I wish there was a sticky just giving an overall outline of what methylation is all about, but not having 10+ pages of replies (as it's very time consuming to sift through it all).
    mattie likes this.
  3. jpcv

    jpcv Senior Member

    SE coast, Brazil
    I feel the same thing.
    Mel9 likes this.
  4. PinkPanda

    PinkPanda Senior Member

    This is a picture of the methionine cycle. The methionine cycle produces SAMe (S-adenosylmethionine), which is used for synthesis of alpha lipoic acid, choline, Q10, carnitine, etc.
    You can have mutations that reduce the activity of enzymes like MTHFR, MS and MSR. When MTHFR functions too low, this reduces the production of 5MTHF/Methylfolate. Methionine Synthase Reductase (MSR) produces methylB12 from hydroxoB12 and a mutation might reduce this reaction.

    The idea of the methylation protocol is, if you have a mutation that reduces production of methylfolate/ methylB12, you take methylfoalte and methylB12 supplements to compensate for this metabolic weakness.
    That is the idea, but whether the approach is right for ME/CFS in not proven. Whether taking methylation supplements, is the right way to compensate for these mutations is not sure.
    This is where you are confronted with a lot of personal experience and different theories.

    Some people seem to experience improvement on methylation protocol, a number of people also react badly.
    I think you definitely have to be careful with taking methylB12, methylfolate, especially in high doses. Even in the short time I am on this forum, I have encountered a number of threads by people ending in the ER after taking methylation supplements with symptoms like anxiety, panic, racing heartbeat, nerve symptoms, ..

    Another personal experience:
    My approach is to supplement cofactors for enzymes like MTHFR and MSR, like hydroxoB12 and riboflavin. Reactions to these supplements differ individually again though, not everyone tolerates these supplements well. In case you are interested, I wrote more on the role of cofactors in mutated enzymes here.

    That's a bit offensive :meh:

    Edit: I don't think that having an MTHFR mutation necessarily concludes having to take folate. Folate as a vitamin might still be important because of other reasons, if you have folate deficiency,..
    Last edited: Dec 3, 2017
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  5. ahmo

    ahmo Senior Member

    Northcoast NSW, Australia
    There are some links in my signature, including methylation for dummies. good luck. Using Freddd's Protocol worked for me. Rich VanK's SMP did not. We're all different.
    mattie likes this.
  6. Hip

    Hip Senior Member

    You can dismiss 99% of what you read about the methylation protocol as pseudoscientific nonsense.

    Trying the methylation protocol is simple and straightforward: you just take the following supplements daily:

    Vitamin B12 hydroxocobalamin 2000 mcg sublingual
    L-5-MTHF 200 mcg
    Folinic acid 200 mcg
    Lecithin 1200 mg
    Multivitamin/multimineral tablet

    Full details here: Revised Simplified Methylation Protocol (this was the last revision Rich Van Konynenburg made to his protocol before his death in 2012).

    If it works for you great; if it does not, then move on. Don't get caught up in all the pseudoscientific nonsense about "methylation blocks" and needing to optimize your genetic SNP mutations before you can get methylation to work.

    People would have you believe that if the methylation protocol does not work for you first time, then it's because you haven't optimized or addressed some obscure SNP mutation that you have, a mutation that causes one of these proverbial "methylation blockages".

    But I have never come across any accounts of people failing to get benefits from the methylation protocol the first time, and then only later succeeding in getting it to work after delving into their genetic SNP mutations and making some adjustments. The methylation protocol either works for you or it doesn't. You don't need to tinker around with your SNPs!

    Some people do better taking methylcobalamin rather than the hydroxocobalamin form of B12, so that's about the only adjustment worth experimenting with. And it can take 6 weeks before the benefits of the methylation protocol begin to appear (and it may take 6 months before the full effects manifest); so you need to give it time.

    But other than that, it's very straightforward.

    Note that Rich Van Konynenburg's informal study found that only 27% of ME/CFS patients made major improvements on his methylation protocol, so you have only around a 1 in 4 chance of methylation leading to substantial improvements in your ME/CFS symptoms.

    And it's worth pointing out that any benefits you get from the methylation protocol may have nothing to do with methylation anyway: vitamin B12 injections were used as an ME/CFS treatment before the methylation protocol came along, and B12 does seem to help some ME/CFS patients, especially with brain fog. But nobody really knows why B12 works for some ME/CFS patients, and it's mechanism of action may have nothing to do with methylation. Professor Martin Pall theorizes that B12 might work for ME/CFS because B12 hydroxocobalamin is a nitric oxide scavenger.
    Last edited: Dec 12, 2017
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  7. Learner1

    Learner1 Forum Support Assistant

    Pacific Northwest
    Methylation is not nonsense. It's essential to life, to proper immune function, neurotransmitter production, DNA replication, etc.

    The problem is that methylation protocols should not be passed around like cookie recipes. What you need is unique to you, and much as I respect Richvank and Freddd and the work they did building protocols, they don't work for me and likely not for you.

    Many people get into trouble because they focus on one or two supplements, like folate and B12. While they're essential, one also needs cofactors, like B6, B2, magnesium, potassium, l-methionine, trimethylglycine, and phosphatidyl choline

    These processes encourage the formation of glutathione, which you need adequate amino acids to make and vitamin C to recycle. Glutathione can mobilize toxins, so you need a good system to eliminate them, with adequate digestion, fiber and water intake, and B1 and molybdenum for your transsulfuration pathway to work.

    Testing is incredibly useful. Saves time and money and frustration in tinkering with all of this. You get information that helps to individualize all of this for you.

    Your genes may cause you to need more or less of various nutrients than other people. But environmental factors, like toxic exposures, stress, or infections may override what your genes say and increase your needs for various nutrients.

    Some nutrients, like B6, are used in multiple biochemical processes like producing heme for your blood or sphingolipids for membranes, so you can run short for methylation.

    The best test I've found to help is a Genova Diagnostics NutrEval test. Its very comprehensive and has been essential in solving some difficult methylation issues. Its available in the US and Europe and likely elsewhere.
    Journeyman likes this.
  8. Hip

    Hip Senior Member

    I am not suggesting that methylation is nonsense; it is a well known area of biology.

    And I am not suggesting that the methylation protocol does not work; we have lots of anecdotal reports that it does help some ME/CFS patients, and Prof Carl-Gerhard Gottfries published a study about the use of B12 hydroxocobalamin or methylcobalamin injections plus oral folic acid for ME/CFS.

    In his study, Gottfries found that ME/CFS patients generally get a better response from B12 methylcobalamin rather than B12 hydroxocobalamin.

    And Gottfries found that ME/CFS patients taking more frequent B12 injections and higher doses of folic acid (a B12 injection of 1,000 mcg every 4 days, plus oral folic acid 7,000 mcg daily) got better results than patients using lower folic acid doses and less frequent injections.

    Gottfries also reports that "response to treatment is generally obvious within a few weeks from start, if the dosage is good enough." So that suggests you will get a faster response to the methylation protocol if you use B12 injections and good doses of folic acid (or better still the active forms of folate like L-5-MTHF and folinic acid), rather than sublingual B12 tablets. Although B12 sublingual tablets are easier to obtain.

    But what I am suggesting is that people on this forum make the methylation protocol sound incredibly complex and Byzantine, when in fact it is pretty simple and straightforward.

    Can you point me to even just one story online where an ME/CFS patient tried good doses of B12 and folate and failed to get any benefits; but then suddenly the benefits manifested once they added the cofactors you mention?

    In any case, the Rich Van Konynenburg methylation protocol includes a multivitamin/multimineral tablet and lecithin to provide these cofactors just in case a patient may be short of them.

    Perhaps the only additional supplement worth mentioning is potassium, as there is some indication that the methylation protocol can cause hypokalemia (potassium deficiency), so a potassium supplement is insurance against that. Rich Van Konynenburg speculated that the potassium deficiency might be due to accelerated cell division when the folate is restored to the cells. Freddd provides a similar explanation here.
    Last edited: Dec 13, 2017
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  9. mattie


    Thank you so much @Hip. This is exactly the response I was hoping to get.
    Very helpful!
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  10. Mel9

    Mel9 Senior Member

    NSW Australia

    Yes, that makes it simpler than I thought it could be. I have weekly methylcobalamin injections for peripheral nerve damage. After about 6 weeks I do think my fatigue might also be Lessening.
    Hip likes this.
  11. Eastman

    Eastman Senior Member

    In my opinion, the supplements and dosages mentioned by Hip that are taken from richvank's Revised Simplified Methylation Protocol are reasonable to start a methylation protocol with.

    However, do note that richvank himself added this paragraph in his post:
    In other words, he thought that the supplements he listed are unlikely to be optimal for everybody.

    There are more caveats further down his post, so even his so-called simplified protocol can get a little complicated.
  12. Hip

    Hip Senior Member

    I think it is only complicated when people turn the simple act of taking B12 and folate into a kind ornate religion, or some long drawn out saga and quest for the hold grail.

    Reading this forum, it is easy for people to get sucked into a vortex of methylation pseudoscience, and instead of using their time more productively, people get bogged down with all this unsubstantiated forum speculation about "methylation blockages" and so forth.

    There are lots of useful ME/CFS treatments other than methylation that patients can try: I have listed some of these treatments in the roadmap of chronic fatigue syndrome treatment. By all means try the methylation protocol; but if it does not work for you, I think your time would be better employed in trying out some of the many other ME/CFS treatments that have proven beneficial, rather than spend countless hours discussing how obscure "methylation blockages" might be preventing the methylation protocol from working.

    As I said above, I have never come across anyone on this forum who initially failed to get any benefits from the methylation protocol, and then only later succeeding in getting it to work after identifying and addressing one of these proverbial "methylation blockages".

    These "methylation blockage" discussions remind me of the disconnected-from-reality philosophy the Medieval scholastics, who would spend hours discussing how many angels can dance on the head of a pin.

    I don't think that is what Rich Van Konynenburg meant. I think Konynenburg's main point is that he thought his methylation protocol would work best for ME/CFS patients whose ability to methylate is poor.

    That's why Rich suggested ME/CFS patients might first want to get their ability to methylate tested using either the Health Diagnostics and Research Institute (New Jersey) test for methylation status, or the European Laboratory of Nutrients (Netherlands) test for methylation status (see their "amino acids analysis").

    However, Rich says here that:
    So it is not clear whether these tests are actually of much use in predicting in advance whether the methylation protocol will likely work for you. So it is probably best just to take the methylation protocol supplements and see if you feel any better after a couple of months.
    Last edited: Jan 9, 2018
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  13. Eastman

    Eastman Senior Member

    I agree that some people do seem to obsess over methylation and ignore other possible treatments. There was a member on PR who was following Freddd's protocol and trying to do what he recommended but suffering pain for it. I suggested to her that her symptoms might be caused by something else, but she kept coming back to the forum to ask for help to find-tune the protocol. Eventually, I suggested she take a vitamin that Freddd suggested to limit while on the protocol. She did, said she felt improvement, and has not come back to the forum since, presumably and hopefully because she is better.

    That said, I think that saying that methylation is simple is going to the other extreme.

    Yes, but the question remains: Why is the ability to methylate poor? As I mentioned in my previous post, richvank mentions a few possibilities in his post, possibilities that he recommended testing for.

    So you don't count Freddd's testimony? Or ahmo's earlier in the thread?

    I think the main reason for richvank coming up with the simplified protocol is to at least allow some people to try it and possibly get some benefit from it, and not because methylation is necessarily simple for everyone.
  14. Hip

    Hip Senior Member

    I think Freddd's protocol is in essence the same as Rich Van Konynenburg's protocol. They are both based on taking B12 and folate, with a few extra supportive supplements. But the core is B12 plus folate.

    Freddd's protocol is given here, Rich's simplified methylation protocol here.

    The primary difference is that Freddd's protocol uses B12 methylcobalamin (with some B12 adenosylcobalamin thrown in as well), whereas Rich suggests starting with B12 hydroxocobalamin first, and then if that does not work, switching to B12 methylcobalamin.

    When @ahmo tried the Rich's simplified methylation protocol with hydroxocobalamin it did not work, but once she switched to taking methylcobalamin, she started getting benefits. That does not mean Rich's methylation protocol did not work for @ahmo; I think it means she just needed to switch to methylcobalamin to get methylation to work, as Rich suggested people should do in cases where hydroxocobalamin yields no benefits.

    Above I mentioned already that ME/CFS patients trying Rich's methylation protocol may need to switch to methylcobalamin if hydroxocobalamin does not work for them (in fact it may be easier just to start with methylcobalamin in the first place when trying Rich's methylation protocol).

    I am not sure how much solid evidence there is that ME/CFS patients have weak methylation. There are almost no studies on this. Are the lab tests Konynenburg used considered solid evidence of poor methylation? There are lots of lab tests around that are not properly validated to proper scientific standards.

    In any case, even if ME/CFS patients do have weak methylation, why that might be is an interesting question, but it's not of any direct importance to patients who may just want to try out the methylation protocol to see if they derive benefit.
    Last edited: Dec 14, 2017
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  15. drob31

    drob31 Senior Member


    Hey, @Hip, just replying to this old thread.

    1/4 isn't bad I would say, if it's just another thing to try.
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