Dismiss Notice
IdeaLabsDC.com February 2016 Giveaway!
Click Here For Giveaway!


Discussion in 'Supplements' started by Jib, Oct 31, 2013.

  1. Jib

    Jib Member

    I was diagnosed months ago as compound heterozygous for two mutations of the MTHFR gene -- C677T and A1298C.

    I've been taking a prescription called Deplin, which is the converted form of folic acid, L-methylfolate. I break the tablets in half and take 7.5mg a day. In addition, I've been taking 2.5mg of sublingual methylcobalamin and 12.5-25mg of P-5-P every day.

    I found that even 1mg of methylcobalamin was messing me up. It would make me feel tired and sluggish and groggy and depressed. It seems like I was overmethylating and my body was getting overwhelmed by that. I seemed to be able to handle 500mcg okay although it still was a tiny bit iffy.

    Interestingly, over the past couple weeks, since I started taking 500mg of niacinamide in the morning and 500mg again in the late afternoon, I've been able to take 2.5mg of methylcobalamin with no noticeably adverse effects. I remember reading on mthfr.net that niacin can act as a methyl 'sponge' that soaks up excess methyl groups.

    Dr. Ben from mthfr.net seems to very rarely if ever recommend Deplin, since he seems to be a fan of using the lowest dose that gets results. I'd agree with that. I get a prescription though and my psychiatrist wanted me to take 15mg because that's what worked in studies on depression, and I wasn't able to get him to prescribe me the 7.5mg tablets which I could've broken up into 3.25mg tablets. So I've been stuck with 7.5mg, although I do have to admit that it does seem to work. When I've stopped taking it for a week or two I definitely notice my suicidal depression coming back full force.

    Anyway, here's an interesting bit on overmethylation, undermethylation, and niacin:

    http://mthfr.net/overmethylation-and-un ... 012/06/27/


    The only issue is the doctor did not realize how effective methylation is at supporting neurotransmitters and thyroid hormone production.

    So what happened is the gentleman decided to skip his methylfolate and methylcobalamin dose, take a lot of niacin (which is a methyl ‘sponge’) and he immediately tanked his methyl groups which caused symptoms of undermethylation.

    Then, upon restarting the methylfolate and methylcobalamin, and maintaining his current dosage of medications, he felt great for a few hours.

    Then anxiety hit due to excessive neurotransmitter production and likely thyroid hormone production.

    So – in order to quiet those symptoms, I told him about how niacin works and how to take it and his anxiety decreased almost immediately.

    "Nicotinic acid (Niacin USP) requires SAMe to be metabolized. SAMe is a major methyl donor. Thus, when one consumes niacin, SAMe gets used up and methyl donors drop. Thereby excessive methylation goes away.

    Nicotinic acid is a cofactor for the COMT enzyme. This enzyme helps breakdown norepinephrine and epinephrine – and estrogen. These are all commonly elevated in those with anxiety. Since the COMT enzyme sped up, the breakdown of these occurred faster.

    Does anyone else here have any mutations of the MTHFR gene? Given how important methylation is, it seems like it would be a good topic to cover in light of Ray Peat's research, although I've read next to nothing from Peat or any of his followers about the MTHFR gene mutations.
  2. iLoveSugar

    iLoveSugar Member

    Rays believes it's a huge medical fad, that can be fixed by diet. I have the mutations as well. He says the supplements can sometimes benefit, regardless of a mutation or not.
  3. Jib

    Jib Member

    I was thinking was that the converted forms of the B-vitamins seem to be safer anyway. I'd love to see an activated B-complex that included all of the B-vitamins. A lot of times you'll see ones with mostly activated B-vitamins but then plain folic acid. I'd imagine it would be good for most people just as a nutritional insurance policy, and it would also be a lot more convenient than having separate bottles of the B-vitamins.
  4. iLoveSugar

    iLoveSugar Member

    Definitely agree! Would love to see an all active B as well.
  5. barefooter

    barefooter Member

    My ND diagnosed me with this from a blood test. I took 5-MTHF for a while. At first it seemed like it might have been helping, but I think it was really that a lot of other things were improving in my life. I take it sometimes now, but I don't feel any effect from it. I did experiment with a little niacinamid (when not taking 5-MTHF) and noticed that it increased my anxiety. I consulted with a different doctor that specialized in orthomolecular medicine for mental issues, who trained at the Pfifer clinic. He told me that there are thousands of genes that regulate folate conversion, and they've picked two, and are now trying to make the claim that it's an accurate way to predict how well your body can make the conversion to the active form of folate. He puts no weight in the test, and thinks it's a being pushed on doctors to sell more of the prescription drugs.
  6. Wilfrid

    Wilfrid Member

  7. Jib

    Jib Member

    Oh man, that's sweet. Super Coenzyme B-Complex huh? Just what I was looking for. Now when my other bottles of B-vitamins run out in a couple years I'll know where to go XD

    And thanks for the other link too -- that's very interesting.
  8. Rinave

    Rinave Member

    I also took the genetic test and I am heterozygous on 677 and 1298. So this new doctor I am seeing prescribed nebulized glutathione, methyl B12 injections, hydroxyB12 drops, and finally Deplin 15mg a day. I was doing ok until I started Deplin, I get depressed and very anxious. He says I am over methylating and said to take only 7.5. I must admit as others are saying here in this thread, that some doctors are exaggerating this situation and going about in a way that causes too many side effects.

    I know for sure I have problems with detoxification, and I believe that glutathione is very helpful, but wonder about the other items doctors are using in large amounts. I also heard that some doctors don't like to use Deplin. And some say that if we get a reaction or over methylation to take Niacinamide immediately and will nullify the effects of Deplin.

    Do you know where I could find what Ray Peat says that this is a fad being used by some doctors?

    Any information on this subject would very helpful!
  9. iLoveSugar

    iLoveSugar Member

    This was my email transcript:

    >> Could I get your thoughts on this? My MD called back tonight:
    >> 1) He thinks Glutathione could benefit me? Either this
    >> <http://readisorb.com/> or IV.
    >> *====Did he explain what it would do? Intravenous glutathione is
    >> currently a big medical fad.**
    >> 2) I had a double mutation of the MTHFR C677T gene. He thinks
    >> Methylfolate and Methyl B12 may benefit?
    >> *====They often help, regardless of the mutation. Was your
    >> homocysteine measured? This is an even bigger medical fad, and
    >> probably more worthless, than the glutathione craze.**
  10. Rinave

    Rinave Member

    Thank you I Love Sugar!

    Very good to know. In my case glutathione nebulized 2 times a day is what is helping me breathe.Before I was having the hardest time breathing. I acquired asthma living in an agricultural area with many other toxins.
    My homocysteine was not measured though. The doctor treating me, also has the compound heterozygous I do and he said that because it helps him, he is also recommending these supplements. I feel like stopping Deplin and just get a supplement recommended above The Super Coenzyme B that has some methyl folate.

    I still don't know much about the MTHFR variants, but I also have been hearing that we can silence bad genes with diet and avoiding toxic chemicals and bad air. My doctor advises me to move out of this area, which means he would lose me as a patient. It appears that he has been honest about it, maybe because he knows first hand how it feels to have this impairment.
  11. iLoveSugar

    iLoveSugar Member

    My alternative MD wants me to go on liposomal glutathione. I was thinking about giving it a go. What do you take? Link? I have all sorts of health issues.
  12. Rinave

    Rinave Member

    my doctor orders mine from a compounding pharmacy and it is liquid glutathione. The pharmacy is Moses Lake Professional Pharmacy in Washington.

    I heard that liposomal glutathione is also good. A lot of supplements are not that good and don't raise the glutathione level in the body.
  13. iLoveSugar

    iLoveSugar Member

    Do you feel great improvement with it?
  14. Rinave

    Rinave Member

    Sorry I didn't see your question before. My hubby had surgery
    And I have been super busy.
    I do feel very good with the nebulized glutathione.
    It is actually the only thing that helps me. I breathe better
    I have more energy. And as far as I know it is a powerful
  15. jag2594

    jag2594 Member

    Ray Peat doesn't give much way to the genetic determinism in todays medical culture. He believes in a lamarckian ideology. What were you symptoms before finding out of the gene mutation.
  16. BingDing

    BingDing Member

    A minor note to this thread but I found an activated Folate supplement made by "Doctor's Best", available at The Vitamin Shoppe. The added ingredients seem OK, one can open up the capsule if desired.

    I decided against the activated B complex Wilfrid posted because of the 50 mg of B6. Too much B6 can cause vivid dreams, not something I need more of. Charlie started a thread about it here

    Otherwise I'm doing good with niacinimide, B1, and methyl B12, still need to get the activated form of B6 and B2.

    And IMHO, this forum does RP fair well by mentioning practitioners who can spot fads and BS in the medical/pharmaceutical industrial complex. Nice!
  17. BaconBits

    BaconBits Member

    How many people have this genetic mutation? Has anybody seen the studies?
    The prevalence of at least one defective gene for making choline from methione was in american studies like 80% and thats huge. Now choline and methionine is the beggining of the methylation cycle and folate and b-12 are near the end of this cycle.

    But the question arises, nowhere in our foods is there any folic acid or cyanocobalamin. The enzymes for metabolising folic acid seem to only have the capacity for 200mcg at a single dose, thats mean that if you dont split in that doses you are not getting the maximum benefit. Also the way body detoxifies cyanide is by bounding it to methyl or adenosyl b-12 and making its own cyanocbalamin that you pee out??

    But the body seems to have a plan B always. Betain can spare folate and B-12.
  18. BingDing

    BingDing Member

    BaconBits, are you saying that folate should be taken more than once a day? I have been taking B complex 3-4 times a day since they are water soluble, is that good?

    Chris Masterjohn has a series of articles about choline, link. He thinks that it is likely the recommended 550 mg/day for men is low. Looking at my diet I am getting nowhere near that.

    After reading more about it, it appears betaine and choline can lower homocysteine, C reactive protein, and TNF alpha, all of which would be good things, I think.

    I've recently added 500 mg betaine anhydrous and 250 mg choline bitartrate to my B vitamin mix and seem to get a very good response as far as energy and mood improvement. For example, this week I handled a cycle of action much as when I was younger- that is, I can start a task, work on it, and finish it, as opposed to leaving it half done for weeks or never even starting it.

    Does keeping methionine intake down and supplementing betaine and choline along with the B vitamins make sense?

    All I've found in RP's writing is about over methylation of DNA and I didn't understand it.

  19. BaconBits

    BaconBits Member

    Yea, I read the Chris Mastrjohn articles. Thing is, that this methylation is extremely complicated. Did you read about the animal studies where the animals were feed a diet deficient in copper but more than enough choline and other nutrients but they got fatty liver. When copper was given everything normalized. Also estrogen was protective even when choline and methionine were deficient in women. You cannot use a reductionistic or linear logic to understand it, at least it seems.
    It would be interesting how progesterone or pregnenolone or T3 or T3 affect this?

    Betain is somehow universal because can spare all the elements in methylation cycle, from methione, choline, to folate and B-12. Betain is trymethylglycine which is kind of methylated glycine? Body can also make pangamic acid or vitamin b15 out of it.

    I would be happy to find some more articles on methylaton if you know of any.
  20. Jib

    Jib Member

    L-methylfolate and other activated B-vitamins probably have specific actions in the body regardless of the presence of genetic mutations or not. It would probably be helpful to study them outside the context of the genetic mutation, although the genetic mutation is what's garnered methylfolate and other activated B-vitamins so much attention lately.

    My symptoms before knowing about the genetic mutation were about 10 years of chronic anxiety, major depression, suicidal ideation, mood swings, insomnia and digestive problems (constipation, diarrhea, acid reflux, difficulty swallowing, poor appetite). They've persisted after I started taking L-methylfolate, but I did notice that in about a week of taking 7.5mg of it a day the symptoms weren't nearly as bad as they used to be.

    Probably the most notable thing I experienced was the reduction in outbursts of anger. I used to have outbursts pretty frequently but since I started the L-methylfolate the incidents of that have dropped significantly.

    It's hard to know how much I can attribute to the L-methylfolate, but I notice that when I've forgotten to take it for a week or two I tend to get extremely depressed and suicidal and feel a lot more irritable. Part of that could be that it throws me off just enough to make me stop taking care of myself, e.g., eating plenty of calories from sugar and saturated fat, getting enough protein, eating throughout the day and getting enough sleep, and then the cumulative effect of neglecting those things leads me into a downward spiral.

    The therapeutic effect of L-methylfolate, mutation or not, is interesting to me, and I wonder how well it could fit into the context of energy production in the body, right alongside other B-vitamins like P-5-P and niacinamide.
  21. Peata

    Peata Member

    I don't know if I have the mutation, or whether I have pyroluria for certain (I have *many* of the symptoms) but I do know since taking the B vitamins I'm almost a different person as far as much more steady moods, less anger and flying off the handle.. things that used to bother me just aren't that big of a deal anymore, less anxiety and depression, more motivation. I take B1, B3, B6 + P5P and most days I take half of another B spectrum supplement. Also zinc, magnesium and others.

    When I went off them for a week or two I saw an increase in the old symptoms, which again started to subside after a week or two back on the supps.

    Off and on over the years I've taken a B complex and/or multi and still hadn't noticed anything from it like I do now from taking these individual supps. Maybe the Peat foods help my body use them better, I don't know. Anyway, that's just my experience.
  22. BingDing

    BingDing Member

    My lab work says I have two C677T mutations. I think RP wrote something like "it's a minor inconvenience that can be addressed with nutrients". I'm not gonna worry about it much; how my new doctor approaches it will tell me a lot about whether he's worth keeping.

    I found this page with some studies about niacin/niacinimide and methyl donors. One person on the thread concluded that niacinimide does reduce methyl donors.

    I was using 500mg of niacinimide/day for quite a while, and my lab work also said my serum homocysteine was high. I suspect they are related, I have to read everything again (or six more times) and I might be able to figure it out.
  23. Mastemah

    Mastemah Member

    An easy way to understand the MTHFR thing is this: all of the things that people are sold expensive version of are things people would benefit from anyway and are commonly low in the modern diet. When people say that have this or that gene issue, its because someone with a vested interest in that outcome has been sold the idea that we know a lot of about genes. Sequencing the genes doesnt mean we understand them. You can know the names of all of the notes, that doesnt mean you can write songs. Dont worry :)
  24. Blossom

    Blossom Moderator

    There is a Peat quote in the ' need to try dairy-free peat???' thread from his January 2014 newsletter that is perfectly in line with mastemah's reply. Peat mentions that people who lack this gene seem to have a reduced rate of cancer. Most people eating common foods on a Peat inspired approach will get plenty of the b vitamins. My personal takeaway is to not mess with methylation. I did take deplin myself many years ago along with fancy methyl b's and now I regret it.
  25. BingDing

    BingDing Member

    Thanks Mastemah and Blossom. One thing I saw on blogs was how little people understand the chemistry of the body, making them so vulnerable to panic and snake oil salesmen.

    I have a pretty good handle on this now so I want to share it. This page has several diagrams and he writes in a style that I can understand.

    The whole point of it all is to produce S−Adenosyl Methionine (SAMe), which is the main methyl donor in the body and is used in lots of important pathways. Norepinephrine -> epinephrine uses SAMe, for example.

    Methionine is the rate limiting substrate in the production of SAMe. The only other factor is ATP and if you're running low on that you have much bigger problems than this.

    When SAMe gives up its methyl group to some other compound it becomes SAH and when an adenosine molecule is taken off the H is homocysteine. If that was the end of it the only way to make more SAMe would be to eat more methionine.

    So there are two parallel pathways from homocysteine -> methionine, both of which simply add a methyl group to homocysteine. One uses methylfolate and the other uses betaine (trimethyl glycine). It is easy to speculate that having two ways of doing the same thing shows how important it is to produce more methionine without having to eat it.

    The enzyme the 677 gene codes for just changes one form of methylfolate to another form of methylfolate, 5,10 MTHF -> 5 MTHF.

    This page has a bunch of info about names and isomers, and says about 70% of the folate in food is in the final usable form, so the enzyme isn't needed at all.

    There are other odds and ends but I'll quit. There is a lot of chatter about high homocysteine and CVD, etc but it seems to me the important issue is low SAMe if the methylation cycle is sub par for any reason.

    Edit: my statement that methionine is the rate limiting substrate in the production of SAMe was incomplete. There is an enzyme involved in addition to ATP, which may be rate limiting.
  26. Poppyseed13

    Poppyseed13 Member


    I am heterozygous for MTHFR C677T and MTHFR A1298C (among other snps). I used 23andme to obtain the raw data and GeneticGenie to filter it in a recognizable/readable format.

    I took these tests after a year and a half of Peating, and although I made great improvements with the diet changes and Thiroyd supplementation, I was still feeling tired ---and I felt there was more to the picture.

    In response to the test results I began supplementing with Methylb12--and had a fantastic surge in energy---I had been taking cyanocobalamin for years in a B-complex. I slowly added each b-vitamin in tiny amounts---and when I started taking the Methylfolate, I had serious headaches, nauseau---I quit for 8 months, and continued with the rest of the bs. Recently, I tried Methylfolate again --microdose/sliver of a tablet---and felt quite wonderful
  27. Poppyseed13

    Poppyseed13 Member

    oops! The Methylfolate gave me more energy --but I think it is critical to have enough b12 in your system when taking methylfolate. I also use niacinamide to help with the minor side-effects (it's supposed to "mop up" the extra methyl groups). It does make the methylfolate-induced headaches go away. And in the last week, I haven't needed any extra niacinamide.... my body seems to be getting used to the methylfolate.

    I will gradually increase the methylfolate to about 400 mcg and see how it sits.

    I don't think the science is definitive about these SNPs and how they affect us. It's in its infancy, and the studies are not clear....

    I will continue to take all the active bs---they clearly help me---more energy, clear thinking, feeling good about life.

    I feel sad that most doctors dismiss much of what we discuss here at RPF --they are not terribly interested in helping patients be optimally healthy---nor do they like patients who want to experiment on themselves. But it doesn't matter, I will continue to take leaps and risks--

  28. BingDing

    BingDing Member

    Nice posts, poppyseed. I know what you mean about feeling there is more to the picture. I am going on two years with this and I've never been stable, or feeling the same day after day. Magnesium, pregnenalone and adequate protein were big boosts for me and I'm better off for it. But I still struggle, I feel like I've been swimming upstream forever.

    I started using betaine anhydrous at first and immediately felt stronger and better. I had good b12 after all that milk but got some more methylb12 and that was good. Methylfolate gave me tinnitus problems so I started using small amounts, too, so far so good.

    Using 2g/day of creatine monohydrate was a huge boost, I am so glad I figured that out. It is critically important for normal muscle function and supplementing it spares SAMe for more important uses like making Co-Q10 and lipoic acid in the mitochondria.

    My biggest takeaway from this, though, is how great it is to have Ray Peat in my corner. And having the people on this forum in my corner! Working through all the steps to understand Ray's research and conclusions has given me a great deal of confidence in what I am doing to get healthy.

    Getting a handle on the methylation cycle and the minor effects of the MTHFR mutation in a few weeks and without much angst has actually been very rewarding.

Share This Page