*Updated March 10, 2016*

After two and a half months on MTHFR supplements I was feeling pretty good. My homocysteine was (and hopefully still is) down and the fatigue I was feeling at the start of treatment was starting to ease. I had my second appointment with my doctor where we looked over my lab results and she ordered a few more tests. One of the things that came up was that my methylmalonic acid (MMA) was elevated. When you’re testing for B12 levels, this is the blood test you want because it shows whether you have a functional deficiency. If we went by my serum B12 levels, they would show no absolute deficiency – but this tells me nothing about what is in the cells. Just because a person has a high level of B12 floating around in her bloodstream does not mean that it’s being absorbed at the cellular level. In a similar way, folate levels are difficult to assess. High serum folate doesn’t show whether you have folic acid or methylfolate in your bloodstream, and it doesn’t tell you whether you have a functional deficiency. At least that was my experience.

methylcobalamin shot

So my doctor sent me home with two prescriptions, one for methylcobalamin (B12) injections and one for Deplin 7.5 milligram (mg) tablets. Off I went to the compounding pharmacy, learning that Deplin costs $500 if the insurance won’t cover it (ours does not cover vitamins). That wasn’t happening. I also sincerely do not believe that I need that much methylfolate. I’ll be speaking to my doctor about this at my next visit, but going from one mg of methylfolate to seven and a half just seemed like a huge jump. Especially as I’ve had symptoms of overmethylation when I took much more than that. Of course, this was before the B12 shots, but I will get to that in a moment. I have since learned that it’s possible to buy the Deplin online at a discount through Brand Direct – so if you need it and insurance won’t pay, consider looking there. **Update** It’s important to know which type of B12 to take – as it turns out, methylcobalamin wasn’t the best form for me. Check out this post about what forms of B12 are out there and how to figure out which one is right for you.

I was so afraid of my B12 shot that I put it off for almost a week. Would my heart race? Would I overmethylate? Would I feel like utter crap the first day? My husband was also procrastinating because he was not too thrilled about having to give me the shot. As it turns out, he’s an excellent nurse. He watched some videos and read some online articles and by the day it was time to do it, both of our nerves were relatively calm. We used a Safetec Insect Sting Relief wipe, giving a nice dose of both alcohol and lidocaine to the injection site (Dr. Neubrander recommends the buttocks). I barely felt a stick and then it was over. Great job, hubby!

I have committed to sharing all my mistakes here on this blog because hey, maybe someone else can learn from them. The lesson here is to double check your dosage before leaving the pharmacy. Make sure you are clear about how much methylcobalamin is in the vial and how often the shot is to be administered. I ended up with a month’s worth of B12 over the course of a week, taken in two separate injections. The pharmacist told me the prescription was weekly so I assumed that meant the entire vial was for one week. They also gave me an odd number of syringes, adding to my misunderstanding. Luckily, I had no adverse side effects. Yes, I know, I could have double checked with the doctor’s office but I’m a busy person and thought I knew what I was doing. It all turned out well and further investigation revealed that the amounts I took were not ridiculously high. But, you know, don’t try this at home.

A few hours after the first injection I did feel some very slight symptoms of overmethylation. I was a little edgy and felt very awake and alert. But after that I transitioned to a calm, clear energy, which lasted for the next few days. By the fourth day I felt more like the pre-shot Andrea. After the second injection I had none of the jitters, just the calm clear energy. The third shot at the normal dosage produced the same results. Needless to say I’ve been very happy with the effects of the methylcobalamin shot and will continue to take them until my prescription runs out.

There was still the matter of the suggested increase in methylfolate. From talking to other people with MTHFR I have learned that dosages of methylfolate change. I have also learned that ideally (everyone is different, consult your healthcare practitioner) one wants to be taking more B12 than methylfolate. As I mentioned, prior to increasing my B12 I couldn’t tolerate more than maybe 1,000 mcg (1mg) of methylfolate. Now that I’m getting more B12 I can handle a lot more methylfolate and I have been taking quite a bit more with no side effects. As Dr. Ben Lynch discusses in his video on methylation and supplementation, everyone’s needs differ. My understanding is that the methylfolate needs methylcobalamin (B12) to form methionine out of homocysteine. Without it, the methylfolate can’t do its job and it simply returns to the blood, allowing homocysteine to build up. This is called a methyl trap.

Professional Supplement Center
Please refer to a site like MTHFR.net for more detailed information should this interest you (and really it should if you are dealing with these problems). And remember, getting a full picture of your genetics is very important. Many people have SNPs that don’t do well with methyl donors like the supplements I’m discussing here. If you react poorly to methylfolate or methylcobalamin, it can be because of all sorts of reasons. I do not advocate self-medicating on this site. Please do find a health practitioner to work with. The video linked above will explain all of this in more detail.

What are your experiences with methylcobalamin and methylfolate?

21 thoughts on “More B12, More Methylfolate

  1. Julie

    Hi Andrea. My new prenatal vitamin contain 800mcg methylfolate and 10mcg methylB12 (167% RDA of B12). I have seen some other prenatals (such as the one made by Dr. Ben Lynch) to have a much higher level of methylB12. Is it necessary to have such a high level of B12? I’m always wary of supplements that are way over 100% RDA; I believe Dr. Lynch’s is about 2000% RDA for B12). What are your thoughts on this? Do you think my prenatal is fine? I also try to eat a lot of organic Whole Foods and limit processed/fortified foods as much as possible. Thank you!


  2. Ryan

    Hey Andrea,

    Did you ever feel Flu symptoms starting the protocol? I started Methylcobalamin (1mg) and Adenosylcobalamin (1mg), along with some b6(p5p), b2, Potassium, and a multivitamin (Amy Yasko’s – All in One) about 3 days ago and have crazy flu symptoms in the afternoon (started methylfolate today at 250mg).

    I’m been pushing through at the moment – as I feel it might be because my body is final dealing with toxins that it hasnt been able process for years (I’m 30). However I’m starting to worry more about the state as it can be pretty intense.
    Any detox symptoms you experienced/know of?


  3. Robin

    I am taking a B-100 multivitamin with my methylfolate, (at 1.2mg per day or 1200mcg) The vitamin b12 on the bottle says cyancobalamin. Is this the wrong type of b12 to be taking? I see it also has folic acid in it. Is this not a good idea either? Do you take just b12 or any other b vitamins? I am taking this for depression. It is helping..I have not been tested for MTHFR but I likely have a mutation.


    1. Andrea Post author

      Yes, cyanocobalamin is the wrong form. Please see this article for more info on B12. It is good for many people to take all the B vitamins (all the active forms) but please consult a doctor for your specific situation.


  4. Deja Westerson

    I just found out about my MTHFR results, which are 1 mutation for C677T and 1 for A1298C. Still not totally sure what this means for me, other than I think it means I am heterozygous. Seeing Dr. tomorrow. I have had a bunch of crazy symptoms for 3 years, thought it was Lyme, MS, etc. and this MTHFR could be the actual cause, which is cool to finally know.
    Question: I went in for a spinal tap to see about MS 1 month ago and nearly passed out after 2 injections of Lidocaine. Is this an issue for people dealing with MTHFR mutations? I am reading about Nitrous Oxide being problematic, but nothing of Lidocaine. Also is Novocaine a problem?
    Thank you!


    1. Ally

      Deja- just curious if you ever got your symptoms figured out. I’m in the midst of trying to figure out if my symptoms are mthfr or lyme related myself. I’m hoping it’s only mthfr! Did you test for lyme?


  5. Jared

    Why are you even considering Deplin? or B12 Shots. To me that seems gross and abusive to your body. The pharmaceutical companies and your doctor are simply taking advantage of you. One, Deplin is stupid expensive and two it is completely unnecessary to purchase this through a pharmaceutical company when you can get the same exact and in my opinion superior stuff at whole foods or Vitamin Cottage. Superior because it doesn’t have all of the other unnecessary ingredients that Deplin has. And of course they don’t cover vitamins. Why would they? You can get all the vitamins you need for next to nothing out of your diet or at vitamin cottage. The only reason Deplin exists is because the pharmaceutical profit mongers realize that people are becoming wise to this MTHFR mutations and that once corrected many of their other MAOI’s and such are finally realized as completely useless to most. So they package up a standard every day vitamin and sell it for ridiculous amounts of money and it is being pushed by ignorant or profit only oriented doctors. Pharmaceutical companies have known about MTHFR for decades. They have kept it a secret and even dried debunking it in many cases. Truth is they have been putting folic acid and methyl folate in their antidepressants for years. Any wonder why Adrenal fatique and MTHFR deficiency isn’t even recognized as a real condition in Western medicine? If it was then people would know how to focus their efforts and big pharma would sell way less drugs. Remember these people want you sick so that you keep giving them your money.


    1. Andrea Post author

      I learned the same thing about Deplin and never took it. As for the B12 shots, I had better results with them than sublingual or other forms. I am aware of the medical establishment wanting to keep people sick, thank you.


      1. Kerbox

        Hi Andrea, as the other commenter pointed out you can get methylfolate very cheaply, 5-mthf is also a good option.

        On the issue with your b12 shots I just wanted to share the option of transdermal oil, a little company out of Australia (b12oils) has a range of b12 products you just rub into your skin, much easier than shots, very effective product as well and cheap, works out to about $1-1.50 a dose. I am 13 years chronic fatigue syndrome, only learnt early this year I am mthfr homozygous, to the obliviousness of several GP’s over the years, 6 months methylation supplements, using B12 daily now, slowly getting my life back.


        1. Alan

          Has anyone verified this companies products? Their website is totally lacking in anything that might indicate that the products they offer are real… nothing about manufacturing, or sourcing or product testing verification…zip. As far as I’d know, they could be selling cheap oil mixed with air. ??? Anyone? Anyone with any info on transdermal b12 effectiveness compared to sublingual?


  6. Kiki

    You can run your genetic tests using 23andme and them put the information into the engine at http://www.knowyourgenetics.com to receive your Methylation Pathway Analysis (MPA) report which will explain alot. You’ll need to look in 23andme at the raw data to find the info to put in the knowyourgenetics engine or run your 23andme data through another engine (dated) like geneticgenie.org to get an easy report to read. The MPA explains all of this stuff in over 50 pages. In it, there is a table about the recommended forms of B12 depending on primarily two genetic mutations CBS and VDR Taq. I am a no methyl person, and I could really tell the difference when I started supplementing with just hydroxy and Adenosyl B12 forms. My husband is a methyl person and does better with primarily with half Methylcobalamin and half all the other kinds. Helped him with cognitive problems, memory, energy and me with depression, energy, outlook.


  7. leeroy

    You may want to be careful with b12. Our bodies accumulate a great deal of mercury due to the environment. Many Universities have published articles on the ability of Vitamin B-12 to convert mercury vapor into the much more deadly “Methyl mercury”. Methyl mercury knows no barriers, and creates far more havoc than other mercury chemicals, because of its ability to travel anywhere in the body without inhibitions. Sometimes the effects of high doses of Vitamin B-12 (over 50 micrograms) take months to correct.


    1. Andrea Post author

      Hi Leeroy – thanks for sharing!
      Could you post the specific studies you are referring to? I have actually done some reading on this after noticing some chatter in an online group about it. Seems controversial. Here are some relevant links and discussions for those also exploring the subject:


      http://forums.phoenixrising.me/index.php?threads/new-test-for-b12.417/ (Rich’s comment and Fredd’s response)





      1. Mila

        Hi Andrea,

        I saw that you didn’t have issues with lidocaine. I have both mutations and am getting amalgams removed tomorrow. Any suggestions on what to avoid? This dentist offers articaine, lidocaine, metivicaine, marcaine or carbocaine. I’ve read to stay away from esters, but who knows? Thanks!


        1. Andrea Post author

          Sorry, deleted last comment – I didn’t realize the lidocaine was in the sting wipes – I wrote this awhile ago. Anyway, all I know re dentist is that we aren’t supposed to have nitrous oxide. You’ve had this procedure by now so hope you did figure out what is best.


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