Did anyone have side effects with methyl? Which form do you use?

I understand that methylcobalamin is absolutely life-giving to many. However, some people do have severe adverse effects and I hope to discuss that here. Hopefully we can avoid getting unnecessarily worse!

I was originally given very high daily doses of methylfolate (1000mcg) and methylcobalamin (5000mcg) sublingual for 4 months and had a number of severe reactions both physical and psychiatric that landed me in the ER.

I didn't understand the effects at the time, and I'm not sure why I responded this way. I suspect it has something to do with genetics. I am not sure if I will ever tolerate the methyl form.

I stopped due to the adverse effects and immediately developed the clear neurological signs of B12 deficiency, even worse than before.

My Dr gives me cyanocobalamin now, but that helps very little with my neuropathy and quickly wears off. I supplemented 1000mcg methyl once every other week for three weeks, and the neuropathy has responded considerably. However, even that small amount of methyl is excruciating- palpitations, diarrhea, cystic acne, burning skin, severe anxiety. They last for weeks after the dose.

As a commenter said on another forum, "I feel like my brain is being microwaved!" The psychiatric side effects rival that of B12 deficiency, so it's quite a pickle to be in.

As MTHFR treatments become more popular, I'm reading more stories like mine. Often the side effects were not expected. Clearly, methylcobalamin is not without side effects for some people.

If you had adverse reactions to methyl, did they go away? Did you acclimate? Do you tolerate other forms? Do they help with neuropathy?

I'm not trying to discourage anyone from taking methylcobalamin since I know it helps so many, just trying to get the side effects on the radar:)

48 Replies

  • You would probably do better with Hydroxy.

  • I tried that for a while too, but it was so close to the methyl I can't be sure of the side effects.

  • I take methyl and folate no problem...... And yes genetics play a big part especially MTHFR. Have you done the 23 and me ?

  • I was looking at the 23 and me website yesterday and it looks as though they no longer test for MTHFR. I may be mistaken but don't assume and order without checking.

  • 23 and me don't provide the MTHFR analysis directly but once you have the 23 and me results you go to the geneticgenie.org website and carry out a Methylation Analysis using the raw data that 23 and me provide. This then shows if you have the mutations for the MTHFR gene.

    I did this a few weeks ago and it works well. It confirmed that I have the double mutation for MTHFR C677T. So I am now supplementing with methyl folate. No noticeable side effects so far.

  • Do you mind if I ask your dosage and the duration?

  • I am taking Pure Encapsulations B-Complex Plus which has 400mcg Methylfolate and 400 mcg Methylcobalamin in each capsule. They seem pretty good. I find them easy to swallow. I have been taking one a day for a month now and I am not getting any side effects so far.

  • If you've had your autosomal DNA tested with a different company (like FTDNA - they call it Family Finder) then you can use this utility - y-str.org/2013/06/autosomal... - to convert. You do need to know how to run a Command Line application in Windows.

  • Yes I did. I am homozygous A1298C they said, plus some MTRR, MTR and CBS off the top of my head. I hear a lot of good things about methyl vitamins from MTHFR C677C people, but I don't have that.

  • Just some thoughts...

    Have you tried smaller doses, perhaps more often? Purchase it with less strength, or get a pill cutter and divide the sublinguals you are taking now.

    Are you sure it's the methylB12 and not an additive you are sensitive to? Have you tried changing brands?

  • I've tried three different brands, the lowest dose 500 mcg. I didn't feel any benefit, but I still had side effects. I'm scared to try it again, even a crumb.

  • I've just been reading that it's the dibencozide (otherwise known as cobamamide or adenosylcobalamin) form of B12 that repairs the myelin sheath around your nerves and that the methyl form is not effective for nerve damage. The link was on this site a couple of days ago. It looks as though a combination of the two is most useful. I've just ordered some from Amazon and will post how I get on.

  • Do you happen to have the link, oozlumbird, I can't seem to find it? Thanks.

  • Oozlumbird - can you post the type of complex you found on amazon?

  • Hi Renee. Yes, it's Country Life Active B12 Dibencozide, 3000mcg. Good luck! It's sublingual and gluten-free.

  • ...dibencozide being another name for adenosylcobalamin (slightly easier to say!)

  • Hi Frodo. here it is:


  • Thanks for this.. I am taking alpha lipoic acid, maybe that's helping a bit.

    Just can't understand what my doctor was thinking going right to 5000 mcg daily for months. A bit overkill in my case.

  • You don't smoke, no? (Just read the study on the link.) On the glass half full side - this is a useful clue. You may have a rare genetic reaction. I and my son have taken loads of methylc - no bad reaction, as you say, an improvement for him, maybe for me too, but it is true it has not cured my pins and needles parasthesias or my repetitive strain injuries. So there is hope here that adenosylcobalimin might help. I will post or add here if it does.

    Thank you v much for posting.

  • No, no smoking.

    My neuropathy improved dramatically last week. I don't know what to attribute it to. It improved suddenly right after a single dose 1000 mcg methylcobalamin. However I am on daily alpha lipoic acid, 10 day cyanocobalamin shots, and glumetza for blood sugar. So it could be any of those but it has improved more than I thought possible. I suspect it's the methylcobalamin plus ala, because each one of these things alone didn't give huge improvement. Or it could just be the passage of time.

  • Thank you so much for this oozlumbird. The quality of the discussion on the PA and hypo forums never fails to astound me. This is one more crucial insight.

  • PS - would you mind saying what the psychiatric effects were - I know this is intrusive so I understand if you do mind. But it is just in case there is a parallel with my son, who is talking very determindly about suicide at present.

  • If the question is for me- I don't mind at all, quite the opposite. I get hesitant to explain them in full because I'm not sure of the response.

    Naturally I have tended toward high anxiety, panic attacks, ptsd, and body dysmorphia since early childhood. I did not do well with drugs, they only made things worse! I have a number of health concerns that could affect mood and were only just diagnosed: celiac, hypothyroidism, prediabetes, vitamin and mineral deficiencies.

    As I became lower in B12 in the years prior to supplementation, my behavior changed. I got uncontrollable mood swings: crying like the world was going to end, or being very short tempered and yelling at my family. I had NOT been short tempered before.

    With the methylfolate and methylcobalamin, the first thing I noticed were nighttime panic attacks that felt different- very dark and harrowing and heavy. It was a very strange feeling, very dreadful. I would be getting ready for bed and all of a sudden want to die. Because I had been prone to nighttime panic, I brushed this off.

    On the methyls I became very agitated. My skin burned and I felt like my brain was on fire. I actually started tearing at my arms and hitting my head in distress. I'd feel violent rages come over me at a moment's notice for no reason at all. Or else I'd switch to horrible dread and hide in my room, pressed up against the wall, eyes wide. In the hours after a dose, my whole body would ache terribly and my brain would be so foggy I couldn't even read email or formulate an answer to a question.

    After a month or two I started getting paranoid. As I walked around my house my mind would play tricks on me and I'd imagine packs of demons around every corner. Not hallucinations exactly, but like the jumpiness you get after a scary movie, only worse and more vivid.

    I was a skeptic, but I became obsessed with conspiracy theories and morbid things. I lost my logic and critical thinking skills. I became paranoid about my family members. I couldn't feel love, affection, or connectedness.

    At my worst I had only a few moods: panic, violent rage, paranoia, suicidality.

    The agitation lasted long after stopping the supplements. I eventually went into a psych ward for a week.

    My doctor had told me they had no side effects and would make me feel great. I had struggled so long with chronic pain and I was desperate to get better. I did have a history of anxiety, plus the recent b12 behavior changes. That's why we didn't pick up on the side effects sooner.

    I'm sorry if this is tmi. I'm probably one of the worse cases, due to the duration of supplementation. I'm sure not everyone gets this bad. Stopping earlier would've been easier on me no doubt.

    I am a naturally gentle, intelligent person. These supplements made me feel like I had someone else's brain.

    I was also on .5 mg paxil at the time.

    I have been looking into cbs mutations and overmethylation which I suspect might have contributed to this, but that's a bit of a rabbit hole with all sorts of dubious information.

    Even if your son is prone to mood disturbances, he could be reacting to the methyls. Other signs to look for would be sudden temper, headaches, racing heart, agitation or electric sensation in head, shoulders, arms, cystic acne, inability to deal with stimulation or information.

    I hope this helps!

  • Thank you so, so much for that. Not too much info at all, very valuable, very moving, very informative. I will read it through again carefully and try to absorb it - there is so much here, and there are a lot of things going on with you. On the glass half full side, it is clear that many moods and even hallucinations can be caused by nutrient deprivation or a lack of balance of nutrients, and that these are curable and transient so long as - this is a big "so long as" one can track the causes down. Your early panic attacks and anxiety might have been due to low iron due to your celiac disease. Thank heaven you found that diagnosis.

    B12 deficiency is closely linked to some of the reactions you note - as you know, and your doctor recognised. There is a case I recently posted, quite well known, you probably have read it, of a young man with extreme mental disturbance including hallucinations, remedied by B12. Hmm, so if adensylcobalamin helps parasthesia according to the Indian study, I wonder if there could be some unresearched pyschiatric effects too? I will order some.

    In your case the methylc caused a swing, the top of the u shaped curve effect I expect. How recently were you diagnosed? If your celiac was v recently diagnosed, you will probably be lacking in so many nutrients that it will be easy to disturb the balance by over-supplying one, I would guess. All the fat soluble vitamins, a lot of minerals....

    you are at the cutting edge. No. You are the cutting edge.

    My son also has had hallucinations (much more minor - on falling asleep, but seeing machines with eyes) and hallucinations linked to panic attacks, so he will walk down the stairs naked and trembling, feeling there is someone behind him waiting to attack. As with you, it is not th essence of him, it is a physical problem presenting as psychiatric disturbance.

    Thank you so much, your willingness to explain may help me help him.

  • I'm so sorry. Allyson that you've had such a nightmare time with this deficiency but thank so much for explaining what you've been through.

    My sister with severe B12 deficiency had many of these symptoms last year and her surgery initially refused to recognise B12 def., instead misdiagnosed dementia and prescribed a psychiatric drug, which had no effect and turned her into a zombie. She made an amazing recovery after we eventually managed to get her monthly Hydroxocobalamin injections, as well as supplementing with Jarrows Methylcobalamin 5000 mcg, SL between injections, which seemed to help symptoms like sore tongue, etc.

    Some of these symptoms have just returned and the surgery, again, are wanting to prescribe the same drug and are refusing to bring her next injection forward, insisting that her blood tests show she has sufficient! I wanted to punch her in the face when she implied with a smirk that my sister was faking the shaking, confusion and inability to walk!!!

    Surgery refuses to believe that these symptoms are severe B12 deficiency, even when shown all the research. My sister is, like you, a kind, gentle, practical and sensible person. I really despair and don't know what the answer is when faced with such ignorance and condescending obstruction.

  • I think you may have crossed wires somewhere..... Methyl is best for nerve repair. Adeno is used in the mitochondria to help make ATP - energy.

  • The source from oozlumbird above seems to say the opposite: nature.com/ejcn/journal/v69...

    Do you have a source? Is the jury still out on this?

  • This is from Dr C's page B12d. I read the article you posted there. They are also saying that tablets work just as well as injections. That contradicts other information I have read too. However it does recommend to use methyl and adeno, and that is something I do anyway..... To make sure I repair the nerves, and feed the mitochondria.

  • I would also say people do find they respond differently to certain forms, so regardless of what you find suggested, I would always ' suck it and see :) '

  • Very true! I think that's the most important take away when treating B12 def. I think if patients are aware of these gray areas from the beginning, they can better fight for the care that works for them!

  • Methylfolate makes all of my joints very painful within a day of taking just one tablet and several days to wear off, and methylb12 injections make me feel as though I've been poisoned and have a brain virus, and feel very mentally low. I noticed the effects almost straight away, tried them separately a few more times with several weeks rest in between trials and it was definitely the methylfolate and methylb12. I seem to be doing fine on sublingual methyfolate and hydroxo B12 injections.

    I hope you find something that helps resolve your problems, what you've been through sounds very traumatic indeed.

  • Thank you! My physical symptoms were so similar. There is a strain of naturopathy in the US who call this detox and seek it out, I hadn't realized my doctor was following them. They tend to have commercial interests in methylated supplements specifically. They tell you the methylated forms are natural and the best bioavailable forms, all else is synthetic poison. Then if you get sick, they sell you more supplements to "open blocked pathways". She led me to believe the vitamins were from a food source and had no side effects! I cannot find evidence that it is detox, nor can I find success stories for people who react this way.

    I think it was the length of time and severity that made it so traumatic - 4 months usage of very high doses was crippling and relentless and very hard to recover from. Had I known to stop earlier before things got seriously out of hand, I would have returned to normal I believe.

    I tried 1000 mcg spray to supplement my cyano shots, and a week later I'm still breaking out, having infections in mucous membranes, gastrointestinal distress, mood problems, and that brain virus feeling. Methyl b12 is definitely not for me!

    Thanks for sharing.

  • I'm so sorry for what you're going through,I only need to get a cold-sore and become a weakling wreck!

    I've been trying to get to the bottom of it because I worry about my folate levels but because of longstanding untreated pernicious anaemia, I start getting information overload and become so confused.

    I wonder if any of the more scientifically minded members can make any sense of it.... I just came across the following article and wonder if it might be relevant but however hard I try, I can't translate it into layman's terms :(


  • Yes, I get information overload very easily too on this topic. Not only is a lot of it highly technical, but you have to wade through a fair bit of marketing too.

    Methylation has become such a focus of natural health circles, and I think a lot of unqualified practitioners are jumping the gun, and there are forums full of people experimenting and getting sicker. I really suspect my neurological problems got worse while on the methylfolate/methylcobalamin. I know my psychiatric state was unlike anything I've ever experienced before.

    I don't really have a grasp on the article either but I can tell you that I was low in methionine and several other amino acids, and my doctor was flooding my body with methylfolate that built up to astronomical blood levels.

    I'd love to have someone explain it in layman's terms, but when I look for that I just find lots of naturopaths trying to sell products.

    It seems to me that perhaps no one really has the answers yet at this point, and so I'm just trying to focus on correcting deficiencies in a moderate way, focusing on both lab results and symptoms. I don't know why methylfolate and methylcobalamin unbalanced me. In the meantime all I can do is supplement with tolerable forms. Hydroxocobalamin is pretty good so far.

    Is there a reason you must take the methylated forms over others? If your folate is low do you respond to folic acid or dietary intake?

    Thanks for the article, I have not seen that one before.

  • Allyson1, is your B12 level elevated? Mine is though it's always been tested within a few days of getting B12 by injection or sublingually so I don't know how accurate it really is.

    I found this article about elevated B12. Not all that much good news here, says long-term injection of B12 can lead to anti-TCB II autoantibodies, or is a symptom of other issues (gastric neoplasm, carcinoma, blood diseases, liver or kidney problems).


  • Thanks tracy, this is interesting...Mine wasn't elevated prior to supplementation, it was in the 400s or so, but I was already developing neurological and psychiatric changes.

    I think this part is interesting from page 508, if I'm reading it correctly:

    "Meanwhile, the lack of reliability of the homocysteine concentration as a metabolic indicator of a reduced conversion towards methionine has been shown in situations with oxidative stress. 52 It is thus no surprise that in patients with diabetes, a disease known to cause oxidative stress, clinical response of neuropathy was noted at cobalamin levels above 400pg/ml (as

    seen above, double the accepted lower limit of normal). 53"

    My homocysteine was never elevated, and my methionine was low. My B12 was in the 400s. I was extremely thirsty and had excessive urination, swelling, sugar cravings, and fatigue. And I was going numb from B12 deficiency.

  • It wasn't exactly clear to me from the article, but it did seem to imply that high serum B12 levels due to oversupplementation are not necessarily safe, particularly for those with liver or kidney problems?

  • I don't know about my homocysteine level as it and MMA were measured 2 weeks after I started B12 loading doses. From what I've read they will drop quickly once B12 levels are back up. I've never had methionine measured.

    My B12 was 196 by the time it was measured and like you, I was extremely thirsty and had excessive urination (7 - 10 times during the night, and nearly that often during the day). I thought it might be diabetes but tested negative. B12 deficiency caused shooting pains in my legs and back, I would have preferred numb over that.

    I almost always have a below normal glomular filtration rate (GFR) that can indicate kidney disease but curiously my doctor has never considered it a problem, was told I was probably dehydrated.

  • Are you still having the excessive thirst and urination? Maybe it wouldn't hurt to get a second opinion or a closer look? My fasting blood sugar was always normal, but a two-hour glucose challenge was not. It's torture, isn't it, waking up every hour.

  • Allyson1, thankfully I'm now beyond the constant thirst and urination, that was when I was very deficient and didn't yet know the reason. Definitely was torture when it was going on. Only thing worse was what happened before that, where I would lie awake in a catatonic state until 2am, sleep until 3am, then lie awake until the cycle repeated. One hour of sleep a night is awful.

    Interesting your fasting glucose was normal but glucose challenge wasn't. I never could convince my doctor to do that test on me. I knew something was wild with my blood sugar levels so bought a glucose meter. Monitored it for a couple weeks and it was all over the map. Some mornings before breakfast it would be high. Then it would be okay for a few days. Crazy. That was in my early days of B12 treatment, things have settled down considerably since then. Perhaps going gluten-free has helped? I'm too scared to try eating it again after my horrible experiences leading up to my B12D diagnosis and changing my diet.

  • There is one genetic combination that can lead to a very low level of diabetes - I think it is sub-type 3 within MODY. Many people with the gene don't actually present with diabetes or generally identifiable problems with their blood sugar levels. If you have a history in your family of the same (it's a dominant gene and its one that isn't triggered by environment) - ie problems with blood sugar but no actual diabetes - and may be a few that did have diabetes - it may be worth trying to get tested for the gene.


  • The article - if it is the one I'm thinking of - is arguing that doctors should investigate where B12 levels are high as well as when they are low.

    High B12 can be an early indicator of liver and kidney problems and if the person concerned has the auto-immune response to high B12 in serum then that means they start to show all the symptoms of B12 deficiency through becoming functionally deficient.

    High B12 doesn't cause the liver and kidney problems.

    The article also suggest that even for people where the most likely cause of elevated levels is being on a replacement therapy - the assumption shouldn't necessarily be that B12 is the only thing that is going on and causing the high readings ...

    Know I had to read the article several times before I really got all of that.

  • Interesting - do you have a link to that article?

    All that I do know is that for the time period 2 - 24 hours after I get a B12 shot, I feel just horrible. Tremors and shaking, inside my chest just to the left of my sternum. I am able to sleep, thankfully. The day after that is a pretty good day for me. Then I gradually start going downhill again until I bite the bullet and get more B12. This has been happening since late last Nov but each time my deficiency symptoms between shots intensify.

    To appease my doctor I tried going a month between shots, still had to supplement on the side with sublinguals and I had two weeks of horrendous tachycardia until my shot last Wed afternoon. As expected, I felt horrible all day Thurs. I've been careful to get lots of potassium in my diet -- several bananas every day and lots of coconut water. I've tried taking extra folic acid (think it caused some acne spots) and some iron. My doctor won't run any more tests for a while, so I don't know if there is something I'm in need of or just overmethylating due to too much B12 or ?? I guess if it gets really bad next time I'll just go to the ER and let them try to figure it out, hoping they don't just say I'm having a panic attack which is what happened when I landed there before my B12 deficiency was diagnosed.

    Wish I knew what was going on with me.

  • The article I referred to was the one you quoted above


    There is also this abstract on functional B12 deficiency and treating patients who have that response


    sorry about the 'tachycardia' - have you tried using a monitor to check that it really is that ...

    not an expert but that sounds more like a potassium problem to me than B12 ... but to emphasis I am not an expert.

  • On the tachycardia - I have a blood pressure cuff that also measures heart rate. I could see that my heart rate was gradually increasing over time. I'd measure it before getting out of bed in the morning, and during the day when I felt relaxed. On the day of my B12 shot last week my HR was usually over 110 and reached over 130 at times. My blood pressure was never excessive, only my heart rate.

    After a B12 shot the tachycardia eased up. For the following day I have an awful vibration in my chest and general malaise that goes along with it so I spend the day in bed. The day after that, I feel more like my usual self and am up and about. In the days that follow, I start declining again.

    I eat lots of bananas, jacket potatoes, and avocados, and drink lots of coconut water and a little orange juice every day so I'm pretty sure I'm getting lots of potassium.

    I've taken some iron (am careful not to take lots, I take 28mg once a week), have tried taking 2000 - 3000 mcg folic acid daily around my shot (though my folate always high). This has never made a difference in the vibration. I used to also take alpha lipoic acid but I never detected a difference so I stopped taking it.

  • The tachycardia sounds concerning, particularly since you notice such a correlation with B12 supplementation. I had terrible palpitations the first few months of supplementing methylfolate and methylcobalamin. I was on waay too much B12 and folate. I also had some other health issues affecting thyroid and adrenals. As far as I know my BP has always been normal.

    Do you have tachycardia with just B12 or is it always B12 and folate together? Are the doses and frequency right for you? Is there a specialist who could look at this? Easier said than done, isn't it, but logically something is going on. It's so stressful when health problems feel like a mystery.

  • I've been reading up on this subject all week !

    A block or slow methylation can obviously

    allow toxins to build up & my thought on

    starting supplementation with Methyl at

    say 1000mcg, you will certainly stir things

    up ! You need to keep eye on Potasium

    & Gluthione levels, as both can become

    depleted. B Complex essential, especially

    B2 & B3. A good antioxidant complex.

    And one Forum suggests start slow &

    increase as can tolerate. Guess that's

    ok if your levels aren't too low ! Also

    Hydroxycobalamin & Methylfolate &

    easier combination initially. It's hard

    to find supps without sweeteners, flavours,

    additives, for those of us that are sensitive

    to these - Metabolics do a pure water &

    the Methyl only. Also read, but can't find

    now that advised to take Methyl 12 / Folate

    (either or both) away from....... can't

    remember what ! Does anyone know ?

    There seems to be so much on this subject

    - you need a degree to understand some

    of it !

  • Sorry I don't think I was clear. My tachycardia got really bad because I was greatly in need of B12. I also had orthostatic issues, like POTS though I've never been diagnosed. On the day of my shot (before I actually got it), my heart rate was as high as 131. After the shot it got much better, though I had one day of feeling awful afterwards.

    My shot was last Wed and it is now Monday. Last night I could feel my B12D symptoms creeping back and used a small amount of methylB12 spray in my mouth, and a small amount again this morning. After a shot I get a feeling of vibrations or pulsations in my chest and stomach. Today I felt some of those vibrations but not nearly so bad, perhaps due to a lower dose than the 1000 mcg jolt from a shot.

    In a couple of weeks I'm seeing a doctor on the "good doctors" list maintained by the facebook PA group. Unfortunately I'm not insured within that medical group so it's one time consultation. But I'll take what I can get.

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