A warning about SAMe, methylcobalamin, and high-dose B vitamins

After reading of some post-Accutane patients on acne.org and phoenix rising having improvements of (unspecified) symptoms by undertaking a methylation protocol according to 23andMe results, I decided it would be wise to attempt the same.

A terrible mistake.

In early August, I bought a bottle of 30 200mg SAMe tablets. I was taking these daily and didn’t notice much of an effect. In mid-August, I bought a bottle of 1,000mcg methylcobalamin (B12) tablets and started taking them daily with the SAMe.

Around the time I added the methylcobalamin, I began waking about half an hour early after being up late the night prior. Went from 7 hours of sleep per night to about 5 and didn’t feel fatigued during the day. This progressed to the point where I was getting 3-3.5 hours of sleep per night by early September, waking up at 2:30AM, feeling wide-awake as if it was 2:30PM.

I ran out of SAMe around Sept. 5th and stopped taking the mehtylcobalamin at the same time. Things crept up on me and continued to progressively get worse after stopping both supplements.

Mid-Sept to mid-Oct:

  • No more than 3-4 hours of constantly interrupted unconsciousness per night. Wouldn’t even consider it sleep.

  • Completely impotent, total (zero) absence of any libido or sexual thoughts, total genital numbness to the point where it was like a finger attached to my pelvis, as some of the worst affected PFS/PAS/PSSD patients describe,

  • Had dry mouth, yet was urinating 20-30 times per day,

  • Constant and intrusive rumination about the past throughout the day and night

  • No feeling of being tired or fatigued, but constantly wired

  • No hunger and lost 12 pounds over the course of 1 and 1/2 months

  • Felt that familiar feeling of derealization from the post-Accutane crash. Everything looked different and I experienced altered consciousness.

  • I began to make mistakes at work on a regular basis.

Can’t say how much of this was due to a lack of decent sleep, and how much was due to direct effects of the SAMe and methyl-B12, assuming they were the culprit.

This past week, I began to have a return to my usual miserable baseline, with only a couple bad days, and couldn’t be more relieved. Managed 8+ hours of sleep the past 4 nights and had slight morning wood yesterday when I woke up. Feeling tired, hungry, and back to my normal state of mind in the past couple days. Not completely back to myself yet, but couldn’t imagine being permanently stuck in the state I was in during the worst of this bad spell. The only time post-Accutane it has been this bad was after abruptly stopping 2 months of TRT and going on sertraline for a few months in 2003. It took 4-6 months to go back to near baseline after that mistake.

There are a few stories online of insomnia lasting up to 2 months from people taking SAMe and from people taking B12 injections and one discussion about insomnia, frequent urination, and anxiety stemming from the combination of SAMe and B12 specifically: https://www.researchgate.net/post/Can_too_much_vitamin_B12_cause_insomnia

Also searched for similar problems among PAS/PFS/PSSD patients and came to discover blackfox/douglasMich/QuantumFaith and Konflict from solvepfs.com both developed severe anxiety and joint pains after taking methylcobalamin.

Should have known this was a bad idea with prior experience taking a megadose B-vitamin complex. An ex was taking it as a diet/energy pill for some time and felt fine, I took one dose of the same thing and felt jittery and terrible anxiety for the next 2 days. This might be something that affects us worse than “normal” people.

Also, if you browse about either SAMe, or B12, on a general health information site, it will be said that it is impossible to overdose on either. Some say that it is impossible to overdose on any B-vitamin, which is clearly not the case with people developing neuropathy from sustained high-dose B6.

Point being, if any of you are considering doing something similar to what I did, heed this warning and just try something else, or cautiously titrate-up the dosage over a very extended period of time.

I think many of us get overconfident from trying so many things that have absolutely no noticeable effect, that we don’t think of the possibility of making this condition much worse or causing additional problems.


I have been preaching this quite a lot lately. This really applies for the severe cases but who is really to determine if you’re a severe case or not? There is no guideline or literature to determine that- only our anecdotal reports. I could kind of tell who is a severe case or not but then again it’s an opinion.

I also think people need to be more cautious with what they try. From reading this website, I have tried 5 things that have only made me significantly worse despite no change in hormone levels. If I did not try any of these I would be in a much much better state than I am in now and regret it every single day that I tried something without thinking before I did.

People need to understand that our bodies do not act fundamentally the same way they used to. Something has been altered causing a phenotypic difference. The fact that the 5 different things I tried made me significantantlt worse, when prior to this condition, these 5 things only made me feel better, only supports that claim.


What were the five things?

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I didn’t list them explicitly because I do not have PFS. I believe I have something analogous with the estrogen receptor.

  1. Nolvadex (binds strongly to both ERa and ERb)
  2. Clomid (binds strongly to both ERa and ERb)
  3. Trimethylglycine (Betaine) (releases estrogen from cells)
  4. Horny Goat Weed (strong phytoestrogen)
  5. Increasing TRT dose (increases estrogen)

There is one guy at SolvePFS, he got fucked from methyl-B12 too…

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What was his username?

Were his side effects from methyl-B12 permanent?

Thankfully, I still seem to be doing much better.

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His nickname is Konflict. You can read his blog, he says that he got worsen from methyl-B12 and vitamin K2

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It sounds like you were overmethylating. I would try some flush inducing niacin to reduce your methyl levels. I (think) I was over-methylating myself, peeing a lot, rumination (rumination on terrible thoughts) and feeling just suppressed. I took some niacin, got a flush and things started getting massively better very quickly.

I do have to note, though, after these methyl groups are removed your serotonin and dopamine (and whatever other transmitters) should drastically drop (as overmethylaters have elevated transmitters beyond normal function) I wouldn’t expect a full mentality back quickly. It seemed like I had to go into the outside world and re-methylate certain areas through experience. Very anecdotal I know, but it has helped. Currently I take niacin (200mg) and a b-complex for the folate. I can say I feel much better. I’m sorry your protocol didn’t work out for you, but I’ve seen people have similar results to yours as they treated themselves for undermethtylation when they were overmethylating and gave themselves panic attacks.


How many more wacky things do we have to put ourselves through …
I’m glad I’m done with all the wacky ideas myself
I’m currently looking into amino acids as some members here say its the way forward i don’t hold out much hope for it myself but it’s harmless trying though I do sometimes feel it’s pointless too as most things have been tried again and again if I was to make a list of everything I’ve tried to overcome the sexual dysfunctions the list would go on and on the only thing that works for me is Viagra the rest may as well hit the bin.
I’m getting to the point where I see that the only real option is to be persistent in asking real doctors to for help.
We can all beat our heads against a brick wall here we may stumble upon ways to help ourselves to some degree but that’s about it really.

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Thanks for the advice. Not sure what was going on, but this combination of SAM-E and methyl-B12 definitely triggered an awful experience. Only took these because I figured “what could possibly go wrong?”

Over the past 3 months, I have been progressively improving from the worst of this and am back to managing 5-8 hours of sleep per night. No more derealization and my mind has been focused on less horrible topics. Frequent urination is gone but still waking at least once every night to go to the bathroom. Not totally impotent any longer. Still not quite back to baseline with any symptom though.

For whatever reason, the apparent recovery ended and over the past week I am back to 3-4 hours total sleep per night. The excessive energy and derealization are gone but sleep problems, impotence, severe genital numbness, complete inability to feel pleasure or relaxation, and severe depression are back.

I will begin to feel very tired around 10pm, but can’t fall asleep for 2 hours after laying down, then sleep for 1.5-3.5 hours before waking. If I manage to go back to sleep it will only last for 90 minutes, then I’m awake again.

Never had insomnia issues before taking methyl-b12 and SAM-e and never thought it was this awful of a problem. Would trade this for the hypersomnia I used to experience any day.

I wanted this to end naturally, but looks like I have no choice but to take sleeping pills.

Just stay the hell away from this combination altogether. Many of us ask “how could this possibly get any worse?”; this is the answer.


Sorry this didn’t work out for you. To take up Down’s point, do you know if you are an under or overmethylator? I want to try this protocol myself, but think I’m an undermethylator as I have high blood histamine.

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I don’t know. I don’t have blood tests for histamine levels. The thing that led me to try this was that others were reporting some benefits from SAM-e and methyl-b12, although not in combination. I also had some 23andMe indicators of insufficient production of methyl-donors.

It was a shot-in-the-dark treatment that was wrongfully assumed to be totally benign. It was total foolishness on my part.


All gets a bit confusing - the Walsh protocol says that undermethylators should avoid folate and B12, but take SAMe and methionine https://askdrgil.com/methylation-therapy/ but I don’t think the Amy Yasko/Konynenberg differentiate between under and over methylation… A user called Gavman on Phoenix Rising had ME after Accutane. He seems to have done well on SAMe and methionine, but badly on B12 and folate. He was advised by Konynenberg that folate and B12 might give a detox reaction, and to build up slowly.
Round and round in circles - I’m 31 years post Accutane…

Dubya - perhaps looking on the bright side, a negative response might be better than no response? It at least gives an indication that you’re barking up the right tree? You’re probably aware of this paper https://lib.dr.iastate.edu/cgi/viewcontent.cgi?referer=https://www.google.co.uk/&httpsredir=1&article=4063&context=etd - to quote from page 42: " it is increasingly important to understand the side effects and consequences of retinoid treatment, which include development of hepatic steatosis, alterations in blood lipids, impaired methyl group metabolism,and depressive symptoms. Seems fairly authoritative?

I also tried SAM-e (400mg) for about a week or two and experienced very similar effects, the most notable being feeling wired and completely detached from reality. One thing that I experienced that you didn’t list, however, is that I got extreme stomach cramps (I suppose this is due to the increase in serotonin production), and this is what made me decide to stop. After I stopped I crashed for about a day or two, and I went through the worst depressive episode I’ve had since actually being on Accutane.

Despite this, I still wanted to experiment with SAM-e more, so I got a lower dose (200mg). I’ve taken 4 doses so far (taken every other day though), and have had a much better response. I have more motivation and energy and definitely more clear thoughts. The stomach cramps have not occurred once, too. Unfortunately my sexual sides are still worse off after my trial with the 400mg tablets.

After this post I’m hesitant as to whether or not I should continue experimenting with SAM-e though.


@johnniehaz: There has been some evidence over the years of a trend toward global genomic demethylation during treatment with vitamin-A and analogues of vitamin-A. This is in contrast to what was reported in the SAM-e paper (no significant effect of retinoic acid on genome-wide methylation).

FYI: That paper wasn’t peer-reviewed or published. Just a thesis paper on record. Interesting to read though.

31 years? Truly sorry to hear that. I hope you weren’t affected severely and have been managing well.

@BearOf17: I truly believe it was when the methylcobalamin was added that my new problems began.The SAM-e felt like it didn’t have much of an effect by itself (maybe a little additional energy and uplift in mood), and I have taken high doses of cyanocobalamin (B12) in the past for increased energy without trouble.

is this some kind of a global dna methylation protocol?
is the combo of sam e and b vit a combo used for inducing methylation?


Wait… does this mean taking Vit B12 and Vit E is bad?? even in small amount??

I don’t understand

This doesn’t have anything to do with vitamin E. I took extremely high doses of B-12 (methylcobalamin) as an oral supplement, in combination with SAM-e, and developed horrible insomnia and worsening of nearly all PFS/PAS symptoms. I was also experiencing derealization and complete impotence during the worst of it. This lasted for over 3 months after I quit taking them and I am still not sleeping right or feeling right. Doing much better now though. There were also a couple guys on solvepfs who also had a terrible reaction to high-dose B12.

Small amounts of B-12, within recommended daily values, should be fine. Myself and the others were taking supplements containing up to %16,000 of USDA recommended daily values.

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