Many people with MTHFR mutations find that methylfolate, the very supplement that they are advised to take, doesn’t seem to agree with them.
“Methylfolate makes me feel awful.”
“Methylfolate makes my child go crazy!”
“I am never taking methylfolate again!”
I’ve heard all of these many times on facebook forums for people with MTHFR mutations. Yet, methylfolate is the most commonly recommended supplement for people with MTHFR mutations – and with good reason.
Amongst the bad advice that many MTHFR patients receive, the two biggest mistakes I see are:
- recommending high-dose folic acid; and
- suggesting that people with MTHFR should go straight out and take methylfolate.
I have already addressed the folic acid question in my previous article, so this article is going to talk about taking methylfolate, and why you shouldn’t rush into that!
So… you’ve found out that you have the MTHFR gene mutation. Since that results in lower levels of methylfolate in your body, and methylfolate is kind of critical, you think you should take some methylfolate.
That makes sense!
So you buy some, you take a capsule, and then …. it gets bad.
Not for everyone. Some people are lucky. But at least 90% of people have side effects.
These are the most common stories I hear:
“I felt jittery, shaky, anxious, ‘weird’, ‘wired’ or panicky.”
“I hurt all over. Every joint and muscle ached.”
“Every symptom I’ve ever had came back at me with a vengeance.”
“I felt nauseous and nearly threw up”
“I had a six-day long migraine”
Children sometimes react a little differently:
“He was bouncing off the walls until midnight!”
“She just cried and cried all day – everything that happened in her day was taken as a total disaster and she just lost it.”
“Meltdown city!”
“I have never seen him so hyperactive in all his life.”
“She had a high fever for two days and was really tired” (I’ve actually heard this story from two different parents, and it kind of perplexes me as it’s a bit of an unusual reaction, but as I’ve learned, with methylfolate reactions, almost anything is possible.)
And my personal favourite – the child who literally destroyed a grand piano when given a dose of Deplin (a very high-dose prescription methylfolate supplement.. and one I would never use).
What causes these reactions? We need this stuff, right? How can a natural nutrient that is already in your body create such havoc?
Let me take you on a little imagination trip:
The body makes methylfolate to perform a function called methylation. (If this is a new area for you, you might want to read my MTHFR primer first.)
Methylation is a critical process that detoxifies steroid hormones, heavy metals, and environmental toxins of all kinds. It also makes neurotransmitters and breaks them down, amongst other things.
Now imagine that methylation is a pipe. But because of your MTHFR mutation, not much methylfolate has been made, so there is a block in your methylation pipe.
Unfortunately, your body has no respect for the fact that your methylation pipe is blocked, so it keeps making steroid hormones, breathing in toxins and pumping out neurotransmitters. (Probably for the best that it does, really!). And just like if you keep pouring waste down a blocked drain, “gunk” has been building up behind that blockage. Ew.
Imagine then that we suddenly remove that blockage – just like that, gone. What happens then? Well, as any plumber can tell you, all that built up gunk immediately flows down the pipe (which can be pretty gross.) Now remember that pipe is your body, as I take you through the top five reasons why you may react to methylfolate……
You started too fast
This is one of the most common mistakes.
Whatever you do, DON’T take the full capsule the first time! Start slowly.
Imagine that pipe is your body. Don’t you think it would be much less disgusting to let just a little of that gunk out at a time, so that it doesn’t flood the whole rest of the pipe beyond the blockage?
You’d be right. Go slow.
One way to go slow is to take a smaller dose, and the other way to go slow is to take it on a full stomach so that the food slows the absorption of the methylfolate. I recommend combining both strategies at once. Your body has to detoxify all of this gunk.
Give it a chance to do that at a pace it can handle.
You overmethylated in response to the sudden increase in methylfolate
This one can get a bit complicated and there is a LOT of misinformation on the web about overmethylation.
Let me just say that overmethylation is not something you do all the time. You are not a permanent overmethylator. That’s simply not possible, despite what some people may have labelled you as.
However some people are prone to overmethylating when they increase their intake of methyls – temporarily.
It’s when your body just can’t keep up with the sudden increase of neurotransmitters in your brain. The brain says ‘hey wow, haven’t had many methyl groups lately, now that we’ve got plenty, let’s go to town on the making of all this stuff we’ve been unable to make for a while!’
But then, seconds later it says ‘ah but hang on, we aren’t used to having so many neurotransmitters around so we’re not equipped to break them down that fast!’ This tends to result in symptoms of feeling ‘weird’ or ‘wired’.
I’m also pretty certain it’s responsible for the angry outburst/meltdown/hyperactive type reactions in children too. It’s akin to unblocking your pipe, only to find that the pipe beyond the block is a bit too small to accommodate the flow of water down the pipe now.
But it’s ok – unlike pipes, your body can adjust to the new flow, and it will. Going slowly also helps to prevent overmethylation reactions. Giving extra niacin (vitamin B3) also helps a lot. Most people only need extra niacin temporarily, but a standard dose of niacin should always be included in your B vitamin regime. Get professional help to know how to handle this type of reaction – overmethylation reactions can be very serious, particularly in persons with mental illness, anxiety or depression.
You were lacking one of the other nutrients required to use methylfolate
This is kind of like unblocking the pipe, but then finding that the pipe beyond the block had holes and cracks – all that gunk had to travel down a pipe that wasn’t fit to carry it.
It’s important to have all of the other nutrients in place that are required to break down toxins and neurotransmitters and work with methylfolate.
These include zinc, magnesium, all the B vitamins, iron and others. This doesn’t mean that you need to be supplementing all of these, but you may need some or all of them if you don’t have enough body stores, or have other genetic mutations that mean you need more of them than you have.
I would say that inadequate B12 is the most common reason I see why people who have started methylfolate slowly have reacted badly. B12 takes the ‘methyl’ from methylfolate and uses it to recycle homocysteine.
If you haven’t got enough B12, the methyl group can’t come off the folate so it gets ‘stuck’ there, unable to be used. (You may have heard others refer to methyl-trapping. This is the phenomenon I’m talking about.) Moral of the story: get the rest of your nutrients in place, especially B12, before starting folate.
The form you are taking may have other ingredients that don’t agree with you
Some of the prescription methylfolate drugs, such as Enlyte, also contain large doses of folic acid.
If you don’t already know why that’s bad, then you might like to read this post.
There are also often other additives in supplements, particularly the high-dose prescription ones. Watch for added colours, sweeteners, folic acid and goodness-knows-what.
This may be the simplest solution to reactions: get a pure, trusted brand, with all excipients declared!
You’re taking too much
To treat the nutrient like a drug and make a patented product, some pharmaceutical companies are making methylfolate products like Deplin with milligram quantities of methylfolate.
In reality you’re unlikely to need more than a few hundred micrograms. Doses such as 15mg of methylfolate have no place in anyone’s body and greatly exceed the amount of methylfolate that any normal person makes, even if they eat a folate-rich diet.
I am amazed that anyone tolerates these products, to be honest.
Stick to low dose supplements (bearing in mind that you may eventually need to take a few capsules, or not) and don’t believe the hype that you need a truckload of this stuff.
The fact is that you don’t need much more than the average person makes from their food folate, which ain’t all that much.
And That’s the Ballgame
There you have it, methylfolate reactions explained.
Work with your practitioner as always, especially when it comes to finding out what other cofactors you need, and most especially if you have had some issues with overmethylation, or know that your genes make you prone to it.
The good news is that I have yet to come across any of my patients who needed methylfolate who could not tolerate it once all of these factors were addressed appropriately. It can be tricky, but in my experience it can almost always be done if it has to be. Best of luck!
I have the mutation gene MTHFR C677T detected Heterozygous my Dr has no ideas on how to help me also said my children an grandies don’t get tested free anymore cold you pls help me I have low thyroid just in March this yr had a cryoblation on heart values have also a Bullous auto immune disorder my body is turning on it’s self I also have dyslexia thanks heaps for your info luv jewels Xoxo
Hi Julianne,
Sounds like you are having a tough time! If you would like to get some specific help for your situation I would need you to make an appointment. You can do that online here. Hope to hear from you soon.
Hi can you recommend a god practitioner who is on the Sunshine Coast QLD?
Hi Carly,
Unfortunately I don’t know of anyone with specific methylation experience on the sunshine coast, however I am in northern Brisbane and I see patients from the Sunny coast regularly. We often do 1 appointment in person and then the rest via skype, however at the moment practically all practitioners, including myself, are using Skype (or other virtual platform) exclusively to minimise travel. If you are interested in seeing me this way then please jump on to my bookings page or contact page. Either one sends me an email when you complete the form, and I’ll get back to you asap.
Cheers, Nicole
I have MTHFR C677T homozygous. The worst one. I can’t go on much longer with the anxiety and depression I have. It’s been years that i have been looking for a doctor that knows how to treat this.
I can’t tolerate any supplement with methylation. Even the smallest amount.
I’m so sorry to hear this Jean. Firstly I would say that the MTHFR mutation may indeed be a large part of the cause of the problem, though you will need to work with a good practitioner who understands all of the interlinking parts, including other genes and environmental factors. If you live in Australia I would be very happy to give you an appointment if you would like to make one. If you are outside Australia, please feel free to send me a message via the ‘contact’ form on this website and I can recommend someone else that you could see who does how to treat these conditions appropriately. Best of luck, Nicole
I’m in Australia, north coast NSW, I found out on my own that I have homozygous c677t, I did get a blood test from doctor to test b12, folate and iron, my thyroid was fine, my urine methylmalonic acid was 1.08ug/mgCR and figlu was 3.7ug/mgCR.
I have really bad anxiety especially in the evening lately and while driving.
It’s just getting harder, I am trying a supplement 3 times a day B6 – 17mg, methylfolate 267mcg, methyl b12 216mcg and trimethylglycine 500mg, not sure if it’s doing anything, not much has changed but it is only day 3 of supplement
HI Christopher,
I really hope that the supplement works for you, and also that you are working with a good practitioner to ensure you are addressing all the factors involved. I always like to emphasise that while MTHFR polymorphisms can make anxiety worse or make you more prone to being ‘triggered’ into developing anxiety, they are never the cause or even a major cause. I highly recommend you read my article on MTHFR is not the answer for some more tips.
Good luck!
A hugely helpful article – thanks so much for being so generous with your knowledge.
Please let me know if someone who can help me with this. Daytona/St Augustine, FL area.
I’m sorry but I don’t know of anyone in the USA whose practice I can recommend. A naturopathic doctor would be your best bet. Sorry I can’t be of more help.
Hello!
I have been taking methylfolate for about four years now. Sometimes I feel very jittery from my prenatal vitamins which contain methylfolate. I have found that I handle the vitamins much better when I am very well hydrated. On days where I forget to drink very much water, I feel very jittery, anxious, and strange. Just wanted to mention this in case it may be helpful to someone.
Thank you for your great article!
Im feeling the same. Its only since ive taken an extra supplement that has methylfolate in it, along side the usual B complex with methylfolate i take. I might be taking too much? I should drink more water too and see if things ease.
Do you know of a doctor near St. Louis, Mo. ?
Sorry, the only practitioner I know of in the USA is Dr Ben Lynch, but I don’t know where he is. If you can consult him via skype or in-person, he’s very good.
People wrongly assume that if one is an “under-methylator” that taking methyl folate is some kind of heavenly prescribed and preferred option. This is not the case.
True, it’s definitely more complicated than that!
Just have to say: I’ve been researching and dealing with MTHFR misery for over 3 years, and this is the most well-written, easy to understand article I’ve read. And I’ve been to ALL the websites. WOW! Thank you! Will be sharing this.
Thanks!
I agree!
This is a great article. Very easy to understand for people that are not in the medical field congrats. I have been severely depressed and with chronic pain for most of my life. I am 41 yrs old. I found out 10 years ago I have 1 Gene of MTHFR (C677T) I was on deplin 15 mg and B12 for about 6 months with no benefit. I have been on at least 20 or more antidepressants and had bad side effects. I am on cymbalta and 1 mg of l- methyfolate. Cymbalta was working at first (but not with out sideffects) now it’s not. I recently tried rTMS ( magnetic therapy). I had high hopes that this would work. I didn’t see any benefits it’s been 2 months now. Over the past couple years my symptoms have gotten worse including anxiety, lethargy insomnia and memory problems. I had a brain MRI, CT scan and other tests. They all came back negative. I am convinced MTHFR is most of my problem. The dozen Dr.s I have seen have not helped much. Any help or advice would be greatly appreciated. Thank you.
Thank you for the compliment on the article, I’m glad you found it easy to understand.
There are a lot of unwell people out there who find out that they are MTHFR positive and hope that this will be ‘the thing’ that fixes all their problems. I’m very sorry to say, but that is almost never the case. As my ‘bigger than MTHFR’ article outlines, it’s only one of a very large number of genes that all impact our susceptibility. However – and this is a big however – susceptibility does not equal disease. What we know now is that environmental influences (gut bacteria, diet, air and water quality) and even more so, spiritual issues (beliefs, stressors, bitterness, unforgiveness, fears, self-hatred etc) play a MUCH bigger role than any genetics do. I know of very many people who have become completely well just by addressing the spiritual issues. If you really want to be well, no matter how much it may cost you (not in terms of money, but in terms of effort and self-examination and humility) then please feel free to use the contact form to let me know where you live, and I will try to refer you to someone who can help you in this way.
In the meantime, your comment has reminded me that I need to write another article on the insignificance of genes compared to these other factors. Thank you.
Thank you for the article. I started Enlyte, and I’m curious as to why folic acid is in it if it’s so bad? I have a reputable physician and I’d be surprised if she was in that dark on that. Thank you!
Unfortunately very few medical doctors have more than bare minimum training in nutrition. As a result, even the most reputable physicians have almost no clue about how bad folic acid is – most are indeed in the dark. Perhaps you can refer her to the folic acid article here if she’d like to learn more!
Wow! Great answer! Very caring. I’d like to meet someone who can help me with those attitudes. I agree. I beat myself up all day. I am in Palm Coast , FL. 32137. Thanks.
Unfortunately I don’t know of anyone in Florida! The USA seems to have a real lack of holistic practitioners that know what they are doing. I actually can’t for the life of me find your original comment – it seems to have disappeared, so I don’t know what I was replying to. If you’d like to use my website contact form I am possibly in a position to offer you an appointment via Skype but I would need a summary of what is going on for you first. Sorry I can’t find the original comment where you told me!
So I have not tested to see whether or not I have any mutations on the MTHFR gene, but yesterday I began Methylfolate (200mcg/day) and TMG (4g/day) simply for general health benefits – nothing specific. Today I am beyond dragging. I am very fatigued mentally and physically. I’m giving it time before I draw up any conclusions, but do you see any correlation between my added supplementation and my symptoms? Something is definitely going on, I just don’t understand how or why exactly. Thank you so much for your time.
Hi Casey – yes, those supplements can make you feel worse if they aren’t needed or aren’t the right forms for you. To be honest, I do not think that it is a good choice to take that sort of thing for a general health benefit. You may well end up finding out that it results in a general health detriment. That is a fairly large dose of TMG – I can think of at least 3 possible negative effects from that straight off the top of my head. As for the folate – that can deplete vitamin B1 which you may have a higher need for than you realise. That’s on top of all the potential side effects from the methylated form. Really, such supplements should only be taken under the guidance of a practitioner who knows your whole health history and has seen your test results. If you really want to take something for general health, a low-dose multivitamin (one containing low dose of methylfolate or folinic acid, not folic acid) would be the safest bet. Better yet, try to get in to see a good practitioner for some more specific guidance.
I have the mthfr c677t gene mutation. My pcp says she may not be able to treat me. Lack of knowledge. I live in Graham Washington and I need to find a mthfr specialist.
hi Tina,
Unfortunately I’m not familiar with practitioners in the US, so I can’t help you out much with that, however please be aware that MTHFR isn’t necessarily a big part of your picture, or maybe not a part at all. If you are otherwise doing well with your pcp there’s no need to move to a specialist as such. Just avoid folic acid in all foods and supplements – aside from that, you may not need any specific treatment for the mutation. It doesn’t affect everybody.
Hi there,
Thank you for your website. Your articles are well written and so informative. I have the C677T and A1298C mutations. About Sox months ago I went from being completely normal and high functioning to a complete mess. I stopped sleeping and had anxiety and depression that was nearly debilitating. My doctors put me on ssris but they just made me a bit better. In addition to the MTHFR Gene, I have the slc-6 a4ss and comt Val Val. About a week ago my doctor put me on bed light. My reaction was immediate and amazing but unfortunately short-lived. I became irritable and I after getting my sleep under control, stop sleeping well again. Now I am taking a much lower dose, about 500 MCG. Since I started on that lower dose I feel great during the day, but I only sleep well every other night. I am very confused by this. I’ve been adding low dose niacin which seems to help. Other than the insomnia I have no other symptoms at this point.
I’d appreciate any advice you have for me. Thanks.
Thank you Jennifer for your comments.
Unfortunately every 2nd night insomnia has me pretty stumped too. I do agree that lower doses of methylfolate are usually better than the very high ones, so glad you dropped down.
The main thing I would advise would be to look at what happened just before you became ‘a complete mess.’ In all likelihood there was an emotional stressor, though sometimes it can be a chemical stressor such as a round of antibiotics or big chemical exposure. Most often however the emotional/spiritual aspects of our personhood are the keys when there has been a sudden downturn, so I would really recommend you put the focus there.
Hello,
This post and all the others relating to MTHFR, folate and folic acid have been extremely helpful. I only wish I would’ve seen them before I made the mistake of purchasing, and then taking a dose of, Enlyte. I have never had a reaction as bad to a “medication” as I did to Enlyte, and after reading this article, it makes sense why I did. Reading this literally helped me get through the night, and saved my husband from dragging my sorry butt to urgent care. So, THANK YOU! 😊
I will not be taking any more Enlyte, and have found a nice whole food vitamin/prenatal with a much, much smaller dose of L-5-MTHF and NO folic acid. I’m hoping it does the trick.
It’s rather discouraging that my Doctor prescribed Enlyte to me in the first place, honestly. I am homozygous for the mutation, and have particularly high homocysteine levels, so I understand why she would. But I would also like to believe that she would be more educated about how that cycle works, and why folic acid should be avoided generally, and especially for people like me. The conspiracy theorist/pessimist in me wonders if she gets some sort of “kick back” for prescribing it, although I really really hope she’s just under informed, as I do enjoy having her as my Doctor.
Any who, thanks again!
Hi Veronica,
I’m so sorry you had this experience, but glad the articles helped – very glad!
Unfortunately there is a misconception out there that if you have a health problem, a doctor is the best person to treat it. This is definitely not the case – if it is a nutritional problem, then a nutritionist or naturopath with extensive experience and training in nutrition is the way to go. Doctors simply aren’t trained in nutrients and with the exception of some real basics like iron supplements for those with low iron, shouldn’t be prescribing nutrients if you ask me. I do applaud them for trying something other than pharma medications, but I do wish that instead of prescribing nutrients, they refer clients to a practitioner with the right kind of training.
Hope your new prenatal works well for you!
Just curious about the data that supports 15 MG of L-Methylfolate (Deplin) in treating Major Depresssion when used as an adjunct to SSRI’s. Large amount of patients studied and none of these side effects reported?
https://www.ncbi.nlm.nih.gov/pubmed/23212058
Yes, it is interesting that they didn’t note these side effects. I haven’t had time to read the whole full text of the study, but it’s possible that they didn’t ask questions about side effects that they may not have been expecting, such as headache. More likely however, it’s the subset of subjects that were less prone to side effects. They chose recipients with SSRI-resistant depression. Firstly, methylfolate is much more likely to impact negatively people with anxiety or with aggressive tendencies, but not so much those with simple depression. Secondly, methylfolate side effects happen due to sudden excess of serotonin, adrenaline and dopamine. If these patients had not already reacted badly to SSRIs, which can do similar things, then they were less likely to react to the neurotransmitter spikes caused by methylfolate.
Hi there, it was a great article to read. I was diagnosed with MTHFR in my 20s due to miscarriages and a baby who got Spina bfida. Hospital did not tell me anything about this gene when diagnosed and I have been suffering all my life. I’ve had debilitating anxiety and haven’t been able to function in society, depression and chronic fatigue. I’ve been googling how to get rid of anxiety and depression for years. I’ve tried everything. Nothing worked until I realised mthfr was causing my anxiety and other symptoms. So I went out and bought B6 and B12 and I started to feel better in 2 days. After 2 weeks I started folinic acid which is ok but sometimes I feel tightness in chest and start stressing out. Overall I feel better but some days I don’t feel right. Not sure if I am taking the correct B vitamins. I am in Adelaide Australia. Please help!
Hi Fiona,
I’m sorry to hear you’re going through this but I’m really glad that you feel better on b6 and b12.
I’m afraid I’m not able to advise on dosages etc outside of consultations due to ethical reasons, but I do do skype consultations if you would like to get in touch about an appointment via the booking page.
Kind Regards,
Nicole
Hi Fiona
I am also in Adelaide and have just started seeing Dr Andrew Owen in Stirling (08) 8339 1222 https://g.co/kgs/MiHpg8. I have been feeling good until i started 5-mthf.
Great article with great answers to questions we all have. If I may add….
Please follow-up with clinical studies. I do beleive suggesting that 15 mg has no place for anybody, now has empiracle evidence that isnt true. Studies are showing statistically significant improvement (depression) for those taking 15mg vrs 7.5. In fact I beleive the 7.5 conferred no significant improvement.
Otherwise this information did help me greatly, thank you so much for writing this comprehensive summary.
Hi David,
Despite the positive outcomes in a number of studies from 15mg methylfolate, I note that no study has been done for longer then 2 years (that I can find, I may be wrong) and no one has studied the long term effect of this high dose on other aspects of biochemistry. The studies have looked for ‘side effects’ which were all self-reported by participants (and there were quite a few), but no one has assessed whether this kind of supplementation may lead to B12 or B1 depletion (they compete), heart attack, stroke, increased cancer risk, or any other long term health consequence. It has been presumed that folate won’t do these things because folate is generally regarded as safe. But this dose is so much higher than you would ever find in any healthy body, no matter how much folate someone tried to get in their diet. At this kind of level the ‘generally regarded as safe’ status should be questioned because this is not a natural dose. In addition, there have been a number of studies indicating that methylfolate may stimulate the growth of pre-existing cancer cells. Until more studies are done, for long enough time frames with broad enough considerations, I will stand by the statement that I don’t believe 15mg doses are a good idea for anyone.
Could you expand on the comment you made here about methylfolate having potential to trigger already existent cancer cells? And how to work with or around this
Sure. Any time you support methylation you are supporting DNA production and therefore cell replication. If you have a situation like cancer where certain cells are replicating faster than others, they will hog resources as such, and the benefit to the cancer cells will far outweigh benefit to normal cells as a result. There are studies demonstrating that methylfolate supplementation can increase cancer growth – I think it was particularly in relation to colon cancer. The way to work around it – don’t give methyls to any person unless there is clear need, and NEVER ever give methylated B vitamins in a person with suspected or confirmed cancer growth. Just don’t do it. I have seen people on methyls have cancer grow much more quickly than expected, and then the growth stop when they stop the B vitamins, so I can confirm it does happen in real life too, not just in studies.
Any chance of Serotonin Syndrome with the 15mg of methylfolate added to an existing SSRI?
I would think the chances are pretty slim. But if there were enough factors at play in a perfect storm, I guess theoretically possible.
I have MTHFR; I took a methylated Folate supplement last night and feeling very anxious and depressed today. Please advice.
I would stop the supplement immediately and go back to your practitioner for advice. Make sure they know what they are doing with methylation. If you are considering harming yourself or someone else, please go straight to emergency or your local doctor, or call a local counselling hotline.
Hi Nicole
Thanks so much for this article. I just recently found out I have the C677T mutation. My doctor said it wasn’t an issue and I didn’t need to do anything about it. I suffer from bouts of extreme anxiety that then cause depression. I can go from being ok to extreme anxiety. The last few times I’ve noticed it happened after supplementing with high doses (50mg) of b6. I don’t do well with b vitamins generally but seem able to tolerate even high dose (5mg) folate. Four years ago I took a prenatal with 45mgs of b6 and was ok (but I think upon starting it I had one of my episodes but it’s a while ago now). 18 months ago I tried to take that again and it triggered massive anxiety. It took months and months to resolve. When I was told I had the mutation and it may cause low b6 I stupidly took the 50mg two days in a row then tried a prenatal with p5p, then stopped because of the massive escalation in anxiety. I’m in a very, very bad way now and don’t know what to do. I’m going to get my folic acid, b6 and b12 levels tested as soon as possible. I don’t know how to reverse the effects of the b6 – it should just leave my system but that doesn’t happen. I just get worse and worse, it takes a long time to resolve each time and I can’t bear that right now. Is there anything you’ve heard of like this? Is there anything I can do? I don’t understand how one vitamin could have such a devastating effect. I’m doing ivf and am worried that I can’t get pregnant because of the b6 issue – it’s the only thing different from last time when I was taking it.
Hi Amy,
I’m sorry to hear of the bad time you’ve been having! Yes, P5P or B6 can cause toxicity in some people if they have a propensity for it to build up in their systems. I have treated a number of patients with this problem, although most people do need to take it for longer to notice those ill effects – in some ways it’s lucky you notice the problem so quickly.
MTHFR does NOT cause low B6 so whoever told you this is ill-informed.
I would definitely test your levels – that will be helpful information, but in order to resolve the issue I really think you will need to work with a practitioner (preferably someone who is more knowledgeable than the person who told you MTHFR causes low B6!!) If you don’t have a good methylation-savvy naturopath or nutritionist then feel free to let me know. I only treat patients in Australia but I do know of some in the USA if that is any help.
Kind Regards,
Nicole
Hi great article!
I’m homozygous for mthfr c677t and comt met/met. I’m finding it difficult to get information on treating both together. I live in Brisbane do you know of any good knowledgeable practitioners here? Or do you consult via phone?.
Regards Roman
My bad, I see your in ashgrove! I’ll contact your clinic
Regards
Indeed we are! Feel free to get in touch via the booking page – I am a methylation specialist so all good!
Hi,
Are you able to take the Prenatal vitamin if you don’t have the gene?
Will there be any side effects?
Thank you
Hi Sarah,
I’m not quite sure if you are referring to a prenatal with methylfolate or one with folic acid.
I don’t think anyone should take one with folic acid, ever. Even if they haven’t got MTHFR mutations.
Methylfolate (in a prenatal or whatever form) is a good form even if you haven’t got the MTHFR gene. However yes it can have side effects for some people (which is actually more determined by certain other genes than it is by MTHFR.) So yes, you can still take a prenatal with methylfolate, but it may have side effects. You can try it and see.
If you dont have MTHFR gene mutations then the best prenatal is probably one with a good dose of folinic acid, or a mixture of folinic and methylfolate. Folinic is a bit hard to absorb in the gut so in Australia the TGA doesn’t approve prenatals with only folinic, as it may not provide enough folate. Probably a good reason to do a prenatal with half and half methyl and folinic. Good luck!
Hi! I’m two months out from starting to try to conceive and I’ve been struggling to find a prenatal for months that doesn’t give me side effects from the methylfolate. I am heterozygous CT677T and want to provide the best possible start for my future baby. I’ve tried two prenatals with methylfolate and one with just “folate” from organic food source. I feel great for a day or s on the methylfolate and then body aches and headaches ok the days following. I feel at a loss of what prenatals to take. Any suggestions?
Thank you!
Hi there,
If you are one of those people who feel great for a couple of days and then feel bad, then I would suggest you’re not going to be able to do what you need with just a prenatal. You will likely need to find a balance with other nutrients. Epsom salts baths may help you push through the body aches and headaches and they may disappear after a few days. You may also need to start the dosing more slowly. Alternatively taking plenty of sublingual methylb12 or hydroxyb12 may be all you need to do. Hopefully you are working with someone knowledgeable who can help you navigate the minefield!
People, please do some research on the MTHFR mutation and learn for yourself that it has not been proven to cause any of the ailments some of the medical community want you to believe. Just do a search on MTHFR myth or something similar and you will see some pretty good evidence from actual geneticists that state they have no actual concrete proof that the mutations cause mental health problems let alone other health issues. That being said mythylfolate is still good for you.
I agree that MTHFR does not always lead to health issues, or to mental problems. In fact, many people have it without any symptoms whatsoever, as my blog describes. However I will disagree with you that it cannot cause mental health problems. Perhaps there is no proof that geneticists are happy with (the medical profession always being incredibly slow to adapt its recommendations to new research, this doesn’t surprise me.) There is however AMPLE high quality research demonstrating the MTHFR snps can raise homocysteine, and that they reduce folate availability. Both raised homocysteine and low folate levels can cause mental problems and there is very strong research backing for this. It is not as simple as MTHFR = you’re going to get x,y or z health condition, and neither is it true that everyone with MTHFR needs to take methylfolate. BUT it is absolutely true that there is increased risk, and that there is very good evidence to show that someone who has inadequate folate due to the mutation/environmental interactions, can experience mental health problems as a result.
Wow, a psychiatrist recommended I take a prescription strength methylfolate supplement. At first I felt fantastic! I thought I had found a miracle pill and was ready to toss my antidepressant in the trash. But 6 weeks later I feel worse than when I started. My doctor never told me to start slow and work my way to a full dose, or that I may not need a full dose. In fact, he said he recommended that particular brand due to its strength. I’m relieved to find this post – it may very well be my miracle pill after all, but I’m reducing my dosage immediately.
Hi there! I am homozygous for C677. I started taking methylfolate and it makes me feel sicker. I have numbness in tongue, fatigue and anxiety. My bloodwork was all normal but my gp said to still take it. Should I try decreasing dose. My homocysteine levels are normal. I was also diagnosed with celiac at the same time so I’m always wondering if my symptoms have something to do with that. Please help. I’m so lost 😔
Hi Tracy,
If Methylfolate makes you feel worse you should not take it! Work with a practitioner that can fix the problem. The symptoms you describe are CLASSIC B12 deficiency. Folate will make this worse until you get the B12 levels up, but you need the right form. Regular over the counter B12 will not help. You will need methyl or hydroxy B12. B12 deficiency is very common in people with coeliac disease – and you may have been told by your GP that your B12 is normal, but the Australian reference range is so low that many people are told ‘normal’ is anything over 150. In fact, in Japan you would be given a shot in the Doctor’s office if anything below 300! The reference range should start at 500 and go up from there. So do not believe that B12 is ok if it was an Australian Dr that told you so – not their fault, they aren’t nutritionists so they don’t know that the reference range from the lab is so so wrong. I hope that helps a little. Please contact me if you need an appointment if you can’t find someone in your area to help.
Thanks for this article. Long story short: if methyls give you horrible side effects, STOP taking them. You might also have COMT or another gene that doesn’t mix well with methyls causing your side effects.
I have MTHFR homozygous C677t. Before I even knew I had it, I was taking a prenatal that happened to have methyl B12 for a few weeks. Then I had a miscarriage and what I thought was a panic attack, but I figured it was just from the miscarriage/dropping hcg levels. Then I got my MTHFR diagnosis, so I kept on taking the methyl b12 and added a small dose of methylfolate. I read Dr. Lynch’s page about starting methyls and followed all of his advice. Nevertheless, I began having symptoms that I thought were panic attacks–severe dizziness, a feeling like something was taking over my brain, unsteady pulse, etc. These symptoms got worse over two months, long after my hcg levels returned to normal. I got my b12 tested tested, and it turns out that it plummeted from my normal range (600s) to just under 200. All of my other levels were fine (including my rbc folate), and my homocysteine was slightly elevated. Once I stopped taking the methyls, I was fine within a week. My B12 went back up, and the symptoms stopped. My holistic doctor ran more genetic tests and she said because I’m hetero for COMT, I might be why I can’t tolerate methyls. She told me to stop taking them. I take a prenatal with folate from greens. I can also tolerate adeno b12 and folinic acid.
Listen to your body. I’m glad I learned that I have MTHFR so I can limit my folic acid intake, but just because you have it doesn’t mean methys are the answer for everyone.
Absolutely right Tracy. In your case, I suspected you might have been having some methylfolate or folic acid in your prenatal – is that the case? Sounds like you needed a lot more B12 than you did folate, so folate caused a deficiency. These things must be in balance. a Heterozygous COMT mutation doesn’t usually cause methyl intolerance like that. But if you do well on Adenosyl B12 and Folinic acid, then that’s all you need. Methyls are indeed not always the answer!
B6 in the prenatal or other b-complex vitamins is often THE problem. It’s stated all over the web that B6 is safe as long as you stay under 50 milligrams a day (which is conveniently the amount used in most b complex products), but there are horror stories from hundreds of folks, if not more, from taking very low doses of B6.
A google search on b6 toxicity will show up if one types in ‘medhelp.org’ in the search field. It’s a classic page started 13 years ago…
You are correct that B6 causes problems for quite a few people! I have treated several people with B6 toxicity. Having said that, the symptoms I mentioned in my article- headaches, nervousness, jitteryness, panic attacks etc are much more likely to be due to the ‘methyls’ than due to B6. B6 toxicity tends to have slightly different symptoms, and certainly most of the people who respond to this blog have had their reactions to plain methylfolate or methylb12, where there isn’t any B6 in the dose anyway. Good reminder though that any nutrient can cause problems if it’s not the appropriate one for that individual!
I was prescribed a dose of 15 mg of Methylfolate (Deplin) a year and half ago for symptoms of depression. I have the the C677T mutation and my other genetic markers were prohibiting any other anti-depressants as an option. I don’t remember having any of the side effects you’ve outlined in this article–it did feel like a miracle supplement in the beginning as my depressive state improved noticeably. However, I am now having some elevated levels of AST and my ALT is at the peak of the normal range. I also began suffering from constipation several months ago and some overall joint stiffness/aches. I’m beginning to wonder if this is related to Deplin as I am not a smoker nor do I drink alcohol and I’m in a monogamous marriage–so the elevated AST should not be related to alcoholism or Hepatitis…. Trying to figure out the cause of the AST elevation before my liver is harmed more. Do you have any insight for me?
Hi – I’m really glad to hear you’ve been one of the ‘lucky ones’ who did well on high dose folate. I can’t see any really obvious link between that and raised liver enzymes, but I would suggest a few possibilities to look into:
1. Deplin has some other ingredients such as preservatives etc I think. They could possibly not be good for you.
2. It could be unrelated to the deplin but related to constipation. Non alcoholic fatty liver disease is linked to toxins in the gut from bad gut bacteria. Constipation would indicate this is a strong possibility.
3. If it is related to deplin, I think it’s quite possible that such high doses (I would never go this high myself) may be depleting B12 and other critical nutrients (all of the Bs, several minerals) and that could cause liver disease. I certainly wouldn’t ever use deplin on its own for such a long time without supplementing the cofactor nutrients that go with it.
I hope that some of this helps!
Hello Nicole,
Your page is singularly the most informative I have found and describes much of what I have been experiencing. I have had intense issues since 2015, early 2016 it went through the roof and unfortunately the very many doctors including 3 times at ER RBWH got it wrong.
It has cost me 2 jobs and I have not been able to work since July 2018, I found 2 very nice functional doctors who might have got it right eventually but when one “expert” sais the other got it wrong and then their prescription causes the same thing makes it impossible to know where to go.
I am so low on funds, can you help via bulk bill?
I have kept reasonable records since August, this may assist. I have records from before that too but due to the misdiagnosis and therefore mistreatment with initial prescription of benzos this can cause so many symptoms anyway, it’s not possible to know if a reaction was due to various supplements, tolerance withdrawal or just withdrawal. I stopped these 24th June 2018.
I am certain my issue is methylation, I had been tested for kryptopyrrole and my SG adjusted result was 34(I don’t know what it should be and this was in 2017), my histamine was 0.4 and homocysteine was 16 (again this was 2017)
I have the heterozygous A1298c
I can increase symptoms by taking individually methylfolate, msm, B12, high dose ascorbic acid.
I also have my data from Ancestry which I have applied to Promethease, this seems to provide an extensive genetics report.
hi Greg,
Thank you for your lovely comments.
Unfortunately not being a medical doctor I don’t get any medicare funding, so unfortunately there is no bulk bill option. Some of my patients do get private health rebates however – and my fees are much lower than that of a functional doctor.
What I can definitely tell you is that you do not have a problematic MTHFR enzyme. Heterozygous A1298C is NORMAL and does not cause any impairment of the enzyme, so treating this is not going to be helpful, and may harm. Your homocysteine is high though, so your methylation is definitely off in some way. It must be other genes such as COMT causing problems with the methylfolate etc that you listed.
I would suggest that you start by reading my latest article (called “MTHFR is not “THE ANSWER””) and make sure that you are addressing all of these areas. I’d be interested to hear back from you once you’ve done that, and hopefully something will pop up there. Please send me an email through the contact form if you need further help.
Kind Regards,
Nicole
Is there any way to know how long it takes to for it to get out of your system? I’ve been on 15 mg of prescription strength Deplin for two weeks. I stopped taking it four days ago. Thank you.
I’m sorry, there is no way of knowing unfortunately. It’s not like a medical drug that is cleared by the liver – because it is a nutrient the body will incorporate it into new DNA and other structures – which could happen very quickly if you were deficient in folate, or very slowly if you are deficient in cofactors like B12. If you mean how long will it take for side effects to disappear – once again it depends on how much of the cofactors you have available. If you have plenty of B12 and minerals in your body, side effects, if present, should fade mostly within a week, with a few remaining for a few weeks after that, at the most. If not, I would seek help to look at what other nutrients you need to utilise all that methylfolate. Good luck!
Thanks so much for this post! I was beginning to think my severe reactions (wired/jittery) to methylated B vitamins was all in my head because everyone else seems to be able to take them! I have tried even a drop or two of liquid methylated Bs with the same reaction. A functional medicine practicioner reviewed my lab tests and said I need help with methylation so what do you do if you can’t take it even in small quantities? Thanks!
hi Debby,
There are many ways to support methylation, (take a look at my latest post for some foundational suggestions) but if B vitamins are really needed and methyls aren’t well tolerated, the options are hydroxyB12 and Folinic acid instead of methylB12 and methylfolate. They are usually tolerated quite well.
Thanks so much Nicole!
hi –
i take ssris and have the homozygous mutation. my doc gave me deplin 15 but it was wayyyy too much. do you have a low dose (400 micrograms) brand of l-methyl that you recommend? thank you
Hi Frank,
I’m afraid it’s a bit outside of ethical boundaries to recommend something specific through a blog, but there are plenty of options available online in that 400mcg sort of range. Look for something with no fillers to speak of, no other ingredients, and the best form is Quatrefolic, or the MTHF as a glucosamine salt. Levemefolate calcium is also ok but not quite as well absorbed. I hope that helps,
Nicole
Hello, thank you for the article! I have chronic low B12 and folate. A practitioner gave me methylfolate to take but did not test me for the genetic mutation. I decided to have myself checked and the test came back negative for any sort of mutation. Should I then just take a regular form of B12 and folate? Or is it still safe for me to take the methylated form?
Hi Megan,
Active forms are fine for anyone to take – methylated if you tolerate methyls, or as hydroxyB12 and Folinic acid if you don’t. Folic acid and cyanocobalamin are NOT recommended for anyone, regardless of mutations. (Please see my article on folic acid for reasons why.) Honestly, I don’t think such ‘regular’ forms should be on the shelves. They are synthetic and don’t work the same way in the body, so best avoided.
Cheers!
Thank you Nicole Hargreaves! I enjoyed your article and will continue to read others of yours. I started taking deplin 15mg five weeks ago for depression. I am also taking Viibryd 40mg. I also have extreme problems with sleep. A week and a half after starting deplin, I felt happy for the first time in years. And my depression even now feels under control. But I am extremely fatigued to the point of missing work. The fatigue could be related to sleep issues but have you seen a link between methylfolate and fatigue?
Thank you for you time! Sam
Hi Sam,
To be honest no I haven’t seen an issue with fatigue and methylfolate. With insomnia, yes, but not fatigue on its own. It could be a reaction to the additives in the deplin and you may be ok if you get a pure one and take less? Just an option… but my first thought is always that if you’re unsure how you tolerate something, stop it, then try it again to see if it has the same effect.
Another strong consideration should be that B12 deficiency causes fatigue, and folate and B12 work together, so if you take large amounts of folate (and deplin is, quite frankly, a whopping great big dose that I would never use)… well then you may have induced a B12 deficiency. I would say that one should never take that much folate without also taking B12. Hopefully that will be the issue and it’s easy to rectify – you would need to take the B12 as hydroxycobalamin – not cyanocobalamin, or methylcobalamin is also likely ok.
Hi Nicole after reading your article I found it so easy to understand and to the point. I have suffered for many years now from severe anxiety and PTSD the from Police Service. I am now retired as I am unable to work and have been interested in trying meth folate as antidepressants are no longer effective and I have become hyper sensitive to medication. I have a strong family history of mental illness with 3 family members having committed suicide and for this reason my doctors have both stated that the gene testing is pointless. Can you refer me to a specialist in this field. I live on the Gold Coast. Regards Steve
Hi Steve,
Unfortunately I don’t know of any practitioners in the Gold Coast that I know work in this field. I am in Brisbane and also see patients via skype if you are interested in consulting with me. Feel free to get in touch via the booking page if that suits you. I have quite a few patients on the coast who come see me for their first visit and then use skype afterwards.
Kind Regards,
Nicole
Thanks Nicole. I saw Naturopath today and he has started me on 500mcg meth folate (up it to 1mg in a week if no response on the lower dose). and 2000mg meth B12. I must admit I do feel slightly better!!! I am taking 25mg seroquel antipsychotic as needed prescribed by my Psychiatrist and have just tapered off aropax as it stopped working for me. Thanks for your prompt response. If I’m not satisfied with my naturopath I will make an appointment to see you. Kind regards Steve
I started methotrexate injections a few weeks ago for Lupus and I was prescribed 1mg daily of folic acid. I have never tolerated B vitamins well, after a few days I get angry, irrational and depressed. So I ordered folate. I’ve been taking it for three weeks and I feel awful. Depressed, crying, everyone is driving me crazy. Im hypersensitive to everything so I’ve been grasping at online research trying to find an answer to why I’m feeling like this stumbled across this article . It made me feel less crazy! So these symptoms could be that my body isn’t used to it yet and it could still adjust? My B-12 is at the low end of normal but I’ve always stopped taking it after a few weeks because of the symptoms it caused.
Hi there – sorry to hear you’re going through this!
If you have low B12, then you will likely react poorly to folate in any form. Perhaps you can find a form of B12 that you do well on, such as hydroxyB12? Either way, with methotrexate it is pretty much mandatory that you take some form of folate as you will get very sick if you don’t. I would suggest you try for folinic acid, as that is not synthetic like folic acid, and nowhere near as reactive as methylfolate.
Good luck!
Thank you so much for your article. After so many years of battling insomnia your information helped a lot. I’ve seen every doctor and have been to every top notch clinic. Only to have wasted a lot of money and not any better. So I had to experiment on my own,which made things worse at times. But I am low in folate and tried methylfolate. Started out on 400 mcg made my insomnia horrible. So after reading your article I took half and the first night I slept good. Second night even better and so on. Thank you so much I’m not 100% cured but moving in right direction.
Hi you say your in Australia but where I live in South Australia are you based here and if not can you recommend a doctor here I can see as most doctors have no idea what you are talking about and can’t help. As I really need help in understanding how to treat this. Thankyou
Hi Sharmane,
I am in Brisbane myself though I do see patients via skype. If you want someone local, I hear good things about Rohan Smith from Elemental Health and Nutrition.
I hope this helps someone. I had been taking a coenzyme b complex and felt amazing. But my hair was falling out like crazy and I developed a weird rash on my face I think from the biotin. I had similar when I took it alone. Best I could find was to get the same methylfolate and methycobalamin separate. The bcomplex has an odd amount of 662 Mcgs or something. But it’s for 2 pills. I was only taking one. Knowing nothing about the side effects I took the whole 1000 mcg of the new methylfolate and was hit with the most severe life threatening depression and body/brain fog. The pills are sublingual and so tiny I’m not sure how I will cut them to appropriate amount but wow I wish I had known sooner. I guess I just stop now and wait for it to clear my system and start again at the low dose. Thank you for an informative article. I found it by looking up methylfolate and depression. This was such a severe reaction I could only attribute it to the one thing.
Hi Bonnie,
sorry to hear what you’ve been through. A couple of pointers: Firstly, yes it may have just been the dose. Secondly, most people need to take the cofactors (i.e. the other B vitamins) in order to tolerate methylfolate well, so your severe reaction to this may have been because you’re taking it alone. You may be better to have a compounding pharmacy make you up the same thing as what you were taking in the B complex, just without the biotin. Thirdly and most importantly, taking methylfolate sublingually is very risky. Not only is the absorption of the methyls into the brain far too quick, but providing methyl groups straight to the oral bacteria can rapidly change your mouth bacterial balance which can throw off your gut flora. I would avoid sublingual forms for folate. (B12 is harder because it is not well absorbed orally, but it’s also less of a problem than the folate.) Choose a capsule rather than sublingual, or as I said, get the whole complex made up by a good compounding pharmacy (shop around, prices can vary widely.) Good luck, and I hope you feel better soon.
I just started taking it. Had a higher dose when I started. Felt side effects, then cut the pills in half (5mil pills) and now have noticed a better sense of wellness, but it’s making me extremely tired as well.
That’s the opposite of what it’s supposed to do side effect wise.
Why is this happening? And should I stop taking it?
Hi Chad,
In some people who have a naturally high histamine level, methylfolate will lower the histamine so well that it feels a lot like taking Benadryl or another drowsy antihistamine. If the effect is fairly short lived after you take it (like a couple of hours) then I’d say this is likely. it’s not a bad thing and I would just advise you take it at bedtime. If however it lasts longer or it makes you tired even in the morning after taking it, or if there are any other symptoms, it may be a different mechanism and it could be worth stopping it or lowering the dose. If it’s helping your overall wellness hopefully it’s the former. It could also be a detox type thing that goes away soon. If in doubt, ask your health care practitioner.
Hi Nicole,
I’m 13 weeks pregnant with my 3rd baby and just found out I have MTHFR. I realized I’m taking a folic acid prenatal and recently purchased one with methylfolate. My Dr. didn’t seem to think me switching prenatals was a big deal but I’m slightly concerned about the potential for my body detoxing to create a harmful environment for baby. I like how you’ve mentioned to start slow. I believe my new medicine is in gummy form and is split up in 6 gummies per day. Any opinions welcome!!
Hi Bibi,
The good news is that the amount in 1/6 of the average prenatal is about right for most people to start on, so you should be fine with that. If you do react, it’s not likely to be in the kind of way that will impact baby.
Best wishes for a healthy pregnancy!
Hi Nicole,
Thanks for writing this article, it’a really helpful! Currently I’m taking 800 mg of Sam-e for almost 6 weeks . It worked very well, since I have (pure) ocd. My intrusive thoughts are less, my anxiety has lessened but some days I still struggle with low mood. Before taking Sam-e I’ve always took magnesium glycinate and that worked very well for 1,5 years. I’ve felt really great while supplementing with that! Could that maybe the reason why the Sam-e some days still doesn’t work that well? Currently I don’t take any magnesium anymore since it stopped working.
Hi Sarah,
Personally I am not a huge fan of SAMe because it depletes folate which can mean it makes you feel great at first (breaking down histamine) but then it stops working, then starts to make you really sick. This won’t happen to everyone of course, but for people with MTHFR, SAMe is a minor disaster waiting to happen. It impairs MTHFR further. So my advice is definitely to be taking other nutrients that support the methylation cycle, including magnesium, and if at all possible, methylfolate or folinic acid, however this needs to be prescribed and supervised by a professional. You may even find that methylfolate (with or without B12) works just as well as SAMe for you, without the risks. Good luck!
Hello,
I was prescribed large dose ofL-Methylfolate and was on it for two years. I just went off of it. My stomach always felt sick and I was sick of taking it. Not sure this supplement was for me but very sure it has made me sick. I see no virtue in it at all and I wonder if I just spent a lot of money that could have been better used for other purposes in my life. A part of me wants to appreciate supplementation as a ticket to good health but another part of me feels supplements are a scam. I don’t want to see it that way but I do.
HI Jay,
I think there’s a middle ground between both ideas. I do not at all believe that supplementation is a ticket to good health. Only getting diet, environment, lifestyle, air quality, water quality and thought/spiritual life right can ever be a ticket to good health, and even then, there can be other random issues that interfere with the best laid plans. On the other hand, individually prescribed supplements by a qualified practitioner can help many people get back on the right track. It doesn’t sound like your practitioner made the right call if you stayed on it for that long without benefit. Unsure if you had a follow up appointment and aired these concerns. If you did, and they kept you on it anyway, then you didn’t have a good practitioner, I’m sorry to say. If on the other hand you were not advised to return to check in, or were just told to take it for life, then that is unwise… I think blanket prescriptions, lifelong prescriptions (in most cases, though not all) and prescriptions just because of a certain gene mutations are essentially scams. Individualised medicine with evidence base is always the way to go. I hope you feel better soon!
I have the MTHFR C377T mut. and have been taking 7 mg Methyl folate for 3 months per my Naturopath. (He seems to prescribe this for all people with the mutation that have anxiety.) I have a history of Sibo and Dysbiosis, and now wondering if the MF has been irritation my gut, because bloating seems to have gotten worse in the last 3 months since taking it. It appeared that my brain fog improved on it however, and that’s why I continued. Should I just stop cold and see if the bloating gets better. It’s so hard to dissect what symptoms comes from what!
HI Kathy,
I definitely can’t advise you on what to do with your supplements since someone else prescribed them, but I do think a 7mg dose is very high and I have never needed to use that much. I haven’t heard of methylfolate causing any gut issues (except in people who have immediate reactions, but not long term) however I’ve also never used such a large amount! I would address the SIBO and dysbiosis and then you shouldn’t need methyl folate – or at least not often or as much. Have a read of my post about MTHFR not being “the answer” for some more ideas about how to step back and look at root causes which far outweigh genetics.
Good luck!
I’m in Walnut Creek California. Can you give me the name of a Naturopath or Nutritionist who can help me taper off 7 mg of methyl folate? I do have the MTHFR C677T mutation and a Naturopath who believes in high doses of MT put me on this. Now I realize it’s not good. I also may have Sibo, but hard to tell since I think the MT is causing GI symptoms now.
Thank you for your very helpful info.
Kathy
Hi, I am a 31 year old nurse anesthesia student, and I have been convinced since I was in my early 20s that I have MTHFR. My main concern right now is the extreme fatigue/brain fog that I can’t seem to kick which is making school even more of a challenge. I have every symptom of a B12 deficiency, but every time I get my levels drawn my serum b12 is sky high. Even when I’m not supplementing with b vitamins (methylated or not). This leads me to believe I have a methylation issue. My folate level is typically on the lower side. I purchased a 23 and Me kit a few years ago, but my sample was deemed inadequate and they failed to mail me a new kit. I’ve never had a homocysteine level drawn. (As soon as I get insurance through school, I’ll request a homocysteine level and MTHFR testing).
My question is: if I do indeed have one of the various MTHFR mutations, would it be advisable to start very slowly supplementing a low dose methylfolate in addition to my methylated b vitamins? Additionally, what are the benefits of supplementing with SAM-e? Would it be safer (side effect-wise) to begin a low dose SAM-e regimen, like 200 mcg BID or QD, rather than methylfolate, or can they be used in conjunction?
Hi TJ,
You may be right that you have functional B12 deficiency, but you will need practitioner help to work out what cofactors you are missing to help you get it into cells. Lithium orotate (or lithium in foods such as lemons) is one that comes to mind which could help but must be prescribed by someone who has taken your whole health history. I would follow up with 23andme – they are supposed to replace the kits!
If you have a mutation you need to reduce any stressors on your enzymes first and foremost (see my post about MTHFR not being ‘the answer’.) After that some people will benefit from supplementing methylfolate or folinic acid, but not all. I would avoid SAMe like the plague. It is unsuitable for those with MTHFR mutations as it slows down MTHFR further. SAMe made me and several of my patients very very sick. (It tends to make you feel marvelous for the first few days though so people get tricked into taking it longer term.) Good luck finding a practitioner to help you!
Hello Nicole. Great article. I am an engineer disabled from the neurological damage caused by benzodiazepines. In an effort to slow the progression of the disability, my doctor decided to reinstate on diazepam. I am now tapering off very slowly, but there is extensive damage, and I have been on it too long, again. If anyone is listening, avoid benzos are intended for VERY short specific medical applications. If you have never taken one, don’t and if you are on one, speak with your doctor about tapering off. The hurt far more people than they help.
I have been studying the heck out of neuroscience and metabolism for years now, and you seem to know your stuff. One of the many bad things diazepam does is slow the clearing of histamine, while simultaneously increasing ones sensitivity to glutamate. So as we avoid free glutamate foods, we also avoid the foods that would nutritiously clear our excess histamine.
Methyfolate can be particularly problematic, as it is a very powerful biogical form of glutamate. I have NEVER felt as bad as the deplin made me feel. Whoa. But at this point I have such histamine overload and folate deficiency I need to do something.
I like the idea of folinic acid, and will have some in my possession by the end of the week. I was going to combine that with both hydroxy B12 and either TMG or SAMe. I am so sensitive that I will be following a very low very slow titration up of everything.
Then I saw your comments above on TMG and SAMe, and I am second guessing myself. I know you cannot give medical advice, so let’s speak generally. If one finds himself folate deficient, and overloaded with histamine, is not MTHFR, (COMT heterozygous, so as you pointed out, pretty normal genetically) but is very sensitive to methylated vitamins and glutamate, can you think of a reason to use or not use TMG or SAMe? I would love to know you thoughts.
Thank you.
HI Eric,
TMG is a very useful supplement to take, and if you’re not hypersensitive to methyls, no downsides to it. I definitely don’t think anyone should be taking SAMe!
And I totally agree you about benzodiazepines. In fact I am not keen on any medical drug that messes with the brain chemistry. None of them are addressing the cause, all have potentially serious side effects or withdrawal effects.
Good luck with your experimentation,
Nicole
I was recommended to take Deplin 15 mg because I don’t process folate due to mthfr mutation. I’m also taking vescepa for cholesterols s triglycerides levels. I had a blood test done when I was experiencing high anxiety and panic attacks and my LDL and HDL levels were awful. I’ve since lost 12 lbs down to 121 lbs and walk everyday. Dr also prescribed coq10 with magnesium and red yeast rice. Also, I had been taking 5 -mthf but stopped to take Deplin. I felt it was all too much and so I’ve only been taking the vasepa, my bio identical hormones of estrogen, testosterone, and progesterone (low doses), DIM, and coq10 2xs a week the red yeast rice makes me feel itchy so I don’t take it.
On and on , sorry I know
II took Deplin 2 days now and strangely I felt more at peace, slept really well last night(which lately has been a real struggle), but almost too well. I woke up feeling dazed and stunned and a little jittery inside. It’s hard to tell if the jitteriness is from feeling anxious for days or from something else. I don’t know if I should continue with Deplin. I need something to help me with my anxiety but don’t want to experience being over Methylated. What is an alternative to Deplin if it’s too strong?
HI Kat,
The idea that you need to take high doses of folate like deplin if you have an MTHFR mutation is a total myth. Some people with mthfr mutations will benefit from taking folate, but not at doses like that.
The biggest issue with deplin is the very high dose. it’s just 5-mthf at silly levels, plus unecessary additives. If you feel some benefit from deplin but also the side effects, chances are you’d be just fine on 500-1000 micrograms of plain 5-mthf capsules. I don’t understand why anyone would stop your 5-mthf just to get you to take the same thing, when they could have simply tried a slightly higher dose. Get any artificial foods, toxic air and water out of your life and you may find you dont’ need any mthf at all! Good luck.
This is an awesome article. Thank you for this. I suspect I may be taking too much Methylfolate but unsure… It’s 800mcg in total now.
I’d been taking 400mcg from my B complex vitamin supplements for a couple months. Recently i was given an iron supplement that ALSO has methylfolate in it (and other B vitamins). On Friday i took both the iron tabs and the B vitamins… and felt quite crap. Been feeling it today too… Is this increase in methylfolate affecting me?
My symptoms are feeling wired but tired, jitteriness, heart palps and tiredness. I dont drink coffee so this hasnt been the cause.
That does sound a lot like over-methylated symptoms. I’d definitely take a break from all methyls for a few days and don’t take so much at once in the future.
Hello,
Im from Brazil. Here in this world…Looking for answer about methylfolate.
I take 1 week deplin (15mg).
First few days increase energy in general, wake up not fatigued, libido better.
After 1 week very angry and nervous.
And after fatigued. Very fatigued.
Do you think it was due to a very high dosage?
Hi Diego,
Deplin causes so many problems. The dosage is WAY too high for anyone and I don’t think it should be on the market. Yes, your response is typical for taking Deplin or anything with such a high dose. You would probably need a break for a few weeks then maybe you would be ok with just 1mg per day. Please find a practitioner who knows what they are doing and uses something better than Deplin!
Do the symptoms go away in time? I’m okay with feeling crummy if it’s going to get all of the gunk out of my pipes. Is there a danger to that?
It depends on what those symptoms are. If it’s muscle pains, fatigue, typical “detox” symptoms then yes, they can go away after the gunk is gone, as you say. But if it’s jittery, high blood pressure, heart racing, nervous, mood problems, then it’s from too many methyls and you would need to discontinue, let it pass, then start back on the supplements in the manner I describe, not taking so much that these symptoms return. They don’t just pass if you continue.
Hi,
I am 47 yrs old male who six years ago suffered from central vein retinal occlusion. Following that incident, I have been diagnozed antiphospholipid syndrome. Genome sequencing showed a homozygous c677t mutation, hetero COMT and heterozygous prothrombin mutation.
I am taking Plaquenil and vitamin K antagonist for preventing thrombosis and one year ago have started taking 1mg of methyl folate and 500mcg methyl b12 due to homocystein being at 12. Short time after the start of methyl Bs, I have developed insomnia and facing restless legs syndrome. My brain fog improved though, probably due to improved methylation.
Recently, I have incorporated DIM , Rhodiola Rosea extract to cope with estrogen dominance (love handles and gynecomastia) and sometimes Niacin before sleep (to neutralize over-methylation) and that seems to help a bit with the insomnia and well being.
Would you advice me to introduce TMG in the morning together with methyl B12 and methylfolate and what other supplements could be beneficiary for fatigue and brain fog?
Hi Nikola,
Thank you for your comment. You have obviously made some really important connections about what’s going on in your body. Unfortunately I can’t give specific medical advice on this blog (i.e. suggest supplements for a specific person) as that really requires a practitioner to have an appointment and make sure that it’s a prescription tailored to the individual. There is just so much to consider. One thing I can suggest is that rather than looking for supplements that can help with fatigue and brain fog, you go looking for the source of those symptoms – is it mould, heavy metals, EMF exposure, stress, poor sleep, poor oxygenation of the blood, chronic virus??? There is a long potential list of causes. I hope you are working with someone who can help you get to the bottom of it!
I have two mutations. I work with a great naturopath here in Colorado. We tried methylfolate but I had the typical reaction. My husband who only has one mutation but has elevated homocysteine took massive doses of the methyl and had a very bad reaction. After that she just suggested eating greens everyday. The problem is that in the current pandemic and being a teacher under a LOT of stress, we agreed that I probably need more folate. We are trying some methyl while I wait to try folinic acid. In your article, you mention taking a smaller dose of methyl – maybe a few hundred mcg. The lowest of methyl I’ve found in the States is 400 mcg. Would you suggest opening one of those up and dumping half? Also, from your experience, do people react to folinic acid the same as the methyl and what is a standard or low dose of that? After reading this, I will pass this off to our ND as she is always learning and growing. Thanks again.
Hi Amy,
If you were taking more than 400mcg to start with that was way too high. I would sometimes start my patients on 400mcg per day but only if I was very confident that they were highly unlikely to be over-methylators – something I would only be confident in if I had their genetic test results or a long history of watching their reactions to supplements. Even 400mcg will be too much for you, yes. I would start with no more than 50mcg per day if you had a terrible reaction. 100mcg if it was moderately mild. Don’t forget to read up about the importance of B12 with it. Folinic acid does not usually cause reactions – or at least not methyl reactions. It can trigger a need for increased B12 however. With folinic, your absorption is only 50% of what it is with methylfolate, so I would say a basic dose of folinic is 800-1000mcg, and there is usually not much reason to start lower than that. Doses could go up to a few grams if you had a compelling reason why you need so much. Stress and COVID I don’t think are adequate reasons to justify more than 1000mcg. Pregnancy justifies 2000mcg, or more if there is a history of birth defects in baby.
As a guide, I personally have 2 mutations and I take 400mcg of combined (50:50) methylfolate and folinic per day in a multivitamin. If I have a reaction to something and I can feel I need detox support, or if I am awake at night with histamine-type symptoms, I will take 1000mcg methylfolate with 2000mcg methylB12 on the spot. (This would happen to me about once per month). If I am very unwell or wide awake for hours, and the first dose doesn’t work, I may take this a maximum of 3-4 more times in that day. This type of high dose I would only be using a few times per year at the most. Hopefully that is a useful guide for your ND about what I have found constitutes a ‘high dose’ vs a ‘standard dose’. My body just LOVES methylfolate and MB12, yet I would never take, or need, doses like the type of thing I often see prescribed in the USA. They just make me shudder!
Thank you for this amazing article
I have been researching and trying different supplements for a while now . I realised I can not take a b complex even with the correct forms of B12 or folinic acid …I just feel fried and then crash around 5pm in a brain fog low mood coma.
I react really bad to any methyl B12 I even started at low dose of 500mg sublingual by cutting the tablet and most in Australia are sold at 1000mg
I have tried a good quality expensive b complex naturopathic brand with a combination of methyl folate….the other b’s and a smaller dose methyl B and still reacted very anxious or Extremely tired.
I read that is that’s the case then I should supplement with folinic acid on its own …
I popped my first folinic acid on its own( seeking health brand) which is Dr Lynch’s brand I believe??
Folinic acid At 800mg I had an instantmigraine and felt like I was so nausea.
Totally lost with this rabbit hole any suggestions would very helpful!
hi Josephine,
What you are describing with your reactions even to folinic is most likely 1 of 2 things:
-Either you are very toxic and even folinic acid is triggering a detox crisis that you are not in a position to handle, or
-You are deficient in something that folate and/or B12 depletes, thus instantly making you worse if you take it. Candidates include B1 and potassium. B12 is another possible deficiency which could make you worse when you take folate, and your reaction to methylB12 could be due to the methyl component. You could maybe ask your practitioner about trying you on hydroxy B12 or adenosyl b12.
More likely I would say is that you are dealing with some kind of toxic load and putting the B vitamins in is too early. If your minerals are not well balanced or you’re full of heavy metals, B vitamins can feel too stimulating, as you don’t have the right resources to deal with the metabolic shifts you are creating when you take them. I would ask your practitioner to help you investigate your mineral status and balance that before trying Bs again.
Bear in mind that you may not need Bs at all.
Good luck,
Nicole
Hi Nicole
Thanks so much for taking the time out to explain all this.
Just the other day I was thinking the same thing that my body has been overloaded with too much processed food etc and I’m going into an instant detox with the folinic acid or Bs..in regards to my migraine reaction to seeking health 800mg well I cut the tablet in half and even that made me have sore muscles and fatigue very similar to how I feel when detoxing from coffee! So go figure.
I have been reading a lot about adeno B12 suppose to the methly ) so I will try that aswell
Once I have fixed up my diet and balanced my minerals such as iron; magnesium and Vit d.
Hi Nichole!
Thanks you for your work on this! Ever since I tried to detox my methylation pathway, per a RN treating people through bio-meridia, I have been dealing with what appears to be schizophrenia. I never ever had this problem before taking mythle protect (optimal methylation support formula) and at first I was just taking the methylation form of B-12 which was even worse. I kept cutting back my dose and cutting back my doses. I finally went fully off a year ago but my life is still a huge struggle half the time because I never returned to “normal”. At first it made some things better like being able to get out of bed much easier in the morning and being a lot less fatigued by the end of the day (I had been previously diagnosed with hypersomnia.) Because of this I continued to take it and just cutting back my dose more and more hoping what I was experiencing was just part of the detox and would eventually go away but it never did. I can’t sleep anymore and have kind of like hallucinations that are very schizophrenic in nature. I have spoke to my naturopathic doctor and they believe that is whats going on with me and it was due to stimulating that pathway. I don’t know they really know I they can help me fix that problem specifically which unfortunately is wreaking so much havoc on my life. I have pcos and my hormones are also a problem so their biggest priority right now is just to get me to go to the bathroom everyday opposed to every other. They have a detox for my liver they want to try me on, and they are just trying to get me to steer clear off anything thats going to stimulate that pathway. Especially folate. I did see what you said about niacin on here and out of desperation I am going to try it but I will very much pay attention to my body and if it seems to be making my problems worse stop taking it immediately. I’m just desperate and is hard not to feel hopeless and like I’m going to be stick like this forever now. If you have any advice at all it would be so greatly appreciated. I feel like nobody really knows alot how to deal with the fall out of this, even the person who originally started treating me. Thank you so much for all you help!!!!
I really hope the niacin helps you. It’s the only obvious nutritional thing I can think of, other than Potassium, which can be depleted by B12 as well. Perhaps your practitioners can assess your potassium needs. Good luck.
Thank you for this article…I have been researching for years that most people and B12 deficient and how beneficial it is for the mind and nervous system to take B12 as if can give your energy etc. I have tried a couple of good brands now of metholcobalin and have even hunted around for the lowest dosages ones that are hard to find!…I then even split the tablet to make 250mg …and yet when I take it I’m so sore all over and feel like a need to lay down just achy..similar to a chronic fatigue muscle aches…
I’m confused I thought its ment to make me focused and perky! Nope.
Anyone else experienced this what the sore body?
Yes this is quite commmon in a methyls reaction. If you changed to Hydroxy/Hydroxocobalamin (both the same thing) then you would probably not have this reaction. I also suggest you steer very clear of methylfolate if this has happened to you from methyl B12!
Thanks for your reply Nicole. I have been Looking for a non Methly B12 here in Australia ..and haven’t been able to find the adeno or hydroxy one anywhere in health shops. Can you recommend a good brand of either the Hydroxy or Adeno one that I can order online ?
Cheers Eleanor
The brands I know of that have a hydroxy B12 are MTHFR Support, RN Labs and I think Biopractica. They are all practitioner brands but you may be able to get them at a health food store that has a naturopath if you don’t have your own practitioner. I do recommend working with someone though as there is the potential for problems any time you are self-medicating. Good luck!
Thank you for this amazing article.
4 years struggling in this area without sound medical support in my country 🙁
Kind of histamine intolerance.
* l-glutamine (very small dosage 200mg), whey or hydrolyzed collagen are kryptonite for me -> hard insomnia.
* oxalate rich vegetables (celery, sweet potato, beetroot) -> alteration of sleeping (groaning), but not too hard insomnia.
* histamine rich foods and beverages -> medium to strong insomnia
I tried two days with methyl-b12 and afterwards I had two days with nervousness / anxiety and insomnia.
* Mg citrate and Mg glycinate are also an issue for me.
* relatively-Intense exercise or stress are also triggers.
I feel my self with the over-methylator profile according to the external character. But anxiety is fully under control 🙂
I don’t know whether over-methylation is making difficult removing histamine but I don’t understand the reaction to oxalates rich foods. My Homocysteine level in blood test 9,05 μmol/L (in a range of 5,46-15,00). Histamine levels is within the interval or not too far over the upper limit. DAO enzyme is perfect. T4 and TSH hormones are also ok.
How can I facilitate histamine degrading ?
Why glutamine is so hard for me ?
What could be good as a rescue for those horrible nights ? niacine B3 ?
I don’t dare to try methylfolate (folinic acid is at Spain only available for hospitals I think) given the reaction to methyl-b12, but maybe it is worth a try in small dosages? going up step by step?
Many thanks for your kind help!
Pedro. Spain
HI Pedro,
Sorry to hear the difficulty you are in. A few things that might help you:
Oxalate triggers a histamine release so that may explain your reaction to it. Also it irritates the bladder so much that this can disturb sleep.
Magnesium citrate and glycinate can both trigger release of stored oxalate from the body, which may cause the same symptoms.
Over-methylators are people who tend to overmethylate when given methyls, but they can still be undermethylating the rest of the time. This is probably you.
I would consider trying to find hydroxycobalamin if you can instead of methyl. It may still be worth trying tiny doses of methylfolate though.
Best of luck!
Many thanks for your help!!
why do you think I react terribly to glutamine, whey, etc….also because they are methyl-donors?
best regards
Pedro
No, that will be because they can convert to glutamate which is excitatory and causes problems for many people. It’s totally unrelated to methylation. It’s the GAD gene snps that will be involved there, and it’s pretty common to react badly to glutamine because of these.
Such interesting information. Came across this post just researching potential things to look out for in supplementing folate.
I have no clue what my genetics are but I do know I don’t get enough of it in my diet. I seem to get plenty of B12.
Either way, if someone doesn’t know their genetics, is Methyl folate best or folinic acid?
Thanks for the post!!
I would always try to increase your dietary folate first (not with spinach – long story, but it’s not a good food!). If that isn’t possible, then folinic acid is a safer bet than methylfolate.
Thank you for helping me understand the weird situation everytime I take Methlyfolate. Could you help me in how do I split up the capsule. It is a shame that it is not in caplet, so it can be divided more easily. Thank you for your help.
You can just pull apart any capsule and tip some of the contents down the sink, or into a spare capsule from a pharmacy if you want to save it. Very easy once you try.
Hi Nicole
Thank you so much for the article, very informative. Also, thank you for answering the comments, I’ve read all of them and the answers were helpful too.
I’ve been struggling with moderate depression since 2-3 years. I have moderate anxiety and occasional episodes of deep sadness.
My genetic testing indicates that I have a MTHFR mutation, but since I started the suplemment (250mcg methylfolate + 150mcg methylb12 + 15mg P5P), around four months ago, I had no improvements, just got worse.
I don’t know what I should try next. In my case, 100mcg methylfolate + 100mcg folinic + 30mcg methylb12 + 30mcg hydroxib12 + 10mg P5P one or twice a day seems too much or too little? Or should I try using only the non-methylated forms?
Thank you for all your attention!
HI Lucas,
I really can’t advise on specific treatment for someone without an appointment, so I can’t say whether that supplement will be helpful for you or not. I would just say that what you have described in both supplements has very low levels of B12, which may be part of your problem (normally B12 doses start at 1000mcg, whether it’s methyl or hydroxy) and also that you should not assume that MTHFR has anything to do with your anxiety or depression. It is MUCH more likely that your gut flora, diet or psychological and spiritual factors are at play. Please read my other article “MTHFR is not THE answer” for more important things to consider than MTHFR. Good luck.
I have an MTHFR mutation and started 7.5mg of Methylpro on March 21st, 2020. I don’t really notice much of a difference, other than the fact that my menstrual cycle is messed up. One week after starting Methylpro, I got my period for the second time that month (I got my period on March 14th and again on March 28th). It is now April 14th, and I again have my period. Do you think it’s possible that the methylfolate is affecting my hormones and could be responsible for the irregular bleeding?
I have not heard of methylfolate worsening hormonal cycle but that might be because I have never used such a high dose, and would never recommend it. So perhaps it is the cause, but I couldn’t be sure. Normally I would never suggest more than 2mg of methylfolate per day, except in unusual circumstances for very short term use.
Thank you so much, Nicole. I have started Jarrow’s methylfolate at 400mcg per your suggestion. Thank you for your insight and help!
Hello! I wish I had found this article years ago! I have a homozygous MTHFR A1298C mutation and was prescribed 5mg of methyl-foalte (Thorne’s Methyl-Guard product) AND IT WAS FRIGHTENING! But I felt crazy mostly because every source was telling me how much better it should make me feel! Ugh, so confusing and misleading. I’ve been basically afraid to take any extra methylfolate (or methylcobalamin, bc I thought that was a part of the problem too for a while)…but am glad to read this post and understand that I should start back up slowly.
Am I wrong in thinking that high doses of activated B12 could also be a culprit in making me feel so shaky/crazy/sick/anxious?
HI Madeline,
I’m so sorry to hear you went through this. Yes, methylB12 can also cause problems, even at low doses, though I find that slightly less common than reactions to methylfolate. It probably helps that few people prescribe ridiculously silly high doses of B12, unlike with folate. Be mindful that just because you have MTHFR mutations doesn’t mean you need to supplement at all! That should be assessed based on symptoms and preferably testing of your levels.