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Methylfolate: why do some people feel so bad when they take it?

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:

  1. recommending high-dose folic acid; and
  2. 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!

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Reader Interactions

Comments

  1. 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

    Reply

    • 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.

      Reply

  2. 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.

    Reply

    • 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

      Reply

  3. 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!

    Reply

    • 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.

      Reply

  5. 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.

    Reply

  6. 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.

    Reply

  7. 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.

    Reply

    • 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.

      Reply

      • 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!

        Reply

        • 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!

          Reply

  8. 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.

    Reply

    • 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.

      Reply

  9. 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.

    Reply

    • 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.

      Reply

  10. 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.

    Reply

    • 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.

      Reply

  11. 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!

    Reply

    • 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!

      Reply

    • 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.

      Reply

  13. 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!

    Reply

    • 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

      Reply

  14. 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.

    Reply

    • 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.

      Reply

    • I would think the chances are pretty slim. But if there were enough factors at play in a perfect storm, I guess theoretically possible.

      Reply

    • 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.

      Reply

  17. 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.

    Reply

    • 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

      Reply

  18. 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

    Reply

  20. Hi,
    Are you able to take the Prenatal vitamin if you don’t have the gene?
    Will there be any side effects?
    Thank you

    Reply

    • 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!

      Reply

      • 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!

        Reply

        • 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!

          Reply

  21. 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.

    Reply

    • 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.

      Reply

  22. 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.

    Reply

  23. 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 😔

    Reply

    • 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.

      Reply

  24. 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?

    Reply

    • 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!

      Reply

  25. 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.

    Reply

    • 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

      Reply

  26. 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.

    Reply

    • 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!

      Reply

  27. 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!

    Reply

    • 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.

      Reply

  28. 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

    Reply

    • 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

      Reply

  29. 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?

    Reply

    • 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!

      Reply

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