The best dose of methylfolate for MTHFR mutants

MTHFR mutation is a huge factor in physical and mental health but we’re still learning the basics because it’s all very new research so the best dose of methylfolate for MTHFR mutants isn’t really a straight answer.  The good news is there are lots of ways to read your body and to learn the best dose of methylfolate for YOU. If you’re a little fuzzy on this whole MTHFR thing, then check out this post on the MTHFR basics.  This will give you a good framework for the whole conversation – also if you suspect you have the mutation, read more about how to know you’re a mutant here. If you, like me, already know that you’re a mutant then let’s tackle the hard problem of finding the best way to compensate for your body.  Finding the right dose of methylfolate can help to reduce anxiety and depression, stabilize mood, boost fertility, protect your heart and cardiovascular system and generally keep your body at peak performance so it’s important to take some time and do this the right way.

Finding the Best Dose of Methylfolate is a Process of Trial and Error

I wish there was just one answer – this is the right dose, but sadly it all comes down to what is the right dose for your body.  First off, I never suggest taking methylfolate by itself without any other B vitamins.  The B vitamins all have overlapping functions and so it’s important to have decent doses of all of them.  Typically though I start clients with a B complex that has a reasonably low dose of methylfolate – like maybe 400 mcg.  I really like the one from Pure Encapsulations called B Complex Plus. It’s basic, simple, and most people – even hard core mutants – tolerate it pretty well, but I’m not married to it. Any good multi-B with a low-dose methylfolate will do or you can look for a multivitamin that has methylfolate in it like Thorne Research Basic Nutrients.  Occasionally even this low dose creates a bad reaction – if that happens then we’ll have to start with a low dose MTHF by itself and split the capsule apart but this is the option of last resort. First, let’s try the low dose B complex or multivitamin and see what happens.

Keep in mind the first three days of any MTHF might be difficult and there may be some adjustments. You may  notice that you’re a little agitated, or anxious, or depressed or just feel a little spacy or off. With any luck that should pass pretty quickly and we’ll wait for things to stabilize before increasing the dose.

If the Low- MTHF  B Complex or Multi Works for You

Great! We’re on the right track.  Even if this is the right dose for you there might be a few odd adjustment days in the beginning – that is totally normal.  Just wait until everything settles down and see how you’re feeling.  Typically with this low dose people may notice a small spike in energy or a little boost to mood, but often it isn’t enough methylfolate to start to touch the issues – that’s okay because it’s enough to get the ball rolling.  The next step would be to add a 1 mg (1000 mcg) MTHF by itself to the B complex you’re already taking. We’re looking to make forward progress without rocking the boat too much.  Each time you increase the dose there may be another adjustment reaction as your body gets used to things, so try to stick it out for 3 days before you make a final judgement about it.

If the Low-MTHF B Complex or Multi DOESN’T Work for You

Then we switch to plan B.  Plan B is a little messier and more tedious, but it could make all the difference for how you’re feeling on a day-to-day basis.  Start with a 1mg MTHF – I prefer a capsule so that you can just open it and portion out the powder (instead of trying to cut or crush a tablet). In this situation start with 1/4 of the capsule – easiest is mixing it with some peanut butter, applesauce or yogurt and taking it that way.  It tastes pretty gross, but hopefully you can hide it in something. Again count on about 3 days of adjustment, but we’re starting with very low doses here so hopefully that will be fine and if it’s still too much then you can cut it down even further. Once you get to the dose you can tolerate, keep it there for a couple of weeks and try to slowly increase.  By now your body has started to process some of the back-log of work so it might be easier to tolerate a bigger dose. Now would be a great time to try going to the B complex with MTHF or multi with MTHF because you do still need all those other B vitamins.

What to Do If You Can’t Tolerate ANY MTHF?

Yup – I’ve seen clients like this. They take the tiniest amount and spiral into depression or anxiety attacks or start to feel itchy. Not fun at all!  In this situation it’s tiny-dose niacin to the rescue.  For whatever reason taking about 10-50 mg of niacin  – this is usually 1/10th or even less of a 500 mg niacin tablet.  It’s a tiny dose, but for many people it really helps to ease the transition into MTHF.  Start again with a small dose from the opened MTHF capsule (maybe 1/4) and add a tiny shaving off the niacin capsule and see how you do.  The niacin seems to buffer things a big so that the MTHF is a little bit easier to tolerate – again it’s about helping your body to do some of the work that has piled up in the absence of activated B vitamins. If niacin doesn’t help then sometimes hydroxycobalamin will.  This is a little bit mysterious because you’d think it would be methylcobalamin (the methylated form of B12 which MTHFR mutants also have a hard time making).  Oddly, the hydroxycobalamin form seems to be the most helpful when you’re starting MTHF dosing and when niacin doesn’t take the edge off, a lot of times hydroxycobalamin will.  Do you see what I mean about trial and error?

Methylation, it's complicated. The best dose of methylfolate is out there for you - you just have to find it. Thanks to flickr user Franklin Park Library for the image.

Methylation, it’s complicated. The best dose of methylfolate is out there for you – you just have to find it. Thanks to flickr user Franklin Park Library for the image.

How Do I Know I Found The BEST Dose of Methylfolate?

We are doing all of this to help you feel better as a whole human.  Methylating your B vitamins or taking methylfolate is supposed to help boost your energy, stabilize and elevate your mood, help your body with detox reactions and reduce a wide variety of symptoms over time.  So how do you know you’re’ at the perfect dose for you?  Well – you should feel better.  Keep in mind the prescription methylfolate comes in 7 mg and 15 mg doses (deplan).  Those are a whole lot bigger than the doses we’re starting with above so when you find a good starting dose for yourself then stay there for a couple of weeks.  If you’re feeling fine and stable but not a lot of improvement then try a higher dose and see how you feel with that. For everyone there is a sweet spot where they feel better and more energetic, but not anxious or wound up.  Keep in mind every time you increase dose those first 2-3 days may be a little bit odd.  Don’t judge by those days.

Things to Remember:

  • You need all the B vitamins, not just methylfolate so don’t leave those out of the mix. A good methylated multi or methylated B complex is a great foundation to start with.
  • Methylation affects neurotransmitter formation, inflammation and detoxification so lots of random symptoms can pop up when you increase the dose. Give it a few days before you make judgements.
  • Increasing doses slowly is easier for your body to tolerate than just dumping a high dose in all at once.
  • Tiny doses of niacin can help smooth out the transition.
  • Hydroxycobalamine, a form of B12, can also help to make taking MTHF a little easier.
  • Every body is different so the best dose of methylfolate for you could be completely different from the perfect dose for someone else.
  • Every MTHFR mutant has mutations in different spots and combinations plus a whole host of other genetics to deal with. Don’t get discouraged – there is always a perfect solution, you just have to find it. Generally though the more mutations you have the longer it might take to find the right balance.
  • Methyl donors like Trimethylglycine (TMG)  which is also called betaine anhydrous can also support this process by donating methyl groups for your newly-functioning methylation pathways to use.
  • Riboflavin-5-phosphate also supports methylation and homocysteine metabolism (which tends to build up if you’re not a great methylator) so sometimes a small dose of this will help things out as well. It should be in a good B complex.
  • It’s important to avoid sources of folic acid (which there are many – think all of the “enriched” grain products like cereals, breads, pasta) including multivitamins with folic acid or vitamin-enhanced foods. Plain old folic acid will compete with the methylfolate you’re taking and make it harder for those pathways to work.

Specialty Methylation Products

There are a few great methylation products out there that have a combo of supportive ingredients.  One of my favorite is Methyl-Guard Plus by Thorne Research, which combines a reasonably high dose methylfolate with methyl-B12, TMG and riboflavin-5-phosphate.  It can be a high dose to start with though, so especially if you have a few mutant genes it’s a good idea to start with the lower dose products and work your way up. There is no sense shocking your body. Too high a dose can cause as many problems as too low a dose so it’s important to find your sweet spot.

The bottom line is that this is no different from any other aspect of health. You need to find the right thing for YOUR body and there is no one size fits all.  The best dose of methylfolate for you is out there – you can find it.  I feel like the biggest thing is to ease your way into it and not over-flood your body. Start slow and work your way up – better to get there slowly than to give up because you felt so bad when you tried the high dose.

276 thoughts on “The best dose of methylfolate for MTHFR mutants

  1. Gary Smith

    Hi Amy, I sent a note about my year long insomnia to a doctor in Mexico. He suggested that I get tested for MTHFR gene regarding the depression I have lived with since I was 6. That is how I stumbled upon your blog. I am scheduled to get blood work in two weeks for my 6 month endocrinologist appointment. I called her office and they added the MTHFR test to my order.

    I have seen four sleep medicine doctors without any real help or solutions. The first put me on Sleep Restriction Therapy for three weeks that did not really address the insomnia, the second recommend additional sleep medication and the basic FAQs on insomnia that anyone can find on the internet, the third wants me to do a sleep study (I did one with the first doctor but he did not include the sleep apnea portion) and the fourth recommended more medications. I have now tried 7 medications! None have worked any better than the supplements I have tried.

    I have had depression since I was 6 years old. I am presently 52. Over a 5 year period I tried 11 different medications with two different psychiatrists. The last 2.5 years I was on a cocktail of Lamictal, Zoloft and Abilify. I weaned off of all three according to my psychiatrist’s directions. The last pill I took was Abilify on October 8, almost one year ago. About one week later I developed pretty bad insomnia.

    I fall asleep most nights right away (though I have had some rough times falling asleep since being off of the sleep restriction therapy). I get into bed at 10:30 pm and fall asleep around 11 pm. I wake up around 2 or 2:30 am and am unable to fall back asleep within 25 minutes or so. So I go downstairs, read and go back to bed maybe 20 minutes later. I generally fall asleep right away and wake up maybe an hour later. If I am lucky I fall asleep for another hour or so before being wide awake an hour to an hour and a half before my alarm or whatever time I wish to get up. I get on average 4.5 – 5 hours or choppy sleep.

    I don’t know if I am living with withdrawals from the medications or if my brain has been harmed from 5 years of being medicated. I don’t know if the insomnia will resolve some day with time or if this is caused by the depression. Have you worked with patients who have weaned off of heavy depression medications?

    I have now tried 7 sleep medications in addition to close to 40 different supplements just for the insomnia.

  2. Tamera Shoemaker

    Hi! I found this article while experiencing some severe symptoms of depression. I wracked my brain and the only thing I had changed was my supplement. I switched from the Thorne methyl guard (2 caps) to the Thorne Methyl-Guard Plus (1 cap). It’s been a little over 2 weeks and I feel like I’m going crazy! I have been on 50 mg pristiq for the last 4 years.
    So my question is…can switching those cause this much havoc??
    Please help!
    I reached out to my naturopathic doctor and she said she hasn’t seen this before. She suggested I stop the Methyl-Guard plus and see how I feel in a week. Meanwhile I can’t work, I’m sleeping horribly and I feel like crap. 🙁

    1. amyneuzil Post author

      Hi Tamera,
      This is a strange one, because really, the dose between 2 Methyl-Guard and 1 methyl-Guard Plus isn’t that significantly different. Having said that, anything is possible and I think it’s worth doing your own self-testing and switch back to see if that helps. Honestly, with the MTHFR mutation, it seems like every body is so very specific in the things that it responds well to. It just isn’t safe to assume that because I don’t see the reason for the changed reaction that it couldn’t be a contributing factor (or, the actual cause). IF you do try taking a break from the M-G Plus or switching back to M-G, please let everyone know how it goes!

  3. ragen gwin

    I am trying to find the right supplements to take for my MTHFR gene mutation.
    I got my lab results back and I carry one MTHFR C677T mutation (heterozygous) and my MTHFR enzyme activity is reduced to 60% of normal activity.
    my test details involved:
    MTHFR- Genotype: 1298a>C AA and the allele tested 1298A>C,
    as well as
    MTHFR- Genotype: 677C>T CT and allele 677C>T.

    the test summary stated below:
    Gene: ANKK1/DRD2- phenotype: Unaltered DRD2 function
    Gene: CYP2C19- Phenotype: Normal Metabolizer
    Gene: CYP2C9- Phenotype: Normal Metabolizer
    Gene: CYP2D6- Phenotype: Rapid Metabolizer
    Gene: CYP3A4- Phenotype: Normal Metabolizer
    Gene: CYP3A5- Phenotype: Poor Metabolizer
    Gene: VKORC1- Phenotype: Low Warfarin Sensitivity

    the supplements I am currently taking are:
    Fish oil 1000mg with 300mg Omega-3
    Now EVE capsules Superior Womens Multi
    Pantothenic Acid 250mg- taking for acne
    l-carnitine 250mg- taking for acne
    niacinamide 250mg- taking for acne

    my question is what would you recommend supplement wise to support my gene mutation? the multi vitamin contains 25mg thiamin, 25mg riboflavin, 30mg niacin, 25mg vit B6, 800mcg filate, 200mcg vit b12, and 50mg pantothenic acid.

    if you could give me any advice as far as adding supplements that would be amazing. I was taking deplin l-methylfolate at some point but it got too expensive and I forgot the amount I was taking.

    Thanks so much!

    1. amyneuzil Post author

      Hi Ragen,
      It can be so confusing, can’t it? The first step is to check with the manufacturer of your multivitamin to see if the folate is actually natural folate or if it’s folic acid — sadly, labels aren’t always clear. If it’s folic acid then switching to a multi with 5-LMTHF would be better. The next thing is to think back to the time when you were taking the deplin. Did you feel well with it? If you did, then it would be a good idea to start adding a pretty hefty dose of the 5-LMTHF on top of your multi. Normally I don’t like to add big doses quickly, but if you felt well with the deplin then you were already taking a hefty dose (I’m assuming without side effects.) If you remember having trouble with it or not feeling well, then I’m afraid the best policy is to do what everyone else is best doing and add a low-dose 5-LMTHF (400 mcg to 1 mg) and wait to see how you respond. Keep taking that dose for a while (2-4 weeks) and when you’re ready, try increasing. If you did feel well with deplin and didn’t have side effects, then you were already taking either 7.5 or 15 mg (!!!) It’s a pretty giant dose and if I took that you’d have to peel me off the ceiling, but if you tolerated it then that gives you some idea of where you might end up dose-wise. I hope this is helpful!

  4. Amy

    Dr. Amy,
    My 13 yo daughter was diagnosed MTHFR Heterogeneous C677T about a year ago. She also has some ADHD and anxiety which they feel is increased due to the gene mutation. We have tried so many different things and I just cannot get a handle on what works best. It does not help that she is 13 and her body is growing and changing. We tried Deplin, but I am looking to use supplements instead. I have tried her on 400mg Methylfolate and 750mg but neither has been the perfect amount as yet. She has also been on 1000B12 but I have noticed she is somewhat more angry when she takes this consistently with the folate. Most recently I looked into Seeking Health (Dr. Lynch) multivitamin for kids but 6 large capsules a day is not going to fly with a teenage girl. There is also a HomocysteX plus I considered but not sure appropriate for her age. Any thoughts on multi vitamin or regimen that is morning only. We have also played with anxiety and ADHD meds but nothing has been the perfect combination. Thanks

    1. amyneuzil Post author

      Hi Amy,
      Teens are so hard – it’s really difficult to find the right dose simply because everything changes for a teen every day anyway. I would try separate multivitamins and folate, just because it will be easy to find a good one-a-day multi (one capsule here being better than 6) and then one folate on top of that hopefully won’t be too much. I would be careful with the B12 every day – it might be too much for her right now. Is her anger better if it’s every other day or three times weekly? For multivitamins, I really like Pure Encapsulations UltraNutrients or Nutrient 950 (only one cap per day for a teen). Then you can continue to play with the dose of methylfolate using the multi as her background dose. I hope this helps!

  5. Neeltje

    Hi Amy,

    Thank you so much for sharing this very clear guide on how to increase folate in a safe way. I have Hashimoto and am still increasing thyroid hormone to find optimal dose. Is it a good idea to start increasing folate very slowly at the same time or is it better to wait until I have a good thyroid dose? I have depression and so far it seems increasing folate increases depression a bit, I read the undermethylated depression article which was very helpful to me. Tyrosine and 5htp help me out so far regarding depression, I already upped iron and B12 which were low besides folate. Many thanks for reading.

    1. amyneuzil Post author

      Hi Neeltje,
      I would wait to increase your folate until your thyroid is stable. If you’re changing two things at one time then it becomes very difficult to know what change is responsible for what symptom. Keep us posted – it could be that getting your thyroid back on track will make taking folate easier, but it might still increase your depression. I’d love to know what works for you.

  6. Lauren

    Hi Dr. Neuzil,
    My 7 year old son was found to be compound heterozygous , both mutations. He was doing great with gradual upping to 2-4 mg Methylfolate daily (along with 1 p5p and 1 mg b12). It was recommended that he take the 5mg capsule from Thorne (he’s not liking the tablets anymore so we wanted a pill). Does that too sound to you?

    1. amyneuzil Post author

      Hi Lauren,
      I love that product, just make sure he’s comfortable with 5 mg before you switch over because big jumps can be dicey. Otherwise, it’s good to have him on a multi as well simply because all of the B vitamins, not just B12 and P5P, work in tandem. Great that you figured out his mutations while he’s young – I think it makes such a difference. 🙂

  7. Kimberly Queen Roberts

    What’s the difference between Thornes Methyl -Guard & Vitacures Methyl Plus? I’m an undermethlator, two copies of MTHFR, treating mold toxicity & Lymes. I have not taken in B vitamins in 4 years except for P5P and my blood test revealed a High B-12 level, 2000.

    1. amyneuzil Post author

      Hi Kimberly,
      These products are really different and not easy to compare. They both have trimethylglycine, which donates methyl groups. Some people tolerate it well and some don’t. The Vitacures product seems more geared to detox, but that is also tricky because some MTHFR folks do well with protocols that push detox and some fall apart completely. I’d need to know more about you to have an idea of which one was better for you. If you haven’t taken B vitamins in years, then it might be best to start with a methylated multivitamin and add additional methylfolate to it until you find your tolerance. I hope this helps.

  8. Emma Brunner

    Hi Amy, my son has a MTHFR A1298C mutation as well as COMT V158M and COMT H62H and VDR Taq.

    He is 9 years old, can you suggest the dose of Methyl folate and anything else that I should give him?

    Thank you so much. Emma

    1. amyneuzil Post author

      Hi Emma,
      With kiddos it’s important to start the methylfolate even lower than you would with adults. The best place to start is a children’s multi (following the dosing instructions for his age and size) that has the methylfolate in it. I know Thorne Research makes a good one, and my daughter (who is 3 and can’t yet swallow capsules) loves the Kids multi + fiber gummies from Smarty Pants. Once he’s been on the multivitamin for a couple of months (provided he tolerates it well) then you can start to play a bit with adding a separate methylfolate or some antioxidants that cross the blood-brain-barrier for the COMT mutations. Also, a kids vitamin D is a good idea for the VDR. Establish him on the multi first though because that will cover a lot of bases. I hope this is helpful!

  9. Zach

    I am a 25 year old male and heterozygous MTHFR C677T. I have pretty severe anxiety and started taking 400 mcg of L 5 methyltetrahydrofolate (will increase as needed…but starting slow). My B12 levels came back at 545 (high) so I was told I did not need to take B12 (methylcobalamin). You mentioned that you should not take L 5 methyltrahydrofolate without taking B12. Im am confused…can you give me your opinion on if I should still take B12 even if my readings are high? Also opinion on folate dosage for me? My homocysteine reading was 9.

    1. amyneuzil Post author

      Hi Zach,
      If your B12 is showing as high then I’d say you can probably skip it while you’re trying to find the optimal dose of methylfolate for you. If you need to add a B12 later, you can. Also, if you’re taking a multivitamin (please do) then it probably has a bit of B12 in it anyway. And you’re doing it the right way – just increase slowly and back off if you feel like you’re having side effects. In terms of dosage – it is so hard to predict. We’re looking for something that puts your homocysteine in a normal range and helps with the anxiety, but doesn’t make you feel jittery or wound up or interfere with sleep. The range of tolerance is incredible – for instance. Some people do really well on the prescription Deplin, which is 7.5 mg and that amount would easily have me swinging from the chandelier at 3:00 am. Just be sensitive to your own reactions and don’t try to push through, really give your body as much time as it needs to adjust. I hope this is helpful.

  10. Yolanda Brosseau

    Hi – thank you again for all of this really helpful info!
    Do you have a favorite prenatal? I’ve taken seeking health’s and really liked it. But recently a person I really like did a pre-review (gimme the good stuff – Maia) about it and said that it has a ridiculous amount above the daily value of many things and has a potentially harmful form of vitamin a. She suggests naturelo.
    Any thoughts so appreciated!

    1. amyneuzil Post author

      Hi Yolanda,
      I’m actually not familiar with the two you’ve mentioned so I can’t do a good comparison, but I used Thorne Research Basic Prenatal. I felt great with it, but generally, I feel well with Thorne vitamins so if you know of a brand you feel well with (that has a good amount of methylated folate) then go with that. Our bodies are so individual that it’s really hard to generalize about this sort of thing. I hope this helps!

  11. Andrew

    Dr Neuzil

    Great post on a very confusing subject. Thanks for the clarification if offers.

    I have a few questions about my specific case. I am C677T Heterozygous for MTHFR. I lived my whole life with no awareness of this mutation as I had experienced no problems until I took a course of fluoroquinolone antibiotics three years ago. Fluoroquinolones destroy mitochondria in those of us with adverse reactions leading this person who wasn’t affected by slightly below normal methylation in a much deeper hole than before.

    All the horrible side affects of that terrible antibiotic triggered many different issues in my body. I think the large majority of those side affects are now gone, but those that remain I suspect are tied to my MTHFR mutation. I still suffer from digestive issues, nausea, burping and sometimes heartburn (this is actually something that has gotten MUCH better since March, when I had heartburn with nearly every burp and I was burping 100 times a day). My other remaining symptom was very slight and occasional peripheral neuropathy – mostly in my toes. My MTHFR mutation was diagnosed in March. As part of adjusting to being a floxie I started eating organic and eat very small amounts of products including bread – pretty much I just eat tortillas, probably averaging three a week; though I will eat a bun when out somewhere like a sporting event. I eat cereals, oats and eggs for breakfast, but all non-GMO and organic. Most are folic acid free, but some have a tiny amount.

    I have been experimenting on my own with dosing with a bit of help from an integrative medicine MD. I had initially tried taking 400 mg of 5-MTHF in combination with a full dose of the Garden of Life B Complex (which I had been taking for the previous 2 years without known side affects). This led to severe stomach cramping. At the MD’s direction I started taking the Quicksilver Methyl B Complex. This contains folinic acid not the L-5-MTHF form, but not the methylated form of B6. I took double the “recommended” dose along with a normal dose of the Garden of Life B Complex for approximately two months.

    In short, since July 1 here is what I was getting daily for key B vitamins:

    B6 -= 17.5 mg all as Pyrodoxine Hydrochloride
    Folate = 450 mcg labeled only folate (folic acid??) and 500 mcg Folinic Acid
    B12 = 633 mcg as methylcobalmin

    Somehow I missed that despite my new knowledge I was still taking in a supplemental form of what must be folic acid. Though as I noted I had been taking a daily “recommended” dose of this B Complex for over 2 years, with no obvious side affect.

    About three weeks ago I started having tingling and feelings of cold in my lower legs. It isn’t the neuropathy of old as my toes and feet are similar to what they were previously. I also started to get some of the stomach cramping I used to get with the 5-MTHF, not nearly as bad, but….

    I got my B and D levels tested. I stopped all my supplements for two days (I also take Vitamins D and K along with Mg and an herbal designed to keep lymph flowing called Lymphomax) and got my blood work done. I also fasted prior to the tests.

    Here are my results:

    B12 (this was serum) = 1302 pg/ml
    Folate (this was serum) = >20ng/ml
    Homocysteine = 8.7 umol/L
    Vitamin D = 87 ng/ml (which was a huge improvement since I had been hovering in the low 30s for the previous 3 years even going as low as 9 ng/ml about 2 1/2 years ago).

    The B6 didn’t come back yet and it has been some time, but given all these others I am sure it will be high.

    Now my question is where do I go from here?? I really think the folinic acid has been helping my digestion directly or indirectly. I have been off all Vitamin Bs for 5 days now. I am still having tingling in my legs though it was mostly gone yesterday only to return today.

    I do have an appointment with my Integrative MD in about three weeks and while she is a marvelous DR and very attentive, she doesn’t seem to be highly knowledgeable about MTHFR though she was the one to order the initial tests.

    Should I stay off all Bs until the tingling stops?? Or are my high levels due to methylation problems still and I should start using the PureEncapsulation – maybe 1/2 serving (though I am scared of the L-5-MTHF causing problems in my stomach. Should I cobble together an approach of different supplements taking folinic acid along with B6 as pyrodoxial 5′ phosphate and methylcobalmin? If I do this what other Bs do I need? Also if I do this what ratios? Match the Pure Encapsulation??

    Thanks for reading the very long post and for seeming to answer nearly every post on the site. I did look to see if I could schedule a phone consult with you before leaving this huge post.

    1. amyneuzil Post author

      Hi Andrew,
      It gets so confusing, doesn’t it? I can’t tell you exactly what is right for you because I’m not your practitioner, but I do think it’s reasonable to stay off of all Bs until your symptoms subside. When you are able to add Bs in again, start with something that has a full complement of nutrients, not just cherry picking because it’s really hard to anticipate what your particular body will need vs. what someone else might need in the same situation. Instead of a B complex, would you consider starting with a low dose multivitamin that has methylfolate? It might be gentler overall on your system and will be balanced with other nutrients that your body uses in the same processes so that you don’t get stuck in a bottleneck somewhere else. Because of your ongoing stomach issues make sure you take any multivitamin with a good sized meal because some nutrients are irritating to the digestive tract. So – give it a try and if needed we can schedule a consult. 🙂

  12. Kimberly

    Hello Dr. Amy,

    I have the single mutation. C677T. I have been doing a clean, veggie filled ketos diet I have never felt better. I suffered years of depression, anxiety, low energy and menstrual problems.

    I had been prescribed the Thorne but I had insomnia and a fast heart rate for 3 days with it. I was totally wired. So I came off them.

    I then tried another organic brand of methyl B complex. They were capsules and I took just a little bit to start with. I either felt nothing or worse.

    I am confused by this. I have been using Sari foods nutritional yeast.

    I’m thinking of taking an organic, while food multi from Garden of Life. I have taken it before and felt great. Any thoughts? I want to get enough B vits.

    Also does one with the C677T absolutely must use a B supplement?

    Thank you.

    1. amyneuzil Post author

      Hi Kimberly,
      It sounds like you’re doing amazing with the diet and lifestyle changes you have made. Oddly, some people never really can take a supplement form of the 5-LMTHF. I have absolutely no reason why, and it might change over time, but for now I’d say really work on getting your folate through food sources. Nutritional yeast is a great source, and here’s an article about other sources that might help. If you’re doing a keto-type diet then the beans and pulses might not fit into that, but really work to get the folate into your diet every day and see how that does for you. Given that you have a single mutation C677T, I would say it’s important to make sure you have a high folate intake, but not necessarily a supplement. Just increase your food sources if possible. Aim for at least 400 mcg of natural folate per day and see how you feel. Just as with supplements, you might find that you feel better with a higher dose, so play around with it. I’d love to hear how it goes for you!

  13. Michael

    Dr. Neuzil, I was hoping that you could clear this up for me and possibly others. I am homozygous for the MTHFR C6779T and also the MTRR A66G and hetero for CBS C699T. I have tried low doses of methyl folate and b12 and those just seemed to energize me for a couple days then make my nausea and fatigue after that even worse. Anyway my question is with my SNPs, would I be able to turn Hydroxocobalamin into methyl and Folinic acid into methyl folate for proper methylation, or will that not be possible for me? I seem to respond to them better

    1. amyneuzil Post author

      Hi Michael,
      Great questions! I had to do a bit of research on the folinic acid specifically. I’ll answer in two parts.
      First – the hydroxycobalamin. Absolutely this can be converted to the methyl form, even in people with MTRR, and it is converted slowly so that makes this form easier to tolerate. Here’s a link to a post on it because hydroxy- is actually my favorite form of B12 for MTHFR mutants.
      Second – the folinic acid. This is a great question, and actually I had never looked into it specifically. I did find some great research indicating that folinic acid conversion to 5-MTHF is not impaired in MTHFR mutants, so thanks for that! Here’s the research.
      The bottom line is that yes – keep on the protocol that your body seems to be tolerating because even with your mutations they are usable forms for your body. Great luck and keep me posted!

      1. Maggie

        Hello Dr. Neuzil:
        First, thanks so much for an easy-to-understand forum for MTHR mutants. I’m hoping you will be kind enough to help me with my issue.
        I recently tested Homozygous for MTHFR A1298C. I’m not usually a stupid person, but I got way ahead of myself and bought supplementation before thoroughly researching how to start up correctly.
        I took 15 MG of L-methylfolate right off the bat, and to make matters worse, I accidentally doubled that dose for a few days.
        That’s when I started having symptoms of prickling (ranging from a tickle to burning) off and on. I’m not real clear on the difference between Neuropathy and Neuritis, but I’m pretty sure I have one of them.
        I’ve been to a few doctors and they don’t seem to be able to help with MTHFR/methylation/B-12 issues and I can’t get in to see a neurologist until next February.
        I’m pretty darn sure these symptoms are a result of me overdosing myself on L-Methlyfolate. I was tested for my homosysteine level but don’t have those results yet.
        I’d be VERY grateful for your take on it and any advice you might have to help me get my nerve endings get back to normal.
        Just FYI, Yesterday, I started the protocol you posted on your site. (starting with B Complex Plus from Pure Encapsulation).
        Can you please help? Many thanks for what you do!

        1. amyneuzil Post author

          Hi Maggie,
          Oh, I’m so sorry to hear that you’ve had a rough start. Yes – 30 mg for a few days would be enough to send me to the moon, so I’m not surprised you’re having some unpleasant sensations. In my experience the best healer for this type of thing is time. I do believe you’ll get “normal” nerve function back, but I also think it might take a while. In other folks I’ve spoken with who have had side effects it has been anywhere from 4 weeks to 3 months. It might be a good idea to wait to start the B Complex Plus until your symptoms subside. Just work on having a nice clean diet, start to eliminate foods fortified with folic acid and introduce some food sources of folate but mostly just give your body time to heal. It won’t be overnight, but it will happen. Isnt’ it crazy to think that a vitamin can have such a profound effect? Keep me posted – I’d love to hear how it goes for you.

  14. hallie

    Hi Dr. Amy-

    I found out after my 3rd child that I was compound heterozygous for MTHFR. I know that I’m supposed to be eating clean and taking folate with the b vitamins. My doctor suggested prenatal pro which I took for a long time but is almost impossible to get now. I went to our local health food store and found Solaray Methyl B-complex 50, do you have any thoughts on this or any suggestions on what other possibilities for me could be? Thanks!

    1. amyneuzil Post author

      Hi Hallie,
      I actually like the solaray product. It’s nice and simple and covers a lot of bases and most people can find it locally. It’s a great place to start. Give it a try and if you’re not seeing the results you want, you can always continue with it for your basic Bs and add a separate methylfolate for a bit more kick. Good luck and keep me posted!

  15. Holli

    Hello everyone, I have had lifelong anxiety and depression, with panic disorder dx in my 30s, and now at 42 my depression is worsening despite full compliance in current medications and having tried many others. It was in search of a potential solution that I found this site. I am brand new to this, but can make i have several comorbidities, i.e. insomnia, fatigue, headaches, brain fog, difficulty concentrating, difficulty waking up in the morning, unmotivated, and negative self talk. I do have a Dr appt on Monday but am about to try out what’s covered here. It makes sense and i desperately need to put the brakes on this runaway train I’m on. I realize the first days can be rough but in the name of hope I’m a-ok with that. I have never seen this hydroxy form of b12 so I’ll have to hunt for it. I’m crying several times a day, and feel a constant zoning out heaviness sensation, most times. I’m not sure how to avoid other forms of folate bc it’s in multivitamins which I do take one with methyl B12 (yay). I’m praying I can find it at the health store… instead of waiting for it to come in the mail. Seems I have much to learn but I had to say thank you for putting this up and all the work it must have taken. I was really feeling hopeless having tried seemingly everything before I stumbled across your site.

    1. amyneuzil Post author

      Hi Holli,
      It’s such a long journey, right? Honestly, it seems like most people here really have to find their own path. The MTHFR stuff is too new – doctors just don’t routinely check for it yet. Good luck on your journey and I hope you can find something useful here! Keep us posted – we’d all love to know how it goes for you. 🙂

    2. Trish

      Hi Holli! Yup – tons of fun when you’re a mutant – ha ha. It’s been 2 years since my diagnosis (heterozygous 677ct), and I’m still learning. So – just know we all deal with the frustration of not being able to find answers so we end up on the Internet – trying to figure it out. And everyone is a little different thanks to our different DNA SNPs – again, so much fun!

      Wanted to let you know that Source Naturals now offers a very affordable Hydroxocobalamin. I see it is available on Amazon. Swanson Vitamins also offers it. I’ve been taking this brand as soon as it came available at Swanson, so maybe 8mo – 1 year, and I’ve found it works great.

      Also thought I would mention that yes, it gets strange when you can’t take multivitamins. My little corner of our house looks like a pharmacy as I take everything separately now. But the good news is that I am finally feeling much better and just plain normal again – except when I’m at McDonalds and can’t get a small hamburger because the buns contain folic acid…oh well. Best of luck to you!! Hang in there!

    1. amyneuzil Post author

      Hi Lindsay,
      The Dr. Ron’s product looks good! I’ve used a few of his other products (not that particular one) with good results. And honestly, there is no way to know if one capsule per day is enough, but it’s certainly a good place to start. Everyone is so different and there are so many factors that contribute to your B vitamin needs other than just the mutation, that the best policy is to go by your mood and energy. Start with one and see how you feel. Increase or decrease as needed until you hit the right dose for you. It would be great if I could give a one-size-fits-all answer, but there isn’t one. Good luck and let me know how it goes!

  16. KeenKat

    Hi Amy,
    Thank you so much for your wonderful information and guidance.
    I have the MTHFR C677T mutation and not the A1298. I have a 191 B12 deficiency. Doctor prescribed Mitocore. I took one tablet for 2 days and I was manic. So I quit. It has many other ingredients besides B12. I keep asking doctor for something other than methyl but he hasn’t responded. I have ordered Hydroxy from Ben Lynch’s site based on your recommendation. It’s a 2,000 mcg lozenge. I have serious drug sensitivities, have been treating myself with diet and exercise but I’m concerned about B12 deficiency. Homocysteine is high as well.
    Thank you.

    1. amyneuzil Post author

      Hi KeenKat,
      Yeah – methyl B12 can be such a b**ch. I think you will notice a world of difference with the hydroxy form – give it at least 3 months and then test your levels again. B12 can take a while to come up and I’ve seen clients who need massive doses, so it might be a bit of a project. Just stick to it! The homocysteine will probably need a combo of the B12 and also some methylfolate to start coming down. Just go slowly and start one thing at a time. Best of luck!

  17. Christine

    Hi Dr Neuzil,
    I’ve just started on my MTHFR gene journey. I’m homozygous for mthfr a1298c. I began a B complex supplement (NutraCore BPLEX-pro) and have been getting headaches and my bp has increased. I began with one and worked up to two capsules but obviously am not tolerating it well. I’d welcome any suggestions. Thanks!

    1. amyneuzil Post author

      Hi Christine,
      I’d go back to one capsule if you were tolerating that well. Just stay there for a while because your body will have a whole backlog of “work” that needs to be done with the methylfolate – that includes detoxification and all sorts of things that give you symptoms like headaches. Also, make sure you’re drinking enough water because detox can bring your bp up if you’re getting stuck somewhere. If you didn’t tolerate one very well then message back. 🙂

  18. Yolanda

    Thank you for all your help! It is so awesome how you reply to people!!
    I have been taking 1 methyl guard plus (so 1 mg folate) and 1 additional mg folate, along with 50 mg of niacin.
    I’m trying to decide if I should increase, decrease or stay the same… at first I felt spacey, then I felt good, now I’m feel anxious… with intrusive thoughts (I have some sort of postpartum anxiety – three years later – and the thoughts are seeming more suddenly… but I did feel really good at that dose for a couple weeks)
    any thoughts?
    One other question: since starting I’ve been getting strange hives all over my body, they come of fast and hot, last only 30 mins, are triggered (it seems) by coffee and stress… could these be related to the folate? I’ve been cracking them up to stress!

    1. amyneuzil Post author

      Hi Yolanda,
      Hmmm. I think maybe the 2 mg is too much for you right now. I’d cut down your dose to just 1 mg of folate and see how you feel. I think it was good at first until it really started to push detoxification and now it’s just all going too quickly and so the weird anxiety is happening. Try backing down for a few days and seeing how it goes. Also – do the hives happen after the niacin? It is known to cause a flushing/itching reaction that looks like hives in some people. Maybe cut it out for a few days and see if the hives go away. Usually if it’s the niacin the hives will only happen once per day, 15-30 minutes after you take the niacin so I’m guessing if you take your niacin in the morning with your coffee then that might be it. If it’s not the niacin then maybe the lower dose of folate will help? IT could also just be stress, but play with the doses and see. Keep me posted!

      1. Yolanda

        It was the niacin – thank you! I didn’t know about niacin flush and was doing everything you’ve not suppose to (hot drink, no food). I seem to react strongly to it!
        So now I’m on 2 mg of folate (1 mg in that multi you suggest). But I think I felt better with the niacin. Should I try taking it after food?
        I’m also thinking of trying to up the folate – I think my increased anxiety was caused by the niacin flush – I just couldn’t handle that I was allergic to an unknown weird thing – since learning that I was causing it and stopping it I’ve been much much better, just sluggish.
        Any help sincerely appreciated!!!

        1. amyneuzil Post author

          Hi Yolanda,
          I’m so glad you found the culprit! Yeah, niacin can be so difficult. On one hand, the flush is really unpleasant. On the other, it’s really helpful and the flush-free forms just aren’t the same. I’d say you have a couple of options. One is to monkey around with dose and timing of the niacin – find a tablet that you can cut into smaller bits to start small and work your way up. Also, try with no hot drink and food and see if we can find a dose that helps, but doesn’t give you the horrible flush. The other option is to just accept the horrible flush because now you know it’s normal and not harmful (even if it isn’t the best 15 minutes in the world) because then you get the benefits. Or maybe a combination of both? Find the lowest effective dose and the best timing and if that still causes a bit of a flush then live with it? Ha! Keep me posted – I’ll be curious to hear how it all goes.

  19. Hilda

    Hi Dr. Amy- I’m in need of a little guidance. I’ve been diagnosed with compound heterozygous mthfr 665c> t and 1286a> c . I have no idea what I should take. My Dr. Said start with pure brand homocysteine supreme and a msm supplement and I have been taking both with no effect for months. I went in to try to address depression, inability to lose weight, anxiety and vague liver pain. All still very evident. Any help you may have would be so appreciated. I feel crippled by this and don’t know where to look!

    1. amyneuzil Post author

      Hi Hilda,
      I’m compound heterozygous too! My guess would be your dose of the methylfolate isn’t high enough yet, although it’s really just a guess. Maybe talk with your doctor about getting a plain 5-LMTHF supplement to add to your current routine. For whatever reason it seems like people who have the trouble losing weight seem to need higher doses (that is only my observation, not in the actual research). Again remember that the most common prescription for this is deplan, which is either 7.5 mg or 15 mg of methylfolate and you’re taking 2.4 mg if you’re taking 2 caps of the homocysteine supreme. Your body might just respond better to a bit more. Talk with your doc about it and let me know what happens!

  20. Courtney Ivory

    Thank you for this!!! I am on the desperate search of finding out why I feel the way I do and trying not to accept it as “normal”. When I mention this stuff to Dr.’s here they really have no idea what I’m talking about and I don’t want to offend anyone. Is there a specific way to ask for this testing? I may just try your self testing route! I’ve recently seen neuro, psych, and a family practice Dr. with a handful of different tests performed. Symptoms include migraines, chronic fatigue, anxiety, brain fog, blurry vision/dizziness, mood change and more. Family history of bipolar, depression, stroke and suicide. Out of desperation I put myself on High Potency Optimized Folate, L-Meth 5000 mcg a month ago and it’s CHANGED MY LIFE. I ran out 4 days ago and symptoms have come right back. I would love guidance on what to pair it with and if I’m taking too much. Sorry for the novel! It’s beyond exciting to be in touch with a Dr. that can relate to these symptoms!

    1. amyneuzil Post author

      Hi Courtney,
      I’m so glad you tried the L-Meth 5000 – sounds like it’s doing great for you! I think the self testing is probably going to be best for you anyway, just because it sounds like the reaction you are having to the 5-LMTHF is too big to be coincidence. Because of that it sounds pretty clear that you have some MTHFR mutation, but the things that will really help to refine your treatment are all the other things that go with the MTHFR mutation – the other mutations in the pathway. Most doctors just don’t really have access to those tests because they aren’t conventionally done. If you do the testing through 23 and me, then run it through one of the programs specifically for methylation (I like genetic genie’s methylation profile, but there are a few out there) then we start seeing a much bigger picture. In general though it can help to talk with your doctors about the MTHFR mutation. If they don’t know about it then you can help to get them looking into it so that other patients who need this information can also be helped. In answer to your question about what to pair with it and the right dose for you – if you feel good with it, then you’re not taking too much. The prescription most commonly used is called deplan and is either 7.5 mg or 15 mg, so for a lot of people the dosage is much higher. The most important thing is your reaction – in general if you feel better taking it then you’re doing something right. In terms of what to pair it with, the best general next step might be to try a B-complex (with methylfolate, not folic acid) like the B-complex Plus from Pure Encapsulations, just to get the rest of the B vitamins into the mix. The Bs often work together so if you’re getting one but not all then some of those processes get stuck. Outside of that there is always B12, but that’s another whole can of worms – here’s an article on starting that one. So… Sorry for the novel back! 🙂

  21. Laura Byrne

    Thanks so much Amy! Do you think staying on these prenatals after pregnancy is safe long-term? I just love the way I feel on them so wanted to get your thoughts. Thank you!!


    1. amyneuzil Post author

      Hi Laura,
      Prenatals are still safe while you’re nursing, but not long-term because the iron concentration is so high. I really liked my prenatals too so I actually now take them every other day and a multivitamin without iron the rest of the days, just so I don’t overload on the iron.Does that make sense?

  22. Jose


    I have the double MTHFR mutation C677T and I have been taking folate 400mcg and methylcobalamin B12 1000mg for the last 18 months without noticing any difference. I was not deficient before and not deficient today. Now, I still feel weak, brain fog and so on. I did take anxiety medication for 2 1/2 years and just stopped 27 days ago so to my believe this is part of the withdraw symptoms which I started a year ago. I have taken both kinds and they both feel the same to me because they do not make me feel better or more alert.

    I did notice when I take the b12 without the b complex I get this headache right away. My functional never said anything about starting low or going up as needed or taking all B vitamins together. Now I’m wondering if part of the symptoms I have are related to taking this every single day for the last 18 months. I was already disappointed with regular Doctors, but functional are not any better. ;-( I have seen 2 of them the last 2 years and so far I have not much good to say about them. ;-(

    1. amyneuzil Post author

      Hi Jose,
      I know – it’s so hard to find the right answers for you. Part of the problem isn’t the docs, it’s just that MTHFR stuff really is so individual. For sure the withdrawal from the anxiety meds will make things worse for a while – that is to be expected. If you haven’t been noticing a difference with what you’re taking it might be a good idea to switch to a good multi-vitamin that has methylfolate (I love the thorne multis, but there are lots of good ones) to make sure you’re getting all of the mixed B vitamins that you need and then try increasing the dose of the methylfolate slowly. For some of us, 400 mcg just isn’t enough to notice a difference. It can keep you from being deficient, which is a start, but it doesn’t necessarily help you to actually feel better. For me the optimum dose is about 1400 mcg, but it has also gone up and down some with life stressors. Talk with your doctor and see if they might be open to this sort of change for you. I hope this helps!

  23. Laura Byrne

    Thanks for the advice! I’m going to stay at this dose for a while and see how things go. Another quick question…do you recommend a good prenatal vitamin for women in our shoes? I know I need to avoid the usual prenatals with folic acid so I just want to be sure I am covering my bases and taking a good one that won’t interfere 🙂

    Thanks so much for your time!


    1. amyneuzil Post author

      Hi Laura,
      I really like Thorne Research Basic Prenatal – that’s the one I took through my pregnancy. Good luck!

  24. Laura Byrne

    Hi Nate,

    Thank you for the article! I appreciate your help in giving me more info 🙂 I’m hoping for the best. I live a healthy lifestyle and have truly tried everything to help and I still can’t get rid of symptoms of depression/anxiety so we shall see! Take care…Laura


  25. Laura Byrne

    Hi Dr. Amy,
    Thank you for your reply! I appreciate the information and honesty about the research etc. I decided to give it a go 2 days ago. I started with .5mg of both methylfolate and B12. So far, I feel pretty good and don’t believe I’m experiencing any side effects…maybe positive? I was also diagnosed with PMDD and this is the time in my cycle where I’m on the upswing so maybe hard to tell. This is going to be my last try before trying an SSRI in the luteal phase. Have you seen any women with PMDD improve with these vitamins? Also-when should I increase my dose to 1mg? Thanks so much for your help! I’m glad you have felt the benefit along with others. Take care 🙂 Laura

    1. amyneuzil Post author

      That sounds great Laura!
      I have seen it help with PMDD but hormone balancing is also very helpful and sometimes just the methylfolate isn’t enough. I’d wait until you’re stable on this dose for a few weeks before increasing, and that’s a pretty big increase – doesn’t hurt to take it slowly. Trust your own instincts!

  26. Nate

    I just read a 2-year old article called “How I beat my 10-year battle with anxiety after discovering folinic acid” which is a heart-wrenching but informative read of a woman that suffered with MTHFR anxiety symptoms to about the furthest extreme I can imagine. I won’t link the article since that might trip up a spam filter, but if you Google the name of it, you’ll find it. It’s quite long and detailed.

    Folinic acid was the only thing that saved that poor woman.

    When I started checking out supplement reviews on Amazon, I found people saying the same thing. People were able to stop their prescription medicines after discovering Folinic Acid.

  27. Laura Byrne

    Hi Dr. Amy,
    I am going to start slow with the doses but nervous about the side effects. I’m also finding articles that these supplements can cause cancer and the research isn’t solid in that it can help alleviate depression. Have you seen people improve their depressive or anxiety symptoms? I’m willling to try, but I’m apprehensive after reading articles about how Dr. Lynch’a information isn’t solid and he is making money from people who decide to purchase his supplements etc. Any reassurance would help! The last thing I need is more symptoms of depression so I’m trying to figure out if it’s worth the risk. Here is the 23andme article saying that there isn’t solid research done to connect it to health conditions. Thanks for taking the time to respond! I appreciate it….

    1. amyneuzil Post author

      Hi Laura,
      Yes – it can be scary starting anything new. Especially when there is so much debate about it! The research is in early days so truly we know far less than we don’t know. The research showing that MTHFR mutation causes a sharp decrease in the enzyme function, along with hosts of symptoms and associated medical problems is reasonably solid. The research as to the effects of 5-LMTHF supplementation is extremely limited. Even Deplin (registered trademark of Alphasigma) which is the prescription-only medical food, is really only researched in a very narrow window of people, which is obese people with major depression. I can say that clinically I have both seen and experienced personally some tremendous benefit, but that doesn’t mean that it’s right for everyone. So really just weight the possible side effects with the possible benefits for you. Sorry I can’t be more definite than that – all I can say with any certainty is that it’s helped me. If you do decide to try it then keep me posted! I’d love to know how it goes for you. Also, since your major symptom sounds like depression you might want to read this article about methylfolate making depression worse too.

  28. Nate

    HI Dr. Amy,

    Just to be clear, in the article you are suggesting the B Complex + 1000mcg of MTHF eventually. So, that would only be 400mcg of B12 and 1400mcg of MTHF, right?

    I am low in B12 and that’s all. I also have MTHFR a1298c homozygous mutation. I’m not sure if this is the right dosage for me because it seems really lopsided with so much MTHF.

    Thank you for the article. It really sums up my problems with all B12 and methyl folate. I’m afraid to take it now, basically.

    1. amyneuzil Post author

      Hi Nate,
      This is a good starting place, but the right dose for you has to be found by you, if that makes any sense. Generally, I advocate starting small and working your way up until you find the dose that helps you the most without getting into any of the side effects. It’s kind of a process of self-experimentation. Much of the research indicates that people with MTHFR mutation do best with a higher dose of folate than average, hence the 1000 mcg MTHF as a benchmark, but there are many people who feel best taking less than that and many who feel best taking more. It just depends on your body and the rest of your genetic and lifestyle picture. To find the right dose for you I think it’s best to actually go through the process of slowly increasing until you actually feel better. There isn’t really a one-size-fits-all with this. And if you know your B12 is low then it might be best to start there – begin with a good B12 and see what changes that brings about before you try a methylfolate. Here’s an article specifically about the different types of B12 if you’re interested. Good luck!

  29. Kristin

    I just tested positive yesterday for homozygous mutation A1298C and I’m currently pregnant with baby #5. My first 4 had mild mid-line defects and after reading an article about the link to MTHFR I got checked. I switched to a prenatal vitamin with methylfolate (800mcg) and I immediately started having horrible, vivid, high anxiety nightmares, when I stop taking the vitamins it goes away? My OB is completely clueless about this and total me straight up he wasn’t sure what to do (with my diagnosis). I have had horrible post partum anxiety the last 6 years and all the symptoms of low serotonin and such I have. Not sure what to do next? Do you think I should start my vitamins at a lower dose and work up?

    1. amyneuzil Post author

      Hi Kristin,
      Congratulations about baby number 5!! Honestly, in your situation, I’d suggest seeing a specialist. See if you can find an OB with experience with MTHFR mutations because starting methylfolate during a pregnancy is tricky and can be risky for that fetus simply because of all the rapid changes in your body and detoxification that goes along with it. Methylfolate certainly has the potential to help with the post-partum anxiety, etc… but I don’t want to put baby # 5 in any risk at all. Until you talk with a specialized OB I would switch back to a regular prenatal vitamin to cover the rest of your nutritional bases (even though it has the usual old folic acid). Does that make sense?

  30. maryam

    i stopped taking mythylfolate it is making my depression worse:(

    so this is mean my depression won’t get better?? and what about using folinic acid and hydroxocoblamin? is it an alternative to mythylfolate? or should i try SAMe??

  31. maryam

    and how much should i increase each time i i think i have to reach high dosage because i am homozygous and having depression??

  32. maryam

    thank you dr. for the reply

    how long should i stay with each dosage if tolerated? 1 week is enough??
    and should i take mythylcoblamine with the mythylfolate?
    i am planning to take hydroxo coblamin withe niacin to avoide side effect

  33. maryam

    ** i get sever anxity with mythylfolate
    so how many days after stopping it shoul all side effect disappeare ??

    1. amyneuzil Post author

      It depends on the person! Usually within a couple (2-3) days but I’ve seen some people take a week or two. 🙁

  34. maryam

    hello dr. i really thank you for this helpful website ihave read this article more than 3 times
    i have recurrent depression and recently tried many types of antidepressants till my dr suggest to have mthfr test. i found that i am 677 homozygous my dr. tell me that is a good thing to know will help me with my depression to start mythylfolate . i felt happy and feel that will be the magic key.

    he advice me to start 7.5 fore one month and 15 for after .
    after 2 days of starting 7.5 i was just crying and getting crazy of it i continued for 5 days the after reading throw sites i stopped it day after day i felt better

    i have started with 400 after reading your articles and after 2 days i started crying again ??and stoped it again i am really afraid to start again

    i am so sad and upset i don’t know what to do
    is it necessary for my case to have the mythylfolate?? and what can i do that i am not tolerating it and my dr. said you have to take it to get your depression better ?!!

    hop to hear from you
    thank you

    1. amyneuzil Post author

      Hi Maryam,
      I know – it’s so discouraging to have trouble with starting but hang in there! Try starting with a much lower dose – even 50 mcg. The first few days might still be a little strange, but see if you can last past the initial adjustment. We need to take very tiny baby steps and see how you do. If you don’t even tolerate the 50 mcg then it’s possible you have very low seratonin and MTHFR, which means we should try something else – that is kind of a special case and here’s the article about it. Let me know how you do with the tiny dose – I’ll be interested to hear.

  35. LN

    I’m so glad I found this. Thankfully we have a holistic family practice who tests for MTHFR as part of routine bloodwork- so I found out I’m homozygous 677. As I’m reading more about this mutation it’s making a lot of sense- I’m in my 30’s and struggled with anxiety through most of my adulthood, infertility with my first pregnancy- a shout out to acupuncture that allowed us to get pregnant- and subsequent postpartum depression after our first son (We have two healthy boys now.) Unfortunately even though our family practice tests for MTHFR they aren’t really well versed in what to “do” about it. I’m really hoping you can help me with 2 questions:
    First, as far as methylB supplements, I have two: one says Folate (as Quatrefolic 6S -5 Methyltetrahydrofolic acid) and the other says Folate (from folic acid 6S 5- methyltetrahydrofolate.) After reading this and all the comments, I’m not sure which (if either) is ok/correct? It’s so confusing!
    Second, our older son (7) is displaying some mild sensory/asperger symptoms and I wonder if it could be related to MTHFR- my husband is heterozygous for 677 AND 1298- and if we should start him on a methylB supplement. Is it safe to give him without definitive testing ? If so, can you suggest a dose? Thank you SOOOO much!!! This is so helpful!

    1. amyneuzil Post author

      Hi LN,
      I know – I had the same thing. When I first started reading about MTHFR so much of my history clicked into place! It suddenly started making sense. For the first question – both of those forms are great for MTHFR folks. For the second – lots of MTHFR kiddos do have sensory/aspergers/anxiety type symptoms so it certainly could be related (but of course it might be unrelated too). It is safe to give him without definitive testing because we all need folate and this is just a bit better form. In a 7 year old you really do have to start SLOWLY!! The RDA for kiddos 4-8 years old is 200 mcg so start with maybe 50 mcg if you can and work your way up. Also remember that feeling a little odd the first few days is normal, but it shouldn’t last beyond that. I’ll be excited to see what you notice! Keep me posted if you get a chance. 🙂

  36. Naveed Zafar

    After starting L-methyalfolate with low dose of 500 mcg, i am feeling acidity in my stomach and sort of hungry and bowel movements have been increased from 1 to 3, for this acidity i was taking Omperazole and it was well under control,but now i am seeing increased … appetite is also disturbed, do you have any suggestion ..highly appreciated.


    1. amyneuzil Post author

      That’s so interesting – I have this particular symptom as well when I increase dose, but I haven’t seen much about it anywhere else. 500 mcg might still be too high a dose for you to start with – we may want to look at bringing it down to 200 mcg to see if that is better tolerated. We can probably increase later once your body has caught up with some of the methylation work, but for now I’d keep the dose lower.

  37. Naveed Zafar

    Chat Conversation Start

    471 people like this
    Alternative & Holistic Health Service
    MON 5:02PM
    Hello Dr, i have seen your article about MTHFR, i have suffered a lot due to Clinical depression for more than 10 years, i was reading an article about MTHFR and its connection with depression and anxiety , i requested my Psychiatrist to go for this blood work and it came out with A1298C gene mutation … she put me on Optimized Folate 1 mg, 3 times a day, i hardly tolerated 1 tablet… then i cut it into half and took it with B-complex (without folic acid) ,at moment i am taking half tablet once day which makes 500mcg / day, within 2 days my mood was better, and my anxiety is also 80% gone… only side effect i am having is slight headache and little bit sleep disturbance … , btw i am still taking Prozac 40 mg once a day with it… any help or recommendation will be highly appreciated…

    1. amyneuzil Post author

      Hi Naveed,
      That is fabulous news! It sounds like the 500 mcg dose is working well for you. Maintain that dose if you can, but if the headache or sleep disturbance gets worse then decrease the dose even further. The best effects will be from long-term use. Once your body has adjusted to taking the methylfolate you might be able to increase your dose slowly, but honestly I feel like the dose is less important than the duration of supplementation. What I mean is that even at a very low dose we can see great change over time.
      Often with long-term use of methylfolate people are able to decrease their dose of the Prozac or other medications, but listen to your body. If you are doing well, feeling happy and calm then there is no need to change anything. Keep me informed if you can – I’d love to hear how you’re doing long-term.

      1. Naveed Zafar

        Thanks a lot for replying, is it possible to have skype session with you ?

        secondly looks like i cant take high dosage B-complex,e.g i tried Country Vitamins B-complex Coenzyme,it freaks me out , do you suggest what kind / brand i should try, at moment i am taking basic B-complex with lowest B vitamin strength , B12 is not methylated and its 25mcg ,shouldn’t it be more than 100mcg to help methylation process with L-methylfolate, please help.


        1. amyneuzil Post author

          Hi Naveed,
          Looking forward to talking with you! We’ll talk about all of this in our visit. 🙂

  38. Jeremy M

    Thank you so very much for this article and the information you share. My wife is homozygous A1298C and has tolerated the Pure Encapsulations B-Complex Plus (2x daily) very well for over six months now. In fact, after starting on it, her urge to bite her fingernails was curbed completely for the first time in her adult life. Two weeks ago she added 1mg of Pure Encapsulations Folate 1000 (methylfolate) and also tolerated it fine (no noticeable change). This week she wants to increase to 2mg of methylfolate. A couple questions:

    1. If there are no negative symptoms after a week, is it too soon to increase?

    2. What timing is recommended (2mg in the morning along with her B-Complex Plus or 1mg morning/evening)?

    3. Is there a rule of thumb for the amount of B12 (methylcobalamin) needed? Unfortunately our doctor will not test for B12 (yes, we’re getting a new doctor but her appointment isn’t for another two weeks) so we don’t know her current levels. From the advice in the comments, it would seem that excess would be flushed in the urine. Should we shoot for a 1:1 ratio?

    Thanks for your advice and assistance!

    1. amyneuzil Post author

      Hi Jeremy,
      Great questions! First off – I”m so glad your wife is seeing some positive change already. In answer to question 1 – my hesitant nature would say wait another week before upping the dose, but your wife knows her own body better than anyone else, so if she’s comfortable with it then go for it. In terms of timing – for many people the folate is energizing and will keep them awake if they take it at bedtime (I’m one of those). For those people spreading the dose out throughout the day is not really an option. Others don’t notice that at all and do just fine with an evening dose and for those people it’s best to divide dose between morning and evening for maximal absorption. So if she tolerates it well, then do an evening dose. If she doesn’t then don’t push it because sleep is more important than divided doses. 🙂
      As for B12 dosing – most people end up taking a higher dose of B12 than they do of folate. It is water soluble, and tends to be pretty poorly absorbed so typically overdoing it isn’t too much of a problem. Starting with a 1:1 ratio is great, but usually the end point is more of a 2:1 or higher (and often closer to a 10:1 in people with a low methylfolate tolerance).
      Keep me posted – I’d love to hear how it goes for you two!

  39. Trish

    I know this post is kinda late but you asked for responses from other folks who have problems with methylated B vitamins and weight gain. I am a mutant – hetero C677T. I’ve had issues with weight ever since puberty but, while I was young, could manage to lose weight. I won’t go into my whole history but discovered I was a mutant after what I now know was a horrible overmethylation incident while on travel for Thanksgiving 2015. I got tested, did tons of research, and started on methylated B vitamins as we are “supposed” to do. But I kept having overmethylation incidents – usually spurred by eating salads. For me overmethylation included headache, insomnia, non-stop sweating, joint pain, AND weight gain. Every overmethylation incident made me gain 1-2 lbs that I could NOT lose. I would think, surely this is just fluid, and it will go away. Nope. Well, about 16 months later, I’m about 12 lbs heavier and cannot lose it -no matter how little I eat or how much I exercise. I recently quit with methylated B12 and B6. I quit methylfolate early on as even tiny amounts made me totally miserable. I ate a small salad recently and was just fine – a good sign. Now if I could just begin to lose some of this weight or find some guidance to help. I hope this is useful!

    1. amyneuzil Post author

      Thanks so much for sending this Trish, and keep us all posted if you can! I’ll be so curious to hear if the weight drops off now that you’ve stopped the methylated B’s. (Fingers crossed for you that it does!)

  40. Mai

    Hello .. I am totally new to this. I recently had two miscarriages ,after that I found out that I am factor v leiden heterozygous and mtfhr a1298c heterozygous.
    I have been taking 400 mcg folic acid for more than a year !! Unfortunately, in my country there seems to be no knowledge of the problem or the folate . The only effect they tell you about is its effect on the pregnancy.

    I did alot of research and I ordered 800 mcg folte (online). I am planning on TTC this month.will I be able to handle the change and the pregnancy?
    Your article is almost the only helpful thing that I found about dosing.
    So i think I should start with smaller doses and then increase.
    I will really appreciate any advice or suggestion.
    Thank you so much

    1. amyneuzil Post author

      Hi Mai,
      I certainly think you should start with a smaller dose and increase slowly – especially if you’re already pregnant. A sudden switch from folic acid to methylfolate can be a difficult adjustment and I don’t want anything to jeopardize your baby. Good luck and let me know how it goes!

  41. Jenn

    The best supplement I have ever found with the right forms of all the nutrients for MTHFR is Daily Essential Nutrients

  42. Amy

    Hello! So glad I found you. I may need a phone consult. I have 677tc and 1298ac. Cortisol is high but not out of range. I am deficient in choline and glutathione. Folate was off the charts high last March. A different test this past Dec. Showed it was fine but it could be wrong. My b vitamins are fine. Does any of this make sense? I feel fine overall except for major histamine issues. I eat a very clean diet and have been good and environmental allergy tested. I am extremely moody and go back and forth between fight or flight mode and calm, kind of depressed or anxious. Any thoughts would be great. My functional doc does not think this has anything to do with mthfr because my homocystein levels are at 6.

    1. amyneuzil Post author

      Hi Amy,
      Ha! I hear that a lot. Honestly, homocysteine shows up as out of balance for some of us wacky MTHFR mutants, but certainly not all. Actually it seems like not even half. Also homocysteine levels don’t reflect the severity of the MTHFR issue. Also the glutathione deficiency indicates that the MTHFR is actually an issue, plus the mood swings, out of control histamine despite the clean lifestyle and also the high folate. My friend it sounds like getting the MTHFR issues under control could help a lot. Check out this post on undermethylation – this is the issue that is most likely with the high histamines. But yes – I think whether it’s through your current doc or through me or someone else, getting the methylation under control will help tremendously. Keep me posted!

  43. Shavonne Boyle

    Hi amy,
    I know this thread is a little old so I’m hoping that you still see this comment. I just had a recent miscarriage at 6 weeks and 5 days. I have the heterozygous MTHFR C677T and during the ultrasound they found quite a few cysts on my ovaries, leading to the possibility of PCOS, yet I am fairly skinny for my height and have never had any issues with overgrowth of hair. BUT, I have quite extreme hormonal and cystic acne. This is made worse whenever I start taking the B-activ with the methlyated folate in it. I started taking the B-activ supplement as soon as I found out I was pregnant and two days later lost the baby. My acne had also cleared up the weeks before I knew I was pregnant but was and as soon as I started taking it my acne has increased ten fold. Does any of this make sense?
    Thank you

    1. amyneuzil Post author

      Hi Shavonne,
      I’m so very sorry to hear about your loss. Wow. With C677T mutation and possible PCOS you’re going to have to be really careful with your body and your health, especially to have an easy pregnancy. The hormonal and cystic acne could certainly be a sign that your testosterone is too high which would also point to PCOS even without some of the “classic” PCOS signs and symptoms. I have seen other women who have acne in response to the methylfolate. There is a link between the MTHFR and estrogen, so it could be related to that, but it could also be related to detoxification. Sometimes the acne doesn’t happen (or happens briefly and then settles down) if you start with a lower dose of the 5-L MTHF and work your way up, but for some people, it always happens no matter how low the dose. In any case, starting now to work on your 5-LMTHF intake and finding the right dose for you will help to put your body into a much better position for the next pregnancy and keep things more stable so that you aren’t trying to get balanced when things have already started to change. So – yes what you’re saying makes sense, and hopefully now you’ll have an opportunity to get things balanced out and get your body in the best health possible so that you start the next pregnancy with everything going right. Good luck and I hope this is helpful!

  44. David

    Hey Amy,

    Curiosity got the cat. I started taking the methyl folate, SAMe, and MethylB2 was amazing for 2 days. Then it wasn’t. It’s been a week. Brain fog is incredible. I want my old brain back very badly. Looking at my variants below can you hypothesize where i went wrong? Also whats a realistic time frame for getting the old version of myself back again? I will never self-diagnose again I have learned my lesson. I thinks it very cool that you actually take the time to respond to so many people.

    VDR Taq rs731236 AA +/+
    MAO-A R297R rs6323 TT +/+
    CBS C699T rs234706 AA +/+
    MTRR A66G rs1801394 GG +/+
    ACAT1-02 rs3741049 AG +/-
    MTR A2756G rs1805087 AG +/-
    MTRR A664A rs1802059 AG +/-
    BHMT-08 rs651852 CT +/-
    AHCY-01 rs819147 CT +/-
    AHCY-19 rs819171 CT +/-

    1. amyneuzil Post author

      Hi David,
      So – I don’t know what doses you started with, but the methyl folate and SAMe both push the same methylation cycle, so they have a bit of an additive effect (which could have been too much too quickly by the sounds of the brain fog). Also the MethylB 12 might be too quickly processed for your body because you have MTR and MTRR issues – it could be tydroxycobalamin would be better (here’s a whole post on why that might be). And don’t worry – your old brain will come back, just stay away from the supplements for a while. Typically I’d expect 2-3 weeks of slow progress, but I’ve seen people even take a month or more. Crazy how much those simple B vitamins can do to you, right? Don’t worry – you aren’t the first person to overdo it a little and you won’t be the last. You will bounce back, it will just take some time for your body to catch up. Good luck!

  45. Kerry Lifestyle

    Great article, thank you. This is a bit easier for me to take in than Dr. Lynch’s protocol. I believe I have other mutations than just the Hetero for C677T but I didn’t get our genetic testing ordered before the FDA shut down the 23andMe results from being released so I need to look into other ways to get this information. I attempted the methylfolate/B12 protocol and even at an extremely low dose I had extreme side effects and reaction so I know something else is at play. I’m pregnant now and need to explore my other options for getting the supplementation I need! Hoping that I am able to book an appointment with you at some point as we just moved to CO. I look forward to following your work & blog and am hopeful I’ll get my body what it needs to treat the mutation for me and baby.

    1. amyneuzil Post author

      Hi Kerry,
      Thanks so much! I love Dr. Lynch – he’s incredibly knowledgable and I think has more knowledge with the biochemistry, but I agree it can be a bit overwhelming! I’m trying to make things a whole lot simpler. So – 23andme still tests for methylation issues, they just don’t make the information as accessible. Still if you get your results you can run it through an independent methylation analysis. I really like genetic genie They have a great methylation panel and only ask for a small donation for their services. Congratulations about the baby! That’s wonderful news. Be really careful with supplementation when you’re pregnant – we don’t want to encourage any detoxification that might be harmful to the baby. Keep me posted and certainly schedule a phone consult if you feel like you need more guidance. 🙂

  46. Bree A.

    I’m also new to this whole MTHFR gig.
    After my latest missed miscarriage at 17 weeks, my OB took a bunch of blood tests and I have MTHFR C677T.
    My Dr. started me off with Life Extension Optimized Folate 5,000mcg and Methyl B-12 5,000mcg. I’ve been taking it for 5 days and I feel like crap. Tired, muscle soreness in the neck, and basically no energy.
    I know I neee to give my body a chance to adjust, but am I starting too high of doses?
    I also have Hypothyroidism & PCOS. Fun, right? Lol
    I was taking Metformin but heard it’s not great to take with L-Methylfolate. I am still taking 50mcg of Synthroid.
    I just need some advice on all these meds coursing through my veins and how I should be dealing with all this?


    1. amyneuzil Post author

      Hi Bree,
      Jeez – you have the trifecta of trouble. MTHFR, PCOS and hypothyroid. That isn’t fun at all!! My best suggestion would be to talk with your doctor because it sounds like you’re starting on too high a dose for your body. Even just check with your OB to see if you can start with 1/4 and work you way up. I don’t think it’s worth it to try to push through the crappy feeling to wait for your body to adjust, because honestly this might be too high a dose for you even once your body is used to all of this. Also if your OB is willing could you start one at a time so we know what is doing what? The methylcobalamin might not be the easiest B12 for your body so that could be part of it too. Good luck and keep me posted!

  47. Rachel R.

    I stopped taking it and, after the first day off of it (which didn’t seem to make any difference), I feel sooo much better. It could be coincidence (I don’t think I want to challenge it — ick), but I really think either the methylfolate or the methylcobalamin was bothering me.

  48. Rachel R.

    This might be a crazy question, but I don’t know who to ask other than someone who’s very familiar with supplementing methylfolate in mutants. I’m 7 weeks pregnant, and feeling very nauseated — which is pretty weird, because I have four children already (both sexes), and have been pregnant for at least 8 weeks on two other occasions and never experienced any nausea of note. It could, of course, just be a matter of getting older, etc., but it just occurred to me that my folate is different than before.

    I’d tried a few months back to go on methylfolate, and half a dose, one time (total of 200mcg) made me feel drugged for several days, so I never tried again. When I learned I was pregnant, I started taking Plexus’ X Factor, which has both methylfolate (200mcg in the one pill I’m currently taking/day) and methylcobalamin (250mcg) and was thrilled that it didn’t give me that drugged feeling. Is there any possibility it’s the FOLATE making me sick?

    1. amyneuzil Post author

      Hi Rachel,
      Oh wow – great question! And honestly, I’m not sure but I would say it’s certainly possible. Do you have any of your regular multivitamins around that you could try for a week or so just to test it and see? I find any B vitamins make my stomach a little bit icky, but haven’t heard too much either way for a difference between folic acid and methylfolate. But of course, since you had a strong reaction to the methylfolate before this could be a related reaction. If you do try your old multi for a few days let me know how it goes – I’m always curious to hear how these things pan out for people. Good luck!

  49. Angela Lindsey

    So glad I found your article. It is straight forward and an easy guide. I’m new to the MTHFR, just finding out I have this. I’m hetero. My nurse practitioner checked to see if I had this genetic defect because of constant elevated b12 around 900 to 1200. My new blood work shows my methylmalonic acid being 80 with a range of 87-318. My folic acid is 15.7 with normal being >5.4. My homocysteine is 10.5. Normal being <10.4. So I don't know if I need to start with a small amount of methyl folate in a multi vitamin along with the methyl b12 and just switch those two forms. I've always taken regular whole food vitamins but no methyl folate or methyl b12. Just the synthetic forms. But with high b12, I am afraid to take large doses of it or methyl folate. I want to address the slightly high homocystine level, too. Will methyl folate and methyl b12 help decrease homocystine? I have to be careful with some herbs in my vitamins like ashwaganda and also alpha lipoic acid because I understand they interfere with my Synthroid medication. I had thyroid cancer and had my thyroid removed. So I am thinking start slow with a multi vitamin with the methyl folate and methyl b12. See how it goes. Do I always continue taking this multi vitamin if it works for me or must I be concerned with the methyl folate. I'm taking a multi suggested in your article. Thank you for you time. It's greatly appreciated.

    1. amyneuzil Post author

      Hi Angela,
      It’s all so complicated starting out, isn’t it? I completely understand your concerns about driving the blood folic acid or B12 levels up further, and honestly I have seen some people whose blood levels stay high even after getting on the forms that their body is able to use. Priority one though, should be getting that homocysteine down because it is a cardiac risk factor, it’s associated with high inflammation and there is even some emerging research about homocysteine levels and cancer. So yes – start slowly with the multivitamin and work your way up. Try to eliminate forms of synthetic folic acid from your supplements and also from your diet (many foods have folic acid added to make them look healthy – especially grain products) and of course take the multivitamin away from your thyroid medication like everything else. Maybe talk with your doctor to recheck your blood levels in 6-12 months and be patient. This all takes time to unwind. Great luck and keep me posted!

  50. Gibson's Mom

    Hi there,
    Is there a recommendation for methylfolate dosage for infants?
    I am compound heterozygous for the mthfr mutation, as is my 4.5 year old daughter. We also have a 3 mo old son, who at this point we are assuming has at least 1 of the mutations although he has not been tested. I give him as much breast milk as I can, but I have struggled with milk supply issues with both my children. We are currently supplementing my breast milk with a homemade goat milk formula that is whole-food based (recipe from Weston A Price Foundation). Should I be supplementing this with liquid methylfolate? Thank you for assisting!

    1. amyneuzil Post author

      Hi Gibson’s mom.
      Gosh this is an issue that I’ve had to explore recently with my daughter too because it’s too early for testing in any practical way, but it’s likely that she might have some MTHFR differences from average. Supplementing with infants is tricky because the dose issue applies just as much to them as it does to us (possibly even more so) and it can be really hard to find such tiny doses. In general the US RDA for folate in infants is 63 mcg per day (tiny) and the smallest liquid dose I’ve stumbled across is 400 mpg per drop. So if you’re making formula in large batches and try adding a drop in it’s still likely to be more than the suggested dose. You could maybe add a drop to a cup of water and then use a bit of that to try to cut down the dose? It’s all very complicated. We ended up not doing it and relying on breast milk, but her diet was mostly breast milk with only formula as a night time supplement. So??? All in all I’d be very careful about starting with a tiny dose (TINY!!!) if you do start. Another of my clients recently started her tiny person with some and it kept her awake for about a day and a half, so that idea was quickly shelved until her daughter is a little older. Let me know what you end up doing – it’s such a puzzle for parents!

  51. Kathy

    I just read this article and I feel like my husband’s naturopath needs to read it, too. My husband is in really bad shape, and has been for a long time. He started seeing the nat in May. After blood work showing his homocysteine at 17.9, hypothyroid, low testosterone, low cortisol (saliva test) and low dhea, she started him on 3 Methylguard Plus’s per day, dhea 50, liothyronine and nature-throid, weekly iodine and 2 adrenal complex capsules. Seriously, every day gets worse. In July he got shingles on his face and for the past month he has been sick with a cold/allergies/sinus infection? We don’t know, but he started on cephalexin and the symptoms have improved slightly. He now has anxiety, which has not been a problem until all of the supplements. In the beginning, when he thought the Methylguard Plus was making him feel sick, she switched him to 6 Polyphenol nutrient capsules per day and to try to start the MGP again. So, he was taking 6 PVN’s, 3 MGP’s, 2 adrenal complex’s and DHEA 50. In the middle of all that, she had him get b12 injections for 6 weeks and then blood work. His homo went to 12, so she said he should start the testosterone, but he doesn’t think he can handle anything else right now. He stopped the adrenal complex, dhea, PVN’s and MGP a week ago to see if it would lessen the anxiety, and it has, but not entirely. His psych has him on Abilify and Lexapro for depression and yesterday, upped the Lexapro, hoping that would help with anxiety. The nat advised him to get back on the MGP, so he can start the testosterone. He tried 1 today and said he was very sick and anxious all day. After reading your article, I think he should stop all of the supplements and start with 1 PVN and increase 1 per week if he can tolerate it. I apologize for this long post, but I’m so afraid my husband’s going to end up in a mental hospital or worse. I would love your feedback.

    1. amyneuzil Post author

      Oh my goodness Kathy,
      Sounds awful for both of you. Honestly – I don’t know as much about your husband as his naturopath does (obviously) so I hesitate to say anything, but generally if supplements are making a person worse I think it’s a good idea to reexamine them. It sounds like your husband might need a little bit more of a gentle start to things, because really he shouldn’t have to increase his pharmaceutical drugs just to be able to cope with his natural protocol. Maybe a second opinion? Good luck and keep me posted if you can!

  52. Fran

    I just read
    The Anxiety Summit – How Methylfolate can make you Feel Worse and even Cause Anxiety, and What to do about it
    I have been on Pristiq and Xanax Xr for many years. My husband was diagnosed with Pancreatic Cancer over two years and though he is Thank God doing fine I have been feeling depressed. So I found a new psychiatrist as we had to move to another state through all of my husbands treatments and she recommended Deplin 15. Since taking it I have felt so many horrible side effects. Tingling in my arms and legs. Joint pains. Nausea. So after one week I stopped it. It is now almost 3 weeks since I stopped it and I still have these side effects. While I am upset and nervous about it, your article at least made me feel I wasn’t hallucinating these feelings and feel it was definitely too coincidental to be anything other than the Deplin. But no where in your article does it say WHAT TO DO ABOUT IT. Maybe I missed it but how do I get rid of these side effects. I’m drinking lots of water to get it out of my system but wonder how long it takes. I have so much on my plate between my husband and mom I can’t afford to feel this way every day. How do I get this methyl folate out of my system. It’s scaring me. Any advice would be so appreciated. I hope I haven’t caused damage to my body by taking this Deplin15. I feel paranoid that it was a big mistake and it will never go away. Please help

    Fran Finkelstein

    Sent from my iPad

    1. amyneuzil Post author

      Hi Fran,
      Ugh. I’m so sorry to hear about it. Honestly the Deplan 15 is such a massive dose, I’m not surprised your body freaked out. I’ve spoken with a few people in the same situation and honestly, all I know to do is wait it out. You can try a low-dose niacin supplement (just straight niacin – the old fashioned flushing kind) and for some people that helps to “quench” the extra methylation that is happening. Most of all it’s just time. I haven’t ever seen anyone that didn’t get better afterward, but I’ve seen plenty of people who didn’t stop having side effects as quickly as they wanted to. It’s an awful feeling and I’m so sorry you’re having to deal with it on top of everything else. The low dose niacin is worth a shot – even just 0.5mg per day could help. Other than that it’s just time. Just keep your hope – it will go away. Good luck!

  53. Nicola

    Hi, I am compound heterozygous for MTHFR and I also am homozygous for VDR taq, VDR Bsm and MAO-A. I notice that I feel best on only 400mcg of methylfolate and 1000mcg of hydroxocobalamin. I also take the other b vitamins individually as couldn’t find a b complex that had the forms and amounts I wanted to take. My question is that my GP called after I had a blood test to say that my B12 levels are super high, outside of the typical range and that I should stop supplementation with B12. She also said my thyroid was showing signs of being underactive and that she would do another blood test in three months and check my B12 levels. I stopped taking B12 about two weeks ago, but still take the other B vitamins. I can no longer sleep and think it’s due to the absence of B12. Is it possible that 1000mcg of hydroxocobalamin or methylcobalamin is too much to take daily?

    1. amyneuzil Post author

      Hi Nicola,
      This is such an interesting question. Honestly I’ve heard the same thing from a lot of other MTHFR folk – that lab tests show their B12 is really high but either they don’t supplement and never have and so they don’t know where it’s coming from, or they do supplement but if they stop they don’t feel well. Honestly, my thoughts would be that sleep is more important than a number on a lab test so maybe talk with your doctor about going back on it anyway. In general B12 is water soluble and conventional medical knowledge says that taking extra just washes out in your urine. There are some conditions that show up as high B12 in the blood, but those usually show up in other ways too (such as high liver enzymes, irregular white blood cells, and the like). So this is kind of an unknown situation. I would say just be honest with your doctor and say it isn’t worth it to stay off of the B12. If he or she has concerns about the amount you’re taking (other than the number on your blood work) I’d love to hear them, but as far as we know there isn’t any valid medical reason why taking B12 should cause problems. Let me know what your doc says!

  54. Robin Heberling

    Does it matter if the niacin is nicotonic acid or inositol hexanicotinate? Flus free + time release of course

    1. amyneuzil Post author

      Hi Robin,
      The niacin has to be just straight niacin. The flushing kind. As far as I know, this is the only form that helps, although it can be used in a dose low enough that most people won’t actually flush. So just plain old niacin (not the same thing as nicotinic acid or inositol hexanicotinate).

  55. Robin

    I just found out I am heterogenous a1298c. I started l-5-mthf 9 days ago. I suffer from depression and anxiety. After 1 full week doctor said I could go up to 2 pills per day. I am hesitant. I do see improvements, but I need to really work at it with exercise and redirection. Make any sense?

    Curious about the niacin.does it have to be a special form of niacin?

    1. amyneuzil Post author

      Hi Robin,
      If you haven’t had any trouble with the one pill, then your doctor might be right that you could increase although I also think you have to be 100% comfortable with it before you do anything. I completely understand about working at it, and honestly – that’s the biggest part. Listen to your doctor AND your gut. 🙂 In terms of the niacin, it’s actually the straight niacin form (in a very low dose) – not the flush-free or time release. I hope this helps! I’d love to hear how the methylfolate does for you in the long-term.

      1. Nicole

        After being on THORNE 5-MTHF 2mg/day I have felt significantly better, but as soon as started taking this I have gained significant weight fast. I put on 6lbs in the first two weeks without changing my diet habits. And still keep adding lbs. I have started running again in thoughts that it was just me, but I am not so sure since its happened along the introduction of this supplement. Have you heard of this type of side effect?

        1. amyneuzil Post author

          Hi Nicole,
          I haven’t heard of people putting on weight with it, but that doesn’t mean it can’t happen. It could be connected, although I have no idea why. Honestly I”d expect weight loss more than weight gain just because it does help give you more energy and it also helps detoxification. So… ? Keep me posted – also if anyone else has experienced this would you share? I’d love to know what’s going on here. Nicole if it keeps happening let me know. I’m hoping it’s a short term adjustment thing, but honestly this is new to me. 6 lbs in 2 weeks is a lot, and I would typically think water weight, not actual fat accumulation, so hopefully it will come off once your body adjusts. Keep me posted please!

      2. kim

        Hi Amy,

        I have a quick question. My naturopath put me on methyl b12 in the morning 5000mcg and methylfolate (1000mcg, morning and afternoon). She put me on other stuff too but I have had a response after about 3 weeks. All places I had inflammation from past injuries have flared up. My doc said its a response to the methyl folate. Is that true and is this safe? I have stopped everything and just want to make sure I can move through this without taking any other supplements. I actually am taking prednisone and doesn’t seem to work. She recommended Niacin but I’m just so skeptical to put anything in my body. I’m been off the methyl folate for a week now with now change.
        Thank you, Kim

        1. amyneuzil Post author

          Hi Kim,
          So I’ve heard of plenty of people having side effects from the methylfolate, but for whatever reason none of my clients have had the joint pain (not that it doesn’t happen – it’s well documented, just by some coincidence none of my folks have had it). So I can’t say for sure, but my best guess would be to approach it the way I would approach any other side effect, which would be to decrease dose of methylfolate and methylcobalamin and increase some of the nutrients that can be supportive to the process – antioxidants, water, low-dose niacin and that sort of thing. Honestly the doses your doctor started you with are good doses to aim for, but they’re high to start because if you’re new to this then it can be a lot of change for your body. I’d talk with your ND and just see if they can help you to back off a bit and start a little slower. Does that make sense? Keep me posted! I’d love to know how the joint pain changes over time (don’t worry – it will get better, your body is just a little freaked out).

  56. S E

    I’m SO happy to have found your site! I haven’t been tested yet. Adding methylcobalamin and methylfolate has helped IMMENSELY! And also pretty immediately. Having read through all the posts, I’ll sift through the suggestions for manufacturers of supplements and products, knowing I need a B-Complex and some multi with trace minerals. I’ll happily be researching those next! And also take the hint to move slowly with changes.

    Thank you

    1. amyneuzil Post author

      So glad it’s helping! Amazing what a difference the right supplement can make. Best of luck!

  57. Kelley

    I have been taking 7.5mg of methylfolate for a few years now and feel SO much better with it. If I don’t take it I feel like I can’t function. Two questions – 1. I just found out I am pregnant and am wondering if this high dose is OK? My ND didn’t have a very clear answer. 2. With taking a high dose, will a B complex like you mentioned be enough? I was taking methyl B-12 for a long time but it started to not make me feel well. Thank you!!

    1. amyneuzil Post author

      Hi Kelley,
      Congratulations on the pregnancy! So exciting. If your body feels best with the 7.5 mg methylfolate then that is probably the best thing for you in pregnancy – and honestly your folate usage will be a bit higher in the first trimester especially so most of the docs I’ve spoken with seem to think it’s better to overdo than to undergo, but make sure you run everything by your OB or whoever is taking care of the pregnancy. During pregnancy I would switch over from a B complex to a methylated prenatal – Thorne Research has a good one called Basic Prenatal (that’s the one I took during my pregnancy and it went well, but make sure you take it with food). Some women take a separate B12 and some don’t seem to need it. Just depends so go by how you feel and keep good communication with your doctor. Congrats again!

      1. Kelley

        Thank you very much! Have you seen the study that talks about high doses of folate and b12 leading to a 17 fold increase in autism? That’s what got me really worried about the dose.

  58. Elizabeth

    Hi – I could use your help!
    I was just diagnosed as heterozygous for the C677T polymorphism in the MTHFR gene. I’m having trouble finding what supplements will be best for me and what dosage to start out at. Do you have any recommendations on specific supplements/dosage etc? I’d be mainly using this for my ongoing anxiety.
    Any assistance or information you could help with would be great! You seem so knowledgeable, more knowledgeable than anyone or any website I have found.
    I appreciate it so much.

    1. amyneuzil Post author

      Hi Elizabeth,
      The best option is finding a good practitioner (or working with me remotely) – especially with a longstanding issue like anxiety. If you can’t find anyone local or would rather manage this yourself then honestly the best advice is to start small and work your way up. Most people are okay with a 200 mg dose but that’s too much for some so it can be really hard to say. The best plan is just to start small and easy and use a B complex or a multi-vitamin so that you’re getting other B vitamins too (multi vitamin is my favourite – I usually use Thorne Basic Nutrients III or IV and just starting with one capsule per day and working up from there – the suggested dosage is 6 caps daily. I”m not married to this one, but it seems good and easy enough to get from Amazon).

  59. Dawn Rode

    Hello! I could really use some help, please. My son is 6 years old and is heterozygous. His doctor completely dismisses this because she had admitted to not knowing what this is, at all. My son has ADHD. ANXIETY, OCD along with a few other things. I cannot seem to find enough info on dosages of vitamins for kiddos. Please help! I would so appreciate this. I dont know where to start because most info is about adults.
    Thank you so much,


    1. amyneuzil Post author

      Hi Dawn,
      God yes it can be so confusing when we’re working with kiddos. We know that obviously children are smaller, but they are also in the process of growing and forming, which means some systems might work better because they’re newer, so to speak and some might not work as well because they’re still growing. All of this to say, I’m a fan of VERY conservative dosing in kiddos. Here’s an article about dosing that gives paediatric calculations. Honestly, for myself I typically start with a conservative adult dose, adjust to body weight (so if the “typical” adult is 150 lbs and your kiddo is 50 lbs then 1/3 of the adult dose) and then use HALF of that. So essentially you’re adjusting to weight and then cutting it in half – we can always bump up the dose according to how your kiddo does, but if he has a bad reaction you can’t undo the dose you’ve given. Does that make any sense? Just FYI I typically start heterozygous adults around 400 mg. I hope this helps!

  60. Marina

    Dr Neuzil
    Thank you for a very informative post
    I believe I have methylation issues, I feel nauseous when I take B vitamins and even food based B complex or individual B vitamins
    I had ulcerative colitis for close to 20 yrs and a few years ago breast ca and chemo
    With all that I went through I have developed Adrenal insufficiency and trying very hard to get back on track with clean diet and rest
    No dairy gluten and carbs all organic and clean with lots to booked vegetables for supplements but I feel I’m depleted nevertheless and need to supplement
    I was wondering if you are consulting long distance?
    If you are how could I possibly have an appointment with you or at least a conversation as how do I begin to help myself?!
    Appreciate your reply

    1. amyneuzil Post author

      Hi Mariana,
      God with all of that no wonder you’re depleted! I do consult from a distance – all of the new client information is here and you’re more than welcome to schedule a free 15 minute meet and greet to see if this feels like a right fit. Sounds like you’re doing so many things right, you just need that last little nudge. I look forward to talking!

  61. Cheryl Stanescu

    I could really use your suggestion .. I have twins that are 17 years old now that both have Autism. They were both diagnosed years back with both the MTHFR and Factor V Liden gene mutation. We were told to just supplement them with a b12 folic acid supplement.. 1gm of b12 and 400mcg folic acid.
    And side note that we did find my husband has both these genes as well. We were told just to do this and kind of left high and dry on the issue with no follow up with this specialist that we were sent to after we found these gene mutations on blood work my son was having then we all got tested.
    My son is non verbal and my daughter has language but cannot express herself appropriately so it’s not like they can tell me exactly how they feel.
    We just recently took my son off an SSRI medication in April that we know was doing him more harm then good and are now doing the same for my daughter but learned in the process to taper much much more slowly no thanks to the neurology doctors.. You have to take things in your hands sometimes.
    But if you can please give me and recommendation I would so appreciate it.
    I’m always nervous that the b vitamins over stimulate and the folic acid I now hear is not as absorbable so I don’t know what to truly give them.
    Thanks for any information and so glad I came across your article.

    1. amyneuzil Post author

      Hi Cheryl,
      Jeez. MTHFR issues are difficult enough to figure out when people can express exactly what is going on – it would be so much harder when they can’t. Not knowing exactly which MTHFR mutation they have or how bad the compromise is I can’t honestly say, but no matter what I would switch from folic acid to 5-methyltetrahydrofolate. Even with mild compromise the folic acid seems to be a sticky issue. Also especially with kiddos on the autism spectrum I would start extra slow, with an extra small dose, and work your way up. Just try to log behavioral ups and downs because that will probably be the best feedback you get. Also for B12 the methyl form might be too much too fast – lots of mutants don’t handle it well. Maybe try the hydroxy form. Great luck and keep me posted!

  62. Jessica

    Hi. I’m new to trying to learn about mthfr. I suspect I have a mutation but no testing yet. I’m 17 weeks pregnant. I feel extremely anemic after months of vomiting and feeling sick. I’m pale and shaky and weak but can’t seem to get fruits or veggies in without gagging. I heard that zinc could help with gagging/issues when eating. But now I’m nervous to supplement with zinc or iron not knowing my mthfr status. Any suggestions? I don’t want iron infusions but also don’t want to cause damage to my baby. :'( I have yet to find any one discussing zinc supplementation with possible mthfr issues. I’m already taking all the methyl forms of b vitamins. Thank you!

    1. amyneuzil Post author

      Hi Jessica,
      First off, if you suspect anemia then go to the doctor for testing and certainly get on a good iron supplement because severe anemia can be threatening to the pregnancy – we want to make sure your baby is getting lots of oxygen in the blood flow and also enough iron for it’s own development. Is there a reason why you don’t want iron infusions or suppelements? Just to clarify – too much iron is not a good thing for MTHFR mutants because it is linked to cardiac inflammation, but it’s still important to have enough iron so blood testing is a good idea to make sure you’ve got adequate levels. The zinc helps for some people but actually makes it worse for others so certainly you could try, but don’t be discouraged if it isn’t the answer for you. I also haven’t seen any problems for MTHFR folks taking zinc – it should be fine from that angle. Also eating high protein meals (even though it probably makes you want to vomit) for some women really helps the nausea. I hope the protein helps and please get the iron levels tested and supplement if necessary. I hope this helps Jessica and HUGE congratulations about your pregnancy!

      1. Jessica Perez

        Hi! Thank you for responding. I did go to the doctor and get tested for anemia. Everything with my blood work according to them is perfect though and they have no explanation for my dizziness or passing out. I have been feeling better though since adding Garden of Life Healthy Blood to my vitamins. I was concerned about the iron infusions because I am trying to avoid anything that could contain harmful additives, preservatives or synthetics…I just can’t find a lot of information on the infusions. Thankfully I don’t need them. I’ve been eating liver once to twice per week, adding more protein through some organic pea protein shakes and have been doing a little better now. Thank you so much!

  63. Frank

    Hi Amy,

    Are you familiar with Dr. Walsh’s work? He believes that population can be divided into 4 different depression/anxiety cases with 2 of them are “overmethylated” and “undermethylated”, with the majority of the population being “undermethylated”. Reason why I put it into quotes, is because Dr. Ben Lynch uses those terms differently. So when I put in quotes, i’m referring to the way Dr. Walsh sees it.

    By Dr. Walsh definition, “undermethylated” means your body doesn’t produce enough methyl. He basically says, that the “undermethylated” can’t tolerate too much folate, because it is a serotonin reuptake promoter (as opposite to SSRI). And people who are “undermethylated” already have low sertonin activity. Dr. Walsh calls methylfolate a suicide nutrient because it “loses its identity very quickly” in the methylation cycle. If your body doesn’t make enough methyl (“undermethylation”) and you struggle with depression/cognitive impairments, it will strip more methyl than it provides and make you feel worse.

    On the other hand, it’s funny, Dr. Ben Lynch believes methylfolate is a methyl donor and believes otherwise.

    So my comment is: It could be that when a doctor tries to blindly detox a patient by prescribing large dosages of methylfolate and start having bad side effects, it could be that they just don’t respond well for many reasons: one reason is, they are “undermethylated” by Dr. Walsh’s terms. In other words, some people may not need methylfolate at all (or even folate) even with or without SNP. For those people, he recommends B6, magnesium, fish oil, and other methyl-donors (like sam-e and methinione).

    It’s interesting to see how many people keep “pushing” to take methylfolate and keep working up despite side effects. It’s a possibility they just don’t need it.

    Your thoughts?

    1. amyneuzil Post author

      Oh thanks for writing Frank!
      This is such an interesting idea because really, the way we see methylation is entirely open to interpretation. We know that we need methylfolate for some reactions, but we also need SAMe, trimethylglycine, and all of the many hundreds of natural forms of folate that are out there (folate is actually a category of molecules, rather than one specific nutrient – which makes all of this very difficult to sort out!). I think the big thing that you’re pointing to is the frankly terrifying cycle of getting stuck in one “RIGHT” way to do things. I have seen a lot of really bad outcomes that come from a practitioner or expert being so married to the way they do things (that normally works for them) that they can’t see a client struggling in front of them. They’re so convinced that their current way of looking at things is correct that they keep trying to make it work for everyone, when really there isn’t anything in the world that works for everyone (not pharmaceutical drugs, not diets, not nutritional protocols, not anything). So yes – I think there are probably plenty of people out there who have a genuinely bad reaction to methylfolate even though they’re supposed to “need” it.
      Having said that, every human on earth needs some form of folate that works for them – whether it’s methylfolate, folate from foods or even folic acid. The hard part is just figuring out what is right for you as a human.
      Just as an aside – I also don’t view methylfolate as a “methyl donor” in the way I think you mean it. Certainly it goes through chemical pathways in which a methyl is surrendered, but that’s more of a “methyl user” in my view. To me “Methyl donor” is something like trimethylglycine which can shed methyl groups easily for all sorts of uses. Thanks for posting Frank – great comments!

  64. Beth

    Hello. I suspect I have mthfr mutation given both children and nephew have tongue tie. I’m three months post partum. Dairy free and no prenatal currently due to babes intolerance with nursing. I’m experiencing sudden onset and progression of symptoms of b12 deficiency, specifically numbness. I need help advocating for the right kind of medical advice. Where should I start with supplementing? What bloodwork should I request? I’m very overwhelmed and need support. Recommendations for knowledgeable professionals in the Chicago land area? Thank you so much.

    1. amyneuzil Post author

      Hi Beth,
      Ugh – it can be really overwhelming at first. First off, I do think it’s important for you to find a good local practitioner. Here’s a link to our National association, the AANP. I would call around to local docs in your area (sorry, I don’t know anyone off hand to suggest) and ask if they have experience with MTHFR issues. In terms of supplementing, it sounds like you’re concerned about B12 most of all and that one is reasonably easy. The hydroxycobalamin form is well tolerated by mutants and non-mutants alike and that can be an easy place to start. Methylcobalamin is sometimes a little too much, but a mixed B12 with a few different forms can also be a good place to start. In terms of bloodwork, there are tests for MTHFR as well as for blood levels of folic acid, B12 and homocysteine (which shows up abnormally high in some mutants). Generally though with numbness it’s important to work with a practitioner because there can be other causes too (like nerve impingement and neurological issues) so it’s important not to just assume it’s B12 and ignore other possibilities. Good luck and keep me posted!

  65. Scared and confused

    I am a newly diagnosed mutant (lol). After 3 miscarriages, my OB did a whole workup. Everything was normal except that I was “POSITIVE FOR TWO COPIES OF THE A1298 C VARIANT.”
    She prescribed DEPLIN 15 mg to be taken once daily. I feel that this may be too much.
    What are your thoughts on taking Deplin ( L- methylfolate Ca) @ this dose?

    1. Scared and confused

      Some more info: All three of miscarriages were in first trimester and babies seem to stop growing around 6-7 weeks. The last pregnancy was identical twins that stop growing at 6 week 4 days and 6 weeks and 5 days. I carried them until 10 weeks then miscarried. Thankfully I have 3 healthy living children.

      Should I also be taking a prenatal without folic acid. What B vitamins are safe to take? I also take Levothyroxine and Vitamin D.

      1. amyneuzil Post author

        Hi again,
        For mutants I suggest taking prenatals without folic acid (so with the 5 methylfolate). The one I took in my pregnancy was Thorne Research Basic Prenatal. You still need the full complement of other B vitamins so it’s important to take a prenatal. All are safe for you except for the folic acid which competes with methylfolate at receptor sites. So glad you have three healthy kiddos – what a blessing!

    2. amyneuzil Post author

      Hi Scared and Confused,
      I’m so sorry to hear about the miscarriages – I know how awful that can be. As for the deplin, that’s a pretty big dose – you’re kind of jumping to the top of the range, but if you’re looking for a quick pregnancy and don’t have a lot of anxiety or depression (unrelated to the miscarriages, of course) then it could be the best course of action. I would see either take it and see how you feel because there are plenty of people who take deplan with no problems and for fertility and pregnancy a hefty dose can help. If you’re not comfortable with that then talk with your doctor and see if she is really attached to the 15 mg or if maybe starting with the 7 mg dose would be alright. Does that sound reasonable?

  66. Rebecca

    Hi! I am heterozygous A1298C and am 6 weeks pregnant. I’m taking a prenatal with l-methylfolate, and although my OB recommended “additional folic acid – 3 grams”, I know I should be taking the l-methylfolate. (it’s incredible how so many Dr.’s just don’t know about this!) I’m confused about how much additional I really need to take and if it needs to be combined with additional B vitamins. Should I just add the Pure Encapsulations Super B Complex to my regimen, with maybe additional l-methlyfolate? Is there such a thing as too much B complex during pregnancy? If I add only l-methylfolate, will the smaller amount of other B vitamins in my prenatal be sufficient?

    Confused with thanks,

    1. Rebecca

      I also meant to ask, are prenatals with FOLATE good to take? I’m hard pressed to find one that completely comfortable with that has l-methlyfolate.

      1. amyneuzil Post author

        Hi Rebecca,
        Folate should mean the natural forms of folate, but doesn’t always because of weird labeling laws so the best way to know for sure is to call the company that makes them and ask what they use. If it’s a natural source folate then it’s perfect. If it’s really folic acid then not so much.

    2. amyneuzil Post author

      Hi Rebecca,
      It really can be confusing – in my recent pregnancy (even doing this for a living) I was asking everyone what the “Best” thing to do would be. Sadly, my doctors didn’t really have much info either. I aimed for 1mg l-methylfolate every day and the standard doses of other B vitamins. I’ve never had an issue with B12 so I didn’t do anything special there, but if you tend to run low it can be a good idea to add extra. There isn’t really “too much” B complex, but for some women the B vitamins make nausea worse, so it’s sometimes beneficial to only take what you really need and not more (especially if more makes you lose what you’ve taken). Ha! Pregnancy is so glamorous. 😉 Congratulations on your good news!!

  67. Donna

    I am at the end of my first day on Thorne multi. My urine has been neon all day and this evening I started itching like crazy. Could this just be part of the process and will balance out, or is itching always a sign of intolerance? For the time being, I will continue taking them and hope it all balances out in 3 days.

    1. amyneuzil Post author

      Hi Donna,
      Itching isn’t always a sign of intolerance, but it can be. Make sure you’re taking the lowest dose possible and just listen to your body. Hopefully things will smooth out in a couple of days, but if not then don’t keep trying to make them work. Good luck!

  68. Anton

    Hi Amy

    I tried a lozenge with b12 1000mcg and methylfolate 800mcg but felt very wired and edgy/anxious. Weird thing is Ive had b12lozenges with the folate with no problem and I’ve had methylfolate as swallowed caps and was fine. Now I’ve been on a be B comlpex with 400 mehtylfolate and upped to two caps (800) for a while. I’m ready to try the lozenges again but I’m a bit nervous. I think I might absorb lozenges much better than through my gut. My question is, I’ve heard that if you feel bad after a lozenge you should actually take more until you feel better. That a small dose can be worse than a bigger dose. Is this true? Or should I just keep taken the one lozenge (800) for several days even if I feel terrible? I also have some niacinamide (550 mg), should I take that if I feel bad?

    1. amyneuzil Post author

      Hi Anton,
      Yes – I’ve seen a few people who notice this same thing. I think for some of us the lozenge is actually getting the methylfolate in where the capsule isn’t so much. I honestly still suggest starting small, and the great thing about most lozenges is that they’re big enough to cut in halves or even quarters and start that way. It’s a whole lot less scary to take a quarter dose and work your way up than it is to start out with the whole thing. I have heard of people trying the take-more-until-you-feel-better strategy, but honestly it scares the bejesus out of me simply because what if you swing over into over-methylation and don’t know it? Then it just stays bad? How would you know? I think if you start slow then you won’t need the niacinamide, but there can still be a weird few days of adjustment at first – even with a low dose.

  69. Fern Lehmann

    I am a compound heterozygote as well. I am very confused and frustrated; because I can’t find what works for me. I had B12 levels off the chart and it couldn’t even be measured, because it was over 1999. I am taking methyl folate and tolerating it okay I think. I am taking 800 mcg a day. I am not taking B12, because my levels were so high and I was advised not to take it due to my levels. I am not sure this was good advise. I suspect my body is not properly absorbing the B12 and it’s just floating around in my blood. I believe I need a good B complex, but havn’t found one that doesn’t have folic acid and/or the wrong form of B12.

    I also need to take something for joint support. I cannot take many products due to a sulfur allergy.

    I am looking for advise since my own doctors don’t seem to be able to figure out what I am supposed to do. Thanks for any advise or recommendations you can give me. I truly appreciate your dedication to this subject.

    1. amyneuzil Post author

      Hi Fern,
      Ugh. I know it’s so much trial and error for all of us. Honestly, that’s been my experience too so just hang in there – we’ve all got to learn our own particulars for ourselves. I agree that I don’t think you’re utilizing the B12, so it is just floating around in there. It might be interesting to try adding a hydroxycobalamin or adenosylcobalamin (B12, but different forms than you typically see) lozenge to see if you feel any different (hopefully better). I’m not 100% sure, but it seems like when your body gets some B12 it can actually use it feels more comfortable dumping the rest of it out. Some of my clients have seen a decline in their high B12 levels after switching forms of B12 and I feel like that’s why (although I’ve never seen a study on it). Maybe then it would be a little easier to start a B complex like the Pure Encapsulations B Complex Plus without worrying so much about the B12 in it. The good news is that any B12 that you take in a capsule or tablet form (that is swallowed, instead of absorbed under your tongue) is pretty poorly absorbed so as long as it isn’t a big dose you’re probably not getting too much out of it anyway. Keep me posted if you try it – I’d love to hear how it goes for you! As for joint support, it is hard with an allergy. Have you tried Lyprinol? It’s a little pricey but it’s from the green lipped muscle and seems to work well for some folks. The other one that people seem to like is Flexcin, although I think it may have some MSM in it – I’m not sure if you react to that or not. Anyway – keep me posted and great luck!

  70. Mel

    Hi Amy—

    I’ve got a frozen embryo transfer in a week. I’m not MTHFR, but I am wondering about switching from folic acid to methylfolate (also worried about the autism link to folic acid I read about today). I am now taking 800mcg methylfolate in my prenatal, and 1.5mg folic acid in a supplement. I just saw that you said they compete, but I’m not MTHFR so am wondering if it’s ok. What SHOULD I be taking? Thanks!

    1. amyneuzil Post author

      Hi Mel,
      This is such a great question and I wish I had the perfect answer, but it’s actually a really weird issue. My personal preference is to stick to 5MTHF if you’re a mutant or not, simply because it is the form your body needs and folic acid does have some pretty sketchy research out there (there are links to cancer too and all kinds of issues). The problem is that switching 1:1, meaning keeping exactly the same dose of 5MTHF and folic acid, sometimes doesn’t work out. As it turns out even if you’re not a mutant the 5MTHF can be stimulating or agitating and some people really feel hyper or agitated when they take it. So if you’re thinking about switching over I’d say keep doing the prenatal and maybe get a 400 mcg 5MTHF and add in one at a time until you’re back up to the dose you want. Make sure you clear all of this with the fertility group doing the embryo transfer though because we want to make sure that goes perfectly! Great luck with the transfer and keep me posted on what you decide to do and what your fertility folk have to say about it. It’s always interesting.

  71. Ashley

    Hello, I was recently diagnosed with heterozygous c677t. I did not have any symptoms/problems before finding out other than a miscarriage in February. I have been seeing a chiropractor/functional medicine doctor who has put me on several things. I found out this weekend that I am pregnant again and am very concerned that I am taking too much. All of this is very confusing to me and I can’t seem to find a straight answer on what exactly I should be taking and the appropriate dosage. This is what I am currently taking. Could taking too much harm my pregnancy?

    (contains 1000 mcg of folate as calcium L-5 methyltetrahydrofolate)

    Methylation Complete (twice daily)
    Amount Per Serving:
    Vitamin B12 (Methylcobalamin) 5,000 mcg
    Vitamin B12 (Hydroxocobalamin) 2,000 mcg
    Vitamin B6 (Pyridoxal-5-phosphate) 2 mg
    Proprietary Blend of: Quatrefolic™ (Tetrahydrofolate) and (6S) 5-MTHF (5-Methyltetrahydrofolate) 3.2 mg

    Methyl Folate Plus: (twice daily)
    Vitamin B2 (as Riboflavin-5-Phosphate) 30 mg (2147% DV)
    Calcium -L-Methyltetrahydrofolate 5 mg
    Folinic Acid 2 mg
    Vitamin B3 (as Niacinamide) 125 mg

    1. amyneuzil Post author

      Hi Ashley,
      Congratulations on your pregnancy! That’s very exciting. I haven’t seen any research that indicates that too much active folate is a problem, but I would question whether or not you actually need all of that. Anything your body isn’t using should get flushed out in your urine, so it could be that a lot of that is actually being flushed away. Looks like you’re getting 1mg folate from prenatals, then an additional 3.2 from the MEthylation complete and 7 from the Methyl folate plus. That’s a lot. I would talk with the doctor who made the recommendations and see if you can keep the prenatals but maybe reduce the other two (once a day? once on alternate days?). He or she will know your particular situation far better than I do and may have had a reason for giving you such hefty doses so check it over with them. Great luck with this pregnancy!

    2. Mary


      The chiropractor/ functional doctor that I am seeing also suggested this exact supplement. She suggested taking one in the a.m. and one at night. I took 1/2 of a tablet and experience negative side effects for 5 days. I think her recommended dose is too much for my body. I am a small petite person, and tend to be very sensitive to certain things, especially b vitamins. I have been seeing her for 5 months, and her protocols have not worked well for me.
      Not too mention the cost of these supplements are pricey. I have a bag of multiple supplements that I have purchased from this doctor, have used them once or twice, and none of them work for me due to negative side effects. The upsetting part is they do not take returns even with a receipt under any circumstance. I am beginning to have second thought about this doctor. Sorry for going on a tangent! But I recognize the above Methyl Complete. Best of luck and congrats!

  72. Daniella Bewley

    Hi Dr Amy,
    I’m Homo C & taking 8mg of Methyl Folate. My Dr had me start the Methyl Folate with an activated B Vitamin. I’ve been on this combo for a good 7 months with no side effects or benefits either. A few days ago she me swap the activated B’s for a Methyl B (500mcg) which has finally made me feel happy & energised. The only issue is with sleep, I seem to be over stimulated. My Dr suggested I go back to the activated B however the only benefit I have felt is with the Methyl B. What can I do? Perhaps the combination of both is just too much ?

    1. amyneuzil Post author

      Hi Daniella,
      Great question! So – the first few days can be a little weird anyway, I’d say hang in there for a minute and see if the sleep sorts itself out (a lot of the time it does). If it doesn’t, then I’d talk with your doctor to see if you could stay on the Methyl B, but decrease the Methyl Folate and see if you can keep the benefits without the side effects. It sounds like your doctor is actually doing a really good job so just hash over options with her -she’ll help you come up with a good plan. Let me know what works for you!

  73. nicole

    I started to take the thorne Basic B complex and began having severe anxiety. Is this common? I am also seeing hair loss as well. Any recommendations?

    1. amyneuzil Post author

      Hi Nicole,
      The anxiety could be a sign that it’s just too much too quickly for you. It’s kind of a pain to do, but if you can take the powder out of the capsules and split it in quarters and start with that it might help. The powder is totally gross, of course, but you can usually hide it in something like applesauce or yogurt (still gross, but less than trying to just gag it down with water or something). It’s messy and inconvenient but will hopefully help with the anxiety. Once you adjust to 1/4 dose for a while (at least a couple of weeks) then you can try increasing a little bit and see how it goes. The hair loss is a new one for me, but honestly people have so many weird reactions wtih methyl-Bs that I would guess that it’s also probably a dose issue. Give it a try and let me know how it goes for you!

    1. amyneuzil Post author

      Hi Theresa,
      It’s possible, but not always easy and usually you have to get the methylation under control so that you can get inflammation down and detoxification happening. If inflammation is high it’s near impossible to lose weight and if you can’t detox then forget about it. So the short answer is step 1 needs to be balancing your methylation. Once that has happened then you can actually start. Good luck! And great question – I’ll add this to the list of things to write a post about. 🙂

  74. Kim

    Just found this website.. I love it. Thank you. I’m getting pretty desperate for help. I’ve been to several doctors, natural and MD and I’m running out of money running to different doctors. I’m miserable. I’m a compound heterozygous for MTHFR and found out I am heterozygous for the COMT val158met. I have no idea if that one matters. Anyhow the MTHFR report said I’m at 48% function. My fingernails have been losing lunulas over the past few years. I barely have any on my thumbs. My nail beds are pale and they have now developed red bands across the top like Terry’s nails. I’m always having cold hands and feet, sluggish thyroid, hard to warm up. Hard to lose weight unless I starve or do keto. My iron was low last labwork in December and have been taking Iron Bisglycinate since then. My B12 was high. Very high. >2000 actually. Folate said >20. This made me feel scared to take anymore B12 or folate. I had taken high dose methyl B12 and methylfolate on and off since my mom is also a compound heterozygous. I did not take any supplements before testing either. I’m a Life Extension member and I use mostly their supplements. I take their 2-per-day multi and fish oil, extra magnesium, R-Lipoic-Acid, extra Vitamin C and few others. I pulse dose everything except multi, fish oil, Vit C and Iron. So is it safe to take more methyl B12 with B12 that high? Or folate? Oh yeah and at the same time my labs were done I took a urinary methylmalonic acid test to see if my body was in fact using that B12. Turns out the result was low so it seemed I didn’t need more B12. Here’s the results.. Methylmalonic Acid 3.3 range 1.6-29.7. MMA-Normalized (crt) 1.4 range 0.4-2.5. I dunno what to do. I keep reading disappearing lunulas means B12 is low but seems mine isn’t. I do have a yellowy complexion and have for a long time. I’ve had major anxiety and depression since a child. I just feel like I’m at my wits end. I’m so tired of doctors telling me I’m fine because my labs look good and I’m not overweight. I need help please. My circulation needs help. I read constantly and try to figure out how to treat myself as best as I can.

    1. amyneuzil Post author

      Hi Kim,
      Sounds like a mess. So – you’ve been taking the methyl B12 and 5MTHF off and on for a while, do you ever notice a difference with (or without) them? I wouldn’t worry too much about the lunulas – it can mean low B12, but for some people they disappear without any relation to B12 so the labs are more relevant in your case. The COMT is a big issue unfortunately as people with the COMT mutation tend to metabolize some of their neurotransmitters extra quickly – meaning they’re gone before you get any benefit out of them. This creates a lot of metabolic waste in the brain which can then interfere with other things. For the COMT issue it’s important to take fat soluble antioxidants that can cross the blood brain barrier, like the gamma form of vitamin E or alpha lipoic acid (but keep an eye on your blood sugar because high dose ALA tends to bring blood sugar down, so if you tend to be a little up and down it’s important to have it with a high protein meal). If the methyl forms of the B vitamins aren’t really giving you any results it might be useful to try the hydroxy form of B12, but honestly you’ve got so much going on that the best course of action is to find someone you can work with on a whole body level to really help to guide you through this. It’s too messy otherwise if it’s just a little bit of advice here and a little bit there. I hope this helps!

      1. Kim

        I sooo wish you were my doctor. I have a good doctor. She’s an MD and a natural doctor. She knows methylation but doesn’t seem to take me as seriously as I hoped. She didn’t think it serious enough to do my methylation testing so I’m doing it on my own. Yes I have been taking methyl B12 and methylfolate on and off for a few years. I haven’t noticed a whole lot when I take them. In fact I notice more when I take iron. I took them hoping I’d start to feel better from being cold all the time, my thyroid is slow, I’m yellow skinned, swollen tongue with my teeth marks all along the sides, my digestion is so slow, I can’t sweat anymore upon exertion, serious anxiety since childhood causing me trouble to achieve milestones.. It goes on and on. For awhile I was having trouble breathing. It got so bad I could barely go up stairs. The iron helped that, I breathe better but not wonderful. I used to be super active. I ran, a lot. I can’t breathe enough to run any notable distance anymore. None of these things went away after taking methyl B12 and folate. I have calmed down some which is good. My anxiety is slightly less and I’m less aggressive now. Then I noticed my labs. My B12 being >2000, low Methylmalonic Acid and Folate >20. Homocysteine 6.5, Vitamin D 39.8, Ferritin 69, Iron serum 44 Range 35-155, TIBC 310 Range 250-450, Iron Saturation 14 LOW Range 15-55 I was too scared to take anymore B12 and folate. Now in my multi(Life Extension) I have low dose methyl B12 and methylfolate and I get a small dose daily but I’m afraid to take any extra. I was concerned with my lunulas disappearing because I watched them shrink and disappear within 3 years. I know something is happening in me but I don’t know what it is. Some nutrient is low or something slowed down. I’m now missing all my lunulas and have 2 tiny sliver lunulas on my thumbs. They are almost gone too. Ok so this COMT thing really is a big deal. I’ve been desperately trying to learn methylation. So this is another problem I need to address. I take RLA instead of ALA since it’s more bioavailable. I also pulse dose a natural Vitamin E from Life Extension. I pulse dose A and D too. I intend to get Amy Yasko’s test done to learn whatever else I can about what’s up with my methylation. I’m tired of living like this and I want to change it even if I have to do it myself. Thank you for taking the time to make a difference. I’m glad I stumbled upon this website. Oh I have another question. If unusable B12 builds up in the blood and unusable folate.. What happens to it? How can it be lowered so only the methyl B12 and folate are in the blood? BTW I’m 33/f.

        1. amyneuzil Post author

          Wow Kim – what a journey.
          So interesting about the iron – and honestly across the board it sounds like your numbers are low, so it could be that iron is more the deficiency than B12/folate. I really admire you digging in to all of this information – it isn’t easy and it takes lots of time, but you are always your own best advocate. With the unusable B12 and folate – they are still water soluble so your body should be able to flush them out (make sure you’re getting enough water) but the problem is that while they’re there they compete with the active forms. We only have so many receptors for folate and if they’re all full of folic acid then we don’t get the benefit of the 5-MTHF even if we’re taking it. Because of that it’s really important to work on the diet too and get rid of a bunch of the folic acid fortified foods (wheat is the big culprit). It’s not easy, but it helps SO much. Honestly I feel like when I started my journey I noticed more of a positive difference from getting rid of wheat than I did from the 5-MTHF (although that made a difference too). Also they just started adding folic acid to corn flour, so that’s off the list too now. Sigh. Great luck and keep me posted!

          1. Kim

            So it’s a little past 3 months since I posted. My iron is at normal high levels. I pulse dose my iron now. I only take iron MWF. I’ve recently started taking Hydroxocobalamin. 1000 mg twice a day. I’m not feeling anything yet and it’s been about a week. My multi has 300 mcg methyl B12. I still have poor circulation and my lunulas on my thumbs are nearly gone. I keep reading that lunulas are a B12 problem. Also I have many other symptoms of B12 deficiency even tho my lab tests showed B12 over 2000. So I guess no matter what the tests show I will keep taking B12 and try to get my lunulas back. MTHFR is such a pain. I also take Iodine now. I take the Terry Naturally iodine with Tyrosine. I take it once a week and also dump out half the capsule since high dose iodine bothered me at first but now I don’t have any side effects with my breathing. Lucky for me the iodine has appeared to help my thyroid kick up a bit. I am now growing hair back on my outer eyebrows! Incredible. Unfortunately something I’m doing is causing my facial hair to get worse. I have to pull out more hairs from my chin and they are darkening too. I have changed my diet. I am now doing green smoothies for breakfast. 2 cups Greens, 1 cup almond/coconut milk, 1 TBSP either coconut flour or chia seeds and 2 cups of either berries or vegetables mixed. This starts my day. My fiber has been up near 25 grams daily. I’m trying to eat more vegetables all day. Work in progress.

          2. amyneuzil Post author

            Ha! *Always* a work in progress. Sounds like things are moving in the right direction though, which is awesome. If your thyroid is changing a bit that might be changing your female hormones too – potentially part of the issue with the facial hair? Has your cycle changed? Keep up the good work!

          3. Kim

            Well my cycle had gotten really bad and it’s improving. It was frequently a week late with horrible symptoms of pregnancy. It would confuse me and my husband and I would be crazy until we tested. Now it’s been more like 1-2 days late. So the cycle is improving. The facial hair had been a problem, every year seeming to bring another hair or 2 on my chin. Now there are several more at once. I’m 5′ and weigh around 125-126. I’m a bit overweight so if I can lose some weight perhaps I will improve more. Weight is a battle. I’ve tried it all too. Low carb high fats, low calorie, intermittent fasting, etc. All I did was successfully slow down my thyroid and make myself cold and fat. What I need to do is take away all foods and only eat fruit, veg and lean meats. I can tell my digestion is terrible and inflammation is high. I cough up mucous after nearly everything I eat. I know what I need to do I just need to get to it.

  75. Erica

    Hello, I have been having issues for years with being fatigue, agitated, absent minded, confused, ext. I just recently found our that I have heterozygous c677t and a1298 MTHFR. I am 29, and I really don’t know what any of this means! I read above to start B vitamin supplements, so I bought the super b complex from Pure Encapsulations, I keep reading to start slowly and go slowly, but these are capsules so they can only be taken one way. Is that a good vitamin to start with? I just want to feel better, I want my anxiety to go away and to feel somewhat “normal”. Also has anyone had any other vascular issues from having both of these mutations together? I have a vascular lesion in my brain that occasionally bleeds (small amounts of blood) and my neuro ran a ton of tests to see if that was caused by a bigger vascular problem, but when the test came back abnormal, she didn’t say much about it. I just need to know what things to avoid and what vitamins to start feeling better! FAST! 🙂

    1. amyneuzil Post author

      Hi Erica,
      Is it the B complex Plus? I can’t find a super B complex from Pure. I really like that one and *most* people are okay to start with one per day because it’s only 400 mcg of 5-MTHF, but occasionally someone has a bad reaction to even that low a dose. I think it’s worth a try and just remember the first three days you might feel a little bit funny anyway, but try to stick to it because usually things normalize (unless the dose really is too high). If you find out the dose really is too high with those you can always empty part of the powder out of the capsules. It’s not precise, but it works in a pinch. Take a look at the foods to avoid too – that is really important when you’re having symptoms and it makes a huge difference! In terms of vascular issues – MTHFR is certainly linked to some vascular inflammation, but the lesion sounds like a different thing. As far as I’m aware MTHFR is more often linked with clotting disorders rather than bleeding disorders, but honestly there is so much we don’t know that there still could be some correlation. So bottom line is start with the B complex Plus and give it a few days before you make the decision about whether or not it’s a good starting place, then take a look at your diet and really work to take out the folic acid and add in good sources of natural folate. Then we’ll see where things settle out! Keep me posted!

  76. sue

    Thank you for setting up this website. I am compound heterozygous for C677T and A1298C, low in b-12 and have CFS (had mono several years ago). Energy and focus ( like the dog named Doug in, “UP”……. “Squirrel,” LOL) are hard to sustain as well as experiencing overwhelm and anxiety. Want to be positive, upbeat….
    So between the overwhelm and not knowing what to do,, where would be a good place to begin? Would SAMe be good to consider?
    Thank you so very much!!!!

    1. amyneuzil Post author

      Hi Sue,
      Honestly – I”d start with a GOOD multivitamin with 5-MTHF. The one I use personally is Thorne Basic Nutrients (I use III currently because I don’t need iron at the moment but choose the number that’s right for you). Start with the lowest dose possible and slowly (SLOWLY!!!) work your way up. Most people notice an uptick in mood and energy at the right dose, but of course with MTHFR mutations finding your right dose is entirely individual. SAMe is good for some MTHFR mutants, but not all and often I see it work tremendously well for 3 months, only to stop working because something else isn’t supported. With SAMe it helps to be working with someone who can help to manage the process. Start simple and if you need more help then find a great local practitioner or give me a call.

  77. Emily Wagner

    Hello! So I found out about a month ago that I have MTHFR c.665C>T and A222V Homozygote. I really have no idea what any of this means and am having trouble finding things online about my particular type of mutation. My Doctor had no idea what MTHFR even was. I started taking The B complex from pure encapsulations two days ago to see how i feel. I haven’t noticed an increase in mood or energy and I still feel pretty regularly icky but my main concern is my pee is now bright yellow and I read somewhere that your pee being bright yellow means your body isn’t absorbing the b vitamins at all. So pardon my ignorance about everything but if anyone has any information they would like to share with me that would be really wonderful! Thanks 🙂

    1. amyneuzil Post author

      Hi Emily,
      It can all be a little bit overwhelming, can’t it? So – the bright yellow pee is a sign that extra B vitamins are being released in your urine. It’s like the (somewhat literal) overflow valve. It doesn’t necessarily mean you aren’t absorbing any B vitamins, just that you aren’t absorbing all of them. Honestly, that’s pretty normal. You’re off to a good start, so just keep researching and see what feels right to you. If you hit a stumbling block let me know!

      1. Emily Wagner

        Thanks so much! Ive been taking the pure encapsulations b complex for about 3 weeks now and I noticed a little bit of a difference but not much. Do I just need a higher dose of folate? My anxiety and depression has gotten a little better but not as much as I would like! My doctor just doesn’t know anything about MTHFR and isn’t really interested in helping me much. How can I go about self medicating? Where can I get a really great quality folate supplement and how much should I take? Thanks so much 🙂

        1. amyneuzil Post author

          Ha! So can I tell you how hilarious I think it is that your email is muffinbutton? That is just great. If you’ve been taking it for 3 weeks and feel pretty stable then you could probably add in a higher dose of the 5MTHF and see where that takes you. I really like the Seeking Health products, Pure Encapsulations or Thorne Research. All of them seem to standardize very well so that what is on the label is actually in the bottle. Amazon is my usual source for all things 🙂 Just increase your dose really gradually because it can get really rough if you jump up too quickly. Also things get messy if you over-do it, so slow and steady. Also check back – I’m putting together a class for MTHFR mutants about how to do it yourself because there are so many of us and so few doctors who really work with this. Maybe increase by 400 mcg at a time and see how it goes. Great luck!

          1. Emily Wagner

            wonderful! Thanks so much! So I’m going to get the Thorne Research – 5-MTHF Folate Supplement – 1 mg Folate – 60 Vegetarian Capsules and am wondering about dosage. should i take one a day or half of one a day?
            Thats a great idea! I would love to know more about treating myself!

  78. Nancy Hordis

    My husband has had depression/generalized anxiety disorder for years and recently had a gene test done and found out he has this MTHFR mutation. Do you think it is necessary to take an ammonia and/or glutamate scavenger before starting the methlyfolate? He took each of those for about a week or so and didn’t notice much difference so he stopped and is now taking the methylfolate and B12 (3 days ago)…he still isn’t feeling great, but how does one know if it’s from the supplements or just regular anxiety/depression symptoms?? Also he is thinking about adding L theanine and Sam e, what are your thoughts on that?

    1. amyneuzil Post author

      Hi Nancy,
      Yes – it’s all very confusing and honestly it’s hard to tell what are just someone’s “normal” symptoms and what is caused by the supplements. Honestly it may help to keep a symptom diary – rate each “normal” symptom on a scale from 1-10 every day and then add supplements in low doses one at a time and keep track of those same symptoms and add any new ones. It can really help to sort out what is caused by what. If he’s only been on the methylfolate for 3 days I wouldnt’ add anything else just yet until you know how he’s responding to this. It just makes everything confusing. I try to give everything a couple of weeks alone before adding or changing doses or whatever – it’s slow, but at least you have a handle on what changes are causing what. Remember with any of this stuff the first three days can be pretty strange anyway because your body is trying to adjust to different neurotransmitter levels and detoxification.

  79. Ian

    Very confused. I have c677t. My folic acid is over 19.9. I was prescribed methyl b12 which has folate 5 methyletrahydrofolic acid in it. Is this good or bad for me?

    1. amyneuzil Post author

      Hi Ian,
      So – this is the right form of folate for us mutants, so it should be good for you. Still you may feel a little odd for the first three days and if the dose is too high then you may feel odd in general. Just be aware of how you’re feeling and generally change doses slowly so you know what’s going on.

  80. Heather

    Hi Amy,
    Thank you for all of this wonderful information. I’ve been going crazy for years trying to figure out the culprit of my symptoms. I have been diagnosed as homozygous for c677t and am just now trying to figure out supplementation. I would like to have a baby in the near future and am trying to figure out how this fits into the situation. I would like to start with a b-complex as you suggested, but can I take a prenatal with appropriate active vitamins as well? Also, as I increase methylfolate should I increase methyl b-12 as well?
    Thank you so much. I’m looking forward to feeling better soon!

    1. amyneuzil Post author

      Hi Heather,
      Yes – so supplementing the 5-MTHF is especially important if you’re looking at having a baby because without folate we’re at risk for all kinds of issues with the pregnancy. It is safe to take the prenatal (with methylfolate – I used the Basic Prenatal by Thorne Research) along with the active B complex, although increase your dose slowly to make sure you’re not overdoing it. If the dose of the two together is too much for you then just stick with the Prenatal. A good one should have 1000 mcg of the methylfolate. As for the B12 the methyl form may suit you or the hydroxy form – there is a whole post about it here. You don’t necessarily have to increase one as you increase the other, but you will feel best if you find the right dose of both for your body. Again it’s individual, so there isn’t really any “typical.” Good luck and keep me posted!

  81. melissa

    Whoever made this website is an absolute angel. I’ve been feeling kinda bad lately, more than I ever tell anyone, and just going along, at almost 43 years old…I was diagnosed with MTHFR mutation 14 years ago, during my pregnancy, and was put on folic acid…I’ve always just taken one or two baby aspirin 1 X per day, as they told me I had a “rare blood-clotting disorder” but that it would really only affect me if I got pregnant again, in which case I did, and nearly had a spontanious abortion [miscarriage) but somehow managed to make it to 33 weeks and my water broke, thankfully my last son pulled through and is a strapping 145 lb. 12 year old…so I managed to have 4 sons with the MTHFR mutation, although I was considered high-risk and had to be monitored 3 X per week, (also having insulin dependent gestational diabetes also)…my children are truly miracles! So, I manged for many years with no symptoms…. it’s always been in the back of my mind that I had this strange condition, and now, I’ve been having symptoms, didn’t even realize MTHFR would cause symptoms outside of pregnancy, I feel so empowered! I don’t feel like it’s a mystery anymore…I know why I feel the way I do, and I can take the 5-B Complex and at least try to get my health in a better state… and I’m commenting to let you know this website is so appreciated, I’d like to see a donation button to help with the expenses you must incur 🙂 and I appreciate how it must be helping COUNTLESS people suffering and even just informing people that are unaware, as I was, that they are at risk for so many health problems from this…. so, I also comment in the hopes that someone might gain something from my experience with this…I was told when I was diagnosed that they didn’t know too much yet about it… I’m told it’s inherited, I did have an aunt on my father’s side that had many miscarriages and still births, she managed to have 1 child to term that lived…as far as I know, none of my siblings have it, and I know my one sister was checked and was negative, so I don’t know why I was the odd one. Hope this post helps someone, thanks again.

  82. melissa

    wow, so…if taking folate in b-complex, we need to stay away from eating foods rich in folic acid?

    1. amyneuzil Post author

      Great questions Melissa!
      So – foods rich in natural folate are actually great for MTHFR mutants, but foods that have been fortified with folic acid (which is synthetic and needs to be converted to folate using the MTHFR gene) is a problem. It’s mostly grains that are fortified – I wrote a whole post about it here. I hope this helps!

  83. Elize

    Greetings from Elize

    I am hetro c677t. Would biotin be good for me to use as I have Hashimoto and developed tremors that affect my right arm and head. MRI indicated white matter but no lesions or any other issues. I eat gluten, dairy, soy, sugar, grain free.

    1. amyneuzil Post author

      Hi Elize,
      So – it’s hard for me to say just because it sounds like your situation is highly complex, so the best person to ask would be your neurologist. Biotin deficiency can cause symptoms of both hair loss and tremors that mimic essential tremor, but hashimoto can also be responsible for hair loss and the tremors being right-sided only makes me think it may not be a whole body issue (like a vitamin deficiency would be). Talk with your neurologist about it. To my knowledge MTHFR mutants don’t have any differences in the way we handle biotin so from that angle the biotin should be fine. Good luck and let me know what your neurologist says and how it all goes!

  84. Amy

    I was told years ago that I have MTHFR and was told to take Folic Acid. I am on Venlafaxine 150mg a day for anxiety and panic attacks for about 4 years now. Should I have my blood tested again and see how my blood is doing?

    1. amyneuzil Post author

      Hi Amy,
      So, the bummer about MTHFR is that there isn’t a great blood test to tell you how you’re doing or not. For some of us mutants homocysteine will show up high, for some it doesn’t. For some folic acid gets super high or weirdly low, for some it doesn’t. I’d say go more by your symptoms – they’re a better indicator. Also double check with your doctor to see if they still feel the folic acid is the best thing for you, or if perhaps folate or 5-MTHF would be better. Our knowledge has expanded significantly even in the last 2 years, so the doctor may have some different things to say.

  85. Marianna


    which Vitamin B medication that includes all B’s and folate for an MTHFR mutant do you recommend? I want sublingual because I heard its better absorbed than swallowing pill.

    There are many types on Amazon but I want to know which one to take as some are missing some B vitamins.



    1. amyneuzil Post author

      Hi Marianna,
      Sadly I don’t know of any complete B complex vitamins that are sublingual. There is a B complex liquid from Pure Encapsulations that might be closest to what you’re looking for, but it doesn’t have any folate in it so you’d have to take a sublingual methylfolate separately. I know Dr. Ben Lynch makes a sublingual MTHF and B12 lozynge, but I don’t believe he makes a sublingual B complex that has all the other B vitamins in it. All in all it seems like there aren’t a lot of perfect solutions – it just comes down to finding what works best for you.

  86. stan tomaszewski

    Hi, I recently learned i have the MTHFR issue with C667T and A1298C.
    I started to take B12 methylcobalamin and 5MTHF. I was taking 1 milligram each and felt not well. So i cut it to 1/4 milligram each. I felt great for a week or so, then I seemed to crash and now i feel back to how I used to feel, sluggish, brain foggy,head achy, cant sleep, not up beat etc. I am not sure what the right thing to do now may be. Alter the dose up or down? Take niacin? Should i take only one of the supplements at a time and if so which one and then how much of the other? I am also mercury toxic along w/ several others like aluminum, tin, nickel,arsenic, lead. I have mineral derangement from the mercury. I appreciate your help very much.Thank you for having this available as this is not easy to figure out.

    1. amyneuzil Post author

      Hi Stan,
      Ugh. Yes – it’s a highly complicated guessing game/process of elimination. Sad, but true. Honestly I”d start with only the methylfolate and work to find a good dose for you before you try adding the B12. Sounds like the 1/4 mg was okay so go back to that without the B12 and if you don’t see any improvement then increase. If increasing makes it worse then decrease. It’s like playing a logic game with your body. Best policy is always to work with someone who can help and guide you, but while you’re finding that person try a simple process of elimination. Great luck!

  87. Lisa


    I commented back in the summer about taking methylfolate before getting pregnant and if it helps correct adhd. You helped a ton and in August I started taking the “pure” brand you mentioned plus 2000mg extra of the methylfolate. Every time I tried to increase the dose my mood changed so I’ve stuck with the 2400 mg total. Well I just found out last week im pregnant (hooray!) and wanted to know if I need to cut back on my dose or if I’m feeling great just leave it? I also take vitamin d, extra b6, zinc, liquid chlorophyll, and carlsons fish oil. Is there anything else you would recommend taking since I won’t be able to see my obgyn doctor until about week 10. I’m also staying away from as many chemicals and toxins and completely off of gluten as to steer clear of folic acid in any form. I also exercise daily to help with methylation. Thank you so much for your wealth of knowledge!!! You have no idea how much you have already helped me. Lisa

    1. amyneuzil Post author

      Oh my gosh Lisa – CONGRATULATIONS!! That is fabulous news. If you’re feeling well on that dose then I’d say stick to it – your body always knows best. In general a good prenatal vitamin and fish oils are the best things in early pregnancy and the vitamin D is icing on the cake. Thorne Research makes a great methylated prenatal vitamin called Basic Prenatal that has 1000 mcg methylfolate so if you choose to start that one just decrease your MTHFR dose appropriately. I am so pleased to hear how well you’re doing! Keep me posted about your little one. 🙂

  88. Laura Young

    Thank you for this information! I have a double A1298c mutation. I’ve had severe anxiety for years and must take several mgs of lorazepam. I also spiral into depression easily, and have been told I’m probably rapid cycling. No antidepressant has ever worked for me longer than a month or two. It’s so discouraging and frustrating. I take 15mg of deplin but see little help in that. I’m desperate to find something that works. I have seven children. Two have autism and two have ADD/ADHD. They take no supplements. We eat very clean. Again, don’t see a huge success with this unless my oldest autistic eats gluten. Suggestions??? Thank you!

    1. amyneuzil Post author

      Hi Laura,
      Ugh. It’s so hard with MTHFR mutations because really the medications don’t work the same for our neurochemistry. The 15 mg deplan is a pretty hefty dose – could you talk with your doctor about trying a greatly reduced dose to see if that feels better? For a lot of people the 15 mg will overmethylate them and a smaller dose actually brings greater relief. It is really frustrating and will probably take a lot of monkeying around, but my first guess would be that you’re actually taking more than your body needs. Give it a try and if you have a minute let me know how it goes!

  89. Terry caples

    Dr Amy…..Hi. I just received report from serum testing..
    I am Mthfr C677T on one allele. Heterozygous A?
    I’m confused I’m a 63 yo female.
    Anxiety , depression.
    My physchiatrist prescribed Deplin. 15 mg.
    I took it a few weeks.
    Never told me about B12 or other vitamins.
    I’m so confused.
    He doesn’t know a lot, said its a new thing he’s doing.
    My family doctor is also un educated in this booming area of health..

    What should I do?
    They don’t know. Just told me to take the Deplin forever..
    Never mentioned natural food ..only to say, my body couldn’t process it due to blood brain barrier..
    So my diet is not enough.
    My serum levels of folate were >20…
    B12 was 936.
    I’m lost…

    Should I find a new doctor in my area thAt is a natural path ?

    I’m really down , not sure what I’m doing…
    Thank you. Terry

    1. amyneuzil Post author

      Hi Terry,
      Honestly for most doctors this is a pretty new area. The deplin can work for some people, but doesn’t really help for everyone because it’s such a huge dose. Did you feel any different with the deplin? If not talk with your psychiatrist about it because that might not be the best thing for you. There are over the counter multi-vitamins with the methylated B vitamins that could be a good place to start, simply because they’re balanced with all of the vitamins you need but also have the methylated Bs. If you don’t feel up to tackling it yourself then I’d suggest finding a naturopathic doctor in your area and make sure before the visit that they’re familiar with MTHFR issues. You can look up Naturopaths here.

  90. Chris

    Hi there! I am trying to understand the common recommendations of supraphysiologic doses of methyl folate. I see that you advise to start of low but to titrate up to higher amounts. I have looked high and low in the published clinical research and I have emailed experts in the field, and nobody has been able to tell me exactly how much methylfolate is endogenously produced in the body per day, but the universal agreement is that 400 mcg or thereabouts of supplemental methylfolate would at least approximate endogenous production, if not surpass it. With that being said, I am not sure why some people recommend dosages above that level because, at that point, it seems to me that you’re using pharmaceutical dosages, for lack of a better term. Specifically what I mean is you are using dosages that are non-physiologic and the result is you are procuring a pharmaceutical effect. This is similar to taking megadoses of niacin to treat hypercholesterolemia. There’s nothing inherently wrong with that necessarily, but you are certainly not restoring homeostasis in doing so because you’re going way beyond restoring the levels that are inefficiently produced due to the polymorphism.
    I’d very much appreciate any input you mat have! Thanks again!

    1. amyneuzil Post author

      Hi Chris,
      Great question! So – first point is that folate is NOT endogenously produced and is supposed to be acquired from our diet. We aren’t able to make it de novo, so we need good food sources. The best food sources can be found here. The problem comes when taking folic acid or foods that are fortified with folic acid. Folic acid is entirely man-made and needs to be methylated to be used (natural folates generally don’t – they are usable as is.) The 400 mcg actually comes from research on undernourished moms – essentially this is how much folic acid (the synthetic form) is needed to prevent spinal defects in babies. To me, that means it’s the bare minimum necessary, although that’s entirely open for interpretation. Also, that research was done with folic acid and not folate. Honestly I haven’t seen anything about how much folate is necessary or even how much folate was in our ancestral diet. We can’t use the modern diet as a guidepost because we don’t eat particularly well these days and certainly not in a way that represents nature. So essentially I feel like we’re stabbing in the dark in terms of doses, but to me a good individual guidepost is how you actually feel in your real life. With something like methylfolate most people have a dose that makes them feel noticeably better, and going above or below that makes things worse. Sometimes that isn’t the case, but most of the time it works out that way. I hope this answers your questions!

  91. Lisa Tenenbaum

    I recently found out I am homogyous for C677T
    Negotiate for A1298C
    I have sever depression which began in childhood. And am not able to work. Almost all antidepressants have not worked or make me very sick, or have seri or side effects. My doctor gave me
    Meta genius FolaPro L 5?methyltetrahydrofolate
    800 mcg folate per tablet
    2 pills a day !!
    I was so sick, depressed, agitated etc any ideas how to proceed? Does all treatment have to be with “active” folate? Thanks

    1. amyneuzil Post author

      Hi Lisa,
      You could try increasing the food sources of folate in your diet first before trying a supplement – for some people that’s a far easier introduction than jumping right into pills. It’s so common though for us mutants to not react the same way to medications – I’ve heard that over and over again. I really feel like our brain chemistry is just different. If the food sources aren’t enough then you can start to add supplemental methylfolate, but make sure you start with a low dose and gradually increase – don’t just jump right into a big dose. Also expect the first few days (three-ish) to be a little odd as your body adjusts. I hope this helps!

  92. PRAVAL

    I am 27 male from India I always feel tired,exhausted,depressed and the situation got worsed when eat something. Nothing is working for me. Totally feeling helpless. Please do needful. Thanks in advance.

    1. amyneuzil Post author

      Praval I’m so sorry to hear that you’re not doing so well. Without knowing anything else it’s hard to say where to start, but if everything is worse when you eat something then maybe digestion is the place to look. The best would be to talk to a local doctor, but if that isn’t possible then start with a digestive enzyme and small amounts of foods that are high in natural folate. If there is an undiagnosed MTHFR issue that might be the gentlest way to begin.

    1. amyneuzil Post author

      Hi Joanna,
      Always start small! 9 year olds can be getting close to adult sizes, but they still have child systems so start with 1/4 to 1/2 the adult dose. So 100 – 200 mg at first and please work with a doctor for a kiddo – just to make sure everything is going well.

  93. Sasha

    I really appreciate the detailed information on methylation side effects! From what I understand this article is about responses to methylfolate, is it possible to have negative reactions to methycobalamin? And if you take niacin to help with folate, what would you suggest to help with a reaction to B12? Thank you!

    1. amyneuzil Post author

      Hi Sasha,
      Great question! I have seen a number of people have negative reactions to the methylcobalamin and they’re very similar to the negative reactions to methylfolate. Honestly it seems like it’s the same problem, you’re just coming at it from a different direction. It seems like the methylcobalamin can push that cycle too quickly, which creates a back-up at a different place in the cycle (just like taking too much methylfolate). Typical symptoms are agitation, anxiety, feeling wound-up or “over-caffeinated” but I’ve also seen it swing the other way into depression, sadness, hopelessness. In my experience agitation is more common, but depression can also happen. I’ve also seen people get some skin flushing or redness and a sort of itchy or prickly feeling in their skin. For a reaction to B12 I’d honestly suggest switching forms to prevent reaction and starting with a smaller dose. The hydroxycobalamin seems to be easiest to tolerate, and starting with a lower dose could help. Let me know what your experience is if you try it!

  94. Staci

    If I tried a fraction of the pure bcomplex and got the shakes followed by incredible fatigue, do I cut back even more? I tried less than an 1/8 capsule.

    1. Staci

      I don’t have my test results yet so it’s possible I don’t even have the mutation. Would that cause me to have this extreme reaction?

  95. Pam

    I have the MTHFR gene mutation but unfortunately haven’t been told which variant yet (C677T or A1298C). My Psych gave me samples of Deplin 15mg to try. It seems to make a difference but I do tend to have “up” better day and then next day may wane. What is your opinion on mega high doses of L-methylfolate in lieu of OTC good quality B-Complex and B-12 supplement? Also I have some concern if Mega doses could cause other side effects if I am not absorbing properly. Psych told me I couldn’t take enough B-Complex supplements or eat enough leafy greens to help with the MTHFR issue. Not sure how he would knows this since I don’t even know when variant I have. When I asked I was told, “That’s getting out in the weeds.”, as if to dismiss my question. Deplin is extremely expensive so even though I am feeling some significant benefit, although up and down, there is no way I could afford $100+ per month for this “Rx food” that is not covered by insurance. Thank you, in advance, for any direction you could give me.

    1. amyneuzil Post author

      Hi Pam,
      Deplan can be a great option for many people, but then it’s too much too fast for a lot of people too. Honestly, EVERYONE is pretty much giving you a best-guess answer to the question of what is best for you and it’s important to take any advice with a grain of salt. Listen to your body and find the solutions that work for you. Even if we know what variant you have an issue with, there are so many other genes that play into the whole picture that nobody can ever answer the question of what will be *best* accurately. It’s your body, and I honestly feel the best policy is to experiment with different products that seem reasonable and see what makes you feel best. Deplan can be just right, or way too much, or not the right thing. Just like everything else. I know that’s horribly confusing to hear because it essentially means there is no “right” answer, but sadly it’s the best answer. Your body is different from everyone else’s so trust your own judgement.

  96. Staci

    If I’m taking a b-complex 50 that is not metholAted is that enough to start the methyl folate? Or should I switch to a different bcomplex first? Also, if I splitting the 50 in half because it makes my chest tight otherwise will the methyl folate make that worse?

    1. amyneuzil Post author

      Hi Staci,
      If you know you have an MTHFR issue then it’s really important to switch to a methylated B complex. Starting with a low dose is nice an easy for your body – but for sure switch to a methylated form.

  97. Maria

    My daughter and I are both +/+ for COMT 158 and 62 and MTHFR 1298 and are +/- for VDR Taq, MAO, MTR 2756 and MTRR 66.

    I was under the impression COMTs couldn’t handle methyl groups and should avoid methyl folate, etc. but am now reading that we should be supplementing with small doses. So should we be starting with hydroxy B12 and adding very small amounts of methyl folate until we find a dose that works for us? This is all so confusing.

    My daughter has extreme OCD and anxiety, and I have depression and a general “negative” attitude. Thanks for your help!

    1. amyneuzil Post author

      Hi Maria,
      It can be SO confusing. Honestly much of the information for COMT mutations comes from people with COMT but not MTHFR issues, or COMT-only type situations. I think it’s reasonable to work with all the mutations you’re carrying and not just lump yourself and your daughter into a COMT box or a MTHFR box. Everything has got to work together at the end of the day, so might as well look at the picture from all angles. With a mix of genes like that the best path forward (in my opinion) is simply to start with tiny doses, one small change at a time, and listen to your body. Any time you make a change the first three days can be a little weird as your body is adapting so for sure give things a chance to level out before you really evaluate them. Bottom line is small changes, slowly, and listen to your body. There is no one-size to any of this and even with similar mutations you may find that you and your daughter respond well to totally different things so just hang in there and take baby steps!

  98. stephen

    Dr Amy,

    I’ve been doing a lot of research on amino acids + folate + MTHR, and I just have a question. Basically, I’m confused why there are folate prescriptions when they are available over the counter? Are they not the same? There are L-5-MTHF and the (6S) versions available OTC. What is the difference with the prescription ones? I just want to make sure I’m still benefitting from the OTC ones.

    I can’t seem to find this answer anywhere else so your answer would greatly benefit me. Thanks for your help!

    1. amyneuzil Post author

      Hi Stephen,
      Great question! There are differences, but not differences that change effectiveness/benefits. Deplan is NOT a drug – it’s actually registered as a “medical food,” which means it’s supposed to be administered under the supervision of a physician and has to follow food labeling, but hasn’t actually been subject to the rounds of testing that substances labeled as “drugs” have to undergo. This is probably in part due to the L-5-MTHF being found in nature and therefore not able to be patented. So – as long as you’re buying from companies that have the integrity to comply with the FDA labeling laws, then 5-MTHF or the 6S methylfolate should be the same in one product as it is in another. Hope that helps!

  99. Marilyn

    Hi Dr Amy, I have been diagnosed with MTHFR gene mutation, homozygous. I am going through infertility at the moment, waiting for my second ivf cycle. My RE first put me on a high dose of folic acid (5mg) plus B6 (25mg) and B12 (50 mcg) supplements. Now after speaking to the nutritionist at my fertility clinic, I have been told to exchange the folic acid with 1000mcg of folate (metafolin). After reading your article, I am worrying if I am taking the right dose. what do you think?

    1. amyneuzil Post author

      Hi Marilyn,
      Honestly it’s so hard to know if that’s the right dose without seeing any of your blood work or health history, or knowing how you’re actually feeling. Sounds like you’ve got a good group of practitioners on board though so I would trust them to guide you right and if you’re hitting a wall or not happy with your options then consider making an appointment and we can get into it in more depth. At this point they have far more information about you than I do though, so their input is the best one for the moment! Great luck with the IVF – I hope you get great success.

  100. Mary

    I was supplementing with vitamins and I began getting neuropathy symptoms. I was taking vitamin 50-65 mg B6 for 2 months alone, and then I added folic acid 1900mg and a multivitamin. I have been off all supplements for 1 month and still have symptoms. My doctor did bloodwork a month ago and my B12 and folic acid levels were normal, but my B6 came back high. After looking this up online, I realized it could have something to do with the MTHFR gene mutation (my sister tested positive for it, but I have had no testing done.) Do you have any suggestions for me? I wonder if I should be supplementing with methylfolate to get my body back on balance. (I have had anxiety all my life, from childhood, and also 3 miscarriages.) Please tell me what steps you would take to help fix this all.

    1. amyneuzil Post author

      Hi Mary,
      I would certainly take the time to do the testing – especially when we’re talking about pregnancy losses and fertility. If your sister has the MTHFR mutation then there’s a good chance you do too (plus you have symptoms that are commonly associated). In terms of supplementing – honestly I’d either wait for the testing or start with a balanced, methylated multi-vitamin that won’t push any particular pathway but will give your body the basics to do everything. If you do test let me know what shows up!

  101. Lisa

    Hi Amy!

    I recently found out about the MTHFR mutated gene and I’m 100% positive I have it. Haven’t been tested but I have ADHD and both of my children have it as well. We all have tied tongues and both kids have tied lips. I want to get pregnant by the end of the year but am so hesitant. Can taking methyl folate help reverse things in my body so baby won’t have adhd or midline defects? Need some answers. Can I start taking menthol folate without being tested? How long does it take to detox from folic acid? Thanks so much for your help!

    1. amyneuzil Post author

      Hi Lisa,
      Wow – yes – sounds like you’re a likely candidate for MTHFR stuff, but never can be 100% sure without testing. Taking the methylfolate before and during pregnancy can help protect your baby from the midline defects etc… but you’ll still pass along the same genes so it may help with the ADHD but it may not – and we don’t have enough research or experience yet with methylfolate yet to say for sure either way. You can start taking methylfolate without being tested because it’s sold over the counter, but as you may have read in other posts starting methylfolate can be fraught with difficulty (see this post if you haven’t heard about it). And honestly figuring out your “best” dose and clearing out some of the toxins that may have built up before you were taking methylfolate depends entirely on your body – I’ve seen people adapt really quickly and I’ve seen it take years. Sorry that’s so vague, but of course it’s not just the two MTHFR genes that are involved – there’s a whole host of genes that feed into this so it gets complicated really quickly. In short, it depends very much on what type of mutations you have on the MTHFR genes themselves and what mutations you have in the supporting genes, as well as your overall health and nutritional status. Sorry it’s so vague – just remember to start with a low dose and work your way up. I hope this helps!

  102. Elham

    Hi Dr/Amy
    thanks for your effort, ti’s very useful article
    I have MTHFR GENE MUTATATION heterozygous type and Iam not start taking medication yet
    Iam hesitated between two product throne B Complex ( which contain folate 400mcg+methylcobalamine 600mcg +riboflavin +niacin+biotin ) and throne basic nutrients (which contain folate 1000mcg+methylcobalamine 450 mcg +multivitamins +minerals)
    In your opinion which one should i start with?
    in my country no many doctors are professional in this field so i have to start medication by myself through self search on internet (Iam pharmacist), so help me to choose any of them , the ideal dose and what is the next step? and when will I take throne methyl guard? OR it’s not needed ?and will i add folate 1000 mcg to one of the previous products?
    thanks a lot

    1. amyneuzil Post author

      Hi Elham,
      It really can be difficult to navigate when you’re doing it alone so I’m glad you’re taking steps in the right direction. I really like the Thorne Basic Nutrients, just because it’s also a complete multi-vitamin. The dose on the bottle says 6 per day, I usually start with 2 or 3 just to see how it’s tolerated by your body and then adjust from there. There is no right answer for everyone, so keep to a low dose for a few months and then experiment with adding more methylfolate in to see how you actually feel – always with MTHFR it’s important to listen to your body. I hope this is helpful!

  103. Brian

    Hi Dr. Amy-

    Thanks for writing this up and sharing this publicly. I’ve been fighting with this for a while. My genetic genie profile revealed two copies of MTHFR C677T and a few others with two copies (VDR tag, MTRR A664A, and MAO-A R297R). I’ve tried a whole bunch of methylation supplements at various doses over the past few years.

    Currently nothing seems to really work, and only one thing is for sure, the more I take of methylation supplements the worse I feel. Currently I take Basic Nutrients V (half dose) in the morning and 1 Folapro 750mcg at night. This dose doesn’t make my symptoms any better, but the negative reactions are minimal and I stay on it so at least I’m getting some methylation vitamins every day.

    I noticed something interesting though. Mercury poisoning was one of my big issues when I started having health problems, and I did chelation for years to treat it (DMSA + ALA every 3 hours on the weekends). I have plateaued with this a while ago, and haven’t made any therapeutic progress in a couple of years. However I noticed that if I’m in a chelation cycle, I can suddenly temporarily tolerate and get great benefit from my methylation supplements, even at very large doses.

    I would love to find a way to feel like this everyday, without the chelation supplements which weaken my immune system if I stay on them too long.

    Is there anything to this? My only thought is that the methylation supplements cause a toxin dump that normally makes me not tolerate them, but the chelation supplements bind and neutralize the toxins.

    I’m curious to see if you have any insight.

    Thanks for reading.


    1. amyneuzil Post author

      Hi Brian,
      It seems like part of the issue with people with severe MTHFR compromise who do start taking the methyl-Bs is that they start to detox things that have been building up. Rapid detox, especially if it has a tendency to get stuck somewhere always feels a little bit bad. I think it would be a great idea to work with a practitioner who can help support your detox process – not necessarily specific to chelation, but basic detox. Boost liver function, get some toxin-binders into the protocol and start making sure your routes of elimination are open. That might allow you to slowly increase the dose of methylated Bs over time and generally feel better.

  104. K

    Dr Amy,

    I am homozygous C677T, and my doctor prescribed 15mg L-Methylfolate. I have been taking this for three days along with 5000mcg methylcobalamin, and am feeling quite irritable. After stumbling upon your website, I am now concerned this is too much right off the bat, and this may be the source of my increased irritability. Should I stick it out and see if this subsides, and maybe add some niacin, or switch to a smaller dose? We are seriously considering having a second child, so I would like to get things ironed out quickly. It’s so frustrating there’s not an easy fix to this!!

    *Also, in case this info helps, homocysteine was normal, and folic acid was very high at >24.

    Thanks for your help. I’m so glad I found your site!

    1. amyneuzil Post author

      Hi K,
      Honestly I’d give it a while before you make any other changes. There’s always a bit of an adjustment period any time you start any kind of methylation support so stick with the prescribing doc and see if you can ride it out. Three days could just be your body working to adjust. 3 weeks would be a different story – but there is also a 7 mg prescription methylfolate that your doctor might be able to switch you to, and if that isn’t enough then some of the methylation quenchers like niacin or whatever could be helpful. Just hang in there – the first little bit is always a bit rocky! And honestly, this is the best path for baby-making so sounds like your doctor does know what he or she is doing. Always good news! 🙂

  105. Lauren B.

    Hi. I just stumbled across your website. My naturopath dr recommended methyl folate for my anxiety and depression I’ve had since forever. I’ve been taking her recommended dose blindly here and there of 2000mcg. I have not been tested for the gene mutation. After reading some of your posts I am realizing this is a really high dose? I am 35 next week and have dealt with acne since 15 and depression/anxiety since I can remember. Lately my acne has been so bad that my depression has also worsened. I’ve also started taking spironolactone at the recommendation of the same nd. I’ve read methyl folate can cause potassium issues as does the spiro. Should I not be combining these? I was completely unaware of side effects with methyl folate and now am a little concerned that I shouldn’t be taking it at all? I’ve noticed a little nausea here and there, but didn’t attribute it to the methyl folate, I also had a really bad issue with itchy skin on my legs and arms after doubling my dose of spiro but now I’m thinking maybe it was the folate and the spiro? I don’t know. I’m so confused and overloaded. I’m also thinking I’m in way over my head with this methyl folate and perhaps better off without it, especially if it’s going to aggravate my already aggravated acne? Help!

    1. amyneuzil Post author

      Wow -that’s a lot going on! Honestly your naturopath is probably on the right track, although I’d take the time to do the testing just to make sure we’re not assuming there’s a methylation issue without knowing for sure what it is or how severe. If they don’t have good testing options my favorite is still with the results run through the methylation profile at – that combo gives really great results that can translate into good clinical steps that your ND will be able to help you with. 2000 mcg isn’t a super high dose, but it isn’t a low dose either and everything with methylation is so individual. Bottom line is that it’s hard to even guess at a dose you’d need without knowing what your methylation genes are. I’d guess the itching is more likely coming from the spironolactone, but it’s always hard to tell… All in all I’d say talk to your ND to see if it might be wise to back off of the methylfolate until you test fully and then figure out what you need to do. Does that make sense?

      1. Kelly Richards

        Hi Amy,
        Was just reading the post above and wanted to tell you about my 15 year old daughter. She is hetro C677T and pyrolles, with a variety of issues which have been helped by using Dr Ben Lynch’s multi products for kids, a compounded zinc and B6 cream, evening prim and inositol. It’s working well, but what I wanted to say, was that she had a major systemic acne problem. A doctor put her on low dose antibiotic for three months. Initially she felt her depression was worse but stuck with it and now as the acne is going, so is her depression, fatigue and anxiety. She seems like a different girl. Obviously not having bad acne itself makes you feel better, but this seemed to also been a physiological reaction. I work for a phycologist who mentioned that she has seen cases of anxiety linked to systemic acne like that. I thought it would be worth mentioning.

        I also wanted to say how well I have been going on inositol. I have terrible trouble processing methyl folate and was always taking naicin to mop it up. The two things that helped were MSM initally, was able to take my dose of methylfolate taking that, then inositol which finally got rid of my migraines and helped with sleep. I have not yet had 23 and me testing, so there is probably reasons why I react to methylfolate, but with these two supplements added, I’m cruising along with my protocol, including taking a reasonable dose of methylfolate.

        I take Methylfolate and B12 in drops so I can control the dose, a multivitamin without the previous two added, MSM, inositol, Vitamin D with K and sea iodine and evening primrose. It has taken ages to get this right, without a practitioner around to help. My daughter has been sick, so all available money for treatment goes to her and I just try to work my stuff out from research. I am now studying naturopathy.

        Thanks for the info above

        1. amyneuzil Post author

          Hi Kelly,
          Thanks so much for taking the time to post this! And also sorry for the delay in replying – I had a baby Sept 1st so things have been a bit hectic here (in a wonderful way, of course). That is so fascinating about your daughter and her reaction to the antibiotic – it really goes to show you how very individual all of this is and how much we have yet to learn. I’d be curious to see how she progresses with time though and I”d love it if you’d keep me posted. Great about you too – and it’s funny. I’ve found the inositol helpful with a number of people but haven’t really figured out *why* in terms of their mutation patterns or anything. I can’t necessarily connect it to any particular gene issue or anything like that, but usually it’s one of the things I throw into the mix if we’re stuck somewhere or just can’t seem to get past a particular issue. Great to know your reaction. And honestly – Ben Lynch’s protocols are fantastic – he’s so knowledgeable and has so much great information to share. Thanks again for the post!

  106. Rebecca Hill

    Ok. How do we not commit suicide while we up methylation? I am at that point. I started with about 200 mcgs. I literally feel like I am losing my mind and I want to die.
    The b12 hasn’t helped me at all. This isn’t worth the suffering to me.

    1. amyneuzil Post author

      Hi Rebecca,
      Yes – honestly I have had a couple of beloved clients who we just can’t seem to make any dose, ever, worth it. It’s rare but it happens. Certainly if you feel that way on that low a dose I’d back off of it. We know for some people it fixes a lot of things, but that doesn’t mean it fixes things for you – and certainly if you’re feeling suicidal that’s not productive (and please don’t do anything rash other than discontinuing the methylfolate and calling someone you can talk to!!!) There are times when it really is just too much and we don’t yet have good enough work-arounds to make it work out at all. Also I’d suggest if you have that strong a reaction with it to work closely with an expert – don’t try to do it on your own, it’s just too much.

  107. James

    Hi Dr Amy,
    I started taking the Thorne multi you recommended for men. I noticed in the ingredients that with the methylfolate is niacin. Doesn’t the niacin cancel out the effects of the methylfolate?

    1. amyneuzil Post author

      Hi James,
      The niacin helps if you’re having an excessive reaction to methyl-folate, which is a god-send when you need it but happily it doesn’t cancel out the benefit and you do still need some niacin. Generally I think it also makes the multi a little easier to tolerate and gives you a bit of a safety-zone if you start adding a higher dose of the MTHF on top of it. I do think us MTHFR folks get into a bit more trouble if we do really high-dose niacin like they use for some cardiovascular protocols, but the amount in the multi is typically pretty beneficial. I hope this helps!

  108. JJM

    Hello, Dr. Amy.

    First, thank you for taking the time to provide such valuable information regarding the MTHFR mutation. I’ve found it very helpful, and, clearly, many other people have found it useful, too. Much appreciated.

    My recent genetic testing revealed that I, too, am compound heterozygous (one C677T and one A1298C).

    Most of the research I’ve done (Including what you’ve indicated above) seems to indicate that Thorne Research Methyl-Guard Plus is an ideal supplement for a person with this mutation. I’m inclined to agree, but…I notice Methyl-Guard Plus does not include B1 (Thiamine), B3 (Niacin), B5 (Pantothenic Acid), or B7 (Biotin).

    If I decide to take Methyl-Guard Plus, do you have any practical suggestions for how I can get those four other B vitamins that are missing from Methyl-Guard Plus? Or is there a good reason why those four vitamins have not been included?

    I currently take one B-complex capsule every day. (It’s an inadequate supplement that I need to replace because it contains folic acid, not folate.) I’m not terribly enthusiastic about replacing my one-capsule B-complex with one Methyl-Guard Plus and 4 other individual B vitamin capsules. Seems like a lot of individual capsules to take every day, although I would do that if it’s the best option.

    Too bad the Methyl-Guard Plus formulation isn’t a complete B-complex. If it were, taking all of my B vitamins would certainly be easier.

    Your thoughts?

    1. amyneuzil Post author

      Hi Jerry,
      First off, let’s hear it for the compound heterozygotes out there (that’s me too). Secondly, I feel your pain about the ever-increasing number of pills. It doesn’t make sense that this isn’t a complete B complex, but it isn’t. A good compromise (although still a couple of pills) is to use Pure Encapsulations B Complex Plus as the general B complex because it’s very complete, and has methylated folate (but a very low dose). Then as you’re finding the right dose of methylfolate for you, you can add in other products, like the methyl-guard plus, slowly to find your perfect fit. It’s not perfect, but since the dose of 5-MTHF usually needs some tinkering with anyway it’s as close as I’ve come. I hope this helps!

      1. JJM

        Thanks, Dr. Amy.

        That makes sense, and I was thinking along those same lines: one good B-complex capsule along with Methyl-Guard Plus would be the simplest option. I appreciate the feedback.

        That said, I have a more difficult question that relates directly to this type of supplementation: as I mentioned, I’m compound heterozygous (MTHFR C677T +/- and MTHFR A1298C +/-). My genetic testing profile shows that I’m also homozygous for the COMT V158M (+/+), COMT H62H (+/+), and MAO A R297R (+/+) mutations. Some of the reading I’ve been doing indicates that these additional mutations may affect my methylation supplementation. i.e. everything we’ve just discussed regarding supplements might need to be altered or tweaked. My gut feel is that I would still benefit from the plan to use the B-complex along with Methyl-Guard Plus, but I thought it worth inquiring about these additional mutations first.

        I realize, like so many other doctors and patients probably do, that our individual genetic profiles can be a bit complicated. And, therefore, and supplementation choices become tricky.

        Your thoughts?

        1. amyneuzil Post author

          Ouch! Yes the COMT especially makes things tricky. Honestly with that pile of things going on I’d suggest one of two options with a strong emphasis on the first. One: work with someone, like myself or one of the other practitioners who focuses on MTHFR, to help give you perspective and make sure you’re safe while you’re experimenting to find the right things (it’s still experimentation simply because genetically you have so much going on – but at least this would make it highly educated experimentation). Two would be stick to the self-experimentation route, but proceed with extreme caution. Make sure every change is a small change because with that combo you’re just as likely to over-methylate than you are to under-methylate so it’s tricky finding a delicate balance. Also because of the COMT and MAO mutations your brain is probably dealing with a lot more oxidative stress than average so side-effects have the potential to be amplified. Just make sure that if you’re working with someone or doing it yourself that you’re making slow changes and not over-pushing your body. I hope this helps and no matter what you choose keep me posted – I’d love to know how it’s going for you!

          1. Rebecca B

            Wonderful! These are the exact questions I had! I too have the same MTHFR mutations, but am unsure about the COMT (For some reason my results came back with no info on COMT. Weird.) However, I too was trying to decided between the Thorne Methyl-Guard Plus and/or b complex. I’d run to the co-op yesterday only to find myself disappointed and confused by the selection of folate and folic acid supplements. They did. It have one b complex that had methylfolate in lieu of folic acid! Luckily, as soon as I got home I started googling and found your website! What a god send! My sweet, amazing OB/GYN ordered the gentic testing for me at my request, but she was unable to adequately read my results. With the help of good old google and my nerdy chemist turned psychologist husband I’ve been able to piece together what I think might be a good start for getting a little methylation going, and my lifelong battle with anxiety and worsening depression underway. Thank you so much for the info!

          2. amyneuzil Post author

            So glad you are pursuing this path! It’s a wacky kind of world, but makes so much difference for so many people. Great luck and keep me posted.

  109. James

    Hi Dr Amy,
    Thanks for such an informative website. I have found out I am C677T homozygous, my homocysteine levels are normal and my b12 is elevated. I have had underlying anxiety (so have many of my family members) and chronic stomach issues. My Dr didn’t seem to think I needed to take methyl folate as my homocysteine levels are normal. What are your thoughts on this?

    1. amyneuzil Post author

      Hi James,
      Great question! Homocysteine is one marker for poor methylation, and it’s the one that medical practitioners use most frequently, but it’s not the only consequence of having an MTHFR mutation and clinically it may not even be the most significant. With a homozygous mutation it is a reasonably assumption that your body struggles to build neurotransmitters, may not detoxify properly and has higher levels of inflammation than average so yes – I would say support those systems fully. Having said that I wouldn’t start with a high-dose of methylfolate. Maybe add in a daily multi that has a reasonable amount? I really like Thorne Basic Nutrients III for men (it has methylated folate and doesn’t have iron, which can be a cardiac risk for men) and suggest taking 3 per day instead of the 6 suggested on the bottle. It’s highly absorbable and for a lot of MTHFR folks (myself included) it’s the only multi they say they feel a difference with. Also make sure you’re getting rid of any supplements you might take that have non-methylated forms of folate.

      1. curious

        Dr Amy, to clarify…do you take the men’s supplement? You mentioned the multi being highly absorbable for a lot of folks, yourself included.

        1. amyneuzil Post author

          I take Basic Nutrients IV (for men III is better), which has iron in it and is more appropriate for women – but otherwise it’s the same. Thorne Research, the company that makes these vitamins does really well to make sure everything is active and bioavailable so they’re typically the multi-vitamins that I both suggest and use.

  110. Abigail

    Hi Dr. Neuzil,
    I have suffered from anxiety and depression since I was a child, and as an adult have developed food allergies and thyroid/adrenal problems as well. I have tried everything under the sun (it feels like!) to fix these issues (neurofeedback, diet changes, homeopathy, supplements) but nothing has been a permanent fix. I just recently had a gene test done and tested positive for the MTHFR mutation. My doctor gave me a bottle of Designs for Health L-5-MTHF, and even taking 1/4 of a capsule, it made my anxiety and depression worse, and the effects lasted longer each time I took it (after three tries, I gave up). I am about to go back on an antidepressant because I need to be more functional and stable than I am, but I know it isn’t solving the problem, and I have read such positive reviews of people’s experience with taking 5-MTHF. But I am so EXTREMELY sensitive, that I fear there is no solution out there for me since I often do not tolerate supplements. So I guess my question is…is there any hope for someone as sensitive as I am in being able to treat this issue (with something besides medication)?

    1. amyneuzil Post author

      Hi Abigail,
      Ugh – I can totally sympathize. Honestly, there is hope absolutely but for you there will never be a “quick fix.” When you’re truly sensitive AND have gene mutations finding the right protocol can be like walking in a mine-field. My best advice is to do what you need to do to feel more balanced now – if that’s a low-dose antidepressant, then great. I’d say don’t aim for perfect with the antidepressant, just aim for good-enough and find a practitioner you can work with to find the best MTHFR protocol for you who will work SLOWLY! Jumping right into big doses isn’t going to work for you and honestly supporting your thyroid and adrenals first might help to make the MTHF more tolerable because you’ve got so much going on. The MTHF allows your body to start to catch up on detoxification, which is great unless you feel crappy anyway and then it just makes you feel crappier. Find a good practitioner and plan on working with them regularly for probably a couple of years to really build your body and health up slowly. I’m so sorry that there isn’t an easy answer – but don’t give up hope. There IS a perfect answer for you, it’s just going to take slow and careful discovery. I’d love to work with you if you’re interested, but if you have someone who specializes in MTHFR in your area that would probably be best for you.

      1. Abigail

        Thanks so much the response and info, Dr. Amy! I am very happy with the practitioner I am working with right now (she is the first doctor I’ve worked with to have me genetically tested so I am very grateful for that) but unfortunately she is a couple hours drive from my house (and does not do Skype consultations) and although she has worked with a lot of MTHFR mutants, makes no claim to be an expert with this particular issue. I will certainly keep your name in mind if it turns out that I need to make a change down the road. Thanks again!

  111. Dawn

    I have the A1298C mutation. I also have hypothroidism and take both Armour and levothyroxine. My doctor started me on 1g 5-mthf in the morning and 1g at night. I became very breathless, and anxious. I felt like my heart rate was really high when I was working out. I took some time released Niacin and I felt better after. I decided I should take less folate, so I only took one pill. Should I take it in the morning w/my thyroid meds or at night wih my other vitamins? Should I add methyl B12?
    Thanks for your help!

    1. amyneuzil Post author

      Hi Dawn,
      So – as with everything else it’s hard to say for sure because we’re all so different and so many genes play into this whole thing (the MTHFR mutation is one of many possible related mutations). Given the symptoms you have described it sounds like the dose might be pushing your body a little bit quickly – sometimes if there is too much MTHF too quickly then the methylation cycle gets stuck in other places because other cofactors are missing. Taking anything at all at the same time as your thyroid meds can cause the thyroid meds to be less effective, but typically I do like to take any B vitamin more towards the morning because they can boost energy. Adding some other B vitamins, if you aren’t already taking them would seem like the next logical step (although those may be in your “other vitamins” list). If you’ve already got those on board then a B12 is a great idea. Some MTHFR folks do really well with the methyl-B12 form and some do better with the hydroxy-B12 form. Play with it a little and see how your body responds (also I’ll be doing a post on this shortly). Also if you run into road blocks it’s a great idea to talk to the doctor who prescribed them – they know your particular case better than I do and will be able to give you more specific suggestions. I hope this helps!

  112. Sara

    I was put on folgard for my mutation but reading how bad it is. It helped me carry two babies to term but now I want to try again and not sure if it’s the best choice plus I can’t seem to loose any weight . Any advice ? Thanks

    1. amyneuzil Post author

      If folgard has helped you in the past and you tolerated it well then it might be a fine option for you. There are over the counter options for methylated B vitamin combos as well – I like several from Thorne Research and Pure Encapsulations – but getting the dosage right for you can be a challenge (with prescription or OTC) so if you found one that works well enough to help you have babies then it’s an okay option for you. In terms of the weight – sometimes getting your methylation factors balanced will help because it helps with detox, but there are so many things that can be involved (like diet, exercise, hormones, thyroid levels etc…) that sometimes it takes more than just a good B vitmamin.

  113. Debra Howard

    Thank you so much for the in depth information on this – I just found out today that I too am a “mutant” and my initial reaction was anxiety (like I need more of that!). After reading your info and thinking a bit, I am RELIEVED that there is a reason for my moodiness, depression, anger, anxiety. I have fought so hard for so long to be “normal”. I am hoping that taking 5-MTHF and Methylcobalamin will help.

    1. amyneuzil Post author

      Hi Debra,
      Yes! It’s strangely empowering to suddenly start to understand why you’ve felt like this. It isn’t always easy finding the right balance of supplements to help, but it’s so worth it. Best of luck to you and let me know if you need any help at all.

  114. katy

    Hi Dr Amy, I stumbled upon an article about MTHFR recently and immediately ordered a dna test. B12 deficiencies on both paternal and maternal. Depression on both sides as well. I have a feeling my results may be in the red area of your illustrated table! Funnily, am hoping I am a mutant because at least then I’ll be given a reason for a lifetime of stress and depression from an early age

    1. amyneuzil Post author

      Ha! You’re not the first person I’ve come across who is hoping to be a mutant. It really does explain a lot and gives you a great pro-active way to address the issues so I totally agree. Mutants unite! 🙂 BTW I *love* your website – actually made me laugh out loud.

  115. Katie

    Hi Dr. Amy,

    Thank you for the helpful and informative article. I recently found out that I have an MTHFR mutation from one of my parents. What I don’t understand is this: If I only process (methylate) 50% as much folate as someone without the mutation, why can’t I just double my folate intake by eating more vegetables, beans, etc.? Why do I need to take methylfolate? Thank you!


    1. amyneuzil Post author

      Hi Katie,
      So – it really depends on your mutation. Each mutation doesn’t give you a 50% reduction – they’re all very different and the ways your body has adapted to work around the problem are different. If you only have one bad copy of one gene then getting a higher dose of the natural forms of folate (which are typically easier for your body to process with the MTHFR gene than synthetic folic acid) may be enough for you. If you have two bad copies of one gene then the compromise might be too much for that to work out. A lot of it depends on your symptoms. If you’re experiencing symptoms of a MTHFR mutation (typically anxiety, depression, mood swings, anger, irritability – these are usually the most noticeable symptoms) then starting with a low-dose methylfolate may help to relieve symptoms where food sources might not be enough. The bottom line with MTHFR is that it all depends on your body. Does that make sense?

  116. Marie Young

    Hi Dr Amy–

    Thanks much for the simplified explanation–it really helped to crystallize the stuff I’ve read from Ben Lynch and Amy Yasko. I’ve got the dreaded homozygous c677t–ugggh! Just started back on Pure encapsulations today. Also use Dr. Kendal Stewart’s Neuro Immuno Stabilizer but it doesn’t say how much Methylfolate is in each pump so I’m wary. What are your thoughts? Also, I read somewhere that even leafy green veggies can cause problems for us mutants. What’s been yr experience? Ty and love your site!

    1. amyneuzil Post author

      Thanks Marie!
      Yes – it’s so hard to know. I honestly don’t buy the leafy green veggies issue – simply because it doesn’t make sense that they would have anything but the active forms of folate and other vitamins. Clinically it doesn’t seem to pan out either – I haven’t seen anybody have a negative methylation-type reaction to them. It can take so long to find the right protocol for your body – especially with the dreaded homozygous. Ha! I *love* that phrase. I like Neuro Immuno Stabilizer in some situations, but I also don’t like it. First off – you’re totally right, we really have no idea how much methylfolate is in each pump and Dr. Stewart’s office is reluctant to answer questions because it’s their proprietary blend. So I don’t honestly think we’ll ever know. Outside of that I’ve seen several people start getting rashes – not at first but after using it for a while. It’s still my first choice for kiddos who can’t swallow pills and for people who seem to have a vivid and dramatic reaction to any oral methylfolate, but like everything else it isn’t the perfect solution (don’t you wish there was THE perfect solution?) Honestly though with the pure encapsulations it may really help to get you over the hurdle of that initial detox body freakout reaction. I’d love to hear what your experience is once you’ve used it for a while! Thanks for posting. 🙂

  117. curious

    In terms of trying to find the right balance of methylfolate for me, does it matter if I have 2 different mutations of MTHFR? I have C677T and A1298C.

    1. amyneuzil Post author

      Ha! That’s me too – it’s called compound heterozygous mutations. It matters, but we’re not exactly sure how – although in my experience with other clients it seems to be less serious than having two of the same mutation, so 2 bad copies of one of the genes. Hopefully you’ll find that you don’t have too much trouble if you start slow and work your way up. Fingers crossed, anyway.

      1. Jaime

        Hi Amy!

        I recently found out I am homozygous A1298C (after a stillborn, 4 month miscarriage, preeclampsia and post partum depression). I am now starting to change my diet and take the right kind of active folate and B vitamins BUT I would like to know what the max amount of methylfolate I should be consuming with this particular gene mutation? Everything I google sounds scary, that if I take too much then horrible things can happen…? And if I stay on it too long bad things can happen…? I am curious what you recommend daily in methyl folate and for how long? Also, when I plan to become pregnant again should that dose change?

        Also, if I am homozygous is it likely my 2 kids have it as well?

        Thank you so much!

        1. amyneuzil Post author

          Hi Jaime,
          I’m so sorry to hear about your baby troubles – MTHFR is a b*tch. These are great questions, but there aren’t easy answers. There isn’t really a too much, but there is a too much for you, if that makes sense. So too much 5-LMTHF for one person might not be enough for another. For me, I start having sleep issues around 3,000 mcg per day and I don’t notice much of a change in benefits between 1500 mcg and 3,000 mcg so I keep my daily dose around 1500 mcg (sometimes it changes by 200-400 mcg if I switch multivitamins). I have lots of clients who can only tolerate 400-800 mcg daily and I also have clients who can tolerate Deplan at the 15 mg dose (that translates to 15,000 mcg. That one would knock me right into next week). I think the bottom line is to start low and increase slowly and keep good records so that you know how your body responds.

          I don’t agree that if you stay on it for too long bad things will happen. If you have this mutation then you will need some amount of active folate for the rest of your life, so if you find the right dose for you, then it’s best to stay on it. In terms of pregnancy, I usually increase my dose during pregnancy and while breastfeeding and I find that my body’s tolerances change – I don’t notice the same symptoms when I increase (although I still max out around 3,000 mcg but I feel better around that dose during pregnancy).

          If you have a homozygous mutation (meaning both copies of your A1298C gene are bad and both copies of your C677T are good) then your kids have one bad copy each of the A1298C from you and the copy from your partner could be good or bad, just depending on your partner’s genetics. They also get a good copy of the C677T gene from you, so that’s good.

          I’m so glad you found your mutation, this will help you prepare better for the next pregnancy, if you’re looking for a next pregnancy. Still with MTHFR mutations we have higher risk of miscarriages and issues, but our chances are better if we’re supplementing than if we’re not. Best of luck to you and I hope this helps!

          1. Jaime

            Wow, I can’t thank you enough Amy! You shed some light and reassurance that I’m not taking too much methylfolate. I started taking an active B as well. Thank you so much for sharing your information which will help guide me. This helps me more hsn you realize because i’m very frustrated that my internist, OBGYN, hematologist all tell me MTHFR does not cause miscarriages whatsoever, and they’re the ones prescribing me synthetic folic acid. I am so glad I do my own research and follow my gut. I also have a PAI-1 mutation which I believe causes tiny blood clots so I started a low does aspirin and if I do get pregnant, possibly Lovenox injections as well.
            Thanks again!!

Comments are closed.