If you’ve just been told you have an MTHFR issue, or if you’ve started researching it and are pretty sure this is you, then you are in the right place. This is a quick summary with links to more detailed articles if you want to dive deeper. If you’d rather work with Dr. Amy one-on-one and have expert help, click here to schedule a free 15 minute consult. Start here for MTHFR!

MTHFR Basics – What it is, What It Does, and Why It’s Like A Magic Chair
MTHFR, or methylenetetrahydrofolate reductase, is a gene that tells your body how to build an enzyme of the same name. An enzyme is like a chair that something common (like folic acid) sits in to be transformed into something valuable (like 5-LMTHF, which is the active form of folate.) So essentially, this chair makes folic acid or folate active. To read more about this, go here.
When you have a “mutation” (I like this word only because it implies eyeball laser beams, but the correct term is “polymorphism”), the chair changes shape so that it’s hard for folate to sit there, so less of it is transformed. And each mutation changes the shape of the chair in different ways. Two variants make a difference in how the MTHFR enzyme works. They are called C677T and A1298C.

So I have a mutation. What Now?
Having an issue with MTHFR means that your body has a hard time activating folate, so all of the things your body needs folate for (which is essentially ALL OF THE THINGS) get a little messy. You can see a complete list of issues that can stem from the MTHFR mutations here, but the biggies are:
- Issues with neurotransmitters – so depression, anxiety, anger, addictions, ADD, autism
- Issues with energy – fatigue, chronic fatigue, hyperactivity, restlessness, or agitation
- Issues with sensitivities and toxins – allergies, food, and chemical sensitivities, toxic-type reactions to smells, perfumes, and actual issues related to the inability to detoxify.
- Issues with cell repair and reproduction – fertility problems, repeat miscarriages, cancer
- Midline problems – these are mostly developmental – hair lip, cleft palate, spina bifida, neural tube defects.
- Issues around aging and oxidative stress – macular degeneration, cataracts, skin, and cellular aging, Alzheimer’s disease,
- Heart and cardiovascular disease – heart attack, stroke, abnormal clotting, high blood pressure, preeclampsia.

So, that’s a lot of stuff. It’s important to remember that MTHFR alone doesn’t cause all these problems. MTHFR is an epigenetic issue, meaning that by using nutrition and lifestyle, you can modify the effect this gene has on your health. So the problems we are looking at are poorly-managed MTHFR problems, but by taking care of your MTHFR, you can help your body function at its best and minimize your risk of those health issues.
MTHFR Comes With Superpowers, Too.
No joke. With the MTHFR gene, you are likely to be:
- Highly intelligent
- Highly creative
- Have stronger and faster than average muscle fibers
- Have a greater than average chance of surviving malaria.
These are just a few of the advantages MTHFR gives us. Granted, it isn’t eyeball-laser beams, but it’s a start.
Managing MTHFR Mutations The Best Way Possible
MTHFR is complex, but managing it doesn’t have to be. I’ll give you a quick list of steps here, then details about the steps in stage 1 below. By the time you get to stage 2, you’ll be much more versed in MTHFR.
Start Here for MTHFR
**If you’re pregnant or trying to get pregnant** If you’ve recently found out that you’re pregnant or you’re trying to get pregnant, you must work with a naturopathic doctor, genetic counselor, fertility specialist, doctor, midwife, or OB/GYN who understands MTHFR and can address it. This is a vulnerable time for your health and your baby’s health.
This list is general steps with links to more in-depth information about each topic. This is a general introduction, but it gives you an easier starting place.

STAGE 1: GENERAL TO ALL MTHFR FOLKS
- Eliminate artificial folic acid from supplements, foods, and prescriptions. Talk with your doctor about prescription alternatives without folic acid.
- Join Genetic Rockstars, the MTHFR Community. This supportive group of folks is on the same journey as you. It’s less than a fancy coffee each month and full of amazing information.
- Add food sources of natural folate.
- Hydrate, Make sure you’re getting eight 8 oz glasses of water (about 2 liters) daily with good electrolytes.
- Find your pattern. Begin to explore your basic state and symptoms, and use a symptom tracker to get to know your red flags and measure progress.
- Clear the toxins out of your house. This is skincare, cleaning products, food containers, cookware, air fresheners, pesticides, weed killers, and that sort of thing.
- Add a multi-B vitamin or Multivitamin that doesn’t have either folate (in any form) or B12 (in any form). The B vitamins work as a group, and to methylate properly, you need all of them. The only ones I know of are from Seeking Health. “B Minus” is the B complex, and “Multivitamin Sensitive” is the multi.
- Talk to your family. You got your MTHFR issue from someone in your family, and your siblings and children might also have inherited it. Is someone else in your family who would benefit from changing their diet and state of health?
- Add some gentle detox to your life. Saunas, anything that induces sweating, castor oil packs, boosting fiber or taking clay internally, dry skin brushing, Epsom salts baths, etc…
- Boost your self-care. Make sure you’re getting good sleep, reducing stress, reducing inflammation, boosting antioxidants, and giving yourself the best foundation possible.
- Learn. Taking a course like MTHFR for LIfe to help you understand the impacts of this mutation, how to talk to your doctor, how MTHFR interacts with prescription medications, and how to get started supplementing with some extra support.

STAGE 2: UNIQUE TO YOUR BASIC STATE GROUP
- Understand your basic state. Are you an overmethylator? An undermethylator? or neutral? Begin to address the common issues for your group.
- Make specific changes for your basic state group.
- Add 5-LMTHF and/or folinic acid and B12 If you tolerate high folate foods.
- Add folate alternatives plus B12 if you don’t tolerate high-folate foods.
- Fine-tune your dosages and dosing patterns

STAGE 3: OPTIMIZE FOR YOUR PERSONAL SYMPTOM PROFILE
- Eliminate your food sensitivities
- Do an antioxidant/oxidative stress review
- Manage your specific symptoms
- Allergies and sensitivities
- Toxic symptoms
- Hormone imbalance
- Energy level
- Cell repair and reproduction
- Heart and Cardiovascular
- Other
MTHFR Is For Life
Your genes are your genes – we don’t yet have the technology to change them easily, but we can certainly change their impact on your health. Finding out that you have an MTHFR polymorphism can be an incredible turning point in your life where you get to decide to become the best you possible.

What is Next?
- Sign up for the mailing list to stay on top of all the great tips, tricks, and lifehacks for MTHFR folks, and get a free downloadable version of this document and a symptom tracker along with some other free goodies.
- Join us in Genetic Rockstars – our amazing MTHFR community- other MTHFR folks need to hear your story, and they know exactly what you’re going through. Like you, they are on the same lifestyle path and becoming better humans.
- Take a Course from Dr. Amy. If you’re committed to doing it yourself, then make sure you’re doing it with the best information possible to save yourself some heartache.
- Get one-on-one health coaching with Dr. Amy. If you’re struggling and you need help, I’m here for you. Learn more about all of it here.
Years ago I did a research study on genetics and also participated in the study, it only involved a DNA swab from buccal mucosa. At the time I was on very few meds and the study involved looking for genetic abnormalities that might affect the usefulness or toxicity of certain drugs. At the time I was not on methotrexate but I started it last weekend. Looking at my results it found my MTHFR activity was slightly reduced, but also “no increased risk of hyperhomocysteinemia” was mentioned, hopefully meaning my activity was so minimally reduced, I should have no issues. genotype 1298A>C AA 677C>T CT. MTHFR 677C>T ALLELE
I started met at 10mg and plan on slowing increasing to 20mg. No side effects so far with the 10mg.
Strong family history of depression and anxiety, 2 alcoholic siblings, both parents had Alzheimer’s dementia and a daughter needing a fertility doctor (unable to conceive)
Hi Scott,
I’d interpret those results to mean that you have a heterozygous mutation in the C677T gene. That means one C copy – which is the wild type – and one T copy, which is the polymorphism. According to the research I’ve seen, that means you have about 65% function of your MTHFR gene and 35% impairment. It’s not what I would consider insignificant, especially given your family history, which is riddled with MTHFR-type issues. I’m glad you aren’t having any side effects of the methotrexate – that’s great news. Certainly, keep your doctor posted if you do end up having symptoms and take steps with your diet and lifestyle to manage the MTHFR as much as possible. Methotrexate is such a helpful drug, it would be best if you could continue to take it with no problem. Let me know how it all plays out for you!
Scott – I meant to add this too – here’s a link to my other website with a good article explaining C677T mutations. 🙂
Hi Amy,
Im from Australia and need some help
Recently i was tested and these were my results:
MTHFR – c677T heterozygous mutation detected
MTHFR – A1298C heterozygous mutation detected
Apparently ”this combination of genotypes is unlikely to be clinically significant ” – well what my test notes said anyway
Is that true?
Will i need to worry so much?
Ive listened to so many of your podcasts and felt i related with the symptoms of MTHFR and ive started making sure i include more naturally rich folate foods and B vitamins. I do feel it helps but sometimes I also feel the same.
Thoughts?
Any further testing needed?
Thanks so much!
Hi Jade,
I also have a compound heterozygous mutation (one bad copy of each) and it’s arguably one of the most significant mutations possible because it compromises the enzyme in two different ways. So, in my view it is clinically significant and in my life it certainly has been. Great start with the diet – that’s always the foundation. Supplements would be the next step. Did you download the guide? Thanks for being here!
This is great information. I am homozygous C677T and also have the COMT. I haven’t had my 4 children tested yet but am almost sure they are homozygous as well. I have two children with ADHD and other symptoms. Finding out about this gene is a game-changer as far as managing health goes. I just found out in February of this year so I’m still working towards making changes, but I’m already starting to feel a bit better. Thank you for this website and your podcasts. I plan to listen to all of them and learn as much as I can about this.
I’m so glad you found this and if you have questions, send them along and I’ll see if I can answer them either in a blog post, a podcast episode, or to you directly. Finding out about MTHFR has been a game-changer for me, so I want to help as many mutants as I can!
I recently graduated with a certification in Functional Diagnostic Nutrition and a fellow practitioner told me to learn everything that I can about MTHFR, that it will make a huge difference in helping clients heal. I have spent all weekend going through your website and listening to your podcasts and I can’t thank you enough for your work and education. I am hungry to learn! I will watch in anticipation of your course (I have signed up for emails).
Thank you- thank you!!
Kimber
Kimber, I’m thrilled to hear from you! I’m glad you are learning something and if you have questions please let me know!
Thanks so much for this information it has been most helpful! I just found out I have 1 copy A1298C variant and my physician sent me your link. I have hoshimotos and I have one child with celiac disease. I haven’t gotten through all of your information yet but I’m sure there is a connection. I also lost a sister to breast cancer that ended up having AML. We were told it was from the chemo she received for the breast cancer treatment but now I am wondering if it was genetics. Thanks so much for all of the information.
Hi Lisa,
I’m so glad you’re here! Hashimoto’s and autoimmune disease, in general, could certainly be related (same with celiac). The risk of some cancers is related as well – especially breast, prostate, and colon but those have a wonderful U-shaped correlation. So with MTHFR and low folate status, the risk is increased, but with MTHFR with healthy folate status and normalized methylation, new research is showing that there is somewhat of a protective effect. One more reason to really work on following the plan and getting the folic acid out and bringing in the good natural forms of folate. Thanks so much for being here and keep me posted if there is anything you’d like to hear more about on the site or in the podcast. 🙂
Thank you so much for replying. I had trouble finding this spot again on the website, I am glad I made it back here. My dad also had prostate cancer in 2019, he is doing well thank God. I need to figure out how to get the podcast, I don’t want to miss a thing. Thanks again, Lisa
Hello, me again, since finding out about my gene mutation I have been trying to take Seeking Health Active B12 with L-5-MTHF that my functional medicine Dr. prescribed back in April but I can not seem to take it without getting a migraine. I wasn’t sure if it is just a dosage issue or maybe I am sensitive to one of the ingredients. Do you hear that complaints often? Thanks, Lisa
Hi Lisa,
*LOTS* of MTHFR folks have trouble with methylfolate and various forms of B12. Migraines, trouble sleeping, anxiety, panic – they’re all really common. It could be a dosage issue – maybe just too much too soon, or it could be that these forms are difficult for you. This is part of why I think with MTHFR we should start each ingredient separately so we know how our body reacts. Always start with eliminating synthetic folic acid from your diet and supplements. Then add in good B vitamins (withought methylfolate or any B12), then try B12 until you find a form that agrees with your body, the last try methylfolate. It takes time to do it right and it’s really tempting to rush the process, but it really matters to figure out how your body is responding to things because we are all different on this journey. I hope that helps! If you’re looking for more resources, check out the podcast on Apple podcasts here or join the free MTHFR community Genetic Rockstars here. Thanks so much for reading!
Thanks so much for your response, it was very helpful.
Thanks Amy! I’ve found all your work very interesting. I am writing to you from Argentina, after several years with studies where homocysteine was super high. My doctor realized that it was a genetic issue. My results were: Result: Genotype 677 Heterozygous CT Result: Genotype 1298 Heterozygous AC. Any specific tips about my diet? Or any supplement? I’m diving into your podcast. Thanks a lot!
Hi Federico,
I’m so glad you’re here! I have the same mutation pattern you do (compound heterozygous) so welcome to the family. My biggest tip would be to start tracking your symptoms right now if you haven’t already. They’re your best guide moving forward. Also, make sure you add other B vitamins in before you try starting methylfolate – it goes much more smoothly that way! Keep me posted and let me know how your homocysteine does now that you’re working on balancing your methylation. Also, if you’re interested in talking with other folks with the MTHFR mutation, the MTHFR community Genetic Rockstars is amazing.
I’m so glad to have found your video on YouTube today. I’m bedridden with 2 years of treatment of Lyme, I was doing great and crashed and now I know it’s ok. And I now know why. I just don’t know how to get that stressor out of my bucket (because she lives in my yard now ). She’s my Childhood trauma source that never ended. My daily reminder. I have mold exposure all in my body I just found out, too. I want to get back to where I was and be able to live in the world and not exist in my bed bubble. I’ll read your info on this site and digest it all. Thank you for the info in such a great way I could understand!
Hi Adasha,
I am so glad you’re here! And yes – the childhood stressors are the *hardest* ones to get out of our buckets, especially as time moves on and family roles change. I know you’ll get out of the bed bubble, just be kind and gentle and patient with yourself. Regaining health takes time and sometimes “bed bubble” time is a big part of that. If you have questions about anything, please don’t hesitate to ask! Big hugs from me.
Hi Amy! This is the best resource (you and William Walsh) for health advice I have ever found. Question about the B minus product. Is the inositol hexanicotinate ingredient recommended for us overmethylators? Also, have you found low-normal creatinine levels in overmethylators generally? Is it likely my level will go up with folate supplementation ? thanks Amy!
Hey Kelly,
Thanks so much! I appreciate that – I’m really trying to make this a good resource for us MTHFR folks.
In terms of the inositol hexanicotinate – it’s a great form of B3 and as far as I know it’s well tolerate by both over- and under-methylators.
I haven’t seen a link between creatinine levels (which is a measure of kidney clearance) in MTHFR generally, but creatine levels (the muscle fuel) are often low with MTHFR – both patterns. It does need to be methylated, and so it can be hard for us to really keep up with our body’s demands. The creatinine levels probably won’t change with folate supplementation, but creatine might. 🙂 Thanks for being here!
Thanks! I would love to know if you come across another b multi without folate and inositol and biotin. The biotin is causing me to breakout in lots of pimples. Ive tested it separately many times and it’s definitely the biotin.
Hi Dr. Amy!
Do you still have a mailing list? I would love to get the downloadable symptom tracker.
Thank you!
Hi Caitlin,
I’m in the process of upgrading my sign up forms, but I emailed you the symptom tracker so let me know if you don’t get it!
Thanks for asking,
Amy