Methylation Series Part I – Methylation and Folate



A few of you know that a part of my current health journey has been finding out that I am compound heterozygous for the MTHFR mutations, C677T and A1298C, both of which can result in impaired methylation (if that all sounds like gibberish to you, read on for definitions!). I’ve been holding back writing articles on this topic mostly because it is quite difficult to boil down for the purpose of educational blog posts, but I think it is important to write about considering how prevalent optimizing methylation is for those of us with chronic health issues and autoimmunity. This is why the series is broken up into three parts, which will be posted over the next few months.

Last year when I lived in Seattle, I had the fortune to attend a couple of lectures as well as a weekend seminar on methylation by Dr. Ben Lynch, who is one of the leading experts in the field. The information he shared helped me understand why I had been misguided in developing a personalized supplement protocol to help my methylation issues, and why these supplements had made me worse and created new symptoms I had never suffered from before. I had made the mistake of treating myself only based on genetics, without taking into consideration how methylation was actually happening in my body and without considering what effect my dietary and lifestyle modifications were having on methylation.

In the next few months, I’ll be posting a series of articles with the basics that I have learned of methylation. I have had many requests to share what I have been learning, and honestly, I haven’t had enough understanding of this topic to write these articles until now. I hope some of you are able to find some clarity in my explanations, and possibly figure out some of the pieces of your puzzle and learn about how best to guide treatment—hopefully with the help of a skilled practitioner!

Part 1 – Methylation and Folate

What is Methylation?–Simply put, methylation is a biochemical process that occurs in every cell in our bodies countless times throughout the day. For the chemistry nerds—it is the addition of a methyl group (a single carbon atom bonded to three hydrogen atoms) to a compound. Its proper functioning is absolutely essential for optimal health—just check out the list below:

Functions of Methylation:

  • Gene regulation and expression
  • Detoxification
  • Neurotransmitter production (which affect everything from mood to digestion and sleep)
  • Neurotransmitter metabolism
  • Hormone processing (especially Estrogen)
  • Building immune cells (T and NK cells)
  • DNA and histone synthesis
  • Producing energy
  • Producing myelin (protective coating on nerves)
  • Building and maintaining cell membranes

Because it is so essential to health, when methylation is impaired it can affect almost any organ or system of the body. Some of you in the autoimmune and chronic illness communities are probably familiar with the MTHFR mutation, or other genetic mutations that can impact methylation (more about that in the next part of this series!).

Here are some ways methylation can be disrupted:

  • Lack of nutrients (folate, B12)
  • Lack of cofactors (zinc, b2, magnesium, cysteine, b6)
  • Certain medications (antacids, methotrexate, metformin, nitrous oxide)
  • Nutrients that deplete methyl groups (niacin)
  • Environmental toxicity (heavy metals and other chemicals)
  • Excessive cofactors in the diet
  • Excessive stress, anxiety, and sleep disturbances
  • Genetic mutations (like the MTHFR genes we will we talking more about)

Thus, in order for a healthy individual without any genetic predisposition otherwise to have proper functioning methylation, they need to have the right amount of nutrients and cofactors to drive the process as well as not be exposed to an excess of medications, toxins, or stressors that can affect the process. Given how toxic and stressful our modern lives are, it is safe to assume a lot of people struggle with methylation. This doesn’t mean we all need to supplement—please stay tuned for the final article which will have some great recommendations.

Folate, Folic Acid, and B12

The two foundational nutrients needed for proper methylation are folate and B12. The lack of folate and excess of folic acid in our modern diet is a big factor affecting the prevalence of methylation issues today. It is very important to know the difference between folate and folic acid—they are not the same thing!

Folate is a general term describing over 150 different forms of folate, a water-soluble B-vitamin that generally comes from food (but it can include synthetic folic acid). It is found mostly in uncooked leafy green vegetables.

Folic acid is completely synthetic and did not exist before it was created in a lab. Biochemically, it does not metabolize the same way as the natural folates derived from food, and actually makes it more difficult for us to absorb natural folates.

Folic acid is found in all manner of processed foods—cereals, breads, pasta, and tons of multi-vitamins and supplements. Recently, research has shown that a high intake of folic acid is problematic—some studies link it to increased rates of cancer, cognitive decline, anemia, and heart disease. Considering the prevalence of this synthetic nutrient in our food supply, this is certainly troubling!

Since folate is an incredibly important nutrient to proper methylation, we need to ensure that we are getting the right kind of folate—that which is found in real food! Raw leafy greens are an excellent source of folate, and supporting methylation is a reason why you should include them in your diet every day.

Vitamin B12 is also important to the methylation process—without it our bodies cannot use folate properly. Many of us, especially those eating on the Autoimmune Protocol eat plenty of B12, which can be found in all muscle meats, organ meats, fish, and shellfish. Those that have impaired digestive function may need to be tested to find out if they are absorbing, as a properly acidic environment in the stomach is needed to absorb B12 properly (this podcast is an excellent resource for anyone looking more into testing and supplementing with B12)

Fortunately, the Autoimmune Protocol naturally sets us up for supporting methylation, because it avoids synthetic folic acid (check your supplements to make double sure!), provides a good source of natural folate from food (make sure to eat some raw greens every day!), and provides plenty of sources of vitamin B12.

In Part II of this series, I will talk about some of the common gene mutations affecting the methylation cycle (like that pesky MTHFR). Stay tuned!

References/Further Reading:

About Mickey Trescott

Mickey Trescott is a cook and one of the bloggers behind Autoimmune Wellness. After recovering from her own struggle with both Celiac and Hashimoto’s disease, adrenal fatigue, and multiple vitamin deficiencies, Mickey started to write about her experience to share with others and help them realize they are not alone in their struggles. She is a certified Nutritional Therapy Practitioner by the Nutritional Therapy Association, and is the author of The Autoimmune Paleo Cookbook, a guide and recipe book for the autoimmune protocol, and AIP Batch Cook, a video-based batch cooking program. You also can find her on Instagram.


  • Catherine miller says

    Thank you for this post! My son and I both have the mthfr c677t and a1298c mutation. This was so informative and looking forward to your future posts on this.
    By the way, your book is fabulous!!!

    Thanks again!
    Catherine Miller

    • Mickey Trescott says

      So happy you found it helpful Catherine! Wishing you both the best.

  • Angie says

    So glad to read this post, MTHRF is very confusing. I am looking forward to more posts to try to figure this all out. Wondering what you think of the supplements mentioned in this post:

    • Mickey Trescott says

      Hi Angie,
      I don’t think it is wise to supplement based on genetics alone. Also, a supplement that corrects one methylation imbalance can exacerbate another. I recommend working with a practitioner who can do some testing to see how you are currently methylating, and then suggesting supplements based on that evidence. Good luck!

  • Tiffany says

    I like to use yeast flakes, but even the brand that lists folate in the dietary percentage chart shows folic acid in the ingredients list! Do you know of any yeast flakes that contain actual folate, instead of folic acid? Thanks.

  • Shannon says

    Thank you so much for broaching this topic on your blog . MTHFR is a brand new diagnosis for me after suffering chronic illness for most of my life and being told over and over , “you’re fine”. I’m so glad to finally know what it is! It’s a godsend for me that you started writing about it when you did. I can’t wait to see more of what you will post in the future.

    • Mickey Trescott says

      I hope you find the series helpful Shannon! Wishing you luck.

  • Leslie says

    Forgive me for posting this here, I couldn’t find a contact point…
    Have you considered posting on Genetically Modified Food? The Environmental Working Group is gathering signatures for a petition here:
    You all have such a large readership, and most who would care about eating non-gmo foods. Perhaps we can help ewg get the signatures they need to make sure gmo foods are labeled?

    • Mickey Trescott says

      We share about this issue on Facebook!

  • Beth says

    Excellent info – thank-you. This is exactly what I am dealing with now and have seen such improvement. I hope you don’t mind if I share. 🙂

  • Linz says

    Thank you for this article! I’m curious if you worked with any great practitioners in Seattle that were knowledgeable on the subject? Thanks!

    • Mickey Trescott says

      Linz, I haven’t, but I would check out Dr. Lynch’s resources on to start. Good luck!

  • Marcia says

    I’m so glad you are doing this series. I just found out a couple of months ago that I am compound heterozygous. My doctor gave me a methyl folate, B6, and B12 supplement but no other info. I’m searching on my own (and not taking the full dose she gave me because I don’t yet know about co-mutations or how my body is functioning).

    • Mickey Trescott says

      I think you are right to be skeptical of taking supplements without knowing how you are actually methylating. My next two articles give some info about how to go about this process–good luck!

  • […] jump back to methylation. Mickey Trescott of Autoimmune Paleo recently started a series about methylation, and she describes it as the […]

  • […] This is the second article in a blog series about methylation. To read the introduction as well as the basics of methylation, click here. […]

  • […] you are interested in supporting methylation, you’d better be eating lots of raw, green, leafy vegetables in order to get your body the […]

  • […] To read the introduction and first article in the series that covers methylation and key nutrients click here. To read the second article about genetic mutations that affect methylation, click […]

  • Rita says

    My functional medicine practitioner tested me and discovered two heterozygous mutations (not the ones you mentioned): MTHFR C665T and MTHFR A1286C. His clue was that my homocysteine level was very high, even though I do the Paleo diet and eat animal protein every day. He prescribed L-methyl-folate which I take every day. It keeps my homocysteine at a safe level. But you’ve said that you experienced new, unpleasant symptoms as a result of supplementation. Would you be kind enough to say what these symptoms were? Not that you and I are identical, but I’m curious what to look out for. Thanks!

    • Mickey Trescott says

      Hi Rita!
      I found myself suddenly very itchy, irritable, and had trouble sleeping. Hope it helps!

  • Margo says


    Thank you so much for your work with MTHFR. My functional doc told me I have both genes and gave me supplements with folate not folic acid. In fact, it says it’s methylated B5. Have you heard of this? I hope these supplements are okay.

    • Mickey Trescott says

      Hi Margo,
      B5 is not a form of folate, it is pantothenic acid. I’d suggest requesting some further testing from your doc to determine optimal supplementation, not just going on genetics alone.

  • Dimitra Osborne says

    I have MTHFR gene mutation (C677T) My GP has given me ACTIVATED B COMPLEX capsules, this is all very confusing for me, is there anything I could take instead that is natural that will do the same job.


    • Mickey Trescott says

      Hi Dimitra,
      I have no way of knowing which supplement is best to you–your best bet is to inform yourself by reading the whole series of articles on MTHFR, finding a knowledgable doc, and coming up with a supplement protocol that best supports your test results (not just genetics). Hope it helps!

  • […] Methylation Series Part 1- Methylation and Folate – Autoimmune Paleo, Part 2 – Gene Mutations that Affect Methylation & Part 3 – Methylation Treatment and Support […]

  • […] with a functional medicine doctor in Atlanta who tested me for the mutation, and sure enough I was homozygous for MTHFR, which in turn, ended up guiding my course of […]

  • kari dunlop says

    Hi there

    It’s my understanding that folate and folic acid are actually harmful if you have undermethylation. It’s great for people who are overmethylating. From what I’ve learned, 70% of the population have great methylation, 22% have undermethylation and 8% experience overmethylation. There are also connections to histamine and as a consequence food considerations as a result of which side of the methylation fence you are sitting on. I’ve discovered as an undermethylator with high histamine, spinach, avocados, tomatoes can be troublemakers. Dr. Bill Walsh from the Walsh Research Institute is a phenomenal resource with respect to methylation. It’s a fascinating. There are so many pieces to his puzzle!

  • […] Test – To educated eyes, this test provides a ton of information. You’ve heard of the MTHFR mutation? It’s a genetic mutation that many people with autoimmune disease have that can interfere […]

  • […] We’ve talked about methylation on the blog before (for more info start here), and sometimes those who have impaired methylation, whether from genetics or another cause, can […]

  • […] blood sugar and cholesterol levels were within healthy ranges. My thyroid hormones were optimal. My methylation was working well in spite of having a heterozygous MTHFR mutation. My liver, kidneys and adrenals […]

  • Sue says

    Hi Mickey. About 6 years ago I became very ill (it turned out to be a hiatal hernia but was causing my heart to race). Long story short, I ended up finding a holistic practitioner that diagnosed the problem & made an adjustment. He also did a lot of blood work. One of the things he found was that I have MTHFR (both chromosomes as you do). He told me that this can cause many problems & put me on a supplement called DMG (Dimethylglicine) & prescribed B-12 shots (methycobalamin). I am very thankful he found this disorder. I am hearing so much more about MTHFR in some documentaries that I viewed and articles I have read but it still seems to have some “mysteries” about it. Certainly the mainstream healthcare practitioners do not know much about this. In trying to educate myself, I find myself with many more questions. For instance, during an interview with a Dr. on a video I watched, she briefly noted MTHFR & said that people with this disorder should definitely avoid certain medications but she was so general, she didn’t say which ones. In your article, you talk about not just supplementing, but that it’s important to know how we our bodies are methylating. How do we find out how are bodies are methylating. I am trying to learn as much as I can about this so I can be proactive in my health & that of my daughters (as I have passed this on to them). My daughters were taking the same medications however, one has been under considerable job stress the last 4 years & is now on a FODMAP diet – I think she needs to learn how she’s methylating. I appreciate any & all the specific information & resources you have & will give. I look forward to reading the rest of your articles on this subject & am so glad you were able to learn from an expert in this field. Thanks for passing on your knowledge to the rest of us. I am sorry it has come at such a cost to you. Please know you are greatly appreciated! May you be blessed with good health!

    • Mickey Trescott says

      Hi Sue! I am sorry to hear about your experience but happy you are finding my writing here helpful. I agree, educating ourselves is key! I have found the best information from Dr. Ben Lynch at Wishing you all wellness!

  • Kayla says

    Thank you for a great post 🙂 What if you can’t yet digest raw leafy greens due to SIBO? Only cooked greens.

    • Mickey Trescott says

      Hi Kayla! There should be some raw leafy greens that work for those who have SIBO – like lettuces, spinach, etc. Also getting the SIBO treated so you can get on to eating a wide range of veggies should be your first priority! Good luck.

  • Susan Wheeler says

    Mickey, have you read the book “Could it be B12 an epidemic of misdiagnoses” by Sally Pacholok and the work of Martyn Hooper founder of the Pernicious Anaemia Society in the U.K.? I think you would find it helpful.

    • Mickey Trescott says

      Susan, no but thank you for the recommendation!

  • […] about B Vitamins, a family of nine different compounds that are important for cellular metabolism, methylation, energy, and immunity. It is important to consume and absorb all of the different B Vitamins […]

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