What is a Methylation Disorder?

By Samantha Gilbert, FNC, CHNP, CNC     Last updated on November 16th, 2021

Hundreds of cellular processes involve methylation, a chemical reaction that begins when a methyl group attaches to an atom or molecule.[1]  It’s a vital metabolic process that takes place in every cell and organ in your body.

Methylation is profoundly connected to mental health. If serotonin isn’t properly methylated, for example, it will become inactive, which leads to depression. Since I was born undermethylated and have also experienced copper overload, I’ve traversed the ins and outs of methylation disorders my entire life, and I’m eager to share what I’ve learned so you can better understand your own experiences. 

What is Methylation?

DNA methylation is one of several epigenetic mechanisms that cells use to control gene expression. Methylation controls the activating and silencing of genes; when a methyl group binds to a gene, it changes that gene’s expression. 

Methylation happens when one molecule passes a methyl group (a carbon atom plus three hydrogen atoms) to another molecule. Methylation involves the conversion of the amino acid methionine into S-Adenosyl methionine (SAM-e). SAM-e then travels around your body and contributes methyl groups to various compounds that directly affect most of the essential processes in your body. At the end of its journey, SAM-e turns into homocysteine and gets recycled back into methionine to begin the entire process again.

When a methyl group is added to a biochemical cellular process, it’s called methylation. When a methyl group is removed, it’s called demethylation. Methylation and demethylation occur billions of times per second. Billions of switches inside your body get turned on and off, directly affecting your brain chemistry, immune response, inflammatory response, energy production, cellular repair, and more. 

Proper methylation is crucial to happiness and well-being. Making too much or not enough methyl impairs the ability to think clearly, have meaningful relationships, have a healthy body, and live a fulfilling life. In today’s world, methylation problems are commonplace due to food and environmental toxins, emotional trauma, genetic errors, and stress. 

Methylation is automatically occurring all day, every day; it’s something we don’t even think about, so we’re less likely to suspect methylation as the cause of disruptions in our physical or mental health. 

How Do You Know if You Have a Methylation Problem?

If you don’t methylate well, your body’s detoxification processes will become impaired, leading to a buildup of toxins (like heavy metals) in the body. Your DNA/RNA expression will change, often leading to chronic disease. You may also notice the onset of any number of psychological conditions (including behaviors typical of individuals on the autism spectrum) due to neurotransmitter imbalances.

Symptoms of Poor Methylation

I often get asked, “What does poor methylation cause?” Proper methylation is essential to fundamental processes in the body and affects almost every tissue and organ system, so poor methylation can disrupt just about anything.

That said, the largest clinical issues most often involve the gut, the body’s detoxification system, and the brain (cognitive and personality issues).

What Are the Personality Symptoms of Undermethylation?

Undermethylation is much more common than overmethylation, and undermethylated parents have higher rates of autistic children due to epigenetic insults.

If you’re undermethylated, you’re likely to be a high-achiever who’s constantly striving for greater levels of career accomplishment. Undermethylated personalities tend to have at least graduate-level education and may come from affluent backgrounds. Entrepreneurs, corporate executives, professional athletes, doctors, lawyers, producers, and scientists all fit this type. 

Looking at Hollywood and Silicon Valley as a whole, I can tell straight away the vast majority of these folks are undermethylated. Highly perfectionistic, no detail goes unnoticed. Despite accomplishments and accolades, undermethylated individuals may suffer from severe inner turmoil, yet remain calm on the outside. 

If you’re undermethylated, you may have been self-motivated in school and probably come from a family of high-achievers. You have obsessive-compulsive tendencies you can’t seem to shake, and they drive you nuts. You’ve always been very strong-willed with a high libido. Despite poor concentration, ritualistic behaviors make you feel in control and you tend towards addiction.

You probably have a low tolerance for pain. Seasonal allergies and headaches may be a problem, yet you respond quite well to antihistamines. You respond well to antidepressants, but may isolate yourself socially because you feel misunderstood and struggle with phobias.

What Are the Personality Symptoms of Overmethylation?

If you’re overmethylated, you’ll experience the opposite of undermethylation. You’re likely to be creative and sensitive, with high empathy for others. 

You may experience a high level of internal tension and anxiety, often causing learning issues or underachieving. You may have little motivation for scholastic achievements because you have trouble sitting still. 

Hyperactivity, panic attacks, and a high tolerance for pain are also part of your profile. You may also have a tendency to overreact, feeling like everyone is “out to get you.” In clinical studies, about 45% of persons diagnosed with schizophrenia were found to be severely overmethylated.

Physically, you may be overweight with a pear-shaped body (but not always), have heavy body hair, struggle with eczema, have dry eyes and mouth, and experience upper body/head/neck pain.

You may struggle with depression, have trouble sleeping, and experience food and chemical sensitivities; low libido is also a part of your daily life. 

If you’ve tried antidepressant medications, you probably didn’t respond favorably. Overmethylators have elevated serotonin and dopamine with low levels of histamine, which is why antidepressant medications can actually cause suicidal ideation in these individuals (SSRI’s increase neurotransmitter activity at the synapse). 

Can Methylation Cause Anxiety?

Both methylation biotypes struggle with anxiety and addiction. The main difference is the cause. Extra neurotransmitter activity causes high anxiety and panic in overmethylators, which can lead to substance abuse. Too little neurotransmitter activity causes undermethylators to become obsessive-compulsive with a substance or concept (for me it was food/sugar/starving myself/being perfect no matter what).

The tragic suicides of Robin Williams and Kurt Cobain are classic examples of overmethylation, while Karen Carpenter was a classic undermethylator.

How Do You Treat Methylation Problems?

There is no such thing as a one-size-fits-all approach. Determining methylation status is not just about chemistry, but also about understanding you as a person. There are myriad variables within each biotype. And understanding each personality, combined with the complete range of functional and diagnostic testing, is how we create effective nutrient therapy protocols.

Does this post resonate with you? Or do you know of someone struggling in these areas? If so, please share your story in the comments below. It is through sharing your story that we create community, eliminate guilt and shame, and bring about healing.


[1] Walsh, William J. (2012). Nutrient Power: Heal Your Biochemistry and Heal Your Brain. (185). New York, NY: Skyhorse.


265 thoughts on “What is a Methylation Disorder?”

  1. I have Kryptopyrrole, a genetic blood disorder, which I believe I was born with. Am working with a Naturopath who has sent me to a Family Practice Doc, Endocrinologist, and Neurologist. Once she gets all the pieces (and there are so many) together, she is going to get me feeling better. I am an undermethylator . . . always an overachiever and this put me literally on my butt. I have been pushing it away for the last several years in a big way and really just was diagnosed in October 2013. Additionally, I have major depression, hypoinsulemia, PTSD (raped by old boss), about 40 of the Pyrrole symptoms, and acute insomnia to name a few things . . . Hoping for the best. Feel caught up in the medical system right now and don’t like it at all. Can’t wait to get some real sleep and feel better.

      1. Thank you for sharing your story Jeannie. This takes much courage and strength. I know you’ll get there, so stay the course.

      2. Hi,

        I just saw a naturopath and she mentioned I am undermethylated. She said i do not absorb the B vitamins normally so I need an active B-complex. When you mention you do not recommend it, what do you mean? The regular one or even the active one? I am confused now, because I thought taking the complex will benefit me.

      3. Hi Alex,
        B-complexes usually contain a range of b vitamins including folic acid. If you are undermethylated, you need to be mindful of folates.

      4. Hi Alex
        Just reading your post and I only wanted to chime in here to tell you I had the same exact confusion
        From what I’ve read and according to the doc I’m working with now , Folic acid should never be taken and you have to be careful about it being in the process bread and other items however the type of b vitamins that should be taken are not supposed to be taken until the gut is worked on, supposedly because you wouldn’t be able to use this type of b that is desperately needed and you could make all your symptoms worse if the gut is not corrected first
        Try to find yourself the right naturopath to work with in your state possibly ,
        Best of health to you ,

        Sincerely, Lana E.

      5. Hi There, My identical twin sister and i have chiari malformation. Both sides of my family have depression and anxiety. My father committed sucide. I have pylouria. My question is does MTFHR run in families, we have high histamine and allergies. Could we histallia and be undermethyolated?

      6. Yes, it does run in families (epigenetic) and you can have histamine intolerance and be undermethylated.

      7. Sounds just like me I have systemic Whipple’s disease that’s causing me porphyria attacks due to liver damage don’t know if my body is over or under methylated right now because of that fact I think it might be overmethylated but I’m not sure.

    1. I have ptsd from a childhood of abuse. This year at 24 when I got Ross river the lifetime of symptoms I thought were my personality were diagnosed. Having a pyrol disorder (trust me this one while hard to live with is easy to treat with vitamins) hyperthyroidism and undermethylation (plus an allergy to dairy and celiac). If your just starting your health journey I’m sure your just plodding along in good faith. I just want to say be prepared for a complete life turn around. While I had to change my lifestyle somewhat and the dedication to myself has been quite a shock (low self worth has to be thrown out the window). I am just so amazed at how fun and beautiful life can be. Don’t be shocked if you go through a grieving process of who you thought you were and use this opperunity to create the amazing you you’ve always wanted to be.

      1. People with homociteina has little methylation (not convert homocysteine to methionine). Then they need the active forms: methyl folate and methylcobalamin (not metabolize folate and cyanocobalamin in their active forms,
        This contradicts what you say

      2. This is incorrect. If you read the post in its entirety, there is a very clear distinction between over and undermethylation as it relates to folates. The only time an undermethylator would need folate is if homocysteine is high, in which case folic acid would be used in a specific dose for a very specific amount of time to bring it down into a functional range. Then an undermethylation protocol would ensue.

    2. Try magnesium glycinate – ask naturopath for best dosage – I took four in the am & four pm & slept like a “normal” person – dreams were bliss…

  2. Sami, Can you tell us where to get all the tests to know if we’re under or over methylaled, and have copper deficiency, etc. If I work with you, will you provide all that information. I have just started an SSRI and I am scared of meds. I feel like I lost my “happy gene”. When I read the description of under and over methylation, I have pieces from both, so I don’t know which I am. I have panic attacks, anxiety, depression, GI issues, insomnia, fear of most everything. Would love to have a consultation with you but not sure how to reach you. Sincerely, Marcia

      1. Hi Melissa,
        Are you looking for a practitioner to work with or just reading materials? I highly recommend Dr. William Walsh’s book Nutrient Power: Heal your Biochemistry, Heal Your Brain.

      2. Hey Sami,
        What other reading/listening resources do you recommend, in addition to Dr. William Walsh’s book?

      3. Hello. I also have stuff from both groups of under and overmethylated. My biggest problems right now are sleep and itching…all over body itching that is so chronic it is ridiculous. I am on a “nutritional balancing program” with an associate of Dr. Lawrence Wilson and have not been able to calm down the itching or get sleep without RX. What I am using now is Ativan and I am a bit more depressed than usual, so am concerned about that. Not sure what to do at this point. Any ideas?

      4. Hi Moria,
        Hair tissue mineral analysis is a great tool, but it needs to be used in conjunction with other testing methods to get a clear picture of your overall chemistry.

      5. This is in response to Moira’s comment I couldn’t reply directly under her remark but I have the same issues with the itching and severe insomnia. Porphyrins buildup can cause that have you ever been tested for porphyria? Just a thought. I’ve had some porphyria attacks lately and they are painful and horrific. Burning nerve pain like you wouldn’t believe. Crazy itchy skin too.

  3. Hi Sami! I’ve enjoyed your writings. I know about most of what you’ve written. But, just to be sure, is there a list of lab testing that is done on a depression work up? I understand that each person is different and testing sometimes has to be individualized. So, I’m not asking for a recommendation for a specific person, but more the general list of tests outside of standard CBC and general lab tests that are typically done by conventional physicians. And, I’m wondering what laboratory does the kryptopyrrole testing. In the past, I’ve used Vitamin Diagnostics, but currently don’t trust their results. Thank you!!!!!!!!!!!!

    1. Hi Stephen,
      Thanks so much for your comments and I’m so glad you are enjoying my posts! This is a great question!
      1. The full work-up kit can be ordered through me.
      2. For blood/serum, I only work with LapCorp (all directions are included in the kit). You’re right to be leery of other labs’ inaccuracies.
      3. Regarding pyroluria and kryptopyrrole testing, it’s really important to keep urine away from light and freeze it right away. It’s also best to do the test during a state of stress and anxiety. After the cup is filled up (do it in a dark room if you can), I covered it with a towel and ran to the freezer, still keeping it covered, then it’s overnighted. I mention it because without this protocol, the results can get skewed.

  4. Hi Sami!

    I’ve enjoyed your writings for a few months now! You have such good vibes and I always love what you post about, and I truly admire your bravery in sharing your story and the work you do to inspire so many! I was just more curious about over and under methylation…I have some traits from both, and I am so excited to get all of this sorted out! Being a perfectionist and overachiever my whole life was severely exacerbated by attending an Ivy League school. I’m taking time off right now to heal up my digestive tract among a few other things. I’m about to start the GAPS diet. Have you heard of it? It’s very interesting and seems like a good fit for me. In addition to that, I want to get this methylation thing sorted out. How do we test for this, and once we do, what do we take to fix it. Should I have a consultation with you?


    1. Hi Izzy!
      Thank you so much! I know exactly how you feel. The role methylation plays in the body is quite complex. I am very familiar with GAPS and I think it is wonderful you are taking an active role in your healing. I’d love to offer you a complimentary strategy session to see how I can help. If that feels good to you, I’ll have my assistant get you scheduled.

  5. Hi Sami

    Im undermethylated with high histamine I have been very fortunate to receive excellent care as far as my mental health issues go. Unfortunately the only thorn in my claw is treatment resistant OCD which drives me nuts (and my husband). Recently my GP has introduced NAC to the list of meds I currently take apparently it has received positive results. I also take SAM-e as well as zinc, b6, snri. I am feeling quite optimistic about this as nothing else has really made significant improvement.

    1. Hi Ann,
      Thank you so much for sharing your story, and I’m so happy you’re receiving excellent care for your undermethylation. I’m excited to see how the NAC works for you. I’ve also found OCD to be one of the most difficult aspects of undermethylation as well. I mean how many times do I have to read that damn email! 😉 Big hugs to you and please let me know how it goes!

      1. Can headaches be from overmethylation? My son has very high pyrroles results and low homocysteine test and now waiting results for histamine blood test. He suffers from constant bad headaches and nausea.

    2. Ann, How is your treatment protocol for “undermethylation/high histamine” going?

      Are you still on NAC, SAM-e, zinc, B6 (P5P??) and snri?

      Thanks, Tan

  6. Hi Sami,

    I just stumbled upon your website via a comment you left on Chris Kresser’s blog, and I’m very interested in your ideas about the underlying causes of mood disorders, etc. (I’m also curious about how your path evolved into that of a coach – someday, I’d like to do something similar…)

    For now – the following is a comment recently posted elsewhere, because I would greatly appreciate your thoughts on my experience supplementing with B9/B12:

    For two months, starting at the beginning of my most recent (unplanned) pregnancy (my fourth), I experimented with taking SAM-E and B9/B12 as per Dr. Lynch’s suggestions. My first three kids have lip/tongue ties, my oldest has ASD symptoms, and I have suffered from mood issues since adolescence, plus post-partum and severe pregnancy depression (hence: why we were NOT planning to do this again!!).

    In any case: I felt increasingly great for those first two months, until I suddenly got an unrelenting two-week headache, culminating in several days of high anxiety and panic attacks.

    Over the past six weeks, since that headache, I continued to experiment and also stopped taking SAM-E. Strangely, despite having taken increasing amounts of B9/B12 for the two months previous (with excellent results), I find that I really can’t take _any_ B9/B12 now without it triggering a severe headache. For the past six weeks I’ve tried: reducing my dose incrementally, taking it only every three days, then every week, and yesterday, taking a tiny dose after ten days of not taking any at all.

    But even with that tiny dose (100mcg), I felt intense anxiety and then an intense headache, and I imagine there must be more at play here than I can hypothesize about! I’m curious about some of your thoughts concerning overlapping reactions, copper overload (I was a lifelong vegetarian until the age of 30), and how this might play into depression and symptoms of undermethylation.

    I’m also wondering if others ever experience this paradoxical reaction – a really seemingly _good_ response for so long (two months), followed by terrible responses even with lower doses. I’m hoping this means that my body has enough folate from the foods I’m eating to sustain my pregnancy…and someday, I’d love to understand what’s going on, and be able to help others heal from the hell that mood disorders can be.

    My doctor has recently ordered a thyroid panel and standard iron checks (although I’ve never been low). I’d be curious what else one might need to check.

    Thanks very much for your time,

    1. Hi Sarabeth,
      Thank you for reaching out. I understand how agonizing this must be. Things are certainly more complicated when you are pregnant and folic acid is a nutrient you need to be very careful with. The right kind of diet for your specific biotype is essential especially while you are pregnant. Paleo in and of itself isn’t going to cut it.

  7. Can you please tell me where to get all the tests to determine under or over methylaled, and have copper deficiency, etc? I would like a complete assessment.

    I appreciate your sharing this information.


    1. Hi Barb,
      All testing is done through me. If you get testing done on your own you’ll need to work with a qualified practitioner to interpret the results and get a treatment protocol. Are you looking for a practitioner to work with?

      1. I would be interested in finding a practitioner in my area. I live in Lilburn GA and suffer from depression, addictions and probably other things I don’t know the name for. I am interested in getting Dr. Walsh’s book, but I would also like to know if there is a doctor I can see to treat me.

      2. What if you live in NY, is it still possible to get testing done? NYS has stupid law to not allow mail order tests from other states and not all NYS labs have all tests i.e. I’ve yet to find a lab to test for pyroluria ad I have all the symptoms.

        So we poor unhealthy New Yorkers either have to do without or spend gobs if time and money to travel out of state to get some necessary yet unusual lab tests.

      3. Hi Maria,
        Yes, unfortunately you would need to travel to PA or CT due to NY and NJ laws, but I can still get you accurately tested. Another option is to travel to one of our outreach clinics on the east coast.

      4. Do you mean, I need to go to a practitioner in either PA or CT? CT is closer for me. Where are the outreach clinics on the east coast? Tks, Maria

  8. So very interesting! I have a 22 year old ads, add and ocd son who is a total mess! His ocd is huge problem and has stopped him functioning. After a lifetime of antidepressants, ritalin and other meds, I went down the road of supplements – blood tests came back positive for undermethylation as well as pyroluria. Supplements were in line with Dr Walsh protocol. It made some impact… his ocd was still there but he felt he wasn’t as bad. We discussed with his doctor that there was slight improvement. Then…. he started on SAMe and innositol. The anxiety increased in intensity. He paced and raged. The doctor told me that it would not be caused by these “natural” supplements… so I took him off everything and within a few days he was back to “normal”. We then went back onto traditional psychiatric meds and once again unhappy! Could it be the B vitamins causing the issue? Very confused as he has both under and over methylations indicators. He went from being a talented artist to someone who couldn’t even draw a circle! Need to work out the puzzle!!!!

    1. Hi Judy,
      Thanks for sharing your story. Your questions are difficult to answer without a full assessment and review of labs. Did you work with a practitioner trained in Dr. Walsh’s protocol?

    1. Hi Andrew,
      Because every undermethylated individual is different, I don’t have a specific dietary protocol I can share.

      1. Thank you for your response. I am very much enjoying your posts. Could we have one concerning what you ate as part of your nutrient protocol?

      2. Thank you Andrew. I’m glad you are enjoying my posts. I’ll definitely put your question into my blog queue.

  9. Hi Pierce,
    My first question is where you properly tested? In other words, did you just do genetic tests or did you have other functional testing done?

      1. Hi Pierce,
        If you would like me to create a protocol for you, the initial session is the way to go.

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