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. Hi Sami my daughter is suffering from withdrawal symptoms as she tries to come
    off Lexapro. She is on 10 mg now and would like to eventually begin the process
    again very slowly to get off the medication. We believe the underlying (root) cause
    is could be histamine related and of course testing needs to be done.

    Can you recommend a practictioner or how to find one in SC.?

    Also, she is trying The Roadback Program to deal with symptoms but really needs
    testing and professional guidance for all of this.

    My daughter has responded well to the antidepressants but has the weight gain and
    other symptoms that she is longer wanting to live with.
    So if she is an undermylator and on lexapro and takes folate and B12..do you think
    that is helping or hurting her symptoms..? If I understand correctly probably does
    not need to be taking the B vitamins at all.

    Thank-you for any recommendations! and how does she make an appt for a consultation with you?


    1. Hi Debbie,
      Thanks for reaching out. Your daughter really needs proper testing her to provide guidance. If you’d like to schedule a session with me, you can do so here.

  2. hi Samantha, I just got off the phone with Dr. Mensa and he reported to me that I am a severe Iundermethylater with high very high copper and when I just read your report on under methylation , it totally described me . Dr. Mensa said that I was very similar to you and said I should contact you, I told him I was already on your email list. Wow what an eye opener. He is sending me my results along with my protocol.. Basically everything that I was doing Neutra bullet greens and berries and all of that were not in my best interest and I felt they weren’t but I wasn’t sure so I kept doing it.I have Lyme disease along with the MTHFR mutationso I thought that I should be doing all the greens and the berries etc. etc. Dr. Mensa said no no I should be more of a carnivore.it’s truly amazing what you can learn to the right blood test andthe right doctor I’m so grateful I spoke to him.I love to see what you’re doing you ll educate a lot of people. Thanks.

    Patty K

    1. Hi Patty,
      Thank you for sharing your story and I’m so glad you reached out. It’s amazing what diet dogma does to society as a whole. We’re pretty much brainwashed to believe that we need greens for health, when the opposite is true for many of us (much higher % of undermethylators vs overmethylators). Dr. Mensah is right, we (undermethylators) do better on high protein diets.

  3. Dear Sami,
    Thank you for sharing complicated information in an understandable format. Reading through your explanation of methylation and personality tendencies, I realized I have traits on both over and under methylation with the exception that I am not an underachiever. I have been deemed a complex patient, and have several diagnoses. My insurance didn’t think genetic testing was necessary, so I have been going along on my own with a little help from two of my doctors. I have many food intolerances and sensitivities to chemicals and electromagnetics. I have followed most of the diets prescribed by my doctors with little relief. Now, I am in the process of determining if I have MCAD or mastocytosis.
    Which tests do you recommend for determining copper, zinc, folate, and B6 levels?
    Thank you.

    1. Hi Cynthia,
      Thank you for sharing your story. I’m glad my posts are helpful to you. Keep in mind there are no tests that can accurately determine these levels. Functional testing for methylation, copper and zinc status needs to be performed by a qualified practitioner. You can email us here for more information.

  4. Hi Sami,

    It was an aha moment for me reading this! I am a classic overmethylator and my biggest frustration since being put on different supplements for MTHFR, long term depression, fatigue, overweight, fibromyalgia, gut problems and allergies is that my creative ability has GONE. My art is my life and it’s gone! I’ve been given a number of methyl donors and reacted really badly and now I don’t know what to do. My ND has me on NAC very low dose as higher dose made me very anxious and sad and in more pain.
    I’ve been on a Paleo diet and including bone broths, kefir, veg juicing and fermented veg. Am I on the wrong track? Have always been anaemic and toxic feeling and suffer with tingling and weakness and poor memory. Where to now?
    Thank you in advance for your generosity.

    1. Hi Liz,
      Thanks so much for sharing your healing journey. I’d love to offer you a complimentary consultation to see how I can help. You can email us here and my assistant will get you taken care of.

  5. I’m and undermethylater (I think). I have high homocysteine levels and have for years. I DO have sinus issues well controlled by antihistimines and I respond favorably to Lexapro (SSRI). However, even with the anti-depressant, I suffer from depression, isolationism, social anxiety, etc. I’m better than I was 3 years ago, but still am plagued by nearly suicidal depression occasionally – I think this occurs when I take too many methyl donors. Does that sound right to you? I am MTHFR 677++.

    1. Hi Lea Ann,
      Thanks for reaching out and sharing your story. It’s impossible to advise you without a proper assessment and testing. You can read more about working with me here.

  6. just found out that myself and my three sons have these symptoms and we trying to find the single minerals and vitamins etc where we live but it seems impossible, has anyone got ideas what foods we could try in the meantime.

    1. Hi Adrianna,
      Thanks for reaching out and sharing your story. Without knowing your biotype, that’s a difficult question to answer. You can read more about working with me here.

  7. My daughter tested for pyroluria and came back positive.
    We have seen many pyroluria plans, most of them suggesting
    manganese as part of the plan. Seems to me I read something
    from Dr. Walsh or Dr. Mensah about avoiding manganese for
    an undermethylater. Do you know why niacinamide and manganese
    should be avoided? I would appreciate any information.

    1. I have read that some undermethylaters tend to be low in copper which automatically increases the body’s absorption of manganese. This means some undermethylaters may have too much manganese already which could create serious side effects if a person were to supplement with it (destruction of brain cells and Parkinson’s type symptoms). Niacinamide uses up what methylation is working so hard to make. The more Niacinamide a person takes the more of an undermethylater they will become. If a person eats healthy they should not require niacin as a supplement in their diet. Niacin is good to have on hand in case a person overmethylates and wants to reduce the symptoms of overmethylation.

  8. Hi Sami,

    I am wondering how through you we can get labs ordered? I was diagnosed undermethylator within the last year with a 24 hour urine with Genova labs and my PCP. Yesterday, just to confirm how methyl support formula is working and from Walsh Institute/Mensah medical online info I asked my PCP for a whole blood histamine level test. It’s a send out test so no immediate results.

    Interesting and sad how the doctors today don’t know anything about methylation and I’ve not been helped by the methyl support formula..I UNDERSTAND WHY NOW.in-fact food intolerances increased and muscle wasting occurred. My breasts shrunk completely!I diagnosed myself with fibromyalgia within the last three months and my PCP concurred.

    My oldest son was diagnosed last year (23 yo) w schizoaffective disorder. I wanted to check out Mensah Medical for the whole family but the cost issue has me at a standstill.

    We desperately need qualified help. Any suggestions are appreciated.

    1. Hi Beth,
      Thanks for sharing your story. I agree it’s disheartening that most doctors aren’t aware/don’t understand methylation cycles and how critical they are to health and well-being. You can learn more about working with me here.

  9. Hi!!! Wow, this is all very complicated. I struggled with anxiety for what seems like all my life. Medicine nor anxiety or depression was never thought of for me; as I was too busy ‘fixing’ others’ lives! I never realized I had depression too until after trying ‘Paxil’ anti depressant for severe panic attacks and anxiety due to a beautiful son that became a drug addict. Not only did the ‘Paxil’ stop the anxiety and panic immediately; but eventually my mood was lifted in such a way that I never realized I had depression until I stopped the medicine and felt the same as I used to.(I stopped due to weight gain and what I thought was no libido due to the medicine.) Little did I know I would go into severe withdrawals to get off of it. I weaned off three times only to be hospitalized the third time. I have not been on ‘Paxil for seven years. But have spent those years and the present researching, in and out of doctors offices, going to three different natural paths for MTHFR treatment; and on and off different alternative anti depressants and recommended nutrients. All of which were no long term lasting help and only made me feel worse. I have been tested for genetic mutations and am compound heterogeous. My past labs also revealed very low vitamin D’s (27), low magnesium, normal iron, high folate (38ish), B12 (600 ish), awesome homosystiene, up and down tsh and free t4 throughout the years. My basic food sensitivities are dairy -high, chocolate – midway, oranges-midway, and tomatoes-midway, and very low gluten. More labs I am sure but I can’t rememembr or need not go on for it will be way too long! I have been prescribed the methylated folate and B12; along with P5P B6. For the MTHFR; which I have had different reactions from each but all and all emotionally I felt much worse on all three for any long period of time.
    I have been trying to stay away from dairy, and all of the other sensitivities , but eat small amounts of bread as I crave it at times., I stopped all supplements at this time and am only on the vitamin d, 4000 IU’s, magnesium citrate 400 mgs.’s at night and 200-400 during the day; along with melatonin to sleep. The lexapro anti depressant is only at a low dose and really does nothing all winter. I left it a lone and I feel better with depression since spring has arrived as I am out in my yard and gardens most of the day. I take .25 of clonazopram am and ..3150pm. I am trying to wean off of that-it is not easy
    The latest natural path wanted to add more supplements like fish oil and C; along with iodine in high doses. But I am too afraid to do any more at this time. I feel like I have been living the past seven years in hell at times and hiding it all inside so my family does not get overwhelmed with my issues.
    The profiles of Dr. Walsh’s are interesting because I can see myself in both of them. Though I am not pear shaped and was a very slender teen and young women. My dreams of careers were homemaking, teaching, nursing. I enjoy family and gatherings, home and yard decorating; but if I start a project I enjoy I can not stop.. I have had counseling in the past couple of years due to my son’s addiction; and also have been addressing ‘my fix it’, ‘co dependent’ and ‘suggestive’ personality. We also address possible insecurities that cause me to try to control situations.It was pointed out that I fall heavily on the Empath Side.
    I feel like I am making some small bites of progress in the past month sense my last crash from methy folate and B12 as I have been steering clear of it for a while. Unfortunately I live in Vermont and am unable to travel the distances required for someone with Dr. Walsh’s expertise; so if after reading this you are able to share any ideas or point me to a recommended specialist that might be closer I would really appreciate it. Also one of my natural paths said he would be willing to take offered ideas from a specialist if they were open to it (not sure what the legalities would require for that). All of the natural paths I see say my system is incredible sensitive and complicated.Go figure!! LOL. If you got this far-thank you for taking the time to read this. In closing I should say with saddness and humor too most of my father’s side of the family is a regular trainwreck!! Many brilliant people with either mental illness, or addicts of some sort and many young lives lost because of addiction overdoses, hep C, or body’ gave out. I am the only one searching for an answer other than just a pill. I don’t mind the medicine; but I want to feel my best on a medicine; be healthy at the same time; and fulfill my purpose.

    1. Thank you for sharing your story Matina. I work with clients via phone and Skype so the fact that you are in Vermont is not an issue. Click here to learn more about working with me.

  10. Interesting info. I’ve done the 23&me test and still not sure where I am on all this. No red bits in MTHFR but have a COMT variant. The article got me a bit confused with switching discussion between under and over methylation though.
    In the discussion you said both Folic Acid [I know that’s not too good] and Folates are not recommended but not sure if you meant for your case of undermethylation, – or all cases, & including ‘normal’.

    1. Hi Trev,
      Great question! In general, folates are wonderful for overmethylators, but terrible for those of us that are undermethylated.

      1. hi- I’m still not sure if I’m overmethylator though. Does the COMT variant say that- or is it all on the back of MTHFR having no homogynous bits? When you’ve been in this awhile it’s probably all obvious 🙂

      2. Genetic testing cannot determine the net effect of SNPs that enhance/depress methylation. They are good for determining a mutation for Alzheimer’s disease for example, but they have no way of telling you how much methyl is present in your body. That’s why we use functional testing because it gives us a really good snapshot of what’s going on at the present time.

      3. On Dr Yasko’s NRI site report on my 23&me results she says clearly in a chart what B12 different combos of SNPs I can take.
        This seems to indicate that ,on average, at least,, a trend has been established.
        I have thus bought Adenosyl B12 [not from her site] and having no probs with it. It is more expensive, but that is minor compared to having the wrong support.
        I know muscle testing can be useful- is this the only way you can confirm these subtle reactions to supplements?
        I think she using a scientific approach to what can or can’t work in the body from enzyme productions etc.
        This seems a fair way to proceed, to me!

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