What is a Methylation Disorder?

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

What is a Methylation Disorder?

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.


267 thoughts on “What is a Methylation Disorder?”

  1. Irene Kasprzyk

    I feel crappy all the time mentally and physically! I want to feel “normal” and healthy. As well as help my family get healthy too!!

  2. This was fascinated to read, as I’ve been trying to get to the bottom of my children’s myriad issues for many years now. I finally discovered the MTHFR mutation, and, through labs, found we do carry this. My reading led me to believe we needed methylcobalamin and methylfolate. We’ve been doing a specific supplement regiment that increases doses week by week. My eldest became so severely anxious (anxiety is not something she normally deals with. Rather, she has been diagnosed bipolar, is high achieving, just got her bachelor’s degree, has many physical health issues) that she discontinued the supplements. My two other kids have severe anxiety and depression. SAM-e increased anxiety drastically for one, and she is unresponsive to medications, the other doesn’t want them. Both are severe underachievers. Your article makes me think my eldest is undermethylated, maybe, and younger two are overmethylated. But how to help???

  3. Hey,
    a small update. I am now in week 7-8 of my nutrition therapy. I am feeling much more better. Its amazing. Of course there are still issues and also days where I fell completly bad, but its getting better and better.

    In the meantime I have read and heard the many posts and podcasts here and from other sides about copper toxicity, methylation and pyrolle disorder. It was good to know, but now I am also sometimes worried if my practitioner did all the “important test” or if she did everything which is needed and so on. Especially why we made no hair test and no test for other heavy metals.

    So yes I know more and I understand my symptoms better but on bad days this information make me more depressed. So maybe it is not recommended for everyone.

    All in all I feel much more better than before the therapy. I am curious what will happen in the next weeks. I will update soon.

    PS: I have found this calenders and will use them soon. Maybe for someone it is also useful.

    Source: http://www.mensahmedical.com/patient-resources/frequently-asked-questions-faq-for-patients-and-prospective-patients/

  4. Hey,

    I got my Walsh test almost 2 weeks ago and started with supplementation (B6, Methyl-B12, P5P, Vit.E+C, Molybdenum, Zink).

    I am undermethylated (high Histamin, but normal SAM, SAH and SAM:SAH) and have high free cooper (normal serum copper and a bit low plasma zinc compared to the Walsh ranges). I have also bipolar status of the pyrrole disorder. All in all the jackpot.

    Now after 2 weeks of supplementation I feel okay and I am happy that it will get better in the next weeks and months.

    I have heard a lot of your podcasts and now all my hystorie makes sense. 2 years ago I made a minerals whole blood test and I had a copper and manganese deficiency in the whole blood. So I started to supplement and I got much more anxiety. Cracy, but after hearing of your copper toxicity podcast I know why this happens. Because I had also at this time copper toxicity but it looks not like that because noone checked my Ceruloplasmin. My ceruplasmin is in the range but very low there and my free copper is around 40%. 2 years ago I had probably also too much copper and through the copper supplement my anxiety got worst.

    Also my multiminerals were bad for me and made me feeling very bad. It includes folid acid, which is extremly bad for me. Also manganese and B5 are bad for me. I tested both in the last too weeks. 😀

    I have started now a low folate diet because even a bit too much vegetables make me worse. I realised it after all of the information I got through the Walsh test. I have bought your ebook bundle and will maybe book a coaching with you, if possible for people outside of USA.

    It is all so cracy. Everything makes now sense. I am happy about that, because I can heal now. I need only to take all my supps and reduce the folates in my diet. That makes me happy. 🙂

    1. Hi Joanna – many people have traits for both. The key is to get properly tested so we know for sure what your methylation status is and how we can help you balance it.

  5. May I ask, why are you not recommending folates for undermethylation? I did see that William J. Walsh is saying that they are a good thing for undermethylation, except when you have depression. Also, on http://mthfr.net/ they are recommended. Do you have any thoughts on that?
    Do you have any experience with people with low homocysteine like me? What would that be, undermethylation?

  6. Hello!

    I came across your article because I have undermethylation / high histamine and I desperatley want to solve this issue in the safest way possible. Because my naturopathic doctor has me taking Active B-complex and tri-magnesium, which after reading your article, among some others, I have found can actually make things worse! 🙁 I’ve heard taking mythlfolate (active b-complex) can cause cancer in those who undermethlylate, which is horrible news! I have really bad health anxiety and I really don’t like being at a higher risk for health issues. I just want to be healthy. I need to know how to correct undermethylation. Something that you mentioned about diet really scares me because you said you got a big health problem from being on a plant based whole foods diet, and that’s a diet I recently switched to because I want to be healthier. Is this diet going to cause me health problems in the long run? I would really appreciate any feedback!

    1. Hi Ana,
      Unfortunately, I cannot provide specific guidance without consulting with you. If you’ve been properly tested, I would caution a vegan lifestyle based on what you’ve shared.

  7. Just wondering – I thought that methylation status was static. My daughter was first diagnosed as being undermethylated with a whole blood histamine of 117. Now the exact same test a year later from the same lab comes back 51 – normal. What gives?

  8. Hello. I suffer from very severe depression for 10 years now with few years of relief while taking antidepressants but they always developed tolerance so I looked for treatment alternatives. I found out about Walsh protocol and was diagnosed with pyroluria and undermethylation. My consulting doctor said that it might take up to 12 months to fully correct undermethylation. It’s been almost 5 months now and I feel improvement but changes are happening really slowly and I am afraid I will not fully recover. Is it possible that undermethylation takes longer than 12 months to correct?

    1. Hi Lina – In some cases, the process is slow and can take more than 12 months. Hang in there. Healing is occurring, it’s just taking time.

  9. I think the best form is L-Methylfolate which is different from Folate and Folic. But I am not sure if it works for everyone.

  10. Sheila Harriman

    I have always had depression and anxiety from as long as I can remember. An empath, learning challenges all my life (I’m 54), never sleep all night, over weight, hashimos, celiac, allergies to fruit, nuts, trees, grass. Migraines, nerve pain
    Antidepressants don’t work so I turned to medical cannabis.
    ( having great results).
    Life in general has always seemed just outta reach

  11. I read through your blog post here. I have a question I was hoping you might be able to help with. What are some common signs of ADHD in adults? My brother was recently diagnosed and I’m trying to help him out. Thanks in advance for your answer.

  12. Hello,
    I live in Poland and Im wondering how i can get a whole blood histamine testing (it doesnt seem to be available here, i did histamine test but it turned out to be just serum)? Also, I am curious if methyl b-12 would be suitable for overmethylators?

    1. You would need to get tested by our lab here. Anything methyl is contraindicated in overmethylation because the body already makes too much.

  13. My son is 19 and suffers from ADD. He has always had trouble with his stomach and now in college is experiencing rapid weight loss and intolerance to many foods. He has never had problems with histamines. He is also experiencing severe depression although he swears he is loving the college life. I am so worried about him. We have mental illness and suicides in both our families. Do you have any suggestions for him. I just mailed him Pure Encapsulations – Adenosyl/Hydroxy B12 – Hypoallergenic Blend with Vitamin B12 for Nerve and Mitochondrial Support – but after reading your information, I’m not sure that is the way to go. Any thoughts? Thanks so much.

  14. I was diagnosed in June, 2013 with OSTEOARTHRITIS of the spine and both knees, symptoms started with severe back pain, joint swelling and stiffness in my knees and eventually the feeling spread to my shoulders and neck, i couldn’t lift my arm without pain medications. I was prescribed tramacet and arcoxia for 8 months but had to stop them due to bad effects. In 2017, I started on OSTEOARTHRITIS HERBAL FORMULA from RICH HERBS FOUNDATION, this natural herbal treatment reversed my osteoarthritis. Visit ww w. richherbsfoundation .c om. The treatment worked incredibly for my arthritis condition.

  15. I know your work is mostly related to women’s health, but i have a general question about methylation and folic acid. If over methylation is a lack of folic acid, then if you are undermethylating you have too much folic acid? I have asked this of my doctor, but have not been able to get an concrete answer. First blood test showed elevated levels of folic acid and B12, decreased levels of B6 and low levels of Vit D – all the guys that point an issue with methylation. So a year of taking a supplement to help with methylation and homocystein. However, the blood test a year later shows a decrease in B12 levels, stablizing of B6 (but drop in iron), but a double increase in folic acid. Slightly concerned about that, but the doctor is not. This would then definitely mean undermethylation?

  16. So, I started doing some research on overmethylation because while we are pretty sure I have at least one copy of an MTHFR mutation, I haven’t taken the test yet because my insurance won’t pay for it. Based on the results of my most of my mom’s siblings and some of my cousins, we are pretty sure that both of my maternal grandparents have at least one copy of a MTHFR mutation each, and not the same one. Also, all of them have experienced blot clots. My mom who is a Nurse Practitioner, has said for a while that she thinks I overmethylate because I can’t handle multivitamins without my anxiety going through the roof. I can take a multivitamin, but I better have a solid 60-90 minutes per day for exercise, and I’ll need to hit at least 12k steps to not feel like I’m going to crawl out of my skin.

    In high school, I was diagnosed with ADHD, GAD, and Bipolar II with rapid cycling. I was diagnosed with ADHD and started taking short acting adderall my freshman year of high school; then I switched to Adderall XR. At the beginning of my junior year of high school, I became very depressed and couldn’t understand why. Then, after my best friend’s mom died, I was put on Prozac, early November. By the middle of December, I became suicidal. I knew it was the medication, because it felt like my mind was being controlled by this dark cloud. Even when I had been depressed before, I never wanted to committ suicide, I just cried all the time, had a hard time getting out of bed in the morning, had zero motivation for anything, etc. But this time was different, I felt compelled to hurt myself, but at the same time I didn’t want to, but I didn’t know what else to do. I ended up locking myself in the chapel at my high school after I barely made it back to the school after a fight with my mom. I had a death grip on the steering wheel the whole way to the school because I wanted to turn the wheel of the car and drive into a tree. I was terrified and locked myself in the chapel because I felt it was the only place I couldn’t harm myself, if I truly didn’t want to, which I didn’t then I would be safe there with God. After I was able to fully explain things to my mom, she had me taken off the Prozac immediately. After that, instead of going back to my PCP, I went to see a Psychiatrist that worked in concert with my Psychologist. He had me try Effexor XR next, and that was no better. I was not even remotely close to a “therapuetic dose” when I started to feel things that reminded me of how I felt the last two weeks leading up to the chapel incident and demanded to be taken off of it immediately. The two weeks it took to taper me off because I had severe withdrawal symptoms; it was living hell. I yelled at my spanish teacher after class one day for docking me participation points for not talking during class, when I wasn’t talking because I was doing everything within my power not convince myself that I did not need to run to the bathroom to puke my guts up. I literally spent most of the class period with my fist in front of my mouth. After I was finally off the Effexor XR, my Psychiatrist had me do some tests (rating scales and such) that were different from the ones the Psychologist had me do, and determined that with the combination of the results of the tests and my reaction to a typical SSRI and SNRI, that I was most likely Bipolar II with Rapid Cycling in addition to the ADHD and GAD my Psychologist had diagnosed me with. They put me on Lamictal and I ended up working my way up to 300mg; he even taught me how to adjust my Lamictal dosage for my slight SAD (everyone in Seattle has SAD) and my Adderall XR dosage for really long nights of writing college papers. I was on the 300mg of Lamictal and 60mg of Adderall XR for about 5 years when I decided to try EMDR therapy and after three years, I was able to decrease my Lamictal dose to a steady 150mg with an increase to 175-225mg for Nov-Feb. For the last 3 years, I have been taking 50-60mg Vyvanse, 3mg Intuniv, 25mg Toprol, and 150-225mg Lamictal.

    I have also always suffered with seasonal allergies. I have IBS and have determined that the sugar molecule attached to the gluten molecule is really not my friend. I have reactive airway disease, which we thought was exercise induced asthma, but after realizing that how severe my symptoms were depended on my environment, it was changed to reactive airway. I have a tendency toward auto-immune reactions; after getting whooping cough during the outbreak in Washington state in like 2012, I ended up with a rare eye condition called Multiple Evanescent White Dot Syndrome aka MEWDS, and after a bout of norovirus two years ago, I ended up with this thing called “slow moving stomach” that apparently can be an auto-immune reaction to a virus or bacteria that affects the gut; it acts and feels like a disease of the gall bladder, but that is just a reaction to the fact that fat is sitting in your stomach nearly rotting and it takes 6 to 9 months to fully clear up. I couldn’t even eat chicken breast most of the time without pain. I lived off of tilapia fillets, tuna with BBQ sauce (couldn’t do even a tsp of mayo), non-fat yogurt, plain carbs, and veggies. Many members of my family have thyroid issues, my mom actually had post-partum Graves Disease, and although I have had times where I swear to God my thyroid levels are low, they never are. I also have had symptoms of anemia, my CBC always comes back fine, but my ferritin levels are on the lower end, but not significantly low. Last issue that I have always dealt with in my life, is migraines. I have many triggers, some of which are psychological, fluorescent lights are a problem, but as typical a huge one is hormones.

    I recently have started to look more into the overmethylation and the MTHFR mutations because I am now 30, and have been on oral contraceptives since I was 13. I first started taking them because of a cyst on my right ovary, and then just continued. I have tried many different ones over the years, but have had the most success with Yasmin, Yaz, and recently Safyral. However, within the last few years, my cycle has really started changing and I was getting different and worse symptoms with the Safyral. I was getting really bad cystic acne on my jawline and browline (something I had never really had an issue with other than occasionally as a teenager) and while it had done a great job with my mood for years, all of a sudden, I thought I was going to murder someone on the first day of my period. I would lock myself in my room and not answer the phone or anything all day; in fact most of the time, I would try to take something that would just make me sleep most of the day so that I didn’t have to worry about it. So, being that I was getting close to 30 and we knew we were going to have to talk about getting off of such a high mic pill, I decided to see how I would do off of it. It was okay for a bit, but then I started getting really severe cramps with my period, 1-2 days mid cycle and the day before I start my period I could swear I hadn’t taken my meds when I actually had, and most recently, a resurgence of my migraines. They had been really bad in high school and college, but they were starting to taper off, and I had developed a pretty good migraine protocol. But now, with my hormones, I am experiencing an new type of migraine; it’s almost like a migraine without a headache, but we think it’s actually this weird type of migraine called a vestibular migraine. I’ve had almost every type of migraine out there, and have had all different kinds of auras and symptoms, but never holes in my vision or tunnel vision. I often tell people I can’t see when I have a migraine, but that’s not really what’s going on. It’s more like the connection between my optic nerve and the processing center are not communicating correctly. My two favorite examples are – 1. if I were to drive, and see brake lights come on in front of me, I would see the brake lights, think red lights, oh brake lights…..oh, that means I need to stop, or 2. if I try to read it goes something like this, the word on the page is cat….I see/think c-a-t, c-a-t, cat (just the word cat no meaning), then after a pause think, “oh, cat, like meow, cat”. I have also been known to talk almost like I’m having a stroke when I have a migraine. However, the weirdest part of my migraines is that I ALWAYS crave chicken and the worse the migraine the more intense the craving. and eating chicken actually helps. Somewhere, once in a desperate search to find out why I crave chicken, I read something about B vitamins, and so the next time I had a migraine, I took one of my roommate’s food based B complex vitamins and it worked just like the chicken. So, sometimes when I get migraines and I am craving chicken really bad, but my stomach is saying “no food”, I’ll take a multi-vitamin or a B complex (depending on what I have around), but that is the ONLY time I can handle a B complex.

    Now, that I have rambled for forever (sorry, my Vyvanse wore off about 3hrs ago), I guess it’s time to get to my point/questions. My mom, being an NP, is like really traditional on her outlook on medicine, and has to have lots of hard core scientific research for everything (I wanted to use plain yogurt with live active cultures for my last yeast infection because the diflucan wasn’t working and the monistat was making my skin raw and she said I was crazy), so I’m not sure how she would take information like what is posted here. I am also very scared that if I do get tested for the MTHFR mutation and have it, and do get tested for overmethylation, that we are going to have to adjust the dosage of my medications to work with the overmethylation, and I am terrified of that. I have everything very carefully balanced, and throwing one thing off, could possibly ruin my life. I do not cope well with the emotional instability and ADHD symptoms and could potentionally lose my job, and put significant strain on my relationships, not to mention that I am a student hot air balloon pilot, and last year spend $12k on a hot air balloon and I can NOT fly if I am not 100% sure that I am emotionally stable at the time. Are there people who are experts at balancing this many different medications and symptoms with trying to treat the overmethylation, once I move back to Seattle next August, (I am currently living in Gallup, NM) I could start doing EMDR again to help with things, but I’m still terrified of depressive episodes, hypomanic that are almost full blown manic episodes, and even worse long periods of mixed episodes, I’m terrified of my ADHD and anxiety getting so bad that I can’t function at work and will lose any job I have, and I’m terrified of the extreme uptick in migraines that comes with all of this (they become a psycho-somatic coping mechanism for all of the stress – if you have a migraine so severe that you can’t function, you can’t go to work where you keep experiencing near panic attacks and just general extra high levels of stress and extra high anxiety all day long). So, I don’t want just anyone helping me through anything I might have to do, I want an expert who is going to listen to me and understand all of my weird quirks.

    Also, knowing that I am probably going to have to find a new birth control method and have been having all these symptoms with my cycle, any recommendations for what to try?

    Last notes, I am also overweight, and know that diet and exercise are typically a huge part of these things, but I live in an area where it is very difficult and very expensive to live a healthy lifestyle. Healthy food is very expensive and not great quality around here, so it’s really hard to stick to a healthy diet because after you spend the extra money on “fresh” fruits and veggies that have hardly any flavor, they go bad pretty quickly because they really weren’t that fresh. The only way to get good healthy food for a remotely decent price is to drive 2hrs to Albuquerque, and then you spend $50-$75 in gas, and almost even out any savings. Exercising is also difficult because gym memberships are expensive and it is not safe to go walking outside by yourself (or really even with a friend) in most of the neighborhoods, and I live in a very small apartment, and with the reactive airway disease, I can’t always handle certain workout regimes, walking is truly the best for my needs and my favorite cardio, and I can’t do a lot of it here.

    1. Copper overload is not the same as Wilson’s disease and methylation is a separate variable in copper metabolism. Clinically, we see both over and undermethylated individuals with a wide range of copper values from high to low and normal functional ranges.

  17. Hello, I suffer from depression and OCD BDD and anxiety, I was suspecting undermethylation and maybe copper overload but the results came back following: histamine 0.49 ug/l (2000 pg/ml (191-663). So zinc and b12 only eleveted according to polish standard levels. How can i interpret it according to methylation? Im still waiting for b6 and selenium results to come back.

    1. In my previous message, blood test results were deleted for some reason, they are following: histamine 0.49ug/l (2000 pg/ml (191-663); folic acid 13.03 ug/ml (3.9-26.8);
      Cerruloplasmin 0.22 g/l (0.16-0.45);
      Copper 1038 ug/l (800-1550); zinc 19.8 umol/l (9-18)

  18. Thank you Samantha for the article and this forum.

    I feel compelled to share my son’s journey. His condition deteriorated at age 20 and he just had his 28th birthday. He was a good student and athlete through high school, accomplished a lot and received many honors. Went on to college and did very well, dean’s list freshmen yr, resident advisor of dorm second year, etc. his third year his report card was all NC or D’s. Literally the beginning of the end. Since then we have seen 8 doctors and received multiple diagnoses from schizpphrenia to clinic depressant. After being declined by a university doing a study on brains of schizophrenics because they concluded after a 4 hour interview he did not fit the profile, we pursued alternative medicine. Started with Amen Clinic and now working with Mensah Medical. After extensive blood tests, a nutritional regimen was prescribed to treat pyroluria (73) and UNDERMETHYLATION last year. We started regimen Jan 2018, initially his condition seemed to improve with more energy although sometimes accompanied by anger. But, the most alarming result was his mental makeup changed dramatically for the worse, He no longer remembered things he knew well before like boulevard streets that border the street he grew up on, how to lock the back door, and he started asking permission to do things like a 12 year old, like can I sit on the front porch? Can I go out with a friend? He became very juvenile in his thought process. It was like the nutrition scrambled his brain. I decided to abort nutrition plan in May until we could determine why the paradoxical effect? He was tested for possible infections, and had a slight urinary infection and yeast growth in intestine. He was/is being treated for both. While not taking anything but antibiotics for infection over the summer, he was constantly fatigued and stayed in bed for 16-20 hours per day. So we talked with doctor and decided to just work on pyroluria not methylation issue and really just taking morning and evening composite and evening primrose oil. I thought with yeast infection perhaps he was not digesting nutrition so I give it to him in liquid form (smoothie). We have also been very conscious about diet. Once again, he gas great energy and somewhat angry but it is the mental disorientation that has surfaced again and that is a huge concern. He constantly repeats himself and belabors irrelevant stuff.

    I am desperate. My child has missed out on the last 8 years of his life housebound -cannot work and yearns to…what are we missing? Is there any explanation for the mental decline? I have read about adrenal fatigue syndrome and if you have it that needs to be corrected first before pyroluria but it appears the nutritional plan seems similar. Please share any insight. We need help. I don’t want to stop nutrition plan but I cannot watch my child’s mind deteriorate. What about this copper level, when you take zinc and your body begins releasing copper could this affect your mental capacity? I have not read that would happen but please help.

    Thank you for any help from anyone.

  19. Hi Sami,
    My 70 year old friend moved from NY city to the west. He suddenly shed all of his skin and became allergic to MOST foods. What is going on with him?

  20. Hello Enia,
    I have a son with schizo effective disorder which became evident after taking antibiotics.
    Please let me know what you were able to test your son.

  21. Hello Samantha,
    My 19 year old son became very ill with psychosis after an intense antibiotic treatment. He recovered for a few months, but now having a major relapse. For last 4 months he has not left our home, he lays in bed and responds to stimuli with continues laughter. The diagnosis is of course schizo effective disorder.
    He has not responded to anti psychotic medications; Im a desperate mother, I can’t get him to go to any type of doctor.

    What can I do? He has put on 50 lbs in 4 months on Rispedone, and its not even helping.

    I have tried to implement antioxidants in his diet, but he is not moving.

    He needs help!


  22. Phillip G light

    Further to my comment above,
    I have been taking mega multi B’s for several years or more. Just checked and it has 500 mcg folic acid in it.

    Since I’m currently struggling financially,which B vitamins would be most important. I’m not able to buy all the B’s individually, so I have to be selective

  23. Phillip G light

    There are too many comments in this list for me to read, so I may repeat what’s already been said.

    Yes, I relate strongly to your article. Thank you so much.
    Last year I diagnosed myself with Asperger Syndrome (Autism Spectrum Disorder), and got an official diagnosis at the end of last year. So, I first related to under-methylation. Although I’m not a high achiever and I’ve never strived for career accomplishment etc. Money has never been important to me, despite needing it.

    I also relate to over-methylation! I have symptoms of both!

    Thank you Sami <3

  24. Hello Sami, I’ m so happy I came across to your site! I’m writing you from Europe. My son (22 yo) has OCD since he was 9, and a year ago he was diagnosed shizoaffective disorder too. He’s on antidepressant, antipsyhotic and anti-anxiety drugs, and I don’t like it at all. He is also on cognitive-behavioral therapy.Though he’s felling better when on drugs, OCD symptoms didn’t disappear and he is pretty drowsy.
    I read W. Walsh “Heal your brain” book, and it was a great discovery for me.My son and me both think he is undermethylated. W.Walsh also said that all cases of shizoaffective disorder he worked with was undermethylated. However, we are not sure. Our problem is that we can’t find any lab (not even in another state) to run tests: whole blood histamine test or SAMe/SAH ratio test. Still, we done same blood tests, and I was told by biochemist that:
    1. Homocysteine level in blood shows methylation status (in most cases low homocysteine equals undermethylation)
    2.If levels of folic acid and B12 are ok, than homocysteine is ok
    3. Basophiles count shows histamine level in blood. If it is ok, than histamine in blood is ok
    4.Indirect methylation marker in blood is whole blood histamine level

    Is that true? Should we go to homocystein test, is it reliable for methylation status? Otherwise, we have no alternative, than to try with SAMe+ cofactors, and see what will happen?
    Thank you so much and sorry for possible mistakes! K

  25. Hi Sami, I did the FEBS profile testing in Ireland which revealed I am dramatically undermethylated , have excess copper, low zinc. I was recommended a programme of taking high dose of SAMe (1000mg) along with many other supplements & I was already taking SSRIs. I reacted badly after a while to all this, with lots of panic, anxiety & low mood. My practitioner says I am sensitive to biochemical changes so we must now build up slowly over time. I am not sure I trust him anymore given my bad reaction + I don’t know where to go from here! Can SSRI s & Same be taken simultaneously? Thank you

    1. Hi Kelly,
      Labs are determined after a consultation. I use whole blood histamine or methylation profile to determine methylation status. Please note genetic testing does not determine methylation status.

    1. Yes, if you are referring to histamine intolerance, which can be seen in over, under, and normally methylated individuals. Pyrrole disorder is a separate issue to methylation and can be present in any biotype. It is more common than most people realize.

  26. Hello Sami G,

    Very interested in this article. From my DUTCH /Organic Acid Test results my FD said I was under methylating and my previous FD had me on the wrong B Vit supps apparently. I am now on BioMedica BioActivated B but a little worried after reading what you said about B Vits and Folic Acid. Mine has Calcium Folinate equiv. Folinic Acid. Are they still OK to take? Basically she said “You are undermethylating but this should be being corrected by your supplementation – we need to do this slowly. You are metabolizing primarily down your protective estrogen pathway” which is why she also prescribed me some DIM. I am also on a continuous hrt patch as I am post meno. Should I re-address the B Vits with her do you think please?

  27. Hi,
    Is there a relationship with peripheral Neuropathy, high B Vitamin levels, and MTHFR?
    (Trying to resolve my neuropathy- and my B Vitamin levels were sky high!)

  28. Dear Samantha,

    The “OVERMETHYLATION TRAITS” really suit me I think:

    Just some informations about me (I’m 21 years old, male)

    – I’m easily stressed and terrified.
    – I’m very sensitive and passive
    – Everything feels like a chore for me, even things I enjoy
    – I’m often depressed
    – I have developed vitiligo 2 years ago
    – I suffer from constipation a lot.
    – Sleeping is often a chore for me

    – I’ve got extraordinaly a lot of body hair for my age (Even some hairs on the back and shoulders already). On the other hand, I’m skinny fat (despite of having a low weight), potruding breasts (just a bit), have very small hand and feet for my height and my body is in general rather like an hourglass (shoulders are about as wide as my hips) and I’ve got barely any muscle mass. My brother, who is younger, also has quite a lot of body hair, but he is very tall, has broad shoulders, big feet and hands, a much deeper voice than me etc. At the beginning I thought it was testosterone that caused so much body hair, but compared to my brother and for my age I rather seem to be “underdeveloped”:

    – Your description of addiction suits me very well. I’ve never had troubles with drugs, but I often struggled to eat more healthy (I’m a very picky eater), obssessed with my appearance and I feel ugly most of the time.

    – Besides vitiligo I often suffer from rashes, dandruff, oily skin, but a very dry mouth and eyes.

    – About my libido… I don’t know. Normally I don’t have a high sex drive and I’m still a virgin (I had my chances to lose my virginity, but never did).

    – I’ve got an essential tremor.


    How should I test now if I have overmethylation? What can I do against it if I have it? I’m living in Switzerland, hence my options are limited…

    Best Regards,


  29. I suspect I have similar issues. I’ve been dealing with “allergies” and sinus headaches for years, IBS, weight gain, and some OCD. My question is what type of doctor will know what to test for? I’ve seen many doctors on my journey with very little help from anyone.

    1. Hi Jamie,
      Unfortunately, most doctors don’t know about this science or what to test for. Click here to book a complimentary session with me to see how I can help.

  30. Hi Samantha,

    excuse me, i found after many years of bad health i have kryptopyrroles in urine (with candida infections ecc.).
    How do i discover if there is a problem of methylation ? and which way does it affect my b6\Zinc therapy ?


  31. My son is has extremely high methionine but has low SAM. The problem is high homocycsteine. We have been treating with magnesium but his under methylation traits have not improved. We also gave him D-Serine to treat his high cystothionine however resulted in heightened agitation. His OCD and ADHD is quite out of control and as a 24 year old we need to find an answer. Starting on SAMe to see if this will help but concerned with the increase in homocysteine levels. So confused!!!!

  32. I too have symptoms of both…..
    Thin build
    Allergy tested(environmental)and reacted to everything(mostly 3’s on a 0-3 scale)
    Over react

    Where would I get tested, and what type of test should I ask for? I do have a Naturopath about 3 hrs. away.

  33. Hi Sami,

    I am on a massive learning journey having recently been diagnosed hypothyroid and with 4 x cortisol highs (4 point saliva test). In addition I have been on anti-depressants for 10 plus years. I have had so many labs done privately to get to the bottom of all my issues. I am waiting for 23andme and hair analysis to add to that. My question is, do you have a colleague in the UK (London?) that you recommend that has similar skills as you? I would love someone to put all my results together and make a plan. I am bamboozled by all the information I have and really need to pull it together and start healing my health. Thanking you,

  34. I have been seeing an integrative doctor and naturopath and have been disagnosed with both pyroluria and Homozygous c677t MTHFR. The problem is that no one has been able to say if I’m over or under methylating and protocols work some of the time and then don’t seem to work. I can barely tolerate methyl folate (max 200mcg) which doesn’t help the Mthfr but can seem to tolerate methyl b12. I take a third of the regular dose of an activated b multi which is high in P5p and low in methyl folate and supp extra zinc picolinate. Copper and zinc ratios now in balance, diet very good. My homocysteine is 7.1 and histamine is .8. The problem is that around my period and ovulation I flip out into more undermethylation symptoms and I am low progesterone (take vitex except during period which helps) and not estrogen dominant. My naturopath thinks I’m flipping between over and under methylation at times of hormonal change but is not sure how to proceed. I’m also struggling to keep weight off. I can’t seem to find the right integrative doctor here in Brisbane QLD that understands hormones, MTHFR and pyroluria. Any advice would be appreciated. BTW I’m heaps better ( no more migraines and acne, less mood swings, more energy ) and all this supplemental treatment and nutrition DOES work but I’m still struggling at hormonal or particularly stressful times when I flip out and become hyper vigilant, angry and can’t concentrate properly.

  35. I didn’t know that there’s something like under- and over-methylation until I’ve read your article, Sami- thanks for this information.

    But to be honest now I’m more confused than before because I cover over 50-60% of the symptoms from under- AND over-methylation.
    My biggest issues are:
    – underweight (though I eat for two, at least….)
    – itching skin , dry eyes
    – low – wait – no libido
    – non restful sleep (no matter how long)
    – flu symptoms 1-2h after physical strain (1h shopping is enough to knock me out)
    How does CFE/Me plays a role in here?
    Many thanks!

    1. Hi Carl,
      I’m glad my post was helpful to you. Please don’t try to fit yourself into any one biotype because many of them can produce the same symptoms (anxiety being the most common). You must get properly tested with a complete assessment to ascertain true biotype status.

  36. Hi,
    My naturopath feels I’m a slightly over-methylator. I believe this is based on whole blood histamine load test of about 79 and a several old labs he reviewed: extensive leaky gut test came back negative (finally healed that, yay!!), Homozygous 677tt, Hashimotos, and a few other things. Have a SIBO test at home that I’m trying to find the right time for to rule that out or in.
    My question is I’m majorly confused being an over methylator and if I should cut out all food that have folate or not? I’m basically paleo and don’t take any supplemental folic acid but do eat a ton of folate rich foods. I’m having symptoms flair up that could potentially be a methylation issue and need to know if I should restrict any folate foods or not. Any help you can provide would be excellent.
    Thanks in advance!! 🙂

      1. Really? I will bring this up with him and find out what he’s basing that off of. Thanks so much!! Back to my folate question….should I continue to eat folate rich foods or back off? Thanks again, Sami.

  37. I have been seeing an integrative doctor and naturopath and have been disagnosed with both pyroluria and Homozygous c677t MTHFR. The problem is that no one has been able to say if I’m over or under methylating and protocols work some of the time and then don’t seem to work. I can barely tolerate methyl folate which doesn’t help the Mthfr but can seem to tolerate methyl b12. I take an activated b multi which is high in B6 and low in methyl folate and supp extra zinc picolinate. Copper and zinc ratios now in balance, diet very good. The problem is that
    Around my period and ovulation I flip out into more undermethylationf symptoms and I am low progesterone (take vitex except during period which helps). My naturopath thinks I’m flipping between over and under methylation but is not sure how to proceed. I I’m also struggling to keep weight off. I can’t afford to see my integrative doc at the moment so I’m really not sure how to adjust my protocol. Any advice would be appreciated. BTW I’m heaps better ( no more migraines and acne, less mood swings, more energy ) and all this supplemental treatment and nutrition DOES work but I’m still struggling.

  38. I’m really struggling with dizziness, fainting and fatigue. The Dr has found my folate and potassium to be low. I tried taking a folate supplement but it made me feel worse, potassium supplements have helped. I’m really depressed and just want it all to end. I live in the uk. Would it be worth getting tested and do you recommend any uk practitioners. Thanks in advance

      1. You say folate isn’t an indicator of methylation status but a lot of the talk on here about taking folate and other B vitamins to address methylation issues. Wouldn’t it be logical to think that if I’m low on folate and folate is required in methylation then my methylation might be effected by the low folate status. In the process of trying to find the best person to help. Thanks

        1. For folate and B6 status (and many other nutrients), deficiency is not indicative of need. Nor is folate appropriate for all biotypes.

  39. I am pretty sure I read that you feel choline is a poor supplement choice for undermethylators. I can not find it now. Is that your take and if so, can you point me to more in depth information about why?

  40. Eleonor Hammargren

    I know I have undermethylation from a test I have taken recently.
    Can I find a food list anywhere ? What to avoid and what to eat?
    I have histamin issues as well ( maybe as a result)
    Best regards

  41. Hi Samantha,
    I think I am a overmethyl. I have been on an activated b from Metagenic for a while now that helped. Symptoms of postnatal depression, anxiety and having to go to the bathroom a lot before a talk in front of other students in class. I was curious of your statement that we should stay away from SSRI’s. I do well on St John’s. Would this SSRI be slightly different, or do you think I should stop the St John’s to see if I do even better?
    I know you also stated that we are all different and came be a mix.
    Kind regards,

  42. Does anyone know of methylation testers (or other biochemists) in Malaysia or Singapore.
    I am in contact with several parents of autistic children in Kuala Lumpur who are clearly undermethylated but have had no explanation, help etc. and present advice to them has been wrong (blaming the parents) or useless (medication)
    I would like to help them,
    Tks Beverley

  43. Hello, my 12 year old son has struggled 2.5 years with Obsessive Compulsive Disorder. About 1.5 years ago we found out he has MTHFR T677T (homozygous) mutation but the doctor brushed it off and said it was unrelated. The more I read the more I believe it is related, he is currently not being treated for the genetic mutation. I am assuming there is a methylation issue here? We live in the Dallas, TX area and I need to find a doctor that can help with this, but I’m falling short. Any suggestions would be appreciated.

    1. I would strongly recommend going to a Dr well versed in MTHFR issues because too many lack a working knowledge of the mutation and either incorrectly believe that it’s not important or give you wrong info. 2 great websites are MTHFR DOT COM and search “find a practitioner” and
      mthfrsupport DOT com/find-a-practitioner/ or one of Sami’s outreach sites.

      You can always do a search engine search on “mthfr find a practitioner”. Dr. Ben Lynch started his own organization: Seeking Health Educational Institute (SHEI) which specializes in MTHFR and has numerous you tube video’s explaining the mutation in detail.

      1. Thank you for your response. Do you by chance know how you get tested for over or under methylation? So far the two doctors I have talked to do not know how/where to test for it, I was surprised. Thank you.

        1. I don’t either. I have symptoms for both over & under and strongly suspect I have Kryptopyrrole disorder which is assoc. with undermethylation. Lately I feel much better from taking extra zinc. Zinc and copper need to be in the right ratio to be healthy as well as essential fatty acids. Homocysteine also seems to be an important indicator and my father has several major heart attacks early in life. I find it very difficult to detox.

          I wish the article would mention the test. Perhaps it’s not a specific lab test but rather taking a detailed health history, along with MTHFR test and existing labs while examining the whole person and making a determination while monitoring specific combinations of supplements to see what works best for each individual. This may be a better strategy with a trained practitioner because sometimes lab tests can be incorrect or misinterpreted as in thyroid issues and the person can be medically mistreated until they happen to go to another Dr that hopefully catches what the 1st Dr. missed.
          Otherwise how easy would it be to say take “x” test to determine if your over/under methylating?

          1. Yes, it requires a proper assessment and lab work that is determined afterward. I strongly caution anyone from trying to do this on their own, and this is why I do not give generic advice on my blog. You could potentially create an even worse situation. Each individual’s chemistry is unique. Keep in mind MTHFR testing is strikingly inconsistent and dubious at best, especially in the area of mental health. Pyrrole disorder and undermethylation are two separate chemistries. They are often seen in the same individual, but they are not mutually inclusive.

    2. I would strongly recommend going to a Dr well versed in MTHFR issues because too many lack a working knowledge of the mutation and either incorrectly believe that it’s not important or give you wrong info. 2 great websites are MTHFR DOT COM and search “find a practitioner” and
      mthfrsupport DOT com/find-a-practitioner/ or one of Sami’s outreach sites.

      You can always do a search engine search on “mthfr find a practitioner”. Dr. Ben Lynch started his own organization: Seeking Health Educational Institute (SHEI) which specializes in MTHFR and has numerous you tube video’s explaining the mutation in detail.

      Hopefully in the future this mutation will be automatically tested and treated.

  44. I’d like to find out if I’m over or under methylated. Where to get the tests and a practitioner near Houston, Texas please?

    I’m on my 3rd bout with depression. Have taken Effexor XR since 1997 – it seemed to work fine until a year ago. My psychiatrist is having me try methylfolate – I’ve worked up to 15 mg. My blood pressure has increased since taking it.

  45. Do you have a list of practitioners that can do the same testing in Eastern Canada?

    If not, how does it works…for testing if from Canada??



    1. We don’t have any practitioners in Eastern Canada, but I can work with you remotely. Testing can be completed in Canada and sent back here to the states for analysis.

  46. Hi Sami!
    Great blog here. I could read the comments for hours, but I’ll get straight to the point. In 2015 I had a new Healthcare Savings account refreshed so I paid for a neurotransmitter test that normally was done through a Naturopath but had just been regulated in the state of California so that she could not administer because she was a PhD, not an MD. I ordered the test through the lab she used. Bad mistake. They were also the compounding pharmacy and they were horrible with customer service and explaining to me. I had no idea what the results of the test meant and the treatment plan was so expensive I could barely afford it. I was not able to afford to retake the tests, but I already decided not to use their service anyway.

    The results of my test showed that I was an undermethylator and my body did not produce SAM-e. I am learning more, Mensah Medical has some good YouTube videos, and I just found out that SAM-e produces creatine in the next step of methylation among other things. All my life I have battle having varicose veins and yucky cellulite on my legs. It finally makes sense that my skin isn’t like any one else’s. I’m happy I’m finally learning this.

    I’d love to hear more about your services as I am looking at my options now. I had been off my SAM-e for about three months recently and started feeling depressed on the inside while my normal consciousness is thinking otherwise. I immediately ordered 400 mg tabs of SAM-e and have been on them for about three days. I think I can tell a difference, but am curious if I need a larger protocol, and is there anything I can do to support my skin and veins now?

    Thanks so much for your help! Sorry for the long message.

  47. Hi Sami,

    Very interesting info. The under/overmethylation stuff did not make sense
    to me in the beginning. I understand it better now. Thanks.

    I would like to ask you a question. Is b12 allowed for undermethylation? Why
    is vitamin b6 good for undermethylation?

    1. The MTHFR paradigm is neither an accurate assessment nor an appropriate guide for true methylation disorders. MTHFR testing is very significant in the realm of autism and in multiple sclerosis, however, in the area of mental health, it is strikingly inconsistent and dubious at best.

    1. We use whole blood histamine and/or SAM/SAH methylation profile. This must be determined via a qualified practitioner.

  48. Are people with avoidant/anxious personality disorder (a Cluster C personality disorder) undermethylated?

    1. Please do not assume that psychological diagnoses correlate with biochemical findings. The only way to know is for you to get properly tested. We see personality disorders such as Obsessive Compulsive Personality Disorder (OSPD) a result of overmethylation, with traditional OCD being an undermethylation trait. These biotypes contain diametrically opposed chemistries.

  49. What chance do people who are extremely shy / anxious / neurotic have at leading a normal social life free of all these symptoms? Are they doomed to be victims of their genes or can they be turned around completely?

  50. Hi there, I’m based in Melbourne, Australia. Are you able to advise whether you are aware of any practitioners/testing that can be conducted in Australia?

    Many thanks

  51. Hi… Based on the article I seem to be an over methylator… How can I determine for sure about what category I fall in and how expensive are these tests..

  52. Hi Sami, and thank you for the enlightening and interested article.
    I have a 14 months old boy who although has excellent health records at birth and after (also all milestones OK until 10 months old), it has been noticed that afterwards became very hyperactive, poor communication skills (non verbal yet – only babbling), sometimes out of the blue anxiety and phobia symptoms. His dietary is very rich and 99% organic. But I have also noticed, that many foods we are often feed him are very rich in folade, e.g avocado, lentils, spinach, plus the folic acid in his milk formula, the latter has been just yesterday replaced with goat fresh milk), there are not any pathological symptoms of any kind and just recently have him taken a standard blood test with the only following irregular results :
    – high glucoze 125mg/dl – normal values between 70-110
    – Although B12 seems OK, 696pg/ml – normal values between 200 – 900
    – Folic Acid is 36,1ng/ml !!! with normal values ranging for his age between 3 – 20.

    Do you see any potential interconnection between the above high values, his unusual behavior and perhaps an underline issue related with his methylation. I have also read that high folic acid may mask B12 deficiency.

    I would be grateful to read your view on this

    1. Hi Ted,
      I encourage you to get your son properly tested. These values do not give the full picture. Click here to schedule a complimentary session with me to see how I can help.

  53. Your article advises not to self diagnose the methylation/treatment. But where do we get these tests? Im certain the NHS won’t do them. Doctors see this stuff as quackery, sadly. Here in the Uk at least. I have no money for expensive private tests… Any ideas? Thanks

    1. Hi Anne,
      Unfortunately, private testing is the only option in most cases. I can get you properly tested, but it would be an out of pocket expense.

  54. Just a few questions. I was recently diagnosed with mast cell activation syndrome after having symptoms for 7 months post pregnancy. These symptoms included but certainly not limited to joint pain, fatigue, anxiety, night sweats, weight loss, insides burning, congestion (sinus and chest), sore throat, tingling of mouth or extremities, always cold, irritability etc.

    While my symptoms coincide with mast cell activation syndrome, something me just isn’t quite sold.

    Are you saying in this article that if you fix the methylation situation (whether over or under), the histamine tolerance could be cleared?

    I just can’t come to terms with the fact that suddenly I have this syndrome. There must be a reason.


  55. greg.walmsley

    hi-Sam, I was just Wondering how a high Protein Diet can be used by someone who has Bi-polar etc and not Effect their absorption of Magnesium

  56. Hi Samantha-

    By all means, I am an overmethylator!! I’ve struggled all my life with all of the symptoms. I suspected I was MTHFR and sure enough, I am homogenous c677T along with other heterogenous factors-COMT and others. Being born with dual kidneys and uterous, it is all making sense. ive struggled with many other factors- anemia, anorexia, low folate. My Question is; if I’m an overmethylator, why do I seem fine on methylacobolimum ? Reading

    1. Hi Michelle,
      Unless you’ve been properly tested, please don’t assume based on symptoms that you are overmethylated as there is usually more at play. Genetic testing does do not reveal the net effect of SNPs.

  57. Hi Sami, I am living in Australia. Needing blood tests for both my son and myself. Can you help?

    1. Hi Jacqui,

      I saw your comment in eatfor.life website asking Sami about proper testing for yourself and your son for methylation, nutrient status, etc as I noticed your in Australia, so am I, I’m in Melbourne. Did Sami help you at all?

  58. Hi Sami!

    I’ve benefitted from your expertise on all things ‘methylation’. As a result of one of your articles, my ND and I decided to ease up on the methylfolate.

    Also as a result of the valuable information you provide, I’ve decided to make an appointment with the good people at Mensah Medical.

    As a result of your affiliation with the doctors, I know our paths will cross again.

    MANY, MANY THANKS for the great work you do.


    Bob V.

  59. Hello Samantha, can you tell me about the MtFhr test? My son had a work up from Genova, and i see in it that there is a Methylation Cofactor marker test that was run..two things Methylmalonate, adn ?Formiminogluatmate..are these the right tests to know about the the gene problem.. He has never been able to take folic acid because of twitches. But the test says he is fine..it is 0.6 and 0.5.. with a range of lower than 2.3 okay. Does he need another test?

    1. Hi Lisa,
      The best tests we have for determining methylation status are whole blood histamine and/or SAM/SAH ratio, so I encourage proper testing before any nutrients are administered to your son.

  60. I am an undermethylator, with no degrees 😉
    I am a high achiever but have moved 33 times and suffer with adrenal fatigue that usually means I never get to the final grading of any courses I do. (I’ve started several diplomas, I assure you).
    I have been diagnosed with pyrroles disorder and admit I am better now than I once was, but currently frustrated by my agoraphobia flaring up again. I know I get worse in summer as the heat and humidity wipe me out and leave me un-motivated, so looking forward to cooler months (here in Aus).
    I have OCD, ADHD, severe depression (suicide attempts from as early as 10 years old), I have PTSD from my violent marriage that I am happy to have escaped from.

    However, I cannot maintain a health relationship because of the abuse I have suffered throughout my whole life (even before I started school) and difficulty trusting people. I imagine there may be some people in this world with the patience to deal with these issues, but they would be few.

    Unfortunately, after I started improve from my diagnosis and treatment (doctor) I received a severe course of antibiotics that have severely damaged my digestive tract and now have even more allergies than I had before (currently wheat, all animal products (except fish), coconut, soy, mushrooms).

    It is difficult to explain to people why I can’t work fulltime (although I would love to pay off my medical bill debts), so I just tell them I have adrenal fatigue and leave it at that. I once had a boss tell me to be careful who I tell that I suffer with depression as some people will discriminate against me, so I do not offer that information to anyone I don’t consider to be a friend or at least someone with an actual understanding of what depression is.

    I have also suffered with hypoglycaemia and low blood pressure from time to time, I think some are related to my synthetic meds I take, other times there seem to be other triggers.

    Although I do not have bipolar, I do tend to oscillate from doing next to nothing to working several jobs and trying to help everyone and doing a hundred other things. I think this is in some way related to me wishing I could do more when I can’t, then trying to make up for lost time. Of course, this results in a vicious cycle of exhaustion again.

    I’m not sure if there is more I should be doing medically right now, but I have just come out of a long spell of ‘distraction’. I sink my brain into reading and watching things, along with working lots and sleeping little to stop me thinking about my situation. This last episode lasted 12 months after an extremely bad job (controlling boss that made many traumatic memories resurface) and attempting a relationship.

    At least in the last week or so I have picked up to the point that I don’t wake up every day wishing I was dead as I did the last 12 months, so I guess I should be happy for progress, but I am just wishing I could just get out of bed and do things and function like a normal person. Instead, just eating and showering and getting to work for a few hours a day seem to consume all my emotional, mental and physical existence.

  61. My gynecologist did some genetic testing on me and I received a result of heterozygous for MTHFR C677T and A1298C with a high risk of development of hyperhomocysteinemia when deficient in folate, b6, or bit B12. So it was recommended that I supplement fully active b-12, B-complex w L-5-MTHFR, and I use a coenzymated B-6. The B-6 has been giving me super intense headaches that do not go away until I take the extra b-6 away. Which I have. I feel over methylated my whole life but I’m having a terrible time understanding this all. Which is a trait of overmethylation. Any comment would help if any of this makes any sense. Thanks

    1. Did they actually check your levels or are they just supplementing you off the genetic test? Be cautious of too much b6. It is neurotoxic.

    2. Hi Rose,
      This would require proper testing to ascertain as genetic tests do not give the full picture and are not a viable means of treatment. Click here to book a complimentary session with me to see how I can help.

  62. Thanks for the article. You seem to use folic acid/folate interchangeably in your writing. From my research, people with MTHFR need to avoid folic acid as it’s not the natural form of folate and can bind up the folate receptors. Thoughts?

    1. Hi Beth,
      All forms of folate, whether folic acid, folinic acid, methyfolate, etc. perform the same over time.

      1. Cheryl Jacobson

        folic acid is not the same as folinic acid, folic acid is chemically made, and actually blocks the folate receptors, the body can not utilize folic acid, and it stops folate absorption.

  63. hi, i dont know what is happening with my body i am having like weight loss , constipation , high homocysteine level dont now what test to undergo to check for my body , please suggest or tell what shall ido

  64. BTW, he is responding very well to the L-methylfolate and B12 supplement!! Better mood, smiles more, less aggression.

    FYI…his test indicated that his COMT gene also displayed “low activity” and that SAM-e could be therapeutic. But this is a no-no for an overmethylator, right??? This part was very confusing!

    1. I’m not sure how long your son has been on the methylated vitamins, just know that those of us who have experienced side effects often feel them several weeks in. We may feel great at first. Just something to watch out for.

  65. My autistic son’s MTHFR gene tested as “low activity” and his doctor prescribed L-methylfolate, along with methyl B12. I assumed since my son could only process methyl forms of these B vitamins that this meant he was an undermethylator. But based on the vitamins prescribed, it would appear that he is actually an overmethylator, since they typically need folate, where an undermethylator has to be cautious when taking folate. So my question is: can an undermethylator still be deficient in folate and B12?? I realize that only testing will determine for sure what he is, but was interested in your opinion.

  66. Sami,

    I recently tried the over methylation protocol again (after giving up on it way too soon a few years back) and I was really sensitive to the vitamins this time. I got really nauseous and sick. Do you know why? Could this be gut issues I’ve developed since the first time?

    I’d so love to try this protocol again.


      1. There are many reasons one would have a reaction to nutrients such as low zinc levels and blocked detox pathways. Low stomach acid is a symptom that requires further investigation. Taking HCL and probiotics without complete knowledge of one’s chemistry is not advisable.

  67. Interesting post Sami! I can tick features off both the under and over-methylation lists – what do you make of that?

    I have more of the under- list, but most definitely low libido from the over- list. Ever come across that before?

    1. Hi Jeff,
      It is very common for individuals to have traits of both. This is why proper testing is essential before embarking on a treatment protocol.

  68. Hi sami I was talking with you on the phone before I am undermethlathed and you thaught that my symptoms sounded like copper overload I just seen on your website that you used to binge eat on sugar and I was wondering how beat it I have candida and have tried the diet twice but both times on the 2 week mark the cravings would get the better I feel very addicted to sugar do you have another way to treat candida ? Thanks

      1. hi ..yes i have got the test done in ireland and i came up high histamine undermethlated zinc was fine and a diffrent tewst for candida showed medium to high candida

        1. Hi Pierce,
          If you’d like to schedule a session so I can help you with that, you can do so. After purchase, my assistant will contact you with booking information.

      1. L-glutamine is neuro excitotoxic. It is not a good choice for those with mental health issues, nor is it good long-term for the general population.

  69. Last year my ND gave me high dose 5MTHF for a couple months. I felt progressively worse until I was housebound with depression. I also lost my libido completely. Before that I was highly sexual, sometimes up to 3 orgasms a day. But since then I have zero interest in sex, very difficult orgasms and Im still depressed. I dont take any folate and limit it in food now. I am an undermethylator 114 with compound hetero MTHFR and several COMT and CBS snps that affect my response to B6 and all methyls. I am at a loss as to how to recover from this. I follow the recommendations in Table 10.2 of Nutrient Power for increasing dopamine and serotonin but nothing has helped recover my sex drive and eliminate depression.

    1. Hi Betty,
      It’s really important to get properly tested as genetic testing does not tell us the net effect of what the snps are doing.

  70. I’m so confused with the b’s . I have just gone down this journey of under methylation and pyroluria .. I am 3 days in of b6 100mg p-5-p 50 mg zinc 60 mg , methonine500mg and inositol. Prior to getting to this point my year began with A horrid skin condition like rosacea which was coincided with bad immune system. I found a naturopathic skin specialist which put me on a blood type diet. I am A- . The big part of the diet was removing high hystermines .. I was taking for four months a tonic with supplements containing all the good things including folic acid. Also eating bunches of greens like kale.. Juicing etc. I started getting nightly body tremors and feeling off balance in general. Like vertigo. Then came The racing heart and anxiety. I had also started to take ( my own doing) magnesium powder with added b vitamin, iron supplement with added b and lastly a b vitamin spray thinking this would help my tremors… So here I am today on a whole new regime which I have listed at the start of my paragraph… My question is . If pyroluria requires the b zinc complex does the under methylation part not cope with it? Is it all the one thing? What is there to eat when I’m also avoiding high hystermines ?

    1. I had nightly body tremors too, and methylated b vitamins made them worse. All my neurological symptoms got worse. I dropped the naturopath, found a good endocrinologist, and was diagnosed with celiac and hashimotos, adrenal insufficiency, and prediabetes, and anemia.

      Now the neuro symptoms are healing, but as they worsened under the naturopath some may be permanent.

      Don’t be afraid to see a doctor. And don’t overdose on b vitamins, especially b6 which can cause nerve damage.

      1. Blindly giving nutrient advice without a proper assessment and testing is not advisable. Everyone’s B6 and P5P requirements will vary based on biochemistry and symptoms. Some need more, some less.

  71. If one is undermethylated, is it still safe to take a moderate amount of folate supplement, say around 400 mcg, instead of the high doses such as found in Deplin and other special folate supplements that some try to prescribe for depression?

  72. I am pyrolysis and under methylation. can you suggest which ssri’s in particular may be beneficial? I have taken so many andifferent would appreciate an idea of where to start again. many thanks x

    1. Hi Debbie,
      I recommend an advanced nutrient therapy protocol that addresses your unique needs based on proper testing and evaluation. Everyone responds differently to SSRI’s so it wouldn’t be appropriate for me to advise you.

  73. Hi Sami,

    I haven’t been tested for methyl yet, but high for pyrrole and suffered depression most of my life, I’m wondering if you know if spina bifida may be linked, as I have level 3 of that as well and the folate and vit b seems to be common in both instances. I have spent thousands trying to find out what was wrong with me, each symptom treated as its own issue, but now starting to see links. I’m 38 and really just want to manage it all before I get too tired to work it out, as you can imagine, pyrrole, spinabifida and chemical depression all together is exhausting and I work full time 2.5 hours from where I live. Thanks, Sarah

    1. Hi Sarah,
      Thank you for sharing your story. I don’t have any research regarding a direct link with spina bifida, but I encourage you to make sure to address the pyroluria as soon as possible.

      1. Isn’t low folate during pregnancy directly linked to spina bifida? Isn’t that the main reason for mass supplementation of folic acid?

  74. Sorry I forgot to ask this. I of course have several other snps like ACE, COMT, MAO, etc…do you also specialize in other gene mutations as well or more specifically with MTHFR? Thank you!


  75. Sami, you are a true angel. I have suffered very bad anxiety and depression for over 20 years and still do that has made me miss many many years of my life. I just found out about a year ago I have Lyme and co infections, etc. I’ve done lots of research and luckily havent bombarded my body with antibiotics. My Dr did do the 23&me test but didn’t say if I was under or over. I have symptoms of both like a few above me here. I’ve been taking a supp similar to Vessel care. And did the Nutrival test and was low in B3 but heard there’s contraindications with it. But have heard high doses of Niacin can be hugely helpful with anxiety and depression. I know I need more proper testing for my Hitamine etc but not sure all the tests. I live in San Diego. Money is an issue. Please help, it’s been way too long. Thank you. Rodge

  76. Wow you explained that all great 🙂 and my foggy head understood. I’m clearly an Undermethylator caused by my homo c677t genes but cant take methylfolate cause it makes me so depressed. I started taking Cymbala for anxiety and panic attacks which it is working but i still feel low most of the time probably low dopamine. Now I’m 51 i don’t know what else to do

    1. Hi Carl,
      Thank you, I’m glad my article was helpful to you. I’m happy to offer you a complimentary consultation to see how I can help. You can email my assistant here and she’ll get you scheduled.

      1. Wow. I took methylfolate and was suicidal within 24 hours. My practitioner had told me it had no side effects. I suffered nerve damage, worsening thyroid problems, scarring cystic acne, hair loss, memory loss, psychosis, and hallucinations. From a vitamin. A year and a half later I am not myself. I wish she had called it the suicidal nutrient, I would have been warned! Instead it was the “natural bioavailable form your body can use it’s impossible to overdose” Now I don’t have much trust in the alt health world. What proof is there for any of these claims?

        1. Hi A,
          Thank you for sharing your story. Nutrients are very powerful and should not be recommended lightly. Most practitioners prescribe dosages that are much too high and without proper testing (in other words they are inappropriate for an individual’s biochemistry), and this is why so many people are having the reactions you’ve described.

  77. pierce mcmanus

    hi sami i did a session with you a bit back .i was just wondering is there a vitamin that lowers folate ? and as a undermethlator do you have to avoid histamine foods like bananas ? thanks

    1. Hi Pierce,
      As an undermethylator you don’t want to strip away what you already don’t have. You don’t have to avoid bananas if you don’t have a histamine intolerance issue, but they are very high in sugar. Stick with the tips I gave you regarding diet (especially high protein) and keep up the great work!

      1. hi .thanks i will keep on it .also i cant take l glutamine for some reason gives me anxiety and makes me agitated do u no why this would be ? also l tyrosine gives me anxiety ?.thanks

        1. Hi Pierce,
          Keep up the great work! I don’t recommend l-glutamine because it is neuroexcito toxic and that is why it makes you agitated. In other words, it kills off brain cells at a rapid rate.

  78. My doctor prescribed me 1000mcg methylfolate and 5000 mcg methylcobalamin due to mthfr a1298c homozygous, and nothing else. I had adverse reactions which she ascribed to detox. I was used to feeling bad, and had been told it had no side effects. I desperately wanted to get better so stayed on it for four months, tolerating the adverse effects and adding charcoal, yucca, all sorts of nonsense to “quench” the excess methyl. I had no idea the trouble I was in, I was following my Dr. I ended up so horrifically sick I became suicidal. This has been, hands down, the absolute worst hell and biggest regret of my life. I was a beautiful intelligent woman with a good life. Now I have endured over a year of psychosis and permanent disfigurement. It’s been terribly traumatic and brought me right back to my years of struggling with antidepressants, which I was trying to put behind me. I can’t believe this stuff is lightly given to children. I can’t believe there are naturopaths out there marketing this to everyone. Some people like it, but this little vitamin absolutely destroyed my life and my mind. My doctor is still practicing.

    1. Hi A,
      I’m so sorry you went through this. Unfortunately, too many doctors follow the ill fated advice of prescribing methylfolate based on genetic tests alone, which have no way of indicating how much methyl is present in the body. Only functional testing can tell us that. If you’d like a complimentary session to see how I can help, please email my assistant here and she’ll get you scheduled.

      1. Wouldn’t methylmalonic acid test, folate and homocysteine levels would a good indicator if b6, b12 and folate deficiency? I live in Vancouver Canada and may find good results that way?

          1. Thank you for the insight!
            The methylmalonic acid test is more sensitive than the vitamin B-12 test. As a result, it’s better able to identify vitamin B-12 deficiencies at the lower end of the normal range.
            I also found the kryptopyurloila test helpful to determine low b6.
            Any suggestions for test for deficiencies of folate other than MTHFR gene?
            Thank you

          2. Thank you for the insight!
            The methylmalonic acid test is more sensitive than the vitamin B-12 test. As a result, it’s better able to identify vitamin B-12 deficiencies at the lower end of the normal range.
            I also found the kryptopyrolli test helpful to determine low b6.
            Any suggestions for test for deficiencies of folate other than MTHFR gene?
            Thank you

            1. You’re welcome Tan. Yes, it is, but still not an accurate measurement for help with B12 deficiencies related to mood and other disorders. Kp is wonderful for determining high oxidative stress related to zinc and B6 deficiency. Keep in mind that genetic tests are not accurate either because they have no way of telling you how much methyl is present to determine if folate is needed or not, so I don’t recommend them for treatment purposes. Whole blood histamine and/or SAM/SAH is the best way to figure out methylation status to determine over or undermethylation and folate need.

              1. That’s great information. You’re lovely! Wish I lived closer. I will have to find a local FMP. Following you on Facebook

  79. Davina Montgomery

    Hi Sami,

    Thanks for such a clear and helpful website.

    I have recently been diagnosed with pyroluria and undermethylation. My worst symptom s are severe leaky gut/ candida that I am hoping the zinc and extra nutrients will help to heal. In the meantime I am still struggling with food sensitivities and am unsure of what to eat as I feel that I am reacting to everything. Is there a particular diet that you recommend?

    I am a student so would appreciate any help.

    Thanks so much,


  80. HI, I find this topic fascinating and there is so much to learn. Are there any practitioners in Canada, specifically, Ontario?


    1. Hi Rita,
      We currently don’t have any practitioners in Ontario, but I do have many clients in Canada and can work with you via Skype. Click here to learn more about working with me.

  81. Hi Sami

    I am so glad to find someone who is heart based in their working and for everyone sharing their story. I have hidden my depression for so long or isolated myself. I want to release my shame, sharing here I suffer from depression it is not shameful.

    I have tried loads of alternative therapies, including metaphysical, I have read Dr Walsh’s book and done plenty of research. I am in the UK and was looking for someone who could support me with skype and it seems like I could have found someone. I am doing all the things to keep myself going even though I don’t want to – going to singing at gospel and Motown choir, Tango lessons, volunteer work! I am still depressed and recently it has worsened so I am not seeing pleasure at all from any of these activities.

    I am having a methylation test done which also tests along with histamine, Sam e/Sah ratio. I am going to have copper and zinc tested. Is there a consultation where we can chat to see whether we are able to work with each other and that the testing in the UK is something that you can work with. I have limited funds also.

    Best Wishes

    1. Hi Deborah,
      Thank you for reaching out and sharing your story. If you’d like to book a complimentary consultation to see how I can help, please email my assistant here.

  82. How did you find out you had too much copper? Isn’t it more usual for an undermethylator to have too little? I think I might be in your shoes.

    1. Hi Shelley,
      Testing is how I determine copper status. It’s not accurate that most undermethylators have too little copper.

  83. Hi Sami, literally all signs point to that I’m undermethylated. I have OCD, responded well to inositol which is very good for undermethylated, high histamine patients, I am a perfectionist, highly motivated, etc. Even down to the 2nd toe being bigger than the big toe in high histamine people. My earlier neurotransmitter test revealed that I have low serotonin, dopamine, GABA, and like every other neurotransmitter and DHEA. I don’t want to spend another hundred dollars for test that I am very confident I have the answer in as my family is not financially free. Is there a cheap way to know if you are under or over methylated?

    1. Hi Jeremy,
      I appreciate the fact that you’ve done your research and that money is a concern, however, without proper testing it can be very dangerous to self-diagnose/treat. I’ve had clients that thought they were undermethylated only to find out through testing they had pyrrole disorder; they made their situation much worse with improper nutrients. Keep in mind that symptoms cross over all the time and that neurotransmitter testing is not accurate. Proper testing can save your life.

  84. Hi sami . I have been trying to buy the 50 dollar session but it says you have to be a patient with a certain medical center .iam a undermethlator and just have some questions about Sam e and folate can I pay you directly to answer them ? Also do you take supplements .thanks

  85. 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 🙂

        1. 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.

          1. 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!

  86. 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.

  87. 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.

  88. 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.

  89. 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.

  90. 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.

  91. 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.

  92. 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.

  93. 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.

  94. 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.

  95. 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. pierce mcmanus

              hi .how much would it be to have a talk about undermethlation treatment as others have not worked for me ? .thanks

    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?

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

  96. 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?

  97. 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.

        1. 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.

          1. 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.

            1. 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

  98. 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.

  99. 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

  100. 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.

  101. 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.

  102. 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.

        1. 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?

          1. 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.

        2. 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.

  103. 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.

        1. 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.

          1. 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.

          2. 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.

        2. 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?

      2. 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

          1. 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…

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