Even though methylation is a hot topic in the world of medicine right now, most of the conversation revolves around undermethylation.
If your attention perked up when you saw that today’s blog is about overmethylation, I’m guessing you’re already a bit familiar with MTHFR mutations and some basic concepts of methylation. Perhaps you’re even taking folate or niacin to support your genetic mutations. Maybe you suspect that you’ve become overmethylated in the process, which is actually pretty common in people who are working to correct an undermethylation problem.
But if that all sounds foreign to you, then here’s a quick recap.
Brief Recap – What is Methylation?
Methylation is a biochemical process that’s actually used throughout your body. Simply put, methylation is when one carbon atom and three hydrogen atoms are added to a molecule. One carbon plus three hydrogen atoms is called a methyl group, which is why this process is called methylation.
Methyl groups can be thought of as little light switches for very important processes, including:
- Stress response
- Flight or flight reactions
- Synthesis of neurotransmitters
- Synthesis of glutathione (your body’s master antioxidant)
- Folate metabolis
- Hormone regulation
- Energy production
- DNA repair
- Gene expression
- Scavenging free radicals
- Supporting appropriate immune system response
Methyl groups turn on many of these processes and if you don’t have enough of them, it can cause a lot of health problems. For example, maybe you have plenty of a neurotransmitter, but you don’t have enough methyl groups to activate it – then it might not be doing you any good.
You’re probably thinking, methylation sounds great and in most cases it is. Which is why there was a flare of concern when scientists discovered MTHFR gene mutations that can cause people to not produce enough methyl groups.
Having a shortage of methyl groups is a big deal because it can cause a vital process to become compromised, making you sick. Abnormal methylation has been linked to conditions like autoimmune disease, so it’s something I regularly check for in my practice.
But what’s been largely overlooked is that some people cause overmethylation in their body when they are treating their undermethylation. Though more often than not, an overmethylator has been experiencing overmethylation beginning at birth. Due to the lack of information, they are completely unaware this is a problem for them.
This leads us to the obvious next question. What do overmethylation symptoms look like?
12 Symptoms of Overmethylation
Genetics, nutrition, and environment can all lead to both undermethylation and over methylation. Though overmethylation is less common, it’s still a problem I see in my office fairly regularly. So I suspect that overmethylation is actually a bigger problem than we’ve yet to discover. The end product of methylation is called SAMe, when your body becomes overmethylated there’s too much SAMe floating around.
Symptoms of overmethylation include:
- Panic attacks
- Attention deficit hyperactivity disorder (ADHD)
- Behavior disorders
- Sleep disorders
- Histamine intolerance
- Sensitive to environmental toxins
- Highly creative
- High energy
People who are experiencing overmethylation are generally very anxious. This is because overmethylation can create high levels of dopamine, norepinephrine, and epinephrine in the brain. In general, your neurotransmitter activity is strongly associated with your ability to appropriately use methyl groups. Which is why if you’re struggling with any mental health disorders, it’s a good idea to look into your methylation potential.
MTHFR genetic mutations that can contribute to overmethylation include: AGAT, GAMT, CBS and MT. Keep in mind that just because you have an MTHFR mutation doesn’t mean that you’re going to experience under or overmethylation. In fact, if there is one thing you take away from today’s blog I hope it’s that.
Easy access to genetic testing like 23andMe has led to people discovering that they have the potential for over or undermethylation and becoming unnecessarily worried. This is why I strongly recommend if you suspect you are experiencing over methylation, you seek the support of a functional medicine doctor.
Methylation & Histamine
We can tell if you’re overmethylated because we can measure the concentration of methyl groups in the body. Plus, there is an inverse relationship between methyl groups and histamine. So if you tend to have high methyl groups, you’ll also likely be low in histamine. This is why people who are overmethylated also often struggle with histamine intolerance.
Another interesting interaction between methylation and histamine is when there’s too much histamine in the body, and there is already inflammation due to some other cause (maybe it’s environmental toxins or something else) – high histamine can become depleted (histamine intolerance), which then contributes to overmethylation. This can become a reinforcing cycle.
When we compare methyl groups to histamine levels, we can get a better idea of what exactly is going on in your methylation process.
What To Do if You’re an Overmethylator
If you’re an overmethylator, you’re going to respond really well to plant-based diets because of the high levels of folate. In fact, if you’ve ever done a juice cleanse and it felt fantastic, there’s a good chance that you are overmethylating.
Foods high in methionine (an essential amino acid) are likely to contribute to higher levels of methyl groups because it’s needed in the methylation process. Foods high in methionine include things like red meat, eggs, and milk. If you think you are overmethylating, you might want to cut back in some of these.
If you related to many of the symptoms listed above and you found that you do really well on a heavily plant-based diet, there’s a good chance that you are experiencing overmethylation. Folate will also help if you are overmethylating, which might seem counterintuitive if you already know that it is also what’s recommended to people who undermethylate. But in an overmethylator, methyl-folate helps reduce the activity of the neurotransmitters that are contributing to the high-energy and anxiety.
For most people who experience overmethylation, it can be easily managed if you know that’s what you’re working with. But because there isn’t a lot of information on overmethylation, most people don’t realize that it’s a huge factor contributing to their overall health. This is why experimenting with your food and supplementation safely is so important. Methylation is in a perfect example of how our bodies are unique and require individualized practices.
* These statements have not been evaluated by the Food and Drug Administration. The product mentioned in this article are not intended to diagnose, treat, cure, or prevent any disease. The information in this article is not intended to replace any recommendations or relationship with your physician. Please review references sited at end of article for scientific support of any claims made.
Really wondering why the article is talking about Fokic Acid rather than Folate. I’m of the understanding that Folic Acid is contra-indicated when one is an under methylater & that Folate is what they should be taking.
Otherwise a great informative article. Thanks
I seem to get a ton of upper back pain when I try to add in folate or even b12 sometimes, I’m trying to figure out how to stop it . For awhile yucca worked, then it became part of the problem then charcoal works and now it doesn’t… any suggestions on how to calm down the pain .. I’ve stopped all my methelation supplements. I feel like something is getting blocked in the spinal . I have a slow CBS Double mutation and single Mtrr, and MTHFR A1298 and c677… those are the ones I’m focused on . Plus I know I have douple slow histamine snip.
Potassium can be depleted when taking methyl donors. B12 increases production of RBC , which increases requirements for potassium. Foot cramps are very common as well.
Very interesting article! You mention “We can tell if you’re overmethylated because we can measure the concentration of methyl groups in the body.” How exactly is this measured? Thank you!
There are various specialty labs that will measure markers such as SAM and SAH and levels of B vitamins and end products like glutathione.
I am utterly amazed that you are promoting folic acid & not methylfolate!!
Folic acid is used in this article to represent all the forms, including methyl-folate
I find it curious that folic acid is mentioned as a remedy when it’s my understanding that mthfr can’t process folic acid and require folinic acid or methylfolate instead. Please explain further.
In this case folic acid is used as a generic term for all of the types including methyl-folate or folinic acid which are what I use in clinical practice
I am certain I am an over-methylator…My psychiatrist has been trying to regulate me on SSRIs for 20 years and it has been excruciating. Acclimating to them causes horrendous anxiety which I now know is because I am an over-methylator. Earlier this year I started tapering off of the 10 mg of Lexapro that I had finally adjusted to with my doctor’s approval and had done very well. I got down to 2.5 mg every other day for a week and then stopped, thinking I would be fine. I started having withdrawal symptoms and after a week of quitting completely my doctor put me back on 2.5 mg to ease the withdrawal symptoms….I have been experiencing horrific anxiety since the re-addition of the 2.5 mg of Lexapro. I knew there had to be something else going on. I remembered going to a Integrative doctor a few years ago who told me that I had the MTHFR gene mutation. I started researching and realized that I am an “over-methylator,” as opposed to an “under-methylator”….my psychiatrist had tried putting me on “Deplin” before but it further exacerbated my anxiety so this time he suggested an OTC Methylfolate measured in mcgs. I bought it. This also produced anxiety on top of the anxiety from the SSRI Lexapro. I am waiting to get back in with the Integrative doctor that found the mutation years ago…I know that as an over-methylator my body produces an abundance of serotonin, norepinephrine, and dopamine. I’m sure this is why I cannot tolerate the SSRI. My question is: is “Folate” the protocol for overmethylation as opposed to Folic Acid? And then I’ve heard the word “Folinic Acid? I’m confused….What about “Niacin?” Can I take Niacin to dump the extra methyl groups? I’m desperate here…my psychiatrist doesn’t test for MTHFR mutations…and it may be awhile before I can get an appointment to see the Integrative doctor (today is Memorial Day and they’re closed) I’m trying to hang in…but the re-addition of the Lexapro is sending me over the edge with anxiety…I suspect my father and his father as well both were over-methylators and they tragically took theirs lives. Please give me some information so I don’t carry on this legacy. Thank you.
I recommend using folinic acid instead of any methylated forms
Hello doctor, great info here.
I am an over mether and have been all my 69 years. I have a great doctor who is well versed in the processes and monitors me closely. Last year she put me on o.5mg folic acid to which I responded really well. After some bloods she decided to stop the course to which I had an immediate response. Many of us suffered effects from the Australian fires of late last year: my histamine reactionsreactions skyrocketed to the point of getting only marginal relief from over the counter pills and the issues continue. Off to get mote folic acid I think. Cheers.
I’m still a bit confused about how overmethylation occurs. I have the MTHFR mutation, and take methylated B12 and Folate. If someone takes too much methylB12 and Folate, is that overmethylation?? Wouldn’t an annual blood test detect too much B12 and Folate?
Overmethylation is not that simple… B12 and folic acid are involved but they are used in many processes including methylation. There are specialty labs that measure by-products of methylation but serum B12 and folic acid would not tell you much about methylation directly
Are you in agreement with the late add Carl Pfeiffer
And Dr. Walsh?
This is what they teach.
My functional doc performed a methylation panel and I was deficient in methionine and SAMe. Does that mean I am an under-methylator? I drink organic green juices all the time and feel fine. Should I stop drinking so many? I am confused… THANK YOU so much for your insight.
This may be undermethylation but your symptoms matter as well. The SAMe/SAH ratio is important
Hi! My daughter , my son and myself are all overmethylators. My son has pyrrolles, compound hetero for both MTHFR genes and low dopamine and serotonin. My daughter(17) and I have very high Dopamine levels almost no estrogen. I am compound hetero for “A”mutation my daughter is hetero for same. What could be causing our high dopamine levels and how can we lower them? Is there something else we should be looking at?
But if you can be more specific about the tests I should do.
My histamine is very low, I am anxious and sleep is not good.
What else I can test? Urine for OAT will tell me about the B vitamins levels and can give more clues about over methylation ? If so which ones?
Glutathione measurement is in the blood or in OAT?
I also have height homocysteine 8.7 and high methionine in the blood amino acids
Thank you 🙏
Best to work with your functional medicine doctor. You can check homocysteine on any major lab. Other markers are open to interpretation and must be discussed in context with your symptoms.
Hi, great article! I’m confused about how low histamine in your blood (overmethylation) makes you more prone to histamine intolerance. Thank you very much.
methylation is one way we break down histamine
Hi Dr. Jill – great article, thank you. I think I might have accidentally become overmethylated by getting too many methylcobalamin injections over a short period of time. The first injection was a true miracle worker, it helped so much with my complete exhaustion state, but then I had three more injections, in the same month. High anxiety, a “wired” feeling and insomnia symptoms came on quite suddenly and have remained “through the roof” for about three weeks now. Is there anything I can do to help remedy this situation? Thanks again, you and the information you provide on this website, are most appreciated!
Overmethylation symptoms can sometimes be helped by a low dose niacin
Did niacin helped????
I am so confused and overwhelmed.
Some physicians say to take methyl folate if you are an overmethylator and some physicians say to avoid methyl folate and take folic acid instead to avoid the methyl group.
Exactly what I am confused about. If you are overmethylating, shouldn’t you be avoiding foods and contributors to create further or additional methylation? This seems very counter-intuitive to me and I read so many different conflicting ‘opinions’.
An online company sets up a visit with my local lab for so I can test for MtMath mutation. Would that tell me if im over or under methylating or just that I have the genetic glitch? What other tests would I need?
My homocysyeine is 20. I seem to have overmethylated issues all my life. Racing thoughts, anxiety, O C D.
B12 is 597. Folate 17.9.
I don’t have a naturopathic doctor to help me.
You do sound more like you have an undermethylation problem
Sorry for spelling errors. Lab sets up test for MTHFR.
I have run across your page and am hoping you can point me in the right direction to do my own research and further my understanding of methylation and under or over methylation.
I recently started my otherwise healthy 6 year old son on smarty pants vitamins and after about a week he became a different child. He went from a very confident, happy, independent 6 year old boy to an anxious. depressed, child who was obsessing over making mistakes in his behavior. He is not an overly touchy affectionate child but he started spending most mornings sitting curled up in my lap crying saying he couldn’t handle his sadness. After three weeks of trying to figure this out I realized it might be his vitamins. I quit giving them to him and after about 5 days he was back to normal. Do you think this has something to do with the l-methylfolate in the smarty pants vitamins? I am new to this and just trying to figure out what happened and what I need to be aware of for his potential future health issues relating to this issue.
yes, absolutely possible…
Hello Dr. Carnahan!
So, you made a comment about feeling better on a plant-based diet, and that’s a sign of overmethylation.
Whenever I go plant based, and I increase my greens, I respond with body aches and joint pain, especially if I add in green smoothies.
Just found out I am hetero for both MTHFR. Any thoughts you could share?
Appreciate your time!
you may have issues with oxalates or salicylates
Is there a way to heal a methylation problem or is it just something you have to manage? My 18 year old daughter has awful anxiety with any supplement that has a methyl group(l methyl folate, methyl cobalamin, Sam-e & TMG). Yet she is deficient in b12 & b3 & b6 on her OAT test. We’ve seen 2 functional medicine doctors but still haven’t gotten her depression & anxiety resolved. Any suggestions?
If you have genetic issues, you may need lifetime support of methylation but there are many factors such as environmental load and toxicity that influence methylation.
she sounds like, she might be an overmethylator. B12 injections with hydroxocobalamin and NAD might work well.
You said: “So if you tend to have high methyl groups, you’ll also likely be low in histamine. This is why people who are overmethylated also often struggle with histamine intolerance. ”
This makes absolutely no sense. How in the world can people have histamine intolerance (high levels of histamine) if they ‘also’ have ‘low histamine’ due to high methyl groups?
Yes I was wondering this EXACT thing. I have all the symptoms of over methylation but have become apparently histamine Intolerant after too many months of antibiotics battling chronic Lyme. My gut got all messed up and ever since histamines have caused major issues. (They never were before.)
I’m confused because histamines are cleared by methyl groups (as well as dao), so shouldn’t an overmethylator have too low of histamines and thus be able to eat, and even require, more histamine foods?
Could you elaborate please?
Exactly what I thought as well…. Unless she meant that the body gets so accustomed to being histamine deficient that when it finally does receive enough it retains to much, like survival mode, and that temporarily causes symptoms of histamine intolerance, I actually had that happen after using the recommended histapenia supplements
Thanks for this response. I had not thought of that but it seems to make sense with my experience. After extended supplementing with methyl b12 (I am an undermethylator) I start to feel really bad and get super sensitive to histamine. Yet, histamine (and histamine raising agents) also seems to help my energy/mood while vitamin C and other histamine-lowering agents make me sleepy/depressed.
Hello doctor :). I did histamine test and it is 33(walsh protocol says must be at least 40). So I’m overmethylated. My folate level is also very low. My main problems are ocd depression ect. How much do you suggest I have to take supplements(walsh protocol: Niacinamide, Vitamin C, Folate, Manganese, Vitamin B-6, and zinc)