Methylation 101

This is a copy of an email that went out to my list. If you'd like to become part of my mailing list, please click here.

Let’s talk about methylation today, since it’s mentioned a lot but rarely explained.

Methylation is a process that your body runs constantly in the background, billions of times a day. It involves attaching methyl groups, which are small molecules your body assembles from nutrients in food (especially B vitamins and choline) onto other molecules in your cells.

They work like little sticky note with instructions that your cells attach to things to tell them what to do: Turn this gene on. Break down this compound. Clear this out of circulation. This is all happening inside your cells; your body is routing sticky notes to thousands of targets every second.

MTHFR: the name of an enzyme and the gene that codes for it

One of the key enzymes in that system is called MTHFR. Its job is to convert folate into a form the methylation cycle can run on (folate is vitamin B9, found in food and supplements; it’s not usable by your body without this conversion step).   

When your MTHFR enzymes are working well, the whole system hums along. When it isn't, the sticky note delivery slows down and processes that depend on the methylation “sticky note” instructions start to back up.

Here's where genetics comes in. A significant portion of the population (between 40 and 60%+) carries a genetic variation in the MTHFR gene that reduces how efficiently the MTHFR enzyme works. So having MTHFR mutations isn’t rare at all.  If you do have mutations, it means your methylation pathway may need more support than someone without the variant(s), and things downstream of methylation may be running slower than they should.

Two of those downstream processes that can get less efficient are histamine clearance and thyroid hormone conversion.

Histamine gets cleared through a methylation pathway called HNMT 

you can read more about HNMT in this blog post: The Other Histamine Enzyme: Meet HNMT.

If your methylation is sluggish, histamine can accumulate and cause symptoms even when you're eating a clean diet, taking DAO enzymes, and doing everything else right. There may be a bottleneck upstream that diet alone can't fix. This causes symptoms like flushing, hives, headaches, heart palpitations, brain fog, itchy skin, air hunger, feeling wired but also exhausted. If that list sounds familiar, your clearance pathway is worth looking at.

Thyroid hormone conversion depends on methylation too. 

Converting T4 (the storage form your thyroid produces) into active T3 (the form your cells actually use) requires methyl donors, the raw materials the methylation cycle runs on. A sluggish MTHFR pathway can slow that conversion, which means you could have decent T4 levels and still feel hypothyroid symptoms, like fatigue that doesn't improve with sleep, hair loss, cold hands and feet, brain fog, weight that won't budge despite doing everything right.

Most practitioners would tell you to take methylated B vitamins here and call it a day.  But this advice does not help everyone.  Again, it comes down to genetic variation. 

COMT is another enzyme responsible for breaking down certain neurotransmitters, including dopamine, norepinephrine, and adrenaline. When COMT is also running slow (a different genetic variant that is also common), flooding the system with methyl donors can backfire. Some people who start high dose methylfolate feel more anxious, more wired, or like they want to jump out of their skin. That’s because those neurotransmitters build up faster than they can be cleared out. 

Methylated B's are genuinely helpful for a lot of people; but if you have a slow COMT, trying different forms may feel better. 

So, if you are dealing with symptoms of histamine overload, MTHFR may be part of the reason why. The gene variant alone does not confirm it, but it does mean your histamine clearance pathway may be running slower than ideal. 

Want to Go Deeper?

Inside my Histamine Discovery Panel, I use the Fluids iQ Intestinal iQ to look at:

↣ histamine levels

↣ DAO activity (the enzyme that breaks down histamine)

↣ gut barrier integrity (zonulin)

You’ll complete the at-home blood spot test, and I’ll connect your results with your symptoms to give you a clear, personalized breakdown and next steps.

If you're curious about your own genetic SNPs, including MTHFR and COMT, fill out this form and I'll send you over some options for testing!

If you're not sure if gut health, thyroid, or histamine is an issue for you, and you've been chasing symptoms that don't have a clear explanation, it's worth digging a little. The quiz takes about two minutes and tells you where imbalances may be showing up in your symptoms. Take the quiz →

If you just want more of this kind of content, I cover the symptoms most practitioners don't connect in my weekly newsletter. Join the newsletter →

Jennifer Scanlon, MS, FDN-P, holds a Master of Science in Holistic Nutrition and a Bachelor of Health in Cardiopulmonary and Diagnostic Sciences. Before starting her nutrition practice, she spent more than a decade as a respiratory therapist working alongside physicians and nurses as part of the critical care team. Her role included neonatal resuscitation, ventilator management, blood gas analysis, and the assessment of critically ill patients, providing a strong foundation in physiology and clinical reasoning.

After facing her own health challenges that weren't fully explained by conventional testing, Jennifer returned to graduate school, completing her master's capstone on Hashimoto's disease and the gut-thyroid connection. She has since pursued advanced training in functional health assessment and spent years studying thyroid disorders, gut health, iron deficiency, histamine intolerance, MCAS, and the complex interactions between body systems.

Today, Jennifer helps women uncover potential contributors to symptoms that often fall through the cracks of standard evaluations. Her approach combines nutrition, lifestyle factors, functional testing, and conventional lab data to identify patterns and connect the dots between thyroid, gut, histamine, and hormone issues, helping women make sense of symptoms that are often dismissed when standard lab work comes back "normal." Visit the website here.

Disclaimer: I do not diagnose, treat, prevent, or cure any disease or condition. Nothing I share with my clients is intended to substitute for the advice, treatment or diagnosis of a qualified licensed physician. I may not make any medical diagnoses or claim, nor substitute for your personal physician’s care. It is my role to partner with you to provide ongoing support and accountability in an opt-in model of self-care and any changes should be done under the supervision of a licensed physician.