The Other Histamine Enzyme: Meet HNMT

HNMT: The Histamine Enzyme Nobody’s Talking About

If you’ve looked into histamine intolerance before, you’ve probably heard all about DAO.

DAO is the enzyme that breaks down histamine in your gut. It’s the star of the show when it comes to reactions after meals, like hives, bloating, or heart palpitations. If your symptoms go beyond digestion, it could be time to look at a different enzyme: HNMT, or Histamine-N-Methyltransferase.

Symptoms of low HNMT:

• Brain fog

• Anxiety

• Sleep issues

• Hormone fluctuations

• Skin irritation

• Symptoms that flare up even without eating a high-histamine food

What is HNMT?

HNMT is the enzyme responsible for breaking down histamine inside your cells, especially in the brain, lungs, and other soft tissues. Unlike DAO, which works in the gut and bloodstream, HNMT works inside the tissues themselves. Think of it as intracellular cleanup. DAO issues tend to show up quickly (like post-meal reactions), but HNMT dysfunction can cause more lingering and systemic symptoms, especially those involving mood, sleep, and cognitive function.

Why would this enzyme be low or sluggish?

• Genetics. Some people have SNPs (gene variations) that reduce HNMT activity

• Chronic stress and poor sleep, which deplete nutrients and increases histamine

• Oxidative stress from inflammation, infections, or toxins

• Elevated histamine from environmental, immune, or food triggers

• Hormone changes. Estrogen in particular can increase histamine levels

• Poor liver function, where HNMT does a lot of its work

• Nutrient deficiencies: B12, folate, magnesium, and SAMe, which support methylation (the process HNMT relies on)

• Use of certain medications

Plus, some compounds can directly interfere with HNMT. This includes alcohol, which competes for the same enzyme systems, and possibly some plant compounds. For example, secondary metabolites found in Nigella sativa (black seed oil) and Curcuma xanthorrhiza (a turmeric relative) were found to act as HNMT inhibitors in one study. That doesn’t mean everyone should avoid them, but it may explain why curcumin supplements or even turmeric-heavy meals make some people feel worse, especially if they’re already overloaded with histamine. If something “healthy” keeps making your symptoms flare, it’s worth considering whether it could be impacting histamine clearance.

How to support HNMT

Even if you’ve never done genetic testing, there’s a lot you can do to support this enzyme.

• Focus on liver support and gentle detox practices. Your liver is a key player in methylation and histamine clearance

• Avoid alcohol

• Make sure you’re eating enough protein and supporting digestion

• Get your B vitamins in, especially B12 and folate (ideally in their active forms like methylcobalamin and methylfolate)

• Magnesium and SAMe* can also help, but talk to a practitioner before jumping into supplements. *SAMe may not be well tolerated by those with slow COMT; it can increase stimulation and anxiety in some people.

• Reduce exposure to toxins and mold, which place extra burden on methylation and detox pathways

• Support nervous system regulation. Stress slows everything down, including methylation

TL;DR

You don’t have to know your exact SNPs to start seeing improvements. Supporting HNMT can be especially helpful for people who’ve tried low-histamine diets or DAO supplements without much relief. So, if histamine intolerance is on your radar but the usual tricks aren’t working, it might be time to go a little deeper and see if supporting HNMT is helpful for you.

I have a free histamine & hormones guide if you'd like to learn more about how they interact, including information on the OG histamine enzyme, DAO.

If you've been chasing symptoms that don't have a clear explanation, histamine reactivity is worth ruling out. The quiz takes about two minutes and tells you whether it's likely part of your picture. Take the quiz →

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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 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.