COMT: The Burnout Gene?

COMT: The Burnout Gene?

Why this overlooked gene may be sabotaging your mood, hormones, and mental load — and what to do about it.

Let’s talk about a gene that doesn’t get enough attention — but probably should.

She’s called COMT (Catechol-O-Methyltransferase), and if you’re a high-performing, emotionally sensitive, mentally wired, hormone-rollercoaster-riding woman — this one’s for you.

What does COMT do, anyway?

COMT is the gene responsible for breaking down catechols: think oestrogen, dopamine, adrenaline, and noradrenaline. These are your feel-good and stress-response molecules.

In other words? COMT is one of your body’s clean-up crews for both hormones and neurotransmitters.

When it’s working well, you metabolise and clear those chemicals at a healthy rate. When it’s not? You might feel overstimulated, anxious, wired but tired, PMS-y, moody, or stuck in emotional intensity.

Personally, I carry the heterozygous COMT-rs4680 AG and COMT-rs4633 CT genotypes — meaning my detox pathways are partially compromised. I’m not “slow-slow,” but I’m also not quick to recover when life gets loud. This insight helped explain so much about my sleep, mood swings, and caffeine sensitivity after having kids.

The COMT “slow vs fast” story

Your COMT gene can run in two main speeds:

Slow COMT
You clear oestrogen and stress hormones more slowly. This can lead to heightened sensitivity, longer stress responses, hormone imbalances, and a tendency toward overwhelm or mood crashes. You may have the Met/Met (AA) or Met/Val (AG) genotype.

Fast COMT
You clear those molecules more quickly. This may be helpful for stress resilience but could leave you feeling flat, unmotivated, or low in pleasure and reward. You likely carry the Val/Val (GG) genotype.

At Legacy, I commonly see women with heterozygous COMT variants who feel stuck in between — highly driven but easily frazzled, deeply compassionate but exhausted by emotional labour, brilliant at caregiving but forget to care for themselves.

✨ Sound familiar? This was me in the thick of postpartum — mentally switched on but emotionally fried. Once I started supporting my COMT properly, everything began to stabilise.

The mental load gene

COMT impacts how you experience the world emotionally and physically — and how quickly you can recover from stimulation.

If you:

• Struggle with sleep after a busy day or screen time

• Cry easily or feel like emotions linger too long

• Crash with PMS or feel angry before your period

• Have a “racing brain” that never shuts off

• Feel wired by caffeine or anxious after chocolate

• Get overwhelmed by noise, mess, or conflict

...your COMT gene might be nudging your body into fight-or-flight more often than it should.

Why it matters for women

Because COMT clears oestrogen, a slow COMT can increase your risk for:

• PMS, PMDD

• Heavy periods

• Fibroids or endometriosis

• Hormonal migraines

• Breast tenderness

• Mood swings and rage

It’s also connected to how efficiently you detox from both stress and xenoestrogens — meaning the products in your bathroom cupboard might hit your system harder than someone else’s.

And if you're in the perimenopause zone or recovering from postnatal depletion? The load on your detox and methylation systems just got a whole lot heavier.

What I do (and what I guide clients through)

You can’t change your genes, but you can change how they express. Here’s what I personally do — and where we start at Legacy Nutrition:

1. Magnesium is Queen

Magnesium helps COMT function. It’s non-negotiable if you have a slower COMT.
I take magnesium glycinate every night, and recommend threonate for clients with nervous system overwhelm or brain fog.

Start here if your brain doesn’t shut off or your sleep is erratic.

2. Support methylation

COMT requires methyl donors to work well. That means:

• Leafy greens (spinach, rocket, coriander)

• Methylated B vitamins (especially B6, B12, folate)

• Avoiding synthetic folic acid (especially if you’re also MTHFR-compromised — more on that in an upcoming post)

I use a practitioner-only methylation support blend and track how my mood and cycles shift through each season. Even small tweaks matter here.

3. Lower your toxic load

Simple swaps can lighten the burden on your COMT pathways:

• Use natural skincare, cleaning products, and filtered water

• Eat more cruciferous veg (broccoli sprouts, cauliflower, kale — if tolerated)

• Avoid synthetic fragrances and harsh household chemicals

My own home detox journey began with switching to low-tox laundry powder and removing synthetic perfume — the changes in my skin and mood were noticeable within weeks.

4. Create space for decompression

You can’t biohack your way out of a life that’s too loud.

Your nervous system needs:

• Noise-cancelling headphones

• Breathwork or grounding

• Low-stim mornings (no scrolling!)

• Journaling, walking, or “white space” in your calendar

I set strict tech boundaries after 8pm and prioritise forest walks or barefoot garden time on frazzled days. That space is sacred.

But what about coffee... and cheese?

Ah yes — two of my last “vices.” Let’s unpack why they matter.

Caffeine & COMT

Caffeine increases adrenaline and dopamine — and if COMT is slow, it hangs around longer.

That can look like:

• Jitters or anxiety after one coffee

• “Wired but tired” evenings

• Headaches or mood swings

• Reliance on coffee just to “feel normal”

What works for me:

• Never caffeine on an empty stomach

• Delay coffee until after breakfast

• Switch second cup for matcha or cacao

• Start the day with protein + magnesium to support dopamine naturally

Dairy & COMT

Dairy can amplify estrogenic and histamine symptoms, especially if your detox pathways are sluggish.

When I removed dairy for six weeks, I saw major improvements in PMS, skin clarity, and my mental clarity mid-cycle. I now use A2 milk and organic butter in small amounts — and always track what changes.

You’re not too sensitive. You’re just wired differently.

Understanding my COMT status changed everything — and I’ve seen the same for clients.

You don’t have to live on kale and air.
You do need to listen to your body’s unique thresholds.
Your symptoms aren’t random — they’re data.

Want to know your COMT status?

At Legacy Nutrition, we use FitGenes or NutritionGenome testing to map your genetic profile and guide you through a personalised, root-cause plan. COMT is just one piece of the puzzle — but when it’s off, everything else feels harder.

Book a free 30-minute discovery call and let’s figure out what your body’s been trying to tell you all along.

References

PubMed – COMT Polymorphisms and Stress Response
NCBI – COMT Enzyme and Hormone Metabolism