Trapped Neurotransmitters: How Iron Deficiency Overloads a Slow COMT Brain

Written By Malek Hamed, MD

In this article:

Why Anxiety, Insomnia, and Fatigue May Come from Hidden Iron-Based Catecholamine Overload

  • You already know slow COMT affects how you process dopamine and norepinephrine. But what if your body’s other clearance pathways are also blocked because of low iron?

  • This article shows how iron deficiency can impair MAO, leading to trapped stress chemicals, chronic overstimulation, and neurological burnout.

  • It explains why low iron doesn’t just cause oxygen-delivery fatigue but can also cause anxiety, sleep issues, and emotional dysregulation, especially in people with slow COMT.

  • Learn what to test (and why most iron tests fall short), how to identify the real issue, and how to fix it without making things worse.

If you’ve cleaned up your diet, supported methylation, and still feel overstimulated and exhausted, this may be what you’re missing.

THIS ARTICLE WILL BE AVAILABLE FOR 24 HOURS ONLY. AFTERWARDS, IT WILL BE EXCLUSIVELY AVAILABLE TO SLOW COMT ROADMAP MEMBERS.

“Wired but Tired” Syndrome

A surprisingly common scenario these days: anxiety, poor sleep, feeling overstimulated yet exhausted, "wired but tired," and daytime fatigue despite restless nights.

People with this pattern often get dismissed by their doctors. They get labs done, and the results come back “normal.” But deep down, they know something’s very wrong. Something is off in their inner machinery.

The medical establishment readily dismissed their situation, offering little more than a vague label like “chronic fatigue syndrome” or even a psychiatric diagnosis, ignoring the possibility of any potential organic cause of their illness.

But some patients dig deeper. They stumble across terms like slow COMT, and begin to suspect that their genetics.

But the real key is in the interaction of those genetics with other common modern variables.

One of the most common and unrecognized problems that interacts with slow COMT is iron deficiency. I’ll be addressing:

  • How exactly iron deficiency interacts with slow COMT variants,

  • How you can tell if iron deficiency is in fact the problem?

  • What you can do if you have both issues without making things worse.

 

The rest of this article is available exclusively to Slow COMT Roadmap members. Your first month of the Roadmap is FREE.

Want me to build you a supplement plan?

To work together one-on-one:

Keep in mind that this is not official medical advice. No doctor-patient relationship is established through this article or through any other information provided on this website.

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Trapped Neurotransmitters: How Iron Deficiency Overloads a Slow COMT Brain
Trapped Neurotransmitters: How Iron Deficiency Overloads a Slow COMT Brain

Why Anxiety, Insomnia, and Fatigue May Come from Hidden Iron-Based Catecholamine Overload: “Wired but Tired” Syndrome.

A surprisingly common scenario these days: anxiety, poor sleep, feeling overstimulated yet exhausted, "wired but tired," and daytime fatigue despite restless nights.

How Zinc Might Fix BOTH Your Sleeplessness AND Your Sleepiness
How Zinc Might Fix BOTH Your Sleeplessness AND Your Sleepiness

Sleep is undoubtedly one of those lingering mystery of modern science. It’s tempting to say that it’s one those “last frontiers”—i.e. those things that we still don’t really understand, despite how much we apparently know—like the trenches of the ocean, or deep outer space…

But, of course, that’s not true.

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You’re Probably Taking Methylfolate Incorrectly. What To Do Instead:

Methylfolate has dramatically increased in popularity over the past few years. While most multivitamins and B-complex supplements used to contain only folic acid—the synthetic and potentially harmful form that I strongly discourage—many brands now include the so-called "methylated" form of folate instead. This shift is largely driven by the skyrocketing interest in MTHFR gene testing and the assumption that methylfolate is always better.

But is it really?

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Why I DO NOT Recommend Multivitamins—The Case of Copper

Multivitamin supplementation is extremely common. Probably somewhere around one in three U.S. adults takes some form of multivitamin on a regular basis, hoping to improve their health. That hope is often directed toward reducing the risk of disease—namely chronic illnesses like Alzheimer’s disease, heart disease, and so on—or simply improving day-to-day functioning (i.e., “feeling better”).

The problem is: I do not recommend multivitamin supplementation for the vast majority of people—for the vast majority of multivitamin formulations on the market.

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Slow COMT in the Context of Sulfur Intolerance

Managing slow COMT variants requires a tailored mix of (balanced) methylation-supporting strategies, neurotransmitter-modulating strategies, and so on. However, these measures may at times clash with those required for the management of sulfur intolerances.

COMT and Protein — The Ultimate Guide to Optimizing Your Protein Intake for Your COMT Variant
COMT and Protein — The Ultimate Guide to Optimizing Your Protein Intake for Your COMT Variant

Starting with the most general question—i.e. how much protein should someone with slow or fast COMT function consume—my answer is pretty straightforward…

What Supplements Should You Take if You Have a COMT Mutation?
What Supplements Should You Take if You Have a COMT Mutation?

Generally speaking, if you have a “mutation” in this gene, what that really means is that you have an under-functioning polymorphism that is less effective at breaking down dopamine, estrogen, and other metabolites…

Supplements to Avoid with a Slow COMT
Supplements to Avoid with a Slow COMT

As you may remember from our previous articles, catechol-O-methyltransferase (COMT) is an enzyme that breaks down catecholamines (most relevantly, dopamine), undesirable forms of estrogen, and other toxic substances in the body…

Why ‘Natural’ *Is* Actually Better
Why ‘Natural’ *Is* Actually Better

There is a society-level push to distance humans from human nature.

Consider the claim commonly made by health influencers and media pundits that “just because something is ‘natural’ it doesn’t mean that it’s ‘better.’”

Then just look at the sheer number of articles written…

Why You Probably Should Not Take SAMe
Why You Probably Should Not Take SAMe

SAMe is found in virtually every single cell in your body.

It’s involved in producing neurotransmitters like serotonin and dopamine, detoxifying the liver from toxins and alcohol, supporting the gut-brain connection, and even regulating the expression of your own genetic code.

What Supplements Should You Take if You Have a CBS Mutation?
What Supplements Should You Take if You Have a CBS Mutation?

The CBS gene is an incredibly important gene that can affects things like your mood, perceived energy levels, susceptibility to heart disease and cancer, your ability to tolerate high protein diets, and a lot more.

What Supplements Should You Take If You Have a MAT1A Mutation?
What Supplements Should You Take If You Have a MAT1A Mutation?

The MAT1A gene doesn’t get much attention in the methylation world. In fact, many “methylation tests” don’t even test for your MAT1A variant—instead, they just focus on five genes: MTHFR, MTR, MTRR, AHCY, and COMT.

But that’s a big loss, as the MAT1A is actually highly important to your ability to properly methylate.

In fact, MAT1A is arguably the gene with the most direct impact on methylation.

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Most people do need to supplement magnesium. The magnesium content of our fruits and vegetables has declined dramatically over the last several decades, and that’s a very bad thing. Magnesium is involved in facilitating hundreds of enzymatic reactions in the body...

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Doctors are notorious for being pretty temperate in their lab ordering: A CBC (blood count), CMP (kidney and liver markers), TSH (thyroid), A1C (diabetes screening), Lipid Panel (heart disease risk screening), and maybe a Vitamin D/B12 level are pretty much all that most doctors routinely order.

Malek Hamed, MD

MTHFRSolve is my brainchild.

I’m an IFM-trained Functional Medicine physician with experience solving a wide variety of disorders still seen as mysterious by the modern medical paradigm.

I love solving those mysterious problems.

But doing so—I’ve found—requires two things that are, unfortunately, much too rare in our times: Authenticity and Depth.

MTHFRSolve is my way of giving you a little bit of that.

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How Zinc Might Fix BOTH Your Sleeplessness AND Your Sleepiness