Is Your Morning Thyroid Hormone Tanking your DAO enzyme and making MCAS worse?
What really causes Mast Cell Activation?
Inflammation, high histamine, and Mast Cell Activation
I figured out it was mast cell activation mid-sentence when my husband interrupted me “yeah, you’re histamine-y. Just take an allergy pill.”
I’d been getting inflamed (raw and histamine-y feeling) for months after breakfast and it kind of felt like my GI tract was being scoured from the inside.
Like most people with Mast Cell Activation Syndrome (MCAS), I ordered some DAO enzyme off Amazon and eliminated two categories of food… histamine liberating foods and high histamine foods. The DAO enzymes definitely helped. The new diet was too restrictive.
The connection between MCAS and Hashimoto’s
Someway, somehow this felt tied into the Hashimoto’s. If you have Hashimoto’s or low thyroid and are on thyroid replacement hormone, you’ve probably been told to take it in the morning on an empty stomach. What you’re not told is how free T3 actually peaks in the middle of the night.
In case this concept of dosing thyroid hormone by circadian rhythm is new to you, Paul Robinson, a hypothyroid patient himself, pieced together the research and came up with his own timing for dosing T3 especially. Reason being, if we were to look at cortisol rhythm, cortisol begins to rise about the time T3 peaks and cortisol itself peaks just after sunrise.
These rhythms scream of a connection between thyroid hormone and adrenal function. T3 and T4 both impact breakdown and clearance of cortisol from the body. Taking an entire physiologic replacement dose of T4 and/or T3 combo just after waking? Well, that hastens cortisol’s clearance from the body.
Which is really unfortunate because cortisol itself is anti-inflammatory and necessary for life. When cortisol levels fall in response to that rapid clearance with the morning dosing of thyroid hormone, the brain gets this emergency warning “We need more cortisol in here stat!”
So, the hypothalamus secretes more CRH (a pro-inflammatory hormone). The pituitary receives that CRH signal and secretes more ACTH, which is about the equivalent of dropping napalm in your backyard to take care of a couple of weeds in the lawn.
ACTH is not specific. When the adrenals get that ACTH signal, they don’t just respond with more cortisol, they also secrete more adrenaline. Adrenaline itself? Pro-inflammatory.
So… if you’re on thyroid replacement hormone and taking your full dose in the morning when you wake up, you’re supporting clearance of anti-inflammatory cortisol. When cortisol drops too low the body freaks out and feedback loops tell the brain to secrete CRH (pro-inflammatory) and ACTH which stimulates release of both cortisol (anti-inflammatory) and adrenaline (pro-inflammatory).
Thinking this was a “simple” problem of too much pro-inflammatory signal, I adjusted my thyroid hormone dosing schedule as soon as I made that connection about mast cell activation.
It helped… but ultimately, I was still struggling with some of the symptoms of MCAS, most notably GI problems.
Nutrients for histamine clearance
What’s really interesting, when you look at the DAO enzyme itself (which the body makes), it requires these necessary nutrients:
·Tyrosine
·Copper
·Vitamin B6
We’ll cover tyrosine in a separate article. Chances are you also already know the importance of B vitamins (not just B6 but basically every single B vitamin) in regulating glucose (and supporting insulin sensitivity) within the body.
Here, we’re focusing on copper for a hot minute.
Is copper deficiency really wide-spread?
Two copper atoms sit at the center of an active DAO enzyme. Without those two copper atoms, the enzyme doesn’t work. Copper deficiency is actually fairly widespread due to several reasons. Here’s a few of those reasons.
1. Overconsumption of Iron and Zinc
·The Iron Traffic Jam: Many foods are supplemented (fortified) with iron (cereals, grains (enriched rice, enriched flour). Several studies have found that iron supplementation decreases copper absorption. I’m not going into the mechanism of that here, but if you’re curious, check out the references below from the James Collins lab (University of Florida).
What we don’t talk about often: Iron cannot be safely moved or used by the body without copper-dependent enzymes (like hephaestin and ceruloplasmin) acting as electron donors*. Overwhelming the body with iron reduces copper absorption by over 50%.
*The TLDR on the necessity of copper for moving and recycling iron within the body: Copper deficiency suppresses the expression of the liver enzyme (ATP7B) that’s required to load copper into ceruloplasmin (a protein that allows for safe transport and recycling of iron to make new red blood cells).
What this means for MCAS… Copper deficiency also deprives tissues of the copper required to make diamine oxidase (DAO), slowing down histamine clearance.
The Zinc Trap: Many bioavailable zinc supplements (like zinc picolinate) act like Trojan horses allowing zinc to bypass normal checkpoints and get inside the cells of the intestines (enterocytes). These cells recognize that excess zinc as a hazard, and in response the cell generates metallothionein, a protective metal binding protein.
Because metallothionein has a much higher binding affinity for copper (several orders of magnitude higher than for zinc and other metals), metallothionein binds relentlessly to any dietary copper that also enters the cell. Instead of letting that copper pass through to your bloodstream, metallothionein keeps it trapped inside the gut cell.
The intestinal lining replaces itself every few days, and when those copper-loaded cells die and slough off the gut wall, they carry that trapped copper right out of the body in stool.
2. Environmental Exposure to Glyphosate (Roundup)
Before glyphosate was ever sprayed on crops as a weedkiller, it was patented (in 1964) as an industrial descaling agent designed to strip mineral buildup out of commercial pipes. Glyphosate is a highly aggressive chelator with a special affinity for… you probably guessed it already. Copper.
When you eat foods containing glyphosate, it binds the copper that you eat in that same meal (and depending on which studies you put merit in may also strip copper from the body). While I don’t ascribe to all of Stephanie Seneff’s theories around glyphosate, for me the research is ample regarding this particular way that this ubiquitous weedkiller messes with our health.
Glyphosate’s also insidious… cane sugar for instance. Sprayed with glyphosate to dry it out before it’s harvested. Wheat. Same. Oats. Same. If it’s a grain or any kind of sugar (molasses, cane syrup, etc.), it needs to be organic so you know that glyphosate wasn’t used during harvesting.
The problem with GMO: Moved onto beet derived sugar? Sugar beets have been genetically modified to withstand glyphosate. (Table beets… red beets, orange beets, etc. are exempt from this and still okay as of the date I originally wrote this article May 25, 2026).
Corn. Most corn in the US is now GMO (Roundup Ready), so unless it’s labeled organic or non-GMO corn or you know the grower (and know their farming practices), assume it’s been sprayed with glyphosate.
3. The Organic Catch-22: Industrial Margins and Excess Phosphorus
Even the most beautiful, certified organic vegetables don’t deliver the same amount of copper they did 70 years ago. This is the ultimate Catch-22 of not growing our own food. Copper isn’t needed in abundance by plants, but it is a necessary micronutrient. I’m picking on organic crops for a sec because chances are high you’re already eating organic (and I’m not suggesting you stop, I’m just painting the pic that industrial farming practices… whether organic or not… are creating an environment where we are malnourished).
Organic farmers may be using natural sources of fertilizer: manure, bone meal, etc. but when you look at the nitrogen : phosphorous : potassium (N-P-K) ratio of these natural fertilizers, there’s an excess of phosphorus relative to plant’s needs.
Phosphorus in fertilizers (whether manure or synthetic fertilizers) can be in phosphorus form or phosphate form. Over time, as fields are treated with heavy doses of fertilizer (again either organic or synthetic fertilizers doesn’t matter), phosphorus accumulates because it’s too much for what the plant needs.
The phosphate in that fertilizer is able to bind to copper in the soil creating insoluble copper phosphate that the plant roots can’t absorb. The result? Copper content even in organic fruits and vegetables has dropped by 30% to 75% over the last several decades.
I get this is starting to sound a bit dooms-day-ish. Stay with me. This is the low point.
4. The Monotone Diet Trap (Same Stuff Different Day)
Let’s be completely honest about what a modern "clean diet" actually looks like. Typically, even the healthiest eaters fall into a rigid, repetitive food monogamy: organic chicken breasts, pasture-raised eggs, avocados, wild-caught salmon, and baby spinach (okay, if you’re MCAS, this is bok choy or arugula or some other low histamine green).
While this is clean in one respect, skeletal muscle meats and standard greens are naturally very low in copper.
By comparison, just a few generations ago (as late as gasp the 1940s and ‘50s), people in America ate the entire animal (and grew their own food… or bought directly from someone who grew the food – just planting the seed for how dramatically our food supply has changed in under a century). Now back to the convo around meat…
Today, we eat muscle. Not liver. Not spleen. Not kidneys. Not other organ meats. Muscle. Regardless of the animal.
The liver is the primary copper storage organ of any mammal; a single ounce of grass-fed beef liver contains more bioavailable copper than a person typically consumes in an entire month of eating clean chicken breasts. By eliminating organ meats, our monotonous modern diets have left us copper deficient.
Reclaiming the Timeline
It’s incredibly easy to look at this landscape… the depleted soil, Roundup, iron added to dietary staples, and feel overwhelmed (and wondering if there’s some kind of deep conspiracy here… or maybe that’s just me). The good news is this… your body is remarkably resilient and incredibly smart. It knows its way back to wellness. In fact, that’s how it’s designed. Wellness is your birthright.
And, when you start giving the body what it needs, nature will take care of the rest.
Why Copper Alone Isn't Enough
Reading this, you’re likely wondering how to get more copper in your diet and what the best copper supplement is.
If you introduce copper too quickly into a hyper-reactive body, you’ll likely get a backlash… in the form of symptom flare. The unbound copper reacts with excess free iron, triggering the Fenton reaction, a cascade of cellular oxidative stress that destabilizes mast cells further, flares the GI tract, and will probably make you feel ten times more "histamine-y" than when you started.
That’s because the infrastructure is missing. Necessary nutrients to build the antioxidants that quench that oxidative stress. Necessary nutrients that build the proteins that safely transport copper through the body. Necessary nutrients that build the precursors to the DAO enzyme… before the copper and vitamin B6 and vitamin C needed for making that DAO enzyme.
This opens the door to a conversation around fatty acids, vitamin A, vitamin E, and more. And, you’re anxious to get back to your day.
Why I Created the Reclaim Wellness Protocol
I’ve spent the past decade piecing together the beautiful tapestry of essential minerals, vitamins, and other necessary nutrients the body uses so elegantly to weave life. I started with a knotted ball of lots of different color threads. I won’t pretend that I have all of those threads sorted. And, I’m beginning to believe life doesn’t intend for us to reduce it to purely biochemistry.
What I do know is this.
What I have pieced together from these threads has saved other women years… if not decades… of living with symptoms and band-aiding over them.
I specifically work with women who are struggling with mast cell activation whether that’s showing up as GI trouble, inflamed/raw/histamine-y feeling, or interstitial cystitis/chronic UTI symptoms.
I’ve personally navigated all of these symptoms alongside brain fog, severe headaches, neck stiffness, fatigue, insomnia, and a seeming inability to regulate my own body temperature. I’ve been patient zero. The case study. And, then I’ve taken what I learned and refined and honed it into a program that not only shows you how your body really works but also lays out a path back to wellness, one designed even for the most reactive body.
Right now, the doors are open for the beta launch of this program. It includes three months of in-depth conversations around the necessary building blocks the body needs, a strategic introduction of these building blocks, and live calls for real-time support. We kick-off on Friday, May 29th. If this is what you’ve been waiting for, claim your spot here.
References
Thyroid, Cortisol, and Mast Cell Activation
The direct link between stress hormones (CRH) and mast cell degranulation:
Theoharides, T. C., et al. (1998). Corticotropin-releasing hormone induces skin mast cell degranulation and increased vascular permeability, a possible explanation for its proinflammatory effects. Endocrinology.
How stress-induced pathways activate human mast cell receptors:
Cao, J., et al. (2005). Regulation of corticotropin-releasing hormone receptor-2 expression in human cord blood-derived cultured mast cells. Journal of Molecular Endocrinology.
Read the Full Study via the Journal of Molecular Endocrinology
The Intestinal Iron-Copper Traffic Jam
How excess dietary iron antagonizes and blocks copper absorption:
Doguer, C., Ha, J.-H., & Collins, J. F. (2018). Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver. Comprehensive Physiology.
How high iron intake specifically disrupts intestinal copper transport mechanics:
Ha, J.-H., doguer, C., & Collins, J. F. (2017). Consumption of a high-iron diet disrupts homeostatic regulation of intestinal copper absorption in adolescent mice. American Journal of Physiology-Gastrointestinal and Liver Physiology.
How copper dynamically stabilizes the ATP7A protein structure from rapid degradation:
Xie, L., & Collins, J. F. (2013). Silencing of the Menkes copper-transporting ATPase (Atp7a) gene increases cyclin D1 protein expression and impairs proliferation of rat intestinal epithelial cells. American Journal of Physiology-Cell Physiology.
Environmental Chelation (Glyphosate History)
The original chemical patent for aminomethylenephosphinic acid (glyphosate) as a heavy mineral descaling agent:
Toy, A. D. F., & Uhing, E. H. (1964). Aminomethylenephosphinic acids, salts thereof, and process for their production. U.S. Patent No. 3,160,632. Washington, DC: U.S. Patent and Trademark Office.
