Hashimoto's disease hits about 14 million people in the US and is approximately 7 times more prevalent in women (more on that later).
This disease is just the tip of the iceberg as you can have reduced thyroid function long before there's an official diagnosis.
Obviously, steroidal hormones are intimately linked as we'll see below but the culprit may lie more in our diet.
There's a fascinating case of mistaken identity with a key protein in gluten from grains that may figure directly into damage which leads to a weakening of the thyroid gland.
This can be reversed by dietary intervention but let's face it…it's difficult to cut out or reduce gluten in today's world.
Maybe a deeper dive into the actual mechanism might be the backup resolve we need.
There's also another way to support this pathway separately which involves the gut barrier that's quite a bit easier.
We'll cover it all in these sections:
- A quick intro to the thyroid
- Gliadin and the gut barrier
- Gliadin protein mimicry with thyroid
- Progesterone's effect on gut barrier
- Other options to support gut barrier
Let's get started!
A quick intro to the thyroid
The thyroid is a powerhouse in the endocrine (hormone) system.
It produces two key chemicals, T3 and T4.
Simply put, they control the rate of activity in your body's cells. Metabolism.
Since it's such a baseline player, every system in your body is impacted by these levels with T3 being the activated version (T4 works like storage).
Both are heavily dependent on iodine but hypothyroid (not enough production) increases with age, specifically for women regardless of iodine levels.
The side effects START with the following:
- Fatigue
- Increased sensitivity to cold
- Constipation
- Dry skin
- Weight gain
- Puffy face
- Hoarseness
- Muscle weakness
- Elevated blood cholesterol level
- Muscle aches, tenderness, and stiffness
- Pain, stiffness, or swelling in your joints
- Heavier than normal or irregular menstrual periods
- Thinning hair
- Slowed heart rate
- Depression
- Impaired memory
- Enlarged thyroid gland (goiter)
https://www.mayoclinic.org/diseases-conditions/hypothyroidism/symptoms-causes/syc-20350284
The brain and heart are especially sensitive which makes sense since they are such energy hogs relative to other areas of the body (muscle being a third runner up).
But again…every system in the body is dependent on T3 to….run (not walk).
There's a range of potential causes but a large percentage of cases are tied to autoimmunity…Hashimoto's hypothyroidism.
This is the immune system turning on itself…in this case, the thyroid.
Why? How? Let's look at one very compelling pathway.
Gliadin and the gut barrier
Gluten is a key constituent of most grains but especially wheat.
Within this protein is a component piece called gliadin. The definition:
Gliadin (a type of prolamin) is a class of proteins present in wheat and several other cereals within the grass genus Triticum. Gliadins, which are a component of gluten, are essential for giving bread the ability to rise properly during baking.
https://en.wikipedia.org/wiki/Gliadin
The first step in the process that leads to Hashimoto's is a breakdown of the barrier between our food and us.
This is the highly complicated gut barrier composed of immune cells, tight junctions (like lego-locked cells), a film of material, and even helpful gut bacteria.
We have a key sentinel in the gut called zonulin which manages our gut barrier to allow nutrients in but keep foreign entities or pathogens out.
Look at gliadin's effect:
Gliadin induces an MyD88-dependent zonulin release that leads to increased intestinal permeability, a postulated early element in the pathogenesis of celiac disease.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653457/
Gliadin is an apt burglar of sorts that is able to bypass our security and get access into our bodies via the gut barrier.
It's just a happenstance of chemistry really. Its chemical keys just happen to fit the lock to our gut barrier.
With this, gliadin can gain entrance into the body and travel about till the immune system detects its presence.
That's where we have a problem. To the thyroid!
Gliadin protein mimicry with thyroid
There's a chemical that's very abundant in the thyroid but prevalent everywhere.
Transglutaminase. "Meat glue". Basically, it's a chemical party-starter. It speeds up chemical processes throughout the body.
Here's the issue with gliadin:
Gliadin looks like transglutaminase, an enzyme specifically abundant in the thyroid. The body’s antibodies attack both the gliadin and transglutaminase. The thyroid gland is under attack whenever gliadin is in the blood stream.
https://juniperpublishers.com/jojph/pdf/JOJPH.MS.ID.555563.pdf
The immune system has an APB for gliadin but will also attack transglutaminase which is at high levels in the thyroid.
In fact, a test for celiac disease looks for antibodies to transglutaminase to determine positives for the disease.
This means the immune system is actively targeting a key component of our body generally (and our thyroid in particular).
This is common. For example, the tie between strep throat and psoriasis (see psoriasis review).
What's interesting is that transglutaminase's very function might be part of the problem.
When it comes to contact with gliadin, it chemically alters it which makes the resulting chemical more obvious to our immune system.
Tissue transglutaminase (tTG) seems to be the target self-antigen for endomysial antibodies in coeliac disease (CD) and to catalyse the critical deamidation of gliadin which strengthens its recognition by HLA-restricted gut-derived T cells.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1808891/
At this point, gliadin is embedded in the tissue and the thyroid happens to be a big user of transglutaminase.
The immune system attacks the thyroid!
T3 falls as a result and we'll direct you to the symptoms above.
One note…the antibodies do go down if completely stop taking in gluten but it takes time:
The majority of non-celiac gluten sensitivity patients (93.2%) showed the disappearance of anti-gliadin antibodies of IgG class after 6 months of gluten-free diet
https://bmcgastroenterol.biomedcentral.com/articles/10.1186/1471-230X-14-26
Okay…so why women?
Hello, progesterone!
Progesterone's effect on gut barrier
It's not just about reproduction.
Progesterone is a master regulator of the immune system but more importantly, a key mediator of…the gut barrier!
Progesterone decreases gut permeability through upregulating occludin expression in primary human gut tissues and Caco-2 cells
https://www.nature.com/articles/s41598-019-44448-0
Remember zonulin above…the stealth key that gliadin uses to open the tight junctions of the gut barrier?
Meet its opponent…occludin.
Here's the issue…progesterone starts dropping around age 20 and drops by 50% at age 40. It continues down from there…forever. We really weren't designed to live past 35!
There's a known tie-in between Hashimoto's and PCOS which signals an imbalance between progesterone and estrogen.
Estrogen continues pretty strong until perimenopause, mid to late 40s when it drops off a cliff.
Average age for Hashimoto's diagnosis?
Oh…47.7.
So roughly a decade of low progesterone and the entire auto-immune complex (see autoimmune) starts to spike.
No fair testing women's progesterone starting in the 30s at the annual visit. Failure!!
Estrogen also has a role in the gut barrier:
Progesterone and estrogen improved wound healing and epithelial barrier function in intestinal epithelial cells via upregulation of tight junction proteins. Furthermore, these sex hormones significantly reduced ER-stress and reduce pro-inflammatory cytokine production in intestinal epithelial models.
https://pubmed.ncbi.nlm.nih.gov/30893871/
Generally speaking, progesterone calms immune response and estrogen drives it. They work together as in every other pathway of the body.
Bioidentical support becomes essential as these numbers drop.
That's the big driver. Let's look at other ways to support the hole in the dam.
Other options to support gut barrier
We have a full review on the gut barrier here.
Let's assume you're not able to completely stop eating gluten.
Are there ways to support the gut barrier generally?
Yes!
First and foremost, you need to reduce or cut out the following:
- Processed food
- Excess sugar
- Artificial sweeteners, colors, and flavors
- A range of medications including NSAIDs (common pain meds…see Tylenol and gut barrier)
- More Omega 3 fats (less vegetable oil)
- Dairy can potentially be a similar issue to gluten depending on genetics
The inflammatory state in the gut is especially important.
There are tools that have been shown to calm gut inflammation and even support the gut barrier.
A quick list:
- Magnesium glycinate
- CBD isolate
- Vitamin D
- Berberine
- Medicinal Mushrooms
We have massive reviews on each of these but some quick takes for the gut barrier specifically.
First, mag.
Lots to unpack here:
Compared with the mice fed the control diet, mice fed the Mg-deficient diet for 4 d had a lower gut bifidobacteria content (−1.5 log), a 36–50% lower mRNA content of factors controlling gut barrier function in the ileum (zonula occludens-1, occludin, proglucagon), and a higher mRNA content (by ∼2-fold) in the liver and/or intestine of tumor necrosis factor-α, interleukin-6, CCAAT/enhancer binding protein homologous protein, and activating transcription factor 4, reflecting inflammatory and cellular stress
stress.https://academic.oup.com/jn/article/140/3/509/4600408
Goodness. So mag deficiency (which is very common due to pesticides and mono-crop farming) is tied to:
- A reduction in the powerful controllers of our gut barrier walls
- An increase in inflammatory pathways in the liver and intestins
Check out the review of magnesium glycinate here.
CBD Isolate and the gut barrier
We have a massive review of CBD and gut barrier or CBD and gut inflammation.
Cannabidiol restores intestinal barrier dysfunction and inhibits the apoptotic process induced by Clostridium difficile toxin A in Caco-2 cells
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721977/
C diff is a monster in destroying the gut barrier and the microbiome is front and center.
We looked at the microbiome specifically here since it's really the guardian of our gut.
Another review looked at how CBD can protect the gut from NSAIDs here.
Let's look at another great supporter of gut balance and barriers. Berberine.
Berberine and gut barrier
Berberine is a natural analog for metformin. Both have powerful effects on the gut.
It can even support pretty amazing species of gut bacteria like akkermansia.
As for the barrier??
Berberine reduces gut-vascular barrier permeability via modulation of ApoM/S1P pathway in a model of polymicrobial sepsis
https://www.sciencedirect.com/science/article/abs/pii/S0024320520312133
Or look at the powerful connection between diabetes and gut barrier:
However, the treatment with BBR significantly reversed the above changes in diabetic rats, presenting as the improvement of the high glucose and triglyceride levels, the relief of the inflammatory changes of intestinal immune system, and the attenuation of the intestinal barrier damage.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290458/
Just a head's up…metabolic dysfunction and glucose are becoming enemy #1 for heart, brain, and longevity itself.
A great deal of our GABA and most of our serotonin is made in the gut as a result of our gut bacteria (if we have the right mix).
We have a full review of berberine here.
Next up…Vitamin D.
Vitamin D and gut barrier
Vitamin D is actually a steroid we get from the sun. But we're not in the sun 8-10 hours a day like our ancestors.
Vitamin D deficiency is incredibly prevalent and goes up as we get older.
As a regulator of Toll-like receptor 4, vitamin D preserves intestinal epithelial barrier function and the vitamin D/vitamin D receptor (VDR) pathway has been shown to have intestinal protective effects in inflammatory bowel disease by inhibiting intestinal epithelial apoptosis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430230/
Where mag and CBD isolate work fast, Vitamin D builds up slowly. 3 months generally.
You need to get tested and the endocrinologist want numbers between 50-60 nmol/Ll at a minimum (not the ridiculous 30 RDA).
Another longer player is our fungi cousins.
Medicinal mushrooms and gut barrier
We have a huge review on medicinal mushrooms (with a focus on mental health).
Just one example (of dozens) with lion's mane:
Hericium erinaceus maintains intestinal barrier integrity, and increases the diversity and richness of gut microbiota.
https://www.sciencedirect.com/science/article/pii/S1756464621001870
Medicinal mushrooms basically help our body to rebalance the immune response (inflammation) and this always has a foot in the gut.
We chose these options because they don't build tolerance which is critical!
Iodine is also critical for the thyroid and there's no getting around steroidal hormone support.
Worse case, gut barrier support is the first step since this is how gliadin gains entry into our body to trigger the immune response which accidentally targets the thyroid.
Be well. Take care of each other. Take care of yourself!
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.