What Is the Shoemaker Protocol?

A Step-by-Step Guide to the Only Evidence-Based Treatment for CIRS

It often starts with frustration. You’ve gone from doctor to doctor, chasing diagnoses—fibromyalgia, chronic fatigue, MCAS, MCS—but nothing fits. Or worse, everything fits, and you’re drowning in diagnoses with no roadmap. You finally stumble across the term Chronic Inflammatory Response Syndrome (CIRS) and, for the first time, things make sense.

But now what?

If you’re here, you’ve likely already discovered that most mold detox programs are heavy on binders and guesswork but light on real science. Maybe you’ve done a urine mycotoxin test. Perhaps you’ve tried activated charcoal, glutathione, or sauna protocols. And maybe, like many before you, you still feel sick.

That’s where the Shoemaker Protocol comes in—the only peer-reviewed, medically recognized protocol designed to treat CIRS at the root cause. Created by Dr. Ritchie Shoemaker, this 12-step protocol is the gold standard for addressing the immune dysregulation that defines CIRS. Simply put: the Shoemaker Protocol is the best treatment for CIRS.

This article walks you through each of the 12 steps—what they are, why they matter, and what most websites won’t tell you.

Step 1: Remove Exposure to Biotoxins

You cannot heal in the environment that made you sick. The first step of the Shoemaker protocol for mold is getting out of exposure to biotoxins, most commonly mold from water-damaged buildings (WDBs). According to Dr. Shoemaker, more than 50% of buildings in North America have water damage capable of producing biotoxins.

This step requires precise diagnostic testing to confirm that your home and work environments are safe. Testing needs to be done for all known CIRS biotoxins:

Mold,
Actinobacteria,
Endotoxins,
Beta Glucans,

Without proper environmental testing, you risk going in circles, re-inflaming your immune system even as you try to heal. This is the most important step in the entire protocol. It is also the most challenging. Make sure you’re working with a knowledgeable practitioner or Indoor Environmental Professional (IEP) to ensure you are testing your house properly.

Do you think you have CIRS? Book a complimentary 15-minute phone chat with one of our Shoemaker practitioners!

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Step 2: Use Binders to Remove Biotoxins

Once you’re out of exposure, the next step of the CIRS Shoemaker protocol is to begin the process of binding toxins from the body using cholestyramine (CSM) or Welchol. These are not over-the-counter binders like activated charcoal or bentonite clay. CSM, a prescription bile acid sequestrant, binds biotoxins in the gut for safe removal.

Shoemaker’s research shows that CSM improves visual contrast sensitivity (VCS) scores and reduces symptom clusters in CIRS patients. (Shoemaker et al., 2010)

Step 3: Treat MARCoNS in the Nasal Passage

Up to 80% of CIRS patients have multiple antibiotic-resistant coagulase-negative staph (MARCoNS) colonizing their sinuses. This bacterium produces exotoxins that perpetuate inflammation and further lower MSH levels.

Treatment in step 3 of the Shoemaker protocol for mold involves BEG spray (Bactroban, EDTA, Gentamicin), but only after VCS scores begin to improve. Testing is done via a deep nasal swab through Microbiology Dx Lab.

Step 4: Correct Antigliadin Antibodies

Many CIRS patients have elevated anti-gliadin antibodies, suggesting gluten sensitivity. This isn’t classic celiac disease, but it’s enough to trigger immune activation. Eliminating gluten during the fourth step of the CIRS Shoemaker protocol will reduce inflammation and improve GI integrity; vital when treating a syndrome that affects the gut-brain-immune axis.

Step 5: Normalize Androgens

In CIRS, androgens typically decrease due to an upregulation of the aromatase enzyme. The effect is often low DHEA and/or testosterone and elevated estrogens. Avoid TRT as this will suppress natural testosterone production.

Treatment for step 5 of Dr. Shoemaker’s mold protocol is done through DHEA supplementation.

Step 6: Normalize Antidiuretic Hormone (ADH) and Osmolality

Low ADH levels with high osmolality can lead to chronic thirst, frequent urination, salt cravings, and unrefreshing sleep—all common in CIRS.

Correcting this balance helps regulate blood pressure, hydration, and inflammation. Shoemaker recommends increased fluid and salt intake or desmopressin in specific cases.

Step 7: Correct Matrix Metallopeptidase 9 (MMP-9)

Elevated MMP-9 contributes to cytokine storms and inflammation, damaging capillaries and leading to symptoms like headaches, fatigue, and muscle cramps.

It’s reduced through a low-amylose diet and omega-3 supplementation. The low-amylose diet that is necessary during step 7 of Dr. Shoemaker’s mold protocol is often overlooked but plays a critical role in controlling inflammation.

Step 8: Normalize Vascular Endothelial Growth Factor (VEGF)

Low VEGF impairs oxygen delivery to tissues, resulting in fatigue, muscle weakness, and poor exercise tolerance.

Treatment involves managing underlying inflammation, correcting hypoxia, and, in some cases, using low-dose erythropoietin.

Steps 9 and 10 : Correct C3a and C4a

The Goal is to get C3a <780 and C4a <2830.

High-dose statin therapy is used until C3a levels return to normal. C4a is one of the most sensitive markers of immune activation in CIRS and correlates with symptom severity. Statins are being used less and less due to the side effect profile of said medications. Most practitioners today are using VIP to correct C3a and C4a.

Step 11: Normalize Transforming Growth Factor Beta-1 (TGF-Beta 1)

High TGF-beta 1 levels are linked to fibrosis, autoimmunity, and airway reactivity—making this a critical marker in patients with asthma-like symptoms or MCAS.

Treatment may include VIP or losartan, depending on individual lab findings. This step is rarely discussed in mainstream resources, but TGF-beta 1 control can be a game-changer for recovery.

Step 12: Replace VIP Levels

Vasoactive intestinal peptide (VIP) influences metabolism, immune regulation, and brain function. Low VIP is associated with poor sleep, fatigue, and neuroinflammation.

Reintroduction of intranasal VIP (only after passing VCS and confirming a safe environment) can restore normal brain structure and function, as confirmed through NeuroQuant MRI scans.

Step 13: Return to Life (not part of the Shoemaker protocol but vitally important)

This final step is the most rewarding—and the most personal. It’s where patients regain energy, tolerance, focus, and joy.

But it’s also where relapse prevention becomes crucial. Continued environmental awareness, ongoing screening, and occasional lab testing ensure long-term remission.

Why This Matters

The Shoemaker Protocol is the only science-backed, peer-reviewed treatment for CIRS. It’s not a “detox” or a supplement regimen—it’s a medical framework for reversing immune dysregulation. It is the best treatment for CIRS, and following it is the only method to make CIRS go away.

At Flourish Clinic, we’re trained and experienced in guiding patients through the full 12-step protocol, including those with overlapping conditions like fibromyalgia, chronic fatigue, MCAS, and MCS. We understand that every patient’s path is different—and that healing requires more than hope. It requires a plan.