Silver Tree Wellness Center | Phoenix, AZ

CIRS: An Examination of Chronic Inflammatory Response Syndrome from Exposure to Recovery (Part 4 – CIRS Treatment)

CIRS: An Examination of Chronic Inflammatory Response Syndrome from Exposure to Recovery (Part 4 – CIRS Treatment)

Welcome to the fourth and final part of this series on Chronic Inflammatory Response Syndrome (CIRS). This article covers the treatment of CIRS using the Shoemaker protocol for biotoxin-related illness. CIRS treatment using the Shoemaker protocol should be attempted only after a differential diagnosis is confirmed, which you can read about in parts one, two, and three of this series. The Shoemaker protocol provides a proven, precise approach to reversing the root cause of the inflammation and overactive immune system characteristic of this condition, which is also sometimes called mold illness or sick-building syndrome.

Here at Silver Tree Wellness Center in Phoenix, Arizona, we treat mold illness, Lyme disease, and other biotoxin-related illnesses with the Shoemaker protocol and integrative therapies under the direction of Dr. Jennifer Smith, a Shoemaker-certified naturopathic physician. Read on to learn how our treatment approach can help you recover from CIRS and get your life back…no matter how long you’ve battled with this complex condition.

Mold Illness (CIRS) Treatment Overview

The process used by Shoemaker-certified practitioners to treat mold illness (CIRS) has been studied and validated through two double-blind randomized controlled trials. It’s a series of steps taken in a specific order that is often compared to climbing a pyramid. Each step is completed before moving to the next. If a full recovery is achieved at one of the steps, treatment is stopped. There’s no need to move to the next step. You may get well after the first step, for example, which is removal from exposure.

Throughout the treatment protocol, C4a, TGF beta-1, MMP9, and VEGF and any other abnormal biomarkers are regularly monitored. The Visual Contrast Sensitivity (VCS) test is administered at each step to check for improvement. Targeted interventions are progressively implemented, one at a time, until every abnormal CIRS biomarker is corrected….and you feel like your true and healthy self once again.

CIRS Treatment Step One: Removal From Exposure & Avoidance

Removal from exposure is the first step in the Shoemaker CIRS protocol. Mold and other biotoxins must be strictly avoided at every step of the treatment sequence. No matter where you are on the pyramid, if you’re re-exposed, you’ll have to start the protocol from the beginning.

You can learn more about exposure in part one of this series. But exposure to mold and other inflammagens in water-damaged buildings (WDB) makes up 80% of all CIRS cases so is of greatest concern when practicing avoidance. Unfortunately, if you’re dealing with CIRS-WDB, you’ll have to leave your home or stop going to work or school, depending on the source of exposure. You should only return to the water-damaged building after remediation is confirmed successful.

You’ll want to use a mold-specific quantitative polymerase chain reaction (MSQPCR) test known as an Environmental Relative Moldiness Index (ERMI) from or to determine environmental safety. This is true for the suspected source of exposure as well as to test the new environment before moving.

The ERMI samples dust from the indoor environment and uses DNA for identification of the mold species. If your melanocyte stimulating hormone (MSH) is less than 35 and your Complement C4a is less than 20,000, avoid a building with an ERMI higher than 2. However, if your MSH is less than 35 and your C4a is greater than 20,000, that number moves to negative 1. 2

CIRS Treatment Step Two: Use a Binder to Clear Biotoxins from the Body

The second step in the Shoemaker protocol is to begin to clear the biotoxins circulating throughout your body. Clearing the mycotoxins and other microbes such as actinomycetes, endotoxins, exotoxins, beta glucans, and mannans is accomplished with Cholestyramine (CSM), Welchol, or another practitioner-recommended binder.

Cholestyramine in the Shoemaker Protocol for Treating CIRS (Mold Illness)

During his initial work, Dr. Shoemaker observed CSM quickly reduced symptoms of Pfiesteria toxicity such as headaches, diarrhea, and cognitive issues. Since his 1997 discovery, several studies have validated the effectiveness of CSM to treat biotoxin-associated illness, including CIRS-WDB.3

Cholestyramine (CSM) is an FDA-approved medication that was used to reduce cholesterol until statins became widely available in the 1970s. It’s a cationic polymer composed of a strong, non-absorbable resin that binds to negatively-charged ionophores (biotoxins are ionophores) and removes them via the large intestine. This prevents the chronic reabsorption of biotoxins in the bile during enterohepatic recirculation. 4

In 1999, the FDA determined there is no increased risk of using CSM to reduce biotoxin carriage in the body. Although it’s used “off-label” and does not have FDA approval to treat CIRS, it’s exempt from repeating FDA trials to prove that it’s safe. The four gram dose is mixed in six ounces of water and is followed by another six ounces of water. It’s taken 30 minutes before meals up to four times daily.

CSM may interfere with the absorption of other medications or vitamins, so it’s important to follow the dosage and frequency instructions of your practitioner. Constipation, bloating, and reflux are common side effects caused by excess CSM that’s not absorbed. If constipation occurs, fiber, magnesium, or another digestive stimulant may be needed.

Welchol and Other Binders in the Shoemaker Protocol for Mold Illness (CIRS)

If you’re unable to tolerate CSM because of the side effects or another issue such as food allergies or chemical sensitivity, a substitute binder may be prescribed. The most common is Welchol, another FDA-approved cholesterol medication. Wechol is also best for those who are already constipated. 5

Welchol is only 25% as effective as CSM, so laboratory markers will take longer to return to normal. Although it has fewer side effects, it’s more expensive than CSM. Two 625 mg tablets of Welchol are taken up to three times a day with food. Activated charcoal, chlorella, sterols, and other binders can also be used but are even less effective than Welchol.

Other Considerations in the Use of Binders for Treating CIRS

Binders can make some people feel quite ill, especially those with CIRS-post Lyme syndrome. Dr. Shoemaker labeled this an “intensification reaction,” and it’s accompanied by an elevation of matrix metallopeptidase 9 (MMP-9) and a further decline of VCS. The intensification can be reduced by a combination of the low-amylose diet and by preloading with three to four grams of omega-3 daily (2.4 g EPA and 1.8 g DHA), beginning five to seven days before starting the binder.

Once binders are started, the VCS test is administered every 30 days until it has normalized. If the vision test is clear and an ERMI confirms a safe environment, Welchol should be reduced to one 625 mg tablet twice per day, and CSM can be taken just once a day. If you rarely go out, you can stop your binder altogether. In cases of re-exposure, however, full dose CSM or Welchol should be used for a minimum of three days.6 Finally, if binder use fails, misdiagnosis, non-compliance, a false-negative ERMI, or untreated MARCoNS should be considered.

CIRS Treatment Step Three: Eliminate MARCoNS from the Nasal Passage

Multiple antibiotic resistant coagulase negative staphylococcus (MARCoNS) may be present in the nasopharynx of those with CIRS (mold illness). A MARCoNS nasal culture test will be given during your first appointment as part of your baseline lab report. If MARCoNS is found, it’s necessary to eradicate this bacteria before moving forward with the Shoemaker Protocol.

MARCoNS bacteria create a biofilm shield that prevents many antibiotics from penetrating and destroying it. The test is positive if the bacteria is resistant to two or more antibiotics. Treatment for MARCoNS should start 30 days after beginning CSM with high dose BEG (Bactroban/EDTA/gentamicin)  nasal spray.7 The correct dose is two sprays to each nostril three times daily. Treatment often takes 30-50 days.

A Jarisch-Herxheimer reaction can occur from die-off of the bacteria. If so, stopping BEG for 5 days to take Omega-3 and adhere to a low-amylose diet before resuming the spray can help. If symptoms don’t improve after a month, pets or loved ones should be considered as MARCoNS carriers. MMP-9 and VCS should be retested. When symptoms have improved, the nasal culture and VCS tests should be re-administered to confirm eradication of MACRoNS before moving to the next step in the Shoemaker protocol.

CIRS Treatment Step Four: Correct Antigliadin Antibodies with a Gluten-Free Diet

The next step in the Shoemaker protocol for mold and biotoxin-related illness is normalizing antigliadin antibodies (AGA) with a gluten-free diet. Gliadin is a glycoprotein (a carbohydrate plus a protein) in gluten.  Low melanocyte-stimulating hormone (MSH) as part of CIRS can lead to a dysregulation of T-regulatory cells that produce autoimmune conditions such as food sensitivity and inflammation. These are marked by elevated IgA and IgG anti-gliadin antibodies.

If anti-gliadin (AGA) antibodies are present in your initial lab work, it’s necessary to test for transglutaminase antibodies (TTG) to find out if you have celiac disease. If this test is positive, you should stop eating gluten for life. However, if negative, eating gluten-free for three months and then retesting for AGA is standard protocol. If the retest is negative for AGA, gluten is slowly reintroduced. If AGA is positive after a month of eating gluten, you’ll probably feel best maintaining a gluten-free diet indefinitely.  If AGA is negative, you’re ready to move to the next step of the Shoemaker protocol.

CIRS Treatment Step Five: Correct Androgen (Hormone) Levels

Mold illness (CIRS) is often marked by dysregulation of androgenic hormones. The chronic inflammation and lowered vasoactive intestinal peptide (VIP) typical in CIRS can cause upregulated aromatase enzyme, which converts testosterone into estrogens more quickly. This creates a hormone imbalance with low testosterone and high estrogen levels. Women may suffer with painful or long-lasting menstruation, clotting, ovarian cysts, and vulvar pain. In men, testosterone replacement will be ineffective and can make things worse, as it further suppresses natural testosterone production.

The correction of androgen levels is accomplished with DHEA, HCG, or VIP nasal spray. The DHEA treatment is 25 mg twice per day for 30 days. If using HCG, 125 mg per week for five weeks is taken sublingually or via injection. And VIP nasal spray is taken four times a day for 30 days. During treatment, DHEA, testosterone, and estradiol should be monitored to make sure estradiol doesn’t increase from the baseline. Once the upregulation of the innate immune system is corrected, androgen imbalance is typically resolved.

CIRS Treatment Step Six: Correct Antidiuretic Hormone (ADH) and Osmolality

Osmoreceptors are cells in the hypothalamus that respond to levels of serum osmolality. Dehydration, which is an effect of high serum osmolality, causes osmoreceptors to shrink, triggering antidiuretic hormone (ADH) to be released from the pituitary gland. Excess ADH signals the absorption of free water in the kidneys, rehydrating cells and normalizing serum osmolality levels.

Conversely with overhydration, or low serum osmolality, osmoreceptors swell and ADH is blocked. Free water is lost through the urine rather than reabsorbed. For those with CIRS, dysregulation of salt and water is the effect of either low ADH and high osmolality or high ADH and low osmolality.

Frequent urination and excessive thirst from low ADH makes retaining water difficult. Salt accumulates in the blood because there’s little free water available. The salt is released onto the skin, which actually creates an electrical potential that causes frequent static electric shocks. Migraine headaches are also a common CIRS symptom due to dehydration.

About 60% of CIRS patients experience dysregulated ADH and osmolality.8 Remediation, binders, a clear VCS, and eradication of MARCoNS may result in correction of ADH, but it may require additional treatment. DDAVP, a prescription form of ADH, is used to correct ADH/osmolality at this step of the Shoemaker protocol.

A 0.2 mg tablet of DDAVP is taken every other night for a total of five doses. DDAVP nasal spray may be used instead with one spray intranasally twice daily for five days. Weight, blood pressure, and edema are checked daily during treatment. The day after the final dose, serum osmolality, electrolytes, and ADH are tested. If the tests are normal but symptoms remain, frequency of DDAVP is increased to every day for 10 days. Electrolytes, ADH, and osmolality are then retested to ensure they have remained normal.

CIRS Treatment Step Seven: Correct Matrix Metalloproteinase 9 (MMP-9)

The activation of cytokine receptors in the biotoxin pathway upregulates the release of MMP-9 from the endothelium into the blood. Inflammatory molecules are consequently delivered into muscles, tissues, nerves, joints, and the brain. The no-amylose diet and high-dose omega-3 essential fatty acids at 2.4 g EPA and 1.8 g DHA daily are used to lower and normalize MMP-9 levels.

If this proves ineffective, 45mg of Actos once a day for 30 days can be used but is out of favor because of an FDA warning of bladder cancer after long-term use of a year or more. For those with leptin levels <7 or children under 18, Actos should not be used. Kidney function and symptoms of hypoglycemia must be monitored. All labs should be repeated after treatment. This step may also correct VEGF levels.

CIRS Treatment Step Eight: Correct Vascular Endothelial Growth Factor (VEGF)

If VEGF abnormalities persist after MMP-9 is corrected, high-dose omega-3 and the low-amylose diet should be continued. Graded cardio and strength training can also be used to address low VEGF. Anaerobic threshold and cardiopulmonary stress should be tested before exercise.

Start the exercise protocol with five minutes of cardio per day and gradually increase to 15 minutes. Then add five minutes of floor exercises such as sit-ups, increasing to 15 minutes. Finally add five minutes of free weights focusing on the upper body and increase to 15 minutes. After 30 days, return to step one, increasing intensity while repeating the sequence. VIP treatment at the last step of the Shoemaker protocol may also correct VEGF if it remains abnormal.

CIRS Treatment Step Nine: Correction of C3a

If C3a levels are elevated, determining the underlying cause is necessary. Available microbial cell membranes such as those found in Lyme disease causes elevated C3a as does Lupus and other conditions. The underlying condition must be addressed before beginning treatment for elevated C3a related to CIRS.

Treatment begins with 150 mg of CoQ10 for 10 days. This works to minimize the potential side effects of high-dose  statins that are taken to lower C3a. The dose is (80 mg/day)  of a statin such as Pravastatin, Atorvastatin, Fluvastatin, Rosuvastatin, or Lovastatin. Liver and renal function should be monitored before and during treatment. Reversible memory loss, muscle pain, and fatigue are common side effects of statins and should be reported to your practitioner.

CIRS Treatment Step Ten: Correction of C4a

C4a is the gold standard test to determine how severe a CIRS case is. It can cause mast cell and basal cell activation and increase vascular permeability and smooth muscle contraction, which releases chemotactic factors and results in a cascade of innate immune system inflammation. C4a levels increase within 10 minutes of re-exposure, which makes it a good indicator of building safety.

Treatment for elevated C4a was previously low-dose Procrit (erythropoietin), but it’s no longer used due to a black box warning for a risk of blood clotting. Four sprays daily of vasoactive intestinal peptide (VIP) nasal spray (50 mcg/ml) is now the preferred treatment.

Nuero Quant (MRI of the brain) with MR Spectroscopy may show brain volume changes that correlate with hypoperfusion caused by high C4a such as lactate levels (>1.29) in the frontal lobes and hippocampus or low glutamate/glutamine ratio. These changes correlate to decreased concentration, decreased assimilation of new knowledge, trouble finding words, disorientation, and confusion. They often improve with normalization of C4a.

CIRS Treatment Step Eleven: Reduction of Transforming Growth Factor beta 1 (TGF-beta 1)

Transforming growth factor beta 1 (TGF-beta1) is a cytokine of the innate immune system and also a biomarker that is elevated in CIRS . TGF-beta 1 turns on differential gene activation, affecting autoimmunity.

Losartan, a prescription to lower blood pressure, decreases TGF-beta 1 by producing a degradation product. Up to 25 mg of Losartan twice a day for 30 days is the recommended dosage.

Before beginning treatment, TGF beta-1, lipase, and GGTP levels should be obtained and then tested monthly. Blood pressure should be monitored twice a day during the first month of treatment. Those with low blood pressure or who can’t tolerate Losartan can use four sprays daily of VIP 50 mcg/dose intranasal spray as a substitute..

CIRS Treatment Step Twelve: Vasoactive Intestinal Polypeptide (VIP)

By this final step in the Shoemaker protocol most will have seen a 75% or greater reduction of their baseline symptoms.9 Those with severe CIRS can greatly benefit from VIP as a last effort. VIP is a 28-amino acid regulatory neuropeptide neuroimmune modulator.

VIP can decrease inflammation by downregulating cytokines, correct TGF beta-1, normalize hormone deficiency, improve cognitive function, correct proteomics and transcriptomics, as well as improve grey matter nuclear atrophy.10 The dosage is one spray (50 mcg/ml) intranasally four times a day, alternating nostrils at each application.  

Before beginning VIP treatment, ERMI should be <2, VCS test should be clear, MARCoNS should be negative, lipase should be normal, pulmonary artery systolic pressure should not increase more than 8 mm Hg during exercise, pre-VIP vital signs should be taken, and a physical exam should be administered. The first VIP dose should be taken in your practitioner’s office to monitor for blood pressure changes, rash, and abdominal pain. TGF-beta 1 should be drawn 15 minutes after the first dose. A rapid rise indicates ongoing exposure.

VIP can be taken for six to 18 months, titrating up after 30 days if no improvement is seen. Monthly lipase, GGTP, and abdominal exams are required. When symptoms improve, VIP should be tapered down to two sprays daily for 30 days, then to one spray per day for 30 days, and finally discontinued. If rash, abdominal pain, blood pressure, or increased lipase occur at any time, VIP should be discontinued.11

After nine to 12 months of VIP, the NeuroQuant MRI can be repeated to monitor improvement or reversal of atrophy. Six months after titrating off VIP, VCS and labs should be re-administered to show stability.

Conclusion and Resources

Navigating through the Shoemaker protocol is, admittedly, a challenging undertaking. Eradicating biotoxins from the body, stabilizing the immune system, and normalizing the inflammatory process is often complicated. It takes determination, a strong will, and may involve some sacrifice. But a full recovery is possible.

Please note the information outlined in this series is only intended to give you an overview of CIRS (mold illness). Working with a Shoemaker-certified practitioner or another mold-literate physician cannot be overemphasized, as they understand what’s involved and will stand with you to the end. That includes guiding you through any accidental episodes of re-exposure, which is a real concern that can set you back weeks, months, or even years. Please note the information outlined in this series is only intended to give you an overview of CIRS (mold illness). Staying safe is a lifelong commitment if you’re susceptible to biotoxins.

The following trusted resources can help guide you on your CIRS journey.

  1. The Silver Tree Wellness Center blog provides evidence-based articles about toxic mold and other related topics. Refer to the four-part Chronic Inflammatory Response Syndrome series for a more in-depth look at CIRS.
  2. Dr. Shoemaker’s website is the oldest and most trusted online CIRS resource. You can find the list of Shoemaker-certified practitioners, an online visual contrast sensitivity (VCS) test, and much more.
  3. & Information and resources about the mold avoidance approach developed by Erik Johnson, including free downloadable books, stories from mold survivors, and an online forum and Facebook community.
  4. A personal blog about one man’s (Gregory Muske) journey back to health after biotoxin illness. Perhaps the most comprehensive resource for understanding the physical, mental, emotional, and even spiritual intricacies of living with CIRS from the patient perspective.
  5. Dave Asprey (Bulletproof) created the first-ever documentary about mold- related illness to bring awareness of toxic mold exposure to the general public.
  6. The International Society for Environmentally Acquired Illness is a nonprofit professional medical society that aims to raise awareness of the environmental causes of inflammatory illnesses and to support the recovery of individuals affected by these illnesses through the integration of clinical practice, education, and research.

Please also download our free printable guide to help you navigate toxic mold exposure: Mold Illness — Your Mind-Body-Spirit Healing Handbook (7 Steps to Take After Toxic Mold Exposure).