Assessing Shoemaker’s Antifungal Stance for CIRS Treatment

Our private practice specializes in root-cause healing, guiding patients to identify and address the foundational drivers of chronic illness rather than simply managing symptoms. 

 

One of the most powerful tools we’ve used in this work is the Carnivore diet. In our clinical experience, Carnivore serves both as a root-cause solution and as an essential support for clients troubleshooting complex health challenges. Yet, despite its vast healing effects, we quickly discovered that Carnivore alone can’t resolve every health issue. 

 

This realization drove us to continue searching for answers for our most complex, chronically ill patients and clients.

 

Through this journey, we discovered that environmental illness is a significant, commonly underrecognized, missing piece in the health puzzle, particularly prevalent among our community. In our search for effective, clinically replicable protocols for environmental illness, we were introduced to CIRS (Chronic Inflammatory Response Syndrome), a multi-system condition triggered by biotoxins, and the Shoemaker Protocol, developed by Dr. Ritchie Shoemaker. 

 

Since integrating the Shoemaker Protocol as a personalized, core treatment into our practice, we have seen remarkable healing and remission in many of the hundreds of patients diagnosed with CIRS or biotoxin illness.

 

However, a subset of CIRS patients and our community continue to face roadblocks. 

 

Even after meticulous adherence to environmental remediation and the Shoemaker Protocol, these patients still experience persistent CIRS-related symptoms and challenges. In the last five or so years, Shoemaker has focused heavily on actinos (actinomycetes) and secondary, endotoxins, stating they are bigger issues than mold. Shoemaker now believes that indoor toxic molds may only be causing 10% of the CIRS cases, and actinos may be responsible for up to 50% of health effects seen in CIRS patients. While we’ve shared our thoughts and in-depth research on actinos here, what about the patients who’ve followed strict actino protocols with no success? 

 

Actinos are so prevalent that the Shoemaker practitioner group, including Indoor Environmental Professionals (IEPs), share that: 

• Actinos regrow in just two hours on moist organic surfaces, including bed sheets and towels.
• Actinos are present in nearly all homes. They are found in over 95% of tested homes and comprise more than 20% of the microbial population. 
• The most common area of actinos is in the bedroom, not even in basements with water damage. 
• Primary sources are human, soils, and water-damaged materials. Actinos are the culprit of the musty smell that we attribute to mold. 
• Pets can be mechanical carriers reintroducing environmental actinos indoors.

 

Shoemaker’s current actinos model shares that the colonization or shedding of actinos causes an innate immune activation loop. When these bacteria grow on damp skin, bedding, or dust, they release tiny particles called extracellular vesicles (EVs). These particles then become airborne and easily inhaled or absorbed through the skin. This then activates the immune receptors, triggering a chronic inflammatory response where the immune system stays activated and leading to ongoing inflammation seen in CIRS.

 

Thinking logically here, if actinos is >50% of the reasons for CIRS illness, here are some logical questions we have:

• Why has the Shoemaker CIRS Protocol not changed to start with actinos skin and home cleaning and remediation? Why go through the traditional Shoemaker Protocol first, before seeing later if the patient has an overgrowth of actinos?
• If actinos are deemed a problem, the solution is to scrub and clean both the skin and home, but ultimately to go through the steps of the Shoemaker Protocol again. But what if that doesn’t work, especially when patients have already been doing this?
• If actinos grow back in two hours, is healing even possible? Towels that air dry aren’t completely dry in that time, creating an ongoing opportunity for more actino growth.
• If most homes and building structures harbor actinos, and most individuals are shedding actinos, are we inhaling and absorbing these particles anytime when we leave our actino-free home? So no airplanes, grocery stores, public transportation, restaurants, gym, schools, or movie theaters—basically anywhere people, moisture, or fabric surfaces exist? Based on Shoemaker’s research, even after completing an actinos protocol, actinos reexposure can cause the body to start producing extracellular vesicles (EVs) again, creating a perpetual cycle of CIRS immune activation. 
• Oftentimes, antibiotics are suggested with stubborn actino levels, but what about the rise of opportunistic fungi when there are no bacteria to compete? Are antibiotics safer than antifungals? We discuss this more later in this article.
• Are we doing more harm than good? One review found that over 50% of the bacterial population on healthy skin belongs to actinos, including Cutibacterium (previously known as Propionibacterium) and Corynebacterium. 

 

Avoiding exposure would require isolation from other people’s actino shedding and even from pets, which is not realistic nor sustainable. Last we checked, the 85-year Harvard study found that human connection is the number one ingredient for longevity. 

 

Okay, so if maybe it’s not actinos, what about other pieces of the puzzle?

 

To better understand these complex cases, we’ve pursued other drivers, including vector-borne illnesses and coinfections, such as Lyme disease, as well as researching other schools of thought in the environmental illness space. This led us to closely examine Shoemaker’s vehement stance against the use of systemic antifungals, particularly the azole class, which he advises against due to potential risks for CIRS patients. This exploration reviews the nuanced risk-benefit profile of antifungals and how they might fit into a layered, holistic approach for CIRS care.

 

Our commitment to patients who have not yet achieved full healing drives this research since actinos harder just isn’t good enough. Our practice is not married to any diet or protocol. We never opt for dogma as we are dedicated to finding solutions for every individual until they can achieve remission and experience a symptom-free life they deserve. 

 

We will critically assess Shoemaker’s antifungal stance, explore the scientific and clinical rationale behind it, and share our perspective on how antifungals may play a strategic role in CIRS treatment.

 

Key Takeaways

• CIRS is a complex biotoxin-related illness, and some patients don’t fully recover with the Shoemaker Protocol alone.
• Dr. Shoemaker’s antifungal caution is based on theoretical effects of azole antifungals on VDAC, mTOR, VEGF, and NeuroQuant brain changes.
• Many other medications, supplements, diets, and lifestyle tools used in CIRS care can also suppress mTOR and VEGF, not just azole antifungals.
• Low VEGF levels and abnormal NeuroQuant patterns have many possible causes, so they can’t prove azole toxicity by themselves.
• Functional and integrative medicine practitioners may use antifungals when fungal colonization is driving ongoing immune activation in CIRS.
• Antibiotics and binders used in CIRS can also affect mitochondria, blood flow, and brain health, so risks and benefits must be weighed on a case-by-case basis.
• VIP therapy, nutrient-dense diets, exercise, and nervous system support can help protect gray matter and support recovery alongside biotoxin treatment.
• Our practice is grateful for Shoemaker’s work but stays non-dogmatic, using a personalized approach that may include antifungals when clinically appropriate.

 

 

What Is CIRS?

 

 

CIRS (Chronic Inflammatory Response Syndrome) is a complex, multi-system illness triggered when the body is exposed to biotoxins, biological toxins of a certain molecular weight from mold, bacteria, or other environmental sources, and can’t shut off the resulting inflammatory response. People with a genetic susceptibility are unable to clear these toxins effectively, which causes persistent immune activation and widespread inflammation throughout the body.

 

Rather than causing isolated symptoms, CIRS affects multiple systems simultaneously. Clinically, these manifestations are categorized into 13 symptom clusters, reflecting the diverse ways biotoxins disrupt the body. 

 

 

These clusters include neurological, cognitive, and psychiatric effects; pulmonary and sinus issues; hormonal and endocrine dysregulation; cardiovascular disturbances; gastrointestinal dysfunction; musculoskeletal complaints; dermatological changes; ocular and visual disturbances; immune hypersensitivity; sleep disturbances; pain syndromes; autonomic nervous system dysregulation; and chemical or environmental sensitivities.

 

 

Because CIRS impacts so many systems at once, patients typically experience complex, overlapping symptoms that are easily misunderstood or misdiagnosed. Diagnosis requires careful evaluation of symptom patterns, environmental exposures, and specialized laboratory markers, while effective treatment relies on a multi-step, personalized approach to reduce biotoxin burden, modulate inflammation, and restore systemic balance. 

 

You can learn more in-depth about CIRS here.

 

What Is the Shoemaker Protocol?

 

 

Dr. Ritchie Shoemaker is a physician and researcher who has spent decades studying and pioneering CIRS. Through careful clinical observation, he discovered how biotoxins can trigger persistent immune system dysfunction in genetically susceptible individuals. 

 

His work laid the foundation for what is now considered the Shoemaker Protocol, a structured, stepwise approach for diagnosing and treating CIRS that has become a cornerstone in biotoxin-related illness care.

 

The Shoemaker Protocol works by targeting the root causes of CIRS. It begins with removing ongoing exposure: identifying and addressing mold, water-damaged environments, and other biotoxin sources to prevent continued immune activation. Next, it uses prescription binders such as cholestyramine (CSM) or Welchol (colesevelam) to capture circulating biotoxins in the gut, preventing their reabsorption and helping the body clear them safely.

 

From there, each subsequent step of the protocol is designed to correct the specific immune and hormonal disruptions caused by the biotoxin pathway. This includes addressing chronic inflammation, cytokine imbalances, autonomic nervous system dysfunction, and endocrine disruptions. The Shoemaker Protocol systematically restores these systems, helping the body regain balance and supporting multi-system recovery.

 

Importantly, antifungal medications are not included in the protocol. 

 

What Are Azole Antifungals?

 

 

Antifungals are medications designed to inhibit the growth of fungi or eliminate fungal infections. They work by targeting fungal cell structures or processes that are distinct from human cells, making them selectively toxic to fungi while generally sparing human tissues. 

 

Antifungals are widely used for conditions ranging from superficial infections, like athlete’s foot or oral thrush, to systemic fungal infections that can threaten vital organs.

 

Azole antifungals are a subclass of antifungal medications. They work mainly by blocking enzymes that fungi need to make  ergosterol, a key part of their cell membranes. By disrupting ergosterol production, azoles damage fungal cells, ultimately preventing fungal growth or leading to cell death.

 

Common azole antifungals include:

• Itraconazole (Sporanox)
• Fluconazole (Diflucan)
• Voriconazole (Vfend)
• Posaconazole (Noxafil)
• Isavuconazole (Cresemba)
• Ketoconazole (rarely used systemically today due to toxicity risks)
• Clotrimazole, Miconazole, Econazole, Oxiconazole (primarily topical formulations)

 

In the context of mold-related illness or CIRS, azole antifungals are often times prescribed by practitioners outside of the traditional Shoemaker Protocol. Clinicians aim to use these medications to reduce fungal burden, particularly when patients demonstrate chronic sinus colonization or systemic fungal overgrowth (e.g., in the gut). 

 

The rationale is that reducing the fungal load may mitigate ongoing immune activation and symptom persistence in patients with mold or biotoxin exposure. We have come to believe that if antifungals are used, timing and context matter, but they can be a viable option in stubborn cases—and a much more viable option than the actinos protocol. 

 

Important Terminology for Discussion

 

 

While this part gets technical, it’s very important to understand a few key concepts and why Shoemaker ultimately believes that antifungals are not ideal for a CIRS-impacted individual. By understanding these concepts, you can understand his theorized position on the potential impact of antifungals and CIRS.

 

VDAC (Voltage-Dependent Anion Channel)

 

 

Think of VDAC (voltage-dependent anion channel) as a gate on the mitochondria, the cell’s energy factories. This gate controls how energy and nutrients move in and out of the cell, letting molecules like ATP, ADP, calcium, and other nutrients flow so the cell can produce energy and stay balanced.

 

• ATP (adenosine triphosphate) is the cell’s main energy currency, powering everything from muscle contraction to brain signaling.
• ADP (adenosine diphosphate) is what’s left after ATP has been used; it is recycled back into ATP in the mitochondria.
• VDAC allows small molecules and ions to pass in and out. Essential nutrients like phosphate, pyruvate, and NADH (Nicotinamide Adenine Dinucleotide + Hydrogen) move through this gate to fuel mitochondrial processes. 
• VDAC also regulates calcium, which acts as a signaling molecule for numerous cellular processes, including energy production, enzyme activation, and cell survival.
• Metabolites, small molecules produced during metabolism, are transported through VDAC to fuel energy generation and maintain proper cellular function.

 

When VDAC functions properly, mitochondria efficiently produce ATP, giving cells the energy they need to thrive. But when VDAC is blocked or dysfunctional, energy production slows dramatically. 

 

Cells can then no longer function efficiently, entering an energy crisis where essential tasks such as repair, detoxification, signaling, and communication begin to fail. This energy shortage produces symptoms of fatigue, brain fog, poor tissue repair, and systemic stress, which are hallmark experiences for many CIRS patients.

 

Another important term is VDAC1 (Voltage-Dependent Anion Channel 1). VDAC is the general term for the entire family of mitochondrial channels that regulate exchanges between the mitochondria and the rest of the cell. VDAC1 is one specific member of that family that has been studied and VDAC1 is the most abundant form.

 

mTOR (mechanistic Target of Rapamycin)

 

 

mTOR (mechanistic Target of Rapamycin) is often called the cell’s growth and repair manager. It is a master regulator that monitors the cell’s environment and decides whether conditions are favorable for growth, repair, and energy production.

 

mTOR is activated by key signals, including:

• Nutrients, especially amino acids, are raw materials for building proteins and essential for mTOR activation.
• Insulin signals to the cell that energy and nutrients are available. 
• Oxygen supports energy production in the mitochondria.
• VDAC (voltage-dependent anion channel)/ATP (adenosine triphosphate) shows how much energy the mitochondria are making and whether the cell has enough fuel.

 

When active, mTOR regulates cell growth and repair, keeps metabolism running efficiently, boosts mitochondrial function to meet energy needs, and promotes the production of VEGF (vascular endothelial growth factor) to support blood vessel formation and tissue oxygenation.

 

When mTOR is underactive, such as during mitochondrial stress or energy depletion, these processes slow down. Cells repair themselves inefficiently, VEGF levels drop, and blood flow to tissues, including the brain and nerves, is reduced. This is another contributing factor to fatigue, cognitive dysfunction, poor tissue recovery, and systemic stress typical in CIRS.

 

Conversely, when mTOR is overactive, as seen in certain cancers, it can drive uncontrolled cell proliferation and abnormal blood vessel growth. Maintaining balanced mTOR activity is critical for both cellular health and overall tissue function.

 

VEGF (Vascular Endothelial Growth Factor)

 

 

VEGF (vascular endothelial growth factor) acts like a traffic controller for blood vessels, signaling the body to grow new vessels and maintain proper circulation. This ensures that oxygen and essential nutrients reach tissues efficiently, particularly energy-demanding organs like the brain and nerves.

 

When VEGF levels are too low, blood flow is reduced, leading to hypoxia, a state where tissues and neurons do not receive enough oxygen. Over time, chronic low VEGF is linked to gray matter atrophy (brain shrinkage), as neurons and supporting glial (non-neuronal brain) cells struggle to survive and repair themselves. The resulting stress shows up as cognitive dysfunction, memory issues, slowed processing, fatigue, and overall neurological vulnerability. Low VEGF reduces blood flow and nutrient delivery to cells, making it even harder for mitochondria to get the fuel they need, worsening the energy crisis caused by VDAC problems.

 

Pro-Tip: Clinically, we find that individuals with very low VEGF (and total cholesterol of <180 mg/dL) have a higher risk of low mood and suicidal ideation.

 

On the other hand, excess VEGF can make blood vessels abnormally leaky, which can promote tissue edema (swelling) and more inflammation, as seen in conditions like cancer or diabetic retinopathy.

 

In short, VEGF acts as a critical link between energy supply and tissue function. The right amount keeps blood flowing to neurons and mitochondria, supporting brain function and energy, while too little or too much can disrupt both circulation and cell health.

 

How VDAC, mTOR, and VEGF Work Together

 

 

1. VDAC (voltage-dependent anion channel) → mTOR (mechanistic Target of Rapamycin): If VDAC is open, mitochondria function normally, produce energy like ATP, and keep mTOR active. If VDAC is blocked, energy production stalls, and mTOR is suppressed.
2. mTOR → VEGF (vascular endothelial growth factor): mTOR stimulates VEGF production. mTOR also supports more healthy blood vessel growth via higher VEGF. If mTOR is inhibited, this means less VEGF and reduced tissue blood flow.
3. VEGF → VDAC: VEGF maintains healthy blood flow to supply mitochondria with the oxygen and nutrients needed for VDAC to function properly. When VEGF is low, oxygen levels drop, increasing mitochondrial stress and triggering a feedback loop of dysfunction.

 

 

To summarize:
VDAC controls mitochondrial energy → that energy keeps mTOR active → mTOR increases VEGF → VEGF maintains blood flow → blood flow supports VDAC.

 

This loop is critical for brain function, tissue repair, and overall healing. Disruptions anywhere in this cycle, such as with CIRS, can cause widespread dysfunction. Restoring these pathways is key to CIRS recovery and lays the foundation for understanding Shoemaker’s position on antifungals.

 

Shoemaker’s Concerns With Azole Antifungals

 

 

Shoemaker’s caution about the azole class of antifungals applies specifically to CIRS patients, who already experience chronic neuroinflammation, measurable brain volume loss on NeuroQuant (NQ) scans, and increased susceptibility to mitochondrial and blood flow impairments.

 

Let’s explore these concerns in greater depth, examining the physiological mechanisms and clinical rationale behind his stance against antifungals.

 

vDAC, mTOR Inhibition, and Inflammatory Pathways Activation

 

 

Shoemaker has observed that azole antifungals can disrupt inflammatory pathways in some CIRS patients, particularly those with genetic susceptibility linked to specific HLA (human leukocyte antigen) genetic haplotypes. In these individuals, this disruption may trigger an exaggerated neuroinflammatory response that, over time, contributes to structural changes in the brain.

 

The mechanism behind this effect centers on the inhibition of the mTOR pathway. Azoles such as itraconazole can interfere with mitochondrial function and disrupt key cellular signaling networks involving mTOR, VDAC, and VDAC1. These disruptions may hinder neuronal energy production, increasing the risk of neurodegeneration in individuals who are already vulnerable.

 

In addition, there is indirect evidence that azoles may suppress VEGF. Reduced VEGF can compromise oxygen delivery to the brain, which may contribute to low blood flow, neuronal stress, and, in the long term, grey matter vulnerability or atrophy.

 

Together, these cellular effects, VDAC disruption, mTOR inhibition, and VEGF suppression, form the basis for Shoemaker’s caution regarding azole use in CIRS patients.

 

NeuroQuants and Brain Matter Atrophy

 

 

Shoemaker uses NeuroQuant, an advanced MRI tool that measures the size of specific brain regions to detect subtle structural changes in CIRS patients. Unlike a standard MRI report, which provides a visual interpretation, NeuroQuant gives precise numerical data on gray and white matter volumes. This allows clinicians to identify patterns of brain shrinkage or swelling that may reflect inflammation, toxin exposure, or impaired blood flow, helping connect structural changes to functional symptoms seen in CIRS.

 

In patients treated with azole antifungals, Shoemaker has observed reductions in gray matter volume and cortical atrophy, which he links directly to the cellular mechanisms discussed above: VDAC disruption, mTOR inhibition, and VEGF suppression. Essentially, he posits that impaired mitochondrial energy production and suppressed blood vessel growth compromises neuronal health, leading to measurable brain tissue loss over time.

 

Shoemaker correlates that these structural changes correspond with clinical manifestations, including worsening cognitive function, memory loss, and increased fatigue.

 

Now that we’ve outlined Shoemaker’s mechanistic argument against azole antifungals and the supporting NeuroQuant data, we will move into in-depth source reviews of the studies that form the basis of his caution. This will set the stage for a comprehensive evaluation of the overall concerns surrounding azole use in CIRS patients.

 

Analysis of Shoemaker’s Azole Antifungal Stance Sources

Here are the studies Shoemaker references for his azole antifungal argument:

 

Study #1: Puurand et al. 2019

 

 

Shoemaker’s concern about azole antifungals in CIRS patients comes from a 2019 study by Purrand et al., which looked at how certain cell proteins (βII and βIII forms of tubulin) interact with VDAC, a key channel on the outer membrane of mitochondria.

 

Remember, VDAC works like a gate that controls how energy molecules (ATP, ADP), calcium, and nutrients move in and out of the mitochondria. This process is essential for keeping up with the energy demands of organs such as the brain, heart, and muscles.

 

The study found that βII and βIII tubulin can bind to and partially close the VDAC gate, limiting how much energy mitochondria can produce. In some diseases, such as cancer, excess βIII-tubulin can block VDAC, forcing cells to rely more on sugar for energy rather than mitochondria (the Warburg effect).

 

Shoemaker believes some azole antifungals, such as itraconazole, might similarly interfere with VDAC, further restricting mitochondrial energy production. In CIRS patients, whose mitochondria and nervous systems are already under stress, this could worsen inflammation or contribute to brain atrophy, as he posits is reflected in NeuroQuant scans showing reduced gray matter and cortical volume.

 

 

It’s important to note that while the Purrand study:

• Demonstrates how tubulins regulate VDAC and mitochondrial energy flow, especially in the brain, heart, and cancerous tumors
• Shows that if VDAC is blocked, cells lose energy when oxygen and nutrients are limited
• Explains how excess βIII-tubulin can push cells toward sugar-based energy (Warburg effect)

 

…the study does not directly examine azole antifungals or CIRS patients, nor does it provide clinical evidence that azoles cause brain atrophy. Shoemaker’s conclusion is a theoretical interpretation of these cellular mechanisms, supported by his own clinical observations in CIRS cases. Additionally, he has never shared these patient cases, even in redacted form, with any CIRS-certified practitioner, and our thorough review found no evidence that he ever has. This leaves his clinical observations as claims without independent clinical verification or reproducibility.

 

(We hold similar concerns with the GENIE test, as the methods used to select and validate its gene targets remain unclear or reproducible, but that is a separate topic for another day.)

 

Study #2 and #3: Head et al., 2015, 2017

 

 

The remainder of Shoemaker’s caution against azole antifungals is built on insights from two studies by Head et al. (2015, 2017). These studies were conducted in the cancer space to explore itraconazole for potential anti-cancer and anti-angiogenic effects. 

 

While these studies focus on cancer, Shoemaker applies the same endothelial and tumor-cell mechanisms to susceptible CIRS patients, arguing that similar mitochondrial and vascular stress pathways are involved.

 

The research aimed to explain why itraconazole was seen to slow tumor growth and block new blood vessel formation, as its exact mechanism had been unclear. Scientists found that itraconazole directly affects two key cellular systems: VDAC1 and mTOR signaling.

 

Specifically, itraconazole:

• Binds to VDAC1, disrupting mitochondrial function, nutrient sensing, and energy regulation
• Inhibits mTOR signaling, which is often overactive in cancer
• Suppresses VEGF signaling, blocking the formation of new blood vessels, which tumors require for growth
• Targets VDAC and mTOR simultaneously, which is especially effective at preventing new blood vessel formation

 

These findings provide a direct pharmacological link showing that itraconazole can impact mitochondrial function and cellular signaling pathways that regulate energy metabolism and blood vessel growth. 

 

 

Shoemaker applies these mechanistic findings to CIRS-affected individuals. He infers that in CIRS, individuals with chronic neuroinflammation, brain volume loss, and fragile blood flow regulation, the same pathways could become disrupted. This would then cause CIRS-affected individuals to have worsened mitochondrial stress and reduced oxygen and nutrient delivery to the brain when using azoles. 

 

Overall Concerns With Shoemaker’s Azole Stance

While these studies reflect potential and theoretical concerns within the context of CIRS patients and azole antifungals, there are important limitations and considerations to understand.

 

Limited Direct Evidence in CIRS Patients

 

 

Even though azoles have been associated with side effects such as headache, dizziness, and neurotoxicity, there is no direct clinical evidence demonstrating that azoles cause brain atrophy in CIRS patients or other populations. 

 

Shoemaker’s stance relies heavily on clinical observations and NeuroQuant imaging data in the CIRS population, who are already at risk for brain atrophy, rather than randomized controlled trials. To reiterate, he has never released any of these clinical observations with corresponding NeuroQuant data, even to the physicians he has personally trained. The foundational studies he cites show molecular effects in cancer or endothelial cells, but these are not proof of actual harm in CIRS patients at therapeutic doses. 

 

We could test this hypothesis by comparing individuals before any CIRS or mold treatment, using pre- and post-treatment NeuroQuant scans to map brain structure and correlate those findings with typical CIRS labs and symptoms. Two groups could then be followed: one receiving the standard Shoemaker Protocol and the other the same protocol plus antifungals, while keeping lifestyle and environmental factors constant. 

 

Even in this theoretical study, it would still be challenging to determine whether any observed brain atrophy was caused by the antifungals or by the underlying CIRS illness itself. NeuroQuant results can also be influenced by multiple factors, many of which are discussed later in this paper, making it difficult to isolate the effects of any single variable, such as antifungal use.

 

Mechanistic vs. Clinical Translation

 

 

Studies demonstrate that itraconazole and other azoles can impact VDAC, mTOR, and VEGF pathways, which could theoretically affect mitochondrial energy production, cellular repair, and blood flow. While the mechanistic data are real, the actual translation to CIRS patients at standard therapeutic dosing remains unproven in clinical practice. 

 

Patients should understand that although these mechanisms exist, the risk of harm in typical medical use is largely theoretical.

 

Potential Confounders from Underlying Disease

 

 

Many CIRS patients already experience brain atrophy, cognitive symptoms, or reduced blood flow as a result of chronic inflammation, cytokine dysregulation, or other systemic factors. These underlying disease processes make it difficult to determine whether observed brain changes are directly caused by azole therapy or by the natural progression of CIRS itself. 

 

Consequently, symptoms such as fatigue, memory loss, or difficulty concentrating could be attributed to the underlying illness rather than antifungal treatment. Careful evaluation and individualized clinical judgment are necessary, and not simply relying on a NeuroQuant result.

In addition to the underlying disease processes themselves, there are other factors that can suppress mTOR through mechanisms similar to azoles, further complicating the picture.

 

What Else Impacts mTOR Suppression?

 

 

To reiterate, Shoemaker’s strong stance against azole antifungals is largely built on the idea that these drugs inhibit mTOR, disrupt mitochondrial function, and potentially contribute to brain atrophy in CIRS patients. However, mTOR is a highly sensitive pathway influenced by a wide variety of factors beyond azoles. Medications, natural compounds, supplements, lifestyle behaviors, and even certain dietary patterns can all reduce or inhibit mTOR activity.

 

The concern is that the changes he attributes to azoles could be influenced by other mTOR-suppressing factors. Here are common examples of additional influences:

 

Medications

 

Within the Shoemaker Protocol, certain medications are considered essential. Some of these drugs also affect mTOR. Understanding these effects is important because it shows why blaming azole medications alone for mTOR suppression or brain inflammation can give an incomplete picture.

 

Cholestyramine (CSM) and Welchol (colesevelam) are two bile-acid sequestrants used as key binders in the Shoemaker Protocol. Their main job is to grab onto biotoxins in the gut so they can’t be reabsorbed. This helps remove toxins from the body and supports the immune system as it tries to recover.

 

Research shows that medications such as cholestyramine and Welchol can lower levels of FGF19, a hormone released by the gut when bile acids are present. Since FGF19 normally helps activate mTOR and support cell growth and metabolism, lowering FGF19 can indirectly decrease mTOR activity.

 

These binders also change how the body absorbs certain fat-based nutrients and signaling molecules, including cholesterol-related compounds. Many of these molecules act as upstream activators of mTOR. Since cholestyramine and Welchol reduce these activators, they can temporarily lower mTOR activity. This helps explain that even essential CIRS treatments can influence the mTOR pathways discussed by Shoemaker.

 

Doxycycline is another medication commonly used as a first-line treatment for acute Lyme disease and may also be part of chronic Lyme treatment plans. Some CIRS clinicians use doxycycline alongside other adjunct therapies because Lyme bacteria can act like biotoxins, worsening CIRS by triggering ongoing inflammation and immune imbalance.

 

Besides its role as an antibiotic, research shows that doxycycline can reduce the growth of new blood vessels and change the activity of an enzyme called MMP-9 (matrix metalloproteinase-9). Both of these actions can influence mTOR signaling. When VEGF-driven blood vessel growth is reduced and when MMP-9 activity changes the structure of tissues, these shifts can send signals back to cells that result in lower mTOR activity.

 

Natural Compounds and Supplements

 

Besides prescription medications, many natural compounds and supplements commonly used in CIRS support plans also affect mTOR signaling. Understanding these effects shows why mTOR suppression in CIRS patients can’t be blamed only on azole antifungal drugs.

 

Omega-3 fatty acids are frequently used in CIRS treatment as part of a lipid replacement therapy. This therapy is usually started before taking prescription binders such as cholestyramine or Welchol to improve tolerance and reduce stomach issues. Omega-3s help repair cell membranes and also slightly lower mTOR activity and reduce signals that promote new blood vessel growth.

 

Resveratrol is another supplement commonly recommended to help lower high TGF-β1(transforming growth factor beta 1), which is frequently elevated in CIRS, and to provide general anti-inflammatory benefits. Resveratrol works by activating AMPK (AMP-activated protein kinase), an energy-sensing enzyme that then lowers mTOR activity. It also reduces blood vessel growth signals.

 

Quercetin is widely used to reduce inflammation, support people with histamine intolerance or MCAS (mast cell activation syndrome), and help those dealing with long COVID—all of which are common in CIRS. Quercetin lowers both mTOR and VEGF signaling, giving it additional immune and vascular-balancing effects.

 

Curcumin and EGCG (epigallocatechin gallate) are two more anti-inflammatory compounds sometimes recommended by CIRS practitioners. Both can reduce mTOR activity. However, curcumin is usually avoided in our practice because it is high in oxalates, which can worsen other metabolic problems.

 

Berberine is an herbal antimicrobial sometimes used in protocols for SIBO, SIFO, and Lyme disease, conditions that frequently appear alongside CIRS. In addition to fighting microbes, berberine also inhibits mTOR. This further shows how many supportive therapies in CIRS can influence the same metabolic pathways that some attribute to azole antifungals.

Just logically speaking, if a patient is taking any of these supports, how do we know mTOR is inhibited from azoles, cholestyramine, Welchol or one of these adjunct supports?

 

Lifestyle Factors

 

 

Beyond medications and supplements, certain lifestyle practices commonly used in CIRS support can also affect mTOR signaling.

 

Fasting and intermittent fasting are tools that some CIRS patients use. These approaches lower the body’s nutrient signals, which strongly decreases mTOR activity. When the body has less glucose and fewer amino acids available, it shifts from growth mode into repair and maintenance mode.

 

Calorie restriction may also be considered by some patients who experience weight gain or metabolic changes related to CIRS. While we do not recommend long-term calorie restriction or undereating, especially during healing, it’s important to understand that eating fewer calories lowers IGF-1, insulin, and amino acids. All of these normally activate mTOR, so reducing them naturally slows the mTOR pathway.

 

Exercise is another lifestyle factor that influences mTOR. Both aerobic exercise and resistance training activate AMPK, an energy-sensing enzyme that temporarily lowers mTOR activity. Exercise also helps regulate the nervous system and supports neurogenesis, the growth of new brain cells, which is extremely important for CIRS recovery. Because of these benefits, we encourage patients to engage in movement they can tolerate as a core part of their CIRS care.

 

Diets

 

 

Diet is another important factor that can affect mTOR activity, and various diets commonly used by CIRS patients may lower mTOR on their own, separate from any effects of azole medications.

 

Keto and low-carb diets reduce the amount of glucose available in the body. This can indirectly lower mTOR activity because the body releases less insulin and gets fewer nutrient signals that normally tells cells to grow. Low-protein diets also decrease mTOR activity. When the body has fewer amino acids, particularly leucine, which is one of the strongest activators of mTOR, cells receive fewer signals for growth and repair.

 

Plant-based diets, especially those that are low in protein or high in polyphenols, may also reduce mTOR. These diets provide fewer nutrient signals and contain natural compounds that can inhibit mTOR. Time-restricted eating, or structured eating windows, can temporarily lower the nutrients available in the bloodstream. This reduces insulin release and lowers amino acid levels, which decreases stimulation of mTOR and supports the body’s maintenance and repair pathways.

 

mTOR Suppression Key Takeaways

 

 

mTOR is a major pathway that controls cell growth, repair, metabolism, and blood vessel formation. Because of this, both too much activity and too little activity can cause problems. When mTOR stays highly activated for too long, it can keep inflammation going and support unwanted tissue growth, including tumors, biofilms, or even mold colonies.

 

However, pushing mTOR too low, whether through multiple antifungals, medications, supplements, or certain diets and lifestyle habits, can also cause issues. Too much suppression can slow healing, reduce mitochondrial energy, and limit healthy blood flow to the brain, especially if VEGF is already low.

 

For CIRS patients, the goal is finding the right balance for healing.

 

Using mTOR suppression in a pulsed or moderate way helps the body activate repair and cleanup processes such as autophagy and targeted antifungal activity, while still allowing the body to regenerate tissues and maintain enough blood flow for proper healing. Knowing how medications, natural compounds, lifestyle choices, and diet all affect mTOR shows that this pathway is flexible and should be individually tailored rather than over-restricted.

 

Pro-Tip: If you’re thinking about mTOR suppression for cancer, it’s important to remember that mTOR is not the root cause of cancer. It simply responds to what’s happening in the cell. Drugs like rapamycin, everolimus, or itraconazole can slow tumor growth by reducing nutrient use and blood vessel formation, but they address the symptoms, not the underlying causes. Long-term suppression can also weaken the immune system and slow tissue repair. mTOR inhibition can help temporarily, but it does not fix the metabolic or environmental factors that drive cancer growth in the first place.

 

What Causes Low VEGF?

 

 

Another key component of Shoemaker’s concern about azole antifungals is that they may lower VEGF. While this is possible, as we saw with mTOR causes, many other internal and external factors can also cause low VEGF. Azoles are not the sole explanation.

 

It’s also important to remember that the lab markers used in CIRS are not specific to CIRS alone. Shoemaker’s diagnosis criteria rely on a combination of immune markers, symptom patterns, VCS testing, and medical history—not on any single lab result by itself.

 

 

Immune and Infection-Related Factors

• Low MSH (melanocyte-stimulating hormone) and high C4a in mold-sensitive individuals can suppress VEGF production
• Chronic Lyme disease and other coinfections cause immune dysregulation that reduces VEGF signaling
• Long-term mold exposure, even at low levels, contributes to chronic suppression of VEGF

 

Lifestyle Factors

• Lack of sunlight and low vitamin D, which impair endothelial signaling can reduce VEGF
• Poor oxygenation from being sedentary reduces blood flow stimulus
• Chronic stress and elevated cortisol blunt growth factor production
• Smoking or vaping damages endothelial function
• Certain EMF exposures (e.g., low-frequency or radiofrequency) may impair blood-brain barrier integrity, increase permeability, and disrupt VEGF signaling, potentially reducing cerebral perfusion

 

Dietary Factors

• Low-protein or low-fat diets deprive the body of amino acids and fat-soluble vitamins critical for endothelial repair (e.g., arginine, cholesterol, vitamins A, D, E, and K2)
• Low omega-3 intake (EPA/DHA) reduces endothelial support
• Excess polyunsaturated fats and seed oils contribute to oxidative damage in blood vessels
• Inadequate antioxidants such as glutathione, CoQ10, and vitamin C impair vascular health
• Diets lacking adequate micronutrients, especially if mineral stores are depleted

 

Medications, Illnesses, and Physiological Stressors

• Corticosteroids (e.g., prednisone) suppress VEGF production
• Statins may reduce VEGF in some individuals
• Poor thyroid function, especially low T3, impairs vascular remodeling
• Diabetes and insulin resistance cause microvascular damage and alter VEGF signaling
• Anemia or hypoxia (oxygen deprivation) without adaptation downregulates VEGF production
• Mitochondrial dysfunction reduces the energy needed to produce VEGF
• Poor nitric oxide signaling limits blood flow and vascular growth
• Toxins such as heavy metals or pesticides damage endothelial cells and blunt VEGF expression

 

The big takeaway is that VEGF suppression is not caused by a single factor. While azole antifungals can contribute, it’s one of many influences, including immune dysregulation, chronic infections, lifestyle, diet, medications, and environmental exposures. 

 

Pro-Tip: If you’re looking for additional supports for low VEGF levels outside of mold treatment, you can explore the following if tolerated: moderate exercise and movement, heat exposure to increase blood flow (e.g., sauna), oxygen therapies (e.g., HBOT, EWOT, breathwork), nutrient-dense supports (e.g., meat-based diet with collagen, omega-3s), and supplements (e.g., arginine, vitamin D3, vitamin K2, CoQ10, and resveratrol).

 

What Impacts NeuroQuants?

 

 

Since Shoemaker uses NeuroQuant brain imaging as his main evidence against azole antifungals, it’s important to understand what actually affects NeuroQuant results. Shoemaker argues that certain brain volume patterns seen in CIRS patients support his concerns about azoles. While NeuroQuant can measure brain structures in great detail, interpreting these findings is very complicated.

 

NeuroQuant data is extremely sensitive, and many other health issues, separate from CIRS or antifungal use, can change brain volumes. Chronic pain, psychiatric medications, substance use, and various neurological conditions can all affect NeuroQuant results on their own.

 

It is also difficult in both research and clinical practice to fully rule out other chronic infections, such as Lyme disease, other vector-borne illnesses, or long COVID. Without controlling for these factors, it is impossible to say that any specific brain change is caused directly by azole antifungals.

 

Shoemaker has described NeuroQuant patterns he believes are linked to different conditions:

 

Water-damaged building CIRS:

• Increased forebrain parenchyma
• Increased cortical gray
• Increased hippocampus
• Increased pallidum
• Decreased caudate
• Increased cerebellum
• Normal thalamus and putamen

 

Lyme disease:

• Increased thalamus
• Increased cerebellum
• Decreased forebrain
• Decreased putamen
• Normal cortical gray, hippocampus, and caudate

 

However, in our clinical experience, these patterns are not disease-specific. For example, an enlarged thalamus is common in confirmed chronic Lyme patients, but it also appears in water-damaged building CIRS and other conditions. We see a lot of variation from patient to patient, which shows that NeuroQuant findings aren’t definitive and can’t reliably replace established testing methods.

 

Beyond infections and comorbidities, many other factors can change NeuroQuant results. Brain swelling, shrinkage, or volume shifts can come from numerous causes, and even technical issues during the scan can affect the measurements.

 

 

Brain Atrophy Causes

• Chronic inflammation (CIRS, autoimmune disease)
• Chronic infections (Lyme, EBV)
• Heavy metals (lead, mercury, aluminum)
• Pesticides, herbicides, VOCs
• Excitotoxicity: Overactivation of glutamate receptors (NMDA (N-methyl-D-aspartate) receptors) 
• Low VEGF (Poor blood flow, oxygen deprivation)
• Insulin resistance, high blood sugar
• Long-term sleep apnea, chronic sleep disruption (Impairs glymphatic clearance)
• Chronic stress and long-term elevated cortisol
• Elevated TGF-β1 (brain remodeling and tissue breakdown)
• Neurodegenerative diseases (Alzheimer’s, MS, Parkinson’s)
• Mitochondrial dysfunction
• Nutrient deficiencies (B12, choline, DHA, zinc, amino acids that can repair myelin, neurotransmitter/gut)
• Head trauma, traumatic brain injury (TBI): Localized neuron loss
• Long-standing depression or PTSD (post-traumatic stress disorder)

 

Swelling (Volume Gain) Causes

• Neuroinflammation (common in CIRS and Lyme)
• Elevated cytokines (IL-1, IL-6, TNF-α)
• High C4a (brain edema)
• MARCoNS (Multiple Antibiotic Resistant Coagulase Negative Staphylococci)  or chronic sinus infections (limbic swelling)
• Leptin resistance (neuroinflammation and metabolic inflammation)
• Recent immune activation (infection, vaccine, or flare)

 

Factors That Can Impact Scan Results

• Hydration status, dehydration may reduce brain volume
• Alcohol or substance use can distort cortical volumes
• Acute illness or fever can cause transient swelling
• Sleep deprivation can alter hippocampal and amygdala size
• Menstrual cycle and hormonal shifts can cause subtle volume changes (especially hippocampus)
• Medication effects (e.g., selective serotonin reuptake inhibitors (SSRIs), corticosteroids)

 

Technical Errors

• Improper scan alignment may falsely show asymmetry
• Outdated NeuroQuant software version
• Incorrect age-matching or reference database causes misinterpreted z-scores
• Scan field strength (1.5T vs. 3T MRI) causes resolution differences

 

Pro-Tip: This is why our practice doesn’t rely heavily on NeuroQuant results. There are too many variables that can alter brain volumes, leading to misleading conclusions if viewed in isolation. NeuroQuant data is highly sensitive, and multiple comorbidities can alter brain volumes independent of CIRS or antifungal use. Additional factors, including chronic pain, psychiatric medications, substance use, hydration, and other neurological conditions, can all influence NeuroQuant results.

 

Taken together, the numerous factors influencing mTOR suppression, VEGF levels, and NeuroQuant imaging patterns make it clear that attributing these changes solely to azole antifungal use is overly simplistic and not supported by science.

 

Beyond these considerations, there are additional aspects of VDAC signaling and mitochondrial function that further complicate Shoemaker’s argument, which we will explore next.

 

VDAC Considerations

While the points above about mTOR, VEGF, and NeuroQuant imaging provide strong reasons to question Shoemaker’s concerns about azole antifungals, it’s also important to note that he includes VDAC as a key part of his explanation.

 

Remember, VDAC is a major channel on the outer membrane of the mitochondria. It works like a gatekeeper, allowing important molecules, ions, and signals to move between the cell fluid (cytosol) and the space just inside the mitochondria.

 

But VDAC is not the only structure involved in this process; there are several other transporters and channels that also help move molecules in and out of the mitochondria.

 

This next section leans into the biochemical and reads like alphabet soup, but the key point is simple: VDAC is only one component of a much larger mitochondrial transport system. Several other channels also move fuel, ions, and proteins into the mitochondria, so focusing on VDAC alone gives an incomplete picture of how energy metabolism actually works. The following are some of the other supportive players:

 

Adenine Nucleotide Translocator (ANT)

The ANT (Adenine Nucleotide Translocator) sits in the inner mitochondrial membrane and helps swap ADP and ATP between the inside of the mitochondria and the space just outside it. ANT works closely with VDAC to keep the cell’s energy system running smoothly by making sure the ATP made in the mitochondria can move into the rest of the cell.

 

If VDAC isn’t working properly, ANT can still exchange ADP and ATP, but it can’t do it as well, which does lead to reduced overall energy transfer in the cell.

 

Mitochondrial Pyruvate Carrier (MPC)

The MPC (Mitochondrial Pyruvate Carrier) is located in the inner mitochondrial membrane and brings pyruvate into the mitochondrial matrix. Pyruvate is a key fuel that feeds the citric acid cycle, also called the TCA cycle or Krebs cycle, which is the process the mitochondria use to turn nutrients from glucose and fats into energy (ATP). VDAC helps pyruvate move into the intermembrane space first, before MPC pulls it into the matrix.

 

If VDAC is not working well, the MPC can still bring pyruvate into the mitochondria, so the citric acid cycle can still make some energy, although the whole process is less efficient.

 

Mitochondrial Calcium Uniporter (MCU)

The MCU (Mitochondrial Calcium Uniporter) brings calcium into the mitochondrial matrix. This calcium is important for cell signaling and for helping the mitochondria make energy. If VDAC isn’t working properly, the MCU can still bring calcium into the mitochondria, but the process is also less efficient.

 

SLC25 Family

The SLC25 family is a group of transport proteins in the inner mitochondrial membrane. They move important molecules, such as phosphate, dicarboxylates, and amino acids, into the mitochondria to help with energy production and overall metabolic balance.

 

Even if VDAC isn’t working well, these transporters can still do their job inside the mitochondria. However, the whole system may work less efficiently because fewer materials can reach the intermembrane space.

 

TOM/TIM Complexes

The TOM (Translocase of the Outer Membrane) and TIM (Translocase of the Inner Membrane) complexes are transport systems that move proteins made in the nucleus into the mitochondria. These proteins are essential for energy production, including the enzymes needed for the electron transport chain and ATP synthesis.

 

If VDAC is not working properly, the TOM/TIM complexes can still move proteins into the mitochondria, but energy production may not work as well. This is because VDAC problems reduce the flow of nutrients and metabolites that these imported proteins need in order to function fully.

 

Organic Anion Transporting Polypeptides (OATPs) and Carnitine Shuttle

OATPs (Organic Anion Transporting Polypeptides) are transport proteins that help move important molecules, including metabolites, nutrients, and signaling compounds, into cells and into mitochondria. These molecules support energy production and overall metabolic function. The carnitine shuttle is another transport system that carries fatty acids into the mitochondrial matrix, where they are broken down through beta-oxidation to produce ATP.

 

Both OATPs and the carnitine shuttle can continue moving their substrates even if VDAC is not working properly. However, as mentioned for other functions, energy production may be less efficient because VDAC problems reduce the flow of metabolites, ATP, and ions in the intermembrane space that these systems rely on to work at full capacity.

 

Other Small Anion Channels

These mitochondrial channels move ions like chloride, bicarbonate, and phosphate to help keep the mitochondrial matrix balanced and at the right pH. They work together with VDAC to regulate the flow of ions and metabolites, which supports energy production, ATP synthesis, and overall metabolic stability.

 

If VDAC is not working properly, these smaller anion channels can still function, allowing some ion and metabolite movement to continue.

 

VDAC Considerations Key Takeaways

Although VDAC is the main pathway for transporting ATP, ADP, pyruvate, phosphate, calcium, and small anions, other transporters and channels also facilitate their movement and help maintain mitochondrial stability once these molecules reach the intermembrane space.

 

In other words, VDAC is essential, but it is not the only transporter involved in mitochondrial metabolism. Even if VDAC function is disrupted, the other transporters and channels can still work, helping maintain metabolite flow and mitochondrial balance.

 

Nuance and context matter.

 

Other Factors That Impact VDAC Function Beyond Azole Antifungals

 

 

VDAC function can be affected by many internal and external stressors, showing that azole antifungals are far from the only thing that can change mitochondrial transport and the body’s energy balance:

 

• NSAIDs and chemotherapy drugs can damage mitochondria and change how VDAC works.
• Pro-inflammatory cytokines like IL-6 and TNF-α are often high during chronic infections or immune imbalance and can indirectly weaken VDAC function.
• Oxidative stress and high ROS levels can damage VDAC or nearby proteins, reducing metabolite flow.
• Biotoxins from mold, Lyme, and other CIRS-related exposures may affect VDAC indirectly by causing long-term immune activation and calcium problems.
• Calcium dysregulation, especially when calcium levels spike or aren’t well controlled, can overload mitochondria and disrupt VDAC.
• Viral infections, including HIV, hepatitis B, and SARS-CoV-2, can interfere with mitochondrial pathways, VDAC included, to avoid cell death and change host metabolism.
• Metabolic stress, such as low ATP, high blood sugar, or long-term oxidative stress, can decrease VDAC efficiency.

 

With that in mind, we can now take a closer look at how VDAC dysfunction may also relate to diet in the context of CIRS.

 

VDAC, Carbs, and Shoemaker’s Argument Against Keto and Carnivore Diets for CIRS

 

 

One reason our practice began exploring VDAC and cellular energy pathways is because we’ve repeatedly seen how a Carnivore or keto elimination diet can benefit patients with CIRS. For many, lowering carb intake reduces inflammation, a central driver of this illness, and helps restore energy and metabolic stability.

 

Despite this, Shoemaker has long cautioned against these diets for CIRS, citing potential risks tied to impaired VDAC function. After working one-on-one with thousands of clients, including hundreds of confirmed CIRS patients, we wanted to understand why such a contrast exists between his theory and what we consistently observe in clinical practice.

 

Our concern is that by minimizing the role of diet in healing, many patients lose access to one of the most affordable and powerful ways to improve mitochondrial function and energy production. When people assume that “whatever I eat is fine because the root cause is CIRS,” they overlook that CIRS itself is fundamentally a state of inflammation, low energy, and poor oxygen delivery. Nutrition directly supports ATP production and helps restore metabolic balance.

 

Shoemaker himself has stated that endotoxins are a greater contributor to illness than fungus, second only to actinos. If that’s the case, then supporting gut health and nutrition becomes an even more critical part of recovery. The gut is the primary source and regulator of endotoxins like lipopolysaccharides (LPS), and when its barrier is compromised, these toxins enter circulation and intensify inflammation.

 

A nutrient-dense, low-inflammatory diet strengthens the gut lining, improves detox, and reduces the systemic burden of endotoxins. Ignoring diet while acknowledging the role of endotoxins creates a contradiction; if endotoxins drive CIRS pathology, then optimizing gut health through proper (meat-based) nutrition should be viewed as an essential part of treatment.

 

Shoemaker’s argument against keto and Carnivore diets for CIRS patients is built, in large part, on the concept of impaired VDAC function. 

 

According to his theory, inflammation and biotoxins in CIRS can block VDAC channels in mitochondria, limiting the flow of ATP, ADP, pyruvate, inorganic phosphate, calcium, and other essential metabolites. He posits that when VDAC is impaired, mitochondria are less efficient at producing energy from fat—a key consideration for high-fat diets like keto or Carnivore. 

 

To bypass this bottleneck, Shoemaker argues that glucose provides a more readily available energy source. Through glycolysis, sugar can generate ATP independently of mitochondrial fat metabolism, offering quick, though less efficient, energy for the brain and body when mitochondrial pathways are sluggish. 

 

He notes that many patients with CIRS report feeling worse on fat-heavy diets but experience improved energy, oxygen delivery, and reduced neuroinflammation when consuming carbs. This forms the rationale behind his recommendation for including glucose in the diet until markers of inflammation and neuroimmune dysregulation, like TGF-β1, MMP-9, and VEGF, normalize.

 

 

To understand Shoemaker’s argument against keto and Carnivore diets, anchor it to a simple question: How does the body make energy?

 

He argues that when the VDAC gate in the mitochondria isn’t working well, the body can’t turn fat into energy efficiently. Fat is normally an excellent fuel source because one molecule of fat can produce about 129 ATP, but only if the mitochondria are functioning.

 

Glucose can make energy in two different ways.
• Aerobic metabolism: uses the mitochondria and produces about 36 ATP per glucose molecule.
• Anaerobic metabolism (glycolysis): bypasses the mitochondria and produces only about 2 ATP per glucose molecule.

 

Shoemaker’s point is that glycolysis still works even when mitochondria are struggling. From this, he concludes that CIRS patients “need” carbs (any carbs but ideally low amylose) because they provide a backup energy system that does not depend on healthy mitochondria.

 

But this conclusion is incomplete.

 

Aerobic glucose metabolism still requires mitochondria and is only moderately efficient. Anaerobic glycolysis produces very little energy (2 ATP) and cannot sustain the body long-term. So using carbs as a workaround is not as straightforward or reliable as his argument suggests.

 

This is why a blanket statement that CIRS patients “need” higher-carb diets, or that keto or Carnivore approaches inherently fail, does not make sense. Many CIRS patients can adapt to using fat for energy when inflammation is addressed and mitochondrial support is in place. For CIRS patients, a ketogenic or Carnivore approach works best when it’s introduced slowly and steadily. Logically, 129 ATP, even if inefficiently working, seems a lot better than 36 or even 2 ATP.

 

As noted earlier, in our clinical practice we have used Carnivore as a therapeutic tool for thousands of patients, including hundreds of confirmed CIRS cases. Our direct observations, along with the way this diet supports energy metabolism, lowers inflammation, and improves mitochondrial efficiency, continue to call into question the strength of Shoemaker’s VDAC-based argument. 

 

Additionally, we’ve observed that a subset of patients doesn’t fully recover using the Shoemaker Protocol alone. Traditional troubleshooting too often hyperfocuses on actinos testing and then restarting the protocol from step one. Essentially, the proposed solution becomes a repetition of the same steps rather than the introduction of new, actionable strategies. This pattern exposes a logic gap, raising valid questions about whether dietary restrictions and azole antifungal avoidance based on theoretical VDAC impairment are truly necessary for every patient.

 

In short, while impaired VDAC may indeed contribute to energy challenges in CIRS, the idea that all patients require glucose for energy, or that keto and Carnivore diets are inherently unsafe or ineffective, oversimplifies a complex metabolic picture and fails to account for individual variation, adaptive capacity, and alternative therapeutic strategies.

 

Pro-Tip: If you’re a CIRS patient who feels better when including some carbs in your diet, we’re simply recommending focusing on cleaner, whole food sources like organic, lower toxicity, low-amylose vegetables when possible. We strongly disagree with Shoemaker’s blanket recommendations against keto and Carnivore diets, as these approaches can be a lifeline for many struggling with CIRS and environmental illness. The most important factor is finding a personalized diet that supports your individual healing. For many patients, these diets provide the energy, mental clarity, and stability needed to navigate and sustain the demands of a complex recovery protocol.

 

The Role of Antibiotics

 

 

Now that we’ve taken a detailed look at the fundamentals of Shoemaker’s argument, covering VDAC, mTOR inhibition, VEGF suppression, and NeuroQuant imaging, it’s time to circle back and examine the role of antibiotics within the Shoemaker Protocol. 

 

While antibiotics are not necessarily considered an essential step in the protocol itself, their use is widely accepted by Shoemaker and his network of practitioners for managing CIRS patients, especially when there are co-infections like MARCoNS, SIBO, and even elevated actino levels.

 

This creates a perplexing inconsistency: if azole antifungals are strongly discouraged due to their potential impact on VDAC, why are antibiotics, which can also influence mitochondrial function, immune signaling, and other cellular processes, permitted?

 

Common Antibiotic Risks

 

 

The following are examples of common antibiotic risks:

 

Fluoroquinolones (e.g., Cipro, Levaquin): These antibiotics can damage mitochondrial DNA and the enzymes needed for the electron transport chain, which is essential for producing energy in cells. They are linked to serious side effects such as anxiety, psychosis, tendon rupture, and nerve damage. In some tissues, they may also lower VEGF, weaken collagen production, and increase oxidative stress. Because of these risks, fluoroquinolones have an FDA black box warning and are considered the highest-risk antibiotics for mitochondrial and neurological harm.

 

Tetracyclines (e.g., Doxycycline, Minocycline): Tetracyclines can interfere with mitochondrial protein production. Minocycline may offer short-term anti-inflammatory and neuroprotective benefits, but long-term use can still affect mitochondria. These drugs can also affect VEGF levels, with VEGF inhibition seen in tumor studies. They are often used in Lyme disease protocols for their antimicrobial and immune-modulating effects.

 

Macrolides (e.g., Azithromycin, Clarithromycin): Macrolides can mildly affect mitochondrial function, especially at high doses. They help reduce inflammation, which is why they are commonly used in chronic lung disease. However, long-term use may disrupt the gut microbiome and indirectly increase neuroinflammation. In the Shoemaker Protocol, azithromycin is used to treat MARCoNS colonization.

 

Metronidazole (e.g., Flagyl): Long-term use of metronidazole has been linked to brain inflammation (encephalopathy) and nerve damage. In sensitive people, it can harm DNA and mitochondrial membranes, reducing the cell’s ability to make energy. Although it is used for SIBO or protozoal infections, it should be used carefully in people with CIRS or mitochondrial weakness.

 

Sulfa Drugs (e.g., Bactrim): Sulfa antibiotics can interfere with cellular and mitochondrial methylation processes, which may lead to mitochondrial stress, especially when other stressors are present. They are used in Lyme and MARCoNS treatment, but long-term use is usually avoided in sensitive patients because of the risk of metabolic and mitochondrial strain.

 

Some antibiotics have been linked to brain shrinkage or neurodegeneration. This can happen directly through neurotoxicity or indirectly through gut-brain axis disruption, mitochondrial damage, or neuroinflammation. Certain antibiotics, including minocycline and fluoroquinolones, may also lower VEGF, which can reduce blood flow to the brain.

 

Long-term, repeated, or broad-spectrum antibiotic use can worsen neuroinflammation, mitochondrial dysfunction, and VEGF suppression. The use of antibiotics can thus create effects similar to some of Shoemaker’s concerns about azole antifungals.

 

Logically speaking, why does he accept one class of drugs but not the other?

 

Antifungals vs. Cholestyramine

 

 

Cholestyramine (CSM) is a bile acid sequestrant that plays a key role in the Shoemaker Protocol for treating CIRS and other biotoxin-related illnesses. Welchol (colesevelam) is another bile acid sequestrant used as a binder in CIRS. It has a different chemical structure and is not as strong as CSM, but it serves a similar detox purpose.

 

Both cholestyramine and Welchol work by binding negatively charged biotoxins in the gut, especially toxins from mold, Lyme, and other microbes. This prevents the toxins from being reabsorbed through enterohepatic circulation. By removing these circulating toxins, they help reduce inflammation and ease symptoms, which is why cholestyramine is considered an essential binder for many CIRS patients.

 

You can learn more about cholestyramine and the role of binders in CIRS here.

 

 

It’s important to understand that cholestyramine and Welchol do not kill fungi, bacteria, or parasites. They also do not break down biofilms or reach the lungs, sinuses, or small intestine, where fungal overgrowth often develops. They do not treat colonization, such as Candida in the gut or Aspergillus in the lungs.

 

Their main job is to remove circulating toxins, not to fight infections directly.

 

Antifungals work in a completely different way. Azole antifungals, such as itraconazole, which many functional practitioners consider the gold standard for fungal colonization management in CIRS, stop fungi from making ergosterol, a key part of their cell membrane. This weakens the fungi and slows their growth.

 

Itraconazole is usually used when there is confirmed fungal overgrowth, often after treating the gut first with nystatin. Nystatin targets gut fungi by binding to ergosterol and damaging fungal cell membranes.

 

Unlike cholestyramine, itraconazole does not bind or remove biotoxins.

 

What About Fungal Growth?

 

 

Because cholestyramine only removes biotoxins that are already circulating and recycling through the gut, it does not treat fungal growth directly. If a CIRS patient has fungal overgrowth, additional steps are needed to address the inflammation and immune problems it can cause.

 

Fungal growth refers to fungi multiplying in the body. It can appear in two main forms: colonization and invasion.

 

Fungal colonization happens when fungus grows on surfaces like the gut, sinuses, skin, or lungs without entering deeper tissues. It is usually not life-threatening, but it can still cause immune reactions, mycotoxin exposure, and chronic symptoms, especially in people who are genetically sensitive.

 

Fungal invasion occurs when the fungus breaks through tissues or gets into the bloodstream. This is considered life-threatening.

 

Several factors can allow colonization to progress into invasion:

• Biofilm formation and fungal mass: The bigger the fungal load and the stronger the biofilm, the higher the risk that the fungus can break into tissues.
• Tissue vulnerabilities: Problems like leaky gut, sinus inflammation, or damage in the lungs make it easier for fungi to move deeper into the body.
• Antibiotic use: Antibiotics can remove helpful bacteria that normally keep fungi under control, allowing Candida or environmental molds to overgrow, release damaging enzymes, and enter tissues.
• Mycotoxins: Fungal toxins weaken local immunity, damage tissues, and increase inflammation, making it easier for fungi to invade.

 

Areas Susceptible to Fungal Growth

 

 

Fungal overgrowth can occur in multiple areas of the body, with some regions being more susceptible due to environmental exposure, immune status, or prior medical interventions.

 

Gastrointestinal Tract (GI Tract)

Fungal overgrowth, particularly Candida, is common in the small intestine, a condition known as SIFO (Small Intestinal Fungal Overgrowth). This often develops after antibiotic use, PPI (proton pump inhibitor) therapy, or immune suppression, which disrupts normal gut microbial balance.

 

Sinuses

Fungal biofilms can colonize the nasal and sinus cavities, with organisms like Aspergillus or Candida. This is usually associated with MARCoNS, mold exposure, and chronic congestion. In immunocompromised individuals, sinus colonization can become invasive.

 

Skin, Scalp, and Nails

Dermatophytes and other fungi can cause:

• Athlete’s foot
• Ringworm
• Fungal nail infections (onychomycosis)
• Seborrheic dermatitis on the scalp, face, and upper body

 

Oral Thrush

Overgrowth of Candida albicans in the mouth is more common in infants, people with dentures and orthopedic devices, or individuals taking antibiotics or steroids.

 

Vaginal Candidiasis

Candida can overgrow in the vagina, particularly following antibiotic use or hormonal shifts, leading to symptomatic infection.

 

Lungs/Pulmonary Fungal Infections

More common in people with asthma, COPD, or mold exposure, fungal spores like Aspergillus can colonize the lungs. Pulmonary manifestations include:

• ABPA (allergic bronchopulmonary aspergillosis) 
• Chronic pulmonary aspergillosis
• Fungal balls (aspergilloma) in existing lung cavities

 

Systemic/Invasive Fungal Infections (Less Common)

Systemic infections primarily affect immunocompromised individuals, including those with cancer or organ transplants. Examples include:

• Candida: Candidemia, fungus in the blood
• Cryptococcus: Meningitis, infection of the meninges
• Histoplasma, Coccidioides: Infections of the lungs, liver, or brain
• Mucor (mucormycosis): Aggressive fungal invasion that can spread through tissues

 

How Shoemaker Practitioners Approach Fungal Colonization and CIRS

 

 

Shoemaker practitioners approach fungal colonization in CIRS patients very cautiously. This is because Shoemaker views CIRS mainly as an illness caused by biotoxins and immune dysregulation, not as a problem driven by fungal infection or colonization itself.

 

For this reason, they only treat fungal overgrowth when it is clearly necessary, rather than targeting it routinely.

 

For example, MARCoNS in the nasal passages may be treated with BEG (Bactroban, EDRA, Gentamicin) spray, which contains EDTA and antibiotics to reduce local bacterial overgrowth. Visible fungal sinus infections may sometimes be treated with nasal antifungal therapies, but systemic antifungal medications are usually not recommended. Gut dysbiosis may be addressed lightly, but it is not considered part of the Shoemaker Protocol.

 

Shoemaker practitioners do not treat fungal colonization in the gut or lungs unless it causes obvious, serious problems. They do not actively test for fungal overgrowth or colonization. Remember, Shoemaker and his trained practitioners are now focusing more on biotoxins such as actinos and endotoxins, and less on mold. They believe that once biotoxins are removed with cholestyramine (CSM) and the immune system is reset using treatments such as VIP (Vasoactive Intestinal Peptide) therapy, the body will correct itself.

 

According to this model, Shoemaker practitioners maintain that:

• Fungal colonization will naturally resolve once toxins are cleared and the immune system is balanced.
• Antifungal medications are, in majority cases, unnecessary and interfere with healing.
• Antibiotics have a place with actinos treatment because actinos are bacteria and the most prevalent biotoxin driving CIRS. No thoughts have been shared about the well-known concerns of antibiotic use driving fungal overgrowth and gut imbalances, where 70-80% of the immune system resides.

 

The Functional Medicine and Integrative Medicine Perspectives

From a functional and integrative medicine perspective, fungal colonization is not always harmless. While Shoemaker focuses mainly on resetting the immune system and removing biotoxins, many functional medicine practitioners believe that chronic fungal colonization itself can be a continuing source of immune activation.

 

If fungal colonization is not addressed, it can move toward tissue invasion, especially in mold-sensitive patients or in people with conditions like SIFO (Small Intestinal Fungal Overgrowth), long COVID, MCAS (mast cell activation syndrome), or autoimmune diseases. In these groups, ongoing colonization can keep inflammation high, make detoxification harder, and disrupt normal immune function.

 

Functional and integrative medicine approaches usually support using targeted antifungal treatments when colonization is clearly contributing to chronic immune activation. The idea is that reducing fungal overgrowth can help calm the immune system, lower inflammation, and create a healthier environment for detoxification and microbial balance.

 

By treating these microbial sources directly, practitioners aim to give the body stronger support for recovering from biotoxin-related problems, rather than relying only on immune recalibration and binders to remove toxins.

 

This difference in perspective highlights a key limitation in Shoemaker’s approach.

 

While his focus on immune reset and toxin removal is important, it raises a logical question: if antifungals are discouraged because of potential risks, why does the Shoemaker Protocol regularly use antibiotics for issues like bacterial overgrowth or MARCoNS?

 

Both antifungals and antibiotics target microbes that can drive chronic immune activation, yet only antibiotics are routinely accepted. This inconsistency suggests that, for some patients, antifungal treatment may be needed to fully support immune function and detox pathways, especially when symptoms continue even after following the Shoemaker Protocol closely.

 

In our functional medicine practice, we believe that antifungal therapy is very nuanced and personalized. Antifungals should only be considered on a case-by-case basis once the environment has been properly remediated and is conducive for  healing. While antifungals should be an available option for CIRS patients to explore when plateauing or experiencing roadblocks, it typically shouldn’t be the first option in treatment.

 

What About VIP?

 

 

VIP (Vasoactive Intestinal Peptide) plays an important healing role in the Shoemaker Protocol, especially for fixing brain volume loss, reducing neuroinflammation, and improving cognitive problems in CIRS patients.

 

Shoemaker’s research, including the study “Intranasal VIP Safely Restores Volume to Multiple Grey Matter Nuclei in Patients with CIRS”, shows that VIP nasal spray can restore gray matter volume, improve blood flow to the brain, and raise VEGF levels. These improvements were seen when VIP was used after toxins were cleared with cholestyramine. In the Shoemaker Protocol, VIP therapy is a key part of the regeneration phase because it helps repair past damage and supports brain recovery.

 

This leads to an important question for patients who may need antifungal treatment: If someone requires azole antifungals for fungal overgrowth, can VIP still help restore gray matter volume?

 

In theory, VIP can work well as long as certain conditions are met:

• Inflammation must be controlled, so the brain can repair without constant immune activation.
• Biotoxins must be cleared, meaning the patient is out of mold exposure and has completed cholestyramine to lower toxin-related damage and improve VCS scores.
• Other infections, like MARCoNS or bacterial coinfections, should be treated so the brain has a supportive environment for healing.

 

This brings up an important point about Shoemaker’s concerns with azole antifungals. Even if azoles hypothetically affect VEGF, mitochondria, or mTOR, VIP therapy gives the body a powerful tool for neuroregeneration.

 

Shoemaker’s own studies show that intranasal VIP can safely improve gray matter volume, brain blood flow, and VEGF levels once toxins are cleared and inflammation is under control.

 

This suggests that, in well-managed CIRS patients, VIP’s regenerative effects may help counterbalance any potential risks from antifungal use. In other words, VIP may make it possible for patients to use antifungals when needed and still achieve healthy brain recovery.

 

Alternatives for Gray Matter Growth and Preservation

 

 

In addition to VIP therapy, there are several complementary strategies that can support gray matter growth and preservation in CIRS patients. These interventions can be used alongside VIP or serve as alternatives when VIP therapy is unavailable or not well-tolerated:

 

• Exercise (especially aerobic and resistance training): Physical activity increases gray matter in key areas of the brain, including the hippocampus, prefrontal cortex, and motor regions. It also stimulates brain-derived neurotrophic factor (BDNF) and enhances cerebral perfusion, supporting neuroplasticity and energy metabolism.
• Meditation and mindfulness practices: These techniques increase cortical thickness and gray matter in the prefrontal cortex, insula, and anterior cingulate. They also help reduce stress-related shrinkage driven by elevated cortisol.
• Quality sleep: Adequate sleep supports glymphatic clearance and neuroregeneration, while chronic sleep deprivation is linked to gray matter shrinkage.
• Nutrient-dense, meat-based diet (especially DHA, choline, and vitamin B12): These nutrients support myelination, synaptic repair, and mitochondrial function, providing essential building blocks for brain health.
• Social engagement and learning: Engaging socially and mentally stimulates neuroplasticity, particularly in the frontal and temporal lobes, reinforcing neural connections and cognitive resilience.
• Heat therapy (e.g., sauna): Regular heat exposure may enhance brain-derived neurotrophic factors (BDNF) and improve cerebral blood flow, supporting gray matter maintenance and neuroregeneration.

 

Our Cautious Stance On Antifungals for CIRS

 

 

Our approach to antifungal therapy in CIRS is highly nuanced and individualized. While we recognize that antifungals may be necessary as an additional therapy for certain patients, we do not advocate their use as a first-line intervention. A personalized (traditional sans actinos) Shoemaker Protocol, focused on biotoxin removal, immune recalibration, and terrain optimization, remains at the core of treatment for nearly all patients.

 

We work bioindividually, taking into account each patient’s health history, past and current symptoms, previous protocols attempted, and overall tolerance. Antifungals should be considered when roadblocks are experienced, and patients aren’t healing enough with the Shoemaker Protocol alone. Treatment decisions are always collaborative and grounded in clinical evidence.

 

Antifungals are especially considered if a patient has gone through the full Shoemaker Protocol and still have fungal symptoms, stubborn CIRS symptoms, or signs of persistent Candida or other forms of fungal growth. Our practice considers antifungals before actinos protocols, assuming the environment has been appropriately addressed for CIRS healing. We rarely ever recommend prescription-grade antibiotics unless in life-threatening situations. 

 

 

Antifungal Options and Considerations

Several different antifungal therapy options and considerations must be individually tailored for each patient:

 

• Gut Fungal Overgrowth (SIFO): Nystatin, itraconazole, or herbal antifungals such as caprylic acid, oregano, or berberine may be used. Nystatin is particularly useful for localized yeast overgrowth in the gut, oral mucosa, or vagina. It targets yeast without entering systemic circulation, avoids VDAC/mTOR suppression, and does not impair VEGF or mitochondrial function. However, it is not effective for mold or Aspergillus, and it does not penetrate tissues, sometimes requiring longer-term use.
• Lungs and Sinuses: Itraconazole, Amphotericin B, N-acetylcysteine (NAC), or nasal antifungals can be considered when appropriate, particularly for mold colonization or systemic fungal infections. Itraconazole provides a wider antifungal spectrum and supports invasive or extra-GI infections. It is generally used after the Shoemaker Protocol has been implemented, but fungus-like symptoms persist.
• Fluconazole: Useful for systemic Candida infections, recurring yeast, or more severe growth. It can be combined with nystatin, targeting gut versus systemic fungus, but should not be used concurrently with itraconazole due to similar pharmacology and increased risks to liver and cardiac function.
• Phase-Based Strategy (Bioindividual Approach): Here is a sample of a phase-based strategy that may be recommended for a CIRS patient with fungal overgrowth:
  • Phase 1: Fluconazole may be used early or pulsed to reduce yeast burden.
  • Phase 2: Itraconazole is introduced weeks later for deeper mold colonization, sinus or lung involvement, or persistent symptoms. Nystatin may continue in the gut alongside systemic therapy for targeted coverage.

 

Adjunctive Supports

Whenever an herbal or prescription antifungal is prescribed for a CIRS patient, we always recommend personalized adjunct supports to optimize efficacy, reduce side effects, and support overall immune and metabolic function:

 

• Biofilm Disruptors: Interfase Plus, N-acetylcystine (NAC), lactoferrin, and enzymes can help break down fungal biofilms, enhancing antifungal efficacy.
• Immune Support: Optimizing the underlying terrain is essential. Addressing low secretory IgA (sIgA), low MSH, mold exposure, low VEGF, high TGF-β1, and other immune modulators.
• Binders: Used to mop up toxins released during fungal die-off, but they are not a stand-alone solution.
• Organ and Mitochondrial Support: Personalized care should include liver function monitoring, CoQ10 supplementation, and strategies to support mitochondrial and vascular function during antifungal therapy.

 

Ongoing Reasons Why Antifungals Are Needed

 

 

Even with a good diet, gut support, and environmental control, temporarily reducing fungal overgrowth does not mean the fungus is gone for good. Several ongoing factors can allow fungi to stay in the body or come back in CIRS patients:

 

Environmental Re-Exposure: Living in a water-damaged building or being exposed to contaminated air, bedding, or HVAC systems can constantly reintroduce fungal spores. This can lead to fungal overgrowth in the sinuses, lungs, and gut.

 

Gastrointestinal Factors: Low stomach acid or poor bile flow can make it easier for fungi to survive and grow in the digestive tract. A damaged gut lining (leaky gut) allows fungi to get closer to tissues and supports biofilm formation, which protects them from both the immune system and treatments.

 

Immune Dysfunction: Many CIRS patients have low secretory IgA, which weakens the immune system’s ability to control microbes in the gut and mucosal surfaces. Low MSH can worsen dysbiosis and reduce mucosal protection. Low VEGF and poor blood flow can also limit immune activity in tissues, making it harder for the body to clear fungal overgrowth.

 

Fungal Defense Mechanisms: Fungi produce mycotoxins and create biofilms to protect themselves. These defenses help them survive even when environmental exposures are reduced, and supportive therapies are used.

 

Taken together, these factors show why antifungal treatment may be necessary for some CIRS patients. Without addressing these ongoing risks, fungal colonization can remain or return, slowing recovery even when everything else is well-managed.

 

CIRS and Antifungal Case Study

One of our patients, whom we will keep anonymous for privacy, developed a serious complication that highlights why antifungal treatment may be necessary for some CIRS patients.

 

This patient had a long history of mold exposure and chronic symptoms. This patient was following the Shoemaker Protocol without antifungals because the approach discourages treating fungal colonization directly. For a while, the patient’s symptoms stabilized, but over time they began experiencing worsening coughing, chest tightness, and shortness of breath.

 

After further testing, imaging showed Aspergillus growing in the patient’s lungs. Aspergillus is a type of mold that can colonize lung tissue and, in some cases, become invasive. Once fungal growth reaches this point, treatment becomes much more complicated and can even be life-threatening.

 

Could taking antifungals earlier have prevented this? We can’t say for certain, but it is possible. What we can tell you is that we’ll never forget this case, and the what-ifs that come across our mind as practitioners.

 

If antifungals had been used earlier, what if it reduced fungal colonization before it entered the lungs or formed strong biofilms?  While binders like cholestyramine remove circulating toxins, they can’t bind Aspergillus growing inside lung tissue. Fungal colonies in the lungs require either:

• direct antifungal medications, or
• targeted local treatment, depending on the severity and location.

 

Once fungal growth becomes organized within the lungs, it can be very difficult to remove with medication alone. Now, because antifungals may no longer fully resolve the problem, this individual may need a lung biopsy to confirm the type and depth of fungal invasion. This procedure carries risks, especially in medically fragile individuals.

 

Situations like this are a major reason why our practice now considers antifungals when appropriate. Case studies teach us what works (and what doesn’t), and they show that avoiding antifungals completely may sometimes lead to preventable complications. While no single case proves anything (and we have more), it reminds us to consider all reasonable options, especially when many other practitioners successfully use antifungals to prevent fungal colonization from progressing.

 

Another issue this case brings up is the logic behind the Shoemaker Actinos protocol. According to Shoemaker’s view, actinos are responsible for about 50% or more of CIRS cases. But statistically:

• Less than 1% of people worldwide are following the Shoemaker Actinos protocol.
• Yet so many patients in the broader mold community are healing, including people who have never tried the Shoemaker Actinos protocol.
• Many patients who do follow the Shoemaker Actinos protocol still don’t fully recover.

 

If actinos were truly responsible for half of all CIRS cases, we would expect a clear and direct relationship between treating actinos and seeing widespread recovery. But that is not what we observe. Instead, many patients remain sick despite strict adherence to the protocol, while others improve under different approaches.