Healing from Mold Illness:A Comprehensive Approach Integrating Low-Dose Naltrexone

Yoon Hang "John" Kim, MD, MPH

About the Author

Dr. Yoon Hang "John" Kim is a board-certified integrative medicine physician with over 20 years of clinical experience. He completed his integrative medicine fellowship at the University of Arizona under Dr. Andrew Weil and holds certifications in preventive medicine, medical acupuncture, and integrative/holistic medicine. Through his telemedicine practice, Dr. Kim specializes in utilizing LDN (Low-Dose Naltrexone) for treating autoimmune conditions, chronic pain, integrative oncology, and complex conditions including fibromyalgia, chronic fatigue, MCAS, and mold toxicity. He is the author of three books and more than 20 articles on LDN and integrative medicine, and has helped establish integrative medicine programs at institutions nationwide.

Professional: www.yoonhangkim.com  |  Clinical: www.directintegrativecare.com

A Personal Note

Before diving into the clinical details, I want to share something personal. A close family member of mine was completely incapacitated by mold-related illness. The fatigue was crushing, the brain fog impenetrable, and the road to diagnosis frustratingly long. Watching someone you love struggle with a condition that many physicians don’t recognize—or worse, dismiss—is heartbreaking.

But here’s the good news: they made a full recovery. It wasn’t quick, it wasn’t easy, and it required a systematic approach that addressed every layer of the illness. That experience deepened my commitment to understanding mold-related conditions and helping others navigate this challenging journey. If you or someone you love is struggling, please know that recovery is possible.

Healing from Mold Illness:

A Comprehensive Approach Integrating Low-Dose Naltrexone

Introduction

Mold-related illness—often called Chronic Inflammatory Response Syndrome (CIRS)—is one of the most misunderstood conditions in modern medicine. It arises from exposure to biotoxins in water-damaged buildings and triggers a cascade of immune dysregulation that can affect virtually every system in the body. Patients often present with an overwhelming constellation of symptoms: crushing fatigue, cognitive impairment (the dreaded "brain fog"), chronic pain, and a profound sense that something is deeply wrong—even when standard labs come back "normal."

What many people don’t realize is that up to 25% of the population carries genetic susceptibility to CIRS (Dooley et al., 2024). That’s a staggering number. A recent systematic review confirmed that the Shoemaker Protocol remains the only treatment with documented clinical efficacy for CIRS—and it works better than protocols designed for similar conditions like ME/CFS (Dooley et al., 2024).

In my practice, I’ve found that while foundational interventions—removing exposure, binding toxins, treating colonization—form the backbone of treatment, adjunctive therapies like low-dose naltrexone (LDN) can make a meaningful difference. LDN doesn’t cure mold illness, but for many patients, it helps calm the immune storm enough to make the deeper healing work more tolerable and effective. This article walks through a comprehensive approach to mold-related illness, combining validated protocols with promising supportive therapies.

Step 1: Find the Mold and Get Away from It

I cannot overstate this: you cannot heal in a toxic environment. It’s like trying to put out a fire while someone keeps pouring gasoline on it. Dr. Bruce Hoffman puts it bluntly: "For many people, this is the most critical, yet most difficult step. Without removing exposure, treatment cannot succeed" (Hoffman, n.d.).

I know this step can feel impossible. Sometimes it means leaving your home, your job, or making financial sacrifices that seem unreasonable. But I’ve seen patients spin their wheels for years—taking every supplement, trying every protocol—only to finally improve when they addressed the exposure. The body simply cannot outpace ongoing toxic exposure.

Testing Your Environment

The ERMI (Environmental Relative Moldiness Index) test provides a quantitative PCR analysis of 36 mold species. Dr. Shoemaker’s research suggests a safe score is ≤2 for most patients, and below -1 for those with highly elevated C4a levels (Shoemaker, 2010). After remediation, the HERTSMI-2 test can verify whether the building is safe to re-enter—scores below 11 are generally the target.

Getting It Done Right

Professional remediation should follow EPA and IICRC guidelines. This isn’t a DIY project—improper remediation can actually make things worse by stirring up spores. Key priorities include fixing water intrusion, removing damaged materials, controlling humidity, and using HEPA filtration. And here’s something patients often underestimate: re-exposure can happen within 15 minutes of entering a contaminated building. Stay out until it’s truly safe.

Step 2: Bind and Eliminate the Toxins

Here’s the frustrating biology: in genetically susceptible people, about 95% of bile—which carries biotoxins—gets reabsorbed in the gut and recirculated. It’s like a merry-go-round of toxins that never stops. Binders interrupt this cycle by grabbing onto the toxins in your gut and escorting them out through your stool.

The Gold Standard: Cholestyramine

Cholestyramine (CSM) remains the most effective binder we have, backed by two double-blind, placebo-controlled studies. It works because its positive charge attracts negatively charged biotoxins. The standard protocol calls for four doses daily on an empty stomach—which, I’ll admit, can be challenging to maintain. Many patients start with Welchol, which is easier to tolerate even if it’s only about 25% as effective (Shoemaker, 2010).

Other Options

For patients who can’t tolerate prescription binders, we sometimes turn to activated charcoal, bentonite clay, chlorella, or zeolite. These don’t have the same evidence base, but Dr. Neil Nathan has observed that different mycotoxins may bind preferentially to different agents—for instance, bentonite and charcoal seem to work well for trichothecenes (Nathan, n.d.). Some clinicians have also found success with okra and beet extracts, though peer-reviewed data is still pending.

Step 3: Clear the Colonizers

Most CIRS patients harbor something called MARCoNS—Multiple Antibiotic Resistant Coagulase Negative Staphylococci—deep in their nasal passages. These bacteria form protective biofilms and release toxins that break down MSH (melanocyte-stimulating hormone), a key anti-inflammatory peptide. It’s a vicious cycle: low MSH allows MARCoNS to thrive, and MARCoNS further suppress MSH (Shoemaker, 2010).

Testing

A deep nasal swab sent to a specialized lab like MicrobiologyDX can identify MARCoNS. About 80% of CIRS patients test positive, with roughly 60% showing methicillin resistance. The culture also reveals which antibiotics the bacteria are resistant to—critical information for treatment planning.

Treatment

BEG nasal spray—a compounded formula containing Bactroban, EDTA, and Gentamicin—is the primary treatment. The EDTA dissolves the biofilm, allowing the antibiotics to reach the bacteria. The standard protocol is two sprays in each nostril, three times daily, for at least a month. Some stubborn cases require up to six months of treatment.

A word of caution: when MARCoNS die, they release endotoxins that can temporarily worsen symptoms. I recommend patients be on an effective binder for at least a month before starting nasal treatment. Alternatives for those who can’t tolerate BEG include colloidal silver rinses, EDTA-only formulations, or Xlear (xylitol-based spray). Some practitioners are even exploring probiotic nasal sprays to reestablish healthy flora.

Don’t Forget the Fungus

Fungal colonization of the sinuses is often overlooked but can produce mycotoxins locally. Treatment may include amphotericin B nasal spray, oral antifungals like itraconazole, and biofilm disruptors. Interestingly, addressing sinus mold often resolves MARCoNS simultaneously—the bacterial and fungal biofilms seem to support each other.

Step 4: Support Your Body’s Detox Pathways

Binders are essential, but they’re only part of the equation. The body has its own detoxification machinery—liver, kidneys, lymphatics, skin—and that machinery needs support, especially when it’s been overwhelmed by chronic toxin exposure.

Glutathione: The Master Antioxidant

Glutathione depletion is nearly universal in patients with mycotoxin exposure (Guilford & Hope, 2014). This matters because glutathione is central to phase II liver detoxification and protects cells from oxidative damage. Supplementation options include liposomal glutathione (oral), N-acetylcysteine/NAC (a precursor), IV glutathione for more severe cases, and intranasal glutathione for sinus and neurological support. A survey found that over 62% of patients using intranasal glutathione reported meaningful benefits (Hope, 2013).

Additional Support

Methylation support (methylfolate, methylcobalamin, SAMe) helps keep detox pathways running smoothly. Infrared sauna therapy promotes toxin elimination through sweat—preliminary research shows reduced mycotoxin levels when combined with other therapies (Rea et al., 2009). Phosphatidylcholine supports cell membranes and liver function. And don’t underestimate the basics: vitamin D, magnesium, zinc, CoQ10, and B vitamins are commonly depleted in CIRS patients and should be repleted.

Step 5: Calm the Allergic Fire

Many mold patients develop what we call Mast Cell Activation Syndrome (MCAS)—their mast cells become hypersensitive and release histamine and other inflammatory chemicals at the slightest provocation. This can make treatment incredibly difficult because patients react to everything: foods, supplements, even medications meant to help them.

Strategies That Help

H1 and H2 antihistamines can block histamine effects. Mast cell stabilizers like ketotifen and cromolyn sodium prevent degranulation. Natural options include quercetin and other bioflavonoids. A low-histamine diet reduces triggers. DAO (diamine oxidase) supplementation helps those with impaired histamine breakdown. Perhaps most importantly, patients need to identify and avoid their personal triggers—which can include certain foods, fragrances, temperature extremes, and stress.

The Cell Danger Response

Some researchers believe that mold toxicity triggers a "Cell Danger Response"—a protective shift where cells prioritize defense over energy production. This may explain why so many CIRS patients feel stuck in a "freeze" state, unable to muster the energy for normal activities. Supporting mitochondrial function with nutrients like CoQ10, ribose, and carnitine may help cells transition out of this defensive mode.

Where Low-Dose Naltrexone Fits In

Now we get to LDN—and I want to be clear about what it is and isn’t. LDN is not a cure for mold illness. It doesn’t kill mold, it doesn’t bind mycotoxins, and it won’t work if you skip the foundational steps. But for many patients, it’s a valuable tool that helps calm the immune chaos and makes everything else work better.

How It Works

At standard doses (50 mg), naltrexone blocks opioid receptors and is used for addiction treatment. At low doses (typically 1.5–4.5 mg), it does something quite different: it briefly blocks opioid receptors, triggering a rebound increase in endorphins and enkephalins—the body’s natural feel-good and immune-regulating chemicals.

LDN also inhibits Toll-like receptor 4 (TLR4) on microglial cells in the brain, reducing the neuroinflammation that causes so much of the cognitive dysfunction in mold illness. It shifts cytokine balance away from pro-inflammatory (IL-6, TNF-α, TGF-β1) and toward regulatory (IL-10). For patients with MCAS, this shift can be game-changing—the LDN Research Trust reports that about 60% of MCAS patients experienced improvement in symptoms like brain fog, fatigue, and GI distress after starting LDN.

When to Introduce It

Timing matters. I typically introduce LDN after patients have addressed environmental exposure, started binder therapy, and achieved at least partial reduction in their inflammatory burden. Starting too early—when the immune system is still in full-blown crisis mode—can sometimes backfire and intensify symptoms.

Clinical observation suggests that patients with the HLA type 4-3-53 may respond particularly well to LDN. Patient surveys indicate that most who tried LDN for CIRS rated it "critically important or very helpful" in their recovery (Richmond Functional Medicine, 2024). And unlike NSAIDs—which carry risks of GI bleeding, kidney damage, and cardiovascular problems—LDN’s side effects are minimal and usually temporary.

Dosing: Low and Slow

For mold patients, especially those with chemical sensitivity, I start very low—0.25 to 0.5 mg—and titrate up gradually over weeks. The goal is usually 1.5–4.5 mg, taken at bedtime to align with natural endorphin production. Some patients experience vivid dreams or insomnia initially; if this persists, switching to morning dosing often helps.

Important caveats: LDN is contraindicated if you’re taking opioid medications (it can trigger withdrawal), and caution is warranted in liver impairment. You’ll need a compounding pharmacy—standard naltrexone comes in 50 mg tablets, far too high for LDN use.

Other Functional Medicine Approaches Worth Considering

Heal the Gut

Mycotoxins wreak havoc on the gut microbiome, reducing beneficial species like Lactobacillus reuteri and decreasing overall diversity. Research shows that a healthy gut microbiota can actually help eliminate mycotoxins naturally (Draper et al., 2021). Specific probiotics (Lactobacillus rhamnosus, Bifidobacterium bifidum), prebiotics, and an anti-inflammatory diet that avoids commonly contaminated foods (coffee, nuts, dried fruit, rice) all support gut recovery.

Follow the Biomarkers

The Shoemaker Protocol includes sequential correction of specific inflammatory markers: ADH/osmolality (desmopressin), MMP-9 (omega-3s and no-amylose diet), VEGF, C3a (statins), C4a, TGF-β1 (losartan or VIP), and MSH. The final step—VIP nasal spray—can only begin after MARCoNS is cleared. It’s methodical, but there’s a reason: each step builds on the last.

Emerging Options

Mild hyperbaric oxygen therapy (mHBOT) has shown promise in case reports, with one recent case documenting complete symptom resolution after 40 sessions (Frontiers in Immunology, 2025). Ozone therapy, peptide protocols, and other integrative approaches continue to be explored. These aren’t first-line treatments, but for refractory cases, they may offer additional tools.

Healing from Mold Illness:

A Comprehensive Approach Integrating Low-Dose Naltrexone

Final Thoughts

Recovering from mold illness is a marathon, not a sprint. It requires patience, persistence, and a systematic approach that addresses every layer of the problem: the environment, the toxins, the colonizers, the depleted detox pathways, and the overactive immune system.

LDN isn’t a magic bullet, but for many patients, it’s a valuable piece of the puzzle. Its ability to calm neuroinflammation, stabilize mast cells, and reduce the persistent fatigue of CIRS makes it a rational addition to the toolkit—as long as it’s integrated with, not substituted for, the foundational treatments.

I think of it this way: the Shoemaker Protocol is the road map, and LDN is one of the vehicles that can make the journey more bearable. We still need better research—randomized controlled trials specifically in CIRS populations—but the clinical experience and mechanistic rationale are compelling enough that I regularly incorporate LDN into my treatment plans.

If you’re struggling with mold illness, know that recovery is possible. I’ve seen it in my patients, and I’ve seen it in my own family. It takes time, it takes the right approach, and it takes a willingness to address the root causes—but the other side of this illness is absolutely reachable.

About Dr. Kim

Dr. Yoon Hang "John" Kim is a board-certified integrative medicine physician with over 20 years of clinical experience. He completed his integrative medicine fellowship at the University of Arizona under Dr. Andrew Weil and holds certifications in preventive medicine, medical acupuncture, and integrative/holistic medicine. Through his telemedicine practice, Dr. Kim specializes in utilizing LDN (Low-Dose Naltrexone) for treating autoimmune conditions, chronic pain, integrative oncology, and complex conditions including fibromyalgia, chronic fatigue, MCAS, and mold toxicity. He is the author of three books and more than 20 articles on LDN and integrative medicine, and has helped establish integrative medicine programs at institutions nationwide.

Direct Integrative Care

At Direct Integrative Care, Dr. Kim is dedicated to guiding you on your path to wellness through a deeply personalized and supportive approach. We focus on integrative medicine, looking beyond symptoms to uncover the root causes of chronic conditions and develop a treatment plan tailored specifically to your unique health journey. By combining compassionate care with innovative therapies, our goal is to empower you with the knowledge and tools needed to achieve lasting health. We invite you to explore our website to learn more about how our patient-centered practice can help you find balance and vitality.

Yoon Hang Kim, MD

Integrative & Functional Medicine Physician

Virtual Practice Serving IA, IL, MO, FL, GA, and TX

www.directintegrativecare.com

References

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Guilford, F. T., & Hope, J. (2014). Deficient glutathione in the pathophysiology of mycotoxin-related illness. Toxins, 6(2), 608–623. https://doi.org/10.3390/toxins6020608

Hoffman, B. (n.d.). 12 Steps of the Shoemaker Protocol. Hoffman Centre for Integrative Medicine. https://www.drbrucehoffman.com/post/shoemaker-protocol

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Shoemaker, R. C. (2010). Surviving mold: Life in the era of dangerous buildings. Otter Bay Books.

Shoemaker, R. C., House, D., & Ryan, J. C. (2013). Vasoactive intestinal polypeptide (VIP) corrects chronic inflammatory response syndrome (CIRS) acquired following exposure to water-damaged buildings. Health, 5(3), 396–401. https://doi.org/10.4236/health.2013.53053

Surviving Mold. (n.d.). The 12-step Shoemaker Protocol overview. https://www.survivingmold.com/legal-resources/12-step-protocol-overview

Younger, J., Parkitny, L., & McLain, D. (2014). The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clinical Rheumatology, 33(4), 451–459. https://doi.org/10.1007/s10067-014-2517-2

Disclaimer: This article is for educational purposes only and does not constitute medical advice. Treatment decisions should be made in consultation with a qualified healthcare provider familiar with biotoxin illness. Individual responses to treatment vary, and protocols should be tailored to each patient’s specific presentation and tolerances.