Testing for Mold Toxicity

By Todd Maderis

The first step in assessing someone for mold toxicity is by questioning during the medical exam.  Do they currently, or in the past, lived in a building that has had mold growth or water damage?  Have they worked in an environment that smells musty?  How do they feel when they are away from their home, and what is the response when they return home?  Then, do they have symptoms consistent with an inflammatory response?   The mold cluster analysis questionnaire can be highly suggestive as to whether or not a person is creating a chronic inflammatory response syndrome (CIRS) to mold toxicity.

Do Our Genes Make Us Susceptible When Exposed to Mold?

When testing for mold toxicity, we are looking for an inflammatory response the body has made to exposure of mycotoxins and other biotoxins associated with interior exposure of a water-damaged building.  People can develop an allergy to mold, just like they can to pine trees, but this presents as an allergic response, so mold allergy testing is not helpful when evaluating for a chronic inflammatory response.

Human leukocyte antigen (HLA) genotype testing can help identify who is most susceptible to mold exposure.  About 24% of the population has a defective genotype that makes them susceptible to mold toxicity because their immune system does not recognize mycotoxins and other biotoxins [ 1,2].

Biomarkers for Diagnosing Chronic Inflammatory Response Syndrome (CIRS) 



Complement 4a is part of the immune system that is activated in the presence of bacteria, fungi,  viruses, and parasites.  Complement "activates" other immune mediators to aid in fighting infections, but too much C4a causes inflammation that can damage tissue.  Elevated levels of C4a are associated with fatigue due to mitchondrial dysfunciton and difficulty with concentration, recall and assimilating new information

An elevated C4a is not specific to mold toxicity.  Infections such as Lyme disease [4, 5] can cause elevations in C4a, but it is thought levels >10,000 ng/mL in genetically sensitive patients is associated with mold exposure.

Testing for C4a should be done through National Jewish Lab, and the blood sample needs to be frozen to -20 degrees.  False-positive results are common if samples are not handled properly.

TGF Beta-1

Transforming growth factor beta-1 (TGF beta-1) is a cytokine that controls cell growth, proliferation, differentiation, and death.  Elevated levels of TGF Beta-1 indicates an overactive immune system, which can lead to immune suppression and autoimmunity [6].  Increased levels of TGF beta-1 can lead to respiratory symptoms such as cough and shortness of breath, as well as cognitive issues.  Cambridge Biomedical is the preferred lab for testing TGF Beta-1.


Matrix metalloproteinase-9 is an enzyme associated with the breakdown of the extracellular matrix.  High levels of MMP-9 increase the blood-brain barrier and can destroy myelin associated with multiple sclerosis [7].  Elevated MMP-9 can lead to fatigue and cognitive impairment. Biotoxin exposure can lead to an increase in MMP-9, so assessing levels is important for the workup of CIRS.


Melanocyte stimulating hormone (MSH) is neuropeptide that has an anti-inflammatory effect on the body.   Because MSH is a regulatory neuropeptide, it influences hormone production, inflammatory pathways, and immune response.  In mold illness, MSH levels decline leading to ongoing fatigue, chronic pain, insomnia, hormonal imbalances, intestinal permeability, alternating constipation and diarrhea, and increased urination.  Low MSH levels also lead to increased sensitivity to gluten.


Multiple antibiotic coagulase-negative staphylococci is not an infection, but a colonization of bacteria in the nasal passages that produce compounds that will degrade MSH.  80% of people with low MSH have MARCoNS.   MARCoNS is associated with biotoxin illness, and antibiotic use increases the risk for MARCoNS [8].

As you can see, the workup for diagnosing CIRS can be quite extensive.  However, properly evaluating this common and debilitating illness can establish clear objective clinical markers that allow for a starting point and a direction to aid in re-establishing health.