Hello again,

               We are going to continue with our current series: “Common Questions with Dr. Matt.”  Today’s common question is “Does VOCs or mold cause my headaches?”  Headaches are divided into two different categories which are primary and secondary.  Primary headaches are ones that are not due to another disease.  There are four types of primary headaches:  migraines, tension headaches, trigeminal autonomic cephalalgias, and other.  Secondary headaches are symptoms of another disease: such as toxins or a physical problem such as a tumor (1).  Headaches caused by VOCs or mold toxins would be characterized as secondary.  

               The study of on the sum of VOCs or total exposure to VOCs to individuals has only started to gain traction in the last decade. The complexity of these types of studies are magnified by not only the large sum of different chemicals that individuals are exposed to, but also the enormous diversity of genetics and predispositions that subjects introduce into such a study.  One of the most comprehensive studies was undertaken by Chiba University and their “Chemiless Town Project” which was started in 2007. The investigators in this study attempted to set up a control environment on the university campus to assess the effects of indoor air on human health.  Two different buildings were constructed in the study.  One house was constructed with conventional materials and the second with materials that were rated as low emission.  The study found a significant relationship between building related syndromes and VOC concentration (2).  Headaches represent the single most common symptom of most indoor environmental studies (3,4).  These headaches seem to be associated with specific exposures, such as VOCs (5).  

Probably the most common symptoms that drives patients to seek medical help when it involves mold exposure have to pertain to neurological symptoms.  Recent studies have tied exposure to mold and mycotoxins to many different types of neurological problems.  Some of the more common ones are headaches, migraines, Parkinson’s, multiple sclerosis, and Alzheimer’s (6-9).  However, this is nowhere near a complete list.  Many of these diseases have been tied to inflammation.  Mycotoxins trigger multiple different pathways which can lead to induced apoptosis. T-2 and trichothecenes enter cells and trigger expression of MEKK1 and c-jun and the down regulation of Nrf2 (10,11).  These changes will lead to increased oxidative stress and decreased detoxification. Ochratoxin (OTA) has a much more complex method for damaging neuronal cells.  Multiple papers have given result that show a mixture of oxidative stress, inhibition of protein synthesis, and OTA induced DNA breaks can lead to damage to the neuronal system (12,13).  

One study that was performed looked at students that were either exposed or unexposed to mold.  This table from the study, Hyvonenet al, shows that headaches were the most common of the symptoms seen in the exposed cohort, however GI-symptoms, respiratory symptoms, and fatigue were common (14).

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 Table 1: The comparison of risks for symptom manifestations and asthma diagnosis among exposed (n=47) vs. unexposed school children (n=56)

As disconcerting as these results are, there is a lot of hope in the newest research.  There are now studies that have shown that neurological decline can be reversed if the toxin source can be located and treatment is performed (15).  

Resources 

1.            May,A. Hints on Diagnosing and Treating Headache. Dtsch Arztebl Int 115,299-308 (2018).

2.            Suzuki,N. et al. Association between sum of volatile organic compounds and occurrence of building-related symptoms in humans: A study in real full-scale laboratory houses. Sci Total Environ 750,141635 (2021).

3.            Schwartz,B.S., Stewart, W.F. & Lipton, R.B. Lost workdays and decreased work effectiveness associated with headache in the workplace. J Occup Environ Med 39,320-7 (1997).

4.            Schwartz,B.S., Stewart, W.F., Simon, D. & Lipton, R.B. Epidemiology of tension-type headache. JAMA 279, 381-3 (1998).

5.            Schneider,W.J., Furth, P.A., Blalock, T.H. & Sherrill, T.A. A pilot study of a headache program in the workplace. The effect of education. J Occup Environ Med 41, 202-9 (1999).

6.            Inamdar,A.A. et al. Fungal-derived semiochemical 1-octen-3-ol disrupts dopamine packaging and causes neurodegeneration. Proc Natl Acad Sci U SA 110, 19561-6 (2013).

7.            Empting,L.D. Neurologic and neuropsychiatric syndrome features of mold and mycotoxin exposure. Toxicol Ind Health 25, 577-81 (2009).

8.            Purzycki,C.B. & Shain, D.H. Fungal toxins and multiple sclerosis: a compelling connection. Brain Res Bull 82, 4-6 (2010).

9.            Ratnaseelan,A.M., Tsilioni, I. & Theoharides, T.C. Effects of Mycotoxins on Neuropsychiatric Symptoms and Immune Processes. Clin Ther 40, 903-917(2018).

10.          Sehata,S. et al. Morphological and microarray analysis of T-2 toxin-induced rat fetal brain lesion. Food Chem Toxicol 42, 1727-36 (2004).

11.          Chaudhary,M. & Rao, P.V. Brain oxidative stress after dermal and subcutaneous exposure of T-2 toxin in mice. Food ChemToxicol 48, 3436-42 (2010).

12.          Sava,V., Reunova, O., Velasquez, A., Harbison, R. & Sanchez-Ramos, J. Acute neurotoxic effects of the fungal metabolite ochratoxin-A. Neurotoxicology 27,82-92 (2006).

13.          Dirheimer,G. & Creppy, E.E. Mechanism of action of ochratoxin A. IARC Sci Publ, 171-86 (1991).

14.          Hyvonen,S.M. et al. Association of toxic indoor air with multi-organ symptoms in pupils attending a moisture-damaged school in Finland. Am J Clin Exp Immunol9, 101-113 (2020).

15.          Bredesen, D.E. et al. Reversal of cognitive decline in Alzheimer's disease. Aging (Albany NY) 8, 1250-8 (2016).

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