Category: Pathophysiology

Mechanistic factors contributing to pain and fatigue in fibromyalgia and ME/CFS: autonomic and inflammatory insights from an experimental medicine study

Abstract:

Background: Fibromyalgia and ME/CFS are multifaceted conditions with overlapping symptoms(1); the pathoaetiological mechanisms are complex and debated(2), however there is a strong association with features of hereditary disorders of connective tissue (hypermobility) and autonomic and inflammatory abnormalities (1,2).

Objectives: To determine potential autonomic and inflammatory mechanisms of pain and fatigue in fibromyalgia and ME/CFS

Methods: After excluding participants with WCC higher than 10 (suggesting acute infection) baseline markers of inflammation (CRP and ESR) were available for 60 patients with confirmed diagnoses of Fibromyalgia and/ or ME/CFS and 23 matched controls. Participants then underwent full research diagnostic evaluation including a hypermobility assessment(1) and autonomic challenge (60 degree head up tilt, ISRCTN78820481). Subjective pain and fatigue were assessed before and after challenge (VAS). Linear regression models were used to explore predictors, with adjustment for confounders as appropriate. Mediation analyses (looking for mechanistic effects) were conducted according to the method of Hayes (3) and mediation considered significant if bootstrapped confidence intervals of the estimated indirect effect did not cross zero. In these mediation analyses predictor variable was group membership (patient or control), outcome variable was change in 1)pain and 2)fatigue induced by challenge and mediatiors 1)no of connective tissue features in hypermobility diagnostic criteria endorsed by participant; 2)baseline inflammatory markers.

Results: ESR and CRP were significantly higher in patients rather than controls, even after correcting for BMI, age and sex (B=5.15, t=2.05, p=0.044; B=1.77, t=2.15, p=0.044 respectively). Adjusted ESR and CRP correlated with both subjective fatigue (B=0.44, t=2.09, p=0.04; B=1.63, t=2.60, p=0.011) and pain severity (B=0.13, t=2.51, p=0.014; B=0.45, t=3.01, p=0.004) at baseline. Autonomic challenge amplified pain (B=14.20, t=2.87, p=0.005) and fatigue (B=31.48, t=5.95, p=<0.001) in patients to a significantly greater degree than controls, controlling for baseline levels. Baseline ESR and CRP also predicted challenge-induced increase in fatigue (B=0.78, t=370, p=<0.001; B=1.91, t=3.36, p=<0.001) and ESR challenge-induced increases in pain (B=0.46, t=2.35, p=0.021).

Mediation analysis demonstrated that number of connective tissue features expressed in hypermobility criteria mediated the degree to which subjective pain was increased by the autonomic challenge (Bootstraped 95% CI of indirect effect do not cross zero, 0.1572 – 6.8171). ESR mediated the degree to which subjective fatigue was increased by the autonomic challenge (Bootstraped 95% CI of indirect effect do not cross zero,0.7541 – 7.3888).

Conclusion: To our knowledge this is the first study to directly explore autonomic and inflammatory mechanisms of pain and fatigue in a combined population of Fibromyalgia and ME/CFS. This study this adds to the evidence-base of baseline inflammatory abnormalities in fibromyalgia and ME/CFS. It highlights their potential role in predicting symptom severity and their potential mechanistic role in autonomic induced pain and fatigue, suggesting future treatment strategies.

Source: Eccles J, Thompson C, Thompson B, et al. AB1209 MECHANISTIC FACTORS CONTRIBUTING TO PAIN AND FATIGUE IN FIBROMYALGIA AND ME/CFS: AUTONOMIC AND INFLAMMATORY INSIGHTS FROM AN EXPERIMENTAL MEDICINE STUDY. Annals of the Rheumatic Diseases 2022;81:1719 https://ard.bmj.com/content/annrheumdis/81/Suppl_1/1719.2.full.pdf (Full text available as PDF file)

The occurrence of hyperactivated platelets and fibrinaloid microclots in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

We have previously demonstrated that platelet poor plasma (PPP) obtained from patients with LongCovid/Post-Acute Sequelae of COVID-19 (PASC) is characterized by a hypercoagulable state reflected in hyperactivated platelets and the presence of considerable numbers of fibrin(ogen) amyloid microclots or fibrinaloid microclots. Due to substantial overlap in symptoms and aetiology between PASC and ME/CFS, we investigated whether coagulopathies, platelet hyperactivation and/or fibrin amyloid formation differed between individuals exhibiting ME/CFS and gender- and age-matched healthy controls.

ME/CFS patients were statistically far more hypercoagulable as judged by thromboelastography of both whole blood and platelet-poor plasma. The area of plasma images containing fibrinaloid microclots was commonly more than 10-fold greater in untreated platelet-poor plasma from individuals with ME/CFS than in that of healthy controls. A similar difference was found when the plasma samples were treated with thrombin. Using fluorescently labelled PAC-1, which recognizes glycoprotein IIb/IIIa, and CD62P, which binds P-selectin, we observed massive hyperactivation and spreading of platelets in samples from individuals with ME/CFS. Using a quantitative scoring system, this was found to have a score of 2.72 ± 1.24 vs 1.00 (activation with pseudopodia formation) for healthy controls.

We conclude that ME/CFS is accompanied by substantial and measurable changes in coagulability, platelet hyperactivation, and fibrinaloid microclot formation. However, fibrinaloid microclot load was not as prevalent as was previously noted in PASC. Fibrinaloid microclots, in particular can provide a ready explanation, via (temporary) blockage of microcapillaries and hence ischaemia, for many of the symptoms, such as fatigue, seen in patients with ME/CFS. The discovery of these biomarkers pointing to significant and systemic endothelial inflammation, represents an important development in ME/CFS research. It also points at novel treatment strategies using known drugs and/or nutraceuticals that target systemic vascular pathology and endothelial inflammation.

Source: Massimo Nunes, Arneaux Kruger, Amy Proal et al. The occurrence of hyperactivated platelets and fibrinaloid microclots in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), 08 June 2022, PREPRINT (Version 1) available at Research Square https://doi.org/10.21203/rs.3.rs-1727226/v1 (Full text)

Aberrations in the Cross-Talks Among Redox, Nuclear Factor-κB, and Wnt/β-Catenin Pathway Signaling Underpin Myalgic Encephalomyelitis and Chronic Fatigue Syndrome

Abstract:

There is evidence that chronic fatigue spectrum disorders (CFAS-D) including Myalgic Encephalomyelitis (ME), chronic fatigue syndrome (CFS) and chronic fatigue with physiosomatic symptoms including when due to comorbid medical disease are characterized by neuroimmune and neuro-oxidative biomarkers.

The present study was performed to delineate the protein-protein interaction (PPI) network of CFAS-D and to discover the pathways, molecular patterns and domains enriched in their PPI network.

We performed network, enrichment and annotation analysis using differentially expressed proteins and metabolics, which were established in CFAS-D patients.

PPI network analysis revealed that the backbone of the highly connective CFAS-D network comprises NFKB1, CTNNB1, ALB, peroxides, NOS2, TNF, and IL6, and that the network comprises interconnected immune-oxidative-nitrosative and Wnt/catenin subnetworks.

MultiOmics enrichment analysis shows that the CFAS-D network is highly significantly associated with cellular (antioxidant) detoxification, hydrogen peroxide metabolic process, peroxidase and oxidoreductase activity, IL10 anti-inflammatory signaling, and neurodegenerative, canonical Wnt, the catenin complex, cadherin domains, cell-cell junctions and TLR2/4 pathways; and the transcription factors NF-κB and RELA.

The top-10 DOID annotations of the CFAS-D network include four intestinal, three immune system disorders, cancer and infectious disease.

Custom GO term annotation analysis revealed that the CFAS-D network is associated with a response to a toxic substance, lipopolysaccharides, bacterium or virus.

In conclusion, CFAS-D may be triggered by a variety of stimuli and their effects are mediated by aberrations in the cross-talks between redox, NF-κB, and Wnt/catenin signaling pathways leading to dysfunctions in multicellular organismal homeostatic processes.

Source: Michael Maes, Marta Kubera and Magdalena Kotańska. Aberrations in the Cross-Talks Among Redox, Nuclear Factor-κB, and Wnt/β-Catenin Pathway Signaling Underpin Myalgic Encephalomyelitis and Chronic Fatigue Syndrome. Frontiers in Psychiatry 13: 822382. https://www.frontiersin.org/articles/10.3389/fpsyt.2022.822382/full  (Full text)

Neurovascular Dysregulation and Acute Exercise Intolerance in ME/CFS: A Randomized, Placebo-Controlled Trial of Pyridostigmine

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by intractable fatigue, post-exertional malaise, and orthostatic intolerance, but its pathophysiology is poorly understood. Pharmacologic cholinergic stimulation was used to test the hypothesis that neurovascular dysregulation underlies exercise intolerance in ME/CFS.

Research Question: Does neurovascular dysregulation contribute to exercise intolerance in ME/CFS and can its treatment improve exercise capacity?

Methods: Forty-five subjects with ME/CFS were enrolled in a single-center, randomized, double-blind, placebo-controlled trial. Subjects were assigned in a 1:1 ratio to receive a 60 mg dose of oral pyridostigmine or placebo after an invasive cardiopulmonary exercise test (iCPET). A second iCPET was performed 50 minutes later. The primary end point was the difference in peak exercise oxygen uptake (VO2). Secondary end points included exercise pulmonary and systemic hemodynamics and gas exchange.

Results: Twenty-three subjects were assigned to pyridostigmine and 22 to placebo. The peak VO2 increased after pyridostigmine but decreased after placebo (13.3 ± 13.4 mL/min vs. -40.2 ± 21.3 mL/min, P<0.05). The treatment effect of pyridostigmine was 53.6 mL/min (95% CI, -105.2 to -2.0). Peak versus rest VO2 (25.9 ± 15.3 mL/min vs. -60.8 ± 25.6 mL/min, P<0.01), cardiac output (-0.2 ± 0.6 L/min vs. -1.9 ± 0.6 L/min, P<0.05), and RAP (1.0 ± 0.5 mm Hg vs. -0.6 ± 0.5 mm Hg, P<0.05) were greater in the pyridostigmine group compared to placebo.

Interpretation: Pyridostigmine improves peak VO2 in ME/CFS by increasing cardiac output and right ventricular filling pressures. Worsening peak exercise VO2, Qc, and RAP after placebo may signal the onset of post-exertional malaise. We suggest treatable neurovascular dysregulation underlies acute exercise intolerance in ME/CFS.

Abbreviations List: Ca-vO2 (arterial-venous oxygen content difference), iCPET (Invasive cardiopulmonary exercise test), MAP (Mean arterial pressure), mPAP (Mean pulmonary artery pressure), ME/CFS (Myalgic encephalomyelitis/chronic fatigue syndrome), PASC (Post-acute sequelae of SARS-CoV-2 infection), PAWP (Pulmonary arterial wedge pressure), POTS (Postural orthostatic tachycardia syndrome), Qc (Cardiac output), RAP (Right atrial pressure), SE (Standard error), SFN (Small fiber neuropathy), VE/VCO2 (Ventilatory efficiency), VO2 (Oxygen uptake)

Source: Phillip Joseph, MD, Rosa Pari, MD, Sarah Miller, BS, Arabella Warren, BS, Mary Catherine Stovall, BS, Johanna Squires, MSc, Chia-Jung Chang, PhD, Wenzhong Xiao, PhD, Aaron B. Waxman, MD, PhD, David M. Systrom, MD. Neurovascular Dysregulation and Acute Exercise Intolerance in ME/CFS: A Randomized, Placebo-Controlled Trial of Pyridostigmine. Chest, Published: May 05, 2022. DOI: https://doi.org/10.1016/j.chest.2022.04.146

Acute effect of pyridostigmine in exertional intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A randomized placebo-controlled clinical trial

Rationale: One third of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have evidence of small fiber neuropathy (SFN). Neurovascular dysregulation during upright exercise may be associated with impaired venoconstriction resulting in low biventricular filling pressures and impaired arteriolar constriction resulting in a mismatch between perfusion and skeletal muscle metabolism. We hypothesize that pyridostigmine, a reversible acetylcholinesterase inhibitor, may improve vascular regulation and exercise tolerance in ME/CFS by increasing sympathetic outflow.

Methods: 45 subjects (39 women, 6 men) with ME/CFS were assessed. A baseline invasive cardiopulmonary exercise test (iCPET) was performed to confirm presence of low peak exercise RAP (<6.5mmHg). Eligible subjects were blindly administered placebo (n=22) or 60mg pyridostigmine (n=23) at a 1:1 ratio. A second iCPET was performed following a 50 minute combined rest and dosing period. Serial iCPET results were compared to assess changes in oxygen uptake at peak exercise (VO2 max). Secondary outcomes included subject ventilatory efficiency (VE/VCO2), peak hemodynamic response (RAP, PCWP, SV, Qt), systemic gas exchange (Ca-vO2/Hgb), and subjective reporting of dyspnea and fatigue. Results: 39 subjects (all women) were considered in data analysis. There was a significant increase in VO2 max between iCPET 1 and iCPET 2 in the treatment group when compared with the placebo group (p = 0.043).

There was a significant decrease in the placebo group and a significant increase in the treatment group in VO2 (p = 0.008), Qt (p = 0.039), and RAP (p = 0.045) when comparing iCPET 1 peak – rest and iCPET 2 peak – rest between groups. There were no significant differences in peak arteriovenous oxygen content difference (Ca-vO2/Hgb). 38% of subjects had objective evidence of SFN with no statistically significant difference between groups.

Conclusion: Using pyridostigmine as an investigative tool, this study suggests that neurovascular dysregulation underlies acute exercise intolerance in ME/CFS. Additionally, we have new evidence that worsening vascular dysregulation results from prior exercise, which sheds insight into the post exertional malaise that is a hallmark of this syndrome.

Source: M. Stovall, P. Joseph, R. Pari, A. Warren, S. Miller, J. Squires, W. Xiao, A.B. Waxman, D.M. Systrom. Acute effect of pyridostigmine in exertional intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A randomized placebo-controlled clinical trial. American Journal of Respiratory and Clinical Care Medicine, Vol 205, p A2063, May 2022. https://www.atsjournals.org/doi/pdf/10.1164/ajrccm-conference.2022.205.1_MeetingAbstracts.A2063

Elevated ATG13 in serum of patients with ME/CFS stimulates oxidative stress response in microglial cells via activation of receptor for advanced glycation end products (RAGE)

Abstract:

Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome (ME/CFS), is a multisystem illness characterized by extreme muscle fatigue associated with pain, neurocognitive impairment, and chronic inflammation. Despite intense investigation, the molecular mechanism of this disease is still unknown. Here we demonstrate that autophagy-related protein ATG13 is strongly upregulated in the serum of ME/CFS patients, indicative of impairment in the metabolic events of autophagy.

A Thioflavin T-based protein aggregation assay, array screening for autophagy-related factors, densitometric analyses, and confirmation with ELISA revealed that the level of ATG13 was strongly elevated in serum samples of ME/CFS patients compared to age-matched controls. Moreover, our microglia-based oxidative stress response experiments indicated that serum samples of ME/CFS patients evoke the production of reactive oxygen species (ROS) and nitric oxide in human HMC3 microglial cells, whereas neutralization of ATG13 strongly diminishes the production of ROS and NO, suggesting that ATG13 plays a role in the observed stress response in microglial cells. Finally, an in vitro ligand binding assay provided evidence that ATG13 employs the Receptor for Advanced Glycation End-products (RAGE) to stimulate ROS in microglial cells.

Collectively, our results suggest that an impairment of autophagy following the release of ATG13 into serum could be a pathological signal in ME/CFS.

Source: Gottschalk G, Peterson D, Knox K, Maynard M, Whelan RJ, Roy A. Elevated ATG13 in serum of patients with ME/CFS stimulates oxidative stress response in microglial cells via activation of receptor for advanced glycation end products (RAGE). Mol Cell Neurosci. 2022 Apr 26:103731. doi: 10.1016/j.mcn.2022.103731. Epub ahead of print. PMID: 35487443. https://www.sciencedirect.com/science/article/abs/pii/S1044743122000379?via%3Dihub (Full text)

The underlying sex differences in neuroendocrine adaptations relevant to Myalgic Encephalomyelitis Chronic Fatigue Syndrome

Abstract:

Introduction: Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) is a complex multisystem disease characterised by severe and disabling new-onset symptoms of post-exertional malaise (PEM), fatigue, brain fog, and sleep dysfunction that lasts for at least six months. Accumulating evidence suggests that sex and endocrine events have a significant influence on symptom onset and moderation of ME/CFS, with female sex being one of the most consistent and credible predictive risk factors associated with diagnosis. Such sex differences suggest sex chromosomes and sex steroids may play a part in the development of the condition or moderation of symptoms, although this has yet to be explored in detail.

Methods/aims: This narrative review outlines sex differences in ME/CFS in terms of vulnerability factors and clinical phenotype and explores the known sex differences in neuroendocrine systems affected in ME/CFS and how this may relate to disease risk, onset, pathophysiology, and potential treatment avenues.

Conclusions: There is clear evidence of a sex dimorphism with regards to prevalence (3:1 female preponderance), clinical phenotypes, and aetiological triggers prior to symptom onset of ME/CFS. Endocrinological events, particularly those throughout the female lifespan, are associated with ME/CFS and include reproductive menstrual cycle fluctuations, pregnancy, post-partum and perimenopause. Further, there is evidence for gonadal sex, adrenal stress and renal neuroendocrine systems as implicated in ME/CFS, including changes in estrogen, progesterone compounds, aldosterone, and cortisol levels, of which there are established sex differences. The broad effects of steroid hormones on the physiological systems may also speak to the diversity of ME/CFS symptomatology observed in patients. Further attention must be paid to sex, age, and steroid biology in ME/CFS.

Source: Thomas N, Gurvich C, Huang K, Gooley PR, Armstrong CW. The underlying sex differences in neuroendocrine adaptations relevant to Myalgic Encephalomyelitis Chronic Fatigue Syndrome. Front Neuroendocrinol. 2022 Apr 11:100995. doi: 10.1016/j.yfrne.2022.100995. Epub ahead of print. PMID: 35421511. https://www.sciencedirect.com/science/article/abs/pii/S0091302222000188?via%3Dihub  (Full text)

Dyspnea in Post-COVID Syndrome following Mild Acute COVID-19 Infections: Potential Causes and Consequences for a Therapeutic Approach

Abstract:

Dyspnea, shortness of breath, and chest pain are frequent symptoms of post-COVID syndrome (PCS). These symptoms are unrelated to organ damage in most patients after mild acute COVID infection. Hyperventilation has been identified as a cause of exercise-induced dyspnea in PCS. Since there is a broad overlap in symptomatology with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), causes for dyspnea and potential consequences can be deduced by a stringent application of assumptions made for ME/CFS in our recent review papers.

One of the first stimuli of respiration in exercise is caused by metabolic feedback via skeletal muscle afferents. Hyperventilation in PCS, which occurs early on during exercise, can arise from a combined disturbance of a poor skeletal muscle energetic situation and autonomic dysfunction (overshooting respiratory response), both found in ME/CFS. The exaggerated respiratory response aggravating dyspnea does not only limit the ability to exercise but further impairs the muscular energetic situation: one of the buffering mechanisms to respiratory alkalosis is a proton shift from intracellular to extracellular space via the sodium-proton-exchanger subtype 1 (NHE1), thereby loading cells with sodium. This adds to two other sodium loading mechanisms already operative, namely glycolytic metabolism (intracellular acidosis) and impaired Na+/K+ATPase activity.

High intracellular sodium has unfavorable effects on mitochondrial calcium and metabolism via sodium-calcium-exchangers (NCX). Mitochondrial calcium overload by high intracellular sodium reversing the transport mode of NCX to import calcium is a key driver for fatigue and chronification. Prevention of hyperventilation has a therapeutic potential by keeping intracellular sodium below the threshold where calcium overload occurs.

Source: Wirth KJ, Scheibenbogen C. Dyspnea in Post-COVID Syndrome following Mild Acute COVID-19 Infections: Potential Causes and Consequences for a Therapeutic Approach. Medicina (Kaunas). 2022 Mar 12;58(3):419. doi: 10.3390/medicina58030419. PMID: 35334595. https://www.mdpi.com/1648-9144/58/3/419/htm (Full text)

Endothelial dysfunction and altered endothelial biomarkers in patients with post-COVID-19 syndrome and chronic fatigue syndrome (ME/CFS)

Abstract:

Background: Fatigue, exertion intolerance and post-exertional malaise are among the most frequent symptoms of Post-COVID Syndrome (PCS), with a subset of patients fulfilling criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). As SARS-CoV-2 infects endothelial cells, causing endotheliitis and damaging the endothelium, we investigated endothelial dysfunction (ED) and endothelial biomarkers in patients with PCS.

Methods: We studied the endothelial function in 30 PCS patients with persistent fatigue and exertion intolerance as well as in 15 age- and sex matched seronegative healthy controls (HCs). 14 patients fulfilled the diagnostic criteria for ME/CFS. The other patients were considered to have PCS. Peripheral endothelial function was assessed by the reactive hyperaemia index (RHI) using peripheral arterial tonometry (PAT) in patients and HCs. In a larger cohort of patients and HCs, including post-COVID reconvalescents (PCHCs), Endothelin-1 (ET-1), Angiopoietin-2 (Ang-2), Endocan (ESM-1), IL-8, Angiotensin-Converting Enzyme (ACE) and ACE2 were analysed as endothelial biomarkers.

Results: Five of the 14 post-COVID ME/CFS patients and five of the 16 PCS patients showed ED defined by a diminished RHI (< 1.67), but none of HCs exhibited this finding. A paradoxical positive correlation of RHI with age, blood pressure and BMI was found in PCS but not ME/CFS patients. The ET-1 concentration was significantly elevated in both ME/CFS and PCS patients compared to HCs and PCHCs. The serum Ang-2 concentration was lower in both PCS patients and PCHCs compared to HCs.

Conclusion: A subset of PCS patients display evidence for ED shown by a diminished RHI and altered endothelial biomarkers. Different associations of the RHI with clinical parameters as well as varying biomarker profiles may suggest distinct pathomechanisms among patient subgroups.

Source: Haffke M, Freitag H, Rudolf G, Seifert M, Doehner W, Scherbakov N, Hanitsch L, Wittke K, Bauer S, Konietschke F, Paul F, Bellmann-Strobl J, Kedor C, Scheibenbogen C, Sotzny F. Endothelial dysfunction and altered endothelial biomarkers in patients with post-COVID-19 syndrome and chronic fatigue syndrome (ME/CFS). J Transl Med. 2022 Mar 22;20(1):138. doi: 10.1186/s12967-022-03346-2. PMID: 35317812. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03346-2 (Full text)

Prevalence of Aspergillus-Derived Mycotoxins (Ochratoxin, Aflatoxin, and Gliotoxin) and Their Distribution in the Urinalysis of ME/CFS Patients

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a known complex, multi-organ system disorder with a sudden or subacute onset. ME/CFS occurs most commonly among women between 30 and 50 years of age. The current diagnostic criteria of ME/CFS, as defined by the Centers for Disease Control and Prevention, includes: profound fatigue and post-exertional malaise (>6 mo) unrelieved by rest, persistent cognitive impairment or orthostatic intolerance, and chronic unrefreshing sleep.

Despite reported associations between ME/CFS onset and exposure to infectious agents (viral, bacterial, or fungal), the pathophysiology of ME/CFS remains unknown. In this prevalence study, we investigated the rates of Aspergillus-derived toxin levels, Aflatoxin (AF), Ochratoxin A (OTA), and Gliotoxin (GT), in the urinalysis of 236 ME/CFS patients with a history of chronic exposure to mold (i.e., from water-damaged buildings).

Among ME/CFS patients reporting chronic exposure to mold, we found evidence of exposure in 92.4 percent of patients, with OTA being the most prevalent mycotoxin. Mold distributions (OTA, AF, and GT) in the urinalysis all demonstrated right skewness, while the distribution of age of ME/CFS patients diagnosed showed no deviation from normality.

This study aims to provide preliminary, epidemiological evidence among ME/CFS patients who were diagnosed in South Florida with a history of exposure to mycotoxins. Based on these findings, we proposed how future control studies should approach investigating the association between chronic mold exposure and the diagnosis of ME/CFS.

Source: Wu TY, Khorramshahi T, Taylor LA, Bansal NS, Rodriguez B, Rey IR. Prevalence of Aspergillus-Derived Mycotoxins (Ochratoxin, Aflatoxin, and Gliotoxin) and Their Distribution in the Urinalysis of ME/CFS Patients. Int J Environ Res Public Health. 2022 Feb 12;19(4):2052. doi: 10.3390/ijerph19042052. PMID: 35206241. https://www.mdpi.com/1660-4601/19/4/2052 (Full text)