Michael Maes

Michael Maes, M.D., Ph.D., is a clinician at Revitalis, in Waalre, Netherlands, as well as a researcher at IMPACT Strategic Research Center, Barwon Health, Deakin University, School of Medicine, Geelong, Victoria, Australia. He is, also, affiliated with the Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand and Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Brazil.

His special interests include: Behavorial Systems Biology, major depression, inflammatory illnesses and chronic fatigue syndrome.

Neuro-Inflammatory and Oxidative Fatigue (NIOF) Theory
In 2015, Maes developed a new case definition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) called Neuro-Inflammatory and Oxidative Fatigue (NIOF) "based on pattern recognition methods and using neuro-immune, inflammatory, oxidative and nitrosative stress (neuro-IO&NS) biomarkers as external validating criteria." These biomarkers include "IgM / IgA responses against LPS [lipopolysaccharides] of gut commensal bacteria (leaky gut), IgM responses to O&NS modified neoepitopes, autoimmunity to serotonin, plasma interleukin-1 (IL-1) and serum neopterin." Maes sees a "significant overlap between NIOF and chronic fatigue syndrome although NIOF criteria were much more restrictive."

Professor Maes proposes the ME/CFS, as well as other chronic diseases, can be treated by lessening the Neuro-Inflammatory and Oxidative Fatigue with foods and supplements that decrease inflammation and repair leaky gut such as curcumin, N-acetyl-cysteine ​​(NAC), glutamine, zinc, and omega-3 oils.

Books

 * 2011, Nooit Mer Moe (English translation: 'Tired No More, CFS Unmasked'')

Published Studies

 * 2017, Mechanisms Explaining Muscle Fatigue and Muscle Pain in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a Review of Recent Findings (Abstract)
 * 2016, Nitrosative Stress, Hypernitrosylation, and Autoimmune Responses to Nitrosylated Proteins: New Pathways in Neuroprogressive Disorders Including Depression and Chronic Fatigue Syndrome (Abstract)
 * Abstract and link to full text


 * 2016, The role of microbiota and intestinal permeability in the pathophysiology of autoimmune and neuroimmune processes with an emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome"Abstract: 'BACKGROUND: In steady state conditions intestinal immune homeostasis is maintained by a sophisticated bidirectional dialogue between the microbiota and the intestinal immune system. This 'cross talk' is enabled by the presence of highly adapted secretory cells, sampling cells and pattern recognition receptors in the gastric epithelium. METHODS: Herein we discuss the mechanisms involved in the breakdown of intestinal homeostasis and the development of systemic immune activation and neuroinflammation with a view to discussing the importance of these processes, in tandem with genetic and environmental factors, in the pathophysiology of (auto)immune diseases.Data is presented explaining how immune tolerance is maintained and how it may breakdown. CONCLUSION: The breakdown of immune homeostasis following the development of gut inflammation, caused for example by gut dysbiosis, and the consequent increased intestinal permeability, is increasingly considered to be the ultimate source of the systemic immune activation and T helper 17/T regulatory cell imbalances, and maybe neurological disturbances, seen in autoimmune diseases such as Type 1 diabetes and inflammatory bowel disease. Increased intestinal permeability and translocation of commensal antigens into the systemic circulation is also a likely cause of the severe fatigue and an almost bewildering range of neurocognitive, neuroimaging and overall symptom presentations seen in patients with a diagnosis of Chronic Fatigue Syndrome.'"
 * 2015, A new case definition of Neuro-Inflammatory and Oxidative Fatigue (NIOF), a neuroprogressive disorder, formerly known as chronic fatigue syndrome or Myalgic Encephalomyelitis: results of multivariate pattern recognition methods and external validation by neuro-immune biomarkers."'Abstract - BACKGROUND: Chronic fatigue syndrome (CFS) or Myalgic Encephalomyelitis (ME) is characterized by neuro-psychiatric (e.g. depression, irritability, sleep disorders, autonomic symptoms and neurocognitive defects) and physio-somatic (fatigue, a flu-like malaise, hyperalgesia, irritable bowel, muscle pain and tension) symptoms. New ME/CFS case definitions based on consensus criteria among experts are largely inadequate, e.g. those of the US Institute of Medicine. OBJECTIVES: The aim of the present study was to delineate a new case definition of ME/CFS based on pattern recognition methods and using neuro-immune, inflammatory, oxidative and nitrosative stress (neuro-IO&NS) biomarkers as external validating criteria. METHODS: We measured the 12-item Fibromyalgia and Chronic Fatigue Syndrome Rating (FF) Scale in 196 subjects with CFS (CDC criteria) and 83 with chronic fatigue. The 'Neuro-IO&NS' biomarkers were: IgM / IgA responses against LPS of gut commensal bacteria (leaky gut), IgM responses to O&NS modified neoepitopes, autoimmunity to serotonin, plasma interleukin-1 (IL-1) and serum neopterin. RESULTS: Cluster analysis showed the presence of two well-separated clusters with highly significant differences in symptoms and biomarkers. The cluster with higher scores on all FF items was externally validated against all IO&NS biomarkers and therefore this diagnostic group was labeled 'Neuro-IO&NS Fatigue' or 'Neuro-Inflammatory and Oxidative Fatigue' (NIOF). An algorithm was constructed which defined NIOF as chronic fatigue and 4 or more of the following 6 symptoms: muscle tension, memory disturbances, sleep disorders, irritable bowel, headache or a flu-like malaise. There was a significant overlap between NIOF and CFS although NIOF criteria were much more restrictive. Factor analysis showed two factors, the first a fatigue-hyperalgesia (fibromyalgic complaints) and the second a fatigue-depression factor.'"
 * 2015, Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses.
 * 2014, Review Article - "Mitochondrial dysfunctions in Myalgic Encephalomyelitis / chronic fatigue syndrome explained by activated immuno-inflammatory, oxidative and nitrosative stress pathways""Abstract: 'Myalgic encephalomyelitis / chronic fatigue syndrome (ME/cfs) is classified by the World Health Organization as a disorder of the central nervous system. ME/cfs is an neuro-immune disorder accompanied by chronic low-grade inflammation, increased levels of oxidative and nitrosative stress (O&NS), O&NS-mediated damage to fatty acids, DNA and proteins, autoimmune reactions directed against neoantigens and brain disorders. Mitochondrial dysfunctions have been found in ME/cfs, e.g. lowered ATP production, impaired oxidative phosphorylation and mitochondrial damage. This paper reviews the pathways that may explain mitochondrial dysfunctions in ME/cfs. Increased levels of pro-inflammatory cytokines, such as interleukin-1 and tumor necrosis factor-α, and elastase, and increased O&NS may inhibit mitochondrial respiration, decrease the activities of the electron transport chain and mitochondrial membrane potential, increase mitochondrial membrane permeability, interfere with ATP production and cause mitochondrial shutdown. The activated O&NS pathways may additionally lead to damage of mitochondrial DNA and membranes thus decreasing membrane fluidity. Lowered levels of antioxidants, zinc and coenzyme Q10, and ω3 polyunsaturated fatty acids in ME/cfs may further aggravate the activated immuno-inflammatory and O&NS pathways. Therefore, it may be concluded that immuno-inflammatory and O&NS pathways may play a role in the mitochondrial dysfunctions and consequently the bioenergetic abnormalities seen in patients with ME/cfs. Defects in ATP production and the electron transport complex, in turn, are associated with an elevated production of superoxide and hydrogen peroxide in mitochondria creating adaptive and synergistic damage. It is argued that mitochondrial dysfunctions, e.g. lowered ATP production, may play a role in the onset of ME/cfs symptoms, e.g. fatigue and post exertional malaise, and may explain in part the central metabolic abnormalities observed in ME/cfs, e.g. glucose hypometabolism and cerebral hypoperfusion.'"
 * 2014, The emerging role of autoimmunity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/cfs)
 * 2014, Oxidative and Nitrosative Stress and Immune-Inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)
 * 2013, In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation
 * 2013, Case definitions and diagnostic criteria for Myalgic Encephalomyelitis and Chronic fatigue Syndrome: from clinical-consensus to evidence-based case definitions Full text "Abstract: 'The symptom spectrum of Myalgic Encephalomyelitis (ME) was first detailed in 1959 and later operationalised into a diagnostic protocol (Melvin Ramsey). In 1988 the Holmes case definition coined the term chronic fatigue syndrome (CFS). Fukuda's Centers for Disease Control and Prevention criteria are very heterogeneous and comprise patients with milder symptoms than the Holmes case definition. The CDC Empirical Criteria for CFS lack sensitivity and/or specificity. Other CFS definitions, e.g. the Oxford criteria, delineate people with idiopathic fatigue. Some authors make the clinical CFS diagnosis when slightly increased self-rated fatigue scores are present. In 2011, Carruthers' International Consensus Criteria attempted to restore the focus on selecting people who suffer from ME. Cognitive bias in criteria construction, patient selection, data collection and interpretation has led to the current state of epistemological chaos with ME, CFS, CFS/ME and ME/CFS, and CF being used interchangeably. Moreover, none of the above mentioned classifications meet statistically based criteria for validation. Diagnostic criteria should be based on statistical methods rather than consensus declarations. Ongoing discussions about which case definition to employ miss the point that the criteria did not pass appropriate external validation. In 2012, Maes et al. performed pattern recognition methods and concluded that CFS patients (according to Fukuda's criteria) should be divided into those with CFS or ME, on the basis that people with ME display a worsening of their illness following increases in physical or cognitive activity. Both ME and CFS are complex disorders that share neuro-immune disturbances, which are more severe in ME than in CFS. This paper expands on that strategy and details a range of objective tests, which confirm that a person with ME or CFS has a neuro-immune disease. By means of pattern recognition methods future research should refine the Maes' case definitions for ME and CFS by including well-scaled symptoms, staging characteristics and neuro-immune biomarkers, including immune-inflammatory assays, bioenergetic markers and brain imaging.'"
 * 2011, Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome.
 * 2009, A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS."'Abstract: Benign Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) is a debilitating disease which, despite numerous biological abnormalities has remained highly controversial. Notwithstanding the medical pathogenesis of ME/CFS, the (bio)psychosocial model is adopted by many governmental organizations and medical professionals to legitimize the combination of Cognitive Behavioral Therapy (CBT) and Graded Exercise Therapy (GET) for ME/CFS. Justified by this model CBT and GET aim at eliminating presumed psychogenic and socially induced maintaining factors and reversing deconditioning, respectively. In this review we invalidate the (bio)psychosocial model for ME/CFS and demonstrate that the success claim for CBT/GET to treat ME/CFS is unjust. CBT/GET is not only hardly more effective than non-interventions or standard medical care, but many patients report that the therapy had affected them adversely, the majority of them even reporting substantial deterioration. Moreover, this review shows that exertion and thus GET most likely have a negative impact on many ME/CFS patients. Exertion induces post-exertional malaise with a decreased physical performance/aerobic capacity, increased muscoskeletal pain, neurocognitive impairment, 'fatigue', and weakness, and a long lasting 'recovery' time. This can be explained by findings that exertion may amplify pre-existing pathophysiological abnormalities underpinning ME/CFS, such as inflammation, immune dysfunction, oxidative and nitrosative stress, channelopathy, defective stress response mechanisms and a hypoactive hypothalamic-pituitary-adrenal axis. We conclude that it is unethical to treat patients with ME/CFS with ineffective, non-evidence-based and potentially harmful 'rehabilitation therapies', such as CBT/GET."
 * 2008, Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: Effects of age, duration of illness and the translocation of LPS from gram-negative bacteria
 * 2006, Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability.

Talks & Interviews

 * 21 August 2013, Dr Michael Maes: The Immune Pathophysiology of ME/CFS/FM - seminar given at Emerge Australia (formerly ME/CFS Australia (Victoria)) at The Alfred Hospital

Online Presence

 * PubMed
 * ResearchGate
 * LinkedIn
 * Onward thru the Fog blog article about Dr. Maes' research