For the 128th edition of the Research Digest, we highlight research that continues to strengthen understanding of ME/CFS as a complex, multisystem condition, with studies exploring water regulation, immune function, metabolism, hormones, the gut microbiome and vascular pathways. This month’s edition also draws attention to severe ME/CFS and the risks that arise when the illness is misunderstood in clinical care. Encouragingly, recent Australian media coverage reflects growing momentum in biomedical ME/CFS research and hope for improved diagnostic tools, treatments and care pathways.
Contributing Digesters: Sarah, Lauren, Anna & Simone.
Please note: The Research Digest shares current scientific findings for awareness and discussion. It is not a substitute for medical advice or treatment guidance, as much of the research featured is in its early stages and requires further confirmation.
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BIOLOGY
Low vasopressin in myalgic encephalomyelitis/chronic fatigue syndrome
Authors: Huhmar HM, Soinne LS, Bertilson BC, Ghatan PH, Bragée BA, & Polo OJ (Bragée ME/CFS Centre, Sweden)
Publication: Endocrine Practice (December, 2025)
Link: https://www.sciencedirect.com/science/article/pii/S1530891X25013497
Easy Read Overview: This study looked at whether problems with water balance and blood pressure may play a role in myalgic encephalomyelitis/chronic fatigue syndrome. Researchers tested blood and urine samples from 124 people with ME/CFS and found that many had signs of abnormal water regulation, including high blood concentration levels, low urine concentration levels, and very low levels of the hormone vasopressin. Brain scans did not show problems in the parts of the brain that normally control this hormone. The researchers believe these findings may help explain symptoms such as dizziness and feeling unwell when standing, and could support future research into better tests and treatments for ME/CFS.
Orthostatic intolerance is a frequently reported symptom of ME/CFS, suggesting potentially abnormal water homeostasis and hypovolemia. Vasopressin (VP), an antidiuretic hormone, has an important role in balancing water volume and blood pressure, and therefore in orthostatic tolerance. Due to the frequent reporting of polyuria-polydipsia (excessive urination-excessive thirst) in ME/CFS, the authors sought to study plasma and urine osmolarity, and levels of VP in patients.
This was a retrospective cross-sectional study. 124 consecutive patients being treated at the Bragée ME/CFS Centre in Stockholm were included in this study. All participants met theInternational Consensus Criteria. Plasma vasopressin levels (P-VP), plasma osmolality (P-Osm) and urine osmolality (U-Osm) were measured. Samples were taken after 10 hours overnight fasting from food and fluid. Of the 124 patients, 13 patients were unable to have VP measured and instead copeptin measurements were taken. Brain MRI and blood chemistry analysis was also completed on all participants.
The authors found that in 57.3% of patients P-Osm was abnormally high, and in 66.1% U-Osm was low. P-VP was below detection levels in 82.0% of patients. Normal P-VP compared with P-Osm was seen in just 9.9% of patients. Copeptin levels were in the normal range, but at the lower end of normal for most patients. The authors did not find any relevant pathology of the hypothalamus or the hypophysis.
The authors conclude that these findings suggest the presence of chronic down-regulation of VP, in a manner that mimics central diabetes insipidus may be a contributor to the core symptomatology of ME/CFS. The authors suggest that these findings contribute to our understanding of the pathophysiology of ME/CFS, and that further study in this area may help in the development of a biomarker and therapeutic strategies for ME/CFS.
REVIEW
Insights into the complex biological network underlying myalgic encephalomyelitis/chronic fatigue syndrome
Author: Dudova D, Bozhkova M, Petrov S, Nikolova R, Kalfova T, Ivanovska M… Ivanov IN (National Centre of Infectious and Parasitic Diseases, Bulgaria)
Publication: International Journal of Molecular Sciences (December, 2025)
Link: https://doi.org/10.3390/ijms27010268
Easy Read Overview: This review looks at how different body systems may work together in ME/CFS, including the immune system, metabolism, hormones, gut microbes, and blood vessels. It finds signs of immune problems such as weaker natural killer cells, changes in T-cells and B-cells, and autoantibodies, which may lead to ongoing inflammation and poor viral control. Changes in gut bacteria may increase inflammation in the body, while hormone system changes and reduced energy production in cells may contribute to fatigue and brain fog. The authors suggest these problems may reinforce each other in a cycle that keeps symptoms going, and they highlight the need for more consistent research methods to better understand the condition.
This review examines how multiple biological systems may interact to drive ME/CFS, integrating findings across immune, metabolic, neuroendocrine, microbiome, and vascular research.
Immunopathological studies highlight that immune dysregulation is common in ME/CFS, including reduced natural killer cell function, T-cell exhaustion, altered B-cell activity, and autoantibodies, which may contribute to chronic inflammation and impaired viral control. Changes in the gut microbiome involve a reduction in beneficial bacteria and increase in pro-inflammatory species, a pattern that has been associated with increased intestinal permeability and systemic inflammation via the gut–brain axis. Neuroendocrine studies have focussed on changes in the hypothalamic–pituitary–adrenal axis, where reduced cortisol activity and altered thyroid function are reported alongside symptoms such as fatigue and cognitive symptoms. Metabolic dysfunction, especially impaired mitochondrial function and reduced ATP production, is linked to fatigue and post-exertional malaise. Endothelial dysfunction and oxidative stress may further impair blood flow and oxygen delivery, contributing to exercise intolerance.
The authors propose that these systems do not act independently but instead form a self-sustaining cycle. Immune dysregulation, metabolic dysfunction, and neuroendocrine imbalance interact and reinforce one another, potentially triggered by infection, stress, or genetic susceptibility. This cycle may perpetuate chronic inflammation and multisystem impairment over time.
The review suggests that inconsistencies across studies are likely due to differences in diagnostic criteria, disease duration, and patient subgroups. It emphasises the need for more standardised approaches, better patient stratification, and longitudinal multi-system research to clarify disease mechanisms and identify meaningful biomarkers or treatment targets.
CASE STUDY
An overview of severe myalgic encephalomyelitis
Authors: Vink M, Vink-Niese A (Independent researchers, The Netherlands and Germany)
Publication: Journal of Clinical Medicine (January, 2026)
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC12841657/pdf/jcm-15-00805.pdf
Easy Read Overview: This paper examined the barriers severely ill people with ME/CFS can face when trying to access parenteral nutrition (PN), which delivers nutrients directly into the bloodstream when normal eating or tube feeding is not enough. It described the case of a Dutch woman with ME/CFS who was dangerously underweight despite tube feeding, but doctors refused PN because they believed her condition was a functional disorder rather than a physical illness. The authors argued that misunderstanding and disbelief about ME/CFS can lead to harmful treatment decisions, and called for more research and better treatments for people with the illness.
This paper explored the barriers to receiving, guidelines surrounding, and evidence supporting the need for parenteral nutrition (PN) for severely ill patients with ME/CFS suffering life-threatening malnutrition.
When a patient is unable to eat normally, other methods are used to supply nutrition. Enteral (tube) nutrition (EN) delivers liquid nutrients into the stomach or small intestine via a tube. Parenteral nutrition (PN) delivers liquid nutrients into the bloodstream via a catheter and may sometimes be used when EN is not suitable. However, some medical guidelines may prevent access to PN for patients with ME/CFS.
The paper presented a case study of a Dutch woman with ME/CFS whose need for PN was unmet. The patient was in her late 30s and had been receiving EN but was still losing weight. Her BMI fell to 16, dangerously low. Doctors ruled out intestinal failure, so diagnosed her with functional gastrointestinal disease and recommended antidepressants, psychoeducation and referral to a psychiatrist. A psychologist ruled out mental health problems as the reason for her nutrition.
Due to the impact of PN on life expectancy (estimated by one paper to reduce life expectancy by 17 years) and the diagnosis of functional disorder, doctors did not want to treat her malnutrition with PN. The authors highlighted that even though PN might reduce the patient’s life expectancy from 83 to 66 years, without PN the patient’s life expectancy would be only a few months. Therefore, PN treatment would increase her life expectancy. The authors noted that most doctors are not aware that nutritional difficulties are common in severe ME/CFS. Medical misunderstanding and disbelief about ME/CFS can lead to dismissing, misdiagnosing and/or mistreating ME/CFS as a psychosomatic disorder, which can lead to poorer health outcomes and patient trauma.
The authors conclude that further research is urgently needed to understand the underlying disease mechanism and accelerate the process of identifying effective pharmacological treatments to address unmet medical needs for people with ME/CFS.
MEDIA
Study links myalgic encephalomyelitis/chronic fatigue syndrome with changes to immune cells
Authors: Roberts, L
Publication: ABC News
Link: https://www.abc.net.au/news/health/2026-05-09/myalgic-encephalomyelitis-chronic-fatigue-syndrome-research/106642082
The article highlights a recent University of Sydney study of ME/CFS which found abnormalities in immune-cell energy production, immune signalling, and vascular-related pathways. Researchers used machine learning to identify biomarker patterns that may eventually contribute to diagnostic testing. Dr Richard Schloeffel, a co-author of the study, said, “If there’s disturbance in the vascular system, disturbance in the immune system, disturbance in the cell energy function, that would explain why people [with ME/CFS] have 200 or 300 symptoms. Because every tissue and organ in the body is impacted by this illness.”
Ella Engel, who spent 8 years confined to her bed and unable to leave her house and has since improved enough to be able to walk outside, participated in this study. She said, “Being part of research like this gives me hope that more effective treatments, and perhaps one day a cure, are within reach.”
