The work, published in the Journal of Eating Disorders, emerges from the Norwegian Microbiota Study in Anorexia Nervosa, known as NORMA, a project funded by the Norwegian Research Council that examines how gut biology and eating disorders intersect. The team, led by Ida Heir Hovland and Siv Kjølsrud Bøhn of the Norwegian University of Life Sciences together with collaborators at Oslo University Hospital and other Norwegian centers, and including eating disorders researcher Cynthia M. Bulik of the Karolinska Institutet and the University of North Carolina at Chapel Hill, enrolled 42 patients with anorexia nervosa admitted for inpatient treatment and 42 age-matched healthy controls. Blood samples were drawn from patients at baseline, after six weeks, and after twelve weeks of treatment, while the healthy controls provided a single baseline sample for comparison.

The analytical approach was deliberately broad. Using Luminex technology, a bead-based immunoassay platform that can quantify many proteins simultaneously in a small volume of serum, the researchers measured an array of hormones and signaling molecules central to appetite regulation: ghrelin, the stomach-derived hormone that stirs hunger; leptin, the fat-cell hormone that signals long-term energy stores; insulin and C-peptide, markers of pancreatic insulin secretion; adipsin and resistin, adipose-derived factors; adiponectin, another fat-cell hormone with metabolic and anti-inflammatory roles; the incretin hormones GLP-1 and GIP, which are released by the gut after eating and modulate insulin secretion and satiety; glucagon; plasminogen activator inhibitor-1; and visfatin. Dietary intake was captured with a three-day digital food diary and interview, allowing the team to connect hormone levels not just to weight but to what patients actually ate.

The baseline differences were striking. Compared with healthy controls, patients with anorexia nervosa showed significantly lower levels of adipsin, leptin, insulin, and resistin, and significantly higher levels of adiponectin and glucose-dependent insulinotropic polypeptide, or GIP. Ghrelin, the hunger hormone, was also elevated in patients, though the difference fell just short of statistical significance with a p-value of 0.08. No baseline differences emerged for C-peptide, plasminogen activator inhibitor-1, or visfatin. Intriguingly, the size of the group difference in GLP-1 and glucagon depended on age, with discrepancies between patients and controls being greater in older participants, a hint that the hormonal signature of the illness may shift across the lifespan.

These patterns make physiological sense in the context of severe starvation. Leptin is produced by adipose tissue in proportion to fat stores, so its near-absence in emaciated patients is expected. Low insulin reflects reduced nutrient intake and reduced body fat. Elevated ghrelin is the body’s classic cry for food. But the elevated adiponectin and GIP are less intuitive, and their persistence raises questions about whether the gut–brain axis in anorexia nervosa is merely responding to starvation or has been fundamentally rewired by it. Adiponectin typically rises as fat mass falls, yet its other roles in inflammation and energy metabolism suggest it may be doing more than simply tracking body composition.

Then came treatment. Over twelve weeks of structured inpatient care, designed around nutritional rehabilitation, the patients’ mean body mass index rose significantly from 15.5 to 18.2 kilograms per square meter, a substantial gain that nonetheless left most patients below the healthy BMI range. The hormonal response to this refeeding was a study in partial recovery. Adipsin, leptin, insulin, and C-peptide all increased, moving in the direction of healthy control values. Ghrelin decreased and approached the levels seen in controls. In other words, the hormones most tightly coupled to fat mass and acute nutrient flux responded to treatment much as one would predict from basic endocrinology.

But four signals stood apart. Glucagon, adiponectin, GIP, and GLP-1 were largely resistant to change across the twelve weeks of treatment. These are precisely the hormones most entangled with the gut side of the gut–brain axis: GLP-1 and GIP are secreted by intestinal enteroendocrine cells in response to food, and glucagon, produced by the pancreatic alpha cells, governs glucose mobilization during fasting. Their stubbornness suggests that refeeding and weight gain, at least over this timeframe, are not sufficient to normalize every arm of the appetite-signaling network. The authors interpret this as evidence of continued gut–brain axis dysregulation, a molecular echo of the illness that persists even as the body is refed.

Perhaps the most consequential finding of the study concerns diet. When the researchers examined associations between the biomarkers and what patients ate, they found that body mass index alone did not fully account for the hormonal differences between patients and controls. Dietary composition, particularly the intake of fiber and fat, appeared to matter independently for hormone regulation in anorexia nervosa. This is a technically important observation because it implies that the quality and macronutrient profile of the diet, not merely the total energy delivered, may shape how the appetite-signaling system recovers. Fiber is well known to influence gut hormone secretion through fermentation by the gut microbiota, producing short-chain fatty acids that stimulate enteroendocrine L-cells, the very cells that produce GLP-1. Fat intake, meanwhile, influences both incretin release and the absorption kinetics of meals. The NORMA study’s microbiota focus makes this connection especially tantalizing, since the gut bacteria that ferment fiber are themselves altered in anorexia nervosa.

The clinical implications are considerable but deliberately framed as open questions by the authors. Nutritional treatment is a cornerstone of anorexia nervosa care, and weight restoration remains essential, yet the persistence of abnormal levels of glucagon, adiponectin, GIP, and GLP-1 after twelve weeks of intensive treatment suggests that weight gain alone may not fully repair the biological machinery of appetite. Whether these unresponsive hormones can be targeted through tailored nutritional strategies, such as manipulating fiber or fat intake, or through pharmacological therapies aimed at the gut–brain axis, remains to be investigated. The GLP-1 system is already a major drug target in obesity and diabetes, and understanding why it behaves anomalously in anorexia nervosa could open new therapeutic avenues for a disorder where restoring the drive to eat is the central clinical challenge.

The study’s design carries caveats that the authors acknowledge through its framing as exploratory. With 42 patients and 42 controls, the sample is modest, and the healthy controls were only measured once, limiting the ability to model within-person change in that group. Twelve weeks is a short window in the arc of recovery from an illness that often runs a chronic course, and the patients’ BMIs at the end of treatment were still below the healthy range, so it remains possible that some hormones would normalize with further weight restoration. Still, the trial was prospectively registered with ClinicalTrials.gov under identifier NCT06144905, and the longitudinal sampling within treatment gives the findings a temporal texture that cross-sectional studies cannot match. What emerges is a picture of anorexia nervosa as not only a psychological disorder of eating but a systemic endocrine condition, one in which the molecular conversation between gut and brain is disrupted at baseline, partially restored by refeeding, and in key respects strikingly resistant to change. For clinicians and researchers alike, the message is that the scale tells only part of the story, and that the hormones of hunger may hold the rest.

Subject of Research: Appetite-related biomarker changes during inpatient treatment of anorexia nervosa and their association with diet and body mass index

Article Title: Exploring appetite-related biomarkers in anorexia nervosa during treatment: associations with diet and comparison with healthy controls

Article References: Hovland, I. H., Otterdal, K. L., Bang, L., Vinje, H., Herfindal, A. M., Strømland, S. S., Aspholm, T. E., Arsenovic, D., Reistad, H. T., Dahl, J., Ones, M. L., Weider, S., Bulik, C. M., Rø, Ø., & Bøhn, S. K. (2026). Exploring appetite-related biomarkers in anorexia nervosa during treatment: associations with diet and comparison with healthy controls. Journal of Eating Disorders. https://doi.org/10.1186/s40337-026-01752-1

Image Credits: AI Generated

DOI: 10.1186/s40337-026-01752-1

Keywords: anorexia nervosa, appetite hormones, gut-brain axis, ghrelin, leptin, GLP-1, GIP, adiponectin, dietary fiber, nutritional rehabilitation, biomarkers, eating disorders

The research, published in the Journal of Eating Disorders, analysed the medical records of 62 adults hospitalised for anorexia nervosa at a single French centre between January 2020 and December 2025. To be included, patients had to stay in hospital for more than five days, carry a diagnosis of anorexia nervosa, and have no pre-existing liver disease that could confound the interpretation of their liver enzymes. The overwhelming majority of participants, 95 percent, were female, with a mean age of 28.9 years. Their mean body mass index at admission was 13.47 kilograms per square metre, a figure that places most patients deep within the range of extreme, organ-threatening malnutrition.

The findings on the prevalence of starvation hepatitis were striking in their own right. Half of all patients, 31 of the 62 admitted, already had the condition when they arrived, defined by elevated transaminases, the enzymes alanine aminotransferase and aspartate aminotransferase, in the context of advanced protein-energy malnutrition. This liver injury is thought to arise because prolonged starvation depletes the liver of the substrates it needs to maintain its own cells, triggering autophagy, steatosis-like changes and hepatocyte dysfunction. Clinically, it matters because the liver sits at the centre of the metabolic machinery that must be revived when feeding resumes, and because severe transaminase elevations can themselves signal hepatic compromise that requires careful management.

Refeeding syndrome, the study’s second focus, is defined as a clinically significant decrease in plasma phosphate, potassium and/or magnesium within five days of resuming caloric intake. The mechanism is deceptively simple but physiologically profound. In starvation, insulin secretion falls to minimal levels and the body switches to burning fatty acids and ketone bodies, while intracellular stores of phosphate, potassium and magnesium are progressively depleted even though serum levels may look deceptively normal. When carbohydrates are suddenly reintroduced, insulin surges, driving glucose and electrolytes into cells and causing serum phosphate and other electrolytes to plummet. The consequences can include cardiac arrhythmia, respiratory failure, seizures, and death. Clinical guidelines from bodies such as NICE and the French Haute Autorité de Santé already recommend low initial caloric intake and close electrolyte monitoring in high-risk patients, but identifying who is truly high risk remains an inexact science.

In the new cohort, refeeding syndrome occurred in 19 patients, or 30.6 percent overall, within the first five days of nutritional rehabilitation. But the distribution was far from even. Among patients who had starvation hepatitis at admission, 48.4 percent went on to develop refeeding syndrome, compared with just 12.9 percent of those whose liver enzymes were normal when they arrived. That difference, statistically significant with a p-value of 0.006, hinted at a strong biological relationship between the two conditions, one that clinicians had long suspected but that had never before been formally tested in this population.

To confirm that the association was real and not merely a reflection of patients being sicker in general, the researchers performed a multivariate logistic regression, adjusting for body mass index and initial caloric intake, two factors that are themselves known to influence refeeding risk. The result held. Starvation hepatitis at admission was the only independent predictor of refeeding syndrome, with an adjusted odds ratio of 3.6 and a 95 percent confidence interval of 1.08 to 12.2, and a p-value of 0.038. In other words, even after accounting for how thin the patient was and how aggressively calories were reintroduced, the presence of liver injury on arrival more than tripled the odds of the electrolyte crisis that follows.

The biological plausibility of this link is a subject worth unpacking. The liver is the primary site of glycogen storage, gluconeogenesis, and phosphate-dependent ATP production, all of which are central to the pathophysiology of refeeding. A malnourished liver that is already injured may have diminished capacity to handle the sudden metabolic load of renewed nutrition, including the surge in insulin-driven intracellular uptake of phosphate that characterises refeeding syndrome. Hepatic depletion of adenosine triphosphate and phosphorus stores may leave patients with less reserve to buffer the shift, so serum phosphate falls faster and further. The authors propose that starvation hepatitis may therefore serve not just as a marker of extreme malnutrition but as a window into the functional state of the metabolic machinery that refeeding will stress.

What makes the finding clinically compelling is the simplicity of the marker involved. Transaminase measurements are a routine part of the standard blood panel drawn from virtually every hospitalised patient, requiring no specialised equipment, no imaging, and no additional cost. If a team knows that elevated liver enzymes on the admission screen flag a patient as being at especially high risk of refeeding syndrome, they can act on that information immediately: starting calories at a lower level, advancing the feeding plan more cautiously, and scheduling more frequent checks of phosphate, potassium and magnesium over the critical first five days. Electrolyte abnormalities detected early can often be corrected with supplementation before they progress to arrhythmia or organ failure, which is precisely the kind of preventable deterioration that structured monitoring is designed to avert.

The study does have limitations inherent to its design. It was retrospective, meaning the researchers relied on data collected in the course of routine clinical care rather than on a prospectively standardised protocol, and it was conducted at a single centre with a modest sample size of 62 patients. The confidence interval around the odds ratio, while excluding the null value, is wide, reflecting the small number of events involved. Residual confounding cannot be excluded, and the study population, overwhelmingly female and severely underweight, may not fully represent the broader spectrum of eating disorders seen in clinical practice. Nevertheless, the consistency of the effect with known physiology, and the fact that it persisted after adjustment for the most obvious confounders, lend the finding credibility and make it a candidate for confirmation in larger, prospective cohorts.

For clinicians working in eating disorder units, medical wards and intensive care settings, the study offers a practical rule of thumb grounded in evidence: check the liver panel before the first meal. For researchers, it opens a new line of inquiry into the hepatic mechanisms that connect starvation and refeeding, potentially identifying further biomarkers of metabolic reserve. And for patients and families, it is a reminder that recovery from severe anorexia nervosa is a medically intricate process, one in which the pace of renourishment can matter as much as the nutrition itself. A simple blood test, the study suggests, may help clinicians get that pace right for the patients who need caution most.

Subject of Research: The association between starvation hepatitis and refeeding syndrome in hospitalised patients with severe anorexia nervosa

Article Title: Starvation hepatitis and refeeding syndrome in anorexia nervosa: a retrospective cohort study

Article References: DEGLAIRE, J., ROULAND, A., GERSTER, T., BRINDISI, M.-C., BOUILLET, B., LUU, M., & MOUILLOT, T. (2026). Starvation hepatitis and refeeding syndrome in anorexia nervosa: a retrospective cohort study. Journal of Eating Disorders. https://doi.org/10.1186/s40337-026-01779-4

Image Credits: AI Generated

DOI: 10.1186/s40337-026-01779-4

Keywords: anorexia nervosa, starvation hepatitis, refeeding syndrome, malnutrition, liver enzymes, electrolytes, nutritional rehabilitation, hypophosphatemia, eating disorders, hospitalisation, risk prediction, transaminases

The review, registered prospectively on PROSPERO and updated through repeated searches in June 2024, April 2025 and May 2026, cast a deliberately wide net. The researchers included quantitative intervention studies involving adults with longstanding and severe eating disorders, with no restrictions on diagnosis, type of intervention or treatment setting. After screening, they identified seventeen main empirical studies, reported across twenty publications, together with eight additional case reports or case studies. The dominant participant profile was female, and the dominant diagnosis was anorexia nervosa, reflecting the composition of the severe and enduring eating disorder population as it presents in specialist services. Crucially, most of the included studies reported real-world clinical data drawn from actual treatment services rather than from tightly controlled trial environments, which gives the synthesis an unusually strong ecological validity even as it exposes the fragility of the underlying evidence base.

The interventions examined spanned the full breadth of modern practice. Specialist inpatient treatment programs, high-calorie re-alimentation protocols, integrated pathways built around enhanced cognitive behavioral therapy, standalone outpatient care, digital and virtual transition support, pharmacological treatments, neuromodulation and even neurosurgery all came under scrutiny. Yet despite this breadth of therapeutic activity, the review found only two level II randomized controlled trials in the entire literature. One of those trials tested whether adding a low-intensity digital self-management program after intensive treatment could sustain recovery, and found no added benefit. The other, conducted in a small inpatient sample of patients with eating disorders and comorbid post-traumatic stress disorder, reported preliminary benefits from adjunctive infra-low frequency neurofeedback. The scarcity of randomized evidence for one of psychiatry’s highest-morbidity populations is itself one of the most striking findings of the review.

Against that limited trial evidence, the level III cohort studies told a more coherent story. Specialist inpatient treatment and intensive integrated care pathways were consistently associated with improvements in body mass index, eating disorder psychopathology, broader psychological symptoms, day-to-day functioning and, where it was assessed, quality of life. The clearest signal of benefit, the authors report, emerged from integrated pathways that combined collaborative psychological treatment, weight restoration into the normal range, and continuity of care across different levels of the health system, from inpatient admission through to supported outpatient follow-up. In other words, it was not any single therapeutic ingredient but the combination and the continuity that appeared to drive recovery in this hardest-to-treat group.

Perhaps the most consequential clinical insight from the synthesis concerns what does and does not predict outcome. Duration of illness, long treated as a proxy for hopelessness, was not a consistent predictor of how patients fared. What mattered far more was discharge body mass index within the healthy range, which was associated with good outcomes at follow-up. That single observation carries an enormous practical weight: it reframes the therapeutic goal from simply managing an incurable condition toward actively achieving and maintaining physiological restoration as the foundation for psychological recovery. Standalone outpatient treatment and low-intensity digital transition support, by contrast, showed only limited benefits in this population, suggesting that severely unwell adults may require more intensive, structured and supervised care than routine community services typically provide.

The less conventional arms of the evidence base were far less encouraging. Studies of pharmacological interventions, neuromodulation techniques and neurosurgical procedures were small, largely uncontrolled, and produced inconsistent effects on the core outcomes that matter in eating disorders, such as weight restoration, reduced food-related anxiety and normalized eating behavior. For a field in which deep brain stimulation and experimental pharmacotherapy occasionally generate dramatic headlines, the review’s sober verdict functions as an important corrective: the most reliable gains currently come from well-organized, multidisciplinary clinical care, not from technological interventions that remain at an experimental stage.

The authors are candid about the limitations of the literature they synthesized. This is a heterogeneous patient group with high rates of psychiatric and medical comorbidity, yet many studies provided little information on ethnicity, socioeconomic background, comorbid conditions or the legal treatment status of participants. Definitions of what constitutes longstanding or severe eating disorder varied across studies, making direct comparison difficult. Observational designs dominated, follow-up periods were generally short, and reporting of outcomes that patients and families prioritize, including quality of life, relapse, readmission and treatment acceptability, was inconsistent. These weaknesses do not undermine the central conclusion that improvement is possible, but they do mean clinicians and policymakers must interpret the magnitude and durability of those improvements with appropriate caution.

The implications reach well beyond academic debate. In several countries, including the United Kingdom, insurers and health systems have at times restricted access to intensive eating disorder treatment for patients judged to have chronic, unremitting illness, on the reasoning that prolonged disease duration predicts poor response. By showing that illness duration alone does not forecast outcome, while achieving a healthy weight and sustained psychological support does, the review provides an evidence-based argument for expanding rather than rationing access to integrated care. It also aligns with the growing involvement of people with lived experience in eating disorder research; the author team itself includes a peer researcher with lived experience, and the authors call for future studies to prioritize lived-experience perspectives alongside comorbidity, legal status and continuity of care.

The review’s agenda for future research is explicit. The authors call for standardized definitions and outcome reporting so that studies can be compared and pooled, for implementation research that examines how integrated pathways can be scaled in real health systems, for longer follow-up periods that capture relapse and sustained recovery, and for trials that deliberately include the comorbidities and legal complexities that characterize real clinical populations. Until that evidence arrives, the message for patients, families and clinicians is one of qualified hope. Adults whose eating disorders have endured for years are not beyond help. The treatment that works best is demanding, multidisciplinary and continuous, combining nutritional rehabilitation to a healthy weight with evidence-based psychotherapy and seamless support after discharge, and the review makes clear that the real barrier to recovery for many patients may not be their diagnosis or its duration, but the assumption that treatment is futile.

Subject of Research: Treatment interventions for adults with longstanding and severe eating disorders

Article Title: Treatment interventions for longstanding and severe eating disorders: an updated systematic review and narrative synthesis

Article References: Ayton, A., Kumar, A., Downs, J., Boniface, S., & Treasure, J. (2026). Treatment interventions for longstanding and severe eating disorders: an updated systematic review and narrative synthesis. Journal of Eating Disorders. https://doi.org/10.1186/s40337-026-01722-7

Image Credits: AI Generated

DOI: 10.1186/s40337-026-01722-7

Keywords: eating disorders, anorexia nervosa, systematic review, CBT-E, nutritional rehabilitation, weight restoration, inpatient treatment, treatment outcomes, integrated care, digital interventions, continuity of care, Journal of Eating Disorders