Summary: Weight loss in Parkinson’s disease has long been a mystery, but new research has uncovered a hidden metabolic “emergency engine” at play. Scientists discovered that weight loss in Parkinson’s is driven by a selective loss of body fat—while muscle mass remains surprisingly preserved.
This fat loss isn’t caused by poor nutrition alone; instead, it reflects a failure of the body’s primary energy system (glycolysis). When the brain and body can no longer efficiently turn glucose into energy, they are forced to burn fat and produce ketone bodies to survive. This “thinness” is actually a biological warning sign of an internal energy collapse.
Key Facts
- Selective Fat Loss: Parkinson’s patients lose significant body fat, but their muscle mass is generally maintained in the early-to-mid stages of the disease.
- The Failed Main Engine: The study found impaired glycolysis and TCA cycle function, meaning the body’s standard way of creating energy from carbohydrates is broken.
- Survival Mode Activation: To compensate for failed glucose metabolism, the body switches to an “emergency engine,” breaking down fat to create ketone bodies for fuel.
Source: Fujita Health University
Weight loss is a well-recognized but poorly understood non-motor feature of Parkinson’s disease (PD). Many patients progressively lose weight as the disease advances, often alongside worsening motor symptoms and quality of life.
Until now, it was unclear whether this reflected muscle loss, poor nutrition, or deeper metabolic changes. New research shows that PD-related weight loss is driven mainly by a selective loss of body fat, while muscle mass is largely preserved, and is accompanied by a fundamental shift in how the body produces energy.
Although PD is classically viewed as a neurological disorder, increasing evidence points to widespread metabolic dysfunction. Patients often experience fatigue and nutritional decline, yet dietary advice has largely focused on boosting calories.
The new findings challenge this conventional view, showing that weight loss in PD reflects a failure of the body’s standard energy-producing pathways rather than reduced food intake alone.
The findings were published on November 30, 2025, in the Journal of Neurology, Neurosurgery & Psychiatry.
The study was led by Professor Hirohisa Watanabe from the Department of Neurology at Fujita Health University, School of Medicine, Japan, along with Dr. Atsuhiro Higashi and Dr. Yasuaki Mizutani from Fujita Health University.
The team aimed to clarify what exactly is lost when patients with PD lose weight and why the body is forced to change its energy strategy.
The researchers enrolled 91 patients with PD and 47 healthy controls and conducted a detailed analysis of body composition using bioelectrical impedance analysis. This allowed them to separately measure fat mass, muscle mass, and other body components. In parallel, they performed comprehensive plasma metabolomic profiling using mass spectrometry to evaluate glycolysis, the Krebs (TCA) cycle, lipid metabolism, mitochondrial function, and ketone body production.
The results revealed a clear and striking pattern. Compared with healthy controls, patients with PD had lower body weight and body mass index, driven almost entirely by a reduction in body fat. Muscle mass was largely preserved in the early-to-mid stages of disease, and the prevalence of sarcopenia was comparable to that seen in the general aging population.
“We clarified that it is not the muscle that is decreasing, but the fat,” says Prof. Watanabe. “This changes how we should think about weight loss in Parkinson’s disease.”
Crucially, the study revealed that this fat loss is a consequence of a deeper metabolic failure. Key metabolites, such as lactic acid and succinic acid were significantly reduced, indicating impaired glycolysis and dysfunction of the TCA cycle—the body’s primary ‘’main engine’’ for adenosine triphosphate production. This failure means that glucose can no longer be efficiently converted into usable energy.
As a result, the body activates an alternative survival mechanism. Markers of ketone bodies, including acetoacetic acid, were elevated, along with metabolites associated with amino acid catabolism, demonstrating activation of an “emergency engine” that relies on fat and protein breakdown to sustain energy production. In other words, when carbohydrate metabolism fails, the body is forced to burn fat to survive.
Importantly, this metabolic shift was not uniform across patients. Ketone body levels were highest in thinner patients and those with more advanced disease severity. This suggests that as PD progresses, the body increasingly relies on fat breakdown to compensate for impaired carbohydrate metabolism.
“Being thin may signal an invisible energy crisis occurring inside the patient’s body,” Dr. Higashi explains. “The body is forced to burn fat to survive.”
Beyond explaining weight loss, the findings have important implications for future care. Simply increasing calorie intake may be insufficient if the body’s main glucose-based energy engine is not functioning properly.
The study suggests a need to rethink nutritional and therapeutic strategies for PD. Interventions that stabilize glycolysis, improve mitochondrial function, or prevent excessive reliance on fat-derived ketone bodies may represent entirely new treatment approaches, distinct from conventional dopamine replacement therapy.
Together, the results highlight PD as a disorder of both the brain and the body, driven by hidden metabolic dysfunction. By showing that weight loss reflects selective fat depletion due to impaired carbohydrate-based energy production, not muscle loss, the study offers a new framework for identifying high-risk patients and intervening earlier.
Recognizing “thinness” as a biological warning sign could enable more proactive, personalized care to prevent disease-related energy collapse.
Funding information
The present work was supported by JSPS KAKENHI (Grant Number JP22K07508) and the Fujita Mind-Brain Research and Innovation Center for Drug Generation of Japan’s Peak Research Universities Program (Grant Number JPJS00420240019), both funded by the Japan Society for the Promotion of Science and by the Japan Agency for Medical Research and Development (Grant Number 22dk0207055h0002).
Key Questions Answered:
A: It’s not just about calories; it’s about how the body processes them. Parkinson’s causes a “glitch” in the body’s main energy engine (glucose metabolism). Even if a patient eats well, their body can’t use the sugar efficiently, so it starts burning through its own fat stores as an emergency backup fuel.
A: Yes, it can be a major warning sign. Researchers found that the thinner the patient, the higher their levels of “emergency” ketone bodies. This suggests that being thin isn’t just a side effect—it’s a signal that the body is in the middle of an invisible energy crisis and is struggling to keep up with the disease.
A: Simply adding more calories might not be enough. Because the problem is a broken “engine,” the next step in research is finding ways to stabilize glucose metabolism or improve mitochondrial function. This discovery opens the door for entirely new treatments that focus on the body’s energy production rather than just replacing dopamine in the brain.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neurology and Parkinson’s disease research news
Author: Hisatsugu Koshimizu
Source: Fujita Health University
Contact: Hisatsugu Koshimizu – Fujita Health University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Metabolic profiles associated with fat loss in Parkinson’s disease” by Atsuhiro Higashi, Yasuaki Mizutani, Reiko Ohdake, Yasuhiro Maeda, Junichiro Yoshimoto, Sayuri Shima, Yusuke Seino, Akihiro Ueda, Mizuki Ito, Atsushi Suzuki, and Hirohisa Watanabe. Journal of Neurology, Neurosurgery & Psychiatry
DOI:10.1136/jnnp-2025-336929
Abstract
Metabolic profiles associated with fat loss in Parkinson’s disease
Background
Weight loss is a substantial non-motor feature of Parkinson’s disease (PD) associated with worse clinical outcomes, but the underlying mechanisms remain poorly understood. Thus, we investigated the mechanisms of PD-related weight loss by examining the correlation between body composition and various plasma metabolites.
Methods
We enrolled 91 patients with PD and 47 healthy controls between July 2021 and October 2023. Body composition was evaluated using bioelectrical impedance analysis. Plasma metabolite profiling was conducted via mass spectrometry, including short-chain and medium-chain fatty acids, Krebs cycle intermediates, ketone bodies and phospholipids. Subsequently, alterations in body composition in PD and their association with plasma metabolites were assessed.
Results
Patients with PD had lower body weight (p=0.003), body mass index (BMI; p=0.001) and body fat mass (p<0.001) compared with controls. Metabolomic analyses revealed that, in patients with PD, glycolysis and Krebs cycle markers (lactic acid and succinic acid) were reduced, while ketone bodies (acetoacetic acid and 3-hydroxybutyric acid), amino acid catabolism-related markers (2-hydroxybutyric acid and 2-oxobutyric acid) and acetic acid were elevated.
Notably, in patients with PD, acetoacetic acid and 3-hydroxybutyric acid negatively correlated with BMI. Phosphatidylcholine (40:2) was also elevated in PD and showed higher levels in individuals at more advanced Hoehn and Yahr stages.
Conclusions
PD-related fat loss was accompanied by a pattern of lower glycolytic activity and higher levels of lipid and amino acid metabolism-related metabolites, consistent with a potential shift in energy utilisation. These findings highlight metabolic pathways as potential targets for interventions to mitigate weight loss in PD.
