A recent study has found that weight loss in Parkinson's disease (PD) is primarily due to a reduction in body fat, rather than muscle loss. The research, published on November 30, 2025, in the Journal of Neurology, Neurosurgery & Psychiatry, provides new insight into the metabolic changes associated with PD.
The study was conducted by Professor Hirohisa Watanabe and colleagues Dr. Atsuhiro Higashi and Dr. Yasuaki Mizutani from Fujita Health University, School of Medicine in Japan. Their aim was to determine what is lost during weight loss in PD patients and why these changes occur.
Researchers enrolled 91 patients with PD and 47 healthy controls. They used bioelectrical impedance analysis to measure body composition and mass spectrometry for plasma metabolomic profiling. This allowed them to examine factors such as glycolysis, the Krebs cycle, lipid metabolism, mitochondrial function, and ketone body production.
The findings showed that people with PD had lower body weight and body mass index compared to healthy individuals. This difference was almost entirely due to a decrease in body fat while muscle mass remained largely intact during early-to-mid stages of the disease. According to Prof. Watanabe: "We clarified that it is not the muscle that is decreasing, but the fat. This changes how we should think about weight loss in Parkinson's disease."
Further analysis revealed significant reductions in key metabolites like lactic acid and succinic acid among PD patients. These results indicate impaired glycolysis and dysfunction of the TCA cycle—the body's main pathway for producing adenosine triphosphate (ATP), which is essential for energy.
With glucose metabolism compromised, the body turns to alternative methods for generating energy. Markers of ketone bodies such as acetoacetic acid were elevated along with metabolites related to amino acid breakdown. This shift shows an increased reliance on burning fat and protein when carbohydrate-based energy production fails.
Dr. Higashi noted: "Being thin may signal an invisible energy crisis occurring inside the patient's body. The body is forced to burn fat to survive." The study also found that thinner patients or those with more advanced PD had higher levels of ketone bodies.
These findings suggest current dietary recommendations focused only on increasing calorie intake may not be sufficient if glucose metabolism remains impaired. The authors propose that future strategies could include interventions aimed at stabilizing glycolysis or improving mitochondrial function instead of solely relying on conventional dopamine replacement therapy.
Overall, this research highlights that PD involves both neurological symptoms and widespread metabolic dysfunction throughout the body. By identifying selective fat loss as a marker of impaired carbohydrate-based energy production rather than muscle wasting, clinicians may be able to identify high-risk patients earlier and tailor care accordingly.
Recognizing "thinness" as a potential warning sign could lead to more proactive management approaches designed to prevent further decline in quality of life for those living with Parkinson's disease.
