Parkinson’s disease triggers a hidden shift in how the body produces energy

Researchers reveal that weight loss in Parkinson’s disease reflects a metabolic shift from carbohydrates to fat-based energy

2026-02-13

(Press-News.org)

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.

***

Reference
DOI: 10.1136/jnnp-2025-336929

About Fujita Health University
Fujita Health University (FHU) is a private medical university located in Aichi, Japan. Established in 1964, it houses one of the largest university hospitals in Japan. It's 900 member faculty provides diverse learning and research opportunities to medical students worldwide. Guided by its founding philosophy of "Our creativity for the people" Fujita Health University believes that it's students can shape the future through creativity and innovation. FHU has earned global recognition, ranking eighth among all universities and second among private universities in Japan in the 2020 Times Higher Education (THE) World University Rankings. The university ranked fourth worldwide in the 2024 THE University Impact Rankings for contributions to the "Good Health and Well-being" SDG (Sustainable Development Goals) of the United Nations (UN). In June 2021, the university made history as the first Japanese institution to host the THE Asia Universities Summit. In 2024, Fujita Health University was awarded the Forming Japan’s Peak Research Universities (J-PEAKS) Program by the Japanese government to establish an innovative academic drug discovery ecosystem and hub of a multi-university consortium for research and education.

Website: https://www.fujita-hu.ac.jp/en/index.html

About Professor Hirohisa Watanabe from Fujita Health University
Prof. Hirohisa Watanabe is currently a Professor and Chairperson of the Department of Neurology, Fujita Health University, School of Medicine. He received his Ph.D. from Nagoya University and graduated from Mie University School of Medicine in 1993. He completed neurological training at Nagoya Daini Red Cross Hospital and Nagoya University Hospital. His research focuses on aging, brain energy metabolism, biomarkers, Parkinson’s disease, and neurodegenerative disorders. He previously served as a Designated Professor at Nagoya University’s Brain and Mind Research Center and remains active in multiple national neurological societies, with extensive experience in clinical research and translational neuroscience.

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).

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Parkinson’s disease triggers a hidden shift in how the body produces energy

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