Parkinson’s Disease: Weight Loss Linked to Fat Loss & Metabolic Shift, Not Muscle Loss

Weight loss is a common, yet often overlooked, complication of Parkinson’s disease (PD). For years, the focus has been on managing motor symptoms, but emerging research reveals a more complex picture. A new study, published on November 30, 2025, in the Journal of Neurology, Neurosurgery &amp. Psychiatry, challenges conventional thinking about why individuals with PD lose weight, suggesting it’s not simply a matter of reduced food intake or muscle wasting, but a fundamental shift in how the body processes energy.

Traditionally viewed as a neurological disorder, Parkinson’s is increasingly recognized as a systemic illness with widespread metabolic consequences. Patients frequently report fatigue and declining nutritional status, leading clinicians to often recommend simply increasing caloric consumption. However, this approach may be missing the mark, according to Professor Hirohisa Watanabe from the Department of Neurology at Fujita Health University in Japan, who led the research. “We clarified that it is not the muscle that is decreasing, but the fat,” Prof. Watanabe stated. “This changes how we should think about weight loss in Parkinson’s disease.”

The study involved 91 patients diagnosed with Parkinson’s disease and 47 healthy controls. Researchers utilized bioelectrical impedance analysis to meticulously assess body composition, differentiating between fat mass, muscle mass, and other bodily components. Simultaneously, they conducted comprehensive plasma metabolomic profiling using mass spectrometry, a technique that allows for detailed analysis of metabolites – the byproducts of metabolism – to evaluate key processes like glycolysis, the Krebs cycle, lipid metabolism, mitochondrial function, and ketone body production.

The findings were striking. Patients with Parkinson’s disease exhibited lower body weight and body mass index (BMI) compared to the control group. However, this weight loss was almost entirely attributable to a reduction in body fat. Remarkably, muscle mass remained largely preserved, particularly in the early to mid-stages of the disease. The prevalence of sarcopenia – age-related muscle loss – was comparable between the two groups, indicating that the weight loss in PD isn’t primarily driven by muscle wasting.

More importantly, the study uncovered a significant metabolic disruption. Key metabolites involved in glycolysis and the Krebs cycle – the body’s primary pathways for generating energy from glucose – were significantly reduced. Specifically, levels of lactic acid and succinic acid were notably lower in PD patients, indicating impaired glucose metabolism. This suggests that the body is struggling to efficiently convert glucose into usable energy.

In response to this energy deficit, the body activates an alternative survival mechanism. Researchers observed elevated levels of ketone bodies, such as acetoacetic acid, alongside metabolites associated with amino acid catabolism – the breakdown of protein. This indicates a shift towards utilizing fat and protein as energy sources when glucose metabolism falters. Essentially, when the body can’t efficiently process carbohydrates, it’s forced to burn fat to stay alive.

The degree of this metabolic shift correlated with disease severity and body weight. Patients who were thinner and had more advanced Parkinson’s disease exhibited higher ketone body levels, suggesting that the body increasingly relies on fat breakdown as the disease progresses. Dr. Atsuhiro Higashi, a co-author of the study, explained, “Being thin may signal an invisible energy crisis occurring inside the patient’s body. The body is forced to burn fat to survive.”

These findings have significant implications for how Parkinson’s disease is managed. Simply advising patients to eat more calories may be insufficient if the underlying metabolic pathways are impaired. The research suggests a need to explore novel therapeutic strategies that address the root cause of the energy deficit. Interventions aimed at stabilizing glycolysis, improving mitochondrial function, or preventing excessive ketone body production could offer new avenues for treatment, potentially complementing existing dopamine replacement therapies.

This study reinforces the understanding of Parkinson’s disease as a disorder that extends beyond the brain, impacting the entire body through widespread metabolic dysfunction. By demonstrating that weight loss in PD is primarily driven by selective fat depletion due to impaired carbohydrate metabolism, rather than muscle loss, the research provides a new framework for identifying at-risk patients and intervening earlier. Recognizing “thinness” as a potential biological warning sign could enable more proactive and personalized care, potentially preventing the debilitating consequences of disease-related energy collapse.