Potential Synergistic Roles of Ketogenic Diet and Stem Cell Therapy in Parkinson's Disease: A Narrative Review

Parkinson's disease (PD) is a complex neurodegenerative disorder and is the second most common, after Alzheimer's disease. Marked by the gradual loss of dopaminergic signaling and accumulation of abnormal protein aggregates, this condition presents in patients with a combination of motor and non-motor symptoms. While first-line treatments often include exogenous dopamine therapy, such as levodopa-carbidopa, and surgical procedures or deep brain stimulation, these mainstream therapeutics often fail to improve disabling symptoms of PD, induce serious side effects, and have no effect in controlling disease progression. An alternative approach of cell-based therapies has shown to be an effective therapeutic in reducing neurodegeneration. Additionally, diet and exercise modifications have played crucial roles in the management of the condition. Given that certain dietary regimens may be associated with stem cell renewal and regeneration, specifically in the context of tumors and cancer, a potential combination of a ketogenic diet, a high-fat and low-carbohydrate strict dietary regimen, and stem cell therapy with dopaminergic neurons could serve as a beneficial therapeutic option for PD patients, altering the underlying neurodegeneration. Based on several processes of PD pathophysiology, mainly mitochondrial dysfunction, defective protein clearance mechanisms, and neuroinflammation, treating patients with current therapeutics and implementing a ketogenic diet alongside stem cell therapy may significantly improve PD symptoms and progression. This narrative review was conducted using a structured literature search from PubMed and Google Scholar using terms such as PD, stem cell therapy, ketogenic diet, mitochondrial dysfunction, and neuroinflammation. Given the central roles of mitochondrial dysfunction, impaired protein clearance, and neuroinflammation in PD pathophysiology, the combined use of metabolic interventions and stem cell-based strategies represents an avenue for future investigation. Currently, there are no clinical trials using human models to establish the safety, feasibility, or efficacy of the combined therapy using the ketogenic diet and stem cell therapy in PD. Rigorous preclinical validation and well-designed clinical trials are required before such strategies can be considered viable disease-modifying options for PD.