Nutritional Ketosis in Parkinson's Disease — a Review of Remaining Questions and Insights

Abstract

Nutritional ketosis has promise for treating Parkinson’s disease. Three previous studies explored the use of a ketogenic diet in cohorts with Parkinson’s disease, and, while not conclusive, the data suggest non-motor symptom benefit. Before the ketogenic diet can be considered as a therapeutic option, it is important to establish with greater certainty that there is a reliable symptomatic benefit: which symptoms or groups of symptoms are impacted (if non-motor symptoms, which ones, and by which mechanism), what timescale is needed to obtain benefit, and how large an effect size can be achieved? To accomplish this, further investigation into the disease mechanisms based on pre-clinical data and hints from the clinical outcomes to date is useful to understand target engagement and gauge which mechanism could lead to a testable hypothesis. We review research pertaining to ketogenic diet, exogenous ketones, fasting, clinical studies, and theoretical review papers regarding therapeutic mechanisms from direct ketone body signaling and indirect metabolic effects. Through discussion of these findings and consideration of whether the ketogenic diet can be regarded as therapeutically useful for adjunctive therapy for Parkinson’s disease, we identify remaining questions for the clinician to consider prior to recommending this diet.

The Anti-Inflammatory Effect of Preventive Intervention with Ketogenic Diet Mediated by the Histone Acetylation of mGluR5 Promotor Region in Rat Parkinson’s Disease Model: A Dual-Tracer PET Study

“…ough the exact pathology of PD remains elusive, the oxygen free radicals, trophic factors loss, altered calcium homeostasis, and neuroinflammation have been supposed to be involved [6,[43][44][45]. However, these pathological processes associated with PD might be alleviated by the multiple neuroprotective mechanism of ketosis induced by KD [46][47][48][49]. e anti-inflammatory properties of KD also have been verified in other neurological disorders associated to neuroinflammation, including multiple sclerosis, pain, epilepsy, AD, and spinal cord injury [50][51][52].…”

NADPH and Mitochondrial Quality Control as Targets for a Circadian-Based Fasting and Exercise Therapy for the Treatment of Parkinson’s Disease

“…Studies on the effects of a ketogenic diet by itself, without exercise therapy, on PD subject symptoms have recently been reviewed [ 132 ]. Unlike the results from mouse models of PD where the ketogenic diet has shown moderate protective effects, the clinical results from PD subjects showed that the diet did not affect motor symptoms and only showed slight improvements in the non-motor symptoms [ 133 ].…”

Update to the Treatment of Parkinson’s Disease Based on the Gut-Brain Axis Mechanism

“…At a sufficient degree of ketosis, the direct signal effect of the ketone body can induce the gene expression of antioxidant enzymes, reduce apoptosis through a metabolic state similar to fasting, and theoretically increase neurotransmitters. A ketogenic diet with a high percentage of fat, a low percentage of carbohydrates, protein, and other nutrients that cause nutritional ketosis in PD patients has indeed been found to ameliorate the condition to some extent ( Phillips et al, 2018 ; Choi et al, 2021 ).…”