Can a ketone drink reduce the severity of symptoms of Parkinson’s disease?

INTERVENTION: To ensure equal group sizes, participants will be block randomized to a ketone ester or placebo control group. Following a 2‐week period during which baseline measurements will be taken (weeks ‐2 to 0), members of each group will be asked to ingest a drink containing either 25 ml of ketone ester (DeltaG) or an equal volume of a taste‐matched control fluid four times daily for 1 month (weeks 0 to 4). Participants will also be followed for 2 weeks after the conclusion of the intervention to monitor for any lasting changes (weeks 4 to 6). Over the course of the entire 2‐month period, participants will visit the study location on a fortnightly basis and undergo a series of non‐invasive, minimally burdensome motor, nonmotor, and biological tests in order to monitor for changes in functional status and disease pathology. Participant compliance will also be assessed to inform future studies and to inform whether or not we will choose to extend the intervention period. Depending on the preliminary results and participants’ compliance, we may want to extend the intervention by a further 2 months to monitor for cumulative (or additional) positive effects of the ketone supplement. CONDITION: Parkinson's disease ; Nervous System Diseases PRIMARY OUTCOME: ; 1. Overall symptom severity in the drug "off" state assessed using the Movement Disorder Society‐Unified Parkinson’s Disease Rating Scale (MDS‐UPDRS) at weeks 0 and 4; 2. Daily activity and gait assessed using a continuous activity monitor (Axivity AX3) worn on the lower back by participants for 7 days before (weeks ‐2 to ‐1) and during (weeks 2 to 3) the intervention; 3. Motor skills assessed using a smartphone application once a day; 4. Olfaction assessed using the Sniffin’ Sticks 16‐odor identification test at weeks 0, 4, and 6; 5. Selective attention assessed using the Stroop color‐word test at weeks 0, 4, and 6; 6. Cognitive function assessed using the the Montreal Cognitive Assessment (MoCA) at weeks 0, 4, and 6; 7. Fatigue assessed using the Fatigue Severity Scale (FSS) survey over the phone once per week during a randomly‐timed compliance call; 8. Quality of life of participant assessed using the PDQ‐39 questionnaire at weeks 0, 4, and 6; 9. Quality of life of participant's carer assessed using the PDQ‐Carer questionnaire at weeks 0, 4, and 6; 10. Parkinson's disease‐related sleep disorder assessed using the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) at week 0.; INCLUSION CRITERIA: 1. Diagnosis of Parkinson's disease 2. Taking L‐dopa 3. Hoehn and Yahr stages 1‐2 4. Fluent in English 5. Capable of giving informed consent 6. Aged 40‐80 SECONDARY OUTCOME: ; 1. Blood uric acid measured in a fasted state at weeks 0, 2, 4, and 6; 2. Blood glucose measured in a fasted state at weeks 0, 2, 4, and 6; 3. Blood fructosamine measured in a fasted state at weeks 0, 2, 4, and 6; 4. Blood insulin measured in a fasted state at weeks 0, 2, 4, and 6; 5. Blood lipids measured in a fasted state at weeks 0, 2, 4, and 6; 6. Blood C‐reactive protein (CRP) measured in a fasted state at weeks 0, 2, 4, and 6; 7. Blood inflammatory cytokines measured in a fasted state at weeks 0, 2, 4, and 6; 8. Compliance assessed by calling patients at random once per week to ask them when they last consumed the study drink and to request that they blindly (we will mask the monitor) measure their own blood ketone levels by fingerstick; 9. Participant subjective comments on their experiences taking the drink assessed using a consumer‐style questionnaire at week 4; ; Uric acid is a major circulating antioxidant that tends to be depleted in the blood of patients with Parkinson’s disease. Participants’ glucose, fructosamine, insulin, and lipids levels will afford insight into the quality of their carbohydrate metabolism and relative cardiovascular risk. This is relevant because diabetes and heart disease are also age‐related diseases and often present as comorbidities alongside Parkinson’s disease. CRP and inflammatory cytokines are markers of systemic inflammation, a phenomenon characteristic of, and involved in the development of, many age‐related diseases.;