Acute Effects of Medium Chain Triglyceride (MCT) Nutritional Ketosis on Parkinson's Disease (PD) Symptoms and Biomarkers (MCT-PD)

Summary

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While three pilot studies of ketogenic diet (KD) in PD have shown either reduction in motor scores (UPDRS) or improved memory/fluency cognitive testing, there are gaps in knowledge of the time course and mechanisms of reported outcomes. Furthermore, only a standard ketogenic diet was studied while t...

While three pilot studies of ketogenic diet (KD) in PD have shown either reduction in motor scores (UPDRS) or improved memory/fluency cognitive testing, there are gaps in knowledge of the time course and mechanisms of reported outcomes. Furthermore, only a standard ketogenic diet was studied while there are variations such as MCT oil supplementation shown to increase keto-induction, and other adaptations may improve tolerability and micronutrient content. It is the goal of this proposed inpatient metabolic study to address the initial question of effect size and time course of ketosis. If suggestive of benefit in PD, this pilot study may lead to a subsequent larger study of long-term feasibility and effects on disease biomarkers and disease progression, which might also compare alternate diets of interest in PD such as Mediterranean diet. Thus, a pilot feasibility study is proposed, targeting retention rate >80% and adherence in the outpatient setting. Recruitment of 32 participants is based upon power analysis of secondary outcome, testing the Timed Up & Go mobility test that has reported validity in fall prediction, additionally plotting continuous and serially repeated direct/indirect ketosis measurements and motor as well as non-motor symptoms / exploratory disease biomarkers. It is hypothesized that, compared to a non-ketogenic healthy diet (low-fat diet), ketogenic diet supplemented by MCT oil (MCT-KD) will improve mobility tested by Timed Up & Go (TUG), as well as akinesia, tremor, and memory/executive function tasks, and will reduce motor and nonmotor fluctuations within the acute period of keto-induction and early ketogenic timepoints due to improved mitochondrial function and neurotransmitter synthesis. The primary objective is to test the hypothesis that nutritional ketosis (NK) supplemented by MCT oil in a PD cohort (MCT-KD) is feasible for a duration of three weeks. The secondary objective is to show that NK improves PD symptomatology in cognition (improved attention, recall, and executive function), mobility (TUG), and motor function (bradykinesia, akinesia and tremor) to a greater extent than a standard, low fat diet (LFD) within three weeks.

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