A randomized feasibility trial of medium chain triglyceride-supplemented ketogenic diet in people with Parkinson's disease

Abstract

Background: A ketogenic diet (KD) may benefit people with neurodegenerative disorders marked by mitochondrial depolarization/insufficiency, including Parkinson's disease (PD).

Objective: Evaluate whether a KD supplemented by medium chain triglyceride (MCT-KD) oil is feasible and acceptable for PD patients. Furthermore, we explored the effects of MCT-KD on blood ketone levels, metabolic parameters, levodopa absorption, mobility, nonmotor symptoms, simple motor and cognitive tests, autonomic function, and resting-state electroencephalography (rsEEG).

Methods: A one-week in-hospital, double-blind, randomized, placebo-controlled diet (MCT-KD vs. standard diet (SD)), followed by an at-home two-week open-label extension. The primary outcome was KD feasibility and acceptability. The secondary outcome was the change in Timed Up & Go (TUG) on day 7 of the diet intervention. Additional exploratory outcomes included the N-Back task, Unified Parkinson's Disease Rating Scale, Non-Motor Symptom Scale, and rsEEG connectivity.

Results: A total of 15/16 subjects completed the study. The mean acceptability was 2.3/3, indicating willingness to continue the KD. Day 7 TUG time was not significantly different between the SD and KD groups. The nonmotor symptom severity score was reduced at the week 3 visit and to a greater extent in the KD group. UPDRS, 3-back, and rsEEG measures were not significantly different between groups. Blood ketosis was attained by day 4 in the KD group and to a greater extent at week 3 than in the SD group. The plasma levodopa metabolites DOPAC and dopamine both showed nonsignificant increasing trends over 3 days in the KD vs. SD groups.

Conclusions: An MCT-supplemented KD is feasible and acceptable to PD patients but requires further study to understand its effects on symptoms and disease.

Trial registration: Trial Registration Number NCT04584346, registration dates were Oct 14, 2020 - Sept 13, 2022.

Keywords: Biomarker; Clinical trial; Ketogenic diet; Ketosis; Parkinson’s disease; Pilot study.

Fig. 1

Flow chart for the one-week in-hospital, double-blind, randomized, placebo-controlled diet (MCT-supplemented ketogenic diet vs. standard diet), followed by an at-home two-week open-label extension in a cohort of patients with Parkinson’s disease

Fig. 2

Reported AM fasting beta-hydroxybutyrate (BHB) mean values ± SEMs, days 1–7 (inpatient) and at week 3 (outpatient), by group. Day 1: baseline testing on regular diet; Days 2-7: inpatient randomized diet phase-ketogenic diet vs standard diet; Week 3: Assessment after 2 weeks of outpatient open-label ketogenic diet. Top: Total 7 subjects in the KD group vs. 9 subjects in the SD group; Middle: 3 subjects in the KD group vs. 7 subjects in the SD group without metabolic syndrome/insulin resistance; Bottom: 4 subjects in the KD group vs. 2 subjects in the SD group with metabolic syndrome/insulin resistance

Fig. 3

Continuous glucose monitor (CGM) results over 7 inpatient days for representative participants on a standard diet (top 2 plots, average/daily) and on a ketogenic diet (bottom 2 plots, average/daily). The top single line plot for each representative participant indicates mean glucose values, and the bottom multiple line plot shows each day’s values

Fig. 4

Resting-state EEG functional connectivity measure Kappa_w mean values per group KD (ketogenic diet). SD (standard diet) at preintervention (day 1), day 7, and week 3