NCT05469997

Ketogenic Diet Interventions in Parkinson's Disease: Safeguarding the Gut Microbiome

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 52 (actual)
• Sponsor: University of British Columbia · Academic / Other
• Sex: All
• Age: 45 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

Parkinson's Disease (PD) is the second most common neurodegenerative disorder with common gut-related symptoms, which are attributed to alterations in the gut microbiome - the collection of microorganisms that live within the gut. Classical ketogenic diets (KD) have shown to be beneficial in PD and non-PD populations but are associated with alterations in the gut microbiome that are characteristic of a perturbed system. This study aims to investigate the safety of modified Mediterranean-ketogenic interventions that are thought to be safer alternatives to the classical KD, as it relates to the gut microbiome health in patients with PD. We hypothesize that the modified Mediterranean-ketogenic interventions will not be associated with any significant perturbation of the gut microbiome in PD patients.

Detailed description

Background: Parkinson's disease (PD), the second most common and the most rapidly growing neurodegenerative disease worldwide \[1,2\]. Gut-related symptoms are common and often the initial symptoms, suggesting a possible intestinal origin of PD \[4\]. Over a dozen studies have demonstrated gut dysbiosis in PD with reduced diversity, increased pro-inflammatory capacity, and decreased Short-Chain Fatty Acids (SCFA) production as key characteristics \[5-10\] and persistently increased relative abundance of Akkermansia \[5-17\]. Emerging evidence suggests that both ketogenic \[18-23\] and Mediterranean diets \[24-30\] have beneficial and likely complementary effects in PD. Mediterranean diets (MeDi) are primarily but not exclusively plant-based \[24\]. Their promotion of high fiber content intake promotes the production of SCFA and are associated with improved gut microbiome health \[25\]. Ketogenic diets (KD) are high in fat, adequate in protein and very low in carbohydrates \[31\]. KD can provide ketone bodies (KB) \[32\] as an alternative fuel source to glucose, the utilization of which is perturbed in the PD brain \[33\]. Another method for inducing the state of ketosis is by consumption of ketogenic medium-chain triglycerides (MCTs) \[43\]. MCTs are converted to KBs, which can readily cross the blood-brain barrier and be used as an energy source \[43\]. Pilot trials in PD report improved Unified Parkinson's Disease Rating Scale (UPDRS) scores \[20\], cognitive performance \[21\] and non-motor symptoms \[22\] with KD interventions \[23\]. Several studies of classical KDs in non-PD populations have observed significant alterations in the gut microbiome, including an increase in Akkermansia \[47\] and a decrease in fecal SCFA levels \[50\]. By combining the principles of MeDi with ketogenic interventions, we hope to leverage the gut-health promoting aspects of the former with bioenergetics benefits of the latter, in a safe manner. To the best of our knowledge, no clinical trials have been performed into combined ketogenic and Medi-stye dietary interventions in PD yet. Design: A proof of concept, random order, cross-over study in participants with PD examining two 8-week interventions: (1) the Mediterranean ketogenic diet (MeDi-KD) and (2) the Mediterranean diet supplemented with medium-chain triglycerides (MeDi-MCT), separated by an 8-week washout period. Hypothesis: 1. Neither the MeDi-MCT nor the MeDi-KD (pre-post comparison) will be significantly associated with measures of gut microbiome dysbiosis such as increased gut inflammation, impaired gut-barrier integrity, and reduced SCFA content. 2. Retention rates for both diets will be at least 75%.

Conditions

• Parkinson Disease

Interventions

Type	Name	Description
BEHAVIORAL	Mediterranean-Ketogenic Diet	In the MeDi-KD group, the participants will adhere to a modified Mediterranean-ketogenic diet. The ketogenic component of the diet will require limiting the intake of carbohydrates to about 10% of all calories consumed in a day, while obtaining most of the energy from healthy fats, mostly from plant-based sources (\~70-75% of your daily caloric intake) and lean proteins (\~15-20% of your daily caloric intake). The ketogenic ratio (the ratio of fat to carbohydrates) will be gradually increased during the first week from 1:1 to 3:1. The Mediterranean component of the diet will encourage the participants to consume more green leafy vegetables, nuts, and olive oil, while limiting the consumption of processed or fried food, red meat, full-fat dairy, and sweets.
DIETARY_SUPPLEMENT	Mediterranean diet supplemented with medium-chain triglyceride oil	The participants will adhere to the Mediterranean diet. In addition, they will be asked to take two daily doses of medium-chain triglyceride oil (MCT oil). The MCT oil supplement (Nutiva MCT oil, Nutiva Inc.) is approved by Health Canada (NPN: 80086912) and will be used according to its approved condition of use (i.e., source of medium-chain fatty acids which supports energy production in the body at a cellular level \[ATP\]). Each serving of this product provides 130 Calories from MCTs (14 g) with a C8-C10 ratio of 60:40. Nutiva MCT oil can be mixed into any beverage of choice, but cannot be used for cooking. participants will start the intervention by taking 5 mL of MCT oil twice daily for the first day to acclimate their bodies to the supplement and gradually increase the dose to 14 g BID by the end of week 1. The participants may be asked to increase the dose to 20 mL of MCT twice daily if tolerability remains positive.

Timeline

• Start date: 2023-03-01
• Primary completion: 2024-10-30
• Completion: 2024-10-30
• First posted: 2022-07-22
• Last updated: 2026-03-23

Locations

1 site across 1 country: Canada