Ketogenic Diet Interventions in Parkinson's Disease: Safeguarding the Gut Microbiome
- Conditions
- Parkinson Disease
- Interventions
- Behavioral: Mediterranean-Ketogenic DietDietary Supplement: Mediterranean diet supplemented with medium-chain triglyceride oil
- Registration Number
- NCT05469997
- Lead Sponsor
- University of British Columbia
- Brief 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%.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 50
- Age between 40-85 years
- PD diagnosis based on Movement Disorder Society (MDS) criteria [52]
- Hoehn & Yahr score of 1 to 3
- On stable dopaminergic medication for at least one month
- Atypical parkinsonism
- Medical or psychiatric conditions that would prevent full participation in the nutrition intervention
- Significant dysphagia
- Diabetes on insulin
- Anti-coagulation on warfarin
- Inflammatory bowel disease
- Dementia defined by Montreal Cognitive Assessment (MoCA) Scores of less than 21
- Inability to fill in electronic questionnaires or understand study instructions
- Use of immunomodulatory agents
- Probiotic use in the last 4 weeks (except for dietary sources such as yoghurt, kefir etc.), or antibiotic use in the last 3 months prior to the trial
- Use of MCT oil or on ketogenic diet in last 8 weeks prior to the trial
- Allergic to MCT oil, coconut oil, or coconut
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description MeDi(MCT-KD) Mediterranean diet supplemented with medium-chain triglyceride oil The participants in this arm will first undergo the MeDi-MCT intervention followed by the MeDi-KD intervention, after an 8-week washout period. MeDi(KD-MCT) Mediterranean-Ketogenic Diet The participants in this arm will first undergo the MeDi-KD intervention followed by the MeDi-MCT intervention, after an 8-week washout period. MeDi(KD-MCT) Mediterranean diet supplemented with medium-chain triglyceride oil The participants in this arm will first undergo the MeDi-KD intervention followed by the MeDi-MCT intervention, after an 8-week washout period. MeDi(MCT-KD) Mediterranean-Ketogenic Diet The participants in this arm will first undergo the MeDi-MCT intervention followed by the MeDi-KD intervention, after an 8-week washout period.
- Primary Outcome Measures
Name Time Method Change from baseline and difference across interventions in measures of fecal and serum calprotectin, a biomarker for gut inflammation. Preintervention 1 (Baseline 1)/ Post-intervention 1 (Week 8)/ Pre-intervention 2 (baseline 2; Week 16)/ Post-intervention 2 (Week 24) We will assess changes from baseline in levels of fecal and serum calprotectin, a biomarker for gut inflammation that is found at elevated levels in PD patients, before and after each 8-week intervention. We will also compare the two interventions to determine their relative safety.
Changes from baseline and differences across interventions in other measures of gut health, namely short-chain fatty acid production, gut-barrier integrity, and microbial composition. Preintervention 1 (Baseline 1)/ Post-intervention 1 (Week 8)/ Pre-intervention 2 (baseline 2; Week 16)/ Post-intervention 2 (Week 24) We will assess changes from baseline in the following biomarkers of gut health before and after each 8-week intervention:
Short-chain fatty acid (SCFA)/ butyrate production measured in freshly frozen fecal samples Gut microbiome compositions measure in fecal samples. Levels of zonulin, a biomarker for gut-barrier function, measured in fecal and blood serum samples.
We will track any potential adverse events.
- Secondary Outcome Measures
Name Time Method The number of participants who completed the study after successful enrollment relative to the total enrolled participants. Post-intervention 1 (Week 8)/Post-intervention 2 (Week 24) We will assess the retention rate of participants with respect to each intervention to determine the feasibility of the proposed dietary interventions.
Percent time spent in clinically relevant levels of ketosis ( equivalent to >0.5 mmol/L) by each participant throughout each intervention. Post-intervention 1 (Week 8)/Post-intervention 2 (Week 24) Adherence to the ketogenic dietary interventions will be measured using breath ketone analyzers (Ketonix). The participants will take daily measurements of their breath ketone levels and record them in their study journal.
Percent time is determined by the number of days they successfully reach clinically relevant levels of ketosis relative to the total intervention days for each intervention (i.e. 56 days).
Trial Locations
- Locations (1)
Djawad Mowafaghian Centre for Brain Health
🇨🇦Vancouver, British Columbia, Canada