Exercise + Ketone Supplement for Parkinson's Disease

(CYCLE Trial)

Overseen By Austin Luker, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Michigan

Disqualifiers: Cardiac disease, Rheumatoid arthritis, Dementia, others

Compensation: Varies

Number of Visits: 5

Duration: 2-6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining exercise with a ketone supplement (Ketone Ester Beverage) can improve exercise capacity in people with Parkinson's disease. Participants will consume either a ketone beverage or a placebo electrolyte drink before exercise sessions. The trial will compare different session lengths to determine the most effective approach. It suits those diagnosed with Parkinson's who can safely exercise and cycle. As an unphased trial, participants can contribute to innovative research that may enhance exercise strategies for Parkinson's disease.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that ketone ester drinks are generally safe and well-tolerated. For example, research found that these supplements improved exercise performance in people with Parkinson's disease, suggesting they might be a helpful addition to treatment. Another study demonstrated that ketone monoesters (a type of ketone supplement) were safe and well-tolerated in healthy adults. These findings support the idea that ketone esters could be safe for use in humans, including those with Parkinson's disease. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Parkinson's disease because they combine exercise with ketone supplements, offering a fresh approach compared to standard medications like levodopa or dopamine agonists. This study explores the potential of ketone ester beverages, which provide an alternative energy source for the brain, possibly enhancing brain function and exercise performance. The unique combination of ketones and aerobic exercise could lead to improved motor skills and cognitive function, making it a promising avenue for those looking for non-traditional treatment options.

What evidence suggests that this trial's treatments could be effective for Parkinson's disease?

This trial will explore the effects of combining exercise with ketone supplements for individuals with Parkinson's disease. Participants will be assigned to different treatment arms, including those receiving a ketone ester beverage before exercise sessions and those receiving a placebo electrolyte beverage. Research has shown that ketone ester supplements might help people with Parkinson's disease exercise more effectively. Specifically, studies have found that drinking a ketone ester drink can enhance the body's exercise capacity, which could benefit those with Parkinson's. These supplements are also under investigation for their potential to lessen Parkinson's symptoms. While these results are promising, they primarily highlight how ketone esters might aid in exercise and symptom management for Parkinson's patients. Combining exercise with ketone supplements is being explored as a way to potentially improve life quality for those with the condition. ^{1 2 6 7 8}

Who Is on the Research Team?

Chatkaew Pongmala, PhD

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for individuals with Parkinson's Disease who can safely perform exercises like cycling. It's not suitable for those with recent heart issues, uncontrolled diabetes, pregnancy, severe dementia, or conditions that make exercise unsafe such as significant pain or active rheumatoid arthritis.

Inclusion Criteria

I have been diagnosed with Parkinson's Disease.

Exclusion Criteria

I have heart or lung problems that affect my ability to exercise.

I experience severe symptoms like dizziness or pain that prevent me from exercising safely.

My diabetes is not well-managed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo exercise training with either ketone ester or placebo electrolyte beverage for 5 or 12 sessions

2-6 weeks

5-12 visits (in-person)

Follow-up

Participants are monitored for changes in VO2 max and endurance after the intervention

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cycling Intervention
• Electrolyte Beverage
• Ketone Ester Beverage

Trial Overview The study aims to see if a ketone ester beverage improves muscle strength and cardiovascular response when combined with an exercise program (cycling) in people with Parkinson's compared to just exercising while taking an electrolyte beverage.

How Is the Trial Designed?

Group I: 5-Session Ketone Ester Beverage & Exercise Experimental Treatment 2 Interventions

Participants will consume ketone ester (KE) beverage, consisting of 2 scoops (=25 g C8-KE) of Qitone Pro-Ketone Powder™ and electrolyte solution diluted in water, before each of 5 1-hour sessions of aerobic exercise.

Group II: 12-Session Ketone Ester Beverage & Exercise Experimental Treatment 2 Interventions

Participants will consume ketone ester (KE) beverage, consisting of 2 scoops (=25 g C8-KE) of Qitone Pro-Ketone Powder™ and electrolyte solution diluted in water, before each of 12 1-hour sessions of aerobic exercise.

Group III: 5-Session Electrolyte Beverage & Exercise Placebo Group 2 Interventions

Participants will consume placebo electrolyte (EL) beverage, consisting of an electrolyte solution diluted in water, before each of 5 1-hour sessions of aerobic exercise

Group IV: 12-Session Electrolyte Beverage & Exercise Placebo Group 2 Interventions

Participants will consume placebo electrolyte (EL) beverage, consisting of an electrolyte solution diluted in water, before each of 12 1-hour sessions of aerobic exercise

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

Published Research Related to This Trial

In a study involving seven volunteers with Parkinson's disease, five successfully followed a hyperketogenic diet for 28 days, which may help bypass defects in complex I activity associated with the disease.

All five participants showed improvements in their Unified Parkinson's Disease Rating Scale scores during the diet, although the possibility of a placebo effect cannot be excluded.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Parkinson disease with diet-induced hyperketonemia: a feasibility study. Vanitallie, TB., Nonas, C., Di Rocco, A., et al.[2022]

Ketone body supplements are gaining popularity among athletes as a potential fuel source during endurance exercise, but their effectiveness in enhancing performance remains unconvincing based on current evidence.

The sports supplementation industry, including ketone supplements, is poorly regulated, leading to concerns about inaccurate label claims and the need for objective validation of their ingredients and performance benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketone body supplement label claims: what supplement has been supplemented? Da Costa, D., Bangalee, V., Subban, K., et al.[2023]

In a study involving 14 patients with early-stage Parkinson's disease, a ketone ester drink improved their ability to sustain an 80 rpm cycling cadence by 24%, suggesting enhanced endurance performance.

The ketone ester also shifted metabolism away from carbohydrates, indicated by increased β-hydroxybutyrate levels, which may support its role as an adjunctive therapy to improve exercise outcomes in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Ketone Ester Drink Enhances Endurance Exercise Performance in Parkinson's Disease. Norwitz, NG., Dearlove, DJ., Lu, M., et al.[2022]

Exogenous ketone supplements, particularly combinations with medium chain triglycerides (KEMCT), significantly improved motor performance in rodent models, indicating their potential as alternatives to ketogenic diets for enhancing motor function.

The effectiveness of these ketone supplements varied based on the type of rodent, the specific formulation used, and the duration of exposure, suggesting that personalized approaches may be necessary for optimal results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exogenous Ketone Supplements Improved Motor Performance in Preclinical Rodent Models. Ari, C., Murdun, C., Goldhagen, C., et al.[2021]

Ingestion of β-hydroxybutyrate (βHB) salts before exercise successfully induced nutritional ketosis in trained cyclists, with plasma βHB levels significantly elevated during and after exercise.

While βHB salts altered metabolic responses, such as increasing the respiratory exchange ratio (RER), they did not impact lactate levels, perceived exertion, or exercise efficiency, and gastrointestinal symptoms were reported in a majority of participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of acute ingestion of β-hydroxybutyrate salts on the response to graded exercise in trained cyclists. Evans, M., Patchett, E., Nally, R., et al.[2022]

Ingesting a large dose of ketone monoester (600 mg/kg body mass) significantly increased plasma β-hydroxybutyrate levels and markers of cardiorespiratory stress (like ventilation and heart rate) during exercise in endurance-trained adults (n = 19).

Despite the increase in stress markers, the ketone supplementation did not improve performance in a subsequent time trial, indicating that while it affects physiological responses, it may not enhance exercise performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased cardiorespiratory stress during submaximal cycling after ketone monoester ingestion in endurance-trained adults. McCarthy, DG., Bostad, W., Powley, FJ., et al.[2022]

Ingestion of a 1,3-butanediol acetoacetate diester before a cycling time trial led to a 2% impairment in performance among 10 elite male cyclists, likely due to gut discomfort and increased perception of effort.

Despite increasing blood ketone levels significantly, the ketone diester negatively affected performance during a ~31 km time trial, suggesting that its use in a carbohydrate-fed state may not be beneficial for elite cyclists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketone Diester Ingestion Impairs Time-Trial Performance in Professional Cyclists. Leckey, JJ., Ross, ML., Quod, M., et al.[2022]

A novel ketone ester diet significantly increased blood ketone levels in rats while reducing cholesterol and triglycerides, suggesting a safe way to enhance energy efficiency without negative lipid effects.

Rats on this ketone diet showed improved physical performance, running 32% further on a treadmill, and enhanced cognitive function, completing maze tests 38% faster, indicating potential benefits for treating metabolic disorders in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel ketone diet enhances physical and cognitive performance. Murray, AJ., Knight, NS., Cole, MA., et al.[2021]

A study involving 13 recreationally active men found that coingesting ketone salts with caffeine, taurine, and leucine (KCT) significantly improved 20-km cycling performance compared to a carbohydrate placebo, indicating enhanced endurance benefits from this combination.

The KCT supplementation led to greater average power output during the cycling trial compared to both caffeine-free ketone salts and the carbohydrate placebo, suggesting that caffeine plays a key role in maximizing the performance benefits of this multi-ingredient supplement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Ketone Salts-Caffeine-Taurine-Leucine Supplementation but not Ketone Salts-Taurine-Leucine, Improves Endurance Cycling Performance. Quinones, MD., Lemon, PWR.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7556340/

A Ketone Ester Drink Enhances Endurance Exercise ... Ketone ester supplementation improved endurance exercise performance in persons with Parkinson's disease and may, therefore, be useful as an adjunctive therapy.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33100965/

A Ketone Ester Drink Enhances Endurance Exercise ... Ketone ester supplementation improved endurance exercise performance in persons with Parkinson's disease and may, therefore, be useful as an adjunctive therapy.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05778695

Brain Small Chain Fatty Acid Metabolism in Parkinson ... Small exploratory open-label pilot study to assess supplementation of a ketone ester (KetoneAid) as a potential therapy for persons with Parkinson disease (PD), ...

4. isrctn.com isrctn.com/ISRCTN64294760

Can a ketone drink reduce the severity of symptoms ... Ingestion of a ketone ester supplement (DeltaG) will improve the symptoms of Parkinson's disease. Ethics approval(s), Approved (13/05/2019), NHS Health Research ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0378512222001190

Ketogenic therapy for Parkinson's disease: A systematic ... Interventions included ketogenic diets (KDs), supplementation with medium-chain triglyceride (MCT) oil, caprylic acid administration and ketone ester drinks.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0273230019302703

Safety and tolerability of sustained exogenous ketosis ... We conclude that sustained exogenous ketosis using a ketone monoester is safe and well-tolerated by healthy adults.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9359666/

Ketone Ester Effects on Biomarkers of Brain Metabolism and ... Prior research has shown that oral ketone monoester (KME) safely induces robust ketosis in humans and has demonstrated cognitive-enhancing and pathology- ...

8. withpower.com withpower.com/trial/phase-parkinson-disease-6-2023-0f156

Exercise + Ketone Supplement for Parkinson's Disease ... The safety data for exercise and ketone supplements, particularly in the context of Parkinson's treatment, is limited but provides some insights.