Exogenous Ketosis During Bed Rest in Older Adults

NCT ID: NCT05679596

Last Updated: 2024-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-27
• Study Completion Date: 2023-11-15

Brief Summary

The goal of this randomized, double-blind, parallel group interventional study is to evaluate the effect of ketone bodies on healthy older adults (65-85 y) during 5 days of bed rest. The main questions it aims to answer are:

Does supplementation of ketone bodies prevent the typical decline in muscle protein synthesis, muscle size, muscle function, insulin sensitivity, and muscle mitochondrial function that occurs in response to bed rest?

Researchers will compare ketone supplements (KET) to an energy matched control beverage (carbohydrates and fats) to see if the ketones can rescue the decline in muscle protein synthesis rates, muscle loss, muscle function, insulin sensitivity, and mitochondrial function due to 5 days of bed rest.

This may positively impact the heath of older adults subjected to bed rest.

Detailed Description

Bed rest is a common feature of many clinical environments such as hospitals and long-term care facilities. However, physical inactivity due to bed rest decreases muscle size, muscle strength, and physical performance (i.e. rising from a chair) that can lead to a reduced quality of life and a higher risk of disease and death. Eating protein-rich foods and exercising normally helps to maintain muscle size by building proteins found in muscle. However, during bed rest there is a reduction in the rate at which proteins found in muscle are made and this leads to smaller muscles. Bed rest leads to problems with blood glucose regulation and insulin resistance which can increase the risk for diabetes. Both the loss of muscle size and insulin resistance are linked to problems with parts of our cells called mitochondria. Mitochondria do a lot of important things including keeping our cells full of energy. Bed rest occurs more frequently in older adults and also negatively impacts their health more than in younger adults. Sadly, there are limited options to prevent the problems associated with bed rest. Ketone bodies are molecules that come from fat that are normally produced in the body in response to reduced carbohydrate intake (i.e. a ketogenic diet). Recently ketone supplements have become available, which increase the amount of ketone bodies in the body without the need to limit carbohydrate intake from food. Elevated ketone bodies may help protect muscle size and health during bed rest by enhancing the process of building muscle proteins, improving blood glucose regulation, and helping mitochondria work optimally.

Conditions

Muscle Protein Synthesis; Muscle Atrophy; Insulin Sensitivity; Mitochondrial Function; Physical Inactivity; Cognitive Function; Muscle Strength; Functional Capacity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Exogenous ketone monoester (KET)

KET will be provided at a dose of 360 mg kg-1 body mass per serving at 2 servings per day between each main meal (ΔG®; TΔS Ltd, UK, Oxford, UK).

Group Type: EXPERIMENTAL

ketone monoester (R)-3-hydroxybutyl (R)-3- hydroxybutyrate

Intervention Type: DIETARY_SUPPLEMENT

Provided twice a day between meals.

Energy matched control (CON)

CON will be provided at a dose energy matched to the KET supplement and consist of both carbohydrate (i.e., fructose) and fat (i.e., corn and canola oil 50:50 ratio). 1/3 of the supplemental energy will come from carbohydrate while 2/3 will come from fat. We have excluded protein from the CON supplement since it is well established to influence our primary outcome measure (MPS rates). A non-caloric sweetener will also be added to the CON supplement.

Group Type: ACTIVE_COMPARATOR

carbohydrate-fat placebo (fructose, corn and canola oil 50:50 ratio)

Intervention Type: DIETARY_SUPPLEMENT

Provided twice a day between meals.

Interventions

ketone monoester (R)-3-hydroxybutyl (R)-3- hydroxybutyrate

Provided twice a day between meals.

Intervention Type: DIETARY_SUPPLEMENT

carbohydrate-fat placebo (fructose, corn and canola oil 50:50 ratio)

Provided twice a day between meals.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

delta G Oxford Ketone Ester

Eligibility Criteria

Inclusion Criteria

• Healthy, male, and female, older adults.
• Healthy will be defined as screen by the 2020 PAR-Q+, medical screening questionnaire, GAQ, and COVID-19 symptom questionnaire patient screening.
• 'Older' will be defined as being 65-85 years of age.
• Participants are required to not engage in structured resistance training for at least 6 months prior to participation in the study.
• Participants are willing to abide by the compliance rules of this study.

Exclusion Criteria

• Pre-menopausal females: Women must be postmenopausal having not menstruated for at least 1 year prior to study participation. Hormonal fluctuations associated with the menstrual cycle have been reported to alter protein metabolism and may influence indices of muscle protein synthesis and breakdown (69-71).
• BMI <18.5 or > 30 kg ∙ m-2.
• Self-reported regular tobacco use and vaping products.
• Self-reported illicit drug use (e.g., growth hormone, testosterone, etc.)
• Individuals who have participated in studies within the past year involving a stable isotope of 2H.
• A history of thrombosis, diagnosed with type 2 diabetes mellitus by physician or HbA1c values of > 7.0%, dementia, coronary artery disease, musculoskeletal/orthopedic disorders, and severe allergies.
• The use of medications known to modulate skeletal muscle metabolism (e.g., corticosteroids, hormone replacement therapy, non-steroidal anti-inflammatory drugs, metformin).
• The use of over-the-counter supplements (protein supplements, creatine, fish oil).
• Inability to adhere to any of the compliance rules judged by the principal investigator or medical doctor.

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

McGill University

OTHER

Sponsor Role: lead

Responsible Party

Tyler Churchward-Venne

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tyler A Churchward-Venne, PhD

Role: PRINCIPAL_INVESTIGATOR

McGill University

Locations

Research Institute - McGill University Health Centre

Montreal, Quebec, Canada

Countries

Canada

Other Identifiers

427929

Identifier Type: -

Identifier Source: org_study_id