Does Cerebral Substrate Switching Underlie the Beneficial Brain Adaptations of Fasting and Exercise?
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Brain-derived neurotrophic factor, secreted amyloid beta precursor protein
Study Overview
Brief Summary
The brain is constantly active and energetically expensive, making up a quarter of the body's energy budget despite occupying only 2% of its mass. To fuel this incessant activity, the brain relies on glucose, which accommodates 99% of its metabolic needs. In most cases, glucose is the ideal fuel since it is in constant surplus owing to 24-hr access to sugar-rich food. However, the brain is metabolically flexible and capable of metabolizing alternative fuels when glucose is scarce, or, decreasing rapidly. For example, during fasting when glucose stores are dwindling, ketone bodies can supplement the brain's metabolic needs. During intense exercise, when glucose stores are being rapidly depleted, lactate - a byproduct of this glucose turnover - similarly acts as an alternative fuel for the brain. In healthy individuals, exploiting this 'brain metabolic flexibility' may be beneficial in protecting the brain from aging.
The main question is: Does the brain substrate switch that occurs during fasting and high-intensity exercise underlie the beneficial effects on the brain?
Young, healthy participants will fast for 3 days and complete high-intensity cycling exercise, each of which will induce a brain substrate switch. Participants will also be passively infused with ketones (to simulate fasting) and lactate (to simulate high-intensity exercise) in the fed and rested state. In doing so, the investigators will isolate the brain substrate switch from the broader, pluripotent stressors that encompass fasting and exercise.
The main outcome variables are the brain biomarkers: brain-derived neurotrophic factor (BDNF) and secreted amyloid beta precursor protein (sAPPA).
Detailed Description
Objectives:
Primary:
• To determine if brain ketone and lactate metabolism cause the beneficial neurotrophic responses associated with fasting and exercise, respectively.
Secondary:
• To determine if fasting and exercise improve the brain's uptake of glucose, ketones and lactate.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Single (Investigator)
Masking Description
The participant will not be blinded because they must consciously adhere to study requirements, i.e., fasting for 3 days. The investigators will be blinded to the fasting and fed conditions.
Eligibility Criteria
- Ages
- 19 Years to 40 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Regularly physically active, as determined via questionnaires
Exclusion Criteria
- •Current smokers
- •Acute bronchial asthma, chronic obstructive airway or status asthmaticus
- •Obese (body mass index greater than 30 kg m-2)
- •Requiring daily prescription medications that may affect responses to exercise, e.g., anti-hypertensives, anti-arrhythmogenics, inhalers
- •History of disease/dysfunction that could cause complication with exercise, e.g. cardiovascular, respiratory, neurological or musculoskeletal diseases
- •Irregular or absent menstrual cycle (females)
- •Pregnant or may suspect pregnancy, or post-menopausal (females)
- •Any unexpected adverse responses to pre-experimental exercise tests
- •Any contraindication to a lumbar subarachnoid access
Arms & Interventions
Fed
Exercise and passive infusions of ketones and lactate in the fed state. Participants will be fed a small meal in the middle of the protocol, also.
Intervention: Fed (Other)
Fasted
Exercise and passive infusions of ketones and lactate in the fasted state. Participants will be required to fast for 72 hours prior to arriving to the lab for this testing arm.
Intervention: Fasted (Other)
Outcomes
Primary Outcomes
Brain-derived neurotrophic factor, secreted amyloid beta precursor protein
Time Frame: Data collected at rest, during graded infusions of lactate and ketones, pre- and post- 6 minutes of high-intensity cycling exercise
Biomarker to index neuroplasticity and resilience
Secondary Outcomes
- Brain substrate metabolism(Data collected at rest, during graded infusions of lactate and ketones, pre- and post- 6 minutes of high-intensity cycling exercise)
Investigators
Phil Ainslie
Professor
University of British Columbia