Brain Substrate Switch to Ketones and Lactate

NCT06000605 | Unknown

• 1 other identifier: Brain_substrate_switch
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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).

Conditions

Metabolic Diseases; Aging Problems

Keywords

brain; BDNF; metabolism; ketones; lactate

Outcome Measures

Primary Outcomes (1)

• Brain-derived neurotrophic factor, secreted amyloid beta precursor protein

  Biomarker to index neuroplasticity and resilience

  Data collected at rest, during graded infusions of lactate and ketones, pre- and post- 6 minutes of high-intensity cycling exercise

Secondary Outcomes (1)

• Brain substrate metabolism

  Data collected at rest, during graded infusions of lactate and ketones, pre- and post- 6 minutes of high-intensity cycling exercise

Study Arms (2)

Fed

ACTIVE COMPARATOR

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.

Other: Fed

Fasted

EXPERIMENTAL

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.

Other: Fasted

Interventions

Fed OTHER

Participants will eat a light meal prior to testing and be fed a light meal during testing.

Fed

Fasted OTHER

Participants will completely abstain from calories for 72 hours prior to testing and not receive any calories during testing.

Fasted

Eligibility Criteria

• Age: 19 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Regularly physically active, as determined via questionnaires

You may not qualify if:

• 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

Sponsors & Collaborators

• University of British Columbia: lead
• University of Otago: collaborator

Study Sites (1)

University of British Columbia - Okanagan Campus

Kelowna, British Columbia, V1V1V7, Canada

Location

MeSH Terms

Conditions

Metabolic Diseases; Ketosis

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases; Acidosis; Acid-Base Imbalance

Central Study Contacts

Travis D Gibbons, PhD

CONTACT

7785836976; travis.gibbons@ubc.ca

Philip N Ainslie, PhD

CONTACT

2508078089; phil.ainslie@ubc.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants will complete both arms: 1) fasted and 2) fed.

Study Record Dates

• First Submitted: August 14, 2023
• First Posted: August 21, 2023
• Study Start: October 1, 2023
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2024
• Last Updated: August 24, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)