Brain Substrate Switch to Ketones and Lactate

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).