Summary
Shawn Stevenson talks with Dr. Dominic D'Agostino about using nutritional strategies to protect brain health and metabolism. They explore the hypothalamic-pituitary-adrenal axis, how ketogenic diets and exogenous ketones affect neurotransmitters and hormones, and practical ways to use food as medicine for cognitive function and metabolic resilience.
Key Points
- Ketones provide a cleaner, more efficient fuel for the brain than glucose, producing less oxidative stress per unit of ATP.
- The ketogenic diet can shift neurotransmitter balance by increasing GABA (calming) relative to glutamate (excitatory), reducing seizure risk and anxiety.
- Exogenous ketone supplements (esters and salts) can raise blood ketone levels acutely for cognitive benefits without requiring strict dietary ketosis.
- The hypothalamic-pituitary-adrenal (HPA) axis is sensitive to blood sugar swings, and stable ketone-based fueling may reduce cortisol dysregulation.
- MCT oil (especially C8 caprylic acid) converts rapidly to ketones in the liver, offering a practical way to boost brain fuel between meals.
- Metabolic flexibility -- the ability to switch between glucose and ketone burning -- is a trainable skill that protects against neurodegeneration.
Key Moments
Ketones elevate brain blood flow by 30% or more
Dom D'Agostino explains that elevating ketones through fasting, the ketogenic diet, or exogenous ketones can increase brain blood flow by 30% or more, partly through adenosine-mediated vasodilation.
"literature that elevating ketones through fasting through the ketogenic diet or even exogenous ketones can elevate brain blood flow by 30% or more, simply fasting for 24 hours and naive subjects actually increases."
MCT oil improved Alzheimer's patient cognitive test scores
D'Agostino recounts the landmark case of a physician's husband whose Alzheimer's symptoms improved on MCT and coconut oil, sparking his own research into ketones as neuroprotective agents.
"and it was the observation that giving her husband MCT oil and coconut oil together improved his performance in the mini-mental state exam and also the clock test. He was being evaluated at the Bird Alzheimer's Institute at University of South Florida College of Medicine."
Alzheimer's disease as glucose hypometabolism in the brain
A hallmark of Alzheimer's disease is glucose hypometabolism in the brain, visible on FDG-PET scans, suggesting that metabolic health is a key predictor of age-related dementia.
"Metabolic health will predict us getting age-related dementia, including in that Alzheimer's disease. So a hallmark characteristic of Alzheimer's disease is glucose hypometabolism, meaning that if you scan someone who has advanced Alzheimer's disease or even early dementia, what you see in a fluorodeoxid glucose pet scan"
Ketones bypass impaired glucose transporters in the brain
In conditions like glucose transporter type 1 deficiency, ketones can replace glucose as the brain's primary fuel, the same principle that may help in Alzheimer's disease.
"The ketones bypassed the glucose transporters. So for example, and glucose transporter type 1 deficiency syndrome, which is a genetic and born error metabolism, the therapy is actually ketosis, the ketogenic diet, because the ketones then replace glucose as the primary fuel for the brain."
