Can Ketones Help the Brain When Glucose Fails? | Dominic D’Agostino, Ph.D.

Episode Overview

• Peter Attia, M.D., and Dom D'Agostino, Ph.D., discuss Alzheimer's disease as a metabolic issue, highlighting the brain's impaired ability to use glucose.
• They explore the limitations and high costs of current pharmaceutical treatments, which have shown minimal efficacy and carry significant risks.
• The conversation centers on the potential of ketogenic therapies to address Alzheimer's by providing an alternative fuel source for the brain and reducing underlying inflammation.
• They touch on the current state of clinical research, emphasizing the need for long-term studies and the importance of patient selection based on metabolic characteristics.

Key Concepts

• Glucose Hypometabolism: A core feature of Alzheimer's disease where the brain becomes inefficient at using glucose for energy, leading to an "energetic crisis."
• Inflammation as a Primary Driver: The hypothesis that systemic inflammation leads to neuroinflammation, which is a root cause of the disease. In this view, amyloid and tau plaques are considered downstream consequences (epiphenomena) rather than the primary cause.
• Metabolic Therapy: The use of interventions like ketogenic diets and ketone supplements to manage Alzheimer's. This approach has a multi-pronged effect: it provides the brain with an alternative fuel (ketones), helps improve glucose metabolism, and reduces systemic inflammation.
• Patient Heterogeneity: Alzheimer's is not a uniform disease. A subset of patients may be "hyper-responders" to metabolic therapies, suggesting that patient selection based on biomarkers like glucose hypometabolism will be crucial for successful clinical trials and treatment.

Quotes

• At 0:14 - "for whom an energetic crisis is at the core..." - Peter Attia explaining his hypothesis that a subset of Alzheimer's patients are primarily suffering from a deficit in brain energy.
• At 0:59 - "A hallmark characteristic of Alzheimer's disease is glucose hypometabolism." - Dom D'Agostino identifying the brain's impaired ability to utilize glucose as a central and defining feature of the disease.
• At 3:20 - "...symptomatically, brain energy metabolism." - Dom D'Agostino explaining that elevating ketones serves as an alternative fuel that can directly and immediately improve the brain's energy deficit, thereby improving symptoms.

Takeaways

• View cognitive decline through a metabolic lens. The brain's ability to use glucose declines with age, but its ability to use ketones is preserved, making ketones a viable alternative fuel to support brain health.
• Focus on reducing systemic inflammation as a proactive strategy against neurodegenerative diseases. Metabolic therapies like the ketogenic diet are powerful tools for lowering inflammation throughout the body and brain.
• For those at risk or in the early stages of cognitive impairment, providing the brain with an alternative fuel source via a ketogenic diet or ketone supplements may offer a direct, symptomatic improvement in cognitive function by resolving the brain's energy crisis.