How Ketones Support Neurological Health | Dom D’Agostino on Diet Doctor with Dr. Bret Scher

Key Takeaways

  • We have a clear understanding of four mechanisms behind the ketogenic diet: 1. Brain energy metabolism, 2. Neurotransmitters, 3. Adenosine receptor signaling, 4. Inflammation
  • Anti-catabolic effects of ketones are significant
  • Research on ketosis as it relates to epilepsy is much farther along and well understood than other neurological pathologies
  • There will be unique ketogenic strategies for different applications: diabetes, epilepsy, exercise performance, etc  
  • Modified ketogenic diet approach may be advantageous for compliance and efficacy


Dr. Bret Scher sits down with Dr. Dom D’Agostino to have a brief chat about how ketones support neurological health, mechanisms in the body, and effects on performance enhancement

Host:  Bret Scher, MD (@bschermd)

Dr. Dom D’Agostino (@DominicDAgosti2) is an academic researcher and expert on ketones and the ketogenic diet

Website and blog:

Ketogenic Diet Supports Neurological Health: Top Four Mechanisms

  • Of the dozens of potential mechanisms behind how a ketogenic diet works to support neurological pathology, there are four we understand well:
    1. Ketogenic diet enhances brain energy metabolism and contributes to brain homeostasis which balances energy and glucose metabolism
    2. Ketogenic diet takes brain from hyper-excitable state to a more relaxed state
      • Specifically, a ketogenic diet activates an enzyme that converts glutamate (stimulatory neurotransmitter; hyper-activity enzyme) to GABA, an inhibitory brain stabilizing neurotransmitter)
      • This is the theory driving research on other neurological disorders since the underlying response to injury is similar
    3. Adenosine A1 receptor signaling: When adenosine receptor is activated it quiets and stabilizes neurotransmission
    4. Ketone bodies are anti-inflammatory so they can reduce neuro-inflammation triggered by foods, stress, environmental toxins, etc
      • Systemic inflammation typically leads to neuro-inflammation which can lead to seizures, anxiety, headache

Endogenous vs Exogenous Ketones

  • Not all ketones are the same, individual ketone levels matter, and products are not equal  
  • Findings point to the idea that when you mix ketogenic fats (salts and esters) you have a more enhanced response than consuming either alone
  • “If you ingest purely exogenous ketone, you are turning off your own ketone production to some extent but if you mix ketogenic fat with ketone ester and deliver orally, it stimulates endogenous ketone production” -Dom D’Angostino  

Modified Ketogenic Diet

  • The classic ketogenic diet for treating seizures is 4:1 – 4x as much fat as protein and carbohydrates combined
  • Evidence is accumulating that a modified ketogenic diet approach may be advantageous for compliance and efficacy
  • We know diet and degree of ketone elevation matter, but we are unsure of exact formula
  • It appears you can incorporate fats that are ketogenic into a modified ketogenic diet and get same level of ketosis as a more restrictive diet
  • In a recent study, children with epilepsy on classic ketogenic diet did as well when switched to modified approach more liberal in protein

Ketones, Muscle, and Lean Body Mass

  • Ketones are anti-catabolic (protect muscle mass in the body from being broken down)
  • In the context of calorie restriction or cancer cachexia (muscle wasting in cancer):
    • When you are not ingesting food, your body starts to breakdown protein and fatty acid for fuel
    • When you have depleted glycogen stores, you make more ketone bodies
    • Ketone bodies replace glucose as a primary energy source during prolonged fasting (approximately one week)
    • They become anti-catabolic because they’re supplying an energy source which allows your body to spare amino acids
  • Ketones can be an effective intervention to help maintain lean body mass
  • Ketones are unlikely to have positive results if ingesting right before exercise to enhance performance but will likely perform well as an adaptive response to exercise

Research papers mentioned  

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Notes By Maryann

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