hvmn podcast

#197: The Current State Of Ketone Research With Dr. Dominic D’Agostino & Dr. Angela Poff | HVMN Podcast

Check out the HVMN Podcast episode page

Key Takeaways

  • Explosion of ketones as a field of study: (1) ketones are a potent but accessible intervention (legal, accessed through diet or exogenous; (2) scientists are living the lifestyle of what they’re studying which helps credibility, influence, experience
  • “Ketones can rapidly change brain energy metabolism and the neuropharmacology of your brain in a way that’s neuroprotective and anti-seizure.” – Dr. Dom D’ Agostino
  • There should be a duty to disseminate translatable, clear research to the public if funded through government means
  • Ketones improve brain energy signaling metabolism, resilience, and enhance ability to maintain cognitive and physical performance in extreme environments – both environmental and physiologic
  • Even within the ketogenic diet, there are many routes to go and options for exogenous ketones as supplement – like any diet, it needs to be personalized to your needs (a continuous glucose monitor can help)
  • Starting in early middle age, natural uptake of glucose declines but ketone uptake is retained in the aging brain – ketones can circumvent glucose transporter and provide the energy for proper function
  • The greatest effect of ketogenic diet on athletic performance will likely be over time where you’ll see improvements in recovery, epigenetic effects, anti-inflammatory effects
  • Tip: consuming carbohydrates with exogenous ketones (such as a ketone salt, MCT) will minimize glycemic variability  
  • “Completely excluding carbohydrates, fruit, and vegetables to the extent we do that with a clinical ketogenic diet is not optimal [for everyday]. A more diverse diet with plants, vegetables, different protein sources, with exogenous ketones would be more optimal.” – Dr. Dom D’Agostino
    • Instead, try a Mediterranean diet with exogenous ketones for supplementation with about 50-100g carbohydrates

Introduction

Dominic D’Agostino, Ph.D. (@DominicDAgosti2) is an Associate Professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida Morsani College of Medicine. He is also a Research Scientist at the Institute for Human and Machine Cognition (IHMC). His research focuses on ketones and the ketogenic diet.

Angela Poff, Ph.D is a Research Associate in the Department of Molecular Pharmacology and Physiology at the University of South Florida in Tampa, FL, and Co-Founder of Metabolic Health Initiative. Her research focuses on studying non-toxic metabolic-targeted therapies for cancer.

In this episode of the HVMN Podcast, Drs. Dom D’Agostino and Angela Poff breakdown the latest ketone research, including topics like the role of ketones and future directions of research, athletic performance, cancer, chronic disease, and much more.

Co-Hosts: Geoffrey Woo (@geoffreywoo) and Dr. Latt Mansor (@lattmansor)

Excitement Around Ketones & Metabolic Research

  • The only valid application of the ketogenic diet used to be as standard of care for pediatric epilepsy or neurometabolic deficiencies
  • Now, the ketone diet is being explored for cancer, psychiatry, chronic disease
  • In early studies patients are experiencing success treating depression with the ketogenic diet
  • “Ketones are basically a food with drug like properties…no pharmaceuticals have the same type of pluripotent response within the cells and different tissues systemically with the ability to impact the physiology from the brain to all of systems biology.” – Dr. Angela Poff
  • Ketones have the power to put health back into people’s hands
  • Academics are approaching ketone research from the top down: the ketogenic diet works, now deconstruct and identify the mechanisms to optimize applicability for other conditions
  • There are many ways to alter metabolism: diet, synthetic ketogenic agents, natural ketogenic agents (like MCTs), metabolic drugs
  • There’s an explosion of research being done on the ketogenic diet – there are currently 296 clinical trials

Athletic Performance & Ketogenic Diet

  • Ketones can be used to increase adaptation to performance stimulus
  • Study design makes studying athletic performance and ketogenic diet tough – studies generally take high performing athletes and observe them over a short time which yields consistent, but small effect size
  • The greatest effect of ketogenic diet on athletic performance will likely be over time where you’ll see improvements in recovery, epigenetic effects, anti-inflammatory effects
  • Ketones improve brain energy signaling metabolism, resilience, and enhance ability to maintain cognitive and physical performance in extreme environments – hyperbaric chambers, astronauts in space, and disease states in people
  • The jury on use of exogenous ketones to improve athletic performance is out but most studies used acute ketones which may not be ideal – it’s better to use ketones as a training aid longer periods of time

The Science Of Ketones

  • When the mitochondria is burning ketones there’s more efficiency between energy systems and less electron leakage
  • The heart and brain have the highest metabolic demands with liver not far behind
  • Sugar, fat, and ketone burning are not mutually exclusive events – even if you’re in ketosis, you’re max 50% burning ketones
  • “Glutamate is by far the most important, ubiquitous neurotransmitter system in the body. Without it we rapidly die.” – Dr. Dom D’ Agostino
  • Gaba (neurotransmitter): inhibitory, brain stabilizing
  • There’s more glutamate to GABA conversion during ketosis
  • Ketones add an additional source of energy for the body, readily available and convertible to ATP
  • The older we get, natural uptake of glucose declines but ketone uptake is retained in the aging brain – in most neurological conditions (including traumatic brain injury), there is a glucose deficit in the brain but it needs high uptake to maintain proper function

Dosing Ketones

  • More is not better when it comes to ketones – particularly, exogenous ketones like ketone esters are powerful and can have negative side effects
    • In studies, rats get sick above 5 mmol
  • Consistently keeping ketones between 2-4 on a daily basis may disrupt metabolic physiology and start activating counterregulatory mechanisms – anything above 2 mmol may spike insulin
  • Chronically high ketones is unnatural
  • Keeping ketones around 1.5 mmol is usually a sweet spot with how you feel and real world benefit
  • Consuming carbohydrates with exogenous ketones (such as a ketone salt, MCT) will minimize glycemic variability  
  • “Completely excluding carbohydrates, fruit, and vegetables to the extent we do that with a clinical ketogenic diet is not optimal [for everyday]. A more diverse diet with plants, vegetables, different protein sources, with exogenous ketones would be more optimal.” – Dr. Dom D’Agostino
    • Instead, try a low carb Mediterranean diet with exogenous ketone supplementation with about 50-100g carbohydrates
  • Exogenous ketones should be part of a well-rounded fueling system

Diet & Breaking Down The Carnivore Diet

  • Carnivore diet is an elimination diet – much of the benefit is from calorie restriction  
  • Studies on early ancestors clearly indicate that early humans were eating 100-200g of fiber per day (varies geographically)
  • Diet is highly individual
  • Trust your intuition about your body and self-experiment to see what works and what doesn’t – ideally, gather metrics through blood work and/or continuous glucose monitor

Future Of Ketone Research

  • Dietary and metabolic based therapies for the things that kill us most: cardiovascular disease, Alzheimer’s/dementia, cancer, psychiatry
  • Enhancing performance in space and under water will be important for future missions
  • Understanding the signaling side of ketones in terms of epigenetic regulation and gene expression
  • Medicinal mushrooms is a growing field of research improving brain health
HVMN Podcast : , , , , , ,
Notes By Maryann

More Notes on these topics

Top Insights and Tactics From

31 Best Podcasts of All Time

FREE when you join over 35,000 subscribers to the
Podcast Notes newsletter

No Thanks