Dr. Dom D’Agostino Reflects on His 10 Years of Research into Ketogenic Nutrition – STEM-Talk

Check out the Stem-Talk Episode Page & Show Notes

Key Takeaways

  • The ketogenic diet has quite a wide range of applications, some of which include:
    • The treatment of epilepsy
    • Aiding weight loss
    • Aiding cancer treatment
    • Reversing type 2 diabetes
  • There are lots of ways to go about eating a ketogenic diet
    • You can even do it in a vegetarian manner (it doesn’t have to be very cream/dairy-based)
  • In many ways, studies involving the ketogenic diet mimic the benefits of calorie restriction, without any actual calorie restriction taking place
  • The blood glucose lowering effects of exogenous ketones seems to be superior to the popular diabetes drug, metformin
  • It’s common for athletes, when first trying a ketogenic diet, to experience a dip in their performance and energy levels
    • For this reason, it makes sense to transition to a ketogenic diet during your off-season
  • The ketogenic diet seems to mitigate many gut/GI issue
  • It’s important for people to consume higher levels of electrolytes while following a ketogenic diet
    • Liberally salt your food to increase your sodium intake
    • Perhaps consider taking a potassium, calcium, and magnesium supplement
    • Also – stay hydrated
      • Getting dehydrated can contribute to an electrolyte imbalance

Products and Resources Mentioned

Intro

  • Dr. Dom D’Agostino (T: @DominicDAgosti2, IG: @dominic.dagostino.kt) is one of the smartest people on all things ketosis
    • Check out the Podcast Notes from his appearance on The Peter Attia Drive
    • And the Podcast Notes from his appearance on The Joe Rogan Experience
  • Today, the ketogenic diet is the most searched diet on Google
    • In 2016, it wasn’t even in the top 10

First, Some Definitions and Background

  • Ketones are produced by the liver from fat (either from our own body fat during fasting, or the fat we eat) and are used, instead of glucose, to create ATP (energy)
  • A state of ketosis is when you have a blood concentration of ketones greater than or equal to 0.5 mmol
  • The strictest form of the ketogenic diet involves consuming about 90% of your calories from fat and 10% from protein/carbs
  • The modified ketogenic diet involves consuming ~70% fat, and ~20-30% protein/carbs

The Mass Interest in the Ketogenic Diet

  • In 2008, really the only known application of the ketogenic diet was using it to treat pediatric epilepsy
  • Here we are today – now celebrities are promoting it 
    • The diet has quite a few applications, some of which include:
      • The treatment of epilepsy
      • Helping with weight loss 
      • An aid for cancer treatment
      • Reversing type 2 diabetes
  • Thinking evolutionary:
    • Our ancestors were no doubt going in and out of ketosis bssed on the availability of food
  • It’s the only diet that you can objectively measure to see if you’re doing it right (by measuring your blood ketone level)

The Cynicism

  • The biggest argument against the ketogenic diet – a diet high in saturated fat leads to an increased risk for heart disease
    • Dom argues:
      • “A lot of what we know about saturated fat has changed”
      • Nutrition science consensus is very hard to shift – perhaps society is still following old dogmas once thought to be true

Common Misconceptions Surrounding the Ketogenic Diet

  • Early studies showed a classical ketogenic diet causes kidney stones
    • But Dom says this is a non-issue, especially if you supplement with potassium citrate
  • One common misconception – the ketogenic diet is a high-protein diet (it is not)
  • There are lots of ways to go about eating a ketogenic diet
    • You can even do it in a vegetarian manner (it doesn’t have to be very cream/dairy-based)

Scientific Papers

  • One study showed a ketogenic diet extended longevity and healthspan in adult mice (they lived 13% longer)
  • Dom recalls a similar study, except the mice followed an alternate-day ketogenic diet
    • They showed improvements in motor function, memory, fatty-acid oxidation, and muscle mass
  • In many ways, studies involving the ketogenic diet mimic the benefits of calorie restriction, without any actual calorie restriction taking place

Exogenous Ketones

  • They seem to improve blood glucose regulation, especially ketone esters (no brand of ketone ester was mentioned, but this one from HVMN comes with high reviews)
    • “There’s an inverse relationship between blood glucose and ketone levels”
    • Why is this?
      • There seems to be an increase in insulin sensitivity with ketone production/administration – especially once blood ketone levels get > 2 mmol
        • That insulin can facilitate glucose disposal
      • There also seems to be decrease in gluconeogenesis 
    • The blood glucose lowering effects of exogenous ketones seems to be superior to a popular diabetes drug, metformin

Virta Health

  • Virta has published impressive results surrounding their goal of helping people reverse type 2 diabetes through a well-formulated ketogenic diet
    • 60-70% of people have either greatly reduced or gotten rid of their need for exogenous insulin
      • Some people argue the beneficial effect of the ketogenic diet in this realm is due to its secondary calorie restriction effect (people on a ketogenic diet tend to consume less calories) (so you might see the same effects with a high-carb, calorie restricted diet)
        • But Dom thinks it’s more so due to the effect of correcting the underlying metabolic derangement just by shifting metabolism to increased fat utilization
  • They’ve also had impressive results treating non-alcoholic fatty liver disease (NAFLD)

Ketones and Brain Energy Metabolism

  • Studies giving animals dietary ketone supplements in conjunction with medium chain triglycerides (MCTs) have shown an elevation of acetoacetate and beta-hydroxybutyrate (BoHB) in the brain (both are types of ketones) (MCTs also seem to elevate, specifically in the hippocampus region of the brain)
    • So if you orally take a MCT supplement (like MCT oil or MCT powder) it’s crossing the blood-brain barrier and getting into brain tissue
    • Another observation – there’s a big change in the GABA to glutamate ratio (this is important from the anti-seizure point of view)
      • GABA is responsible for stabilizing hyper-excitiability
    • Also observed was a decrease in oxyegn free radicals in the brain (AKA reactive oxygen species)

Kabuki Syndrome

  • This is a genetic disorder that causes altered growth and cognitive dysfunction in children
    • Dom and his team are currently gearing up to do studies on mice with kabuki syndrome to determine if ketone supplementation is of any benefit

Ketone Esters vs. Ketone Salts

  • The difference between a ketone salt and a ketone ester:
    • A salt is an ionic bond between the ketone molecule (like BoHB), a monovalent or divalent cation, or an alkaline amino acid
      • The easiest thing to do is bond BoHB with sodium, potassium, calcium, and magnesium
      • You can buy ketone salts on Amazon (this is what most “exogenous ketones” are)
    • A ketone ester is a covalent, not an ionic bond
    • Ketone esters are much more effective at raising your blood ketone levels

Women and the Ketogenic Diet

  • The transition into ketosis seems to be more difficult for women who try a ketogenic diet
    • Dom suggests first starting with a lower-carb/high-protein diet, and then titrating the fat in, in combination with time-restricted feeding
      • Women tend to be more responsive to lower blood glucose levels – which is why starting out with a full-on ketogenic diet can be difficult

A Vegetarian Keto Diet

Oral Glucose Tolerance Test (OGTT) vs. a Ketone Tolerance Test

  • In an OGTT, you ingest a pre-determined amount of glucose and measure the rise/fall of your blood glucose level over time
    • This gives useful information into the body’s utilization and uptake of glucose
  • In a ketone tolerance test, you ingest a ketone supplement and then measure your blood ketone levels at various points afterwards
    • Your tolerance/ability to absorb/utilize ketones increases over time as a function of being in a state of ketosis
    • Athletes tend to be very good ketone utilizers

Athletes and the Ketogenic Diet

  • It’s common for athletes, when first trying a ketogenic diet, to experience a dip in their performance and energy levels
    • For this reason, it makes sense to transition to a ketogenic diet during your off-season
  • Dom suggests that when a competition/match approaches, after your body is adapted to the ketogenic diet, it might make sense to provide your body with a range of fuel sources:
    • For example, you might want to consume a slow acting carbohydrate (like SuperStarch) that doesn’t cause a large insulin spike (in combination with some MCT Oil + creatine monohydrate)
      • By doing this, you’re training your body to use a range of fuels, and not just one type
  • There are quite a few benefits with the ketogenic diet in relation to muscle recovery/inflammation and protecting your brain (if you’re a boxer or MMA fighter)
    • For this reason, it might make sense to take supplemental ketones after a match/fight

The Microbiome

  • The ketogenic diet seems to mitigate many gut/GI issues
  • A condition known as “small intestine bacterial overgrowth” can develop from the over-consumption of processed sugars and carbohydrates
    • Time-restricted eating seems to help this,
    • Same thing with a low-carb/ketogenic diet
      • Why? – They both change the diversity of the micorbiome and reduce inflammation in a way that’s enhancing the overall health of the gut, even down to the level of the tight junctions (which need to stay tight to prevent things like leaky gut)

Cancer and the Ketogenic Diet

  • Dom and his lab are experimenting with using press/pulse-based combative therapy against cancer
    • What does this mean? 
      • Press-therapy = enhancing a person’s own physiology to compromise the growth/proliferation of cancer (weakening the cancer to make it a vulnerable target)
        • Examples – a ketogenic diet or metformin (a blood glucose lowering drug)
          • These can also enhance the efficacy of chemo/radiation
      • Pulse-therapy = targeted against the cancer
        • Examples – hyperbaric oxygen or intravenous vitamin C
          • When vitamin C gets up to very high levels, it acts as a glucose antagonist, blocking the transport of glucose across membranes (which would be lethal to cancer cells)

Ketone Bodies Prevent Muscle Breakdown

  • Check out the study
  • How?
    • If you’re in the fasted state, you’ll first use up all your stored glucose
    • Your body will then search for gluconeogenic precursors (to make more glucose) to feed the brain
      • These precursors are usually muscle tissue
        • When ketone bodies are present, the brain can utilize these for energy, preventing the need for muscle breakdown

Electrolyte Supplementation

  • A low-sugar/low-carb diet will suppress insulin, which leads to the “dumping” of sodium from the body
  • Dom has noticed his blood magnesium levels drop while following a ketogenic diet, despite eating tons of leafy greens
  • It’s important for people to consume higher levels of electrolytes when following a ketogenic diet
    • Liberally salt your food to increase your sodium intake
    • Perhaps consider supplementing with potassium and calcium 
    • Also – stay hydrated
      • Dehydration can contribute to electrolyte imbalances

Dom’s Current Workout Routine

  • Dom lives on a 24-acre farm, so he gets a LOT of outside physical activity
    • He spends a ton of time cutting trees, digging irrigation ditches, bailing hay, and moving equipment 
    • He estimates he spends~20 hrs./week on physical farm work
  • He and his wife are members at Planet Fitness where he occasionally drops in to do some body weight exercises

Random

  • In some cases, Dom suggests people ease into the ketogenic diet
    • Why? – Their fat tolerance may not be as good as it should be
  • Oxygen toxicity is a syndrome that divers are at risk for when since they’re breathing high-pressure oxygen – it’s expected that a ketogenic diet can greatly reduce the risk
  • Dom has two rescue dogs – a black Lab and Great Dane mix
  • Many stores around the country ran out of Wild Plant Sardines after Dom’s first interview on Tim Feriss’ podcast
    • They’re a staple food for Dom
    • Sardines are typically very low in heavy metals 
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