• Ketones as signaling molecules (beta-hydroxybutyrate-focused)

Core claims

• Ketones are described as both an energy substrate and a signaling molecule (“act like hormones”).
• Beta-hydroxybutyrate (BHB) is described as the primary signaling ketone, with receptor-mediated, inflammasome, and epigenetic effects.

Key quantitative points

• BHB is stated to comprise ~70% of circulating ketones; the other ketones named are acetoacetate and acetone.
• The L (S) form of BHB is stated to be present at ~10% of circulating BHB under some conditions.
• Approximate blood ketone concentrations stated:
  • Typical mixed diet: often below device detection; ~<0.1 mM.
  • After overnight fasting: ~0.3 mM.
  • Prolonged fasting / ketogenic diet: >1 mM up to ~2–4 mM.
  • Diabetic ketoacidosis: “high teens” to “20s” mM.

Timeline summary (mm:ss)

• 00:00–00:45
  • Framing: ketones described as more than fuel; positioned as a metabolic signal coordinating tissue responses during fasting/exercise/ketogenic diet.
• 00:45–03:30
  • Distinction presented: nutrients primarily provide calories; hormones primarily send messages; ketones described as doing both.
• 03:00–07:10
  • Ketone body basics:
    • Ketones named: BHB, acetoacetate, acetone.
    • BHB described as synthesized primarily in liver mitochondria during high fatty-acid oxidation.
    • BHB transport described via monocarboxylate transporters (MCT1/MCT2).
    • Utilization described: conversion back to acetoacetate (BDH1 mentioned), entry into mitochondrial metabolism.
    • Liver described as producing ketones for export and lacking the enzymes to catabolize its own ketones.
  • Physiological concentration ranges stated (see “Key quantitative points”).
  • Enantiomers noted: D vs L (S) forms; comments that some signaling effects apply to both.
• 07:10–12:10
  • Receptor signaling 1: GPR109A (also described as hydroxycarboxylic acid receptor 2; niacin receptor context)
    • Receptor described as Gi-coupled, lowering intracellular cAMP.
    • Expression described on immune cells (macrophages, neutrophils) and microglia.
    • Effects described as anti-inflammatory and neuroprotective in models.
    • Knockout evidence described: when the receptor is absent, BHB/ketogenic diet neuroprotection is described as lost; infarct-size reduction in stroke models described as absent in knockout animals.
• 12:10–15:30
  • Receptor signaling 2: FFAR3 (also called GPR41; described as a short-chain fatty-acid sensor)
    • Short-chain fatty acids named in this context: acetate, propionate, butyrate.
    • Sympathetic neuron findings described involving N-type calcium channels and altered norepinephrine-related signaling.
    • Functional outcome described as consistent with reduced sympathetic outflow.
    • Stereo-selectivity described as not strict; D-form described as having activity at lower/more physiologically relevant levels in this context.
• 15:30–18:55
  • Inflammasome signaling: NLRP3 inhibition
    • A “landmark” Nature Medicine paper is cited in-video as showing BHB specifically inhibits NLRP3.
    • Mechanistic points described:
      • BHB prevents potassium efflux (described as an early step in NLRP3 activation).
      • BHB reduces ASC “speck” formation/oligomerization (adapter protein assembly step).
      • Effect described as specific to NLRP3 (not broadly inhibiting other inflammasomes).
      • Effect described as not dependent on GPR109A, AMPK activation, autophagy, reactive oxygen species reduction, or BHB oxidation through the citrate cycle.
      • NLRP3 inhibition described as not stereoselective (D- and L-BHB both described as effective).
    • Disease relevance list attributed to NLRP3 dysregulation includes: type 2 diabetes, atherosclerosis, gout, Alzheimer’s disease, multiple sclerosis, and others.
• 18:55–23:30
  • Nuclear/epigenetic signaling
    • BHB described as an endogenous inhibitor of class I histone deacetylases (HDAC1/2/3 stated).
    • Inhibition described at ~1 mM (described as within physiological range).
    • Functional consequence described: increased histone acetylation, loosened chromatin, increased transcription of specific gene programs.
    • Genes explicitly named as upregulated in this context: FOXO3A and metallothionein 2 (MT2); both described as supporting oxidative-stress defense.
    • Additional modification described: beta-hydroxybutyrylation (BHB group covalently attached to lysine residues on proteins).
• 23:30–28:26
  • Mitochondrial implications and translational framing
    • Chronic inflammation described as damaging mitochondria; IL-1β described as impairing mitochondrial function, reducing ATP production, and increasing reactive oxygen species.
    • BHB described as reducing IL-1β production (via NLRP3 pathway) and protecting mitochondria from inflammation-induced damage.
    • Oxidative stress framing: ketone metabolism described as not necessarily lowering free-radical production, but BHB-driven antioxidant gene expression described as improving oxidative-stress resilience.
    • Exogenous ketones discussed:
      • Racemic D/L mixtures described as retaining anti-inflammatory benefit for NLRP3-related effects (consistent with non-stereoselective inhibition described).
      • Clinical trials described as examining whether ketone supplements can provide anti-inflammatory/metabolic benefits without dietary carbohydrate restriction.
    • Clinical-interest examples mentioned:
      • Alzheimer’s disease discussed in the context of impaired brain glucose metabolism and lower BHB levels.
      • Heart failure discussed with ketones described as avidly consumed by the heart; elevated ketones described as potentially beneficial adaptation.

Papers explicitly referenced in-video

• The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease (Nature Medicine, 2015) — https://doi.org/10.1038/nm.3804
• The β-hydroxybutyrate receptor HCA2 activates a neuroprotective pathway (Nature Communications, 2014) — https://doi.org/10.1038/ncomms4944

Nutrition link to dementia — transcript-based summary

Framing and core thesis

• Dementia risk is presented as strongly modifiable, with nutrition positioned as a primary lever alongside other lifestyle factors.
• Brain physiology is emphasized: the brain is <2% of body weight yet uses ~20% of blood supply and ~20% of energy, generating ~20% of body heat.

Reported population-level risk framing

• A 2024 “commission report” is cited as indicating the global burden of dementia could be reduced by ~40%, with the speaker stating nutrition is not explicitly included in that list despite being foundational to multiple listed factors.

Diet pattern risk claims and cohort evidence cited in the talk

• Ultra-processed foods:

  • A cohort study is described as following ~10,000 adults for ~8 years, with higher ultra-processed food intake associated with:
    • ~28% faster global cognitive decline.
    • ~25% faster executive function decline.
  • A rule-of-thumb claim is stated: every 10% increase in ultra-processed food intake is associated with ~15% higher type 2 diabetes risk.

• Type 2 diabetes as a dementia risk amplifier:

  • Midlife type 2 diabetes is described as “doubling” dementia risk later in life.
  • Specific multipliers are stated:
    • ~2.3× increased dementia risk in women with type 2 diabetes.
    • ~1.7× increased dementia risk in men with type 2 diabetes.

Mechanistic narrative emphasized

• Sugar chemistry:
  • Sucrose is described as composed of glucose + fructose.
  • Fructose is described as being handled differently from glucose and, at current consumption patterns, contributing to systemic and brain-related harm.
• Fructose-related brain/metabolic claims:
  • Fructose intake is described as reducing ATP and increasing uric acid in neurons.
  • Downstream effects named: oxidative stress, insulin resistance, leptin resistance.
  • Satiety claim: reducing sugar (especially fructose) is described as reducing hunger over time.

Oral health as a dementia-related pathway

• Poor oral hygiene (not brushing/flossing) is described as associated with higher Alzheimer’s/cognitive decline risk.
• Gum disease bacteria are described as able to travel to the brain (Porphyromonas gingivalis is named in the talk).

Risk factors list explicitly named in the Q&A segment

• Sleep deprivation.
• Stress.
• Alcohol: >~4 standard Australian drinks/week is stated to “start to shrink your brain” and increase dementia risk.
• Smoking.
• Low vitamin D (“sun starvation”).
• Sedentary living / low muscle strength (sarcopenia is referenced).
• Air pollution/smog/smoke.
• Traumatic brain injury (“smashing your head”).
• Sensory loss (hearing is implied by “sensory loss,” with emphasis on reduction).
• Chronic severe midlife depression (untreated).
• Low novelty / low mental stimulation.
• Social isolation and loneliness; loneliness is stated to be as damaging as smoking ~15 cigarettes/day.

Dietary strategy emphasized for symptomatic support in dementia

• Ketogenic diet framing:

  • Presented as the primary dietary intervention offered in clinical practice for dementia patients.
  • Rationale given: ketones as an alternative brain fuel when glucose metabolism is impaired.
  • A 12-week modified ketogenic diet trial is described as reporting improvements in quality of life and daily function.

• MCT oil implementation:

  • MCT is defined as medium-chain triglycerides; liver conversion to ketones is described.
  • Source described: coconuts.
  • Practical dosing guidance is described qualitatively (start slow; add to foods such as eggs/vegetables).
  • Anecdotal report: missing a day of MCT oil is described as being noticed as worse cognitive function by some individuals.

Nutrients and supplements emphasized

• Omega-3 fats:

  • Stated as important throughout life.
  • APOE4-specific claim: APOE4 carriers (after ~50–60 years) are described as absorbing omega-3 less well than non-carriers.
  • Vegetarian/vegan guidance: omega-3 supplementation is recommended.
  • High omega-6 diet (seed oils) is stated to impair conversion of ALA to DHA.

• Choline:

  • Described as essential for brain health and as a precursor for acetylcholine (stated as deficient in Alzheimer’s).
  • Food examples stated to contain choline: soybeans, shiitake, broccoli, almonds.

• Creatine:

  • Described as an emerging intervention with limited studies to date.
  • Clinical practice claim: ~5 g/day prescribed for dementia patients.
  • Food equivalence claim: ~10 g creatine from ~2 tins of sardines/day is stated.
  • Sardines are also positioned as beneficial via omega-3 + creatine.

• B vitamins / homocysteine:

  • Biomarkers emphasized: B12 and homocysteine.
  • High homocysteine is described as an early risk signal and linked to brain shrinkage before symptoms.
  • Intervention described: high-dose B6/B9/B12 to lower homocysteine, referencing a named trial.

Papers / Trials (DOI)

• Ultra-processed food consumption and cognitive decline (JAMA Neurology; 2022/2023): 10.1001/jamaneurol.2022.4397
• Modified ketogenic diet in Alzheimer’s disease; randomized crossover (Alzheimer’s Research & Therapy, 2021): 10.1186/s13195-021-00783-x
• VITACOG: B vitamins lowering homocysteine and brain atrophy in MCI (PLOS ONE, 2010): 10.1371/journal.pone.0012244

Title: “I Didn’t Eat for 39 Hours… Then Ran 62 Miles (Fasted) — Carnivore Ultra Runner Interview”

Summary (from the video only; no sponsors, no CTAs):

• Background

• Greg describes discovering the carnivore diet via a relative (his uncle).
• Initial skepticism (“you need fiber/fruit/veg”) shifts after trying it himself.

• Pre-carnivore health/issues

• Long-standing eczema/skin problems treated repeatedly with steroid creams and pills.
• A severe rash two years prior led to more steroids; doctors framed it as “this is who you are.”

• Switching to carnivore

• Adopted a meat- and egg-based diet after conventional approaches failed.
• Within ~2 weeks he noticed significant improvement in skin/eczema.
• Reports steadier energy, reduced food preoccupation, simpler meals, and less stress about recipes.

• Training/running context

• Took up running ~1–1.5 years prior; later got into ultrarunning.
• Began experimenting with fasted training runs (dinner the night before, then run without breakfast).

• The fasted 100K (≈62 miles)

• Entered a 100-kilometer ultramarathon with a plan to remain fasted.
• Did not eat for 24 hours before the start, ate only after finishing.
• Total time without food ≈39 hours (24 hours pre-race + ~15 hours of racing).
• During the race he consumed only water and electrolytes (salt-stick type: sodium, potassium, magnesium).
• Took roughly one electrolyte capsule per hour to prevent cramps/fatigue.
• Reports no GI issues, no energy crashes, and no “hitting the wall.”
• Observed other athletes consuming large amounts of carbohydrates (he mentions ~80–100 g/hour as a common target among ultrarunners) and some experiencing bonks/crashes.

• Perceived effects/observations

• Describes stable, even energy throughout most of the race; acknowledges normal late-race fatigue but no bonk.
• Says he has “never hit the wall” since being on carnivore.
• Notes that conventional endurance advice (high-carb fueling) conflicted with his experience.

• Adaptation period & practical notes

• Warns athletes to expect an adaptation period (possibly 1–2 months of worse performance) when switching diets.
• Emphasizes electrolytes (sodium/potassium/magnesium) and hydration on carnivore/fasted runs.
• Typical pre-run approach outside of races: eat the evening meal, then run fasted the next morning.

• Social reaction & debate

• Fellow runners were surprised he attempted and completed a 100K entirely fasted.
• Mentions critics of carnivore and says he’s open to being a “guinea pig” for testing/measurement in the future.

Referenced papers (as mentioned in the video):
• None explicitly cited; no DOI-identifiable papers referenced by title or author in the conversation.