Podbit · The Peter Attia Drive
Ezetimibe works in the gut and can't cross the blood-brain barrier — but its metabolite, ezetimibe glucuronide, can. Animal studies show it interferes with hexokinase and reduces brain protein glycosylation, producing anti-inflammatory effects. Neurologists already report anecdotal cognitive benefits in patients.
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At 1:19:40 · chapter starts 1:19:30
Peter asks about ezetimibe — a drug that works in the gut by blocking intestinal cholesterol absorption and might seem irrelevant to brain health. Tom acknowledges it shouldn't have a brain effect based on first principles, but then reveals that ezetimibe's main metabolite, ezetimibe glucuronide, can cross the blood-brain barrier in small amounts [1] — Tom Dayspring "Ezetimibe works in the gut and can't cross the blood-brain barrier — but its metabolite, ezetimibe glucuronide, can. Animal studies show it…" 1:19:40 . In animal studies, it interferes with hexokinase and reduces glycosylation of brain proteins, producing anti-inflammatory effects. Neurologists who specialize in Alzheimer's prevention — Tom names Richard Isaacson and Kelly Endiotes — have anecdotally observed cognitive benefits in patients taking ezetimibe, beyond what would be expected from ApoB lowering alone. Tom frames a plausible clinical strategy: for APOE4 carriers with elevated ApoB, a combination of low-dose statin plus ezetimibe may target both cardiovascular and brain health simultaneously. He notes that existing trial biobanks from ezetimibe studies could in principle be mined for pre- and post-treatment P-tau and amyloid-beta-40/42 data without needing a new trial.
Ezetimibe itself cannot cross the blood-brain barrier, but its metabolite ezetimibe glucuronide can penetrate in small amounts and has shown anti-inflammatory effects in the brain in animal studies.
AI nailed Andrew Huberman's vertigo-vs-low-blood-pressure diagnosis because that pattern has been reported millions of times. But every patient's liver is different and data on liver surgeries is scarce worldwide — making solo robot surgery dangerous. The rule is simple: data abundance means AI can help; data scarcity means keep the human in the loop.
Fei-Fei Li's father had liver surgery performed by a da Vinci robot guided by a surgeon. The result: 10 times less blood loss than a typical procedure. This isn't replacement — it's the gold standard of human-machine collaboration, where the human's judgment and the robot's precision combine.
US drug overdose deaths fell from 110,000 to roughly 70,000 — the biggest CDC-recorded single-year drop ever. Men's rates fell 27% in one year, and the steepest decline of all was among 15–24-year-olds, down 37%. The crisis narrative around young men needs to make room for signs of genuine progress.
Kessler thought his grief expertise would protect him. It didn't. When his son David died unexpectedly, he found himself on the floor — and eventually realized that acceptance alone wasn't enough. That unmet need became the sixth stage: finding meaning.
Grief isn't just death — it's any unwanted change. Kessler lectured at Coca-Cola and General Mills not because they had lots of funerals, but because change management is grief management. People who grieve well live well.
Witnessing someone's grief isn't just emotional support — it's an essential act of healing. Kessler argues grief is a severance and connection heals it. But real witnessing has two steps: seeing the pain AND affirming the person's capacity to recover.
Avoiding grief isn't free — it's exhausting. Kessler's beach ball metaphor nails it: pushing a small balloon down is easy, but holding a massive beach ball underwater takes constant, draining energy. Unattended feelings don't disappear; they just consume you.
Most people try to control their environment to avoid triggers. Kessler flips this entirely: triggers aren't problems to manage around — they're a detailed map to your pain and your healing. Every trigger points directly to what needs attention.
Running from pain doesn't leave it behind — it accelerates the chase. Whatever we run from pursues us, and whatever we face transforms us. Both Kessler and Lewis Howes testify to knowing both roads firsthand.
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