Supplements for Longevity & Their Efficacy | Dr. Peter Attia

Attia lays out a framework for longevity (behaviors, disease-targeting drugs, geroprotective molecules, and the kitchen-sink approach) before he and Huberman take a deep, skeptical dive into the NAD pathway. They trace the science from sirtuin overexpression in yeast through resveratrol's collapse, the failure of NR in the rigorous Interventions Testing Program, and weak human studies on NMN. Both conclude there is no evidence NAD-boosting supplements extend lifespan, with the only possibly genuine signal being reduced basal/squamous skin cancer risk. They contrast this with rapamycin, which Attia takes and considers the most promising geroprotective drug, and close by sharing their full personal supplement regimens while stressing that sleep, exercise, nutrition, and emotional health dwarf any supplement.

• Attia and a few patients personally raised ~$2.5M to keep Matt Kaeberlein's dog aging rapamycin study going after NIH funding fell short.
  00:23:35
• Attia states flatly there is zero evidence sirtuins and caloric restriction work through the same pathway, despite 20 years of belief they do.
  00:38:16
• Attia describes IV NAD as feeling like 'somebody stepping on your chest with a boot' for the first 10 minutes.
  01:08:29
• NR was a notable failure in the Interventions Testing Program: no lifespan extension, no healthspan improvement.
  01:14:44
• Both agree NAD supplements do not extend lifespan: 'the answer appears to be unambiguously no.'
  01:35:42
• Attia pinpoints the 2014 everolimus immunity study as his personal turning point toward taking rapamycin.
  01:43:35
• Attia: 'I don't take these supplements full stop ... I passionately do not believe they do anything for me.'
  02:27:54

• Attia takes 8 mg of rapamycin once a week, cycling on and off because it gives him canker sores in about 10% of users.
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• Only two interventions have ever extended lifespan across yeast, worms, flies, and mammals: caloric restriction and rapamycin.
  00:20:28
• Skin loses about 60% of its NAD over a lifetime, versus roughly 15-20% in the brain and ~20% in blood.
  00:54:54
• A 2015 study found NAD drops with age but NADH rises by the same amount, so what really declines is redox potential, not total NAD.
  00:57:00
• Mouse efficacy doses run 500-1,000 mg/kg; at human equivalents that would cost roughly $300/day, making them infeasible.
  01:11:04
• The one genuine NMN/NR signal Attia found: a 60-80% reduction in basal and squamous cell carcinomas, but no effect on melanoma.
  01:27:53
• Generic rapamycin costs about $5/mg, so Attia's 8 mg weekly dose runs ~$40/week.
  01:41:29
• Living at sea level gives ~1 millisievert of radiation a year; a DEXA scan delivers less than a cross-country flight.
  01:55:37
• Pendulum is, per Attia, the only company that can make anaerobic Akkermansia probiotics, requiring Pharma-grade nitrogen-infused vats.
  02:17:33
• Attia's analogy: supplements are like whether the Titanic served lobster or steak; sleep, exercise, nutrition and mental health are the ship's heading.
  02:25:48

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