Supplements for Longevity & Their Efficacy | Dr. Peter Attia

KEYPOINTS

• 01

  Living longer today means delaying chronic disease

  Attia notes that a century or more ago, living longer meant surviving childbirth, infection and trauma. Now it is mathematically equivalent to delaying cardiovascular, cerebrovascular, metabolic and neurodegenerative disease and cancer. He sorts tools into three groups: unavoidable behaviors done well or badly (eating, sleeping, moving); drugs that target specific diseases (statins, PCSK9 inhibitors, bempedoic acid, SGLT2 inhibitors, GLP-1 agonists, metformin); and 'geroprotective' molecules aimed at hallmarks of aging.

• 02

  Attia takes rapamycin as his one purely geroprotective drug

  He takes 8 mg once a week, pausing when he gets painful mouth ulcers (aphthous ulcers), which hit about 10% of users and are 'paradoxically the only biomarker' that it's working. Generic rapamycin costs about $5 per mg, roughly $40 a week. He also takes a PCSK9 inhibitor, bempedoic acid and an SGLT2 inhibitor, which he considers probably broadly geroprotective too.

• 03

  Weekly pulsing changed his view of rapamycin's immune effects

  Daily rapamycin is an immunosuppressant, approved in 1999 for transplant patients. A 2014 study by Joan Mannick and Lloyd Klickstein gave 65-year-olds the related drug everolimus on intermittent schedules and found better responses to flu vaccine. For Attia, that marked the shift from 'cool in mice' (the 2009 ITP result) to 'maybe we should take this', since the drug appears to modulate immunity in either direction.

• 04

  The Interventions Testing Program is the strictest test of longevity molecules

  The ITP tests compounds in genetically diverse (non-inbred) mice in triplicate at three institutions; of more than 50 molecules, very few extend life. Rapamycin worked even when started at about 21 months, roughly a 60-year-old human equivalent. Canagliflozin (an SGLT2 inhibitor), acarbose and 17-alpha estradiol also worked. Resveratrol did 'categorically nothing'.

• 05

  Glucose control may matter independent of weight

  Acarbose, which blocks glucose absorption in the gut, and canagliflozin, which makes you excrete glucose in urine, both extended mouse lifespan without lowering body weight. Attia reads this as evidence that tight glycemic control itself has longevity value.

• 06

  NR failed the ITP at mega-doses

  Nicotinamide riboside, an NAD precursor, was tested at roughly 500–1,000 mg per kg of body weight and produced no change in lifespan or healthspan. Mouse-equivalent doses for a 100-kg person would cost about $300 a day. Huberman says NR crosses cell membranes readily, while NMN's phosphate group is cleaved in the gut, which may favour NR at 300–600 mg over NMN at about 1,500 mg.

• 07

  Human NR trials show statistical blips, not clinical benefit

  In a roughly 100-person fatty-liver trial (MRI liver fat; above 5% counts as fatty liver), neither dose changed liver fat, weight, inflammation or glucose. Only a subgroup analysis (people under 27% liver fat) showed the lower dose dropping from 20% to 15%, while the higher dose did nothing. Attia warns never to confuse statistical with clinical significance, comparing it to lowering blood pressure from 160/100 to 157/97.

• 08

  One intriguing signal: non-melanoma skin cancer

  Attia found one study (NR or NMN — he considers them roughly equivalent) reporting 60–80% fewer basal and squamous cell carcinomas, with no effect on melanoma. He'd like to see it replicated. It might matter for people with heavy sun exposure, and he notes skin shows the largest age-related NAD decline.

• 09

  Biological-age tests are mostly noise for now

  Clocks that combine glucose, vitamin D and methylation markers are too variable to tell whether you measured the same 'state' a year apart. Attia says that, last he checked, companies weren't truly sequencing the epigenome base by base, just averaging methylation. He thinks the epigenetic piece may prove useful eventually.