#02 – Rhonda Patrick, Ph.D.: paradox of IGF-1, ketogenic diets and genetics, benefits of sauna, NAD+

KEYPOINTS

• 01

  IGF-1 sits in a paradox between growth and longevity.

  Higher IGF-1 tracks with more cancer in human polymorphism data, while very low IGF-1 risks frailty and loss of lean mass. Peter describes a right-skewed U-shaped all-cause mortality curve that nadirs around the 70th percentile of IGF-1; above that, the uptick is mostly cancer, while cardiovascular and neurodegenerative risk largely flatline. Peter jokes that living forever at the absolute bottom of IGF is not the clinical goal the U-curve suggests.

• 02

  Cycling high and low IGF may beat living permanently suppressed.

  Valter Longo's work and short water fasts (including clinical 48-hour protocols around cancer care) sit in this frame: periods of growth alternating with periods of lower IGF, rather than chronic caloric restriction alone. Rhonda notes rodent fasting results are hard to translate because mice lose ~20% body weight in a 48-hour water fast.

• 03

  A meaningful minority of keto patients are lipid hyper-responders.

  Peter estimates roughly 10–20% of people he has seen on a standard ketogenic pattern—often ≥40% of calories from saturated fat, ~40–45% mono—see LDL particle number explode even as triglycerides fall. One relatively young patient who loved keto came back with LDL-P above 3,500 nmol/L. He stresses he has personally seen dozens of patients on keto over his career, so the hyper-responder fraction is not a one-off anecdote.

• 04

  Genetics around PPAR pathways may help explain who thrives on keto.

  Rhonda discusses PPAR-related fat-metabolism genetics and free vs comprehensive genetic reports as a way to match phenotype to genotype. Both want larger cohorts of hyper-responders genotyped rather than blog debates about whether sky-high LDL-P 'doesn't matter on keto.'

• 05

  Exogenous ketone esters can spike blood ketones dramatically.

  Rhonda reported going from about 0.1 mM to 6 mM within an hour on a BHB ester—far above the ~0.5–1 mM she sees from overnight fasting or her usual feeding pattern while nursing (often an 11–12 hour eating window). Dom D'Agostino's ketone work comes up as context for how unnatural that spike is compared with fasting physiology.

• 06

  VO2 max falls about 1% per year with age—and is trainable.

  That ~10% per decade decline roughly parallels age-related muscle loss. A study she cites found 24 sessions of HIIT (about 45 minutes with warm-up/cool-down and hard intervals) raised VO2 max by roughly 12%, enough to offset years of drift.

• 07

  Finnish dry-sauna data is dose-dependent and hot.

  Observational work (Jari Laukkanen and colleagues) on men using traditional saunas around 175–179°F for ~20 minutes: 2–3 times per week associated with ~20% lower cardiovascular mortality vs once weekly; 4–7 times per week associated with ~40% lower all-cause mortality in the comparison Rhonda recounts. Dementia risk also looked ~20% lower at 2–3 sessions. She contrasts that with infrared cabins that top out near 140°F and cannot reproduce the same thermal load.

• 08

  Infrared saunas at ~140°F are not the same stimulus.

  She argues you need the high heat and roughly 20 minutes (11 minutes showed smaller effects) to match the Finnish protocols. Sweat-based detox claims get less weight than the cardiovascular and mortality associations.

• 09

  Cold after heat is an additive recovery and mood tool.

  Her stack is ~20 minutes of sauna then a cold shower or immersion. She has swam in Colorado River water around 42°F when air was hot enough to make it tolerable, and notes 50°F ocean swims of a few hours for a milder version of the same vasoconstriction/afterglow effect. Peter recounts that 42°F swim only worked because air temperature was near 90°F; the same water on a cloudy day would have been untenable.

• 10

  Exercise remains hard to beat for brain health.

  Despite coming from a deep molecular-biology background, Rhonda says the minimum-effective-dose question for aerobic work plus HIIT keeps winning against supplement stacks when the outcome is brain and healthspan.