NMN, NR, Resveratrol, Metformin & Other Longevity Molecules | Episode 4
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Recommendations from this episode
In transcript order-
Sponsor read
Sponsor read: personalized nutrition platform analyzing blood and DNA data with biological age test.
“InsideTracker is a personalized nutrition platform
Certaintypersonal onlystrong endorsement -
NAD precursor; raises NAD levels and lowers inflammation in humans; some evidence for ALS function when combined with pterostilbene.
“NR has been taken over the counter…since 2014
Dosage250 mg to 1 g per day; takes 9–10 days to peakCaveatsMany mouse benefits (lower blood sugar, insulin sensitivity, mitochondrial increases) not yet borne out in short human studiesCertaintyhedgedrecommendation -
Taking plain vitamin B3 doesn't raise NAD levels as effectively as NR or NMN.
“it doesn't raise NAD levels anywhere near the level that NR does
Certaintyexplicitmild caution -
Resveratrol-like molecule shown when combined with NR to improve function in ALS patients.
“combined NR with pterostilbene…ALS patients…improvement
Certaintyhedgedoffhand mention -
Organic (prompted)
Intravenous NAD drips are used for addiction, depression, hangovers; lacks placebo-controlled evidence.
“NAD IVs, do they work? My answer has to be, we don't know yet
Dosagehour-long IV dripsCaveatsNo placebo-controlled trials yetCertaintyhedgedoffhand mention -
mTOR inhibitor; extends lifespan in every organism tested; potentially toxic and immune suppressive; ~10 mg/week considered for longevity.
“it's extended the lifespan of every organism it's been given to
Dosage~10 mg per week (low, non-immunosuppressive dose)CaveatsCan be toxic; immune suppression at higher doses; not generally availableCertaintyhedgedrecommendation -
Alternative
Plant-derived AMPK activator with metformin-like effects; useful alternative for those who can't tolerate metformin.
“berberine…can mimic the effects of metformin
Dosage1–2 g/day, taken with food (yogurt/olive oil) for absorptionCaveatsPossible diarrhea, constipation, gas, upset stomachCertaintyexplicitrecommendation -
In a protocol
Sirtuin activator; Sinclair takes 1 g/day with yogurt or olive oil; shown to reduce fasting glucose and improve insulin sensitivity in humans.
“I take about a gram of resveratrol every day
Dosage1 g/day in the morning, mixed with fat (yogurt or olive oil) for absorptionCaveatsInsoluble in water — must take with fatCertaintypersonal onlypersonal use -
In a protocol
Used to dissolve fat-soluble supplements like resveratrol; also reportedly activates sirtuins.
“olive oil…seems to be really good for activating sirtuins
Dosagesmall amount mixed with supplementsCaveatsHigh in caloriesCertaintyhedgedpersonal use -
In a protocol Alternative
NAD precursor; Sinclair takes 1 g every morning; raises NAD ~2-fold and shows insulin sensitivity benefits in humans.
“I take one gram of NMN every morning
Dosage1 g in the morning; can go up to 2 gCaveatsCaution in people predisposed to pancreatic cancer (Nacarelli 2019 mouse study); consult physicianCertaintypersonal onlypersonal use -
In a protocol
AMPK activator; Sinclair takes 800 mg at night with dinner, skips on workout days; lowers risk of cancer, heart disease, Alzheimer's in diabetics.
“I take 800 milligrams at night
Dosage800 mg at night with dinner; skip on days before exerciseCaveatsCan cause lactic acidosis (rare, severe); upset stomach; may slightly reduce exercise gains; requires prescription in USCertaintypersonal onlypersonal use -
In a protocol
Autophagy inducer; Sinclair takes ~1 g/day in the morning; shown to improve memory in older adults at 1.2 g/day.
“I've added that to my protocol
Dosage~1 g/day in the morning (memory study used 1.2 g/day over 3 months)CaveatsSinclair advises the company that makes it (disclosed conflict)Certaintypersonal onlypersonal use -
In a protocol
Plant-derived senolytic; Sinclair takes ~0.5 g/day; Mayo Clinic trial dosing 20 mg/kg one day per week.
“I take about half a gram of each every day
Dosage~0.5 g/day maintenance; clinical trials use 20 mg/kg one day per weekCaveatsEarly days, less data than quercetin+dasatinib; safety not fully establishedCertaintyhedgedpersonal use -
In a protocol
Routine liver enzyme blood testing to monitor for harm from supplements.
“You can measure what's called AST, ALT. I do that routinely
Dosageroutine monitoringCertaintyexplicitrecommendation