Stilbene polyphenol from red grapes · allosteric SIRT1 activator (Howitz/Sinclair 2003 · Nature). Combo with NMN to potentiate sirtuins: NMN provides substrate, resveratrol activates the enzyme. Pterostilbene is the methylated cousin · 4× bioavailability.
4Resveratrol appears in 4 protocols personalizable→Stilbene polyphenol present in red grapes, wine, peanuts and berries. Allosteric SIRT1 activator · critical combo with NMN (NAD+ substrate) to potentiate sirtuins.
Resveratrol (3,5,4'-trihydroxystilbene) is a stilbene polyphenol produced by plants in response to stress (fungi, UV, wound). Natural sources are red grapes (~1-2 mg/L red wine), peanuts, blueberries and berries. A therapeutic dose (250 mg) equals ~125 liters of red wine · impossible to obtain from diet.
Howitz, Sinclair and colleagues (2003 · Nature) demonstrated that resveratrol is allosteric activator of SIRT1, one of the 7 human sirtuins (SIRT1-7). Sirtuins are NAD+-dependent deacetylases regulating DNA repair, autophagy, mitochondrial biogenesis and epigenetic silencing · molecular pillars of aging.
Pterostilbene (3,5-dimethoxy-4'-hydroxystilbene) is resveratrol's methylated cousin · present in blueberries. It has 4× the oral bioavailability of resveratrol (Kapetanovic 2011) due to methoxy groups that avoid hepatic glucuronidation. Both activate SIRT1, but pterostilbene also modulates AMPK more potently.
5 pivotal studies · Howitz 2003 cardinal mechanistic · human cardio-metabolic RCTs · NIA ITP · pterostilbene bioavailability.
| Study | Finding | Hallmarks |
|---|---|---|
Resveratrol SIRT1 activator · cardinal study Howitz, Sinclair et al · Nature 2003 | Cardinal study · screening 18 STACs (SIRT1 activating compounds) polyphenols · resveratrol most potent (EC50 = 35 µM). Mechanism: allosteric conformational change increases SIRT1 substrate affinity. Mechanistic foundation of the field. | SIRT1Mechanistic |
Resveratrol and metabolic improvement obese Timmers et al · Cell Metab 2011 | 30-day RCT · n=11 obese men · 150 mg/day trans-resveratrol · improved insulin sensitivity, reduced systolic blood pressure 5 mmHg, reduced plasma TG. Mimic effects of caloric restriction. | MetabolicInsulin |
Pterostilbene bioavailability and safety Kapetanovic et al · Cancer Chemother Pharmacol 2011 | Comparative PK study in mice · pterostilbene has 80% oral bioavailability vs 20% resveratrol (4× more). Half-life 105 min vs 14 min. Confirms pharmacokinetic superiority of methylated cousin. | Bioavail.PK |
Resveratrol and CV mortality diabetics Marx et al · Br J Clin Pharmacol 2018 | Meta 15 RCTs · n=898 T2 diabetics · 100-1,500 mg/day resveratrol · HbA1c −0.5%, systolic pressure −7 mmHg, LDL −10 mg/dL. Clinically relevant effects at 12+ weeks. | DiabetesCV |
NIA ITP · resveratrol does NOT extend male mouse lifespan Strong et al · J Gerontol 2013 | NIA ITP program · resveratrol 300-1,200 mg/kg diet did not extend median lifespan in male mice. IMPORTANT finding: contradicts earlier studies · human evidence is weaker than public believes. | ITP-NIANegative |
My Protocol generates 3 personalized plans with exact form, dose and combos based on your profile. No commitment.
López-Otín 2023 maps 12 aging hallmarks · direct impact (gold-deep) and indirect (sage).
Trans-resveratrol 150-500 mg/day with fat · optimal with yogurt or oil (8× absorption vs fasting) · combo with pterostilbene 50 mg for extended half-life.
Start with Timmers 2011 RCT dose. Take with Greek yogurt, olive oil or avocado (fat increases absorption 8×). Some report facial flushing first 1-2 weeks (tolerable, diminishes).
Canon combo · resveratrol covers SIRT1 activation + pterostilbene extends half-life + modulates AMPK. Take with fatty breakfast (yogurt, eggs + avocado). Maintain 3-6 months.
Sinclair canon protocol documented in Lifespan 2019. Metformin is medical prescription · DO NOT self-medicate. Combo targets sirtuins (R+NMN) + AMPK (metformin) · mimic caloric restriction.
Some authors suggest seasonal breaks due to long-term adaptation doubts. Limited evidence · pragmatic: if budget tight, pause summer when sun exposure increases endogenous sirtuins.
Chemical form absolutely critical · trans-isomer (active) vs cis-isomer (inactive). Only trans has SIRT1 activity. Pterostilbene optional but recommended by PK.
Absolute criterion · ≥99% trans-isomer (no cis-trans mix · cis is INACTIVE). Seek HPLC ≥99% trans + batch third-party COA.
Dose: 250 mg ResVida® + 50 mg pterostilbene / day
Form: Trans-R 99% · pterostilbene ≥99%
Cert.: GMP · third-party COA · MIT-licensed
Fillers: Vegetable capsule · zero excipients
Dose: 600 mg trans-resveratrol/capsule
Form: Trans-R 99% (Polygonum cuspidatum)
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Fillers: Cellulose · non-GMO
Dose: 200 mg trans-resveratrol/day
Form: Trans-R from Polygonum cuspidatum
Cert.: GMP · vegan
Fillers: Maltodextrin · cellulose
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Indirect biomarkers · no commercial SIRT1 test available · use insulin sensitivity + blood pressure + lipid profile.
HOMA-IR (insulin sensitivity). Timmers 2011 showed +20% insulin sensitivity with 150 mg/d in obese. If taking resveratrol for metabolic effects, measure HOMA-IR baseline and at 12 weeks. ~15 € general analytic.
Systolic blood pressure. Typical 5-7 mmHg reduction in hypertensives with elevated baseline at 250-500 mg/d (Marx 2018 meta). Detectable change in 8-12 weeks. Measure 2× daily for 1 week baseline/12 weeks.
HbA1c (diabetics). Marx 2018 meta showed −0.5% HbA1c in T2 diabetics. If taking for metabolic, measure HbA1c baseline + 3-6 months. ~12 € general analytic.
HbA1c + HOMA-IR + apoB + Lp(a) + advanced insulin sensitivity. Allows measuring cardio-metabolic effect of resveratrol pre/post 12 weeks.
Good general safety profile · but real pharmacological interactions via CYP3A4 inhibition and anti-platelet effect.
4 combos · resveratrol is SIRT1 activator · each combo increases or complements sirtuin activation.
Sinclair canon combo · NMN provides NAD+ (sirtuin substrate) + resveratrol activates SIRT1 directly. Substrate + activator = cardinal mechanistic synergy.
Quercetin + resveratrol mild senolytics · emerging combo for cellular senescence. Quercetin also inhibits CD38 (protects NAD+ pool).
Pt is methylated cousin · 4× bioavailability · half-life 7× longer. R + Pt combo covers entire day with single dose.
Both polyphenols modulate inflammaging NF-κB · combo amplifies anti-inflammatory effect. Curcumin + R + pterostilbene = complete anti-inflammaging stack.
8 real questions · scientific literature-based answers (including NIA negative trial).
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