Pterostilbene — Supplements
Resveratrol analog with 80% oral bioavailability (vs. 30% for resveratrol), superior blood-brain barrier penetration, and comparable SIRT1/AMPK activation with longer half-life.
Overview
Pterostilbene (trans-3,5-dimethoxy-4'-hydroxystilbene) is a naturally occurring polyphenol found primarily in blueberries (highest dietary source), grapes, and Pterocarpus marsupium heartwood. It is the di-methylated analog of resveratrol — the two additional methoxy groups dramatically improve pharmacokinetics: oral bioavailability ~80% vs. ~30% for resveratrol, longer plasma half-life, superior blood-brain barrier penetration, and significantly lower rate of hepatic glucuronidation. These pharmacokinetic advantages translate into sustained systemic and CNS exposure at lower doses than resveratrol. Pterostilbene activates SIRT1 and SIRT3 (longevity-associated deacetylases), AMPK, and Nrf2, and suppresses NF-κB — the same mechanistic targets as resveratrol but with greater potency and duration. A 2013 human RCT (Riche et al., 2013) demonstrated safety at 250 mg/day over 8 weeks, with favorable effects on blood pressure and LDL-C. Pterostilbene functions as a senomorphic (SASP suppressor) rather than a direct senolytic — it reduces the pro-inflammatory output of senescent cells without directly inducing their apoptosis. It also demonstrates significant neuroprotective, cardiometabolic, and anticancer properties in preclinical models.
Indications
- Cognitive aging and neurodegeneration prevention (preclinical)
- SASP suppression and inflammaging reduction
- Cardiometabolic health — LDL-C reduction, blood pressure support
- Antioxidant and Nrf2-mediated cytoprotection
- Longevity — SIRT1/AMPK pathway activation
Mechanism of Action
Pterostilbene directly activates SIRT1 (nuclear deacetylase) and SIRT3 (mitochondrial deacetylase) at lower concentrations than resveratrol, due to superior bioavailability — deacetylating PGC-1α (mitochondrial biogenesis), FOXO3a (stress resistance), and NF-κB (inflammation) substrates
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Pterostilbene | 50–150 mg | Once to twice daily with food | Lower dose range used for longevity/SASP suppression; commonly combined with resveratrol 150 mg in commercial formulations |
| Pterostilbene (high dose — cardiometabolic) | 250 mg | Once daily | Dose used in the Riche 2013 human RCT; associated with LDL-C changes — lipid monitoring recommended |
Safety & Contraindications
- Generally well tolerated; 250 mg/day shown safe in 8-week human RCT (Riche et al., 2013); no serious adverse events
- LDL-C elevation noted at higher doses (250 mg/day) in some subjects with pre-existing metabolic risk — monitor lipid panel
- CYP2C9 inhibitor — may elevate warfarin levels; monitor INR carefully in anticoagulated patients
- Anti-platelet activity — avoid with NSAIDs/anticoagulants without monitoring
- Weak estrogen receptor agonist in vitro — use caution in hormone-sensitive cancers (breast, endometrial) pending more data
- Avoid in pregnancy and breastfeeding — insufficient safety data
- Dietary sources (blueberries) provide negligible amounts (~100 mcg/serving) — supplemental doses required for any pharmacological effect