Resveratrol
Trans-Resveratrol
Trans-resveratrol is a naturally occurring polyphenol stilbene found in red grapes, berries, and Japanese knotweed, widely used as a longevity-focused supplement with antioxidant and anti-inflammatory properties. It is primarily marketed for cardiovascular protection, metabolic health, and potential lifespan-extending effects based on its activation of sirtuin pathways. Research interest has been driven by the 'French paradox' hypothesis and subsequent studies on its role in mimicking caloric restriction biology.
Mechanism of Action
Resveratrol activates SIRT1 (sirtuin-1), a NAD+-dependent deacetylase involved in cellular stress response, mitochondrial biogenesis, and metabolic regulation, partly by acting as an allosteric activator in the presence of acetylated substrates. It also inhibits NF-κB signaling to reduce pro-inflammatory cytokine production and acts as a potent scavenger of reactive oxygen species through its phenolic hydroxyl groups. Additionally, resveratrol modulates AMPK activation, inhibits COX-1 and COX-2 enzymes, and influences estrogen receptor signaling as a phytoestrogen.
Evidence by Health Goal(18 goals)
Dosing Protocols
With a fat-containing meal to improve absorption
Trans-resveratrol has poor oral bioavailability (~1%) due to rapid first-pass metabolism; taking with piperine (5-10mg) or a lipid-based formulation can significantly enhance absorption. Some longevity protocols use up to 1000mg/day when combined with NMN or NR, though evidence for doses above 500mg providing additional benefit is limited.
Safety & Side Effects
Resveratrol has a generally favorable safety profile at doses up to 500mg/day, with most adverse effects being gastrointestinal and dose-dependent. However, high-dose use (1g+/day) has shown mixed signals in clinical trials including potential pro-oxidant effects and interference with exercise adaptation, and its phytoestrogenic activity warrants caution in individuals with hormone-sensitive conditions.
Possible Side Effects
- !Gastrointestinal discomfort including nausea, bloating, and loose stools at doses above 1000mg/day
- !Diarrhea, particularly with rapid dose escalation or very high doses
- !Estrogenic effects at high doses due to phytoestrogenic activity, including potential hormonal disruption
- !Mild headache reported in some users, particularly at higher doses
- !Potential interference with thyroid function at sustained high doses
- !Joint pain or arthralgia reported anecdotally at doses above 1g/day
- !Reduced platelet aggregation leading to slightly increased bruising or bleeding tendency
Interactions
- -May potentiate anticoagulant and antiplatelet drugs (warfarin, aspirin, clopidogrel) by inhibiting platelet aggregation - monitor for increased bleeding risk
- -Inhibits CYP3A4, CYP2C9, and CYP2D6 enzymes - may increase plasma levels of statins, calcium channel blockers, and other substrates
- -May enhance hypoglycemic effects of metformin or insulin - monitor blood glucose levels closely in diabetic patients
- -Piperine co-administration significantly increases bioavailability but may also amplify interactions with CYP-metabolized medications
- -High doses may blunt aerobic exercise adaptations - some evidence suggests it interferes with exercise-induced AMPK signaling improvements in older adults
Cost & Where to Buy
Bulk trans-resveratrol from reputable suppliers (e.g., Japanese knotweed extract standardized to 98%+ trans-resveratrol) is relatively inexpensive; cost increases with branded formulations, micronized or liposomal delivery systems, or combination products with NMN/NR. Verify purity via third-party COA as adulteration with cheaper emodin-containing knotweed extracts is common.
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