Resveratrol (Stilbene)

Resveratrol is a stilbenoid compound found in grape skins and red wine that activates SIRT1 proteins and provides antioxidant activity. This polyphenol modulates inflammatory pathways and may support cardiovascular health through its effects on endothelial function.

Origin & History

Resveratrol is a stilbenoid phytoalexin (trans-3,4′,5-trihydroxystilbene) naturally produced in plants like grapes, particularly in skins, as a defense against stressors such as UV light and pathogens. It is synthesized via stilbene synthase from phenylalanine-derived precursors and is typically extracted from grape pomace using solvent methods.

Historical & Cultural Context

The research dossier contains no information about traditional or historical medicinal uses of resveratrol. The compound's discovery and use appear to be primarily modern, related to its identification in grape products.

Health Benefits

• Antioxidant properties derived from its stilbenoid structure (evidence quality not specified in available research)
• Anti-inflammatory effects through biochemical activity (evidence quality not specified in available research)
• Note: The research dossier lacks specific clinical trial data to support definitive health claims
• Available research focuses primarily on chemical structure and extraction methods
• Clinical evidence for specific health benefits is not documented in the provided research

How It Works

Resveratrol activates sirtuin 1 (SIRT1) proteins, which regulate cellular metabolism and stress responses. It inhibits nuclear factor-kappa B (NF-κB) inflammatory signaling while scavenging reactive oxygen species through its phenolic hydroxyl groups. The compound also modulates nitric oxide synthase activity in vascular endothelium.

Scientific Research

The research dossier contains no specific clinical trials, RCTs, or meta-analyses with PMIDs for resveratrol. The available research focuses on chemical characterization and extraction methods rather than clinical outcomes.

Clinical Summary

Human studies on resveratrol show mixed results with small sample sizes typically ranging from 20-100 participants. Some trials using 150-500mg daily doses report modest improvements in inflammatory markers and endothelial function. However, many studies lack sufficient duration and statistical power. The evidence quality remains limited due to inconsistent dosing protocols and short study periods.

Nutritional Profile

Resveratrol (3,5,4'-trihydroxystilbene) is a polyphenolic stilbenoid compound, not a macronutrient source. Molecular weight: 228.24 g/mol. Found naturally in: red grape skins (50–100 µg/g fresh weight), red wine (0.1–14.3 mg/L, with typical range 1.5–3.0 mg/L), peanuts (~0.01–1.8 µg/g), Japanese knotweed (Polygonum cuspidatum, richest dietary source at ~187–524 µg/g dry root), blueberries (~32 µg/g fresh weight), cranberries (~17 µg/g), and dark chocolate (~0.4 µg/g). Exists in two geometric isomers: trans-resveratrol (more biologically active and thermodynamically stable) and cis-resveratrol. Key bioactive compounds co-occurring in natural sources include other stilbenoids (piceatannol, pterostilbene, viniferin), flavonoids, and anthocyanins. Contains no macronutrients (protein, fat, carbohydrate), vitamins, minerals, or fiber as an isolated compound. Bioavailability is notably poor: oral bioavailability estimated at <1% due to rapid Phase II metabolism (extensive glucuronidation and sulfation in the intestine and liver). Peak plasma concentration of free resveratrol after a 25 mg oral dose is approximately 1–5 ng/mL (reached within 0.5–1.5 hours). Total metabolite plasma levels (resveratrol-3-O-sulfate, resveratrol-3-O-glucuronide, resveratrol-4'-O-glucuronide, dihydroresveratrol) can reach ~400–500 ng/mL, suggesting metabolites may contribute to biological effects. Half-life of free resveratrol in plasma is approximately 8–14 minutes; total resveratrol metabolites have a half-life of ~9.2 hours. Absorption rate is estimated at ~70% of oral dose (primarily as metabolites). Micronized or lipid-encapsulated formulations and co-administration with piperine (bioenhancer) may improve bioavailability by 2–5 fold. Typical supplement doses range from 100–1,500 mg/day of trans-resveratrol, far exceeding dietary intake from foods (estimated at 0.5–4 mg/day in moderate red wine consumers). Enterohepatic recirculation may provide sustained low-level exposure. Protein binding in plasma is approximately 90–98%, primarily to albumin and lipoproteins.

Preparation & Dosage

No clinically studied dosage ranges are provided in the available research. Forms mentioned include the trans-isomer as the stable, bioactive form, which can be extracted from grape sources. Consult a healthcare provider before starting any new supplement.

Synergy & Pairings

Pterostilbene, piceatannol, grape seed extract, quercetin, vitamin C

Safety & Interactions

Resveratrol is generally well-tolerated at doses up to 1000mg daily, though gastrointestinal upset may occur at higher doses. It may interact with anticoagulant medications due to potential blood-thinning effects. The compound can interfere with certain chemotherapy drugs by affecting cellular pathways. Pregnant and breastfeeding women should avoid supplementation due to insufficient safety data.