Resveratrol and Pterostilbene

Resveratrol is the textbook case of high absorption and near-zero bioavailability: roughly three quarters of an oral dose is absorbed, yet less than 1% reaches circulation as the unchanged molecule. Pterostilbene, its dimethylated analog, resists that first-pass conjugation better. Both are supplement ingredients with no approved drug use.

Chemistry and biology

Trans-resveratrol (228 Da) is a stilbene from grapes, Japanese knotweed and peanuts. It is poorly water-soluble and photosensitive; UV and daylight convert the trans isomer to the cis isomer. Pterostilbene (256 Da) replaces two hydroxyl groups with methoxy groups, which raises lipophilicity and removes two sites for glucuronidation and sulfation. Interest in both stems from sirtuin and AMPK signaling data in cells and animals. Human trials of resveratrol on metabolic and cardiovascular markers have produced mixed, mostly small effects.

Regulatory status

Both are sold as dietary supplement ingredients in the US. Synthetic trans-resveratrol has an EFSA novel food safety opinion and is on the EU Union list of novel foods with conditions of use. Neither is an approved medicine, and neither appears on the WADA Prohibited List. Any finished product must meet the supplement or novel food rules of the target market, including maximum levels where set. Label claims must stay within structure and function language in the US and within authorized health claims in the EU, where none exist for resveratrol.

Why bioavailability is the bottleneck

Resveratrol is rapidly conjugated in the intestinal wall and liver to glucuronides and sulfates, so plasma levels of the parent molecule after an oral dose are in the low nanomolar to low micromolar range, below concentrations used in many cell studies. Pterostilbene showed roughly 80% oral bioavailability in rats against about 20% for resveratrol in a direct comparison. Neither advantage has been shown to translate into a clinical outcome in humans.

Formulation routes in use

Micronized resveratrol, cyclodextrin complexes, lipid nanoparticles and co-administration with metabolic inhibitors such as piperine have all been tested. Light-protective packaging and antioxidants are needed to hold the trans isomer. Pterostilbene is often chosen instead of reformulating resveratrol. Each approach has trade-offs. Cyclodextrins raise apparent solubility but add bulk, lipid nanoparticles need stabilizers, and piperine creates interaction risk with drugs cleared by the same conjugating enzymes. For pterostilbene, the questions are mainly crystal form and dispersion, because its metabolic stability is already better. Comparative human pharmacokinetic data between commercial forms are sparse, so buyers should ask for study design, comparator and analyte (parent versus total conjugates) before relying on any bioavailability figure.

Key facts

• About 70% of an oral resveratrol dose is absorbed in humans, but bioavailability of the unchanged molecule is below 1% because of rapid conjugation (Walle et al. 2004, Drug Metab Dispos 32:1377)
• In rats, oral bioavailability was about 80% for pterostilbene versus about 20% for resveratrol (Kapetanovic et al. 2011, Cancer Chemother Pharmacol 68:593)
• Synthetic trans-resveratrol received an EFSA novel food safety opinion and is listed on the EU Union list of novel foods (EFSA NDA Panel 2016, EFSA Journal)
• Trans-resveratrol isomerizes to cis-resveratrol under UV and visible light exposure (Trela and Waterhouse 1996, J Agric Food Chem 44:1253)

Talk to our formulation team about a light-stable, controlled-release stilbene format.

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