Resveratrol

trans-3,5,4'-trihydroxystilbene

Also known as: Trans-resveratrol, 3,4',5-Stilbenetriol, Red wine extract, Grape extract

Resveratrol is a polyphenol found in grapes, red wine, and berries. It gained fame for the "French Paradox" and activates sirtuins, proteins associated with longevity.

Introduction

Resveratrol is a natural polyphenol compound found in the skin of grapes, berries, peanuts, and Japanese knotweed. It gained international attention in the 1990s when researchers proposed it might explain the "French Paradox" - the observation that French people had lower rates of heart disease despite a diet high in saturated fat, possibly due to red wine consumption.

Resveratrol belongs to a class of compounds called stilbenes and exists in two forms: trans-resveratrol (the more stable and bioactive form) and cis-resveratrol. Most supplements contain trans-resveratrol.

The compound activates sirtuins (particularly SIRT1), a family of proteins involved in cellular stress resistance, DNA repair, and metabolic regulation. Sirtuins are often called "longevity genes" because their activation is associated with lifespan extension in various organisms.

In 2006, a landmark study showed that resveratrol could extend lifespan in yeast, worms, and flies, and improve health markers in mice fed a high-fat diet. This sparked intense interest in resveratrol as a potential anti-aging compound.

However, human clinical trials have been mixed. Resveratrol has very low bioavailability - most of it is rapidly metabolized and eliminated. This has led to the development of various enhanced delivery forms and higher doses in recent research.

Despite bioavailability challenges, resveratrol remains one of the most studied compounds for longevity and has shown benefits for cardiovascular health, blood sugar control, and inflammation in human studies.

Main Benefits

Activates sirtuins (SIRT1), proteins associated with longevity and cellular stress resistance.
May improve cardiovascular health through antioxidant effects and blood vessel protection.
Shows potential for improving insulin sensitivity and blood sugar control.
Has anti-inflammatory properties that may benefit various chronic conditions.
May improve cerebral blood flow and cognitive function in older adults.

Mechanism of Action

Resveratrol exerts its effects through multiple mechanisms:

Sirtuin Activation: Resveratrol activates SIRT1, a NAD+-dependent deacetylase that regulates cellular stress responses, DNA repair, mitochondrial biogenesis, and metabolism. SIRT1 activation is associated with longevity in multiple model organisms.
AMPK Activation: Resveratrol activates AMP-activated protein kinase (AMPK), a cellular energy sensor that improves metabolic health, enhances mitochondrial function, and may mimic some effects of calorie restriction.
Nrf2 Activation: Resveratrol can activate the Nrf2 pathway, which upregulates endogenous antioxidant enzymes including superoxide dismutase, catalase, and glutathione peroxidase.
NF-κB Inhibition: Resveratrol inhibits NF-κB, a key regulator of inflammation. This anti-inflammatory effect may underlie many of its health benefits.
Nitric Oxide Enhancement: Resveratrol can increase nitric oxide production by endothelial cells, potentially improving blood flow and cardiovascular health.
Estrogen Receptor Modulation: Resveratrol can bind to estrogen receptors, acting as a phytoestrogen. This may explain some of its effects on bone and cardiovascular health.
mTOR Inhibition: Resveratrol may inhibit mTOR signaling, which is associated with lifespan extension in various organisms.

Natural Sources

Resveratrol is found in small amounts in grapes, red wine, berries, and peanuts. Wine provides higher concentrations due to fermentation of grape skins.

Examples:

Red wine (highest concentration among foods)
Red/purple grapes
Blueberries
Cranberries
Peanuts
Japanese knotweed (traditional source)

Ease of Sourcing from Diet3/10

Amounts in food very small; would need to drink excessive wine for therapeutic doses; supplementation required for significant intake.

Recommended Daily Intake

No established RDA. Studies use 150-1500 mg daily. Bioavailability is very low (less than 1%), leading to development of enhanced delivery forms.

Reference Values:

Standard resveratrol	250-500 mg/day
Enhanced bioavailability forms	150-250 mg/day
High-dose studies	1000-1500 mg/day

Sources for RDI/AI:

Take with food containing fat for better absorption. Trans-resveratrol is the bioactive form. Bioavailability is very low for standard forms.

Effectiveness for Specific Focuses

Longevity & Aging7/10

Activates sirtuins and AMPK; extends lifespan in animal models; calorie restriction mimetic; mechanistic support for longevity benefits.

Cardiovascular Health6/10

French Paradox association; improves endothelial function; anti-inflammatory; antioxidant; blood vessel protection.

Antioxidant Support6/10

Activates Nrf2 pathway; indirect antioxidant through enzyme upregulation; polyphenol antioxidant activity.

Metabolic Health5/10

Improves insulin sensitivity; activates AMPK; supports metabolic health; blood sugar control benefits.

Longevity Impact

Resveratrol activates SIRT1 and AMPK, pathways associated with longevity. Extends lifespan in yeast, worms, and flies. Human longevity effects not yet proven but mechanistically plausible.

Strength of Evidence for Longevity Claims5/10

Strong animal evidence; calorie restriction mimetic; activates longevity pathways; human longevity data lacking but mechanisms well-established.

Safety Information

Potential Side Effects

Gastrointestinal upset
Headache
Insomnia at high doses
Joint pain (rare)

Contraindications

Pregnancy and breastfeeding (insufficient safety data)
Hormone-sensitive conditions (theoretical phytoestrogen concern)
Surgery (discontinue 2 weeks before)

Overdose Information

Overdose Risk Level3/10

Generally well-tolerated; no serious toxicity observed; very high doses (>2.5 g) may cause GI upset.

Excellent safety profile. No serious adverse effects reported. Mild GI upset most common side effect.

Interactions

Drug Interactions:

Blood thinners (may have antiplatelet effects)
NSAIDs (may enhance effects)
Blood pressure medications (may lower BP)

Drug Interaction Risk3/10

Caution with blood thinners and BP medications; generally safe with most medications.

Other Supplement Interactions:

NMN/NAD+ precursors - synergistic for sirtuin activation
Other polyphenols - may be complementary

Supplement Interaction Risk2/10

Synergistic with NAD+ precursors; safe combinations.

Bioavailability is very low for standard forms. Enhanced delivery forms (liposomal, micronized, with piperine) may be more effective. Take with fat-containing meals.

Forms and Bioavailability

Standard resveratrol has very poor bioavailability (<1%). Enhanced forms include micronized, liposomal, and combinations with piperine or quercetin.

Trans-resveratrol (standard)

Pure trans-resveratrol; bioavailability less than 1% due to rapid metabolism and elimination.

Relative Bioavailability3/10

Very poor bioavailability; extensive first-pass metabolism; most excreted unchanged or as metabolites.

Standard form despite poor bioavailability. Requires higher doses (250-500 mg) to achieve effects. Take with fat-containing meal.

Micronized Resveratrol

Particle size reduced to improve absorption; better bioavailability than standard form.

Relative Bioavailability5/10

Improved absorption through reduced particle size; may achieve higher blood levels at lower doses.

Moderate improvement over standard form. Look for "micronized" on label. May be effective at 150-250 mg doses.

Liposomal Resveratrol

Encapsulated in liposomes to improve cellular uptake and bypass metabolism.

Relative Bioavailability6/10

Enhanced delivery through liposomal encapsulation; may significantly improve cellular uptake.

Premium form with potentially much better bioavailability. Less research than standard form but mechanistically superior.

Resveratrol with Piperine

Combined with black pepper extract to inhibit metabolism and enhance absorption.