What Is Resveratrol?

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural polyphenol produced by several plants in response to stress, injury, or fungal infection. It gained fame as the compound potentially responsible for the health benefits of red wine โ€” the so-called "French Paradox."

Molecular Formula: C14H12O3 Molecular Weight: 228.24 g/mol Natural Sources: Red grapes, blueberries, peanuts, Japanese knotweed Discovery: First isolated from white hellebore in 1939

While not a peptide, resveratrol is frequently studied alongside peptide-based longevity research due to its proposed sirtuin-activating properties and synergy with NAD+ boosting strategies.

Key Characteristics

  • Classification: Polyphenol, stilbenoid
  • Forms: Trans-resveratrol (active) and cis-resveratrol
  • Bioavailability: Low; rapidly metabolized
  • Research Interest: SIRT1 activation, longevity

Proposed Mechanisms

Sirtuin Activation

Resveratrol is known as a SIRT1 activator:

  • Increases SIRT1 enzyme activity
  • May work by inducing a conformational change in the enzyme
  • SIRT1 regulates metabolism, stress response, and longevity pathways
  • Some debate exists about direct vs indirect activation

AMPK Activation

Resveratrol activates AMP-activated protein kinase:

  • AMPK is a master metabolic regulator
  • Promotes glucose uptake and fatty acid oxidation
  • Inhibits lipid and protein synthesis
  • May explain metabolic benefits independent of SIRT1

Antioxidant Properties

  • Direct free radical scavenging
  • Upregulation of endogenous antioxidant enzymes
  • Reduction of oxidative stress markers

Anti-Inflammatory Effects

  • Inhibition of NF-ฮบB signaling
  • Reduced production of pro-inflammatory cytokines
  • COX enzyme modulation

Research Areas

Longevity and Aging

Resveratrol gained attention from lifespan studies:

  • Yeast & Worms: Extended lifespan in early studies
  • Obese Mice: Improved healthspan and survival on high-calorie diets
  • Normal Mice: Less clear lifespan effects in healthy animals
  • Caloric Restriction Mimetic: Activates similar pathways

Cardiovascular Health

  • Improved endothelial function in studies
  • Blood pressure regulation
  • Reduced LDL oxidation
  • Anti-atherosclerotic effects in animal models

Metabolic Health

  • Improved insulin sensitivity in some human trials
  • Enhanced glucose tolerance
  • Increased mitochondrial biogenesis
  • Effects on body composition

Neuroprotection

  • Protection against neurodegenerative disease models
  • Reduced amyloid-ฮฒ aggregation in Alzheimer's research
  • Improved cognitive function in some animal studies
  • Blood-brain barrier penetration

Cancer Research

  • Anti-proliferative effects in cell studies
  • Apoptosis induction in cancer cell lines
  • Anti-angiogenic properties
  • Chemosensitization potential

The Bioavailability Challenge

Absorption Issues

  • Only ~1-2% of oral resveratrol reaches circulation unchanged
  • Rapid metabolism by liver and intestinal enzymes
  • Converted to glucuronide and sulfate conjugates
  • Metabolites may have their own biological activity

This has led to research on:

  • Higher doses to achieve effective blood levels
  • Micronized formulations for better absorption
  • Combination with piperine (black pepper extract) to inhibit metabolism
  • Liposomal delivery systems

Key Published Studies

Year Focus Key Finding Reference
2003 Yeast lifespan Extended lifespan via Sir2 Howitz et al., Nature
2006 Obese mice Improved survival and health Baur et al., Nature
2011 Human metabolism Caloric restriction-like effects Timmers et al., Cell Metabolism
2015 Type 2 diabetes Improved glycemic control Bhatt et al.
2017 Cardiovascular Improved vascular function Wong et al.

Human Clinical Evidence

Human trials have shown mixed results:

Positive Findings

  • Improved insulin sensitivity in diabetic patients
  • Reduced inflammatory markers in some trials
  • Enhanced cerebral blood flow
  • Improved endothelial function

Inconsistent Findings

  • Variable effects on body weight and composition
  • Inconsistent lipid profile changes
  • Dose-response relationship unclear
  • Benefits may depend on baseline health status

Resveratrol + NAD+ Precursors

A popular research combination:

  • Resveratrol activates SIRT1
  • SIRT1 requires NAD+ as a substrate
  • NMN/NR provides the NAD+ fuel
  • Theoretically synergistic effects
  • Dr. Sinclair popularized this combination approach

Current Status

Resveratrol is available as a dietary supplement. While generally considered safe at typical doses, it can interact with certain medications and is not approved for treating any medical condition. The translation from impressive cell and animal studies to human benefits remains an active area of research.

Summary

Resveratrol remains one of the most studied natural compounds in longevity research. While its dramatic effects in cell and animal models haven't fully translated to humans โ€” partly due to bioavailability challenges โ€” it continues to be investigated for metabolic, cardiovascular, and neuroprotective applications. Its role as a sirtuin activator places it at the intersection of multiple aging pathways.

โ† NMN Research Next: Epithalon โ†’