Introduction
When it comes to polyphenol supplements for longevity, two compounds dominate the conversation: resveratrol and pterostilbene. Both activate sirtuins, the so-called “longevity genes” that regulate cellular health and aging. Both come from natural sources. And both have impressive research behind them.
So which one should you choose?
What Are Polyphenols?
Polyphenols are plant compounds with powerful antioxidant and anti-inflammatory properties. Among thousands identified, stilbenes have attracted particular attention for their potential anti-aging effects.
Resveratrol and pterostilbene are both stilbenes—they share a similar chemical structure but differ in key ways that affect absorption and effectiveness.
What is Resveratrol?
Resveratrol (3,5,4’-trihydroxystilbene) is a polyphenol produced by plants in response to stress or infection.
Natural Sources
- Red wine: 0.2-5.8 mg per glass
- Red grapes: Concentrated in the skin
- Peanuts and blueberries
- Japanese knotweed: Primary supplement source
The “French Paradox” brought resveratrol to public attention—French populations had low heart disease rates despite high saturated fat diets, potentially due to red wine consumption.
Research accelerated in 2003 when Dr. David Sinclair published landmark research showing resveratrol could extend lifespan in yeast by activating Sir2 (the yeast equivalent of SIRT1).
What is Pterostilbene?
Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene) is a methylated derivative of resveratrol. The key structural difference: two hydroxyl groups are replaced with methyl groups.
This seemingly minor change has major implications for absorption.
Natural Sources
- Blueberries: Richest dietary source (up to 99 ng/g)
- Grapes: Smaller amounts than resveratrol
- Almonds: Trace amounts
Bioavailability: The Critical Difference
Resveratrol Bioavailability
- Oral bioavailability: Less than 1%
- Half-life: 1-3 hours
- Metabolism: Rapidly conjugated by the liver
Research in Drug Metabolism and Pharmacokinetics showed resveratrol undergoes extensive first-pass metabolism.
Pterostilbene Bioavailability
- Oral bioavailability: Approximately 80%
- Half-life: 7-8 hours
- Metabolism: More resistant due to methyl groups
A study in Molecular Nutrition & Food Research found pterostilbene approximately 4x more bioavailable than resveratrol.
Head-to-Head Comparison
| Parameter | Resveratrol | Pterostilbene |
|---|---|---|
| Oral bioavailability | Less than 1% | ~80% |
| Plasma half-life | 1-3 hours | 7-8 hours |
| Typical supplement dose | 500-1,500 mg | 50-250 mg |
| Fat required for absorption | Yes | Less critical |
| Cost per month | $15-40 | $25-50 |
Mechanism of Action
SIRT1 Activation
Both activate SIRT1, but through slightly different mechanisms:
Resveratrol:
- Binds directly to SIRT1 at an allosteric site
- May require higher concentrations for full activation
Pterostilbene:
- Also activates SIRT1 with different binding kinetics
- May have equal potency at lower concentrations
Research in Aging Cell demonstrated both activate SIRT1, but downstream gene expression differs.
Clinical Evidence
Resveratrol Human Studies
- A meta-analysis of 11 RCTs found significant reductions in fasting glucose and HbA1c
- Studies showed improved flow-mediated dilation
- A study in the American Journal of Clinical Nutrition found improved memory in older adults
Pterostilbene Human Studies
- A trial in the Journal of Clinical Hypertension found:
- Significantly reduced LDL cholesterol
- Lowered blood pressure
- Well-tolerated with minimal side effects
Side Effects
Resveratrol
- Gastrointestinal discomfort (most common)
- Headache and mild nausea at high doses
- Mild estrogenic activity—may not suit hormone-sensitive conditions
Pterostilbene
- Very well-tolerated
- Slight LDL increase observed in some studies at high doses (250mg twice daily)
- Rare headaches
Who Should Choose Which?
Choose Resveratrol If:
- Budget is a primary concern
- You want the most-studied option
- You’re following established longevity protocols
- You can optimize absorption (take with fat)
Choose Pterostilbene If:
- Bioavailability is your priority
- You want lower doses
- Convenience matters
- You prefer sustained blood levels
Consider Both If:
- You want comprehensive coverage
- You’re not seeing results from one compound alone
- You follow an advanced longevity protocol
Synergistic Stacking
Resveratrol Stacks Well With:
- NMN or NR: Resveratrol activates sirtuins; NMN provides NAD+ fuel
- Quercetin: Complementary polyphenol
- Omega-3s: Fat enhances absorption
Pterostilbene Stacks Well With:
- Grape seed extract: May offset LDL effects
- NR: Similar sirtuin/NAD+ synergy
- CoQ10: Mitochondrial support
Practical Recommendations
Starting with Resveratrol
- Begin with 500mg daily
- Take with a fat source for absorption
- Consider splitting doses
Starting with Pterostilbene
- Begin with 50-100mg daily
- Can be taken with or without food
- Once or twice daily dosing works well
Conclusion
Both resveratrol and pterostilbene are legitimate longevity supplements:
Resveratrol: More research, lower cost, but poor bioavailability. Take 500-1,000mg daily with fat.
Pterostilbene: Superior absorption, lower doses effective. Take 50-150mg daily.
For comprehensive coverage, consider using both—either together at lower doses or alternating between them.
Remember: polyphenols work best as part of a complete longevity strategy. Learn more in our guide on how to boost NAD+ levels.
Medical Disclaimer: This content is for informational purposes only. Consult a healthcare provider before starting any supplement regimen.