If you’re serious about extending your healthspan and potentially your lifespan, you’ve probably wondered how to combine different longevity supplements for maximum effect. The truth is, individual supplements can be powerful, but combining them strategically creates synergistic effects that may amplify their benefits.
This guide walks you through building a longevity supplement stack from the ground up.
Important note: This guide is for educational purposes only. Always consult with a healthcare provider before starting any supplement regimen.
Why Stack Supplements? Understanding Synergy
Synergy occurs when two or more compounds produce effects greater than the sum of their individual effects. In longevity science, this happens because aging involves multiple interconnected pathways:
- NAD+ decline - Affects cellular energy and repair
- Cellular senescence - Accumulation of damaged “zombie” cells
- Mitochondrial dysfunction - Reduced energy production
- Chronic inflammation - Systemic damage over time
- Epigenetic drift - Changes in gene expression patterns
A well-designed stack addresses multiple mechanisms simultaneously.
Real-World Example: NMN and Resveratrol
Dr. David Sinclair has publicly discussed taking NMN with resveratrol:
- NMN boosts NAD+ levels, providing fuel for sirtuins
- Resveratrol activates sirtuins, particularly SIRT1
Combining them gives you both fuel and activation, potentially amplifying longevity benefits.
The Core Longevity Stack: NMN + Resveratrol + TMG
NMN (Nicotinamide Mononucleotide)
What it does: Direct precursor to NAD+, essential for cellular energy production, DNA repair, and sirtuin function.
Typical dosage: 250-1000mg daily
Best time to take: Morning
Key considerations:
- Look for third-party tested products
- Sublingual forms may offer better absorption
- Store in a cool, dry place
Resveratrol
What it does: Activates SIRT1 and other sirtuins, has antioxidant and anti-inflammatory properties.
Typical dosage: 250-1000mg daily
Best time to take: Morning with a fat source (resveratrol is fat-soluble)
Key considerations:
- Trans-resveratrol is the active form
- Take with olive oil, yogurt, or fatty breakfast
TMG (Trimethylglycine/Betaine)
What it does: Methyl donor that replenishes methyl groups consumed when NMN converts to NAD+.
Typical dosage: 500-1000mg daily
Best time to take: With your NMN
Key considerations:
- Particularly important at higher NMN doses (500mg+)
- Supports healthy homocysteine levels
Adding Quercetin: Senolytic Power
Understanding Senolytics
Senescent cells are damaged cells that accumulate in tissues and secrete inflammatory compounds. Senolytics selectively eliminate these cells.
Why Quercetin?
Quercetin is a flavonoid with demonstrated senolytic activity, especially in combination with other compounds like fisetin.
Typical dosage: 500-1000mg daily, or higher doses intermittently
Best time to take: With meals
Quercetin Protocols
Daily maintenance: 250-500mg daily
Periodic senolytic protocol: 1000-1500mg daily for 2-3 consecutive days, repeated monthly
Vitamin D3 + K2: The Essential Duo
Vitamin D3
Vitamin D deficiency affects an estimated 40% of Americans. Beyond bone health, it influences immune function, mood, and gene expression.
Typical dosage: 2000-5000 IU daily
Best time to take: Morning with food containing fat
Why K2 Matters
K2 ensures calcium goes to bones rather than accumulating in arteries.
Typical dosage: 100-200mcg of MK-7 form daily
Best time to take: With your D3
Omega-3 Fatty Acids
How Omega-3s Support Longevity
- Inflammation reduction: Help resolve chronic inflammation
- Brain health: DHA is a major component of brain tissue
- Cardiovascular protection: Support healthy lipid levels
- Telomere maintenance: May help preserve telomere length
Typical dosage: 2-3 grams combined EPA/DHA daily
Best time to take: With meals
Quality Matters
Look for:
- Third-party testing (IFOS certification)
- Triglyceride form (better absorbed)
- Low oxidation levels
- Sustainable sourcing
Optional Advanced Additions
Fisetin
Like quercetin, fisetin is a senolytic flavonoid. Research suggests it may be even more potent at clearing senescent cells.
Typical dosage: 100-500mg daily or higher doses periodically
Spermidine
Induces autophagy, your body’s cellular recycling process.
Typical dosage: 1-5mg daily
Berberine
Activates AMPK, supports healthy blood sugar and lipid levels.
Typical dosage: 500mg two to three times daily
Note: May interact with medications
CoQ10 (Ubiquinol)
Supports mitochondrial function and energy production.
Typical dosage: 100-200mg of ubiquinol form daily
Timing and Dosing Schedule
Morning Stack (with breakfast)
| Supplement | Dose | Notes |
|---|---|---|
| NMN | 250-500mg | NAD+ is higher in morning |
| Resveratrol | 250-500mg | Needs fat for absorption |
| TMG | 500-1000mg | Supports NMN metabolism |
| Vitamin D3 | 2000-5000 IU | Fat-soluble |
| Vitamin K2 | 100-200mcg | Take with D3 |
| Omega-3 | 1-2g EPA/DHA | With food |
With Lunch or Dinner
| Supplement | Dose | Notes |
|---|---|---|
| Quercetin | 500mg | Better absorbed with food |
| Additional Omega-3 | 1g EPA/DHA | If splitting dose |
Budget Considerations
Starter Stack (Under $75/month)
| Supplement | Monthly Cost |
|---|---|
| Vitamin D3 + K2 | $10-15 |
| Omega-3 | $20-30 |
| NMN (250mg/day) | $25-40 |
Intermediate Stack ($100-150/month)
Add:
- Resveratrol (500mg): $20-30
- TMG: $10-15
- Quercetin: $15-20
Advanced Stack ($200-300/month)
Add:
- Higher-dose NMN (1g): Additional $30-50
- Fisetin: $25-35
- Spermidine: $30-50
- CoQ10: $25-40
Money-Saving Tips
- Buy in bulk for discounts
- Powder forms are often cheaper
- Prioritize quality over quantity
- Watch for sales
What to Avoid
Redundant Combinations
- NMN and NR together: Both are NAD+ precursors; choose one
- Multiple forms of the same antioxidant: Usually unnecessary
- Excessive vitamin E: High-dose supplementation has shown concerning results
Potential Interactions
- Resveratrol and blood thinners: Use caution
- Berberine and medications: Can interact with many drugs
- Quercetin and thyroid medications: Separate by several hours
Sample Stacks by Goal
The “Sinclair-Inspired” Stack
- NMN: 1g daily
- Resveratrol: 1g daily with yogurt
- TMG: 500mg-1g daily
- Vitamin D3: 4000-5000 IU daily
- Vitamin K2: 180-200mcg daily
- Omega-3: 2-3g EPA/DHA daily
The “Cellular Cleanup” Stack
- Quercetin: 500mg daily + 1500mg for 2 days monthly
- Fisetin: 100mg daily + 1-2g for 2 days monthly
- Omega-3: 2g EPA/DHA daily
- Vitamin D3 + K2: Standard doses
The “Metabolic Health” Stack
- NMN: 500mg daily
- Berberine: 500mg twice daily
- CoQ10 (ubiquinol): 200mg daily
- Omega-3: 2-3g EPA/DHA daily
- Vitamin D3 + K2: Standard doses
Safety Considerations
Before Starting
- Get baseline bloodwork
- Consult your healthcare provider
- Start slowly - one supplement at a time
- Track how you feel
Monitoring Progress
Consider retesting every 6-12 months:
- Vitamin D levels
- Lipid panel
- Fasting glucose and HbA1c
- Inflammatory markers (hs-CRP)
The Bigger Picture
Supplements work best alongside:
- Regular exercise: Both resistance and cardio
- Quality sleep: 7-9 hours
- Healthy diet: Whole foods, adequate protein
- Stress management: Chronic stress accelerates aging
- Social connection: Important for longevity
No supplement stack can compensate for poor lifestyle choices.
Building Your Personal Protocol
Start with the basics: vitamin D, omega-3s, and one NAD+ precursor. Once established, gradually expand based on your goals, budget, and response.
The goal isn’t to take the most supplements - it’s to take the right ones, consistently over time.
This guide is for educational purposes only and does not constitute medical advice. Always consult with a qualified healthcare provider before starting any supplement regimen.