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Living Protocol
David Sinclair’s Longevity Supplement Protocol
The Harvard geneticist’s personal anti-aging stack — continuously updated from interviews, podcasts, and his book Lifespan. The most aggressive longevity-focused protocol of any major influencer.
Who is David Sinclair, PhD?
David Sinclair is a professor of genetics at Harvard Medical School and co-director of the Paul F. Glenn Center for Biology of Aging Research. An Australian biologist, he is one of the world’s most influential aging researchers, known for his work on sirtuins, NAD+ metabolism, and epigenetic reprogramming. His 2019 book Lifespan: Why We Age — and Why We Don’t Have To popularized compounds like NMN and resveratrol. He founded the Sinclair Lab at Harvard and co-founded several biotech companies. His provocative claim: “somebody who might make it to 150 has already been born.” Sinclair has a higher risk tolerance than most, being a researcher with advanced testing and medical oversight.
🔗 YouTube · Sinclair Lab · Lifespan Book
⚠️ Medical Disclaimer: Sinclair’s protocol is significantly more aggressive than typical supplementation. It includes prescription drugs (statins, rapamycin) and compounds with limited human safety data. Sinclair has access to advanced blood testing and medical oversight that most people do not. Several items are controversial even among longevity scientists. This is documentation, not a recommendation. Always consult your physician.
15Active Compounds
3Rx Medications
~$200Monthly Cost (OTC)
2019Book Published
📄 Compare: Peter Attia (conservative, physician-supervised) · Andrew Huberman (neuroscience-focused, cycled protocols)
Evidence Rating Key
★★★★★ Multiple RCTs + meta-analyses in humans
★★★★☆ At least 1 large RCT with positive results
★★★☆☆ Observational / cohort studies only
★★☆☆☆ Animal / in-vitro, limited human data
★☆☆☆☆ Expert opinion only, minimal evidence
NAD+ & Sirtuin Core (Daily)
| Supplement | Dosage | Timing | Purpose | Evidence | Source |
|---|---|---|---|---|---|
NMN (Nicotinamide Mononucleotide) | 1g (1,000 mg)💊 Capsules with water (no fat needed) | Morning | NAD+ precursor → cellular energy, DNA repair. “Doubles NAD levels.” Prefers NMN over NR. Cornerstone of his stack. | ★★★☆☆ | Lifespan p.304 (2019), Diamandis interview (Jun 2025) |
Resveratrol⚠1 | 1g (1,000 mg)🥄 With coconut yogurt or olive oil (fat needed — 5x absorption) | Morning | Sirtuin activator (SIRT1). Works synergistically with NMN — resveratrol activates, NMN fuels. Mixed replication in independent labs. | ★★☆☆☆ | Lifespan (2019), Rhonda Patrick interview, Ben Greenfield pod |
Senolytic & Autophagy Compounds
| Supplement | Dosage | Timing | Purpose | Evidence | Source |
|---|---|---|---|---|---|
Fisetin | 500 mg🍽 With food | Daily | Senolytic — clears “zombie” senescent cells that drive inflammation. Found in strawberries. | ★★☆☆☆ | Multiple interviews, Diamandis (Jun 2025) |
Spermidine | 1-2 mg | Daily | Autophagy inducer — promotes cellular recycling. Found in wheat germ, aged cheese, natto. | ★★★☆☆ | Multiple interviews |
Metabolic & Cardiovascular
| Supplement | Dosage | Timing | Purpose | Evidence | Source |
|---|---|---|---|---|---|
Berberine⚠2 (Replaced metformin) | 1g🍽 With food, skip on workout days | Daily | AMPK activator — same pathways as metformin but OTC and easier on stomach. Lowers blood glucose, improves insulin sensitivity. | ★★★★☆ | Diamandis interview (Jun 2025) |
Nattokinase⚠3 | Not specified | Daily | Fibrinolytic enzyme — breaks down fibrin, may reduce arterial plaque. Chinese study showed 36% plaque reduction. | ★★★☆☆ | Diamandis interview (Jun 2025) |
Alpha Lipoic Acid | ~500 mg | Daily | Antioxidant, mitochondrial support. Was removed, then reintroduced to stack. | ★★★☆☆ | Diamandis (Jun 2025) |
Fish Oil (Omega-3) | Not specified | Daily | Anti-inflammatory, cardiovascular, cognitive support. | ★★★★★ | Multiple interviews |
CoQ10 | Not specified | Daily | Mitochondrial function, especially important alongside statins (which deplete CoQ10). | ★★★★☆ | Multiple interviews |
Low-Dose Aspirin | 81 mg | Daily | Cancer risk reduction, anti-inflammatory. Debated due to bleeding risks. | ★★★★★ | Multiple interviews |
Foundational Nutrients
| Supplement | Dosage | Timing | Purpose | Evidence | Source |
|---|---|---|---|---|---|
Vitamin D3 | Not specified🍽 With fatty food | Morning | Immune, bone, gene expression. Paired with K2. | ★★★★☆ | Multiple interviews |
Vitamin K2 | Not specified | Morning | Directs calcium to bones, not arteries. Essential companion to D3. | ★★★★☆ | Multiple interviews |
Prescription Medications
⚠️ Prescription Warning: These require medical supervision. Sinclair takes statins due to genetic predisposition (family history of heart disease, confirmed via 23andMe). Rapamycin use is experimental and not FDA-approved for anti-aging.
| Medication | Dosage | Purpose | Source |
|---|---|---|---|
Statin | 80 mg daily (since age 29) | Cholesterol management — genetic predisposition. “23andMe basically said, ‘Give up now.'” Also potential cancer/dementia risk reduction. | Joe Rogan podcast |
Rapamycin (Sirolimus)⚠4 | ~4x per year (2025) Reduced from more frequent | mTOR inhibitor — most geroprotective molecule in animal studies. Recent epigenetic aging study showed less effect than fasting/metformin. | Diamandis interview (Jun 2025) |
Metformin (Largely replaced by berberine) | Occasional only Was 800-1000mg nightly | AMPK activator, anti-aging potential. Now occasional — hard on stomach. Skipped on workout days (may blunt exercise benefits). | Diamandis (Jun 2025), Lifespan |
Stopped / Phased Out
| Item | Previous Dosage | Status | Why Stopped | Source |
|---|---|---|---|---|
TMG (Trimethylglycine) | 500-1,000 mg daily | Stopped | Was taken to prevent methyl group depletion from NMN. Human study found no homocysteine changes at up to 1,000mg NMN → TMG unnecessary. | Diamandis (Jun 2025) |
Taurine | 2g daily | Stopped | Despite 2023 hype. Confirmed not taking in Jun 2025 interview. | Diamandis (Jun 2025) |
Quercetin | ~500 mg | Likely stopped | Possible concern over SIRT6 interference. No longer mentioned in recent interviews. | Pre-2024 interviews |
Sinclair’s Lifestyle Protocol
Diet: Practices time-restricted eating — typically skips breakfast and often lunch (“I try to skip one meal a day”). Eats mostly plant-based with some meat. Makes his own yogurt with Bravo culture sachets for resveratrol absorption.
Exercise: Vigorous exercise 1-2x per week. Skips berberine (previously metformin) on workout days to avoid blunting exercise adaptations.
Cold exposure: Has discussed benefits but not a core daily protocol.
Blood testing: Regular biomarker monitoring including NAD+ levels, homocysteine, inflammatory markers, and epigenetic age testing.
⚠️ Drug Interaction & Safety Notes
- Resveratrol: Poor absorption — requires fat for bioavailability. May interact with blood thinners (enhanced anticoagulant effect), diabetes meds, and CYP450-metabolized drugs. Independent labs have had difficulty replicating Sinclair’s original research results. Controversial in the longevity community.
- Berberine: Potent glucose-lowering — can cause hypoglycemia, especially with diabetes medications. Strong CYP3A4 inhibitor — interacts with many drugs including statins, immunosuppressants, and blood thinners. GI side effects common. Do not combine with metformin without medical supervision.
- Nattokinase: Fibrinolytic (blood-thinning) effect. Do NOT combine with anticoagulants (warfarin, DOACs) or aspirin without physician guidance. Contraindicated before surgery. Sinclair takes it alongside aspirin — this combination increases bleeding risk.
- Rapamycin: Immunosuppressant at daily doses. Sinclair takes it only ~4x/year. Side effects include mouth sores, metabolic changes, potential fertility impacts, and increased infection risk. Not FDA-approved for anti-aging. Requires physician monitoring and prescription.
📋 Protocol Change Log
Jun 2025Added Berberine 1g (replacing metformin), Nattokinase (arterial plaque), Alpha Lipoic Acid (reintroduced)
Jun 2025Stopped TMG and Taurine — confirmed no longer taking in Diamandis interview
Jun 2025Changed Rapamycin reduced to ~4x/year. Metformin → occasional only (stomach issues)
~2024Likely stopped Quercetin — possible SIRT6 concerns, no longer mentioned
2019Published Lifespan book — NMN + Resveratrol protocol enters mainstream awareness
~1997Constant Statin — taking since age 29 due to family cardiovascular history
Primary Sources
Peter Diamandis Interview: Full Protocol Update
Lifespan: Why We Age — and Why We Don’t Have To
Joe Rogan Experience: David Sinclair
Rhonda Patrick (FoundMyFitness) Interview
Ben Greenfield Podcast
📄 Compare: Peter Attia — notably, Attia classifies resveratrol as “nonsense” and NMN/NR as “not worth focusing on,” directly disagreeing with Sinclair’s two cornerstone supplements. · Andrew Huberman — takes NMN like Sinclair, but also resveratrol pairing.
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