David Sinclair's Daily Supplement Stack
Dr. David Sinclair has openly discussed his personal supplement protocol in interviews and his book, Lifespan: Why We Age – and Why We Don't Have To. His regimen is not a static prescription but an evolving practice informed by ongoing scientific research. He emphasizes that this is his personal approach, not medical advice for the general population, especially since some of his choices involve off-label use of prescription drugs.
The Core Longevity Supplements
At the center of Sinclair's stack are compounds that target key molecular pathways linked to aging.
- Nicotinamide Mononucleotide (NMN): Sinclair famously takes 1 gram (1000 mg) of NMN every morning. As a precursor to NAD+ (nicotinamide adenine dinucleotide), NMN is intended to boost declining NAD+ levels. NAD+ is a critical coenzyme for cellular metabolism, DNA repair, and the activation of sirtuin genes, which play a role in regulating cellular health. Sinclair often combines it with resveratrol for potential synergistic effects.
- Resveratrol: This plant-based polyphenol, found in red grapes, is taken alongside NMN at a dose of 1 gram per day. It is believed to activate sirtuin enzymes, mimicking some effects of calorie restriction. Sinclair mixes his resveratrol with a fatty substance like yogurt to enhance its absorption, which is otherwise poor.
- Metformin: An anti-diabetic prescription drug, Sinclair takes 800 mg to 1000 mg of metformin in the evening. He uses it for its potential anti-aging benefits, such as improving insulin sensitivity and activating the AMPK pathway, which mimics the effects of fasting. He notes that he skips this dose on days he exercises, based on some studies suggesting it may blunt exercise adaptations.
Supporting Supplements and Vitamins
Beyond his core regimen, Sinclair includes several other compounds to support overall health and specific cellular processes.
- Trimethylglycine (TMG): Also known as betaine, Sinclair takes 500 to 1000 mg of TMG daily. He explains this is to prevent potential methyl group depletion caused by high-dose NMN supplementation, ensuring proper methylation for DNA function.
- Spermidine: This compound, which can also be obtained from foods like wheat germ, is taken in dosages around 1-2 mg. It is known for its role in promoting autophagy, a cellular self-cleaning process vital for removing damaged components.
- Fisetin and Quercetin: These flavonoids are senolytics, meaning they help clear out senescent, or 'zombie,' cells that accumulate with age. Sinclair takes 500 mg of fisetin and may cycle or take quercetin.
- Vitamins D3 and K2: Sinclair supplements with 4,000 to 5,000 IU of vitamin D3 and 180 to 360 mcg of vitamin K2 daily. These vitamins are crucial for immune function, bone health, and directing calcium to the bones and away from arteries.
- Omega-3 Fish Oil and Alpha Lipoic Acid: Recent additions to his stack include Omega-3s for their anti-inflammatory properties and brain health support, and Alpha Lipoic Acid (ALA) for its antioxidant and mitochondrial benefits.
- Taurine: He reportedly takes 2 grams of this amino acid, which supports mitochondrial and heart function.
- Low-Dose Aspirin: Sinclair takes 83 mg of aspirin daily, mainly for its anti-inflammatory effects and potential cardiovascular benefits. He acknowledges the conflicting evidence and risks but continues to take it.
- Rapamycin: A prescription drug that inhibits mTOR, a pathway involved in aging, Sinclair has mentioned taking it on and off, likely on a weekly basis, though the exact dosage is not publicly confirmed.
Lifestyle Interventions for Longevity
Sinclair consistently states that supplements are only part of a larger picture. His lifestyle practices are foundational to his longevity approach.
- Intermittent Fasting: He practices intermittent fasting, often skipping one meal a day (usually lunch) to trigger metabolic benefits and autophagy.
- Plant-Based Diet: His diet is primarily plant-based, low in sugar and refined carbohydrates, and avoids excessive meat consumption.
- Exercise: His routine includes a combination of strength training, cardio, and high-intensity interval training (HIIT).
- Cold and Heat Exposure: He incorporates sauna use followed by ice-cold plunges to activate cellular stress responses.
- Biomarker Tracking: Sinclair regularly monitors his health with blood tests and continuous glucose monitoring.
A Closer Look at Key Compounds: NMN vs. NR
David Sinclair's choice of NMN over nicotinamide riboside (NR), another NAD+ precursor, is a point of interest. The debate often centers on efficiency and bioavailability.
| Feature | NMN (Nicotinamide Mononucleotide) | NR (Nicotinamide Riboside) |
|---|---|---|
| Sinclair's View | Prefers NMN, citing better results in unpublished mouse studies and more direct conversion path to NAD+. | Does not prefer NR, suggesting it is less effective for his goals. |
| Metabolic Pathway | Converts directly to NAD+ in one step via a specific transporter. | Requires more steps to convert to NAD+, potentially making it less efficient. |
| Scientific Support | Strong support for improving NAD+ levels and metabolic health in preclinical studies. Emerging human data exists. | Some studies support NR benefits, but overall efficacy is debated, particularly for longevity. |
| Cost and Bioavailability | Can be costly, and bioavailability may be an issue unless taken with fats or via sublingual route. | Cost and bioavailability are also significant factors, though some formulations are available. |
What the Science Says and Ethical Considerations
While Sinclair's regimen is intriguing, it is crucial to remember that much of the supporting science is based on animal studies or is still emerging. Research from the Sinclair Lab and others has confirmed that epigenetic changes can drive aging, and that restoring the epigenome can reverse some signs of aging in mice, which is a major area of his work. However, translating these findings to humans and ensuring long-term safety is an ongoing process.
The off-label use of drugs like metformin and rapamycin underscores the experimental nature of his protocol. Anyone considering such interventions should consult with a healthcare professional to discuss personal risks and benefits. Furthermore, the high cost of some supplements, like NMN, puts this regimen out of reach for many, reinforcing the importance of focusing on foundational health habits.
For more in-depth information on the foundational science of aging and potential interventions, an excellent resource is the Sinclair Lab at Harvard Medical School.
Conclusion
David Sinclair's daily protocol is a blend of well-established lifestyle factors and cutting-edge, yet still experimental, supplements and drugs. The core of his approach revolves around boosting NAD+ with NMN, activating sirtuins with resveratrol, and mimicking fasting through metformin. This is complemented by a range of other compounds aimed at supporting cellular health, mitigating inflammation, and ensuring proper methylation. While his approach is not a one-size-fits-all solution, it exemplifies a proactive, data-driven mindset toward managing healthspan. For the individual, his routine serves as a powerful reminder that fundamental habits like diet, exercise, and sleep are the bedrock of any longevity strategy.
