What Supplements does David Sinclair Take?

Who is David Sinclair?

David Sinclair is an Australian biologist and professor of genetics at Harvard Medical School. He is best known for his research on ageing and longevity, with a focus on understanding the molecular and cellular mechanisms of ageing so he can develop interventions to slow or even reverse it.

He has made significant contributions to understanding the biology of ageing and exploring interventions that could extend human health span and lifespan. Some key areas of his work include:

1. Sirtuins and Longevity Pathways

Sinclair's groundbreaking research has focused on sirtuins, a family of proteins that regulate cellular health and are linked to longevity. His studies have shown how these proteins influence ageing processes, including DNA repair, metabolism, and inflammation (5).

He has also demonstrated the role of NAD+ (Nicotinamide Adenine Dinucleotide), a molecule essential for sirtuin activation, in maintaining cellular function and combating age-related decline.

2. Resveratrol and Dietary Compounds

While lifespan tells us how long we live, healthspan measures the quality of those years that are spent feeling vibrant, mobile, and free from chronic disease. Think of it this way: what’s the point of living past a hundred, if those years are spent tethered to medications or battling chronic pain? Healthspan revolves around both mental and physical wellbeing.

Fortunately, science is showing us that it’s not an either-or choice. With the right habits and innovations, we can extend both the length and the quality of our lives.

3. Epigenetic Ageing and the "Information Theory of Aging"

He introduced the Information Theory of Aging, proposing that ageing is caused by the loss of epigenetic information, which leads to cellular dysfunction. Sinclair's lab has explored ways to reprogramme cells to restore youthful functionality, including work with Yamanaka factors for partial cellular reprogramming.

4. NAD+ Boosters

Sinclair's research has shown that restoring NAD+ levels in cells can improve mitochondrial function and slow ageing. This work has driven interest in NAD+ precursors like NR (Nicotinamide Riboside) and NMN (Nicotinamide Mononucleotide) as potential supplements for promoting healthspan. Learn more about these longevity supplements.

5. Biotechnology and Startups

He co-founded companies like MetroBiotech, which focuses on developing NAD+ precursors, and Life Biosciences – dedicated to addressing ageing-related diseases.

6. Advocacy and Education

Sinclair's book, Lifespan: Why We Age—and Why We Don’t Have To, has brought longevity science into the mainstream, encouraging public and scientific engagement with ageing research. He frequently speaks about the ethical and societal implications of extending human lifespan.

7. Animal Models and Longevity Studies

His lab has conducted studies on various models, including yeast, worms, mice, and monkeys, to identify conserved mechanisms of ageing and evaluate potential interventions.

8. Awards and Recognition

Sinclair's contributions have earned him accolades, including being named one of TIME magazine's "100 Most Influential People in the World" and receiving numerous scientific awards for his research on ageing.

David Sinclair's Supplement Stack: What He Takes Daily

David Sinclair’s supplement stack focuses on promoting cellular health, combating aging, and enhancing longevity. Here’s a brief summary of his key supplements, benefits, and dosages.

1. Resveratrol

- Why? Activates sirtuins, supports DNA repair, and may mimic calorie restriction.
Dosage:
- 1g daily with fats.

2.  Spermidine

- Why? Promotes autophagy, supports DNA repair, and possibly reduces inflammation.
Dosage:
- 1–2 mg daily or through diet (wheat germ, soy, etc.).

3.  NMN (Nicotinamide Mononucleotide)

- Why? Boosts NAD+ levels, enhances metabolism, and supports cellular repair.
Dosage:
- 1g daily with fats for better absorption.

4.  Vitamin D3 + K2

- Why? Supports bone and cardiovascular health, regulates calcium.
Dosage:
- D3: 1,000–5,000 IU; K2: 100–200 mcg daily.

5.  Metformin

- Why? Improves glucose regulation, activates AMPK, and reduces inflammation.
Dosage:
- 500–1,000 mg daily (split doses).

6.  Fisetin & Quercetin

- Why? Clears senescent cells (senolytic), and may reduce inflammation.
Dosage:
- Fisetin: 20 mg/kg body weight (periodic use).
- Quercetin: 500–1,000 mg daily.

7.  Berberine

- Why? Improves glucose metabolism, activates AMPK, and may aid.
Dosage:
- 500 mg 2–3 times daily.

8.  CoQ10

- Why? Supports mitochondrial function and energy production.
Dosage:
- 100–300 mg daily with fats.

9.  TMG (Trimethylglycine)

- Why? Supports methylation, reduces homocysteine, and aids NAD+ production.
Dosage:
- Dosage: ~1 g daily.

10.  Aspirin

- Why? Reduces inflammation and cardiovascular risk. 
Dosage:
- 81 mg daily (low-dose).

This table summarises the key benefits, dosages, and considerations for each supplement as part of David Sinclair's longevity-focused approach.

2. Spermidine

Spermidine is a naturally occurring polyamine compound that has gained attention in longevity research for its potential to promote cellular health and slow ageing. It is found in many foods and plays a key role in cellular processes, including autophagy, which is the body’s natural mechanism for recycling damaged cells and maintaining cellular function. (2)

Why Would David Sinclair Take Spermidine?

• Autophagy Activation: Spermidine induces autophagy, the cellular "clean-up" process that helps remove damaged organelles and proteins. This is critical for maintaining cellular function and combating ageing.
• Longevity Studies: Studies in animals have shown that spermidine may can extend lifespan and improve healthspan, making it an area of interest for longevity researchers.(3)
• DNA and Cellular Stability: Spermidine supports cellular homeostasis and DNA repair, which aligns with Sinclair's focus on protecting and restoring the epigenome.
• Brain and Heart Health: Evidence suggests spermidine supports cardiovascular health and may protect against neurodegenerative diseases by reducing inflammation and oxidative stress.

Spermidine Dosage

While Sinclair has not consistently shared specific spermidine dosages in interviews or publications, studies and common usage suggest 1-2mg per day. (5) Sinclair prefers obtaining spermidine through a diet rich in spermidine-rich foods like wheat germ, soy, mushrooms, and green vegetables, rather than through supplements, where possible.

Scientific Findings

While spermidine shows promise, clinical research in humans is still emerging. Current studies suggest it is safe and well-tolerated. High-quality spermidine supplements are often derived from wheat germ extract, which naturally contains spermidine – making them ideal when you can’t get the spermidine you need through your diet (11).

3. NMN (Nicotinamide Mononucleotide)

David Sinclair is a strong advocate for Nicotinamide Mononucleotide (NMN) due to its potential to boost NAD+ levels, which are critical for cellular energy and longevity.

Why Does David Sinclair Take NMN?

• Boosted NAD+ Levels: NAD+ (Nicotinamide Adenine Dinucleotide) is essential for energy metabolism, DNA repair, and activating sirtuins, proteins linked to longevity. As we age, NAD+ levels decline, leading to reduced cellular repair and increased aging-related diseases. NMN is a precursor that helps replenish NAD+ levels.
• Improved Metabolism and Energy: Sinclair has noted NMN’s role in enhancing mitochondrial function, which can improve energy levels and overall metabolism.
• DNA Repair and Cellular Health: NAD+ is required for enzymes like PARPs that repair DNA. NMN supplementation supports these repair mechanisms – critical for maintaining genetic stability over time.
• Age-Related Decline: By increasing NAD+ levels, NMN may help counteract age-related conditions like muscle decline, neurodegeneration, and inflammation.
• Longevity Potential: Animal studies have shown NMN can improve lifespan and healthspan by preserving cellular function. While human studies are ongoing, Sinclair sees NMN as a promising intervention. (6)

4. Vitamin D3 and K2

David Sinclair has occasionally mentioned the importance of vitamin D3 as part of a longevity regimen but he has not specifically emphasised vitamin K2 (which is less commonly used as a supplement) in his public discussions. However, vitamin K2 is often paired with vitamin D3 to support health, particularly for bone and cardiovascular benefits.

Why Does David Sinclair Take Vitamin D3?

• Bone Health: Vitamin D3 is essential for calcium absorption and bone mineralisation, which helps prevent age-related bone loss and osteoporosis.
• Immune System Support: Vitamin D3 boosts immune function and may reduce inflammation, which is crucial for longevity.
• Cardiovascular Benefits: Adequate vitamin D3 levels are associated with lower risks of cardiovascular diseases.
• Mood and Energy: Vitamin D3 supports mental health, helping prevent mood disorders, which can impact quality of life as we age.
• Longevity Links: Low vitamin D levels have been linked to increased mortality risk, making supplementation important for maintaining healthspan.

Why Vitamin K2 is Often Paired with D3

While Sinclair hasn’t highlighted Vitamin K2 specifically, pairing vitamin D3 with K2 is common in longevity and health science due to:

• Calcium Regulation: K2 directs calcium to bones and teeth while preventing it from depositing in arteries, reducing the risk of arterial calcification.
• Bone and Cardiovascular Health: The synergy between D3 and K2 supports stronger bones and healthier blood vessels.

Vitamin D3 Dosage

Sinclair has not shared a precise dosage of Vitamin D3, but general recommendations and longevity focused practices suggest 1,000–5,000 IU per day, depending on blood levels and individual needs. Higher doses may be recommended for individuals with Vitamin D deficiency.

Safety and Testing

• Blood Levels: Regular testing of Vitamin D levels (targeting 30–50 ng/mL) is recommended to ensure optimal supplementation and to avoid overdosing.
• Combining with K2: If paired with vitamin K2, 100-200 mcg of vitamin K2 is commonly used alongside D3.

Metformin Dosage

6. Fisetin and Quercetin

David Sinclair has highlighted fisetin and quercetin as part of the growing interest in senolytics – compounds that target and eliminate senescent (ageing and dysfunctional) cells. These cells accumulate with age, contributing to chronic inflammation and tissue dysfunction.

Why Might David Sinclair Take Fisetin and Quercetin?

• Cellular Senescence and Senolytic Activity: Both fisetin and quercetin have demonstrated senolytic properties in research, meaning they can selectively clear senescent cells without harming healthy cells. Reducing senescent cells helps decrease chronic inflammation and supports tissue regeneration.
• Anti-Inflammatory Properties: Both compounds are possible potent anti-inflammatory agents, which can help combat ageing-related diseases such as cardiovascular disease, neurodegeneration.
• Antioxidant Effects: As antioxidants, fisetin and quercetin protect cells from oxidative stress – a significant contributor to ageing and cellular damage.
• Longevity Benefits: Animal studies have shown fisetin extends lifespan and improves healthspan by possibly reducing inflammation and enhancing cellular function. Quercetin has shown benefits in reducing chronic diseases, improving cardiovascular health, and supporting immune function (8).

Fisetin and Quercetin Dosage

While David Sinclair hasn’t explicitly mentioned taking fisetin or quercetin as part of his personal regimen in many public discussions, he has expressed interest in their senolytic properties. General guidance from research and anecdotal use for longevity purposes suggests:

Fisetin Dosage

Studies suggest a dose of 20 mg per kilogram of body weight for 2-3 days periodically (e.g once a month or quarterly) for senolytic effects. When supplementing for general antioxidant effects, lower doses such as 100-200mg daily are also common (9) .

Quercetin Dosage

Quercetin is typically dosed at 500-1,000mg daily for senolytic effects. Lower doses, such as 250-500 mg daily, are used for general anti-inflammatory and antioxidant purposes.

How These Compounds Can Be Taken

• Intermittent Use: Both fisetin and quercetin are often used in senolytic cycles rather than daily. For example, taking a higher dose for a few days every month or quarter to clear senescent cells.
• Fat-Soluble: Fisetin and quercetin are better absorbed when taken with food containing fat or alongside a fat source like olive oil or yoghurt.
• Combination with Other Senolytics: Some longevity protocols combine quercetin or fisetin with other senolytics like dasatinib or supportive compounds like NAC (N-acetylcysteine) for synergistic effects.

Scientific Findings and Safety

• Fisetin: Generally regarded as safe; high doses used in studies have not shown significant side effects in humans (2).
• Quercetin: Safe at typical doses, though high doses for extended periods may cause mild side effects, such as gastrointestinal upset or headaches.

7. Berberine

Similar to metformin, David Sinclair has mentioned berberine as a compound of interest in longevity and metabolic health. Berberine is a natural plant alkaloid with significant effects on glucose metabolism, insulin sensitivity, and cellular health.

Why Might David Sinclair Take Berberine?

• Improves Glucose Metabolism: Berberine helps regulate blood sugar levels by activating AMPK (AMP-activated protein kinase), the "metabolic master switch," much like metformin. This can reduce insulin resistance and support healthy glucose metabolism, lowering the risk of type 2 diabetes.
• Longevity Benefits via AMPK Activation: AMPK activation enhances cellular energy balance, supports autophagy, and promotes mitochondrial health – all essential processes for longevity.
• Anti-Inflammatory and Antioxidant Properties: Berberine reduces chronic inflammation and oxidative stress, which are major contributors to ageing and age-related diseases.
• Gut Microbiome Support: Berberine positively influences the gut microbiome, which plays a crucial role in overall health, immunity, and inflammation regulation.
• Alternative to Metformin: Berberine is sometimes used as a natural alternative to metformin due to its similar metabolic effects without requiring a prescription.

Berberine Dosage

Sinclair has not explicitly shared a berberine dosage, but standard dosage for promoting longevity is 500 mg, 2-3 times daily (1,000-1,500mg/day total). This is often taken with meals to improve blood sugar regulation post-meal.

Some suggest cycling berberine – e.g. 5 days on, 2 days off – to prevent gut microbiome disruptions or tolerance.

How Berberine Works

• AMPK Activation: Like metformin, berberine activates AMPK, which helps cells use energy more efficiently and triggers processes like autophagy.
• Glucose Transporter Upregulation: Berberine increases the activity of glucose transporters, improving glucose uptake by cells and lowering blood sugar levels.
• Lipid Regulation: It helps reduce LDL cholesterol and triglycerides, improving overall cardiovascular health.

8. CoQ10

David Sinclair has mentioned the importance of mitochondrial health and energy production as central to longevity, which makes CoQ10 (Coenzyme Q10) an appealing supplement in this context. However, Sinclair himself hasn’t specifically highlighted CoQ10 as part of his regular regimen, though he has addressed compounds that target mitochondrial function and oxidative stress.

Why Might David Sinclair Take CoQ10?

• Mitochondrial Energy Production: CoQ10 is essential for generating energy (ATP) in mitochondria. As we age, CoQ10 levels naturally decline, leading to reduced cellular energy production and increased oxidative stress.
• Antioxidant Protection: CoQ10 helps protect mitochondria from damage caused by free radicals, reducing the risk of cellular dysfunction and ageing-related diseases.
• Cardiovascular Health: CoQ10 is particularly important for heart health, as the heart is one of the most energy-demanding organs in the body.
• Support for Statin Users: Statins, commonly used to lower cholesterol, can deplete CoQ10 levels. Supplementation may counteract this side effect.
• Synergy with Other Longevity Compounds: CoQ10 might complement other compounds Sinclair discusses, like NAD+ boosters (NMN), by enhancing mitochondrial efficiency.

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CoQ10 Dosage

While Sinclair hasn’t publicly stated taking CoQ10 or its dosage, general recommendations suggest 100-300mg daily for general mitochondrial and antioxidant support.

Higher doses, up to 600mg/day, are used in clinical settings, particularly for conditions like heart failure or severe fatigue. Ubiquinol is the reduced, active form of CoQ10 and is more bioavailable, making it a better option for older adults or those with absorption issues.

Ubiquinone is the oxidized form and may be less effective for individuals over 40 due to declining conversion efficiency.

Timing and Absorption

CoQ10 is fat-soluble, so it should be taken with a meal containing fat for optimal absorption. Also, splitting the dose (e.g. morning and evening) may help maintain steady levels throughout the day.

TMG Dosage

While Sinclair has not provided specific, detailed dosage information for TMG in public discussions, based on general usage and research, the typical dosage range is 50mg-2g daily. The typical dose used in studies and for general health purposes is around 1 gram per day, which can be taken in one or divided doses. (10)

TMG is often used in combination with other methyl donors like folate and B vitamins (B12, B6), as these nutrients work synergistically to support methylation pathways.

Some individuals cycle TMG use, taking it for a few days at a time or using it intermittently, depending on their health goals and responses.

Statins Dosage

David Sinclair hasn’t provided specific details on his own use of statins, but general dosage recommendations based on commonly prescribed statins are:

• Low-Intensity Statins:
  - Atorvastatin (Lipitor): 10-20mg daily.
  - Simvastatin (Zocor): 10-20mg daily.
• Moderate-Intensity Statins:
  - Atorvastatin: 4-80mg daily.
  - Rosuvastatin (Crestor): 5-10mg daily.
• High-Intensity Statins:
  - Atorvastatin: 80 mg daily.
  - Rosuvastatin: 20-40mg daily.

The specific dosage depends on a person’s cholesterol levels, risk of heart disease, and whether statins are being used for primary prevention (preventing disease before it occurs) or secondary prevention (preventing further events in someone with established heart disease).

10. Aspirin

David Sinclair has discussed aspirin in the context of longevity, particularly because of its potential to reduce inflammation and its association with lower risks of cardiovascular disease. While aspirin isn’t a core part of his daily supplement routine, he has acknowledged its role in healthspan and ageing.

Why Might David Sinclair Take Aspirin?

• Anti-Inflammatory Effects: Chronic low-grade inflammation is one of the hallmarks of aging and is linked to many age-related diseases, including Alzheimer’s, cardiovascular disease, and certain cancers. Aspirin works by inhibiting COX-1 and COX-2 enzymes, which are involved in the production of pro-inflammatory prostaglandins.
• Cardiovascular Disease Prevention: Aspirin is well-known for its antiplatelet effects, reducing the likelihood of blood clots, which can lead to heart attacks and strokes. It is commonly used for secondary prevention (for people who have already had a heart attack or stroke) but is sometimes considered for primary prevention in individuals at high cardiovascular risk.
• Longevity Potential: By reducing chronic inflammation and possibly protecting against cancer and cardiovascular events, aspirin could play a role in improving healthspan (the period of life spent in good health) and potentially extending lifespan.

Aspirin Dosage

While Sinclair has mentioned aspirin in a longevity context, he has not specifically outlined a dosage. However, general recommendations for low-dose aspirin in preventive healthcare are:

• Low-Dose Aspirin: 81mg daily is commonly used for cardiovascular protection and is sometimes referred to as "baby aspirin." This lower dose is typically sufficient for preventing clot formation while minimising side effects like gastrointestinal irritation.
• Higher Doses: For pain relief or inflammatory conditions, higher doses (typically 325mg daily) may be used, but long-term high-dose aspirin is usually not recommended for general health or longevity purposes due to risks like gastrointestinal bleeding.
• Intermittent Use: Some people take aspirin intermittently (e.g. a few times a week) to reduce the risk of side effects while still benefiting from its anti-inflammatory and cardiovascular protective effects.

Conclusion

• David Sinclair’s supplement stack is designed to target various aspects of ageing and longevity, with a focus on supporting cellular health, mitochondrial function, and metabolic processes.
• Key supplements in his regimen include NMN for boosting NAD+ levels, resveratrol for activating longevity genes like sirtuins, spermidine to promote autophagy, CoQ10 for mitochondrial energy, and fisetin and quercetin for reducing cellular senescence.
• He also incorporates intermittent fasting, exercise, and sleep optimization to complement these supplements, creating a holistic approach to longevity.
• It's important to note that Sinclair’s regimen is experimental and based on ongoing research, with many of these supplements still being studied for their long-term effects.

As always, you should always speak with a doctor or other health practitioner before starting any new supplements. This will allow you to tailor intake to your personal health needs while considering any conditions for your health and safety.

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