Dr. David Sinclair is one of the most respected voices in longevity and anti-aging research. As a professor of genetics at Harvard Medical School, he has pioneered groundbreaking studies on sirtuins, resveratrol, NAD+, and strategies to extend lifespan. His passion for unraveling the science behind aging has led him on a quest to defy the effects of time.
At 53 years old, Dr. Sinclair leads by example when it comes to pursuing longevity. His daily routine incorporates strategic nutrition, fasting protocols, and targeted supplementation. In this article, we'll explore David Sinclair's go-to supplements and the doses he recommends for enhancing healthspan.
David Sinclair's Longevity Supplement Stack
Dr. David Sinclair's supplement regimen is carefully designed to support longevity pathways in the body, protect against age-related decline, and promote overall wellness. Let's examine some of his top supplement choices.
Resveratrol has become one of the most popular anti-aging supplements due to its potential to activate sirtuins and mimic calorie restriction. This polyphenol compound is found naturally in grapes, red wine, peanuts, and berries. David Sinclaire consumes resveratrol every morning by mixing it into natural yogurt. Resveratrol enhances the effects of his other go-to supplement, NMN.
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Resveratrol is a molecule found in grapes that is believed to be effective at protecting the heart. It improves blood flow and may enhance insulin sensitivity. While there is limited evidence of its potential to increase lifespan in mammals, it remains a topic of speculation.
Resveratrol is thought to be beneficial for preventing atherosclerosis based on promising results from in vitro studies. It targets molecular pathways in atherosclerotic arteries and has positive effects on low-density lipoproteins (LDL). In rodent studies, resveratrol has shown improvements in vasorelaxation, blood flow, and in models of type 2 diabetes. It also improves glycemic control in people with type 2 diabetes, although its effectiveness in increasing insulin sensitivity in people without diabetes is uncertain.
Human studies suggest that resveratrol can be supplemented at dosages up to 5 grams per day with minimal side effects. Some individuals may experience intestinal upset and nausea, which are likely due to the poor bioavailability of resveratrol.
Nicotinamide Mononucleotide (NMN) serves as a precursor to NAD+, a vital signaling molecule that declines with age. By boosting NAD+ levels, NMN may stimulate sirtuins, enhance DNA repair, and protect against neurological decline. Sinclair also combines NMN powder with natural yogurt in the mornings to improve absorption.
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Nicotinamide Mononucleotide (NMN)
Nicotinamide mononucleotide (NMN) is a form of vitamin B3 that is taken to boost levels of NAD+ and for its potential anti-aging effects.
NMN increases physical ability in aging populations, improves cardiovascular disease biomarkers such as arterial stiffness, and increases cellular NAD+/NADH levels. Although these results have shown promise, additional large-scale trials are needed to better understand the benefits in humans.
Studies on humans suggest that NMN can be supplemented at dosages up to 5 grams daily with minimal side effects, which may include some intestinal upset and nausea.
Spermidine is a polyamine compound present in foods like mushrooms, soy, legumes, and mature cheeses. It has been shown to prolong lifespan in animal models, likely by influencing autophagy. Spermidine may also provide protection against neurodegenerative diseases. Dr. David Sinclair takes spermidine alongside his NMN and resveratrol in the mornings.
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Spermidine is a polyamine compound found in various foods that has been linked to anti-aging effects.
Spermidine has shown potential to improve cognitive function and memory in mice, reduce inflammation, and increase lifespan in yeast and flies. However, further research is needed to determine whether these benefits apply to humans.
The optimal dosage of spermidine has not been established yet.
As part of his daily supplement regimen, Dr. Sinclair takes 500 mg of quercetin each morning. Quercetin is a flavonoid compound that belongs to the polyphenol group and exhibits senolytic properties. Senolytic compounds selectively destroy senescent cells, which are cells that have stopped dividing but remain metabolically active. As we age, senescent cells accumulate in the body's tissues and drive age-related inflammation. By taking quercetin, a known senolytic, Dr. Sinclair aims to reduce systemic inflammation and the burden of senescent cell buildup that contributes to the aging process. Research shows quercetin can induce apoptosis in senescent cells both in vitro and in animal models. Dr. Sinclair supplements with quercetin as a proactive strategy against cellular aging.
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Quercetin is a flavonoid found in various foods that has been linked to anti-inflammatory effects.
Quercetin has been shown to reduce inflammation, improve cardiovascular health, and improve exercise performance. However, more research is needed to determine whether these benefits translate to humans.
The optimal dosage of quercetin has not yet been established.
Dr. Sinclair supplements with 500 mg of Fisetin each morning. Fisetin is a polyphenol compound that belongs to the flavonoid group, similar to quercetin. Research in animal models has revealed fisetin's senolytic properties, meaning it can selectively eliminate senescent cells that accumulate with aging. Beyond its senolytic capabilities, studies have demonstrated that fisetin may provide additional health benefits, including alleviating cognitive dysfunction and neuroinflammation, reducing depressive behaviors, protecting kidney function, increasing muscle mass and strength, and extending lifespan. By taking fisetin daily along with other senolytics like quercetin, Dr. Sinclair aims to target the buildup of damaging senescent cells and promote longevity pathways.
Vitamin D is involved in numerous processes, from bone health to immune function. Older adults are at high risk for deficiency. Supplementation may provide anti-aging advantages by reducing inflammation, supporting cognition, and lowering cancer risk. Sinclaire takes 4000-5000 IU daily, but others like Andrew Huberman recommend higher dosages by up to 10,000 IU.
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Vitamin D is a fat-soluble vitamin that is synthesized by our skin when exposed to sunlight. It provides various benefits, including promoting bone health and mood. It can also be obtained from certain foods and supplements.
Vitamin D can improve immune health, bone health, and overall well-being. It may also reduce the risk of cancer mortality, diabetes, and multiple sclerosis. Many of these benefits are only observed when correcting a deficiency.
The recommended daily allowance for vitamin D is 400–800 IU/day, but this may be insufficient for many individuals. For moderate supplementation, a dose of 1,000–2,000 IU of vitamin D3 is generally adequate for most people. Higher daily doses range from 20–80 IU per kilogram of body weight. The upper tolerable intake level is 4,000 IU/day, but some studies suggest it could be as high as 10,000 IU/day.
Vitamin K2 is another one of Dr. Sinclair's daily supplements. This essential vitamin activates proteins involved in calcium metabolism and bone formation. It supports bone mineralization by carboxylating osteocalcin. Vitamin K2 also helps protect arteries by inhibiting calcification and supporting elasticity. Additionally, it plays a role in mitochondrial function relating to energy production. While vitamin K2 can be obtained from leafy greens, dairy products, eggs, and meats, Sinclair supplements to ensure adequate intake for these vital functions. Research suggests vitamin K2 supplementation may provide longevity benefits not easily achieved through diet alone. Dr. Sinclair takes 180-360 mcg of vitamin K2 each day as part of his supplement regimen.
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Vitamin K is an essential vitamin found in plants or produced from intestinal bacteria. It plays an essential role in bone health and regulates blood clotting.
Vitamin K has been suggested to protect cardiovascular health by reducing the calcification and stiffening of arteries. It has also been found to improve markers of bone health. Higher levels of vitamin K may provide additional benefits.
The minimum effective dose for phylloquinone (vitamin K1) is 50mcg, which is enough to satisfy the Recommended Daily Intake (RDI) for vitamin K. The maximum dose for vitamin K1 is 10,000mcg (10 mg).
Omega-3 Fatty Acids like EPA and DHA are essential for health and longevity. These anti-inflammatory fats support cognitive, cardiovascular, immune and visual function. However, most people do not get adequate amounts of omega-3s from dietary sources alone. Supplementation becomes especially important as we age, as low omega-3 levels associate with disease risk. Numerous studies highlight the benefits of omega-3s for reducing inflammation, supporting brain health, lowering heart disease risk, and protecting vision as we get older. Dr. Sinclair prioritizes daily omega-3 intake to maintain healthy EPA and DHA levels, given their significance in aging. He supplements to ensure sufficient omega-3 status and minimize inflammation that drives age-related decline.
- Fish oil provides essential fatty acids that are critical for cognitive health, mood regulation, and cardiovascular function.
- It also helps mitigate inflammation and oxidative damage.
“Ingesting sufficient levels of omega-3 fatty acids is going to support healthy mood and even can act as an antidepressant. More than a dozen studies have shown that ingesting at least 1,000 mg per day of the EPA form of essential fatty acid is as effective as prescription antidepressants in relieving depression.”
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Omega-3 Fatty Acids
Omega-3 fatty acids are a type of polyunsaturated fat that are essential for human health. They play a crucial role in brain function, growth, and development.
Omega-3 fatty acids have been shown to reduce triglyceride levels, improve symptoms of depression, and reduce inflammation.
The optimal dosage of Omega-3 fatty acids varies depending on the desired effect. For reducing triglyceride levels, a dosage of 2-4 grams per day is commonly used.
Metformin is an oral medication that is most commonly prescribed for type 2 diabetes, but recent research reveals its potential anti-aging properties. Studies show metformin can activate AMPK, an enzyme involved in cellular energy homeostasis. By doing so, it improves insulin sensitivity, reduces inflammation, and provides protective effects against diseases of aging. Although standard diabetic doses exceed 1 gram, Dr. Sinclair supplements with a lower dose of 800mg metformin in the evenings to harness potential longevity benefits while mitigating side effects. However, metformin is not completely risk-free—it carries a low chance of lactic acidosis and vitamin B12 deficiency. Anyone considering metformin should carefully weigh the risks against potential rewards under medical supervision. While an exciting area of anti-aging research, metformin requires cautious and informed usage.
Key features of Athletic Greens include:
- A comprehensive blend of 75 vitamins, minerals, antioxidants, and adaptogens.
- Provides comprehensive micronutrient support to fill potential gaps in the diet.
- Contains probiotics and prebiotics for gut health and immune function.
- Rich in antioxidants from ingredients like spirulina and wheatgrass.
- Adaptogens such as ashwagandha and astragalus root help manage stress levels.
“This is one reason why if people say, ‘Well, if I can only take 1 supplement, what should I take?’ I say, well, what’s your budget? If they say they can meet that $100 threshold per month, then my recommendation would be Athletic Greens or something like it.
The Anti-Aging Benefits of David Sinclair's Supplements
What ties David Sinclair's supplement choices together? Let's explore the key anti-aging advantages these compounds offer:
- Activate sirtuins - Sirtuins are a class of proteins involved in healthy aging. Compounds like resveratrol and NMN stimulate sirtuin activity, improving DNA repair and mitochondrial function.
- Boost NAD+ levels - NAD+ is vital for energy production and cell repair processes. NMN acts as a precursor to elevate NAD+ levels.
- Remove senescent cells - Quercetin, Fisetin and Spermidine help eliminate harmful senescent cells that drive age-related inflammation.
- Support autophagy - Autophagy is the body's recycling process, deteriorating with age. Spermidine and Metformin induce autophagy.
- Fight inflammation - Chronic inflammation is a hallmark of aging. Resveratrol, Omega-3s, Vitamin D, and Metformin suppress inflammatory pathways.
- Enhance mitochondrial function - Mitochondria are the powerhouses of our cells. Compounds like NMN, Resveratrol and Vitamin K2 improve mitochondrial health.
- Lower disease risk - From diabetes to neurodegeneration, David Sinclair's supplements help reduce age-related disease risk.
By targeting multiple longevity pathways, Dr. Sinclair's stack provides a multi-pronged strategy against aging. While research is still evolving, current evidence supports the potential of these natural compounds.
Examining the Evidence Behind David Sinclair's Supplement Choices
Dr. David Sinclair bases his supplement recommendations on cutting-edge longevity research. But what does the science say about these anti-aging compounds? Here's a look at some of the key studies:
- In a 2020 human trial, NMN supplementation (500mg twice daily) increased NAD+ levels and improved blood flow in older adults.
- Multiple studies demonstrate Resveratrol activates SIRT1 and AMPK, improves insulin sensitivity, fights inflammation, and provides neuroprotection in animal models.
- Spermidine supplementation prolongs lifespan by 10% in mice. It also shows effectiveness against cancer cell growth in vitro.
- A 2021 review highlighted the senolytic properties of Fisetin and Quercetin in preclinical models. Senolytics may alleviate frailty and restore functions in aged tissue.
- Omega-3s help lower triglycerides, reduce arthritis symptoms, protect cognitive health, and decrease cancer risk, according to numerous clinical studies.
- Metformin displays anti-aging effects by activating AMPK, improving insulin sensitivity, protecting against cancer, and extending lifespan in mice.
While more human data is needed, early research reveals promising longevity effects for supplements like NMN, resveratrol, and metformin. Larger and longer clinical trials will further uncover their potential.
Sinclair's Approach to Dosages
When it comes to supplement dosing, David Sinclair aims for the lower end of suggested ranges. He emphasizes starting low and gradually increasing over time to assess tolerance.
For compounds with limited human data, Sinclair prefers to err on the side of caution. He avoids exceeding doses utilized in the research when possible.
For example, Sinclair limits resveratrol intake to 1000mg daily as most studies use dosages of 1g or below. He consumes 1g of NMN based on current clinical trials using 500mg to 2000mg per day.
Sinclair monitors blood biomarkers and undergoes testing like epigenetic clocks to personalize and adjust his dosages as needed. Tracking biomarkers allows him to gauge the effects of his supplementation protocol.
Additional Longevity Supplements to Consider
Beyond David Sinclair's core stack, other compounds may offer anti-aging and disease-preventing benefits. Dr. Sinclair notes that many supplements below still need some more research but show potential.
Pterostilbene is a natural analog of resveratrol with superior bioavailability. Studies show pterostilbene activates longevity genes, improves cognitive function, and inhibits cancer cell growth. Dr. Sinclair has stated pterostilbene is likely more potent than resveratrol, which has issues with absorption and rapid metabolism.
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Pterostilbene is a stilbenoid compound found in various foods that has been linked to anti-inflammatory effects.
Pterostilbene has been shown to reduce inflammation, improve cardiovascular health, and enhance cognitive function. However, further research is needed to determine whether these benefits apply to humans.
The optimal dosage of pterostilbene has not yet been established.
Glutathione is the body's master antioxidant, protecting cells against oxidative stress. According to Dr. Sinclair, enhanced glutathione levels may help strengthen resilience against cellular aging. N-acetylcysteine can be used to increase glutathione status.
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The supplement Glutathione is an antioxidant that is used by every cell and tissue in the body. It´s is a small amino acid-containing molecule that acts as an antioxidant and is found in the food supply and in the human body. The 'glutathione system' consists of enzymes that synthesize glutathione within a cell and dedicated enzymes that use glutathione to exert antioxidant effects.
Supplementing with glutathione is believed to support the glutathione pool in a cell and maintain the efficacy of the entire glutathione system. While oral glutathione supplementation is not efficient in increasing intracellular glutathione levels, it can be absorbed intact into the bloodstream. Increased blood glutathione levels have been shown to slow the breakdown of nitric oxide, so glutathione supplementation may be useful in combination with nitric oxide boosters such as L-Citrulline or L-Arginine.
Coenzyme Q10 supports mitochondrial function and heart health. Dr. Sinclair views CoQ10 as an important mitochondrial nutrient, especially for those taking statins. However, its longevity impacts require further study.
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Coenzyme Q10 (CoQ10) is a molecule produced in the body. It aids mitochondria in energy production and is part of the body's antioxidant system. It is similar to other pseudovitamin compounds because it is essential for survival but does not necessarily need to be taken as a supplement.
CoQ10 has shown minor improvements in blood vessel function, leading to reduced blood pressure and improved blood flow. It appears to be highly effective in reducing the symptoms of fibromyalgia, although this is based on a few small studies, and further research is needed to confirm this.
The standard dose for CoQ10 is generally 90 mg for a low dose and 200 mg for a higher dose, taken once daily with a meal to enhance absorption. CoQ10 supplementation does not typically show dose-dependence, and 90 mg is often the most cost-effective dose.
Similar to NMN, Nicotinamide Riboside serves as a precursor to NAD+ production. Early clinical trials demonstrate its ability to significantly boost NAD+ levels. Dr. Sinclair sees nicotinamide riboside as a promising NAD+ booster comparable to NMN. However, more research is needed on its long-term efficacy.
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Nicotinamide riboside (NR) is a form of vitamin B3 that is taken to boost levels of NAD+ and for its potential anti-aging effects.
NR increases cellular NAD+/NADH levels and improves mitochondrial function. However, further research is needed to determine whether these benefits apply to humans.
The optimal dosage of NR has not yet been established.
Sinclair highlights PQQ as an emerging mitochondrial nutrient and nerve growth factor. It shows potential for improving mitochondria, protecting brain cells, and enhancing cognition. Human research on PQQ is still in early phases.
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Pyrroloquinoline quinone (PQQ) is a redox cofactor known for its antioxidant effects and ability to stimulate mitochondrial biogenesis.
PQQ has demonstrated the potential to improve cognitive function and memory in rats, reduce inflammation, and increase lifespan in mice. However, further research is needed to determine whether these benefits extend to humans.
The optimal dosage of PQQ has not been determined yet.
Always speak with your doctor before beginning new supplements, especially with pre-existing health conditions or medications. Start low and go slow when adding supplements. Combining compounds can increase risks of side effects.
Following a Comprehensive Approach to Longevity
Dr. David Sinclair doesn't rely on supplementation alone to pursue a longer healthspan. His routine incorporates fasting, nutrition, exercise, stress reduction, and optimized sleep.
Sinclair recommends a whole foods, plant-based, low sugar diet to provide essential nutrients and antioxidants. He exercises several times per week, focusing on strength training and HIIT workouts. Stress management via meditation helps counteract aging effects related to cortisol. Intermittent fasting and time-restricted feeding align with circadian rhythms and support cellular repair.
Strategic supplementation complements these lifestyle components. While research continues to uncover their mechanisms and potential, Sinclair's approach focuses on supporting health from every angle.
At the end of the day, there are no shortcuts to longevity. But evidence-based supplementation, when combined with healthy living, may help us make the most of our vital years. Dr. David Sinclair's perspective and personal regimen provide insights into achieving lifelong wellness.