David Sinclair is a professor of genetics at Harvard Medical School and one of the most influential figures in longevity science. His 2019 book Lifespan and frequent podcast appearances have introduced millions of people to the concept of targeting the biology of aging directly — and his personal supplement protocol has been adopted, in whole or in part, by a large share of the people now taking NMN. Understanding what he takes and why is useful both for people who want to follow his protocol specifically and for those who want to understand the rationale behind it well enough to make their own informed decisions about what to include.
A few important caveats before the list. Sinclair has shared his protocol publicly in multiple interviews and podcasts over several years, and it has evolved as the science has progressed and as he has updated his views. What follows reflects his most recently and consistently stated practices as of mid-2025, but it is worth verifying against his latest public statements since his protocol does change. He has also consistently emphasized that he shares this as his personal practice and not as a clinical recommendation for others — a distinction worth respecting, since his protocol reflects his specific research focus, risk tolerance, and health context, which may differ substantially from yours.
The Core of the Sinclair Stack
Several compounds have been consistent features of Sinclair’s protocol across multiple years of public disclosure. These form the stable core of what he describes.
NMN — 1,000 mg/day
NMN is the centerpiece of Sinclair’s protocol and the compound most associated with his research. He takes 1,000 mg/day, in the morning, mixed into yogurt. The yogurt serves a dual purpose: it provides the fat that improves resveratrol absorption (taken at the same time) and makes the routine easy to maintain consistently.
His advocacy for NMN is grounded in research from his own laboratory and others demonstrating that NAD+ decline is a driver of aging and that NMN supplementation can restore NAD+ levels and produce health improvements in animal models and, increasingly, human trials. The full evidence base for NMN is reviewed in the article on NMN supplements: complete guide, and the human clinical trial picture is covered in the article on what human clinical trials on NMN actually show.
Resveratrol — 1,000 mg/day
Resveratrol is the second pillar of the Sinclair protocol and the compound most closely associated with his STAC (sirtuin-activating compound) hypothesis — the idea that compounds activating SIRT1 can mimic aspects of calorie restriction and slow aging. He takes 1,000 mg/day with the NMN and yogurt in the morning, and has consistently maintained this pairing across multiple years.
Sinclair’s resveratrol research — particularly the mouse lifespan extension findings published with Baur et al. in Nature (2006) — is what originally brought resveratrol to widespread public attention. The rationale for taking it alongside NMN (NMN provides the NAD+ that sirtuins require; resveratrol activates those sirtuins more aggressively) is covered in detail in the article on NMN + resveratrol: why these two are always paired.
Metformin — 500–1,000 mg/day
Metformin is the most significant departure from a standard supplement stack: it is a prescription diabetes drug, not a supplement. Sinclair has discussed taking metformin off-label for its potential longevity effects — its AMPK-activating mechanism, its mimicry of calorie restriction, and the observational data suggesting diabetic patients on metformin have lower rates of certain age-related diseases and cancer than matched controls not on the drug.
Metformin is the subject of the TAME trial (Targeting Aging with Metformin), a large clinical trial explicitly testing whether it slows biological aging in humans — a trial that Sinclair has supported and that, if successful, would be a landmark demonstration that a pharmaceutical can target aging itself.
Metformin cannot be self-prescribed. If you are interested in it for longevity purposes, that conversation belongs with a physician. Berberine — covered in the berberine complete guide — is the most evidence-backed non-prescription alternative for people interested in the AMPK-activation mechanism without a prescription. The similarities and differences between the two are worth understanding before choosing an approach.
One nuance Sinclair has noted publicly: he does not take metformin on days he exercises vigorously, because of the concern (also raised about berberine) that AMPK activation from metformin may blunt some of the mitochondrial adaptations that exercise produces. This is an honest acknowledgment of a real and unresolved question in the longevity space.
TMG — 500–1,000 mg/day
TMG (trimethylglycine) appears in Sinclair’s protocol as methyl group support alongside NMN — supplementing the methyl groups consumed when nicotinamide is cleared from the body after NAD+ synthesis. He has mentioned it consistently as part of the morning routine. The full rationale for the NMN + TMG pairing is covered in the article on NMN + TMG: do you really need TMG with your NMN?
Vitamin D3 + K2
Sinclair has mentioned vitamin D supplementation in multiple interviews, though with less specificity about dose than for the other core compounds. He takes it as part of general health maintenance rather than as a longevity-specific intervention — consistent with the broader evidence base for vitamin D, which supports its role in immune function, bone health, and cardiovascular health but does not position it as a primary longevity compound in the same way NMN or resveratrol are. The complete case for why D3 + K2 belongs in any serious longevity stack is covered in the article on vitamin D3 + K2: why this combination belongs in a longevity stack.
Additional Compounds Sinclair Has Discussed
Beyond the consistent core, Sinclair has mentioned several other compounds at various points. These are less firmly established as permanent fixtures of his protocol and more reflective of his ongoing engagement with the research landscape.
Quercetin and Fisetin
Sinclair has discussed senolytics — compounds that clear senescent cells — in the context of longevity, and has mentioned quercetin and fisetin as compounds he has experimented with or monitors closely. Both have senolytic evidence in preclinical models; fisetin has arguably the strongest animal evidence for lifespan extension of any natural compound currently available. He has not consistently described a specific senolytic protocol as a fixed part of his routine, but the compounds are consistent with his broader approach. The complete guides to quercetin and fisetin cover the evidence and dosing in full.
Rapamycin
Rapamycin — an mTOR inhibitor with strong longevity evidence in animal models — is a prescription immunosuppressant that Sinclair has acknowledged discussing and monitoring in research contexts. He has been more cautious about publicly endorsing personal rapamycin use than some other longevity figures (notably Peter Attia, who has discussed taking it more explicitly). Its inclusion here reflects completeness about his public statements rather than a recommendation — rapamycin has significant immune suppression effects and is not appropriate for self-directed experimentation.
Low-Dose Aspirin
Sinclair has mentioned low-dose aspirin at various points, primarily for its anti-inflammatory and cardiovascular effects. This is a compound he has described cautiously and not as a consistent feature of his standard protocol. Given subsequent meta-analyses showing limited net benefit of prophylactic aspirin in healthy individuals without established cardiovascular disease — and increased bleeding risk — this is one area where the evidence landscape has moved since his earlier mentions, and where medical guidance is most important before self-administering.
What Sinclair Does Not Take (That People Might Expect)
Sinclair has been notably absent on a few compounds that appear in other prominent longevity protocols. He does not prominently feature spermidine, berberine as a primary recommendation (he uses metformin instead, as a prescription alternative), or extensive antioxidant supplementation beyond what his other compounds provide. This is worth noting because the Sinclair stack is sometimes conflated with a broader, more comprehensive longevity stack that includes everything — his protocol is actually fairly focused around the NAD+/sirtuin axis and AMPK activation.
Lifestyle Practices Alongside the Stack
Sinclair is equally forthcoming about non-supplement practices, and treating his protocol as supplement-only misses important context. Several lifestyle practices feature consistently in his public discussions:
He follows a predominantly plant-based diet, eats one main meal per day (a form of time-restricted eating), and avoids sugar and refined carbohydrates. He exercises regularly, including high-intensity interval training and resistance work. He maintains a relatively cool sleeping environment. He monitors his biological age periodically using epigenetic testing and uses those measurements to track whether interventions are working.
These lifestyle practices are not separable from the supplement protocol in terms of outcomes — they are integral to the approach. Supplements on top of a poor lifestyle foundation produce smaller effects than supplements on top of a strong one. The site’s lifestyle section covers the evidence base for these factors in depth, starting with the articles on exercise and NAD+ and fasting, time-restricted eating, and NAD+.
How to Adapt the Sinclair Stack for Yourself
Adopting Sinclair’s protocol wholesale is not necessarily the right approach for everyone, and there are a few specific reasons why adaptation is usually more appropriate than direct copying.
First, metformin requires a prescription and a physician’s involvement. Anyone substituting berberine or simply omitting this component is running a meaningfully different protocol — and that is probably the right call for most people without metabolic concerns or a physician willing to prescribe metformin off-label.
Second, Sinclair’s dosing — 1,000 mg NMN, 1,000 mg resveratrol — reflects his own assessment of his needs and risk tolerance, not an optimized general recommendation. The NMN dosage guide at how much NMN should you take? provides a framework for calibrating your own dose based on age, health status, and goals rather than simply mirroring his numbers.
Third, his protocol is oriented around the NAD+/sirtuin axis — it is not a comprehensive multi-mechanism longevity stack. Depending on your health profile and goals, additions like a senolytic protocol (fisetin + quercetin), spermidine for autophagy support, or omega-3 fatty acids for anti-inflammatory coverage may add meaningful value beyond what the Sinclair core provides.
For a comprehensive approach to building a broader stack that incorporates Sinclair-influenced core elements alongside additional mechanisms, the article on the advanced longevity stack provides that architecture.
Frequently Asked Questions
Has Sinclair’s protocol changed over time?
Yes, meaningfully. His earlier public discussions emphasized resveratrol more heavily, reflecting the period immediately following his high-profile mouse studies. Over time he has emphasized NMN more, added TMG explicitly, and shifted his public statements to reflect newer trial data. He has also become more nuanced about metformin and exercise interaction than he was in earlier interviews. Anyone following “the Sinclair stack” based on older sources may be working from an outdated version of his protocol.
Does Sinclair take any of these supplements because he has a financial interest in them?
Sinclair co-founded a company (Life Biosciences) working on longevity interventions and has been involved with other longevity-related ventures. He holds or has held equity positions in companies working in this space. He discloses these interests, and they are worth being aware of when evaluating his public statements — as with any researcher who has both scientific and commercial involvement in their field. His research publications are peer-reviewed and his findings have been independently replicated in many cases, which provides meaningful independent validation of the science separate from his personal recommendations.
Is the Sinclair protocol appropriate for people under 40?
The core elements — NMN, resveratrol, TMG, D3/K2 — are appropriate for adults of any age over 18, with the caveat that the evidence for functional benefits is strongest in middle-aged and older adults where NAD+ decline is more pronounced. Lower starting doses of NMN are more appropriate for younger adults. The prescription elements (metformin, rapamycin) require physician involvement regardless of age. There is no established harm in beginning NAD+ precursor supplementation earlier in life; the question is whether the benefit is as large when the deficit being corrected is smaller.
How does Sinclair measure whether his protocol is working?
He has discussed using biological age testing via epigenetic clocks — particularly the Horvath clock and related methylation-based measures — to track changes in his biological age over time. He has publicly reported reductions in his measured biological age, though he is appropriately cautious about interpreting these measurements as definitive proof of efficacy given the limitations of current epigenetic age estimation methods. He also monitors standard blood markers. The article on can you actually reverse biological age? covers the science behind biological age measurement in depth.