David Sinclair just shook up his supplement protocol again. In his June 2025 interview with Peter Diamandis, the Harvard geneticist dropped some surprises: he’s ditched taurine and TMG, switched from daily metformin to berberine, and now only takes rapamycin four times per year. If you’ve been following his old protocol, it’s time for an update.

At 55, Sinclair looks and feels significantly younger than his age, which he credits partly to his carefully selected supplements and lifestyle practices. He’s been remarkably open about his personal regimen, sharing details in interviews, podcasts, and his bestselling book Lifespan.

This guide covers Sinclair’s complete supplement stack as of late 2025, including exact dosages, why he takes each one, and what’s changed. I’ve tracked down his actual quotes from various interviews to make sure everything here is accurate.

Quick note: This is Sinclair’s personal experiment on himself. He’s not recommending everyone follow his exact protocol. Always consult with your healthcare provider before starting any new supplement regimen, especially prescription medications.

David Sinclair’s Current Supplement Stack (2025)

Here’s everything in Dr. Sinclair’s confirmed stack as of his June 2025 interview, with dosages and timing:

What He Stopped Taking in 2025

In his June 2025 interview, Sinclair confirmed he’s no longer taking:

• Taurine – Despite the 2023 hype around taurine for longevity, Sinclair has dropped it from his stack
• TMG (Trimethylglycine) – Previously taken as methylation support for NMN, now discontinued
• Quercetin – Dropped in 2023 due to concerns about interfering with SIRT6 and NRF2

Sinclair approaches aging from multiple angles simultaneously, which reflects how complex the aging process actually is. Let me break down each supplement and explain why he considers them worth taking.

NMN: The Cornerstone of Sinclair’s Protocol

If there’s one supplement that defines Sinclair’s approach to longevity, it’s NMN. This molecule serves as a precursor to NAD+, which is critical for cellular energy production and DNA repair. As we age, our NAD+ levels naturally decline, and this decline is linked to many aspects of aging.

Sinclair takes a full gram of NMN every morning, mixing the powder into yogurt or a smoothie. In his book Lifespan, he wrote “I take NMN every morning, often mixed in my yogurt (along with resveratrol).” The reason he chooses NMN over similar compounds like NR (nicotinamide riboside) comes down to unpublished research showing NMN improved endurance in mice by 50%, while NR didn’t show the same benefit. For a deeper dive into his exact protocol, check out our analysis of David Sinclair’s NMN & Resveratrol Protocol.

You might wonder why not just take NAD+ directly? Sinclair has explained that NAD+ molecules are too large to effectively enter cells. NMN, being smaller, can slip into cells and then convert to NAD+ where it’s needed. He stores his NMN in the freezer to maintain stability, something worth noting if you decide to try it yourself.

The FDA created some controversy in late 2022 by banning NMN as a dietary supplement in the U.S., claiming it was under investigation as a drug. Despite this, NMN remains available through various channels, and Sinclair continues taking it daily.

The results Sinclair reports are impressive, though anecdotal. He claims his blood work resembles that of someone decades younger. While human trials are still catching up, early studies have shown improvements in insulin sensitivity and muscle strength with NMN supplementation. If you’re interested in trying NMN yourself, read our in-depth review of Renue By Science NMN to understand what makes a quality product. There are also natural ways to boost NAD levels if you prefer to start there.

Resveratrol: The Red Wine Molecule That Started It All

Resveratrol gained fame as the compound in red wine that might explain the French Paradox, but for Sinclair, it’s much more than a curiosity. This polyphenol activates sirtuin enzymes, particularly SIRT1, which play key roles in DNA repair and metabolic regulation.

Every morning, Sinclair takes a gram of resveratrol mixed into coconut yogurt (he’s switched from regular yogurt in recent years). The fat in the yogurt is essential since resveratrol is fat-soluble and needs it for proper absorption. In a 2019 interview with Dr. Rhonda Patrick, he mentioned “I take resveratrol, about a gram or so every morning in my yogurt” because it “may help my cardiovascular system.”

A gram is a massive dose compared to what you’d get from wine. You’d need to drink hundreds of glasses to get that much resveratrol, which obviously defeats the purpose. Sinclair often jokes about this, saying supplements are a much cleaner delivery method.

He doesn’t fuss with expensive branded versions either, preferring simple bulk powder. Renue by Science Pure Resveratrol Powder (use code ‘brainflow’ for 15% off) is a reliable option that many biohackers use. Just remember to take it with fat for absorption.

The NMN and resveratrol combination is intentional. Sinclair believes they work synergistically: NMN provides the fuel (NAD+) that sirtuins need, while resveratrol activates those sirtuins. Together, they potentially amplify the anti-aging effects beyond what either could achieve alone. We’ve done a full review of Renue By Science Resveratrol if you want to learn more about quality resveratrol supplementation.

Berberine: The New Metformin Replacement

This is the biggest change in Sinclair’s 2025 protocol. In his June 2025 interview with Peter Diamandis, Sinclair revealed he’s largely switched from metformin to berberine because metformin was hard on his stomach.

Berberine is a plant compound extracted from bark and roots that activates many of the same longevity pathways as metformin. Both activate AMPK, lower blood glucose, and improve insulin sensitivity. The key difference? Berberine doesn’t require a prescription and tends to be easier on the digestive system for many people.

Sinclair now takes about 1 gram of berberine in the morning. He still keeps metformin around and takes it occasionally, but berberine has become his primary AMPK activator.

Research backs up the switch. Studies show berberine can lower blood glucose and triglycerides similarly to metformin, activate autophagy through the AMPK pathway, and reduce inflammatory biomarkers and cardiovascular disease risk. Clinical trials typically use 500mg to 1 gram taken 2-3 times daily, though Sinclair appears to take his full dose in the morning.

If you’re interested in berberine, take it with food (yogurt or olive oil works well) since it’s fairly insoluble. Thorne Berberine is a quality option.

Nattokinase: The New Addition for Arterial Health

Another new addition to Sinclair’s stack is nattokinase, an enzyme found in the Japanese fermented food natto. In his June 2025 interview, Sinclair mentioned adding it based on a Chinese study showing impressive results for arterial plaque.

The study (Chen et al. 2022) showed nattokinase reduced carotid artery plaque size by up to 36% in approximately two-thirds of participants. Nattokinase works by breaking down fibrin, a protein involved in blood clot formation, which may help reduce clotting and improve blood flow.

Given Sinclair’s family history of heart disease and his focus on cardiovascular health (he’s been on a statin since age 29), adding nattokinase makes sense as another layer of arterial protection. Double Wood Nattokinase provides 4,000 FU per serving and is a solid choice if you want to add this to your stack.

The Vitamin D3 and K2 Partnership

While not as exotic as NMN or resveratrol, vitamins D3 and K2 form a key foundation in Sinclair’s stack. These two work together in ways that many people don’t realize.

Sinclair aims for 4,000 to 5,000 IU of vitamin D3 daily. In a 2020 tweet, he noted that doctors recommend 400 to 4,000 IU daily, and he personally takes “at least 2,500 IU daily.” He pairs this with 180 to 360 micrograms of vitamin K2, specifically the MK-7 form.

The reason for taking them together is worth understanding. Vitamin D helps your body absorb calcium, but K2 directs that calcium to your bones rather than letting it accumulate in your arteries. Without K2, the calcium mobilized by vitamin D could actually contribute to arterial stiffness. In a 2021 interview with Dr. Steven Gundry, Sinclair specifically mentioned taking K2 “for my blood vessels.”

Given his family history of heart disease, this combination makes sense. Thorne Vitamin D3 and Life Extension Super K are both solid choices if you’re looking to add these to your routine.

Spermidine: Mimicking the Benefits of Fasting

Despite its unfortunate name (yes, it was first discovered in semen), spermidine is found throughout our bodies and in foods like wheat germ, mushrooms, and aged cheese. What makes it special for longevity is its ability to trigger autophagy, the cellular cleaning process that removes damaged components.

In a 2020 Instagram Live chat, Sinclair revealed: “I’ve recently started taking spermidine as well, because we want to induce autophagy. And that would help induce what fasting would already do or accentuate the benefits of fasting.” He takes between 1 and 2 mg daily, viewing it as a way to boost the autophagy he’s already promoting through intermittent fasting.

The research on spermidine is promising. Studies in mice have shown it can extend lifespan and improve cardiovascular health. Human trials have found links to improved memory and heart health markers. For Sinclair, it’s another tool to keep cells in a cleaner, more youthful state by continuously prompting them to clear out cellular junk. For more details on how and why Sinclair uses this compound, see our analysis of David Sinclair’s Spermidine Protocol.

Renue by Science Liposomal Spermidine provides a high-quality option for those interested in trying this lesser-known longevity compound.

Fisetin: The Senolytic That Made the Cut

Senolytics are compounds that help destroy senescent cells, those “zombie” cells that accumulate with age and pump out inflammatory factors. Fisetin is a natural senolytic that Sinclair has kept in his stack even after dropping quercetin.

Sinclair used to take 500 mg each of both fisetin and quercetin daily with yogurt. But in 2023, he dropped quercetin from his regular routine while continuing with fisetin at 500 mg daily.

Why the change? New research suggested that high-dose quercetin might interfere with certain longevity proteins like SIRT6 and NRF2. Too much quercetin could potentially work against some of the anti-aging pathways Sinclair is trying to activate. Plus, you can get plenty of quercetin from a healthy diet rich in onions, capers, and apples.

Fisetin, found naturally in strawberries and persimmons, remains in his stack. Mayo Clinic research has shown it can clear a significant percentage of senescent cells in mice and extend their remaining lifespan. By removing these problematic cells, fisetin helps reduce the chronic inflammation they cause.

If you’re following Sinclair’s current approach, Double Wood Fisetin is a solid choice.

Alpha Lipoic Acid: A Personal Favorite Returns

Alpha lipoic acid holds a special place in Sinclair’s heart since it was the focus of his PhD research decades ago. This unique antioxidant is both fat and water-soluble, allowing it to work throughout the body, including in the mitochondria where energy is produced.

After years of not mentioning it, Sinclair reintroduced ALA to his routine. In a 2021 interview with Dave Asprey, he revealed he takes around 500 mg daily. His decision was influenced by meeting Dr. Denham Harman, who proposed the free radical theory of aging and had been taking ALA most of his life, remaining active into his nineties.

ALA supports mitochondrial function by helping convert glucose into ATP energy. As mitochondrial efficiency declines with age, ALA might help counteract that decline. Sinclair takes it on an empty stomach for better absorption, which fits well with his intermittent fasting schedule. Double Wood’s ALA supplement provides an affordable option at around $9 on Amazon.

CoQ10: Protecting Against Statin Side Effects

Coenzyme Q10 might seem like an odd addition to a cutting-edge longevity stack, but for Sinclair, it’s necessary. He mentioned on Twitter in 2020 that he takes CoQ10 every night specifically because he’s on a statin.

Statins, while excellent for lowering cholesterol, have an unfortunate side effect: they reduce the body’s production of CoQ10. This happens because the same biochemical pathway that produces cholesterol also produces CoQ10. The depletion can lead to muscle aches and fatigue, which is why many doctors recommend CoQ10 supplementation for statin users.

Sinclair likely takes around 100 mg nightly, though he hasn’t specified the exact dose. Beyond just counteracting statin side effects, CoQ10 serves as an antioxidant that protects cell membranes and supports mitochondrial function. Pure Encapsulations CoQ10 is a high-quality choice for this important cofactor.

Fish Oil: A Late Addition to the Stack

Fish oil wasn’t part of Sinclair’s original protocol. He didn’t mention it at all in his 2019 book Lifespan. But by 2023, he had incorporated fish oil supplements into his routine.

While Sinclair hasn’t specified his exact dose, he’s aware that experts like Dr. Andrew Huberman and Dr. Peter Attia take substantial amounts, around 2 grams of EPA and 1.5 grams of DHA daily. Given Sinclair’s mostly plant-based diet, supplementing with omega-3s makes sense to ensure he’s getting these essential fatty acids. Andrew Huberman’s supplement list shares several overlaps with Sinclair’s, showing some consensus among longevity experts.

The benefits of omega-3s for aging are well-documented. They reduce inflammation, support brain health, and may even slow telomere shortening. Some studies have found that people with higher omega-3 levels in their blood have lower mortality rates and slower biological aging. Sinclair has noted that algae oil might be a better choice than fish oil since it’s plant-based and doesn’t have the heavy metals that can be in fish oil. Nordic Naturals Ultimate Omega, which Dr. Rhonda Patrick uses, is a great choice for quality fish oil.

The Prescription Medications: Metformin, Statins, Aspirin, and Rapamycin

Four prescription or over-the-counter medications round out Sinclair’s pharmaceutical approach to longevity.

Metformin was previously a daily staple, but Sinclair now only takes it occasionally due to stomach issues. When he does take it, it’s about 1 gram, and he skips it on days when he exercises hard at the gym because some evidence suggests metformin might blunt the beneficial effects of exercise on muscle growth.

His reasons for keeping metformin around are both personal and scientific. His family has a history of diabetes, and metformin is excellent at preventing it. But beyond that, metformin activates AMPK, shifting the body into a metabolic state similar to fasting. It essentially tricks your cells into thinking they’re in a mild energy crisis, triggering protective and repair mechanisms. Now that he’s switched primarily to berberine, he gets similar benefits without the GI distress.

The statin story is particularly interesting. Sinclair has been on 80 mg of a statin (likely atorvastatin) since age 29. Genetic testing through 23andMe revealed he had high cardiovascular disease risk, prompting his doctor to start him on preventive therapy unusually early. On the Joe Rogan podcast, he joked that his genetic results basically said “give up now” regarding heart disease risk.

Low-dose aspirin at 81 mg daily rounds out his cardiovascular protection. While recent guidelines have become more cautious about recommending aspirin for everyone, Sinclair continues taking it for its anti-inflammatory effects and potential cancer prevention benefits. He’s aware of the bleeding risk but has decided the potential benefits outweigh the risks in his case. Bayer Low-Dose Aspirin is available cheaply if you’re considering this addition, though definitely discuss it with your doctor first given the bleeding risks.

Rapamycin represents the experimental edge of Sinclair’s protocol. This immunosuppressant drug has shown remarkable life-extending properties in animal studies by inhibiting mTOR. But here’s the update: Sinclair now only takes rapamycin about four times per year, not weekly as previously thought. In his June 2025 interview, he mentioned that recent research on epigenetic aging found rapamycin didn’t appear to have effect on that measure, whereas things like fasting, acarbose, and metformin did better.

The Lifestyle Foundation That Makes It All Work

Sinclair constantly emphasizes that supplements are maybe 20% of his longevity strategy. The other 80% comes from lifestyle choices that anyone can implement:

Intermittent fasting is non-negotiable for him. He typically skips breakfast, having just black coffee in the morning, then eating lunch and dinner. Sometimes he’ll even skip lunch for a more extended fast. This eating pattern activates many of the same longevity pathways his supplements target.

His diet leans heavily plant-based with minimal sugar and processed foods. Red meat is rare in his diet because animal protein can raise IGF-1 and mTOR, potentially accelerating aging. He does eat some fish occasionally but gets most of his nutrition from vegetables, legumes, nuts, and healthy fats like olive oil.

Exercise is important, combining both high-intensity interval training for cardiovascular fitness and weight training to maintain muscle mass. Remember, he skips metformin on heavy workout days to maximize exercise benefits.

He regularly uses saunas and cold exposure, despite admitting he hates being cold. These hormetic stressors activate protective cellular responses that may contribute to longevity.

Perhaps most importantly, Sinclair obsessively tracks his biomarkers. He uses continuous glucose monitors, gets regular blood panels, and even tests his epigenetic age. This data-driven approach lets him see what’s working and adjust accordingly.

Should You Copy Sinclair’s Stack?

Sinclair’s regimen represents one of the most scientifically-informed personal longevity protocols out there. By targeting multiple aging mechanisms simultaneously, he’s essentially trying to stack the deck in favor of a longer, healthier life.

He often reports that his biological markers resemble those of someone much younger than his chronological age. While this is anecdotal, it’s interesting coming from someone with his scientific credentials and access to testing.

However, Sinclair himself admits we’re still in somewhat uncharted territory. “While I stand by these supplements, the truth is we are not exactly on solid ground… Most of them remain in a gray area, intriguing, yes, but far from proven.” Human trials are ongoing for many of these interventions, but definitive results will take years.

If you’re thinking about following his lead, start slowly. The basics like vitamin D, omega-3s, and intermittent fasting have broad scientific support and are relatively safe for most people. The more aggressive interventions like metformin and rapamycin require medical supervision and aren’t right for everyone.

What’s most instructive about Sinclair’s approach is how he personalizes it. Because of his family history, he prioritizes cardiovascular health with early statin use. When new research emerges, like the nattokinase studies, he’s willing to experiment. When evidence suggests something might not be working, like with quercetin and taurine, he’s willing to drop it.

The takeaway isn’t necessarily to copy Sinclair’s exact stack, but to adopt his mindset: stay informed, track your results, be willing to experiment carefully, and remember that no amount of supplements can replace good lifestyle habits.

Will Sinclair’s protocol help him live to 120? Only time will tell. But at 55, he appears to have the energy and vitality of someone much younger, and he’s inspired millions to take their healthspan into their own hands. Whether or not we can truly reverse aging, Sinclair’s approach shows we might at least be able to slow it down considerably.

Frequently Asked Questions

What supplements does David Sinclair take in 2025?

As of his June 2025 interview with Peter Diamandis, Sinclair takes NMN (1g), resveratrol (1g), vitamin D3, vitamin K2, fisetin (500mg), spermidine (1-2mg), alpha lipoic acid (~500mg), fish oil, berberine (1g), nattokinase, CoQ10, low-dose aspirin (81mg), a statin (80mg), and rapamycin (about 4x per year). He has stopped taking taurine and TMG.

Why did David Sinclair stop taking metformin?

Sinclair found metformin hard on his stomach. He now only takes it occasionally and has largely switched to berberine, which provides similar AMPK-activating benefits without the GI distress. Berberine is also available without a prescription.

Does David Sinclair still take taurine?

No. Despite the 2023 hype around taurine for longevity, Sinclair confirmed in his June 2025 interview that he is not taking taurine or TMG.

What brand of NMN does David Sinclair use?

Sinclair has made a point not to endorse specific brands. However, he takes 1 gram of NMN powder daily, mixed with yogurt. Many in the longevity community trust Renue By Science for pharmaceutical-grade NMN with third-party testing.

Why does Sinclair take resveratrol with yogurt?

Resveratrol is fat-soluble and needs fat for proper absorption. Sinclair mixes his 1 gram of resveratrol into coconut yogurt (he’s switched from regular yogurt) to maximize bioavailability. Olive oil also works.

How often does David Sinclair take rapamycin?

As of June 2025, Sinclair takes rapamycin about 4 times per year, not weekly as some sources previously reported. He mentioned that recent research on epigenetic aging found rapamycin didn’t appear to have effect on that measure.

What is the Sinclair NMN and resveratrol protocol?

Sinclair takes 1 gram of NMN and 1 gram of resveratrol every morning, mixed into coconut yogurt. He believes they work synergistically: NMN provides NAD+ that sirtuins need as fuel, while resveratrol activates those sirtuins. He stores his NMN in the freezer to maintain stability.

Why did David Sinclair add nattokinase to his stack?

Sinclair added nattokinase based on a Chinese study (Chen et al. 2022) showing it reduced carotid artery plaque size by up to 36% in approximately two-thirds of participants. Given his family history of heart disease and his long-term statin use, arterial health is a priority for him.