David Sinclair is a professor at Harvard University who has been studying aging for the better part of his academic career.
Dr. David Sinclair’s main research interest is the epigenetics of aging, with a focus on epigenetic reprogramming of aging (e.g., reversing aging via Yamanaka factors), NAD+ metabolism and sirtuins, and NAD+ precursors like NR and NMN.
You may have come across his published, New York Times best-selling book on aging, Lifespan: Why We Age – And Why We Don’t Have To, going deeper into those subjects (you can find our favorite longevity books here).
So what supplements does Dr. Sinclair take to live longer?
Keep in mind that to date, Dr. Sinclair has made a point to not promote or endorse any supplement products. We compiled this list from interviews and books in which Dr. Sinclair mentions supplements he takes.
We don’t know if he still takes these supplements or whether he takes additional supplements that are not included on this list.
For example, in his book Lifespan, he mentions on page 304 that he takes NMN and resveratrol every morning, often mixed in his yogurt.
Based on multiple, recent interviews and his book, Dr. Sinclair’s supplement and longevity drug stack likely looks as follows:
1. Nicotinamide mononucleotide (NMN): 1g per day, in the morning
2. Resveratrol: 1g per day, in the morning
3. Metformin: 800 mg, in the evening
4. Vitamin D3: ideally 4,000 to 5,000 IU per day
5. Vitamin K2: ideally 180 to 360 micrograms per day
7. Low-dose aspirin: 83 mg per day
8. Alpha lipoic acid (ALA): recent status unknown
9. Coenzyme Q10 (coQ10): recent status unknown
10. Spermidine: 1 mg per day, in the morning
11. Quercetin and fisetin: 500 mg each, once per day, in the morning
12. TMG (trimethylglycine or betaine): 500 mg to 1,000 mg per day
1. Nicotinamide mononucleotide (NMN), 1g per day, in the morning
Our view: We are enthusiastic about NMN.
It’s interesting to know that Dr. Sinclair takes NMN and not NR (another much touted “longevity” supplement). Despite all the hype on the internet, NR does not extend lifespan (R). Professor Sinclair considers NMN to be superior to NR.
Learn more about the differences between NMN and NR here.
2. Resveratrol, 1g per day, in the morning
Our view: We are lukewarm about resveratrol. We believe pterostilbene is better.
Resveratrol is a stilbenoid found in the skin of grapes in low amounts. Studies have shown that resveratrol can reduce the risk of heart disease, cancer, and neurodegeneration.
David Sinclair believes that resveratrol works synergistically with NMN. Resveratrol is needed to activate the sirtuin genes (which protect our DNA and epigenome), while NMN is needed to fuel the sirtuins.
However, resveratrol is difficult to be absorbed by the gut, and the little resveratrol that ends up in the body is broken down very quickly.
Therefore, pterostilbene is a better alternative. Pterostilbene is a molecule that looks very similar to resveratrol, but it is absorbed considerably better and is far more stable in the human body. For example, a paper that compares resveratrol to pterostilbene states, “Although there are structural and bioactivity similarities between resveratrol and pterostilbene, pharmacological properties of pterostilbene are often stronger than those of resveratrol,” and “Overall, pterostilbene performs better in membrane permeability and metabolic stability than resveratrol. This increases the bioavailability, and enhances the pharmacokinetic profile and pharmacological activities of pterostilbene” (R).
Further, pterostilbene contains three methyl groups that resveratrol doesn’t, which the body can use for, among other things, methylation, which is required for proper gene function.
Listen to David Sinclair speak about pterostilbene and resveratrol in this short clip:
3. Metformin (prescription drug): 800 mg, in the evening
Our view: We are cautiously optimistic about metformin, keeping in mind some caveats.
In humans, we see that diabetics taking metformin actually live longer than healthy non-diabetics who obviously don’t take metformin (R). This was not the case for diabetics on other anti-diabetic drugs.
Taking metformin can, however, have side effects. In the short term, metformin can cause diarrhea and gastrointestinal discomfort, which often subsides after a few weeks. In the long term, metformin can reduce the uptake of vitamin B12.
Metformin probably works as a hormetic substance, meaning that it causes a little bit of damage to our cells so that our cells are put in a repair and protect modus. Metformin inhibits mitochondrial function, so the mitochondria will repair and protect themselves better.
Therefore, given exercise also “damages” the mitochondria somewhat (so that afterwards they will repair themselves, which is one of the health benefits of exercise), he does not combine metformin with exercise given that could put too much stress on the mitochondria. That is why Dr. Sinclair does not take metformin on the days he exercises.
Also, recent studies suggest that perhaps very old people should not take metformin, given metformin causes too much stress on already very old and very stressed mitochondria (R).
We wrote an article about natural alternatives for metformin here.
Furthermore, David Sinclair takes metformin in the evening, before going to bed. He says this because during the night, the body is already in a fasting state and metformin could further advance this state.
However, we would recommend taking metformin always before the largest meal (ideally 20 minutes before mealtime). This way, metformin can make the body more insulin-sensitive when it matters the most: during and in the hours after a meal, when mitochondria have to process the sugars and fats from the meal. This is also how metformin is ideally prescribed according to medical guidelines.
Furthermore, during the night, you are already in a fasting (insulin-sensitive) state. It could be better to get the body more into an insulin-sensitive state during the day, too, especially when processing carbohydrates and fats after a meal.
Dr. Sinclair takes 800 mg of metformin only once per day. We would prefer lower doses spread over the day, like 500 mg twice daily, before lunch (500 mg) and before dinner (500 mg) — not in the morning because this is when the body is already most insulin-sensitive anyhow.
4. Vitamin D3
Our view: We are positive about this vitamin.
Vitamin D can extend lifespan, at least in simple organisms (R). Vitamin D can reduce the risk of various aging-related diseases. Vitamin D deficiency in humans has been associated with an increased risk of heart disease, type 2 diabetes, autoimmune diseases, and Alzheimer’s disease.
Vitamin D activates many genes that confer important health benefits (R).
The dose of vitamin D that most governments advise is too low (e.g., 400 to 800 IU per day). Most vitamin D experts advise to take at least 4,000 to 5,000 IU per day, and get your vitamin D levels checked at least every year.
Vitamin D is one of our supplements everyone should take for optimal health.
5. Vitamin K2
Our view: We like vitamin K (a lot).
If you take vitamin D, you ideally also combine it with vitamin K2 (MK-7 is the best form): the two vitamins work synergistically.
Ideally, doses of vitamin K2 are 180 to 360 micrograms per day.
However, taking only a few vitamins, like vitamin K and vitamin D, is not going to cut it: most people are deficient in many other vitamins, minerals, and micronutrients, even when they eat healthy.
Learn more about the vitamins, minerals, and other nutrients everyone should take here.
6. Statin (prescription drug) — taken since his early 20s due to family history of cardiovascular disease
Our view: We are not big fans.
Statins could lower the risk of heart disease. But there is a lot of discussion about how significant the effect of a statin is on reducing the cardiovascular risk.
Some scientists claim you should take statins if you have an increased risk of getting a heart attack (known as “primary prevention”), while others claim that you should only take statins when you’ve already had a heart attack (as “secondary prevention”).
Other studies suggest that for many people, statins don’t work very well for primary prevention.
This will likely depend on your personal genetic make-up; we see that some people react much better to statins while others derive no effect (R).
Also, not all statins are the same. Some statins seem to be able to extend lifespan in mice (like simvastatin), while other statins do not have this effect. Also, statins can have side effects, like muscle aches or neuropathy (nerve pain), and some statins more than others.
After all, statins inhibit the production of cholesterol, a molecule that is an important component of our cell membranes, especially of neurons and muscle cells.
7. Low-dose aspirin — 83 mg per day
Our view: Neutral, but also a bit disappointed.
A low-dose aspirin could reduce inflammation, reduce the risk of heart attacks, and perhaps the risk of cancer.
However, a recent large study that involved almost 20,000 participants and that lasted 4.7 years showed that a low dose of aspirin did not reduce cardiovascular disease and did not improve survival (R).
In fact, it even showed that it could actually increase cancer risk somewhat (R), despite many other studies showing that aspirin could have health and longevity benefits.
Further studies have to be conducted to sort this out.
8. Alpha-lipoic acid (ALA)
Our view: This antioxidant very likely does not extend lifespan in humans. In fact, it may actually even shorten lifespan.
Note: According to earlier sources, Dr. Sinclair mentioned taking alpha-lipoic acid. However, in recent interviews (done in 2022) David Sinclair didn’t specifically mention taking this supplement.
Alpha-lipoic acid (ALA) is a strong antioxidant. There has been a bit of a hype around ALA, especially combined with acetyl-L-carnitine (ALCAR), to slow down aging.
However, there are various studies showing that ALA does not extend lifespan or slow down aging (R).
Still, alpha-lipoic acid is a strong antioxidant, and scientists have learned that antioxidants could actually accelerate aging (as we explain here).
This is why alpha-lipoic acid is one of the anti-aging supplements you should not take.
In short, we would be careful with taking supraphysiological doses (much greater than you’d ever find in a healthy diet) of antioxidants.
9. Coenzyme Q10 (coQ10)
Our view: This antioxidant probably cannot extend lifespan in humans. It could possibly even shorten lifespan.
Note: According to earlier sources, Dr. Sinclair mentioned taking coenzyme Q10. However, in recent interviews (done in 2022) David Sinclair didn’t specifically mention taking this supplement.
Coenzyme Q10 is an antioxidant that improves mitochondrial functioning. There is insufficient scientific evidence (at least in well-conducted studies with the right disease model mice) that coenzyme Q10 can extend lifespan.
Also, coenzyme Q10 is an antioxidant. In recent years, scientists have learned that antioxidants can actually accelerate aging (for reasons described here). We would be cautious about taking strong antioxidants like coenzyme Q10 to extend lifespan.
That is also why we added coenzyme Q10 to the list of anti-aging supplements one should not take for longevity.
10. Spermidine, 1 mg per day, in the morning
Our view: We think spermidine is an interesting molecule for longevity.
Spermidine is a molecule first found in sperm, hence its name. As a supplement, spermidine is extracted from wheat germ. It can also be found in foods like cheese, soy, legumes, and mushrooms.
Spermidine can impact important aging mechanisms, such as autophagy.
We wrote more about spermidine and longevity here.
11. Quercetin and fisetin, 500 mg each, once per day, in the morning
Our view: we like fisetin more than quercetin. We would also reduce the dose.
Senescent cells are cells that accumulate during aging and secrete substances that damage normal, healthy cells (learn more here).
However, we believe the main reason why molecules like fisetin can extend lifespan is because of other effects than being a “senolytic,” such as by reducing inflammation.
For this reason, we prefer fisetin taken in lower doses (100 mg per day) and in a continuous way, instead of in higher doses (e.g., 1,000 mg or more) once every month in order to “clear” senescent cells.
We prefer fisetin more than quercetin. One reason is that there are more and better studies done with fisetin showing longevity effects, such as studies in mice demonstrating that fisetin extends lifespan (R).
Learn more about fisetin and longevity here.
12. TMG (trimethylglycine or betaine)
Our view: combining TMG with NMN makes sense, but we prefer phosphatidylcholine (or a combination of TMG with phosphatidylcholine).
Dr. Sinclair mentioned in podcasts that he takes TMG (trimethylglycine) to err on the safe side regarding the possibility of NMN reducing methylation in the body.
Methyl groups are small molecules that are put on DNA, proteins, and substances in order for them to work properly.
For example, methylated DNA (DNA covered with methyl molecules) prevents that DNA from being active (learn more about the epigenome here). Methyl molecules are also sometimes linked to specific substances in order for them to be broken down.
NMN is used by cells to create NAD+, a molecule pivotal for health. However, when NAD+ is used by the body, nicotinamide is formed. This molecule needs to be disposed of. In order to do so, a methyl group is placed on nicotinamide so it can be secreted by the kidneys.
So if people take a lot of NMN, lots of methyl groups could be used.
TMG provides methyl groups (TMG consists of three methyl groups per TMG molecule). We agree with Dr. Sinclair that adding TMG could be worthwhile. A proper dose would be, for example, 500 mg to 1 gram of TMG per day.
However, some people experience gastro-intestinal issues from TMG or have difficulty sleeping after taking it. Therefore, as alternatives, one can take phosphatidylcholine, which can also deliver methyl groups. It also improves brain health and cognition.
One can also drink green tea when taking NMN. Green tea contains EGCG, which inhibits the enzyme that puts methyl groups on nicotinamide (the enzyme is called “NNMT”). This way, fewer methyl groups are used to methylate nicotinamide.
We wrote more about methylation and NMN here.
OTHER THINGS DAVID SINCLAIR DOES TO LIVE LONGER
Of course, Dr. Sinclair does not only rely on supplements to live longer and healthier.
He knows very well that nutrition, exercise, proper sleep, and stress reduction are also very important methods to extend lifespan. How does he go about this?
David Sinclair often eats only two meals per day instead of three meals.
He drinks lots of green tea and very little alcohol.
He eats little (red) meat, and consumes lots of vegetables.
Professor Sinclair is a proponent of regular fasting.
We wrote more about Sinclair’s longevity regimen here.
You can read more about the best longevity diet (and download the poster!) here.
Regarding exercise, Dr. Sinclair runs once or twice a week, both in a low-intensity and high-intensity way. He also does weight lifting once or twice a week.
3. Health tracking
Professor Sinclair uses a continuous glucose monitor (CGM) to track how the foods he eats increase his blood sugar levels.
He also does regular blood tests to track his health. We wrote about the best blood tests for longevity here.
We think that the list of supplements that David Sinclair is not bad but can be further improved.
In this regard, we make the distinction between longevity supplements and health supplements.
Health supplements enable our body to work properly: deficiencies of them could accelerate aging.
More about David Sinclair
“Has Harvard’s David Sinclair Found the Fountain of Youth?” (Boston Magazine)
Anti-Aging Approaches (Harvard Magazine)
David Sinclair’s Harvard Medical School laboratory
Watch David Sinclair’s Google Talk: