David Sinclair Supplements List Deep Dive – Updated 2021

Despite being 50 years of age, David looks much younger. Given that his focus is on tackling aging and he appears to exemplify this work – it’s natural to ask – what’s his secret?

David doesn’t give health recommendations or endorse brands, but he does share his personal supplementation:

David’s Daily Supplement Regimen:

• Resveratrol – 1 gram daily – mornings with yogurt (see where to buy)
• NMN – 1 gram daily – mornings (see where to buy)
• Metformin (prescription drug) – 1 gram daily – 0.5 grams in the morning & 0.5 grams at night – except on days when exercising
• Statin – a cholesterol lowering prescription drug taken since his early 20s due to family history of cardiovascular disease
• Aspirin – baby aspirin (81mg) daily
• Further supplements he takes:
  • Vitamin D3
  • Vitamin K2
  • Omega-3 fish oil
  • Alpha Lipoic Acid
  • Coenzyme Q10
  • Quercetin
  • Fisetin (experimenting with)

After touching on David’s diet & exercise routines below, we’ll look in detail at his use of NMN, resveratrol and metformin.

How Resveratrol & NMN are Synergistic

David describes resveratrol and NMN as critical for the activation of sirtuin genes. Sirtuins play a key role in functions that help us to live longer – particularly DNA repair.

He describes resveratrol as the accelerator pedal for the sirtuin genes (increasing their activation), and NMN as the fuel. Without the “fuel”, resveratrol won’t be as effective.

The reason that resveratrol won’t work effectively without NMN, is that sirtuin activation requires youthful NAD levels, but by 50 years old, David says, we have about half the level of NAD we had in our 20s. NAD being a molecule that is essential to energy production in our cells.

Graph showing NAD+ decrease with age – via PLOS paper

So in effect, you take resveratrol to increase activation of the sirtuin genes, and NMN to ensure the sirtuins have enough energy to work properly.

Below we’ll dig deeper into the 3 longevity supplements David takes; NMN, Resveratrol & Metformin.

Resveratrol

First we’ll look at the sirtuin activator David takes; Resveratrol.

Resveratrol is a molecule that’s found (in small amounts) in the skin of foods like grapes, blueberries, raspberries, mulberries, and peanuts.

If you remember the “hype” some years ago around red wine being healthy, part of that was due to it containing tiny amounts of resveratrol.

Unfortunately, all food sources contain tiny amounts, so we need a concentrated supplement in order to see benefits!

Resveratrol is though to act as a “caloric restriction mimetic”, which activates beneficial cellular pathways. Studies have pointed to benefits such as:

• Reduced inflammation and oxidative stress in healthy people¹
• Improvements in memory tasks for obese, but otherwise healthy 50-75 year olds²
• Improvements in metabolic and cardiovascular markers, in people with obesity³, hypertension, type 2 diabetes⁴⁵⁶⁷, fatty liver disease⁸⁹ and cardiovascular disease¹⁰¹¹.

Left pic = 2009 (source), right pic = 2019 (source)

Resveratrol – Where to buy?

Whilst David’s resveratrol comes from excess product leftover from lab experiments, not all of us have this luxury! Therefore we are forced to look online.

If you pop resveratrol into an Amazon search, you’ll find a host of different options, many of (potentially) dubious quality.

The first thing to note is that we should be looking for trans-resveratrol, not cis-resveratrol.

From David’s studies, cis-Resveratrol did not activate the sirtuin enzyme, but trans-Resveratrol did.

Next, the purity of the trans-resveratrol is important, we’re looking for 98%+. David mentions this at 1:17:54 of his Ben Greenfield interview, noting that 50% purity can even give diarrhea, because there’s other stuff that comes along with the molecule. He also confirms that Polygonum cuspidatum (Japanese Knotweed) is a good source for the resveratrol.

To get closer to the quality that David is likely taking, we can look at research published by an old company of his; Sirtris (who were sold to GSK for $720 million). In this paper they were doing clinical tests on a formulation of resveratrol they call SRT501. Noting that:

Due to the poor aqueous solubility exhibited by resveratrol, digestive absorption is greatly influenced by drug dissolution rate. In an effort to increase absorption across the gastro-intestinal tract and thus systemically available parent compound, there has been considerable interest in the pharmaceutical manipulation of resveratrol. Decreasing the particle size of such chemicals can improve their rate of dissolution and thus their absorption. Therefore, the aim of this clinical study was to investigate whether consumption of SRT501, a micronized resveratrol formulation designed by Sirtris, a GSK Company is safe and generates measurable and pharmacologically active levels of parent agent in the circulation and in the liver.

That’s a wordy quote from the paper, but in essence, they were testing a micronized resveratrol formulation against a non-micronized version. Their study found that levels of resveratrol in the blood were 3.6x greater when using the micronized formulation, and other markers they were comparing also improved.

We see this with other molecules too; where reducing particle size increases bioavailability. For example with curcumin, whose absorption can be improved through micronization (for example Theracurmin). So this makes sense.

Micronized resveratrol options include:

Note: Whichever source of trans-resveratrol you take, according to David, you will increase its bio-availability if you take it with a fat source.

David takes it on an empty stomach in the morning, so mixes it with a bit of yogurt. However it should also be possible to take it with a meal containing fat.

Resveratrol – Storage

David mentions in his interview with Rhonda Patrick a few nuances around the storage of resveratrol:

• Resveratrol is light sensitive, and when left exposed to light it turns brown. They found that brown resveratrol no longer works correctly.
• Ideally resveratrol should be kept in the cold and dark – for example, in a sealed container in the fridge.

Homemade Yogurt

David takes his resveratrol in the morning, mixed into a spoon of homemade yogurt (using the Bravo starter culture), in order to increase its bio-availability.

His studies showed that without fat, resveratrol absorption was 5x lower. So consumption with yogurt (or another fat source) is important. David clarified on the recent podcast with Rhonda Patrick that the NMN doesn’t need to be taken with a fat source – he specifically mentions taking his NMN in capsules, downed with a glass of water in the morning.

Of course you don’t need to make your own yogurt, a store bought version will work adequately. However, if you’re interested to make your own version – expand the box below to learn more.

NMN – Nicotinamide Mononucleotide

We talked above about the sirtuin activator Resveratrol, now let’s talk about NMN, which helps provides the “fuel” for the sirtuins to work.

NMN falls into a category of supplements, along with Nicotinamide Riboside (NR), referred to as “NAD boosters” – which have become increasingly popular.

NAD is required for every cell of our body to help facilitate energy production. As discussed above, by age 50 you have about half as much NAD as at age 20!

The intention is that by supplementing precursors we can boost the cellular level of NAD closer to youthful levels.

There’s little to no doubt in the research community that we need to restore NAD function; but the jury is still out on what the best method will be. Currently David has his eggs in the basket of NMN.

Where to buy NMN?

David’s NMN powder comes from excess product left over from lab experiments. This is good to know, but doesn’t help us when it comes to sourcing some. Below we will look at various possible buying options.

Potential considerations when buying include:

• Accuracy – is the product you’re getting actually NMN?
• Purity – assuming it is NMN, how pure is it? 98%… 99%…?
• Contaminants – does it contain any contaminants such as heavy metals?
• Fillers – are any fillers used?

Assuming all the above are ok, the last crucial question is:

• Price – how much does it cost per gram?

What I’ve done below is put some of the more highly reviewed options (within USA) into a table, calculated the approximate price per gram, and added links to any 3rd party analysis certificates the companies display.

The above table provides a start, but for a detailed analysis table see this post, which also includes options for UK buyers.

– Price per gram
The average price per gram appears around $4-$6. For products noticeably cheaper, it would be worth exercising caution around their authenticity.

– Capsulating the Powders
With the bulk powder versions of NMN above, you could put them into capsules yourself at home, using a capsule filling machine.

This emulates the method David uses to take his NMN; in capsules swallowed with a glass of water.

Using size 00 capsules, it takes 3 capsules to capsulate 1g of NMN. Depending on how tightly you fill them you may be a marginally over or under 1g, but it won’t be by much. With enough powder, most machines can fill 100 capsules per time – which would be 33 days (~1 month) supply.

– Testing
There are two main types of tests companies will do. The first is third party testing on the purity of their NMN. The second is contaminant testing, for things such as heavy metals. It’s a positive indicator if they can provide both.

What does David think of Nicotinamide Riboside (NR)?

Nicotinamide Riboside is a precursor to NAD, similar to NMN. David states in his book that his lab finds:

• NMN a more stable molecule than NR
• NMN is able to do some things in mice studies that NR can’t

That being said, he isn’t against NR, he’s just more optimistic on NMN being the better molecule for raising NAD in the long run. He notes in a blog post on NMN & NR that:

• The science is further along for NR, but it’s too early to say which is better for humans.

Where to buy NR?

The brand leader in sales of Nicotinamide Riboside is Chromadex’s Niagen (pictured above). Amongst Chromadex’s scientific advisors is Charles Brenner, who first discovered NR, and showed it could extend the life of yeast cells.

Niagen’s recommended serving size is 300mg (1 capsule) – which may be less efficient at raising NAD levels than 1g of NMN.

If we compare NR & NMN at a price per gram, they’re more similar than I expected. Niagen works out approximately $5.22/gram, and NMN is around $5-$6/gram depending on brand.

NR & NMN Storage

In David’s recent interview with Rhonda Patrick, he discussed details around storage, saying:

• NR and NMN need to be kept cold (fridge or freezer) because they don’t have a long shelf life.
• If they are kept on a shelf, and are not in a stabilized form, they can degrade into nicotinamide. This is sub-optimal because Nicotinamide can have the opposite of the desired effect, and actually inhibit the sirtuins¹². He didn’t elaborate further on what a “stabilized form” means in this context, which would be interesting to know.
• If NMN gets wet, or gets a bit of humidity in the bottle, its only a short time before it’s degrading. This may be the case with NR too (because it applies to many supplements), but when David explained this he was explicitly talking about NMN.

Since David explained this I’ve come to learn that Nicotinamide Riboside, when it its chloride form; Nicotinamide Riboside Chloride (as sold by Niagen), is in a stabilized form. This means that it doesn’t need to be kept cold to have an adequate shelf life. More on that below…

NMN/NR & Methyl Group Depletion?

There has been some concern in the field that consuming NR or NMN could decrease the body’s methyl groups and lead to health problems. The dropdown section below looks in detail at that issue.

In summary, current evidence for this issue is lacking, and as far as I can tell, David Sinclair is no longer taking any supplements to tackle potential methyl group depletion. However, if you wanted to be super careful, Dr Charles Brenner (an NAD researcher) mentions elevated homocysteine in the blood can be a sign of lower methyl status – so one could get a blood test to check that.

Metformin

Metformin is actually a relatively old drug, first discussed in medical literature in 1922, and studied in humans in the 1950s. It is derived from a plant called the French Lilac. It’s primary use in medicine is for the treatment of diabetes, thanks to its ability to decrease blood glucose levels in patients.

Because Metformin has been used for years, and has an established track record of safety, this makes it more attractive as a longevity drug. Molecules that are discovered today will need years of testing before they can even come close to rival the amount of data and “patient years” accumulated by metformin.

It’s thought the longevity benefits are at least in part derived from activation of the AMPK cellular pathway. This has a host of knock-on effects (visualized below), some of which are involved in beneficial processes like mediating inflammation and increasing autophagy (cellular cleanup).

AMPK pathway activation (image via this paper)

Metformin – Where to buy?

Metformin is a prescription drug, and thus needs to be acquired through a doctor’s prescription, at least in most countries. It isn’t (yet) considered a drug that can help improve healthspan or lifespan, and so you may need to find a forward thinking doctor if you want it prescribed for general health. Typically doctors only prescribe Metformin for blood sugar control issues (type 2 diabetes).

Metformin – How often to take?

Typically Metformin is taken daily – both by diabetics, and by people using it for healthspan extension. However, on the latest interview with Joe Rogan, they discussed a 2018 paper which showed metformin inhibits mitochondrial adaptations to aerobic exercise training. David explained that this makes sense, and it’s exactly metformin’s inhibition of mitochondrial function that leads to some of the health benefits. Specifically, they cause the cell to think it’s in a nutrient restricted state, and it turns on pathways typically reserved for times of scarcity. The function of these pathways is hypothesized to lead to better healthspan outcomes.

When not exercising, which is most days for David, he opts to take 0.5g of metformin in the morning and 0.5g  in the evening (for source, see 1:16:45 of his Ivy Lecture, which supersedes what he said in his book). Then on exercise days, he opts not to take it at all. For similar reasons he also skips resveratrol on exercise days (source: see last paragraph of section 1 – “Get Moving” on David’s blog post).

This is viable for David who exercises vigorously in the order of 1-2x per week, but for someone training often, this might be impractical. At which point it would come down to a decision whether the benefits of metformin/resveratrol outweigh the (potential) small impact on recovery.

Is Berberine a non-prescription alternative?

In a Reddit AMA (link) David was asked whether he would take Berberine if he didn’t have access to Metformin. He responds by saying he would likely take Berberine.

Berberine is interesting to many people because it has similar properties to metformin, but it doesn’t require a doctor’s prescription. In common with metformin, it has the ability to:

• Lower blood glucose, triglycerides and fasting insulin in patients with type 2 diabetes¹³
• Activate the AMPK pathway – which, among other things, increases cellular cleanup (autophagy)¹⁴

How to think (big picture) about the molecules David takes

We can attempt to summarize the function of the molecules David into 2 categories;

1) Molecules that emulate fasting
2) Molecules that help restore prior function.

Expand the box below to read more.

Vitamins David Takes

Whilst David generally tries to get all the vitamins and minerals he needs from his diet, he does still take some vitamins daily. Between his book, a podcast with Dave Asprey (from 19m 10s) and Twitter, he mentions taking:

• Vitamin D3 – says he takes at least 2,000IU per day
• Vitamin K2 – doesn’t mention dose. K2 can help facilitate healthy calcium transport, potentially reducing build-up in the arteries
• Omega-3 fish oil – taken daily in the evening
• Alpha Lipoic Acid – mentions taking the “S form”, but doesn’t mention dose. References it as another sirtuin activator
• Quercetin – mentions taking 500mg in the mornings – a plant polyphenol, with many benefits + can increase the half life of resveratrol
• Coenzyme Q10 – often taken by people taking statins (which David does) to reduce any side effects. It also plays a role in mitochondrial energy production

To read more about these supplements and why David takes them, click to expand the boxes below:

How David Tracks + Measures His Health

David uses a blood testing service called Inside Tracker to track his biomarkers. Helping him to understand what is, and isn’t working, in terms of his diet, exercise and supplementation. For example, he shared on Facebook (link) when his Inside Tracker results showed his vitamin B12 supplementation was causing his B12 levels to get too high. Resulting in him removing B12 from his supplements. This test was presumably InsideTracker’s Ultimate product – as it’s the only one that covers all the biomarkers he mentioned.

InsideTracker offer 5 types of products (!), which can be a bit confusing, so I’ll try to summarize them:

• Main product – blood tests – 2 options: Ultimate (which David uses) covering 43 biomarkers & Essentials covering 13 biomarkers.
• Their InnerAge test, which aims to use blood biomarkers to track your biological (rather than chronological) age.
• Their Blood Test Upload – allowing you to get your blood tested wherever you want (useful for non-Americans), and then upload the data for their analysis.
• Their Home Kit which is a fingerprick test that you post back to them, and it covers 7 biomarkers.
• Lastly, a DNA Kit (similar to 23andMe) – which gives you insights on your personal genetics.

It’s perhaps worth noting, if you heard David on Joe Rogan in June 2021 (link), he mentioned working on a product to track the epigenetic clock (based on the work of Steve Horvath). Whilst David is an adviser and investor to InsideTracker – none of their products, yet, track the epigenetic clock.

If you’re interested in trying out Inside Tracker, you can get 25% of your test with this discount code.

Left pic = 2009 (source), right pic = 2019 (source)

To Conclude…

• David is a longevity researcher who is certainly aging gracefully
• He doesn’t give medical advice and doesn’t sell or endorse any brands, however, he’s open to sharing what he does for himself
• We looked at what he does to stay youthful, and what supplements he takes. Covering:
• How resveratrol works and where to buy
• How NMN works and where to buy
• We discussed how Nicotinamide Riboside (NR) is an alternative to NMN
• How metformin works (noting that it’s prescription only)
• He began taking resveratrol around 2004, and added NMN & Metformin approximately 3 years ago
• Lastly, we looked at a simple way to categorically think about how these 3 molecules work

References for David’s Supplementation Info

References for where David has mentioned taking these various supplements are shared below:

• Resveratrol & NMN doses come via David’s recently released book; Lifespan, page 304
• For Metformin dosing, David mentions taking 0.5g in the morning and 0.5g at night in his Ivy Lecture, at 1:16:45
• Daily vitamin K2, D3 and aspirin all also mentioned in his book Lifespan, page 304
• David has discussed taking a statin in his 2019 Joe Rogan interview (link) + 2020 Dave Asprey interview (link).
• Mentions taking Coenzyme Q10, Alpha Lipoic Acid and Quercetin in his March 2020 interview with Dave Asprey (link). Supplement discussion begins at ~19m 10s
• Mentions on Twitter taking omega-3 fish oil daily (link)

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Any questions or comments, please leave them below.

If you liked this post, you may also find these interesting:

• For more discussion on lifestyle modifications (intermittent fasting, foods to eat, optimizing sleep) – see my post on Dr Rhonda Patrick’s Diet
• David Sinclair recently wrote an article on his blog around what his 80 year old father does to stay healthy
• David Sinclair also wrote an article on his blog comparing NR to NMN – which I also linked to above.
• For the supplements Stanford Neuroscientist Andrew Huberman takes, see Andrew Huberman Supplements List

1. An Antiinflammatory and Reactive Oxygen Species Suppressive Effects of an Extract of Polygonum Cuspidatum Containing Resveratrol – Dandona et al (2010)
2. Effects of Resveratrol on Memory Performance, Hippocampal Functional Connectivity, and Glucose Metabolism in Healthy Older Adults – Flöel et al. (2014)
3. Calorie Restriction-like Effects of 30 Days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans – Schrauwen et al. – Cell Metabolism Journal (2011)
4. Pilot Study of Resveratrol in Older Adults With Impaired Glucose Tolerance – Barzilai et al. (2012)
5. Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients – Wittmann et al. (2011)
6. Antihyperglycemic Effects of Short Term Resveratrol Supplementation in Type 2 Diabetic Patients – Netticadan et al. (2013)
7. The Effect of Resveratrol Supplementation on Cardio‐Metabolic Risk Factors in Patients with Type 2 Diabetes: A Randomized, Double‐Blind Controlled Trial – Mozaffari‐Khosravi et al. (2019)
8. Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: A randomized controlled trial – Mi et al – Digestive and Liver Disease journal (2015)
9. Resveratrol supplementation improves inflammatory biomarkers in patients with nonalcoholic fatty liver disease – Hekmatdoosta et al – 2014 – Nutrition Research Journal
10. Consumption of a grape extract supplement containing resveratrol decreases oxidized LDL and ApoB in patients undergoing primary prevention of cardiovascular disease: A triple‐blind, 6‐month follow‐up, placebo‐controlled, randomized trial – Espín et al – 2012 – Molecular Nutrition & Food Research Journal
11. One-Year Consumption of a Grape Nutraceutical Containing Resveratrol Improves the Inflammatory and Fibrinolytic Status of Patients in Primary Prevention of Cardiovascular Disease – Espín et al – 2012 – The American Journal of Cardiology
12. Inhibition of Silencing and Accelerated Aging by Nicotinamide, a Putative Negative Regulator of Yeast Sir2 and Human SIRT1 – Bitterman et al (2002)
13. Efficacy of Berberine in Patients with Type 2 Diabetes – Ye et al. (2009)
14. Metformin and berberine, two versatile drugs in treatment of common metabolic diseases – Luo et al. (2018)
15. A ChIP-seq defined genome-wide map of vitamin D receptor binding: Associations with disease and evolution – Ramagopalan et al. (2010)
16. Vegetables and Mixed Dishes Are Top Contributors to Phylloquinone Intake in US Adults: Data from the 2011-2012 NHANES – Harshman et al. (2017)
17. Circulating uncarboxylated matrix Gla protein, a marker of vitamin K status, as a risk factor of cardiovascular disease – van den Heuvel et al. (2014)
18. The relationship between vitamin K and peripheral arterial disease – Vissers et al. (2016)
19. Lipoic acid: energy metabolism and redox regulation of transcription and cell signaling  – Packer et al. (2011)
20. Coenzyme Q10 and Statin-Induced Mitochondrial Dysfunction – Deichmann et al. (2010)
21. Design and synthesis of compounds that extend yeast replicative lifespan – Sinclair et al. (2006)
22. Sirtuin activators mimic caloric restriction and delay ageing in metazoans – Sinclair et al. (2004)