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:

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

David’s Diet:

  • Coffee in the morning (once per day), then green tea after that
  • Intermittent fasting – aims to skip at least 1 meal per day. Helped by lots of green tea
  • Keeps meat consumption low, and avoids red meat. Will eat meat on workout days
  • Eats as little sugar, bread or pasta as possible. Stopped eating deserts at age 40, except for a “small taste” occasionally
  • Aims to eat lots of vegetables

David’s Exercise routine:

  • Weight lifting – now 3 times per week, was previously just 1 time.
  • Running 1-2 times per week. Preferably using a curved treadmill for lower impact. Does short, fast runs.
  • Sauna weekly
  • He exercises in order to stay healthy and mentally sharp, rather than to be muscular

David’s Lifestyle Choices:

  • He doesn’t smoke, and avoids microwaved plastic, excessive sun exposure, X-rays, and CT scans
  • Aims to keep his BMI in the optimal range for healthspan, which for him he says is 23 to 25
  • Tries to stay “on the cool side” during the day, and at night when sleeping

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.

Searching Amazon for “micronized resveratrol” suddenly shrinks the options to just a few, including MegaResveratrol. However, I noticed something on the page for the Rich Roll interview with David Sinclair. He lists a micronized resveratrol by RevGenetics. This was interesting because during the interview Rich asks David where to get the supplements he takes, and David told him they’d talk about it after the podcast. Maybe RevGenetics was a brand that David mentioned post interview (possible), or perhaps it was just a brand Rich “plucked” from a Google search. Impossible to know without further info.

That said, I looked into RevGenetics a little more, and they certainly seem legitimate, with a high rating on ShopperApproved. They focus on longevity molecules and have been selling resveratrol since 2006. They offer a micronized 98% trans-resveratrol that comes in powder form, and thus could be taken in the morning with yogurt, as David does. It’s named M98 Super Micronized Resveratrol.

If like me, you’re curious about the daily cost… at 1g/day it works out at $3/day ($75 per 25g tub). If you buy 2 or 3 tubs you get a discount, and it comes down to $67.50 per tub, so $2.70/day.

Note: Whichever source of trans-resveratrol you take, according to David, you will increase its bioavailability if you take it with a fat source. Taking it after a meal would work, or if you take it on an empty stomach like David, he mixes it with a small amount yogurt. But something like olive oil could also work.

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.

David has described his yogurt making process as so:

  • He takes a couple of Bravo yogurt starter culture sachets
  • Combines them with whole milk in a mason jar
  • Puts the jar in the oven over night on a low heat (~95F)
  • Next morning he takes it out, and it’s ready to be chilled and eaten

David has specifically mentioned Bravo as the brand of yogurt culture he uses, for example at 1:12:28 of his interview on the Ben Greenfield podcast. Proponents of Bravo yogurt tout it as having a very high amount of gut friendly bacteria, when compared to other similar products. Bravo seems like a fairly expensive product to me, however, once nice trick with yogurts is that you can make a new batch using a small amount from the old batch. Removing the need to use fresh starter sachets again 👌🏻

In terms of further details on the yogurt making process, I’ve summarized some of the key points below:

  • The core yogurt making process is combining yogurt bacteria with milk, and keeping the liquid at around 115°F for 5-10 hours (often overnight). During this period, the yogurt bacteria ferments the milk, turning the lactose sugars in the milk into lactic acid – causing it to thicken and change in taste.
  • A common step prior to this is to heat the milk to 180°F in order to sterilize both the milk and your storage container. David doesn’t mention this part, but it’s good practice in yogurt making to avoid unwanted bacteria multiplying later on.
  • After the milk has reached 180°F you can then cool it down to around 115°F (a milk thermometer makes this much easier; either analogue or digital), and then add your yogurt starter culture.
  • Next you want to store your yogurt mixture for 5-10 hours, keeping it at close to 115°F. David mentions leaving it in the oven, which is ok if your oven can maintain this temperature – worth checking yours to see if it can do so. You want to avoid the oven getting too hot, and then killing all the bacteria!
  • Alternatives to the oven are 1) Wrap your container in a blanket and place it in a warm part of your house. Whilst it won’t stay at 115°F all night, it should hopefully stay warm enough to ferment and turn into yogurt – it’s a very common method 2) Use a dedicated yogurt maker, or a slow cooker (both have thermostats to maintain the correct temperature).

This YouTube video gives a nice (but slow-paced) example of the homemade yogurt making process.

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.

Product Approx. price per gram 3rd Party Analysis Certificate?
Powders    
Double Wood (30g powder) $3.46/gram ($104 / 30g) - when using 20% off coupon code Yes (link) - via Micro Quality Labs dated Jan 2021
PureGen (15g powder) $4.93/gram ($74 / 15g) Yes (link) - via unspecified lab dated Sept 2020
RevGenetics (25g powder) $3.68/gram ($92 / 25g) Yes (link) - via MS Bioanalytical dated Jan 2021
Capsules    
Double Wood (125mg capsules) $5.20/gram ($39 / 7.5g) - when using 20% off coupon code Yes (link) - via Micro Quality Labs dated Jan 2021
Maac10 (250mg capsules) $5.33/gram ($40 / 7.5g) Yes (link) - via Micro Quality Labs dated July 2020
RevGenetics (500mg capsules) $3.66 ($110 / 30g) Yes (link) - via MS Bioanalytical dated Jan 2021

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…

Looking at the data online around stabilized NR, I found:

  • FDA document (link) mentioning the stability of Niagen up to 11 months in both normal and accelerated conditions. In both cases it maintained its NR chloride content well (98.8% under normal conditions and 92.1% under accelerated conditions). This document was published before they had completed testing beyond 11 months.
  • Then similarly a more recent “European Food Safety Authority” document discusses stability (link) of at least 36 months when stored under ambient conditions. Noting that the applicant (Chromadex) who make Niagen recommend it’s stored under refrigerated conditions with a shelf life of 36 months.

What I gather from that, is that NR in its chloride form is stabilized. But like most edible products, cooling it does slow down the degradation that occurs over time. However for most people, the product isn’t intended to sit on the shelf for a long time, and thus it will be consumed before the degradation becomes a problem.

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.

So methylation itself, which utilizes methyl groups (CH₃), is an essential process for a host of critical functions in the body, including regulation of gene expression and the removal of waste products.

Consuming Niacin derivatives (which includes NR and NMN) will require the body to use up methyl groups in order to later degrade and excrete them. There has been some discussion and concern that by increasing the amount of methylation the body needs to do (through supplementation of NR/NMN), we might deplete the body of methyl groups needed to carry out essential processes.

David discussed this in his podcast with Paul Saladino (see 44mins mark), acknowledging that Niacin derivates (including NR/NMN) require methylation for excretion, but asserting that at this stage the idea of methyl depletion is anecdotal, and not something that has been shown in any NR/NMN studies.

Initially (circa 2019) David mentioned taking a supplement called betaine, also known as trimethylglycine. Then he moved to taking a combination of methyl folate plus methyl B12. This was all “in an abundance of caution”, rather than due to any new research that backed up the risk of methyl depletion.

After taking the B12/Folate supplement for a few months, in February 2020 David got some blood tests done, and found his B12 levels were double the recommended maximum – so he stopped taking it (source: David’s Facebook post). He hasn’t mentioned replacing it with anything since.

As Dr Brenner points out below, monitoring homocysteine levels (via blood test) is a proxy for methylation issues.

Methyl groups are primarily derived from nutrients in the diet, including; methionine (amino acid), folate (vitamin B9), choline, betaine, riboflavin (vitamin B2), pyridoxine (vitamin B6) and cobalamin (vitamin B12). For foods rich in these, see the table below (source):

Methyl Type Sources
Choline Cauliflower, eggs, flax seeds, lentils, liver, peanuts, soybeans and wheat germ
Folate and folic acid Folate and folic acid
Methionine Dairy products, eggs, fish, meat, poultry and rice
Vitamin B2
(Riboflavin)
Cheese, eggs, meat and milk
Vitamin B6
(Pyridoxine)
Bananas, fish, grains, legumes, liver, meat, potatoes and poultry
Vitamin B12
(Cobalamin)
Eggs, fish, meat, poultry, dairy products

A further source to add to this discussion is the research done by Chromadex. They hold a patent on nicotinamide riboside production, and make Niagen. In a tweet thread by their chief scientific adviser Charles Brenner, he explains that Chromadex took the potential risk of NR depleting methyl groups seriously. To test this they performed a randomized double blind placebo controlled trial administering 100, 300, or 1,000 mg of NR over 56 days (study link). They used homocysteine levels as a proxy for methylation disturbance, and found no change to homocysteine in any of the dosage groups, including up to 1,000mg (see this image). If there was a shortage of methyl groups, they would have expected to homocysteine levels rise. It’s worth noting the study used NR, not NMN.

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

Berberine dosage in treating diabetes is not entirely dissimilar to Metformin. For example in this study, the patients took 500mg of Berberine 3x per day. Then in this study they took 850mg of Metformin 3x per day. We know with David he takes 500mg of Metformin 2x per day.

Both compounds can induce gastrointestinal distress, so it’s common to start off on lower dosages, and gradually increase to the desired amount. This gives the gut a chance to adapt, and allows the user to back off the dosage if gastrointestinal distress is reached.

Optimal dosage for treating diabetes can be figured out based on testing the effects on fasting and post-meal blood glucose. However, there isn’t yet research on optimal dosage for someone with already healthy blood glucose levels. Using these products for healthspan and lifespan benefits is new territory and needs further research.

Brands & Type?

One benefit of Metformin being a prescription drug is that the manufacturing process is tightly scruitinized. Over the counter supplements aren’t regulated to the same extent, and as such, it makes sense to go with a reputable brand.

In the studies mentioned above they use Berberine HCl (hydrochloride), which is commonly extracted from the Berberis Aristata plant.

Examples of generally reputable brands include:

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.

1) Molecules that emulate fasting

Both resveratrol and metformin can be described as molecules that trigger cells to exhibit characteristics similar to when fasting. Metformin activates AMP-Kinase, Resveratrol activates SIRT1 and AMP-Kinase.

Why is this beneficial?

Cells have evolved to operate in 2 main states; fed and unfed. In times of plenty, they will grow and multiply, and in times of scarcity, they will hunker down and focus on maintenance. Part of maintenance includes things like:

  • DNA repair
  • Removing and re-using non-functioning or superfluous cellular contents (autophagy)
  • Removing toxins

These are all important tasks, and it’s possible that when we exist in a constantly fed state, they don’t get performed as often as may be optimal.

Thus when David takes resveratrol and metformin, and undertakes intermittent fasting, he’s allowing for these fasting dependent processes to take place.

There may be other things going on too – but this is a big chunk of what’s happening.

2) Molecules that restore prior function

Whilst metformin and resveratrol are primarily aimed at preserving existing function, we have NMN which is taken to boost our NAD back to youthful levels.

Fasting can actually boost NAD levels too, but the intention is that using NAD precursors like NMN raises NAD higher and for longer than can be achieved otherwise.

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:

On page 304 of his David’s book ‘Lifespan’, he mentions taking vitamin D3 daily.

Vitamin D is an essential micronutrient, and is thought to exercise significant effect on at least 200 of our genes15. It’s relatively scarce in foods, and so we rely on sunlight for producing adequate quantities. If you’re not getting much sunlight, then it can be necessary to supplement.

Whilst David doesn’t mention in the book what brand he uses, or how much he takes, he mentions in the podcast with Dave Asprey (link) that he takes at least 2,000iu per day.

Examples of reliable brands for vitamin D3 include Thorne D-1000 and Pure Encapsulations D3 1,000IU

David mentions taking Vitamin K2 daily on page 304 of his book ‘Lifespan’.

Vitamin K is an essential micronutrient that’s plays a crucial role in the ability to form blood clots, and to transport calcium around the body. It comes in 2 different forms, vitamin K1 (phylloquinone) and K2 (menaquinone). Vitamin K1 is the most abundant in a western diet, primarily found in leafy green vegetables. Vitamin K2 on the other hand is found in fermented foods, which are less common in a western diet. A source that’s particularly high in K2 are fermented soya beans, also known as “natto” in Japan.

Unfortunately, many people are low in vitamin K1, and therefore may have inadequate levels of K1 to support adequate calcium transport. The NHANES 2011-2012 study found only 57% of men and 37.5% of women (N = 4,306) met the “adequate intake” of K116. This could lead to increased cardiovascular risk as a result17, although more research needed.

So where does the vitamin K2 supplementation come in?

Whilst vitamin K1 is prioritized for use in the liver, vitamin K2 appears to be prioritized for use in the periphery, which will support calcium transport18.

Examples of reliable brands for vitamin K2 include NOW K2 MK4 – 100mcg and Thorne – 3-K Complete

David mentions on Twitter (link) taking his daily Omega 3-6-9. He notes that he especially likes Nordic Naturals ProEFA product for its SIRT1-activating omega-9 oleic acid.

ProEFA comes in 2 forms:

Whilst David didn’t mention which form he takes it in, the composition of the oil is the same for both. However, the daily serving of the soft gels (2) is half that of the daily serving of the liquid (5 mL teaspoon). So to get the equivalent dose in soft gels, you’d need to take 4.

In his podcast interview with Dave Asprey (link), David mentions taking alpha lipoic acid. Not to be confused alpha linoleic acid – which is a source of omega-3 fatty acids, often found in seeds. Alpha lipoic acid is found naturally in certain food, and when digested, is used in the cells as a cofactor in mitochondrial energy metabolism19.

At 37m 20s of the podcast, David shares an anecdote about an early pioneer in the field of aging called Denham Harman. Denham managed to keep working into his 90s, dying at the respectable age of 98. When David visited his family, they let him into a secret – Denham had been taking alpha lipoic acid for most of his life, primarily thinking it was an antioxidant. To which David suggests, at the least, it probably wasn’t causing Denham any harm.

He goes on to say that he takes it daily, and uses the S form, rather than the R form; R-Lipoic Acid. He didn’t however mention the dose that he takes.

Examples of generally reliable brands for alpha lipoic acid are Thorne – Alpha Lipoic Acid (300mg) and Pure Encapsulations – Alpha Lipoic Acid (400mg)

Also in the podcast with Dave Asprey (link), David says that he takes Coenzyme Q10 because he’s taking a statin. He doesn’t elaborate any further on specifics of why he takes Coenzyme Q10, but he’s potentially referring research that suggests statins can reduce Coenzyme Q10 levels in blood20.

He doesn’t mention a specific dose, but just says that he takes 1 large pill daily. Coenzyme Q10 supplements are commonly in the range of 100 to 200mg per capsule.

It’s quite likely that David didn’t talk about Coenzyme Q10 in his book because it’s specific to him and his use of a statin. Which he takes due to a family history of cardiovascular disease.

Examples of reliable brands for Coenzyme Q10 include:

David mentions taking quercetin as recently as July 2021 (link to clip from Modern Wisdom podcast).

He mentions on Twitter (link) that he takes 500mg daily of quercetin.

Examples of generally reliable brands for quercetin include:

As of July 2021, David mentioned he’s experimenting with Fisetin (link to clip from Modern Wisdom podcast). He mentions that his lab showed fisetin extends the lifespan in mice and worms2122, plus recent research shows it has senolytic capabilities. Senolytic molecules have the ability to kill off senescent cells.

Unfortunately he doesn’t mention what dose he’s taking.

The (in-progress) human trial I’m aware of – Mayo Clinic trial NCT04313634 – has subjects taking fisetin 3 days per month. Using a high dose of 20mg per kg (2.2lbs) of body weight. That would equate to over 1 gram per day for most participants.

With the idea to use it intermittently to reduce senescent cell burden. Unlike with resveratrol or quercetin, which tend to be supplemented daily.

In David’s August 2021 Instagram post (link) he mentions taking resveratrol, quercetin and fisetin mixed in to some cottage cheese (fat source).

Fisetin is typically sold in capsules, which could be cracked open and emptied into food if desired. Examples of brands include:

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

Sources for David’s Supplementation

Sources 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)

—-

Currently research in humans is further ahead with NR than NMN. To date, there have been just 2 human NMN studies, which I list below + some of the more interesting NR studies:

Nicotinamide Mononucleotide (NMN) studies:

  • 2021 (June) – A Japanese study (still in pre-print) by Yamauchi et al. showed that 250mg of NMN daily in 65+year old men raised their NAD levels and improved their muscle strength. They measured strength via a 30-second chair stand test, walking speed, and grip strength measurements. One group took it for 6 weeks (n=21) and another for 12 weeks (n=10). They didn’t find any safety concerns or negative health biomarkers. It was a placebo-controlled, randomized, double blind, parallel-group trial. Study link.
  • 2019 (November) – A Japanese study into the safety of oral NMN showed no negative changes to blood biomarkers and other health measurements after doses of NMN at 100, 250, and 500. Study link.

Nicotinamide Riboside (NR) studies:

  • 2019 (August), a 12 person study, taking 1g/day nicotinamide riboside. Showed elevated NAD+ metabolome in skeletal muscle, which I take to mean there was greater metabolic function, which they evidenced by greater NAD and nicotinamide clearance products (need to look into what this means in more detail!). Also showed a reduced level of circulating inflammatory cytokines. This was a placebo controlled, randomized, double blind crossover trial – study link
  • 2019, 32 person study in ALS patients, taking what they called EH301. EH301 is another name for Elysium’s supplement; Basis. 2 capules (1 dose) contains 250mg Nicotinamide Riboside and 50mg Pterostilbene. Participants took 4 capules, twice daily, for a total of 1,000mg NR and 200mg Pterostilbene. The results showed disease modifying benefits for ALS patients – study link
  • 2017, An 8 person, non randomized, open label trial in healthy volunteers. Dose = titrated up to 1,00mg on day 9. No adverse effects. NAD+ was 2x baseline on day 9. – study link
  • 2016, 1 person study, showed that NR raises NAD+ by as much as 2.7x in human blood with a single oral dose of 1000 mg – study link

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

See Post Sources Below:

  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)

Posted by John Alexander

Hi, I'm John, a researcher and writer.

With a keen interest in health and longevity.

Note: not an MD or PhD.

Hope you enjoy the site. If you've suggestions for content you'd like to see - let me know.

Subscribe
Notify of
guest
234 Comments
Inline Feedbacks
View all comments
Bob
Bob
1 year ago

John, fantastic job on rounding up all this information. Sinclair did an interview with Paul Saladino (Fundamental Health podcast) on Nov 4, 2019. Saladino brought up a concern about losing methyl groups from taking Nicotinamide and other niacin derivatives.(about 43:00) and Sinclair says (45:10) “It’s anecdotal right now, but to me it makes sense and in an abundance of caution I’m making sure I have enough methyls in my diet. And you can get them in variety of ways: there’s betaine, which is also know as TMG (trimethylglycine)”…and (45:40) “ What I’ve shifted to do now is, I take a… Read more »

Bob
Bob
Reply to  John Alexander
1 year ago

Thanks so much John.
This very helpful. I really appreciate your putting the energy and insight into this…so helpful! Nice to have a forum where new information can be gathered and analyzed.

Vladimir
Vladimir
1 year ago

Beautiful post, report, analysis, article. Superb.

Unfortunately living in (far) Brazil delivery time would probably degrade NMN or non-chloride NR. As I would be also interested in delaying my wife’s near menopause, and there are some benefits that apparently occur only using NMN, not NR, it remains a mistery (do you agree?) if NR would also improve my wife’s womb health, as apparently NMN improves. (This is debated at Lifespan, around page 140). Maybe only NMN activates specifically this possible benefit.

Anyway: truly beautiful work you built here. Amazing.

Jack
Jack
1 year ago

Have you checked out the products at Toniiq? Prices for NMN and Resveratrol are much more affordable. They also do show the 3rd party testing but without showing the name of the lab.

However, I’m a bit concerned as it seems too good to be true. How do you check to ensure that supplement providers are legit?

Jung
Jung
1 year ago

Putting all these together must’ve been a considerable effort! I can’t thank you enough for doing so!

Jeff
Jeff
1 year ago

Great Article! Thanks. Does it say how much Metformin he takes/his dad?

Phil
Phil
1 year ago

Sent an email to Tru Niagen about the stability of their product and got a detailed email addressing Dr.Sinclair’s concern. In short, their product is stabilized and has a longer shelf life. “Thanks for your email and interest in TRU NIAGEN®. Please note that in the interview, David Sinclair describes both NR and NMN “not in a stabilized form”. Since the active ingredient in TRU NIAGEN®, nicotinamide riboside, is stabilized as nicotinamide riboside chloride (NRCl), refrigeration is not required, and Sinclair’s comments are not relevant. TRU NIAGEN® is formulated with a crystalline form of nicotinamide riboside chloride. This crystalline form… Read more »

Jay
Jay
1 year ago

David Sinclair on the Ben greenfield podcast interview said that he uses the Bravo yogurt kit and mixes with coconut milk.

Melanie
Melanie
1 year ago

“The reason that resveratrol won’t work effectively without NMN, is that sirtuin activation requires youthful NAD levels, but by 50 years old (..)”

If your NAD levels are still high when you’re younger.. form what age onwards does it make sense to start taking NMN?

Im thinking of starting taking resveratrol.. but from what age onwards do you really need to start taking NMN in order for resveratrol to still work?

Probably a question that doesnt have an exact answer, but it would be cool if some one with a but more knowledge than i do, could comment on this..

Aaron Burnett
Aaron Burnett
1 year ago

Hi John, do you have more info on taking NMN with fat? I’ve listened to several David Sinclair podcasts and he seems to make the distinction that Resveratrol needs fat for absorption but not NMN. I’ve seen this in several other places as well. That one twitter reference is the only thing I’ve seen/heard of him saying NMN needs fat. If I recall correctly in their test mice were given NMN in their water. Anecdotally, I’ve used ABNs sublingual and really noticed a difference when taken in small doses throughout the day. But I haven’t tried taking it with fat,… Read more »

Glen
Glen
1 year ago

Should NMN and/or Resveratrol be taken when fasting. I’m talking about a true 48 or 72 hour fast, rather than intermittent fasting of skipping 1 or 2 meals a day. Or should I skip taking either during the days I’m fasting?

Glen
Glen
Reply to  John Alexander
1 year ago

Thanks John. I just started taking NMN and Resveratrol. Unfortunately, I started it the same time I also did a 72 hour fast. I think it makes sense to cycle off NMN and resveratrol during prolonged fasts as I felt that I had less energy than in the past when I did 48 and 72 hour fasts alone w/o taking any other supplements. I’m currently doing a 48 hour fast and have not taken NMN and resveratrol and feel more energetic overall. Moving forward, I think I’m going to take these supplements only when I’m actually eating. I currently take… Read more »

SK
SK
1 year ago

But how can the average person get Metformin? It is prescription only.

Anders
Anders
Reply to  SK
1 year ago

In Europe at least you can get an online prescription for Metformin. Then you don’t need a doctor and can buy it from certain online pharmacies.

Seamus O'Loughlin
Seamus O'Loughlin
Reply to  SK
7 months ago

Thanks for the interesting discussion. I’m from Ireland and take a daily longevity tincture prepared by my Herbalist consisting of Goat’s Rue the natural source of Metformin, Japanese Knot-weed the natural source of Resveratrol, Willow Bark the natural source of Aspirin and St John’s Worth for Liver Cleansing and Mental Health. Natural sources of these molecules are readily available in nature without the nauseating side effects. I also take Organic Turmeric, Vit D, Ginseng and await my first order of NMN. My friend is involved in Bio-Medical Research and has a supply of Rapamycin that I’m pondering about, thinking of… Read more »

SC
SC
1 year ago

Really good job summarizing all this info, much appreciated.

Brooks Jordan
Brooks Jordan
1 year ago

Yes, great post, John, bringing many of the details together about these three supplements and David’s research on and use of them.

Big help, thank you.

Greg Brewer
Greg Brewer
1 year ago

What about the NAD+ IV regimen?

Michael
Michael
Reply to  John Alexander
1 year ago

I believe on the Joe Rogan podcast Sinclair mentioned that IV NAD+ may have a difficult time getting into the cell due to its size. However, NMN can easily get into the cell and then get converted to NAD+

laura
laura
1 year ago

thank you! Great post, you saved me a lot of time on research.

1 2 3 7