David recently garnered attention with his appearances on the Rhonda Patrick and Joe Rogan podcasts. Using his moment in the spotlight to raise awareness for life extension research.
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?
One thing David is fast to point out is that he’s a scientist – not a medical doctor, and doesn’t give health recommendations. Respecting that, this post will only look at what David does, noting that he isn’t recommending others do the same. David does not sell or endorse any brands – so the discussion below on “where to buy” will simply look at options.
David Sinclair Takes:
- Resveratrol – 1g/daily – mornings with yogurt (see where to buy)
- NMN – 1g/daily – mornings (see where to buy)
- Metformin (prescription drug) – 1g/daily – 0.5g in the morning & 0.5g at night – except on days when exercising
- Vitamins? Aims to get majority from diet, but does supplement a few including vitamin D & K2 – see this section
- Statin (prescription drug) – taken since his early 20s due to family history of cardiovascular disease
- Aspirin – 83mg daily
For a complete list of sources for the above, see this section.
What do Resveratrol & NMN do in relation to living longer?
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 – such as DNA repair.
He describes resveratrol as the “accelerator pedal” for the sirtuin genes (increasing their activation), and NMN as the fuel. Without “fuel”, resveratrol won’t work. The reason that resveratrol won’t work effectively without NMN, is that sirtuin activation requires youthful NAD levels, but by 50 years old, 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).
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.
What else is David doing to stay healthy?
- Intermittent fasting – skipping breakfast and/or lunch where possible. Helped by lots of green tea
- Running 1-2x/week low impact and high intensity (using a curved treadmill such as Woodway)
- Weight lifting (ideally!) 1-2x/week
- Sauna weekly
- Coffee in the morning (once per day), then green tea after that
Below we’ll dig deeper into the 3 longevity supplements David takes; NMN, Resveratrol & Metformin.
Table of Contents
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 time ago around red wine being healthy, part of that came because it contains tiny amounts of resveratrol. Unfortunately all foods sources contain tiny amounts, so we need to take it in a concentrated supplement form for it to be useful.
There’s actually a fair amount of controversy around the potential benefits of resveratrol. For example this 2019 literature review is quite critical of the health claims:
Whereas this paper (admittedly co-authored by David Sinclair), points to benefits:
In that paper they hypothesize that resveratrol acts a “caloric restriction memetic”, which activates beneficial cellular pathways.
Given that there are scientists much smarter than me on both sides of the fence, I find it hard to draw a conclusion. But certainly it’s interesting that a scientist like David has taken it since 2003 – and continues to do so to this day.
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, ensure to mix it with a fat source (such as yogurt or olive oil) in order to maximize bioavailability.
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
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 we age, the amount of NAD our cells produce declines, and less NAD = reduced cellular function. According to David, at 50, you have about half as much NAD as at age 20.
The hope 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.
NMN – Where to buy?
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) | $3.83/gram ($115 / 30g) – when using $15 off coupon code | Yes (link) – via Micro Quality Labs dated Jan 2021 |
| PureGen (15g powder) | $4.60/gram ($69 / 15g) | Yes (link) – via unspecified lab dated Sept 2020 |
| RevGenetics Advanced NMN (25g powder) | $15.8/gram ($395 / 25g) | Yes (link) – via Intertek dated Jan 2018 |
| Capsules | ||
| Double Wood (125mg capsules) |
$5.86/gram ($44 / 7.5g) – when using $5 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 |
| Infinite Age (250mg capsules) | $6.66 ($50 / 7.5g) | Yes (link) – via Colmaric Analyticals dated Dec 2020 |
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. Emulating 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.
NR – Where to buy?
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 sirtuins1. 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. This section will discuss 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 David mentioned taking a supplement called betaine (also known as trimethylglycine), and then he moved to taking a combination of methyl folate plus methyl B12. He didn’t cite a particular brand, but examples include Jarrow Methyl B-12/Methyl Folate & Pure Encapsulations – B12 Folate. 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, 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). I haven’t seen him mention since if he’s taking any supplements in relationship to methyl groups.
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.
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)
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 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.
Other Supplements David Takes
Whilst David generally tries to get all the vitamins and minerals he needs from his diet, he does still take some supplements daily. Specifically he’s discussed taking:
- Vitamin D3
- Vitamin K2
- Alpha Lipoic Acid
- Coenzyme Q10
He uses testing from Inside Tracker (which he’s an investor in), to gauge where he may need to add or reduce supplementation.
To read more about these supplements and why David takes them, click to expand the boxes below:
Vitamin D3
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 genes2. 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
Vitamin K2
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 K13. This could lead to increased cardiovascular risk as a result4, 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 transport5.
Examples of reliable brands for vitamin K2 include NOW K2 MK4 – 100mcg and Thorne – 3-K Complete
Alpha Lipoic Acid
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 metabolism6.
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)
Coenzyme Q10
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 blood7.
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 Thorne – Coenzyme Q10 100mg and Pure Encapsulations – CoQ10 120mg
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 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).
- Mention of taking Coenzyme Q10 and Alpha Lipoic Acid in his March 2020 interview with Dave Asprey (link). Supplement discussion begins at ~19m 10s
—-
Currently research is further ahead with nicotinamide riboside than nicotinamde mononucleotide. NMN has only been tested in animals so far, but human studies are in progress currently. I’ve listed some of the more interesting nicotinamide riboside studies below:
Nicotinamide Riboside
- 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 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.
- Dr Peter Attia recently wrote a post on metformin and how it appears to blunt (positive and desirable) muscle and mitochondrial adaptations to exercise – raising questions on whether super healthy people want to be taking metformin if they’re exercising regularly
See Post Sources Below:
- Inhibition of Silencing and Accelerated Aging by Nicotinamide, a Putative Negative Regulator of Yeast Sir2 and Human SIRT1 – Bitterman et al (2002)
- A ChIP-seq defined genome-wide map of vitamin D receptor binding: Associations with disease and evolution – Ramagopalan et al. (2010)
- Vegetables and Mixed Dishes Are Top Contributors to Phylloquinone Intake in US Adults: Data from the 2011-2012 NHANES – Harshman et al. (2017)
- Circulating uncarboxylated matrix Gla protein, a marker of vitamin K status, as a risk factor of cardiovascular disease – van den Heuvel et al. (2014)
- The relationship between vitamin K and peripheral arterial disease – Vissers et al. (2016)
- Lipoic acid: energy metabolism and redox regulation of transcription and cell signaling – Packer et al. (2011)
- Coenzyme Q10 and Statin-Induced Mitochondrial Dysfunction – Deichmann et al. (2010)
I just wanted to thank the author for the incredible amount of work that was put into this document. Its not easy to watch all the interviews and books to summarize all these information. Keep up the awesome job and thank you very much for your work!
Thanks for your kind words! Suggestions for improvement always welcome 🙂
So on days when exercising Sinclair does not take Metformin & Resveratrol. So does he take his NMN alone.
Yes, that fits with my understanding, David only limits Metformin and Resveratrol on exercise days – he doesn’t stop taking NMN.
Hi In your post at one point you mention that David takes Metformin twice a day when not exercising on that day, and then later in the post you mention that David opts to take Metformin only at night before bed so that it’s processed by morning and that he takes such nightly doses on days with no exercise. So which is it. I read or heard that he takes two daily doses, but later in your post you make it sound like he only takes one dose at night. Please can you clarify this for me along with the… Read more »
Hi, thanks for spotting the discrepancy, I’ve now amended it.
Previously David was taking Metformin only at night, but in his Ivy Lecture (at 1:16:45) he mentioned his latest protocol was taking 0.5g in the morning at 0.5g at night.
I had updated the reference in one section of the post, but not in the other!
Thank you for Clarifying.
Any idea when he switched. Personal preference?
I wondered if he is just exercising less so he feels fine doing it morning and night.
And that he took it before only at night so that he could combine it more often with exercise in the first half of the day.
Love your summary and post. Quite useful as I was in the process of doing the same for myself, but it helps to see others come to similar conclusions.
Thanks for the kind words!
I don’t believe David has clarified on why he split the dose into morning and evening. For me to comment on that would just be speculation.
He take it in the morning and at night simply because Metformin stay active for 12 hours.
Thanks for posting this summary, I would concur that it’s smart to build up to 1 gram doses of nmn/trans-resveratrol. I began at full doses and my left arm had a variety of numb/tingling/ pain issues that subsided. With nmn I take about half oral and half sublingual in one or two doses a day. I am a coffee drinker daily but require much less and often forget to make it which is significant. I have tried a few sources so far (powders and enyeric,) and would add a guy man out of CT under brand Mega Resveratrol who also… Read more »
Thanks for sharing your experiences James. Makes sense about light and moisture being the main risks to stability.
Wow. Enjoying the information. I will now become attentive as I wish to know which supplements are safe and can hopefully slow aging.
I have read in a few sources that large doses of Resveratrol block estrogen production and boost testosterone. This might bring the menopause symptoms quite earlier than expected.
Shall there be a modification in doses for females?
Hi Larisa – that’s interesting, and as you say, wouldn’t be good. Do you have the sources where you read that? Can take a look.
If there any difference in effectiveness between taking NMN powder dissolved in a glass of water, vs capsule form? I have the powder NMN, but is hesitant to take the sublingual route.
thanks
To my knowledge, whether it’s taken in capsules, or as a powder with water, both should achieve the same results. With regards to sublingual, David explicitly wrote a blog post saying he doesn’t go the sublingual route (and one can presume he has put some thought in to the decision).
I think he’s mentioned before that one should work up to the 1mg of NMN and 1mg resveratrol, what would he recommend as a starting point?
Hi Graca. Yes, that makes a lot of sense. Especially given that, for example with resveratrol, 1g/day is a higher than the dosage often used in clinical trials.
I don’t suppose you remember where David talked about this? Would like to add the contents to the post – and a reference would help.
I have Gilbert syndrome and I’m a little concerned about taking NMN in such a dose because it will increase bilirubin which I have already elevated. What do you think about it?
Hi Mauro. This is the type of specialist question to take up with your doctor who can advise you specifically, based upon an understanding of Gilbert syndrome, your medical history, and NMN.
Thank you for this very well put together summary of the most important takeaways of the „Lifespan“ book, for a normal person like me who is not a scientist. I have the book and listened to the Audio-Book when exercising. I am still doing my personal research, listening to Dr. David Sinclair’s talks all over the Internet and reading very helpful articles like yours here, before I take a decision about taking metformin, Resveratrol and NMN. However, I am intrigued about the before/after pic of Dr. David Sinclair. During his recent talks I noticed that his forefront does not move… Read more »
Hi Nadine. With regards to David and potential use of botox, whilst it’s possible, I don’t have any special insights into that area. One aspect that sticks out to me is David’s lack of grey hair at 52 years of age. It could simply be good genetics, or there could be something more to it. David has previously mentioned that his brother didn’t take the same supplements, and didn’t look so young. He joked that he was the “control” (referring to control groups in scientific experiments). It would be interesting to see the two side-by-side, but I’m not aware of… Read more »
Hi John,
Thank you for the post. It sure is a time saver!
I just received NMN in loose form from Double Wood. When I was putting it in capsules I noticed that it’s clumpy with many clumps. I was wondering if that’s normal. I am worried that NMN was exposed to moisture and got bad. Do you have any experience with loose form of NMN?
Thank you,
Helena
Hi Helena.
I previously bought NMN from multiple different vendors to compare – including Double Wood.
The good news was that it all looked the same – a bright white “fluffy” powder.
Due to the fluffy nature of the powder, some clumping can take place. But they’re not “hard” clumps.
Without seeing what you’re describing, it’s hard to say much more.
I’d run a picture past their support and see if there’s an issue.
Do I need to put the powder into capsules – why not take the powder directly?
Hi. So as you know, this post is about what David Sinclair does, and he has previously said he puts the NMN into capsules.
Presumably this decision of his pertains to preference and ease of use. I haven’t seen any literature that suggests that capsules are essential to NMN use. David would have said specifically, I imagine, if he was using enteric coated capsules, so I assume he is not.
Enteric capsules will prevent the contents from the stomach acid, such that the contents gets absorbed after the stomach – typically in the upper tract of the intestine.
Dr. Sinclair’s book Lifespan never mentions DHEA. I’ve been taking 25mg for years. Why didn’t he discuss DHEA?
Hi Thomas. Presumably he doesn’t mention it because he doesn’t take it?
What do you take it for, and what evidence base did you use to make the decision to start taking it?
Cultures for Health sell several yogurt cultures from Bulgaria and Finland and elsewhere that are mesophilic, meaning they thrive at room temperature. This means no warm oven or yogurt maker required.
You can put the culture and milk (I use half and half for a thicker yogurt) in a mason jar, cover the top using the ring only, with a coffee filter held by a rubber band and put on your chest of drawers.
Within 12 to 18 hours you will have a very mild, non-acidic yogurt.
Hello John,
I am little confused on resveratrol and exercise issue. I recently read Dr Sinclair stating he does not take resveratrol on days he exercises. Based on what I have read from him, it seems he only does exercise once a week. I however love to run, running 6 days a week. What can you comment on this issue.
Great website, Robert
Hi Robert, it’s a good question. It reminds me a little bit of a discussion had between Rhonda Patrick and Kevin Rose in regards to metformin. This was after studies showed metformin inhibited some benefits of exercise. Her general take was that the benefits of moderate exercise are plentiful, whereas the use of metformin, in already healthy individuals, is not yet clear. Of course, metformin is not resveratrol. With regards to resveratrol, there’s a 2013 study (link) by Danish researchers looking at what happens when you combine exercise and resveratrol. They found that reserveratrol blunted the positive effects on cardiovascular… Read more »
The study noted by John was for high intensity interval training (HIIT) and might logically also apply to strength training. I combine HIIT and strength training 4 days a week and take Resv on the 3 non-workout days. Resv has a 1-5 hour half-life so I’m making an educated guess that will not blunt my workout on the next day. I limit my activity on these non-workout days to walking or anything that keeps me below a zone 3 heart rate to avoid the negative effects of over training. Robert – perhaps you could limit your hard running days to… Read more »
Amazing article! Thank you so much for putting it together! Have a quick questin, too. I’m 45, eat a low calorie, near-vegetarian diet. I don’t fast, technically, but I don’t normally eat between 8pm and 7-8am. I exercise at least 10-15 minutes per day 6 days a week. Would it still be beneficial for me to take NMN? Or would that be overdoing it? Thank you!
Hi Will. It sounds like you’re already doing a lot of the right things. Unfortunately until there are human trials with NMN showing it’s effect on biomarkers associated with health and longevity, I don’t think it’s possible for anyone to answer that.
Hi John,
Thanxs for your great work!!
I was just wondering, though David mentions at his book that the ideal BMI is around 23-5, isnt this difficult to balance with keeping low calorie diet? I appreciate if you could give me your thoughts.
Hi Kenta. I wouldn’t read too much into an “ideal BMI”, unless it’s backed up with references showing where the data was taken from, and what it optimizes for (lifespan/healthspan/etc).
Especially given the data on healthspan benefits associated with caloric restriction, both in animals, monkeys and humans.
Instead I believe what he’s probably suggesting is that going higher than these BMIs may be unhealthy. Whilst ideally there would be references (as I mentioned above). There’s a fairly well established body of evidence suggesting that excess adipose tissue (fat) is not healthy.
Thank you for pulling all this information together. Is’s sure saving me a lot time. Embarking on a project like this or discovery via trial and error is outright dangerous.
Hi John,
may I ask, why you did remove the proHealth NMN powder from the table?
Thanks
When I was updating the table, all the ProHealth products I’d linked to previously were resolving to dead URLs. At the time there must have been a reshuffle from their end in terms of products, and basically everything was out of stock. Next time I update it, I’ll check back and see what the situation is.
David Sinclair also takes alpha lipoid acid.
Hi Peter, thanks for the message. Where did he mention this? Thanks.
There is some discussion on the web, whether alpha lipoic acid does activate or inhibit autophagy (e.g. https://www.youtube.com/watch?v=hKcVmP5ivMg) Personally, I think that David Sinclair wouldn’t take ALA if it inhibits autophagy. Unfortunately, the data on this doesn’t seem to be clear. Any thoughts or comments about this?
Thanks.
Markus
Hi Markus, it’s a good question. I haven’t actually had a chance to dive into the research on that subject, so can’t suggest one way or the other.
https://youtu.be/hKcVmP5ivMg
With the FDA taking Metformin of the market for the time being, does David Sinclair still take it..?
Hi Emmo. Metformin has not been taken off the market. It’s used daily by millions of diabetic and pre-diabetic patients.
I think what you’re referring to is an FDA recall on a specific manufacturer’s (Bayshore Pharmaceuticals) “extended release” metformin, which was too high in a specific compound (N-nitrosodimethylamine).
This only affects 2 lots of their specific product, and doesn’t affect all the other metformin pills on the market. You can read more here.
John, I so appreciate this wonderful column. I have homozygous MTHFR (for 1298 or 677 – whichever the more critical one is – I can never remember) and APO-E4 allele. I appreciate your including the info on experimentation done to try to determine the danger of supplementing with NMN as regards methylation. You have helped me immensely! I am 65, and was set to participate in a brain study, but then the doctor broke her leg. I will proceed on my own to the best of my ability using your column alongside Dale Bredesen’s recommendations. Thank you so very much… Read more »
Thanks Debbie. In addition to the sources you mentioned, I found Rhonda Patrick’s paper on APOE4 and DHA interesting – link. I’m sure you’ve found them already, but generally speaking the APOE4 forums are interesting too.
Hi John,
Thank you so much for writing this!
I was just wondering whether there is data regarding a minimum recommended age to start taking NMN and Resveratrol as I’m currently 20 years old.
Hi Dana. I don’t have to hand where I saw David discuss this, but I remember him addressing this topic at least once on either Twitter, Reddit or his blog. If I come across the link again, I’ll try to share it here.
As you know, NMN decreases with age. However, right now you should be towards the peak of your natural NMN production still. I believe David’s suggestion was for young people to focus on other healthy lifestyle factors such as diet, exercise and sleep quality.
Have you heard about the assay kit to test for NAD levels: https://www.abcam.com/nadnadh-assay-kit-colorimetric-ab65348.html#:~:text=The%20levels%20of%20both%20NADt,by%20absorbance%20at%20450%20nm.
Would be great if you could test for NAD+ levels.
Agree Robert, it would be interesting to quantify NAD/NADH pre and post supplementation, to measure benefit. Would imagine it’ll become more accessible for consumers over time. The kit you link to is the kind of thing a lab would need in order to administer a test.
Hi, Question about dosage here. I recently bought a batch of Revgenetics’ Nitro Super Micronized Resveratrol capsules (with tween). They’re 250 mg each and they say the following about dosage: “Because of the estimated increased absorption that we fashioned after Sirtris resveratrol, we recommend only 1 capsule a day. The dose is powerful as it is equivalent to taking up to 10 capsules of regular resveratrol that you would buy anywhere else. The dosage is based on Albert Einsteins College Of Medicine Study Where People Took about 2 grams a day with positive results”. I was planning on taking two… Read more »
Hi Kate. David has said he’s taking 1,000mg (1 gram) of mirconized trans-resveratrol per day. I can’t comment on whether or not the product you mention can achieve comparable efficacy using less resveratrol, as I haven’t seen any research either way.
Dude, you wrote it yourself. It contains Tween 80 (polysorbate 80)! It’s a detergent which makes resveratrol water soluble. High levels of polysorbate 80 are harmful to your intestines. So, do not take 2 capsules. Moreover, resveratrol is a hormetic drug, so you shouldn’t aim for high doses. I would not even take 1 capsule of that product. If you wanna use it, use only 1 capsule daily on an empty stomach and away from any other supplements/medications.
Hi John, I have been intermittent fasting for about a year, not for weight loss, but for autophagy and ant-aging. I currently fast from dinner to late afternoon or dinner during weekdays and not on the weekends when I tend to do more physical morning exercise. I have just read David’s book and am wondering if it makes sense to reduce the daily doses David uses (1gm per day) for MNM and Resveratrol as i understand that frequent intermittent fasting produces a lot of the same benefits. Do you have a feeling for how much of the 1gm daily amounts… Read more »
Hi Matthew. I don’t think there’s a way to deduce that currently. In the future there may be more accessible ways to measure NMN, which would help in that regard.
Today, I was surprised to hear on the second Rich Roll interview (2/2020) that he eats yogurt and it seems he eats dairy. Has he a viable retort to the WFPB movement’s avoidance of same? Or ha just not got there yet? Does he know, and does he deal with Dr.s Greger, Barnard, Esselyton, Campbell and so on?
Thank you for a fabulous article!
Hi Gayle. My understanding with regards to David’s yogurt consumption, is that it’s limited to approximately 1 spoon per day with his resveratrol.
There’s a saying “the dose makes the poison”.
That said, the use of yogurt is to provide a fat source to increase the bioavailability of the resveratrol. And other fat sources can be used.
You don’t need a fat source for absorption of trans-resveratrol. See below. Food decreases the maximum concentration of trans-resveratrol in blood (Cmax) when compared to consumption on empty stomach, but the total absorption (AUC) is the same for both. See: https://pubmed.ncbi.nlm.nih.gov/19000554/ Here is another study that compares trans-resveratrol consumption with standard breakfast vs with high-fat breakfast. The high-fat breakfast decreased both Cmax and AUC. See: https://pubmed.ncbi.nlm.nih.gov/20528005/ So, don’t believe everything David Sinclair says. He also tells people nicotinamide riboside degrades at room temperature while he knows very well that the patented ingredient used in every product (nicotinamide riboside chloride) is… Read more »
Hi, thanks for sharing those studies.
Yes, as you say, the chloride version of Nicotinamide Riboside is a stabilized form. And it’s that form that Chromadex make and distribute.
Hey,
just read in YouTube comments, two users independently report that Sinclair has stopped taking methyl b folate because of unhealthy B12 levels:
user one: “David Sinclair recently just published some of his health results he had been taking methyl B folate with NMN and his B12 levels were twice what they should be so he said he was going to stop taking methyl B folate.”
another user: “Yes, I saw it too and also switched back to TMG.”
I asked for the source. Maybe someone else can help out.
Hi Florian. If you locate the section in the post “Methyl Group Depletion – Click to Expand” – I’ve covered that in there. Including a link to David’s Facebook post discussing why he made the change.
John, thanks for the in depth response. Since NR has had human clinical trials and NMN has not (to my knowledge) I wonder if there is any risk taking both (300 mg of NR and 1 gram of NMN per day) assuming the expense is not at issue (which it always is!)
Hi Robert. I don’t have any data around risk of combining NR & NMN. Without that, it would all be speculation on my part.
Thank you for writing these, I get so much in being able to take time to read through. Due to the cost of NMN is there still health benefit in your mind of at least starting Resveratrol by itself?
Resveratrol can certainly be used independently of an NAD+ booster like NMN.
You can use Vit B3 Niacin to get the same results, its a different pathway for creating increased NAD+ and a lot cheaper.
Hi Matthew. I can’t say I’ve seen the data to suggest that Niacin supplementation is comparable to NR/NMN for increasing NAD.
That being said, if you have data to suggests otherwise, please link to it.
Hi Matthew
I also consumed B3 Nicotinamide until I red the article on top of this blog about Inhibition of silencing and accelerated aging by Nicotinamide. Then I changed to NMN.
Regards Frank
Dear Frank. There’s a difference between Nicotinamide and Nicotinic Acid. According to that research paper these negative effects are related to Nicotinamide only.
Hi John
Has David mentioned Rapamycin for longevity. It does seem to be tried and tested:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/
Hi Robert. Thanks for the comment. Yes, David has been involved in research into rapamycin and its use in life extension for animal models. For example, he was a co-author on this paper showing it extended the lifespan of mice. However, he hasn’t said anywhere that he takes it. It’s possible that he’s waiting for more research into human use before experimenting. In terms of the few people globally who are using it, they’re typically ages 60-70 and older. From what I understand, this is primarily due to risk/reward trade-off calculations. For example, cancer, cardiovascular disease and other co-morbidities increase… Read more »
Thank you so much for this article!! I’ve been looking for information like this since quite some time and haven’t found anything as detailed as this.
It still hurts my wallet, to pay for NMN, but I guess it’s worth it 😉
You’re welcome Adrienne. Whilst NMN might make sense for some people. If one has limited spare cash, there are quite possibly other health and lifestyle interventions that may make a bigger difference to overall health, and thus be more worthy of the cash.