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)
- Nicotinamide Mononucleotide (NMN) – 1g/daily – mornings (see where to buy)
- Metformin (prescription drug) – 1g/daily in the evenings – except on days when exercising
- Multivitamins? Only vitamin D3 with K2, he aims to get the rest from his diet
- Statin (prescription drug) – taken since his early 20s due to family history of cardiovascular disease
- Aspirin – 83mg daily
– Started taking resveratrol around 2004, and added NMN & Metformin approximately 3 years ago
– Resveratrol, NMN & Metformin doses come via David’s recently released book; Lifespan
– Daily vitamin K2, D3 and aspirin all also mentioned in his book Lifespan
– David discussed using a statin in his Jan 2019 Joe Rogan interview (link), but didn’t mention it in his book
Below, a tweet by David on taking resveratrol in the morning, with a spoon of homemade yogurt (more on his yogurt here):
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.
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.
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
As mentioned above, David takes his resveratrol in the morning, mixed into a spoon of homemade yogurt, in order to increase its bioavailability. 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 - read on.
David has so far only touched on his yogurt making process, saying that he:
- Takes a couple of 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)
David specifically mentions Bravo as the brand of yogurt culture he uses at 1:12:28 of his interview on the Ben Greenfield podcast. Bravo appear (?) to sell directly from their website. There are also similar cultures available on Amazon.
David mentions the above in passing, and so it's worth elaborating on a few details:
- 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 sterilise 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) 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? 95%… 99%…?
- Contaminants – does it contain any contaminants such as heavy metals?
- Fillers – are any fillers used, and if so, what % do they account for of the overall powder?
Assuming all the above are ok, the last crucial question is:
- Price – how much does it cost per gram?
Searching online there are a large number of possible options. Without doing ones own 3rd party lab testing, it’s hard to evaluate the quality of products. What I’ve done below is put some of the more highly reviewed options 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? |
|---|---|---|
| Powder | ||
| Double Wood (30g powder) | $4.00/gram ($120 / 30g) | Yes (link) - via Colmaric Analyticals |
| ProHealth (15g powder) | $4.60/gram ($69 / 15g) | Yes (link) - via Micro Quality Labs |
| Genex (15g powder) | $4.60/gram ($69 / 15g) | Yes (link) - via Micro Quality Labs |
| RevGenetics Advanced NMN (25g powder) | $15.8/gram ($395 / 25g) | Yes (link) - via Intertek |
| Capsules | ||
| ProHealth (150mg capsules) | $5.44/gram ($49 / 9g) | Yes (link) - via Micro Quality Labs |
| Double Wood (125mg capsules) | $6.53/gram ($49 / 7.5g) | Yes (link) - via Colmaric Analyticals |
| Genex (125mg capsules) | $6.66 ($50 / 7.5g) | Yes (link) - via Micro Quality Labs |
| No 3rd Party Analysis Certificate | ||
| Maac10 | $6.66/gram ($25 / 3.75g) | None I can find |
The above table provides a start, but for a detailed analysis table see this companion post.
– Price per gram
The average price per gram appears around $4-$6. For products noticably cheaper, it would be worth exercising some 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. I can vouch for the Wananfu Capsule Filling Machine (Size 00), as a reliable way to mass capsulate powders. 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, the capsule filling machine fills 100 capsules per time – which would be 33 days supply.
– Testing
It’s perhaps worth noting that none of the companies (besides RevGenetics) have demonstrated testing for impurities such as heavy metals, solvents or bacteria – they only test for NMN purity.
NMN Price & Bioavailability
One thing that’s worth acknowledging is that NMN is currently a very expensive supplement, especially if you wanted to emulate David Sinclair’s dosage of 1g/day.
There are a few possible workarounds:
- It may be possible to use lower doses, perhaps 0.25 or 0.5g per day. Given that NAD levels decline with age, this approach of taking a lower dose may be more viable the younger you are - on the basis that if you're younger, you might need less NMN to raise your NAD back to youthful levels. However, this is all theory, we need studies to test the dose dependent effect, and which dose thresholds work for different age groups.
- An idea being discussed by the brand "Alivebynature" is sublingual dosing. Essentially you put the powder in your mouth, under your tongue, and let it dissolve fully before swallowing. With the intention that it's absorbed by the capillaries into the bloodstream, bypassing the liver, and increasing the amount that makes it to the bloodstream. If you can increase the absorption, you can potentially decrease the quantity needed per dose. Sublingual dosing is described in more detail on their site. Having read their description, it's evident that sublingual dosing is not a science backed approach (yet) - it's still speculative. David actually wrote a blog post about sublingual dosing, saying that we still don't have any evidence if this works, and that whilst he doesn't tell anyone what to do, or give health advice - he doesn't personally take NMN sublingually.
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 degredation 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 degredation 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.
David says that in an abundance of caution he's making sure he gets enough methyls in his diet. He mentions having used supplement called betaine (also known as trimethylglycine), which he says is a powder you can eat, and doesn't taste too bad. But says what he now does is take a combination of methyl folate plus methyl B12 - and feels like that's his best solution to this (potential) problem.
David doesn't cite a particular brand that he uses, but options include Jarrow Methyl B-12/Methyl Folate & Pure Encapsulations - B12 Folate.
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):
| Choline | Cauliflower, eggs, flax seeds, lentils, liver, peanuts, soybeans and wheat germ |
| Folate and folic acid | Asparagus, cheese, eggs, fortified breads and cereals, legumes, liver, peanuts, oranges and spinach |
| 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 its 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.
With this in mind, David opts to take metformin at night, so that come the morning, the mitochondrial inhibition is lessened. He also opts not to take it on days when he has been exercising.
How to (big picture) think about the molecules David takes?
We can attempt to summarise the function of the molecules David takes using 2 categories; 1) molecules that emulate fasting 2) molecules that boost existing function.
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 boost existing 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.
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)
- Lastly, we looked at a simple way to categorically think about how these 3 molecules work
Resveratrol & NAD
David recently wrote in his email newsletter that it’s not yet clear whether resveratrol or NMN are good or bad for Covid-19. To quote:
“Many people have asked me, “does NAD boosting or resveratrol work?” The answer is we don’t know. Lives are at stake here. In cell culture, resveratrol does counteract numerous viruses, including MERS, SARS-1, and HIV. Whether or not it works in the human body to slow viruses hasn’t been tested, but it’s relatively safe and I continue to take it while I’m safe at home. As for NAD, it’s plausible, but again we have no human data. NAD may increase the prevalence of the ACE2 that the virus uses to enter cells. But again, we just don’t know.”
Getting/Staying Healthy & Fit
In the email, David goes on to talk about the importance of getting in to the best physical and mental shape over the next couple of months. The specific tips he gave a friend are below:
- Maintain cardio fitness, which will increase capillary and red blood cell counts. Lift weights if possible. Move.
- Don’t be low in iron but also don’t overdose.
- Keep taking your medicines unless an MD says to stop.
- Eat less often during the day. I skip at least one meal, usually breakfast, and eat sensibly at other meals.
- Avoid super intense exercise or long-term fasting.
- Take 2500 - 5000 IU of vitamin D3 a day, which doctors say keeps your immune system in good shape.
- Keep blood sugar levels in check by avoiding sugar and processed grains.
- Focus on plants. Meats should include fish, preferably on the low end of the food chain to avoid heavy metals.
- Eat colored plants, either fresh or snap-frozen, and don’t overcook them. They contain xenohormetic molecules that activate cell defenses.
- Include nuts, avocado, and olive oil in your diet. Oleic acid from these foods will activate SIRT1, the defense enzyme, the same way resveratrol does (fasting also liberates oleic acid from fat stores).
- Keep humidity up in the home to maintain airway health and mucus. If your house isn’t humidified, get a humidifier for the bedroom.
- Turn off breaking news channels. Read a book. Listen to a podcast. Make something.
- Get sufficient sleep. Consider L-theonine. Avoid screens at night. Avoid big meals and alcohol near bedtime. Download f.lux software to dim the screens. If you use your phone in bed, wear blue-light blocking glasses.
—-
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
Thanks for all your great work. So very helpful. In regard to David’s last email newsletter on the virus, sounds like it might be beneficial to stop the NAD during the virus pandemic to reduce ACE2. Do you agree?
Hi Deborah. I’m interested also to know if David continues to take NMN during this pandemic. It wasn’t clear to me from his email (discussed above). I’ve asked him via Twitter (link) – will see if he replies. If you reach out to him to ask the question also, it might expedite a reply.
I just finished reading Lifespan with which I was very impressed. I’m equally impressed with how you captured and packaged the information you shared in this article. Thanks for such an excellent job!
Thanks Carl! Let me know if you’ve any suggestions for improvement / things missing.
Thank you for all this research! Is there any benefit to putting the NMN into capsule form? Why not just add it in powder form to the yogurt with the resveratrol? I’m just trying to save time here, not sure if I’m missing something?
Hey, good question. To my knowledge there’s no reason the NMN has to be in capsule form, so you could in theory add it to the yogurt also if you preferred.
For example in the animal studies they just added it to their water. David doesn’t mention using special enteric coated capsules, which differ from the gelatin ones, by preventing dissolution in the stomach.
The use of capsules serves a couple functions; 1) You don’t have to taste the powder 2) Once they’re capsulated, it’s very quick to throw them down with water.
FYI, David Sinclair just posted on his Facebook page (https://www.facebook.com/davidsinclairphd/) that his latest blood tests show a significant increase in B12 levels (double the recommended max) and thus he’s going to stop taking the methyl-B vitamin/folate chewable tablet he’s been using.
Hi, thanks for sharing that, it helps a lot. Have updated the post to reflect this new info.
Great “clift notes” on Dr Sinclair, thank you! Question: is there any benefit to taking NMN sublingually, vs in capsule form? Sublingual is, frankly, a pain. It seems Dr. Sinclair just knocks it down in capsule form…?
Hi Marky, thanks for the message. If you jump to this section of the post, then click the dropdown that says “Possible Price Workarounds” I’ve kind of covered this there in the second bullet point. In essence, the jury is still out on whether sublingually is better than capsules. That is to say, it hasn’t yet been clinically tested and compared. However, David *has* however commented on this in this blog post called “sublingual nope”, and says he personally does not use this method of ingestion. As you rightly point out, he takes his NMN in capsules, and knocks them… Read more »
Good article – very useful.
Listening to Sinclair, he doesn’t exercise all the much (often just 1 or 2 times a week). For him, taking Metformin on his many off-days is practical.
I exercise 5-6 days/week, would Metformin not be worth taking then? I suppose I could do a trial but I’m wondering if there are other people who take it nightly while exercising every morning. How do active people get around the potential drawback of the drug?
Hi Jordan, thanks for the message. I think it’s fair to say that this is a highly topical point of question at the moment, especially as more data and studies come out. I will defer to two (relatively) well known influencers in the space; Rhonda Patrick and Peter Attia, and just kind of condense what they’ve said on the subject. In essence, both of them are now questioning the benefits of metformin in people who are currently active and exercising regularly. Rhonda Patrick spoke about this on Kevin Rose’s podcast in Jan 2020 (link). She notes that exercise is better… Read more »
Alex, your very informative website is fantastic! Thank you for gathering this information and sharing it.
I am wondering what size capsule would be needed or best to encapsulate 1 gram of NMN powder?
Hi Di, apologies for the slow reply. Have just had a chance to look into this and add a section to the post. Size 00 capsules are very common, and a good blend of being large enough to house a decent amount of powder, but not too large that they’re hard to swallow. You would need 3 of these per 1 gram of NMN powder. Then depending on how tightly you pack the powder into the capsules, you’ll either be slightly over or under 1 gram, but it won’t be by much. Then once you’ve done 1 run through, you… Read more »
Thanks for all the info! I understand that David Sinclair takes 1g/day of reversatrol. What is the suggested amount for someone just starting out of both NMN and reversatrol?
Hi Douglas. In brief, I don’t think there’s a good answer for that. Right now we have the published studies one can look at, and info on what scientists like David Sinclair are doing for themselves. However this isn’t like with essential vitamins and minerals, where we can make approximate calculations on what is optimal and what isn’t. So for example with vitamin D we could infer from healthy (and unhealthy) populations what blood level might be optimal. Then work backwards from there in calculating required doses to reach that level. The latter (essential vitamins and minerals) are required building… Read more »
Hi Alex,
Thanks for putting this together! It’s extremely useful. Just wanted to give you a heads up that David Sinclair was recently on the Goop podcast, where he mentioned he takes a B-vitamin (perhaps it’s the methyl B12) and said he takes resveratrol (or was it metformin?) every other day. Apologies for the hazy memory.
Hi Christian, thanks for the message. Hazy is better than nothing! Regarding the Goop podcast, have just listened to it. At 43mins David talks about how in mice studies with resveratrol they found that mice taking it every other day, with food, had maximal lifespan benefit. Then he goes on to say that you don’t necessarily have to take a supplement every day to see benefits. However it’s worth noting he doesn’t say that he takes resveratrol every other day – that would go back on what he has said numerous times; that he takes resveratrol daily. It doesn’t appear… Read more »
Alex, 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 »
Hi Bob, thanks for taking the time to share that information, including the timestamp and the transcript. This is an important issue to address, and I’ve just added a section on the subject, which utilizes the information you shared, and pulls in a few other bits and pieces into the picture.
Let me know what you think, and if you can suggest any improvements.
Thanks so much Alex.
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.
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.
Hi Vladimir. With regards to your comment “Maybe only NMN activates specifically this possible benefit” – whilst this is possible, it’s unlikely. Based on what we know currently, the beneficial effects derived from NMN and NR *should* come from their ability to raise NAD levels. Thus, if NR can raise NAD levels, then you could anticipate it having the same effect as NMN. The main focus of the debate currently is around the specifics of their ability to raise NAD levels, and which molecule does this better.
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?
Hey Jack. Just had a look at Toniiq. Seems they’re currently out of stock for NMN, but presumably will be back in stock again soon. With regards to their resveratrol – it doesn’t appear they do a micronized version, so you could anticipate the absorption being inferior to micronized options. Not necessarily a deal breaker, but just something to bear in mind. With regards to ensuring supplement providers are legitimate – it’s a bit of a minefield because it’s not a regulated industry like pharmaceuticals. For mainstream supplements, one certification to look out for is NSF. In particular they audit… Read more »
Putting all these together must’ve been a considerable effort! I can’t thank you enough for doing so!
Thanks Jung! Let me know any thoughts for improving it.
Great Article! Thanks. Does it say how much Metformin he takes/his dad?
Hey. Yes – David says he takes 1g of Metformin (that’s in the post above) – I believe he generally takes it at night (has mentioned the timing on podcasts). His Dad is also taking 1g of Metformin. His Dad’s full list of supplements is in a post David did on his Lifespan Book blog (link). To quote: Besides that, there are supplements and medications: Metformin, also known as glucophage (2 x 500 mg/d for borderline high blood sugar). Exforge to lower blood pressure (a combo of angiotensin II receptor antagonist and a calcium channel blocker) Lipitor, a statin to… Read more »
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 »
Hi Phil, thanks for the comment and research. I had a look at the data available online related to this and 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). With the results of longer duration studies pending at the time (I think) – but this document was from 2016. Then similarly the “European Food Safety Authority” discuss stability (link) of at least 36 months when stored under ambient conditions. Noting… Read more »
David Sinclair on the Ben greenfield podcast interview said that he uses the Bravo yogurt kit and mixes with coconut milk.
Hi Jay – thanks for this – hadn’t seen David mention which brand he uses until this podcast. Have now updated the post to reflect this. With regards to coconut milk – I’ve listened back a few times, and David doesn’t mention it. He says that he uses milk – and on other podcasts such as Joe Rogan’s he has specified using whole milk. It’s Ben Greenfield who mentions using coconut milk. But the way Ben says “I do something similar to what you do” – then mentions using coconut milk – can make it sound like David uses coconut… Read more »
“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..
Hi Melanie – totally agree – that’s an interesting question. Seems aspirational to try and answer, but unlikely to be possible at this stage.
On a related note, found a study in PLOS that plots NAD levels from pelvic tissue samples, for people of different ages – link. Found it interesting for getting an idea of change over time.
Hi Alex, 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 »
Hey Aaron! Thanks for the message. So yes – David made it very clear on the recently released podcast with Rhonda Patrick – that the need for a fat source (in his case yogurt) is to help absorb the resveratrol, and isn’t necessary for the NMN. In other discussions he hadn’t said it so clearly, so I’d interpreted it as the fat source helped absorb both. Will update the post to reflect this 🙂
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?
Hi Glen. That’s an interesting question – thanks for noting you mean extended fasting rather than intermittent fasting. Whilst I don’t think I can answer it perfectly, I can certainly share some thoughts around it. So firstly, with the NMN, the goal is to increase NAD levels, which boosts (or restores) cellular metabolism. Its been observed that fasting also boosts NAD levels – for example this paper models that scenario in mice. So even without your NAD precursor, you’ll get an uptick in NAD whilst fasting. Whether or not it’s worth trying to boost that further via NMN? It’s an… Read more »
Thanks Alex. 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 »
But how can the average person get Metformin? It is prescription only.
You would need to seek out a doctor who is willing to prescribe metformin to you “off-label”, and then work with you to ensure it’s a good fit. I don’t have a list of doctors who will do this.
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.
Really good job summarizing all this info, much appreciated.
Thanks SC!
Yes, great post, Alex, bringing many of the details together about these three supplements and David’s research on and use of them.
Big help, thank you.
Hey, appreciate the feedback, glad the article helped!
What about the NAD+ IV regimen?
Intravenous NAD? That’s not something David is using. Although he did mention trying it out of curiosity. For more information on that, you’re best off looking to other people/researchers.
My reservation with intravenous NAD (assuming the science shows that it indeed works, which hasn’t yet been proven) would the frequency of administration. You ideally want to boost NAD levels daily, and supplements will facilitate this more easily than infrequent IV doses. More research is needed to clarify on these questions.
thank you! Great post, you saved me a lot of time on research.