David Sinclair, a leading scientist in aging research, uses specific supplements to promote longevity.
At 55 years old, he appears much younger, sparking curiosity about his supplement regimen.
This article lists the supplements David Sinclair takes and explains how they may support anti-aging efforts.
David Sinclair’s Supplements Stack:
Supplement or Drug | Dosage |
---|---|
Taken Daily | |
Resveratrol | 1 gram daily – with yogurt |
NMN | 1 gram daily |
Fisetin | 500mg daily – with yogurt |
Quercetin | 500mg daily – with yogurt |
Spermidine | 1 mg |
Vitamin D3 | At least 2,000 IU per day |
Vitamin K2 | Daily |
Omega-3 fish oil | Daily |
Alpha Lipoic Acid | Daily |
Coenzyme Q10 | Daily |
Taurine | 2 grams daily (experiment) |
Drugs | |
Metformin | 800mg at night |
Rapamycin | Taken intermittently |
Statin | Daily |
Aspirin | 81mg daily |
N.B. All the sources for David’s supplement doses can be found here.
For a detailed breakdown of what else this article covers, see the table of contents below:
Below we’ll start by looking in detail at his use of Resveratrol and NMN:
Resveratrol
First we’ll look at the sirtuin activator David takes; Resveratrol.
Resveratrol is a molecule that’s found (in small amounts) in the skin of foods like grapes, blueberries, raspberries, mulberries, and peanuts.
If you remember the “hype” some years ago around red wine being healthy, part of that was due to it containing resveratrol (albeit in tiny amounts).
Unfortunately, all food sources of resveratrol contain tiny amounts, so we need a concentrated supplement in order to see benefits!
Resveratrol is thought to act as a “caloric restriction mimetic”, which activates beneficial cellular pathways. Studies have pointed to benefits such as:
- Reduced inflammation and oxidative stress in healthy people1An Antiinflammatory and Reactive Oxygen Species Suppressive Effects of an Extract of Polygonum Cuspidatum Containing Resveratrol – Dandona et al (2010)
- Improvements in memory tasks for obese, but otherwise healthy 50-75 year olds2Effects of Resveratrol on Memory Performance, Hippocampal Functional Connectivity, and Glucose Metabolism in Healthy Older Adults – Flöel et al. (2014)
- Improvements in metabolic and cardiovascular markers, in people with obesity3Calorie Restriction-like Effects of 30 Days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans – Schrauwen et al. – Cell Metabolism Journal (2011), hypertension, type 2 diabetes4Pilot Study of Resveratrol in Older Adults With Impaired Glucose Tolerance – Barzilai et al. (2012)5Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients – Wittmann et al. (2011)6Antihyperglycemic Effects of Short Term Resveratrol Supplementation in Type 2 Diabetic Patients – Netticadan et al. (2013)7The Effect of Resveratrol Supplementation on Cardio‐Metabolic Risk Factors in Patients with Type 2 Diabetes: A Randomized, Double‐Blind Controlled Trial – Mozaffari‐Khosravi et al. (2019), fatty liver disease8Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: A randomized controlled trial – Mi et al – Digestive and Liver Disease journal (2015)9Resveratrol supplementation improves inflammatory biomarkers in patients with nonalcoholic fatty liver disease – Hekmatdoosta et al – 2014 – Nutrition Research Journal and cardiovascular disease10Consumption of a grape extract supplement containing resveratrol decreases oxidized LDL and ApoB in patients undergoing primary prevention of cardiovascular disease: A triple‐blind, 6‐month follow‐up, placebo‐controlled, randomized trial – Espín et al – 2012 – Molecular Nutrition & Food Research Journal11One-Year Consumption of a Grape Nutraceutical Containing Resveratrol Improves the Inflammatory and Fibrinolytic Status of Patients in Primary Prevention of Cardiovascular Disease – Espín et al – 2012 – The American Journal of Cardiology
Resveratrol – Where to buy?
David notes some important aspects when buying resveratrol:
- We want trans-resveratrol, not cis-resveratrol. From David’s studies, cis-Resveratrol did not activate the sirtuin enzyme, but trans-Resveratrol did.
- We want 98% or greater purity. David mentions this at 1:17:54 of his Ben Greenfield interview.
- We want Micronized resveratrol. A study by David’s old company Sirtris found it was 3.6x more bioavailable than non-micronized formulas. David also mentioned the value of micronized resveratrol in this Reddit comment.
Below we look at some micronized resveratrol buying options. If you’re planning to mix it with yogurt, then powders are desirable. Otherwise resveratrol in capsules will be most practical:
Product | Price per gram | 3rd Party Analysis Certificate? |
Capsules | ||
Mega Resveratrol (99% purity) - 500mg capsules x120 | $1.50 per gram ($90 / 60g) + 10% coupon code | Micro Quality Labs CoA - April 2022 |
ProHealth (99% purity) - 500 mg capsules x60** | $1.03 per gram ($31 / 30 g) + 10% coupon code | Twin Arbor Analytical CoA - March 2023*** |
Powder | ||
Mega Resveratrol (99% purity) - 60 grams | $1.25 per gram ($75 / 60g) + 10% coupon code | Micro Quality Labs CoA - Dec 2021 |
ProHealth (98%* purity) - 30 grams | $1.16 per gram ($35 / 30g) + 10% coupon code | Twin Arbor Analytical CoA - Feb 2023*** |
ProHealth (98%* purity) - 100 grams | $0.76 per gram ($85 / 100g) + 10% coupon code | Twin Arbor Analytical CoA - Jan 2023*** |
* 98% purity is significantly cheaper than 99%, due to the extra process of isolation required to get up to 99% purity.
** A word of caution on the ProHealth Resveratrol capsules – they include other compounds, specifically; quercetin, red wine extract, green tea extract and Bioperine. This gets away from taking a pure Resveratrol product.
*** ProHealth’s 3rd party analysis documents no longer test for purity as a percentage, which they previously did.
Note: Whichever source of trans-resveratrol you take, according to David, you will increase its bio-availability if you take it with a fat source.
David takes it on an empty stomach in the morning, so mixes it with a bit of home made yogurt. However, if you’re taking it with a meal, then mixing it into yogurt isn’t necessary.
Resveratrol – Storage
David mentions in his interview with Rhonda Patrick a few nuances around the storage of resveratrol:
- Store in a dark place – resveratrol is light sensitive, and when left exposed to light it turns brown and no longer functions correctly.
- Store in a cool place – the shelf life of resveratrol can be extended by avoiding excessive heat. However, refrigerating it after opening may result in moisture accruing within the container, which would decrease the shelf life.
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 in making 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, one 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.
Resveratrol vs Pterostilbene
Both resveratrol and pterostilbene are classed as naturally occurring pstilbenoid compounds. Their molecular structure is noticeably similar:
^ Image source
Whilst there is some research suggesting that pterostilbene is superior to resveratrol in certain aspects.
David said on Reddit that he knows the resveratrol better, and that’s why he uses it:
NMN – Nicotinamide Mononucleotide
We talked above about the sirtuin activator Resveratrol, now let’s talk about NMN, which helps provide the “fuel” for the sirtuins to work.
NMN falls into a category of supplements, along with Nicotinamide Riboside (NR), referred to as “NAD boosters” – which have become increasingly popular.
NAD is required for every cell of our body to help facilitate energy production. Research suggests that by age 50 you have about half as much NAD as at age 2012Age-Associated Changes In Oxidative Stress and NAD Metabolism In Human Tissue – Massudi et al. | 2012 | PLoS ONE Journal.
The intention is that by supplementing precursors we can boost the cellular level of NAD closer to youthful levels.
There’s little to no doubt in the research community that we need to restore NAD function; but the jury is still out on what the best method will be. Currently David has his eggs in the basket of NMN.
Where to buy NMN?
Generally speaking, David doesn’t recommend sources for where to buy supplements, so we have to do a bit of research ourselves.
Below we will look at various possible buying options.
Potential considerations when buying include:
- Accuracy & Purity – is the product you’re getting actually NMN? And if so, how pure is it?
- Contaminants – does it contain any contaminants such as heavy metals?
- Price – how much does it cost per gram?
The below table looks at NMN brands that have 3rd party
The below table looks at the more highly reviewed NMN options (within USA), possessing 3rd party analysis certificates, ranked by their price per gram:
Product | Approx. price per gram | 3rd Party Analysis Certificate? |
Capsules | ||
SuperNMN - 500 mg capsules | $1.51/gram ($68 / 45g) | Micro Quality Labs CoA - May 2022 |
Renue - 125 mg capsules | $2.30/gram ($68 / 30g) + 10% off coupon code | Micro Quality Labs CoA - March 2023 |
RevGenetics - 500 mg capsules | $1.33/gram ($40 / 30g) | Summit Labs CoA - June 2023 |
ProHealth - 500 mg capsules | $3.33/gram ($100 / 30g) + 10% off coupon code | Twin Arbor Analytical CoA - Feb 2023 |
Powders | ||
Renue - 100 grams |
$0.67/gram ($67 / 100g) + 10% off coupon code | Micro Quality Labs CoA - June 2023 |
ProHealth - 100 grams |
$1.23/gram ($123 / 100g) + 10% off coupon code | Twin Arbor Analytical CoA - Sept 2022 |
SuperNMN - 30 grams | $1.66/gram ($50 / 30g) + 10% off coupon code | Micro Quality Labs CoA - May 2022 |
ProHealth - 30 grams |
$2.66/gram ($80 / 30g) + 10% off coupon code | Twin Arbor Analytical CoA - Sept 2022 |
Whilst the above table is for US buyers, for UK buyers see this post.
An analysis that may be useful to your purchase decision was one done by Chromadex, who tested 22 popular NMN products to see how much NMN they contain.
14 of the 22 products tested were found to have less than 1% NMN in them. More details in this post.
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 about NMN being the better molecule for raising NAD in the long run. He notes in a blog post on NMN & NR that:
- The science is further along for NR, but it’s too early to say which is better for humans.
Where to buy NR?
The main seller of Nicotinamide Riboside is Chromadex, who sell 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). I don’t know if a study has compared NR to NMN to see, gram for gram, which raises NAD levels more in humans.
Niagen works out to approximately $4.44/gram, and NMN starts as low as around $1.80 per gram.
I think this comes down to patents and competition. The NR that Chromadex sells has a patent on it, which then reduces competition. Whereas NMN seems free of patents, and there are lots of sellers.
NR & NMN Storage
In David’s interview with Rhonda Patrick, he discussed details around storage, saying:
- NR and NMN need to be kept cool because they don’t have a long shelf life. Authors note: keeping powders in the fridge, especially once opened, can result in moisture build-up within the bottle, and moisture can rapidly decrease the shelf life. Therefore some caution around fridge storage is warranted. I’d personally avoid it. My interpretation is to avoid storing them in hot locations.
- 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 sirtuins13Inhibition of Silencing and Accelerated Aging by Nicotinamide, a Putative Negative Regulator of Yeast Sir2 and Human SIRT1 – Bitterman et al (2002). He didn’t elaborate further on what a “stabilized form” means in this context, which would be interesting to know.
- As mentioned above, if NMN gets wet, or gets moisture in the bottle, it’s 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) mentions the stability of Niagen for up to 11 months in both normal and accelerated conditions. In both cases it maintained its NR chloride content well (98.8% under normal conditions and 92.1% under accelerated conditions). This document was published before they had completed testing beyond 11 months.
- Then similarly a more recent “European Food Safety Authority” document discusses stability (link) of at least 36 months when stored under ambient conditions. Noting that the applicant (Chromadex) who make Niagen recommend it’s stored under refrigerated conditions with a shelf life of 36 months.
What I gather from that, is that NR in its chloride form is stabilized. But like most edible products, cooling it does slow down the degradation that occurs over time. However for most people, the product isn’t intended to sit on the shelf for a long time, and thus it will be consumed before the degradation becomes a problem.
NMN/NR & Methyl Group Depletion?
There has been some concern in the field that consuming NR or NMN could decrease the body’s methyl groups and lead to health problems. The dropdown section below looks in detail at that issue.
So methylation itself, which utilizes methyl groups (CH₃), is an essential process for a host of critical functions in the body, including regulation of gene expression and the removal of waste products.
Consuming Niacin derivatives (which include 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 45m 42s mark), acknowledging that Niacin derivates (including NR/NMN) require methylation for excretion, but asserting that at this stage the idea of methyl depletion is anecdotal, and not something that has been shown in any NR/NMN studies.
Initially (circa 2019) David mentioned taking a supplement called betaine, also known as trimethylglycine. Then he moved to taking a combination of methyl folate plus methyl B12. This was all “in an abundance of caution”, rather than due to any new research that backed up the risk of methyl depletion.
After taking the B12/Folate supplement for a few months, in February 2020 David got some blood tests done, and found his B12 levels were double the recommended maximum – so he stopped taking it (source: David’s Facebook post). He hasn’t mentioned replacing it with anything since.
As Dr Brenner points out below, monitoring homocysteine levels (via blood test) is a proxy for methylation issues.
Methyl groups are primarily derived from nutrients in the diet, including; methionine (amino acid), folate (vitamin B9), choline, betaine, riboflavin (vitamin B2), pyridoxine (vitamin B6) and cobalamin (vitamin B12). For foods rich in these, see table 1 in this research paper.
A further source to add to this discussion is the research done by Chromadex. They hold a patent on nicotinamide riboside production, and make Niagen. In a tweet thread by their chief scientific adviser Charles Brenner, he explains that Chromadex took the potential risk of NR depleting methyl groups seriously. To test this they performed a randomized double blind placebo controlled trial administering 100, 300, or 1,000 mg of NR over 56 days (study link). They used homocysteine levels as a proxy for methylation disturbance, and found no change to homocysteine in any of the dosage groups, including up to 1,000mg (see this image). If there was a shortage of methyl groups, they would have expected to homocysteine levels rise. It’s worth noting the study used NR, not NMN.
In summary, current evidence for this issue is lacking, and as far as I can tell, David Sinclair is no longer taking any supplements to tackle potential methyl group depletion. However, if you want to be super careful, Dr Charles Brenner (an NAD researcher) mentions elevated homocysteine in the blood can be a sign of lower methyl status – so one could get a blood test to check that.
Fisetin & Quercetin
When David published his book Lifespan in 2019 he was only taking resveratrol with his yogurt in the morning. However, in mid-2021 he mentioned that he was experimenting with adding Fisetin and Quercetin (see this clip).
Then in 2022 he explains he’s now taking 500mg of fisetin and quercetin daily, in the mornings, alongside his resveratrol and yogurt (see this section of episode #4 of his podcast).
Both have senolytic and SIRT1 activating properties. Senolytic molecules have the ability to kill off senescent cells.
Fisetin
David’s lab has shown fisetin extends the lifespan in mice and worms14Design and synthesis of compounds that extend yeast replicative lifespan – Sinclair et al. (2006)15Sirtuin activators mimic caloric restriction and delay ageing in metazoans – Sinclair et al. (2004).
Fisetin is typically sold in capsules, which can be taken with food/fat sources, or emptied into yogurt. Examples of brands include:
- DoubleWood – Fisetin – 60x 100 mg capsules (15% off with this coupon code)
- DoNotAge Fisetin – 60 x 400 mg capsules (10% off with this discount code)
- Doctor’s Best – Fisetin – 30x 100 mg capsules (see 20% off coupon code)
Quercetin
Quercetin is typically sold in capsules, which can be taken with food/fat sources, or emptied into yogurt. Examples of brands include:
- Jarrow Quercetin – 500 mg capsules (see 20% off coupon code)
- DoNotAge Quercetin – 400 mg capsules (10% discount with this coupon code)
- NOW Quercetin – 500 mg capsules (see 20% off coupon code)
Spermidine
David explained that he is currently experimenting with taking 1 gram of spermidine each morning.
However, when we look at the company he’s invested in, Longevity Labs, whose first product is a spermidine supplement under the brand SpermidineLIFE. We see that the daily dose of 1 gram (800 mg) of wheat germ, actually only contains 1 milligram (mg) of spermidine.
You can see this on their site if you scroll to ingredients. Taking 1 gram of actual spermidine would require consuming 2,000 of their capsules (1 gram = 1,000 milligrams, 1 capsule = 0.5 mg of spermidine).
Research on Spermidine & Longevity?
Currently the evidence around spermidine and longevity appears in its infancy. In this section we look at some of the more interesting studies:
For example, an associative study of 829 participants over 15 years found that16Higher spermidine intake is linked to lower mortality: a prospective population-based study – Willeit et al. (2018) | The American Journal of Clinical Nutrition:
“The difference in mortality risk between the top and bottom third of spermidine intakes was similar to that associated with a 5.7 year younger age (95% CI: 3.6, 8.1 y).“
However, because this was a study based on diets, evaluated through questionnaires, it’s possible that other factors were responsible for the health benefits.
More recently, in 2019, Austrian researchers published the results of a double blind study in 79 older adults (~80 years) looking at the effect of spermidine supplementation on cognitive performance17The positive effect of spermidine in older adults suffering from dementia – Pekar et al. (2019) – Wiener klinische Wochenschrift.
They found a noticeable benefit in the subjects with cognitive impairment – which is great news for those in that demographic. A similar study and result was found a year before also18The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial – Wirth et al. (2018) – Cortex, suggesting it’s repeatable.
However, more research is needed for how this would translate to younger or healthier people.
Types of Spermidine Supplements
Whilst SpermidineLIFE is composed of a standardized wheat germ extract, which itself contains spermidine, it is also possible to buy spermidine in a pure form.
Specifically called spermidine trihydrochloride (spermidine 3HCL), with the hydrochloride (HCL) attachment stabilizing it for transport and storage.
For those with gluten intolerance, taking it in a pure form may be more ideal, as wheat germ contains small amounts of gluten.
Spermidine trihydrochloride contains approximately 57% spermidine free base (pure spermidine). So a 10 mg serving of spermidine trihydrochloride will contain approximately 5 mg of pure spermidine.
Examples of wheat germ derived spermidine brands:
- SpermidineLIFE – 1mg per 2 capsules
Examples of spermidine trihydrochloride brands:
- DoubleWood – Spermidine – 10mg per 2 capsules (15% discount with this coupon code)
Spermidine Food Sources?
With resveratrol and NMN, for example, the only way to consume them in large quantities, is via supplementation.
However, with spermidine, it is possible to get large amounts from day to day foods.
Expand the section below to see a list of food products high in spermidine content:
Food item | Portion in grams | Spermidine in mg per portion |
Soybean, cooked | 190 | 9.7 |
Peas, green | 140 | 9.1 |
Pear | 125 | 6.6 |
Lentil soup | 250 | 5.5 |
Mushroom | 50 | 4.4 |
Red Beans | 190 | 3.7 |
Broccoli | 100 | 3.6 |
Cauliflower | 100 | 3.0 |
Popcorn | 50 | 2.1 |
Cheese | 20 | 2.0 |
Potato, cooked | 150 | 1.8 |
Beyond this list, there’s spermidine in many more different foods. This paper is a good resource and is where the above info came from.
Further Supplements David Sinclair Takes
Whilst David generally tries to get all the vitamins and minerals he needs from his diet, he does still take some vitamins daily. Between his book, podcast, a podcast with Dave Asprey (from 19m 10s) and Twitter, he mentions taking:
- Vitamin D3 – says he takes at least 2,000 IU per day
- Vitamin K2 – doesn’t mention dose. K2 can help facilitate healthy calcium transport, potentially reducing build-up in the arteries
- Omega-3 fish oil – taken daily in the evening
- Alpha Lipoic Acid – mentions taking the “S form”, but doesn’t mention dose. References it as another sirtuin activator
- Coenzyme Q10 – often taken by people taking statins (which David does) to reduce any side effects. It also plays a role in mitochondrial energy production
See below for more details on each of these:
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 have a significant effect on at least 200 of our genes19A ChIP-seq defined genome-wide map of vitamin D receptor binding: Associations with disease and evolution – Ramagopalan et al. (2010). It’s relatively scarce in foods, and so we rely on sunlight to produce 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 2,000 IU per day.
Examples of reliable brands include:
- NOW – Vitamin D3 – 2,000 IU (see 20% off coupon code)
- NOW – Vitamin D3 – 5,000 IU (see 20% off coupon code)
- Life Extension – Vitamin D3 – 5,000 IU (see 20% off coupon code)
Vitamin K2
David mentions taking Vitamin K2 daily on page 304 of his book ‘Lifespan’.
Vitamin K is an essential micronutrient that 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 K120Vegetables and Mixed Dishes Are Top Contributors to Phylloquinone Intake in US Adults: Data from the 2011-2012 NHANES – Harshman et al. (2017).
This could lead to increased cardiovascular risk as a result21Circulating uncarboxylated matrix Gla protein, a marker of vitamin K status, as a risk factor of cardiovascular disease – van den Heuvel et al. (2014), 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 transport22The relationship between vitamin K and peripheral arterial disease – Vissers et al. (2016).
Examples of brands for vitamin K2 include:
- NOW K-2 (MK-4 version) – 100 mcg x 100 capsules (see 20% off coupon code)
- Life Extension K-2 (MK-7 version) – 45 mcg x 90 capsules (see 20% off coupon code)
Omega-3s
David mentions on Twitter (link) taking his daily Omega 3-6-9.
He notes that he especially likes Nordic Naturals ProEFA product for its SIRT1-activating Omega-9 oleic acid.
ProEFA comes in 2 forms:
- ProEFA-3.6.9 – Liquid
- ProEFA-3.6.9 – Soft Gels
Whilst David didn’t mention which form he takes it in, the composition of the oil is the same for both. However, the daily serving of the soft gels (2) is half that of the daily serving of the liquid (5 mL teaspoon). So to get the equivalent dose in soft gels, you’d need to take 4.
Alpha Lipoic Acid
In his podcast interview with Dave Asprey (link), David mentions taking alpha lipoic acid. Not to be confused with alpha-linolenic acid (ALA) – 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 metabolism23Lipoic acid: energy metabolism and redox regulation of transcription and cell signaling – Packer et al. (2011).
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 alpha lipoic acid brands are:
- Thorne – Alpha Lipoic Acid – 300 mg (see 20% off coupon code)
- NOW – Alpha Lipoic Acid – 250 mg (see 20% off coupon code)
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 to research that suggests statins can reduce Coenzyme Q10 levels in blood24Coenzyme Q10 and Statin-Induced Mitochondrial Dysfunction – Deichmann et al. (2010).
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 Coenzyme Q10 brands include:
- Thorne – Coenzyme Q10 – 100 mg x 60 capsules (see 20% off coupon code)
- NOW – CoQ10 – 100 mg x 90 capsules (see 20% off coupon code)
Taurine
Taurine recently hit media headlines when a study showed that supplementation in mice increased their median lifespan by 10%.
On the basis of this, David said in this interview clip he’s now experimenting with taking 2 grams of taurine per day.
David was also quoted in a New York Times article (which he tweeted about):
“Dr. Sinclair said he had dabbled with taurine in the past. But based on the new paper, he said he would likely add high doses of taurine to his regimen — with regular blood testing for possible side effects.”
So as mentioned, David will continue to use Inside Tracker testing (discussed below) to ensure his blood biomarkers stay in a healthy range.
Presumably, if after supplementing taurine, he finds his blood test results are problematic, he will simply cut down or cease supplementation.
Examples of taurine brands include:
- Double Wood – Taurine – 1,000 mg x 180 capsules (see 20% off coupon code)
- Life Extension – Taurine – 1,000 mg x 90 capsules (see 20% off coupon code)
- NOW – Taurine – 1,000 mg x 100 capsules (see 20% off coupon code)
Drugs David Sinclair Takes
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. Its 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 rivaling 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).
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 it?
Typically Metformin is taken daily – both by diabetics and by people using it for healthspan extension.
However, in the latest interview with Joe Rogan, they discussed a 2018 paper that 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.
David opts to take 800mg of Metformin at night (see this section of episode #4 of his podcast), except on nights when he plans to exercise the next day.
For similar reasons, he also skips resveratrol on exercise days (source: see last paragraph of section 1 – “Get Moving” on David’s blog post).
This is viable for David who exercises vigorously in the order of 1-2x per week, but for someone training often, this might be impractical. At which point it would come down to a decision on whether the benefits of metformin/resveratrol outweigh the (potential) small impact on recovery.
Is Berberine a non-prescription alternative?
In a Reddit AMA (link) David was asked whether he would take Berberine if he didn’t have access to Metformin. He responds by saying he would likely take Berberine.
Berberine is interesting to many people because it has similar properties to metformin, but it doesn’t require a doctor’s prescription. In common with metformin, it has the ability to:
- Lower blood glucose, triglycerides and fasting insulin in patients with type 2 diabetes25Efficacy of Berberine in Patients with Type 2 Diabetes – Ye et al. (2009)
- Activate the AMPK pathway – which, among other things, increases cellular cleanup (autophagy)26Metformin and berberine, two versatile drugs in treatment of common metabolic diseases – Luo et al. (2018)
Berberine dosage in treating diabetes is not entirely dissimilar to Metformin. For example in this study, the patients took 500mg of Berberine 3x per day. Then in this study they took 850mg of Metformin 3x per day. We know that David takes 800mg of Metformin at night.
Both compounds can induce gastrointestinal distress, so it’s common to start off on lower dosages, and gradually increase to the desired amount. This gives the gut a chance to adapt and allows the user to back off the dosage if gastrointestinal distress is reached.
The optimal dosage for treating diabetes can be figured out based on testing the effects on fasting and post-meal blood glucose. However, there isn’t yet research on optimal dosage for someone with already healthy blood glucose levels. Using these products for healthspan and lifespan benefits is new territory and needs further research.
Brands & Type?
One benefit of Metformin being a prescription drug is that the manufacturing process is tightly scrutinized. Over-the-counter supplements aren’t regulated to the same extent, and as such, it makes sense to go with a reputable brand.
In the studies mentioned above, they use Berberine HCl (hydrochloride), which is commonly extracted from the Berberis Aristata plant.
Examples of generally reputable brands include:
- Double Wood – Berberine – 60 x 500 mg capsules (see 20% off coupon code)
- Thorne – Berberine – 60 x 500 mg capsules (see 20% off coupon code)
Rapamycin
During David’s August 2023 interview with Peter Diamandis (see 38:47) he was asked if he takes rapamycin. His answer was “on and off, yes”.
This doesn’t give us a great deal to go on, as he didn’t mention his dosage or frequency. It may be that when he said “on and off”, he simply meant he’s taking once a week or once a fortnight, which are the two protocols typically used with rapamycin for longevity.
However, another possibility is that he takes it for weeks or months at a time, and then takes a break. We’ll need to wait and see.
Rapamycin is a prescription drug whose primary indication is for use in organ transplant patients to help them avoid organ rejection.
However, after a groundbreaking 2009 study found that it extended the mean and median lifespan of mice – it has been a molecule of interest amongst longevity researchers. This 2023 paper gives a good rundown of the latest rapamycin studies to date.
For more information on rapamycin and longevity, a potential resource is the Rapamycin News forums.
Statin
David said in his interview with Joe Rogan (see 1h 39m) that he’s been on a statin since he was 29 years old. He suggested that due to his family history and genetics he’s at high risk of cardiovascular disease, and that’s his rationale for taking a statin.
Rogan asked what dose he was taking, and he said 80 mg, and then Rogan asked what a normal dose is, and he said 10 mg.
In that interview David didn’t say which statin he is taking, however a couple of things suggest it may be Lipitor (atorvastatin). Specifically:
- David mentioned the normal dose is 10 mg, and a normal starting dose for Lipitor is 10 mg (source).
- In April 2023, David tweeted in detail about the potential benefits of Lipitor.
Aspirin
In this clip David says that he takes a baby aspirin (83 mg) daily.
Remarking that it may reduce the risk of colon cancer and keep inflammation down.
Interestingly, Aspirin was one of the compounds studied in the US intervention testing program (ITP) that noticeably increased the lifespan of male mice.27Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice | Strong et al. | 2008 | Aging Cell
^ This image comes from the study mentioned above. The top right panel shows the increase in lifespan of the male mice taking aspirin vs the control group.
It’s worth noting that aspirin is a powerful anti-coagulant, meaning that it can decrease your body’s blood clotting ability. Therefore it’s worth consulting with your doctor before emulating David’s daily consumption.
David’s Diet, Exercise & Lifestyle Routines
Diet details:
- Coffee in the morning (once per day), then green tea after that.
- Intermittent fasting – aims to skip at least 1 meal per day. Helped by lots of green tea.
- Previously he kept meat consumption low and avoided red meat. More recently he’s been on a vegetarian diet.
- He aims to eat as little sugar, bread or pasta as possible. He stopped eating desserts at age 40, except for a “small taste” occasionally.
- Aims to eat lots of vegetables.
Exercise routines:
- Weight lifting – now 3 times per week, was previously just 1 time per week.
- Running 1-2 times per week. Preferably using a curved treadmill for lower impact. Does short, fast runs.
- Sauna weekly.
- He exercises in order to stay healthy and mentally sharp, rather than to be muscular.
Lifestyle Choices:
- He doesn’t smoke, and avoids microwaved plastic, excessive sun exposure, X-rays, and CT scans.
- Aims to keep his BMI in the optimal range for healthspan, which for him he says is 23 to 25.
- Tries to stay “on the cool side” during the day, and at night when sleeping.
How David Tracks + Measures His Health
David uses a blood testing service called Inside Tracker to track his biomarkers. Helping him to understand what is, and isn’t working, in terms of his diet, exercise and supplementation.
For example, he shared on Facebook (link) that his Inside Tracker results showed his vitamin B12 supplementation was causing his B12 levels to get too high. Resulting in him removing B12 from his supplements.
This test was presumably InsideTracker’s Ultimate product – as it’s the only one that covers all the biomarkers he mentioned (for 10% off their blood tests, see this discount code).
^ An image David shared on Twitter after an Inside Tracker blood test
InsideTracker offers 2 main blood tests:
- Ultimate which covers 46 biomarkers
- Foundation which covers 26 biomarkers
As mentioned above, for 10% off their blood tests, see this discount code.
To Conclude on David Sinclair Supplements…
- 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 David Sinclair 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)
- In terms of timing, he started resveratrol around 2004, and added NMN & Metformin in around 2017/2018.
- Then we went on to look at all the additional supplements David Sinclair discusses taking.
- Concluding with a mention of the blood testing he uses to monitor his health and ensure his supplement interventions are working.
Any questions or comments on David Sinclair supplements, please leave them below. You can search the 300+ comments using the search box at the top of the comments.
Sources for Supplement Doses
References for where David has mentioned taking these various supplements are shared below:
- Resveratrol & NMN: Doses come via David’s book Lifespan, page 304.
- NMN: In his March 18 2023 interview (see 21:25 of the YouTube video), he said he had dropped his dose of NMN down to 500 mg per day. Then, a month later in his April 13 2023 interview, he mentioned 1 gram again (see 43:37 of YouTube video).
- Metformin dosing: David mentions taking 800mg at night in Lifespan podcast episode 4. He also mentions skipping it the night before exercise. That section starts at 1hr 6mins. Then in the April 13 2023 interview he mentions 1 gram (see 43:55 of YouTube Video)
- Vitamin K2, D3, Aspirin: all also mentioned in his book Lifespan, page 304
- Statin: mentioned in his 2019 Joe Rogan interview (link) + 2020 Dave Asprey interview (link).
- Alpha Lipoic Acid, Fisetin, Omega-3 fish oils: see his April 13 2023 UAE presentation. Around 44m 11s of the YouTube video.
- Coenzyme Q10: see his March 2020 interview with Dave Asprey (link). Supplement discussion begins at ~19m 10s.
- Statin: see his interview with Joe Rogan at 1h 39m.
- Rapamycin: see his August 2023 interview with Peter Diamandis at 38:47.
- Taurine – See this interview clip where he says he’s experimenting with taking 2 grams of taurine per day. He also mentioned experimenting with it in a New York Times article (which he tweeted about).
Further Reading
If you liked this post, you may also find these interesting:
- Peter Attia’s Supplements – what he takes & why
- Andrew Huberman’s Supplements – Deep dive into what he takes & why
- Andy Galpin’s Supplements – used with his athletes for sports performance & recovery
References
- 1
- 2
- 3Calorie Restriction-like Effects of 30 Days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans – Schrauwen et al. – Cell Metabolism Journal (2011)
- 4Pilot Study of Resveratrol in Older Adults With Impaired Glucose Tolerance – Barzilai et al. (2012)
- 5
- 6Antihyperglycemic Effects of Short Term Resveratrol Supplementation in Type 2 Diabetic Patients – Netticadan et al. (2013)
- 7
- 8Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: A randomized controlled trial – Mi et al – Digestive and Liver Disease journal (2015)
- 9Resveratrol supplementation improves inflammatory biomarkers in patients with nonalcoholic fatty liver disease – Hekmatdoosta et al – 2014 – Nutrition Research Journal
- 10Consumption of a grape extract supplement containing resveratrol decreases oxidized LDL and ApoB in patients undergoing primary prevention of cardiovascular disease: A triple‐blind, 6‐month follow‐up, placebo‐controlled, randomized trial – Espín et al – 2012 – Molecular Nutrition & Food Research Journal
- 11One-Year Consumption of a Grape Nutraceutical Containing Resveratrol Improves the Inflammatory and Fibrinolytic Status of Patients in Primary Prevention of Cardiovascular Disease – Espín et al – 2012 – The American Journal of Cardiology
- 12Age-Associated Changes In Oxidative Stress and NAD Metabolism In Human Tissue – Massudi et al. | 2012 | PLoS ONE Journal
- 13
- 14Design and synthesis of compounds that extend yeast replicative lifespan – Sinclair et al. (2006)
- 15Sirtuin activators mimic caloric restriction and delay ageing in metazoans – Sinclair et al. (2004)
- 16Higher spermidine intake is linked to lower mortality: a prospective population-based study – Willeit et al. (2018) | The American Journal of Clinical Nutrition
- 17The positive effect of spermidine in older adults suffering from dementia – Pekar et al. (2019) – Wiener klinische Wochenschrift
- 18The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial – Wirth et al. (2018) – Cortex
- 19A ChIP-seq defined genome-wide map of vitamin D receptor binding: Associations with disease and evolution – Ramagopalan et al. (2010)
- 20
- 21Circulating uncarboxylated matrix Gla protein, a marker of vitamin K status, as a risk factor of cardiovascular disease – van den Heuvel et al. (2014)
- 22The relationship between vitamin K and peripheral arterial disease – Vissers et al. (2016)
- 23Lipoic acid: energy metabolism and redox regulation of transcription and cell signaling – Packer et al. (2011)
- 24Coenzyme Q10 and Statin-Induced Mitochondrial Dysfunction – Deichmann et al. (2010)
- 25Efficacy of Berberine in Patients with Type 2 Diabetes – Ye et al. (2009)
- 26
- 27Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice | Strong et al. | 2008 | Aging Cell