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ADJACENT COMPOUNDS

NAD+ and Resveratrol: The Sinclair Stack Explained (2026)

Disclosure: Nadosei sells an NMN supplement that also contains trans-resveratrol. This page explains the research first and names our product in one section near the end. David Sinclair has no connection to Nadosei.

"The Sinclair stack" is a name for the supplement routine that David Sinclair, a genetics professor at Harvard Medical School and co-author of the book Lifespan, has described in public. At its center is a pair: NMN, a precursor of NAD+, and resveratrol. This page explains what he reported, why the two compounds are paired, and what human studies show.

The quick answer

  • What he reported: a 2019 newspaper report said that Sinclair took 1 g of NMN, 1 g of resveratrol and 1 g of metformin each morning, plus vitamin D and aspirin [9]. Metformin is a prescription drug.
  • Why the pair: sirtuin enzymes use up NAD+ as they work, and resveratrol activates the sirtuin SIRT1 in lab studies [1].
  • What human studies show: NAD+ precursors raise NAD+ in people [5], and one NMN trial improved muscle insulin sensitivity [3]. For resveratrol, most evidence comes from cell and animal studies, and the body absorbs little of an oral dose in its active form [2].
  • Before you copy it: the routine includes drugs and high doses. Ask your doctor first.

What does David Sinclair take?

In October 2019, the year Lifespan came out, the German newspaper Berliner Zeitung described his routine: each morning, 1 g of NMN, 1 g of resveratrol and 1 g of metformin, plus vitamin D and aspirin [9]. The same report said that he avoided sugar, bread and pasta where he could, often skipped lunch, and had his blood tested every few months.

Three points matter if you want to copy this routine:

  • It is one person's routine from 2019. It can have changed since then, and nobody has tested it as a protocol.
  • Two items are drugs. Metformin is a prescription drug for type 2 diabetes, and aspirin is a drug with a bleeding risk. Only a doctor can decide if you should take them.
  • The doses are high. 1 g of NMN is four times the 250 mg a day that a 10-week human trial used [3]. Our NMN dosage guide explains the doses that human trials used.

Why pair NMN with resveratrol?

The pair rests on one enzyme family: the sirtuins. Mammals have seven of them, SIRT1 to SIRT7. They take part in stress responses, DNA repair and metabolism [1].

Two facts link the sirtuins to the pair:

  • Sirtuins use up NAD+. In each reaction, a sirtuin converts one NAD+ molecule into nicotinamide and O-acetyl-ADP-ribose [1]. So cells need a steady supply of NAD+ to keep sirtuins active, and NMN is a direct precursor of NAD+.
  • Resveratrol activates SIRT1 in lab studies. It belongs to a group of molecules that researchers call sirtuin-activating compounds, or STACs [1] [2].

The idea is simple: NMN supplies the NAD+ that sirtuins use, and resveratrol raises their activity. Most of the support for this idea comes from cell and animal studies. We found no published human trial that tested NMN and resveratrol together (PubMed search, October 2026).

A sirtuin enzyme with NAD+ flowing into it and resveratrol docked on its surface

What NMN and other NAD+ precursors do in human studies

  • NMN in women with prediabetes: in a 10-week randomized, placebo-controlled trial, 250 mg a day of NMN increased muscle insulin sensitivity in postmenopausal women with prediabetes who were overweight or obese [3].
  • NR in healthy adults: nicotinamide riboside (NR), another NAD+ precursor, raised NAD+ in the blood cells of healthy middle-aged and older adults and was well tolerated [5].
  • NMN in mice: in a 12-month study in mice, NMN reduced several age-related changes in metabolism and physiology without obvious toxicity [4]. Results in mice do not always carry over to people.

For the basics of NAD+, see our NAD+ supplement guide. For a full review of the NMN trials, see our complete NMN guide.

What resveratrol does in human studies

Resveratrol is a polyphenol from grape skins and some other plants. In lab studies, it activates SIRT1 [1]. In people, the main problem is bioavailability: the gut and the liver break down most of an oral dose quickly, so only a small part reaches the blood in its active form [2]. Human trials of resveratrol also differ in dose, length and the people they study, so their results are hard to compare.

So resveratrol is the less certain half of the pair. The 1 g in the 2019 report is a high dose.

Where TMG, quercetin and green tea extract fit

The 2019 report does not list these three compounds. They come from a different idea: support more pathways of cellular aging than the sirtuin pathway alone.

  • TMG (trimethylglycine, also called betaine) for methyl balance. The body clears extra nicotinamide with an enzyme, NNMT, that uses methyl groups [7]. TMG is a methyl donor, and in a meta-analysis of 5 trials, TMG lowered blood homocysteine in healthy adults [6]. Read more in our guide to TMG with NMN.
  • Quercetin for cellular senescence. Senescent cells stop dividing but stay in the tissue. Researchers study quercetin as a senolytic, a compound that targets these cells, mostly in lab and animal work and often together with the drug dasatinib [8].
  • Green tea extract for oxidative stress. Green tea extract supplies EGCG, a polyphenol that researchers study for its antioxidant activity.

Five ceramic dishes with NMN, TMG, resveratrol, quercetin and green tea extract powders

How Nadosei compares with the Sinclair stack

Nadosei is a science-backed longevity supplement with five research-validated compounds, one for each of five pathways of cellular aging: NMN for NAD+ decline, TMG for methyl balance, Resveratrol for sirtuin activity, Quercetin for cellular senescence and Green Tea Extract for oxidative stress.

One daily serving contains 500 mg NMN, 250 mg TMG, 100 mg trans-resveratrol, 150 mg quercetin and 100 mg green tea extract. That is half the NMN and one tenth of the resveratrol in the 2019 report. Nadosei contains no metformin and no aspirin, because those are drugs. See the full label on the Nadosei NMN product page.

Three ceramic dishes with NMN, TMG and resveratrol powders, joined by a gold thread

Is NMN legal as a supplement in the US?

Yes. On September 29, 2025, the FDA confirmed that NMN is not excluded from the definition of a dietary supplement, reversing its 2022 position and restoring NMN's status as a lawful dietary supplement ingredient in the US [10]. This is not "FDA approval": dietary supplements do not get FDA approval the way drugs do.

The bottom line

The Sinclair stack pairs NMN with resveratrol because sirtuins use up NAD+ and resveratrol activates SIRT1 in lab studies. Human trials show that NAD+ precursors raise NAD+, while the human evidence for resveratrol is less certain. The routine in the 2019 report also contains two drugs and high doses. Treat it as one scientist's personal choice, not as a tested protocol, and ask your doctor before you copy any part of it.

FREQUENTLY ASKED

What is the Sinclair stack?

"The Sinclair stack" is a name for the supplement routine that David Sinclair, a genetics professor at Harvard Medical School, has described in public. A 2019 Berliner Zeitung report said that he took 1 g of NMN, 1 g of resveratrol and 1 g of metformin each morning, plus vitamin D and aspirin. Metformin is a prescription drug. Sinclair has no connection to Nadosei.

How much NMN did David Sinclair report?

The 2019 report said 1 g (1,000 mg) of NMN each morning, together with 1 g of resveratrol. His routine can have changed since then. Human NMN trials have used lower amounts, for example 250 mg a day in a 10-week trial. Ask your doctor before you choose a dose.

Why pair NMN with resveratrol?

Sirtuins are enzymes that use up NAD+ when they work, and NMN is a precursor that the body turns into NAD+. In lab studies, resveratrol activates the sirtuin SIRT1. So the idea is that NMN supplies the NAD+ and resveratrol raises sirtuin activity. Most of the evidence for this pair comes from cell and animal studies.

Does resveratrol work in humans?

The human evidence is less certain than the lab evidence. Resveratrol activates SIRT1 in lab studies, but the body breaks down most of an oral dose quickly, so only a small part reaches the blood in its active form. Human trials differ in dose, length and the people they study, so their results are hard to compare.

Can I take NMN without resveratrol?

Yes. The human NMN trial on this page gave NMN alone, without resveratrol. If you want to add resveratrol, ask your doctor first, especially if you take medicines.

Does Nadosei follow the Sinclair stack?

Partly. Nadosei contains NMN and trans-resveratrol, plus TMG, quercetin and green tea extract. The amounts differ: one serving has 500 mg NMN and 100 mg trans-resveratrol, less than the 1 g of each in the 2019 report. Nadosei contains no drugs. Sinclair has no connection to Nadosei and does not endorse it.

References

  1. Bonkowski MS, Sinclair DA(2016). Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds. Nature Reviews Molecular Cell Biology, 17(11):679-690.[PMC5107309]
  2. Mohar DS, Malik S(2012). The Sirtuin System: The Holy Grail of Resveratrol?. Journal of Clinical & Experimental Cardiology.[PMC3613783]
  3. Yoshino M, Yoshino J, Kayser BD, et al.(2021). Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science, 372(6547):1224-1229.[PMC8550608]
  4. Mills KF, Yoshida S, Stein LR, et al.(2016). Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metabolism, 24(6):795-806.[PMC5668137]
  5. Martens CR, Denman BA, Mazzo MR, et al.(2018). Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature Communications, 9(1):1286.[PMC5876407]
  6. McRae MP(2013). Betaine supplementation decreases plasma homocysteine in healthy adult participants: a meta-analysis. Journal of Chiropractic Medicine, 12(1):20-25.[PMC3610948]
  7. Pissios P(2017). Nicotinamide N-methyltransferase: more than a vitamin B3 clearance enzyme. Trends in Endocrinology and Metabolism.[PMC5446048]
  8. Zhu Y, Tchkonia T, Pirtskhalava T, et al.(2015). The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell, 14(4):644-658.[PMC4531078]
  9. Berliner Zeitung(2019). Leben bis zum 150. Geburtstag: Einige Forscher halten einen Alters-Aufschub für möglich. Berliner Zeitung (German-language newspaper), 29 October 2019.[Link]
  10. Venable LLP(2025). FDA Declares Nicotinamide Mononucleotide Is Not Excluded From the Dietary Supplement Definition. Venable LLP, regulatory analysis.[Link]

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