Why We Added PQQ, Resveratrol and Quercetin to an NR Supplement

A plain NR capsule does one thing: supplies a precursor. simplyNAD+ adds three co-factors with separate literature behind them. Here is the reasoning for each, with the studies.

PQQ — 40mg

Pyrroloquinoline quinone is a redox cofactor found in foods like kiwi, green peppers and natto. In cell and animal work, PQQ activates PGC-1α, the master regulator of mitochondrial biogenesis — the process by which cells build new mitochondria (Chowanadisai et al., J Biol Chem 2010). Stites et al. (J Nutr 2006) showed PQQ-deprived mice had fewer mitochondria and lower respiration. If NAD+ is the fuel gauge, PQQ is aimed at the number of engines. A small human study (Harris et al., J Nutr Biochem 2013) reported changes in urinary metabolites consistent with improved mitochondrial function at 20mg/day.

Trans-resveratrol — 150mg

The grape-skin polyphenol. Its relevance to NAD+ is through sirtuins: resveratrol is the original SIRT1-activating compound described by Howitz et al. (Nature, 2003), and sirtuins are NAD+-dependent — they cannot work without it. Pairing a sirtuin activator with a NAD+ precursor is the logic of the stack. We use the trans isomer because that is the active form used in research (Baur & Sinclair, Nat Rev Drug Discov 2006).

Quercetin phytosome — 250mg

Quercetin is a flavonoid with poor oral bioavailability on its own. The phytosome form — quercetin bound to sunflower lecithin — was shown by Riva et al. (Eur J Drug Metab Pharmacokinet 2019) to reach the bloodstream roughly 20 times better than plain quercetin. Quercetin is also studied as a CD38 inhibitor in preclinical work (Escande et al., Diabetes 2013); CD38 is the main enzyme that degrades NAD+, so the idea is to slow the leak while NR fills the tank.

Why liquid changes the math

Buying these four separately means four bottles, roughly eight to ten capsules a day, and around $2.50–$4 per day. One 10g liquid packet holds all of it. The label lists every milligram — no proprietary blend.

How the four fit together

Think of NAD+ as a tank with an inlet, an outlet and a set of engines drawing from it. NR is the inlet — it supplies the precursor the salvage pathway turns into NAD+. Quercetin is aimed at the outlet: CD38, the enzyme that degrades most of the NAD+ a cell loses, is inhibited by quercetin in preclinical work. Resveratrol acts on the engines — sirtuins are the NAD+-dependent enzymes it was first described as activating. PQQ is aimed at building more engines, through PGC-1α and mitochondrial biogenesis. Nobody has run a trial on this exact four-ingredient combination, and we do not claim one exists. What exists is a separate literature for each, and a mechanistic reason they belong in the same packet rather than four separate bottles.

How our doses compare with the studies

PQQ 40mg — Harris et al. (2013) used 20mg per day in humans; 40mg is double that and within the range used in other published human PQQ studies. Trans-resveratrol 150mg — Timmers et al. (Cell Metabolism, 2011) used 150mg per day for 30 days in a placebo-controlled crossover study in men and reported calorie-restriction-like changes in energy metabolism; our dose matches theirs. Quercetin phytosome 250mg — Riva et al. (2019) showed the phytosome form increases quercetin absorption roughly 20-fold over plain quercetin, which is why 250mg of the phytosome is a meaningful dose where several grams of plain quercetin would not be. NR 600mg — inside the 250–1,000mg per day range used across the NR trials.

What we deliberately left out

• NMN — it becomes the same NAD+ through the same pathway as NR; adding it is paying twice.
• Caffeine or “energy” stimulants — they would make the product feel like it works on day one and tell you nothing about NAD+.
• A proprietary blend — every milligram is on the Supplement Facts panel. If we ever change a dose, the label changes with it.
• Preservatives — each packet is sealed and single-serve, so the liquid never sits open.

Safety and interactions

All four ingredients are sold as dietary supplements in the US and have human safety data at or above the doses used here. Two cautions are worth stating plainly: quercetin and resveratrol are both polyphenols that can influence liver enzymes involved in drug metabolism, and resveratrol has mild antiplatelet activity in some studies. If you take anticoagulants, or any medication your pharmacist has flagged for grapefruit interactions, talk to your doctor before starting. simplyNAD+ is not intended for people under 18 or for those who are pregnant or breastfeeding.

Frequently asked

Why phytosome quercetin instead of plain quercetin? Plain quercetin is poorly absorbed; binding it to sunflower lecithin (the phytosome) raises blood levels many-fold at the same dose.

Is the resveratrol from grapes? It is trans-resveratrol, the same isomer found in grape skin and Japanese knotweed and the form used in the human studies.

Do I need the co-factors, or is NR enough? NR alone raises NAD+ — the trials prove that. The co-factors are there because raising the pool and using it well are different problems.

Read next: What is NAD+? · How we test every batch

References

Chowanadisai W et al. J Biol Chem 2010;285:142–152 · Stites T et al. J Nutr 2006;136:390–396 · Harris CB et al. J Nutr Biochem 2013;24:2076–2084 · Howitz KT et al. Nature 2003;425:191–196 · Baur JA, Sinclair DA. Nat Rev Drug Discov 2006;5:493–506 · Riva A et al. Eur J Drug Metab Pharmacokinet 2019;44:169–177 · Escande C et al. Diabetes 2013;62:1084–1093 · Timmers S et al. Cell Metab 2011;14:612–622

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. This article is educational and is not medical advice — talk to your doctor before starting any supplement.