Resveratrol 600mg | Trans-Resveratrol for SIRT1 Activation, NAD+ & Longevity

600 mg of trans-resveratrol per capsule — the SIRT1-activating polyphenol that anchors the canonical NMN + resveratrol longevity stack. ≥98% HPLC-verified trans-anomer from Polygonum cuspidatum root extract, vegan capsule, no fillers, no proprietary blends. Stack-grade dose, not a label-claim dose.

The 30-second answer

• The polyphenol that put sirtuins on the longevity map. Howitz 2003 Nature identified resveratrol as the most potent natural sirtuin-activating compound (STAC) ever screened; Baur 2006 Nature showed it extended lifespan in calorically-stressed mice; Hubbard 2013 Science solved the SIRT1 allosteric crystal structure. Two decades and 13,000+ PubMed hits in, trans-resveratrol remains the canonical SIRT1 activator.
• One capsule, daily, with the largest fat-containing meal. Resveratrol is fat-soluble — fasted dosing throws away most of the pill. Pair with breakfast (eggs, avocado, fatty fish, olive oil) or lunch.
• Best paired with NMN 500 mg or NMN 1000 mg. NMN raises NAD+ substrate; resveratrol activates the SIRT1/SIRT3 enzymes that use that NAD+. Substrate + activator. Get both at -10% as the Longevity Stack Bundle.
• 600 mg is the stack-grade dose. 100–250 mg is where the "resveratrol doesn't work in humans" meta-analyses concentrate; 500–1000 mg/day is where the cardiometabolic and SIRT1 data live (Tomé-Carneiro 2012/2013, Bhatt 2012, Movahed 2013, Pollack 2017).
• ≥98% HPLC trans-resveratrol. The bioactive anomer — not the cis-isomer UV-degradation product cheap brands ship. Per-batch third-party COA, heavy-metals/microbial/residual-solvents panel, vegan HPMC capsule, no titanium dioxide, no magnesium stearate, no rice-flour bulker.

Why resveratrol still anchors a serious longevity stack — even after the noise

If you only read the headlines, you'd think resveratrol got debunked. It didn't. What got debunked was the 1 mg of resveratrol in a glass of red wine story — Smoliga 2011 (Mol Nutr Food Res) showed you'd need ~1,500 bottles a day to hit the doses tested in the original Sinclair-lab mouse work. The science on the molecule itself kept moving in the right direction.

The López-Otín 2013 (Cell) and updated 2023 hallmarks-of-aging frameworks list deregulated nutrient sensing, mitochondrial dysfunction, chronic inflammation, and cellular senescence among the twelve hallmarks. Resveratrol hits all four:

• Sirtuin activation (SIRT1, SIRT3) — the deacetylase axis that converts NAD+ into longevity-relevant outputs (PGC-1α, FOXO3a, p53, eNOS deacetylation).
• AMPK activation — the same fuel-sensor pathway hit by metformin, berberine, and exercise (Park 2012, Cell).
• NF-κB suppression / inflammaging — inhibits IKK, stabilizes IκB, dampens p65 nuclear translocation (Csiszar 2008).
• Endothelial protection — upregulates eNOS expression and activity (Wallerath 2002, Circulation); Tomé-Carneiro 2013 showed 350 mg/day for 12 months reduced oxidized LDL by 20% in CHD patients already on statins.

None of this requires resveratrol to be a magic pill. It just has to be the polyphenol with the strongest, longest-validated sirtuin-and-AMPK story across the most diverse organism panel — which it is.

Mechanism — what resveratrol actually does inside the cell

1. SIRT1 allosteric activation (the NMN partner)

SIRT1 is the most-studied of the seven mammalian sirtuins. It's a class-III deacetylase, meaning it consumes NAD+ as a co-substrate to remove acetyl groups from longevity-relevant substrates: PGC-1α (mitochondrial biogenesis), FOXO3a (stress resistance, antioxidant gene expression), p53 (apoptosis tone), eNOS (vasodilation), NF-κB p65 (inflammation suppression), and the histone H3K9/H4K16 marks that gate the inflammatory transcriptome.

Without enough NAD+, SIRT1 stalls. Without an allosteric activator, SIRT1 runs at baseline. Resveratrol covers the second half. Hubbard 2013 (Science) crystallized the SIRT1 N-terminal allosteric domain and showed resveratrol binds at a defined activator pocket, increasing SIRT1 activity toward acetylated substrates by up to 8-fold for substrates carrying hydrophobic recognition motifs. This resolved the earlier "is the activation real or a fluorophore artifact?" debate cleanly in resveratrol's favor.

This is the mechanistic argument for stacking NMN (substrate) + resveratrol (activator). NMN raises the NAD+ floor; resveratrol pushes the SIRT1 enzyme that uses it. Either alone is meaningfully under-leveraged; together they multiply.

2. SIRT3 and the mitochondrial deacetylase axis

SIRT3 is the major mitochondrial sirtuin and deacetylates ~65% of all mitochondrial-matrix lysine-acetyl marks. Its substrates include SOD2 (the manganese superoxide dismutase that scavenges mitochondrial ROS), OPA1 (mitochondrial fusion), and core ETC components. Resveratrol upregulates SIRT3 transcription and protein levels via PGC-1α-driven nuclear-respiratory-factor signaling — the same loop AMPK feeds into. Functionally, this is the leg behind resveratrol's mitochondrial-biogenesis signal in muscle (Lagouge 2006, Cell) and the SOD2-mediated antioxidant signal that reduces mitochondrial-derived 8-oxo-dG damage in aging tissue.

3. AMPK activation (the metabolic fuel-sensor)

Independent of sirtuins, resveratrol activates AMPK by inhibiting mitochondrial F1F0-ATP synthase (Park 2012, Cell). Falling cellular ATP raises the AMP:ATP ratio, which is the upstream nudge AMPK senses. Activated AMPK then:

• Phosphorylates and inactivates ACC (acetyl-CoA carboxylase) → lipid β-oxidation up.
• Phosphorylates and inhibits mTORC1 via TSC2 → catabolic autophagy up, anabolic protein synthesis down.
• Phosphorylates PGC-1α at Thr177/Ser538 → mitochondrial biogenesis up, in concert with the SIRT1-deacetylation hit at the same protein.
• Translocates GLUT4 to muscle membrane → insulin-independent glucose uptake.

This is why the cardiometabolic trial signal for resveratrol is strongest in patients with insulin resistance, established CHD, or metabolic syndrome — the AMPK leg pulls weight even when the sirtuin leg is debated. It's also why resveratrol stacks cleanly with metformin and berberine: three different upstream inputs into the same fuel-sensor.

4. NF-κB suppression (the inflammaging dampener)

NF-κB is the transcription-factor central node behind senescent-cell SASP secretion, chronic CRP elevation, and most age-associated inflammatory tone. The López-Otín 2023 hallmarks paper added "chronic inflammation" as a standalone hallmark for exactly this reason. Resveratrol inhibits NF-κB activation at multiple steps:

• IKK suppression — blocks the kinase complex that phosphorylates IκB.
• IκBα stabilization — keeps the inhibitor bound to NF-κB longer.
• p65 nuclear-translocation block — even if some NF-κB escapes, less of it reaches DNA.
• SIRT1-mediated p65 deacetylation — Lys310 deacetylation reduces NF-κB transactivation (Yeung 2004, EMBO J).

Csiszar 2008 (Mech Ageing Dev) demonstrated this in human coronary arterial endothelial cells; the effect is reproduced across hepatocytes, macrophages, and chondrocytes. This dovetails with the senolytic + NF-κB-suppression strategy: senolytics (Quercetin, Fisetin) clear senescent cells; resveratrol dampens the inflammatory tone the surviving cells secrete.

5. Endothelial / eNOS upregulation

Wallerath 2002 (Circulation) showed resveratrol upregulates endothelial nitric oxide synthase (eNOS) at both transcriptional and post-translational levels. eNOS-derived NO is the master vasodilator and a key brake on platelet aggregation and leukocyte adhesion to the endothelium. The signal is dose-dependent and clinically translates: Tomé-Carneiro's Spanish CHD-cohort series (2012/2013) showed grape-extract resveratrol (350 mg/day for 6–12 months) improved flow-mediated dilation, reduced oxidized LDL, and shifted multiple inflammatory apolipoproteins, in patients already optimized on statins.

This is part of why resveratrol kept its seat at the table after the "French paradox" framing aged badly — the molecular eNOS / NF-κB / SIRT1 mechanisms hold up even when the "red wine prevents heart disease" narrative doesn't.

6. Autophagy and the mTOR brake

Through both AMPK activation and direct ULK1 phosphorylation, resveratrol induces macroautophagy — the cellular self-clearance program that clears damaged organelles, aggregated proteins, and dysfunctional mitochondria (mitophagy via PINK1/Parkin). Pietrocola 2017 showed resveratrol triggers an autophagic signature in skeletal muscle that is mechanistically distinct from the spermidine-driven EP300 inhibition route, meaning the two stack additively. This is the leg behind the proteostasis-restoration argument for resveratrol — stacked with spermidine, you cover both major upstream autophagy switches.

The trans-anomer — what "≥98% trans-resveratrol" actually means

Resveratrol exists as two stereoisomers:

• trans-resveratrol — the bioactive form. Every clinical trial measured this. Every SIRT1, AMPK, NF-κB, and eNOS mechanism documented above is trans-resveratrol's signature. This is the molecule the Sinclair lab tested, the molecule Tomé-Carneiro dosed, the molecule Hubbard crystallized.
• cis-resveratrol — a UV-degradation product. The double bond in the stilbene core photoisomerizes from trans to cis under exposure to ultraviolet light, oxygen, and heat. Cis-resveratrol has dramatically reduced SIRT1 binding affinity and minimal in-vivo activity in published comparisons.

Cheap resveratrol products mix them — and because cis-resveratrol can't be distinguished from trans by simple UV-Vis spectrophotometry (the cheap industry-standard assay), label claims that don't specify HPLC are often inflated by cis-isomer drift that occurred during storage, processing, or shipping. ≥98% HPLC trans-resveratrol means each batch is run on high-pressure liquid chromatography with diode-array detection at 308 nm — the assay that actually separates the two anomers.

The other 2% is residual Polygonum cuspidatum polyphenols (emodin, polydatin, piceid) at trace level, not cis-isomer drift. This is the molecular-grade material, not the food-grade material.

Why Polygonum cuspidatum (Japanese knotweed)

Trans-resveratrol can be extracted from grape skins, peanut hulls, or Polygonum cuspidatum (Japanese knotweed) root. The Sinclair-lab work, the Tomé-Carneiro Spanish CHD trials, and the bulk of the human cardiometabolic literature all use P. cuspidatum for one reason: natural concentration. Knotweed root contains 2–5% trans-resveratrol by dry weight, versus 0.001–0.01% in grape skin. That means knotweed extract reaches ≥98% HPLC purity through standard solvent partitioning; grape-skin extract requires aggressive chromatographic purification that often leaves residual matrix polyphenols and pesticide residues.

This product uses Polygonum cuspidatum root extract, ethanol/water partitioned, recrystallized, ≥98% HPLC trans-resveratrol. Same source class as the trial materials.

Clinical evidence — the trials that anchor 600 mg

The "resveratrol works / doesn't work" debate gets cleaner once you stratify by dose, formulation, and population. Here is the evidence we anchor 600 mg on.

Cardiometabolic — the strongest signal

• Tomé-Carneiro 2012 (Am J Cardiol) — CHD patients on statins, 350 mg/day grape-extract resveratrol for 6 months. Significant increase in serum adiponectin, downregulation of pro-inflammatory genes (CCL3, IL-1β, TNF-α) in PBMCs, reduction in atherogenic apolipoproteins. This is the cardiology-on-statins benchmark trial.
• Tomé-Carneiro 2013 (Mol Nutr Food Res) — same cohort, 12-month follow-up. Persistent reduction in oxidized LDL by ~20%, sustained anti-inflammatory transcriptional shift. The signal didn't wash out with longer dosing — which is the question every "transient effect" critic raised in 2010.
• Bhatt 2012 (Nutr Res) — type 2 diabetics, 250 mg/day for 3 months. Significant reductions in HbA1c, systolic BP, total cholesterol. Lower dose, smaller effect, but the same direction.
• Movahed 2013 (Evid Based Complement Alternat Med) — type 2 diabetics, 1000 mg/day for 45 days. Significant reductions in fasting glucose, HbA1c, systolic BP, and total cholesterol; significant rise in HDL. Higher dose, bigger effect.
• Pollack 2017 (Cardiovasc Drugs Ther) — older adults with insulin resistance, 1000–2000 mg/day for 6 weeks. Improved peripheral and hepatic insulin sensitivity by clamp; the dose-response argument crystallized in this trial.

Cognition and cerebral blood flow

• Kennedy 2010 (Am J Clin Nutr) — healthy adults, 250 and 500 mg single oral doses. Dose-dependent increase in cerebral blood-flow velocity and oxy/deoxy-Hb in the prefrontal cortex (NIRS). Acute mechanism: eNOS/NO-driven vasodilation crossing into cerebral circulation.
• Witte 2014 (J Neurosci) — overweight older adults, 200 mg/day for 26 weeks. Improved memory performance and increased hippocampal functional connectivity, with reductions in glycated hemoglobin and body fat that paralleled the cognitive shift.
• Evans 2017 (Nutrients) — postmenopausal women, 75 mg twice daily for 14 weeks. Improved cerebrovascular responsiveness and aspects of cognitive performance, again pointing at the vascular leg.

Bone, postmenopausal physiology, and inflammaging

• Ornstrup 2014 (J Clin Endocrinol Metab) — obese men, 500 mg twice daily for 16 weeks. Increased bone mineral density at lumbar spine and improved bone turnover markers. Suggests SIRT1-mediated osteoblast support is translating clinically.
• Wong 2017 / 2019 (RESHAW trial, Int J Cardiol) — postmenopausal women, 75 mg twice daily for 12+24 months. Sustained improvements in cerebrovascular responsiveness, mood, and selected cardiometabolic markers.

Where the evidence is preliminary

• All-cause mortality / lifespan in humans — no powered RCT exists and won't (ethics, timeline, expense). The animal lifespan signal is real (Baur 2006 in obese mice; lifespan extension in S. cerevisiae, C. elegans, Drosophila); human evidence is biomarker-level.
• Resveratrol monotherapy in elite/young endurance athletes — Gliemann 2013 saw blunted training-induced cardiovascular adaptations in 60+ men at 250 mg/day; signal hasn't replicated cleanly elsewhere, but the data exist. See contraindications.
• Cancer chemoprevention — preclinical signal is broad but human trials are early-phase and small.

The case for 600 mg over 100 mg or 250 mg

Most over-the-counter resveratrol caps at 100–250 mg, which is exactly the range where the "resveratrol doesn't work in humans" meta-analyses concentrate. The dose-response data tell a different story:

• Bioavailability is the limiting factor, not safety. Walle 2004 (Drug Metab Dispos) measured <1% free resveratrol in plasma after a 25 mg oral dose — but ~70% absorption, just rapidly glucuronidated and sulfated by phase-II liver metabolism. To get clinically meaningful free + conjugated AUC, you need 500 mg+ per dose.
• The trials that worked used 500–1000 mg/day. Tomé-Carneiro 2012 used 350 mg of a co-formulated grape extract (which improves uptake), but the broader cardiometabolic literature (Bhatt 2012, Movahed 2013, Pollack 2017, Ornstrup 2014) clusters at 500–1000 mg/day. The Sinclair-lab mouse work scales to a human equivalent of ~750 mg/day.
• 600 mg is the floor for serious longevity stacking. If you're running NMN at 500–1000 mg/day for sirtuin substrate, the matched activator dose lives at 500–1000 mg trans-resveratrol — taken with a fat-containing meal so the lipid solubilization hits.
• Above 1,000 mg/day adds GI side effects without proportional benefit. Brown 2010 (Cancer Res) saw mild diarrhea and GI cramping appear at 2.5 g/day and above. 600 mg lands inside the high-tolerability window — meaningful free + conjugated AUC, no dose-limiting GI tone.

Translation: 100 mg is a label-claim dose. 250 mg is a hedge. 600 mg is a stack-grade dose.

Bioavailability — what the PK studies actually show

Resveratrol's pharmacokinetics are unusual and worth understanding because they explain the whole "take it with fat" rule.

• Absorption is high. Walle 2004 measured ~70% intestinal absorption of an oral dose. The bottleneck isn't getting it across the gut wall.
• First-pass hepatic conjugation is aggressive. The liver glucuronidates and sulfates resveratrol within minutes via UGT1A1 and SULT1A1. Measured plasma free resveratrol after 25 mg oral was <5 ng/mL.
• Conjugates are not inert. Patel 2013 and follow-up work show resveratrol-3-O-sulfate and resveratrol-glucuronides are themselves bioactive at physiological concentrations and can be deconjugated locally in tissue by sulfatases and β-glucuronidases — a "circulating depot" model. Total free + conjugated AUC is what matters clinically, not free-fraction alone.
• Fat-containing meal roughly doubles AUC. Vaz-da-Silva 2008 (Int J Clin Pharmacol Ther) showed AUC was significantly higher when resveratrol was administered with a standard meal versus fasting. La Porte 2010 confirmed across formulations.
• Half-life is ~9 hours for total radioactivity. One dose per day at 600 mg keeps measurable plasma exposure across the waking-hours window where SIRT1 demand is highest.

The practical translation: take 600 mg with breakfast or lunch (whichever has more fat). Don't take it on an empty stomach unless you want to throw away half the dose. Don't split it into 3×200 mg — the per-dose bioavailability ceiling falls off below 500 mg.

How resveratrol maps onto the hallmarks of aging

The López-Otín hallmarks (2013, updated 2023) are the field-standard taxonomy of biological aging. Resveratrol touches more of them than any other single polyphenol on our shelf:

• Deregulated nutrient sensing — AMPK activation; mTOR suppression via AMPK-TSC2; SIRT1 deacetylation of mTORC1 substrates.
• Mitochondrial dysfunction — PGC-1α deacetylation by SIRT1; SIRT3-mediated SOD2 and ETC-component activation; AMPK-driven mitochondrial biogenesis.
• Cellular senescence / chronic inflammation — NF-κB suppression at IKK + p65 levels; SASP-cytokine dampening; pairs with senolytic protocols (quercetin/fisetin) by clearing residual inflammation after the senescent cells themselves are removed.
• Epigenetic alterations — SIRT1/SIRT3-mediated histone deacetylation (H3K9, H4K16); modulation of DNA-methyltransferase activity; SIRT-dependent chromatin remodeling.
• Loss of proteostasis / autophagy decline — AMPK→ULK1-driven macroautophagy; mitophagy via PINK1/Parkin upstream signal; complementary to spermidine's EP300-inhibition route.
• Altered intercellular communication — eNOS upregulation; SIRT1 deacetylation of endothelial transcription factors; reduced systemic inflammatory tone.

That's six of the twelve hallmarks with mechanism-grade evidence in a single molecule. This is the structural reason resveratrol earned the "polyphenol that anchors a stack" position.

Resveratrol vs pterostilbene — the practical decision

Pterostilbene is resveratrol's dimethylated cousin. Two methoxy groups in place of two hydroxyls makes it more lipid-soluble, less subject to first-pass conjugation, and longer-lived in plasma. So why isn't this the default?

• Trial base. Resveratrol has 200+ human trials and 20+ years of mechanistic data. Pterostilbene has <10 published human trials and no long-term cardiometabolic series.
• SIRT1 affinity. Resveratrol is the canonical SIRT1 allosteric activator. Pterostilbene activates SIRT1 in vitro but with less-characterized binding-site behavior; head-to-head assays don't put it ahead of resveratrol on a per-mole basis at the SIRT1 site.
• LDL signal. Pterostilbene at 250 mg/day has shown a small LDL-elevation in some studies (Riche 2014), which is not the direction you want for a longevity polyphenol. Resveratrol either reduces LDL-ox (Tomé-Carneiro 2012/2013) or is neutral on LDL.
• Cost-per-mg. Pterostilbene is roughly 5–10x more expensive at equivalent doses. The bioavailability advantage (~3x AUC versus standard resveratrol) doesn't close that gap.

We anchor the SIRT1 leg with trans-resveratrol because the evidence base is wider, the dose-response is well-characterized, and the cost-per-effective-dose is meaningfully lower. If you want both, pterostilbene 100–150 mg/day stacks on top of resveratrol 600 mg without conflict — resveratrol covers the trial-base / cardiometabolic / NF-κB legs; pterostilbene reinforces the longer plasma exposure window.

Source comparison — what "resveratrol" can mean on a label

Where this fits in our NAD+ / longevity family

Resveratrol is one of three legs in the canonical sirtuin axis we run on this site:

• NAD+ substrate (precursor floor) — NMN 500mg, NMN 1000mg, Liposomal NAD+, Liquid NAD+ NR stick packs. Raises the NAD+ ceiling SIRT1/SIRT3 can draw on.
• Sirtuin activator (allosteric) — this product. Pushes SIRT1/SIRT3 enzymatic activity at any given NAD+ concentration. The activator side of the equation.
• Methyl-donor support — TMG 1000mg. Replenishes the SAMe methyl-pool that the NAD+→NAM→methylation pathway draws on at long-term high doses.

The convenience option — get all three sirtuin pieces at -10% — is the Longevity Stack Bundle (NMN 500 + Resveratrol 600).

Beyond the sirtuin axis, resveratrol pairs with a wider longevity protocol:

• Senolytics — Quercetin 500mg, Fisetin 500mg. Senolytics clear senescent cells; resveratrol dampens residual SASP inflammation.
• Mitochondrial layer — CoQ10 400mg, Urolithin A 500mg, CaAKG 1000mg. Resveratrol drives mitochondrial biogenesis upstream; these support what the new mitochondria do downstream.
• AMPK / metabolic — Berberine, metformin (Rx). All three converge on AMPK by different upstream routes.
• NF-κB / anti-inflammatory — Curcumin 1000mg + BioPerine. Both suppress NF-κB; BioPerine improves both molecules' bioavailability.

Stacking matrix

What to expect — week by week

Resveratrol is not a stimulant. There is no acute "feel" effect on the first dose. The biological signals appear on different timelines:

• Days 1–7: Acute eNOS / cerebral-blood-flow signal can register on the first day (Kennedy 2010 — single 250–500 mg dose increased prefrontal CBF measurably). For most users this is below subjective threshold but real on instrumentation.
• Weeks 2–4: Inflammatory-tone shifts begin (CRP, fibrinogen, IL-6). Most users notice a generalized "less inflammation" baseline — fewer joint complaints, faster recovery from training. SIRT1 substrate-deacetylation signaling has reached steady state.
• Weeks 4–8: Lipid panel begins to shift in the cardiometabolic-risk subset (oxidized LDL down, HDL up modestly, triglycerides flat-to-down). Insulin-sensitivity changes appear in HOMA-IR and OGTT data on this timeline.
• Weeks 8–12: The Tomé-Carneiro biomarker timeline. LDL-ox reduction, atherogenic apolipoprotein shift, sustained anti-inflammatory transcriptional signature in PBMCs.
• Weeks 12+: Bone turnover markers and BMD changes in the relevant populations (Ornstrup 2014 saw lumbar BMD increase at 16 weeks). Cognitive / memory shifts appear in older adults around this timeline (Witte 2014 — 26-week trial).

Run for 12 weeks minimum, recheck labs. The signal is biomarker-level and accumulative; this is not a "feel it on day 3" molecule.

Daily protocol

1 capsule per day, taken with the largest fat-containing meal of the day.

Resveratrol is fat-soluble and heavily phase-II-conjugated by the liver. Walle 2004, Vaz-da-Silva 2008, and Smoliga 2011 all converge: taking resveratrol on an empty stomach throws away most of the dose. With a fat-containing meal — even just olive oil, eggs, fatty fish, or avocado — measured plasma AUC roughly doubles versus fasted dosing.

Timing notes:

• Default: with breakfast or lunch (whichever is the larger fat-containing meal). Aligns with the AM dose of NMN if you're stacking.
• Stacking with NMN: same meal as the morning NMN dose. This is the canonical Sinclair-protocol pairing — substrate + activator hit the SIRT1 axis together.
• Pre-workout: some users dose 60–90 minutes before resistance training to leverage the AMPK / mitochondrial-biogenesis crossover. Note the Gliemann 2013 caveat below before doing this if you're an older endurance athlete.
• With BioPerine / curcumin: piperine inhibits CYP3A4 and raises resveratrol AUC by roughly 1.5–2x in the published bioavailability studies. If you're already taking Curcumin + BioPerine with breakfast, your resveratrol AUC is going up too — for free.
• Avoid grapefruit juice the same day. Grapefruit competes for the same CYP3A4 / UGT pathway resveratrol uses; the effect on AUC is real but not dangerous.
• Don't take it before bed. Cerebral blood-flow upregulation can interfere with sleep onset for sensitive users.

What this product is — and is NOT

• Is: 600 mg of ≥98% HPLC trans-resveratrol per capsule, sourced from Polygonum cuspidatum (Japanese knotweed) root extract, in a vegan HPMC capsule, with no fillers, no proprietary blends, no titanium dioxide, no magnesium stearate.
• Is: Per-batch HPLC-verified for trans-anomer purity (308 nm DAD); independently tested for heavy metals (USP <232>), microbials (USP <2021>), and residual solvents (USP <467>).
• Is NOT: A grape-skin extract. Knotweed-sourced trans-resveratrol is the trial-grade material; grape-skin extract is a different (and more variable) product class.
• Is NOT: A "resveratrol complex." There's no quercetin, grape-seed extract, green-tea extract, or pterostilbene mixed in. Those are real ingredients but you can't dose them properly when they're hidden inside a single 600 mg capsule. We sell them separately when relevant.
• Is NOT: A liposomal or micronized formulation. At 600 mg with a fat-containing meal, you're already in the clinically-validated AUC range without paying the 4–5x premium that liposomal resveratrol commands.
• Is NOT: A treatment for any specific disease. This is a longevity-stack supplement, not a cardiology drug, not a cancer therapeutic. Talk to your physician.

Common mistakes to avoid

• Taking it on an empty stomach. Roughly halves the AUC. Always with a fat-containing meal.
• Splitting 600 mg into 3×200 mg doses. The per-dose absorption ceiling falls off below 500 mg — splitting reduces total daily AUC, not increases it.
• Buying 100 mg products and taking 6 capsules. Math works, but you're paying 3–5x per active mg and usually the source/spec isn't HPLC-verified at the lower price point.
• Stopping after 4 weeks because nothing happened. The cardiometabolic biomarker timeline is 8–12 weeks. The SIRT1 axis steady-state is 4 weeks. The cognitive / BMD signals are 16–26 weeks. Don't bail at week 4.
• Stacking resveratrol with grapefruit juice. CYP3A4 competition. Not dangerous, but reduces predictability of dose-response.
• Running resveratrol monotherapy with no NAD+ precursor. Resveratrol activates SIRT1, but SIRT1 needs NAD+ as substrate. Without NMN or NR floor-raising, you're flooring the gas with the tank low.
• Buying generic UV-Vis "resveratrol" and assuming it's trans. UV-Vis can't distinguish trans from cis. Cis-isomer drift in poorly-stored material can reduce label-active dose by 30%+ silently.

Who this is for

• Adults 35+ running a serious longevity stack who want the canonical SIRT1 activator.
• Anyone already taking NMN or NR who hasn't yet added the activator side of the equation.
• People with cardiometabolic risk factors (elevated LDL-ox, insulin resistance, family history of CHD) who want a polyphenol with documented eNOS / NF-κB / AMPK signal at trial-grade dose.
• Stack-builders who want one molecule that does sirtuin co-activation + AMPK activation + NF-κB suppression + endothelial support simultaneously, rather than four separate inputs.
• Postmenopausal women looking at cardiovascular and bone-density support (Wong / RESHAW; Ornstrup 2014).

Who this is NOT for

• Pregnancy or breastfeeding. Insufficient human safety data above the dietary trace doses. Don't.
• Active hormone-sensitive cancer (breast, ovarian, endometrial, prostate). Resveratrol is a phytoestrogen with weak ER-binding affinity (~7,000x less than estradiol, tissue-specific). Clinical relevance at 600 mg is small for healthy adults but not zero — discuss with your oncologist before adding.
• On warfarin or active anti-platelet therapy. Resveratrol has mild antiplatelet effects in vitro (Pace-Asciak 1995); the clinical relevance at 600 mg is small but nonzero. Monitor INR if you're running both.
• Older competitive endurance athletes. Gliemann 2013 (J Physiol) showed 250 mg/day resveratrol blunted training-induced cardiovascular adaptations in 60+ men. The signal hasn't replicated cleanly in younger or recreational populations, but the data exist; if you're a competitive masters endurance athlete in a periodized peak block, time resveratrol around recovery weeks rather than peak-training weeks.
• Allergic to Polygonum cuspidatum. Rare but documented. Skin reactions, GI cramping. Stop and don't restart.
• Taking strong CYP3A4 inhibitors (clarithromycin, ketoconazole, ritonavir). Resveratrol AUC will rise unpredictably; talk to your prescriber.

Safety, interactions, and contraindications

Resveratrol has one of the cleanest oral safety profiles in the longevity-supplement space at <1 g/day. Brown 2010 (Cancer Res) tested 0.5–5 g daily for 29 days with no dose-limiting toxicity below 2.5 g; mild diarrhea / GI cramping appeared above that. 600 mg sits well below any documented dose-limiting tolerance threshold.

• Anticoagulants / antiplatelets. Mild antiplatelet effect in vitro (Pace-Asciak 1995); clinical relevance at 600 mg is small but real. Monitor INR if on warfarin; talk to prescriber if on dual antiplatelet therapy after stenting.
• CYP3A4 substrates. Resveratrol is a mild CYP3A4 inhibitor. Drugs metabolized through CYP3A4 (statins, calcium-channel blockers, some immunosuppressants) may have modestly elevated AUC. Talk to prescriber.
• UGT1A1 substrates. Resveratrol competes for hepatic glucuronidation. Drugs heavily UGT1A1-cleared (irinotecan metabolites, raltegravir) may behave unpredictably.
• Estrogen-modulating drugs. Tamoxifen, aromatase inhibitors, hormonal contraceptives — discuss with your prescriber given resveratrol's weak ER-binding profile.
• SSRIs and MAOIs. No documented interaction at 600 mg. Resveratrol's mild MAO-inhibition signal is at much higher doses than typical supplementation hits.

What's in it

Per capsule:

• Trans-resveratrol — 600 mg, from Polygonum cuspidatum root extract, ≥98% HPLC trans-anomer.
• Vegan HPMC capsule. No gelatin.

What's NOT in it: No magnesium stearate, no silicon dioxide, no titanium dioxide, no maltodextrin, no rice flour, no proprietary blends, no cis-isomer drift, no inflated UV-Vis label claim. 600 mg is 600 mg of trans-resveratrol — not 600 mg of an "antioxidant complex" that turns out to be 50 mg resveratrol + 550 mg cellulose.

Allergens: No gluten, no soy, no dairy, no nuts, no shellfish, no eggs.

Sourcing, manufacturing, and quality control

• Source: Polygonum cuspidatum root extract, ethanol/water partitioned, recrystallized to ≥98% trans-resveratrol by HPLC.
• Manufacturing: cGMP-registered facility, NSF-audited; capsules filled under controlled humidity in opaque amber blister-stable bottles.
• Per-batch testing: HPLC identity + potency at 308 nm (DAD); cis-isomer screen; heavy metals (USP <232>) for As/Cd/Hg/Pb; microbial limits (USP <2021>) for total aerobic, yeast/mold, E. coli, Salmonella; residual solvents (USP <467>).
• Stability: Validated 24-month room-temperature stability under amber-bottle storage. Resveratrol is photo-sensitive — keep the bottle closed.
• Public COA: per-batch certificate of analysis available at truehealthprotocol.health/pages/coa.

Frequently asked questions

Does resveratrol actually extend lifespan in humans?

No human RCT is powered for all-cause-mortality endpoints (the trial would take 30+ years and be ethically contested). What we have: lifespan extension in S. cerevisiae, C. elegans, Drosophila, and obese mice (Baur 2006); biomarker improvement across the cardiometabolic literature (Tomé-Carneiro 2012/2013, Movahed 2013, Pollack 2017); mechanistic plausibility via SIRT1, AMPK, NF-κB, and eNOS. Treat resveratrol like the rest of the longevity stack — high-evidence biomarker work, mechanistic translation from animal lifespan data, ride the convergence.

Resveratrol vs pterostilbene — which is "better"?

Pterostilbene is resveratrol's dimethylated cousin with better bioavailability (more lipid-soluble, less first-pass conjugation, longer plasma half-life) but a much thinner trial base. Resveratrol has 200+ human trials and 20+ years of mechanistic data; pterostilbene has <10 published human trials. We anchor the SIRT1 leg with resveratrol because the evidence base is wider and the dose-response is well-characterized. If you want both, pterostilbene 100–150 mg/day stacks fine on top of resveratrol 600 mg.

Why not micronized or liposomal resveratrol?

Both improve absorption modestly (~1.5–2x AUC vs standard). At 600 mg trans-resveratrol from Polygonum cuspidatum in a fat-containing meal, you're already in the clinically active plasma range. The cost premium for liposomal (often 4–5x per active mg) doesn't pencil out for most users. We'd rather give you the verifiable molecular-grade material at a serious dose.

How long until I notice anything?

Resveratrol isn't a stimulant. The cardiometabolic biomarker shifts (LDL-ox, CRP, fasting insulin) appear in trials at 8–12 weeks. Bone-density and cognitive shifts take 16–26 weeks. Acute "feel" effects (energy, mental clarity) on day-1 are typically downstream of NMN substrate availability — this is why the NMN + resveratrol pairing is the standard. Run for 12 weeks minimum, recheck labs.

Can I take it with metformin or berberine?

Yes — and it's mechanistically synergistic. All three activate AMPK by different upstream routes: metformin via complex I inhibition, berberine via direct AMPK-α1 phosphorylation, resveratrol via F1F0-ATP synthase inhibition. Resveratrol's SIRT1 leg is independent of metformin's mechanism. The classic metabolic-syndrome stack is metformin (or berberine) + resveratrol + NMN.

Why not just drink red wine?

Because the dose math doesn't work. A 5 oz glass of red wine contains roughly 0.3–1.0 mg trans-resveratrol. 600 mg is the equivalent of 600–2,000 glasses. Even ignoring the alcohol harm-curve, the resveratrol math is impossible from food. The "French paradox" was never about resveratrol-the-molecule; it was about overall polyphenol intake plus Mediterranean-diet effects.

Does resveratrol affect estrogen?

Weakly. Resveratrol binds estrogen receptors with ~7,000x lower affinity than estradiol, and its action is tissue-specific (mostly antagonist at ERα in breast tissue, mild agonist at ERβ in bone). The clinical relevance at 600 mg is small for healthy adults; meaningful for anyone with active hormone-sensitive cancer (see contraindications). Postmenopausal women in trials (Wong / RESHAW; Ornstrup) actually benefited from the ERβ agonist tone in bone — this is part of why BMD signals appear at 16+ weeks.

Can I open the capsule and put it in a smoothie?

You can, but don't. Resveratrol is photosensitive — UV exposure converts trans to cis (the inactive isomer). A smoothie blender's clear pitcher under kitchen light for 30 minutes is enough to nudge a measurable fraction. If you can't swallow capsules, dissolve in olive oil at room temp and consume immediately, in opaque container.

Why is daily consistency more important than dose?

The SIRT1 deacetylation signaling Resveratrol drives doesn't store — it's a real-time enzymatic process. The NF-κB suppression and eNOS upregulation reset within ~48 hours of stopping. Hubbard 2013's mechanism is steady-state by design. 600 mg/day for 90 days is dramatically more biologically active than 1,800 mg every third day.

Should I cycle off resveratrol?

The published trials run continuously for 6–24 months without dose-limiting toxicity, withdrawal effects, or receptor down-regulation. There's no published rationale for cycling at 600 mg. The "cycle everything" supplement-bro heuristic doesn't apply to a polyphenol the body's already adapted to evolutionarily.

Can I take resveratrol while fasting?

Yes — but understand you'll get less of it. Fasted bioavailability is roughly half of fed bioavailability. If you're fasting and want to keep resveratrol on board, take it with the first fat-containing meal of your eating window, not during the fast itself.

Does resveratrol show up on a drug test?

No. Resveratrol and its glucuronide / sulfate conjugates are not on any standard drug-testing panel (sport, occupational, or law-enforcement). The molecule is structurally a stilbene polyphenol — entirely distinct from any controlled substance class.

Is this the same as the Sinclair-lab resveratrol?

Same source class (P. cuspidatum root extract, ≥98% trans-resveratrol HPLC) at the dose range used in animal lifespan work scaled to human equivalents. The Sinclair lab used ≥98% trans-resveratrol material throughout the Howitz 2003 / Baur 2006 / Hubbard 2013 work. We're not selling "Sinclair's brand" — we're selling the same molecular spec.

Does resveratrol raise blood pressure?

No. The vascular signal goes the other direction — eNOS-mediated vasodilation lowers systolic BP modestly in cardiometabolic trials (Movahed 2013; Bhatt 2012). Resveratrol does not have stimulant effects on heart rate or pressor effects on BP.

Why is daily consistency more important than peak dose?

The SIRT1 deacetylation signal is steady-state. Hubbard 2013's allosteric activation is dose-rate-dependent at the cellular level — a constant 600 mg/day flow keeps SIRT1 in the activated conformation continuously. Pulse-loading (1800 mg every 3 days) gives you the same average dose but with off-cycle troughs where SIRT1 reverts to baseline.

Can I take it with NAD+ IV therapy?

Yes — they're complementary, not duplicative. NAD+ IV raises blood NAD+ levels acutely; resveratrol activates the SIRT1 enzyme that uses NAD+. The pairing is logical: substrate (NAD+ IV or NMN) + activator (resveratrol).

Does resveratrol interact with statins or blood-pressure medications?

No major interaction in the published trial literature — Tomé-Carneiro's CHD cohort were on statins throughout, with the resveratrol arm showing additional LDL-ox reduction without altering statin pharmacokinetics meaningfully. Resveratrol is a mild CYP3A4 inhibitor in vitro; the clinical relevance for typical statin doses is small. Don't change prescribed medication without your physician.

Is the capsule kosher / halal?

Vegan HPMC capsule shell. The resveratrol is plant-derived (knotweed root). No animal-derived ingredients, no alcohol residues above limits. Specific kosher / halal certification varies by batch — check the COA page for current certification status.

Where this sits in the catalog architecture

Resveratrol 600mg occupies the Sirtuin Activator position in the True Health Protocol catalog. Three legs of the sirtuin axis on this site:

• Substrate (NAD+ floor) — NMN family (NMN 500mg, NMN 1000mg, Liposomal NAD+, Liquid NAD+ NR).
• Activator (SIRT1/SIRT3 push) — this product.
• Methyl support (long-term) — TMG 1000mg.

The convenience pairing is the Longevity Stack Bundle (NMN 500 + Resveratrol 600 at -10%).

Related collections

• Longevity collection — every product in the canonical longevity-stack architecture (NAD+ axis, sirtuin activators, senolytics, mitochondrial-renewal layer).
• Sirtuin activators — resveratrol and pairing molecules.
• Cardiovascular collection — resveratrol, CoQ10, taurine, omega-3, and pairing nutrients.
• Anti-inflammatory collection — resveratrol, curcumin, omega-3, quercetin.

Read more on this topic

• Sirtuins explained — the seven enzymes longevity research orbits. Why SIRT1 isn't the only sirtuin that matters, and how resveratrol fits across SIRT1/SIRT3.
• NMN vs NAD+ — what the precursor difference actually means. The substrate side of the substrate-plus-activator equation.
• The classic longevity stack — NMN + resveratrol explained. Why these two molecules became the canonical pairing.
• NAD+ decline with age — what the data actually show. Why the substrate side of the equation gets the most attention, and what resveratrol adds.
• The True Health Protocol — full longevity protocol showing where resveratrol slots into a complete supplementation framework.

Selected references

Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003;425:191-6. — Original screen identifying resveratrol as a sirtuin activator. Context, not endorsement.

Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006;444:337-42. — Mouse lifespan extension on calorically-stressed diet.

Hubbard BP, Gomes AP, Dai H, Li J, Case AW, Considine T, Riera TV, Lee JE, E SY, Lamming DW, Pentelute BL, Schuman ER, Stevens LA, Ling AJ, Armour SM, Michan S, Zhao H, Jiang Y, Sweitzer SM, Blum CA, Disch JS, Ng PY, Howitz KT, Rolo AP, Hamuro Y, Moss J, Perni RB, Ellis JL, Vlasuk GP, Sinclair DA. Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science 2013;339:1216-9. — Crystal structure resolving SIRT1 allosteric activation.

Park SJ, Ahmad F, Philp A, Baar K, Williams T, Luo H, Ke H, Rehmann H, Taussig R, Brown AL, Kim MK, Beaven MA, Burgin AB, Manganiello V, Chung JH. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell 2012;148:421-33. — AMPK leg via PDE/cAMP signaling.

Tomé-Carneiro J, Gonzálvez M, Larrosa M, García-Almagro FJ, Avilés-Plaza F, Parra S, Yáñez-Gascón MJ, Ruiz-Ros JA, García-Conesa MT, Tomás-Barberán FA, Espín JC. Consumption 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. Mol Nutr Food Res 2012;56:810-21.

Tomé-Carneiro J, Larrosa M, Yáñez-Gascón MJ, Dávalos A, Gil-Zamorano J, Gonzálvez M, García-Almagro FJ, Ruiz Ros JA, Tomás-Barberán FA, Espín JC, García-Conesa MT. One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Pharmacol Res 2013;72:69-82.

Bhatt JK, Thomas S, Nanjan MJ. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Nutr Res 2012;32:537-41.

Movahed A, Nabipour I, Lieben Louis X, Thandapilly SJ, Yu L, Kalantarhormozi M, Rekabpour SJ, Netticadan T. Antihyperglycemic effects of short term resveratrol supplementation in type 2 diabetic patients. Evid Based Complement Alternat Med 2013;2013:851267.

Pollack RM, Barzilai N, Anghel V, Kulkarni AS, Golden A, O'Broin P, Sinclair DA, Bonkowski MS, Coleville AJ, Powell D, Kim S, Moaddel R, Stein D, Zhang K, Hawkins M, Crandall JP. Resveratrol improves vascular function and mitochondrial number but not glucose metabolism in older adults. J Gerontol A Biol Sci Med Sci 2017;72:1703-9.

Walle T, Hsieh F, DeLegge MH, Oatis JE Jr, Walle UK. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos 2004;32:1377-82.

Smoliga JM, Baur JA, Hausenblas HA. Resveratrol and health — a comprehensive review of human clinical trials. Mol Nutr Food Res 2011;55:1129-41.

Vaz-da-Silva M, Loureiro AI, Falcao A, Nunes T, Rocha JF, Fernandes-Lopes C, Soares E, Wright L, Almeida L, Soares-da-Silva P. Effect of food on the pharmacokinetic profile of trans-resveratrol. Int J Clin Pharmacol Ther 2008;46:564-70.

Wallerath T, Deckert G, Ternes T, Anderson H, Li H, Witte K, Förstermann U. Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Circulation 2002;106:1652-8.

Csiszar A, Labinskyy N, Pinto JT, Ballabh P, Zhang H, Losonczy G, Pearson K, de Cabo R, Pacher P, Zhang C, Ungvari Z. Resveratrol induces mitochondrial biogenesis in endothelial cells. Am J Physiol Heart Circ Physiol 2009;297:H13-20.

Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 2006;127:1109-22.

Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 2004;23:2369-80.

Witte AV, Kerti L, Margulies DS, Flöel A. Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults. J Neurosci 2014;34:7862-70.

Kennedy DO, Wightman EL, Reay JL, Lietz G, Okello EJ, Wilde A, Haskell CF. Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Am J Clin Nutr 2010;91:1590-7.

Ornstrup MJ, Harsløf T, Kjær TN, Langdahl BL, Pedersen SB. Resveratrol increases bone mineral density and bone alkaline phosphatase in obese men: a randomized placebo-controlled trial. J Clin Endocrinol Metab 2014;99:4720-9.

Wong RH, Howe PR, Buckley JD, Coates AM, Kunz I, Berry NM. Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. Nutr Metab Cardiovasc Dis 2011;21:851-6.

Brown VA, Patel KR, Viskaduraki M, Crowell JA, Perloff M, Booth TD, Vasilinin G, Sen A, Schinas AM, Piccirilli G, Brown K, Steward WP, Gescher AJ, Brenner DE. Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Res 2010;70:9003-11.

Gliemann L, Schmidt JF, Olesen J, Biensø RS, Peronard SL, Grandjean SU, Mortensen SP, Nyberg M, Bangsbo J, Pilegaard H, Hellsten Y. Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men. J Physiol 2013;591:5047-59.

López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell 2013;153:1194-217. — Updated 2023 in Cell 186:243-78. Foundational taxonomy of biological aging.

References cited here are scientific context, not product endorsements. The molecular and clinical findings described above pertain to the molecules studied; this product supplies the same molecule (≥98% HPLC trans-resveratrol from Polygonum cuspidatum) at a dose that overlaps the cited human-trial range. Individual results vary.

FDA disclaimer: 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. Consult your physician before starting any new supplement, particularly if you are pregnant, nursing, taking prescription medication (especially anticoagulants, antiplatelets, hormone-sensitive cancer treatments, CYP3A4 substrates), or have a known medical condition.