Resveratrol

There is no human evidence that resveratrol extends lifespan, and the mammalian preclinical signal collapsed when independent labs tested it. The NIA Interventions Testing Program (NIA Interventions Testing Program work) found no lifespan extension in C57BL/6J mice at 300 or 1,200 ppm dietary resveratrol. The original Baur 2006 finding was lifespan normalization in obese-mouse pathology, not unconditional extension in healthy animals. The mechanistic story collapsed when a 2010 falsification report on SIRT1 fluorophore artifact (Pfizer/Amgen) showed direct SIRT1 activation was a fluorophore-substrate artifact, and a 2025 GRADE meta-analysis of 11 human RCTs confirmed resveratrol does not raise SIRT1 expression in humans at any level. GSK acquired Sirtris for 720 million USD and discontinued the SRT2104 program after Phase II disappointments. The community has largely migrated from resveratrol to urolithin A, spermidine, and rapamycin.

Peter Attia has stated repeatedly on his podcast and in print that resveratrol is 'absolute nonsense' for two reasons: the proposed SIRT1 mechanism was falsified by a 2010 falsification report on SIRT1 fluorophore artifact, and resveratrol's bioavailability is so low that systemic levels never reach the concentrations used in cell culture or mouse models. Roughly 70% of an oral dose absorbs through the gut, but less than 1% reaches systemic circulation as the parent compound; the rest converts to sulfate and glucuronide conjugates of unknown bioactivity. Attia contrasts resveratrol with rapamycin, which has both validated mechanism (mTOR inhibition) and reproducible mammalian lifespan data (NIA ITP rapamycin lifespan work NIA ITP). Rhonda Patrick takes a more nuanced position, acknowledging some endothelial and cognitive signals in specific populations while flagging the exercise-blunting effect (Olesen 2013) and CYP2C9 warfarin interaction. Patrick has stated she does not personally take resveratrol.

[Popat 2013 (PMID 23205612)](https://pubmed.ncbi.nlm.nih.gov/23205612/) tested SRT501, a micronized resveratrol formulation from GSK's Sirtris subsidiary, at 5 grams per day in patients with relapsed or refractory multiple myeloma combined with bortezomib. Five of 24 patients (21%) developed cast nephropathy and acute renal failure within weeks of starting therapy, one of whom died. The trial was halted by the data safety monitoring board, and GSK shut down the SRT501 program shortly after. Mechanistically the renal injury appeared to involve resveratrol-induced light-chain precipitation in distal tubules, an interaction specific to the myeloma context but never previously reported. The 21% acute renal failure rate at 5 g/day is the single most important safety signal in the resveratrol literature and is why EFSA capped synthetic trans-resveratrol at 150 mg/day with mandatory CYP2C9 warning. Doses above 1 g/day in any context now require active clinician oversight.

Yes, in older men. exercise-resveratrol antagonism work (PMC3810808) randomized 27 healthy aged men to 8 weeks of high-intensity exercise training with either 250 mg/day trans-resveratrol or placebo. The placebo group showed expected gains in VO2max, blood pressure reduction, and lipid profile improvement. The resveratrol group showed BLUNTED gains across nearly every endpoint, including LDL cholesterol that worsened relative to placebo. The mechanism is plausibly antioxidant interference with the redox signaling that drives mitochondrial biogenesis after exercise stress. This finding has been partially replicated in other polyphenol contexts (vitamin C plus E pre-workout literature) and represents a real opportunity-cost penalty for exercise-trained users. Resveratrol should not be co-administered with exercise training in athletic populations seeking adaptation. The exercise-blunting signal does not appear in sedentary or metabolically compromised subjects.

Resveratrol may be unsafe for women with HER2+/ERα+ breast cancer or precursor risk. Andreani 2017 demonstrated in an in vivo HER2+/ERα+ mouse model that resveratrol at preclinical doses previously labeled 'positive' actually shortened tumor latency and increased tumor multiplicity, mediated by proteasome inhibition. Roughly 10% of breast cancers are HER2+/ERα+. This is not an in vitro signal; it is a tumor-promotion finding in a living mammalian model. Resveratrol is also a known phytoestrogen with ERα binding affinity and may interact with hormone-receptor-targeted therapy (tamoxifen, aromatase inhibitors). extended-protocol PK work (PMID 32900519), the only positive postmenopausal cognition trial, was conducted in women without active breast cancer history. Women with personal or family history of HER2+/ERα+ breast cancer, BRCA1/BRCA2 mutation, or active hormone-sensitive cancer therapy should avoid supplemental resveratrol pending more selective biomarker work.

Most commercial resveratrol supplements are extracted from Polygonum cuspidatum (Japanese knotweed) rather than grape skin because knotweed yields 50-100× more trans-resveratrol per gram of starting material. Knotweed extract carries a contamination risk: emodin, a knotweed anthraquinone, has been linked to fluoroquinolone-like tendinopathy in case reports on Longecity and similar forums. Emodin is also a laxative and can cause GI distress. Grape-skin and red wine-derived resveratrol contains lower emodin but also lower active content, making cost-effective supplemental dosing harder. Synthetic trans-resveratrol (Evolva resVida, DSM Veri-te) eliminates the emodin issue entirely and is the form used in EFSA-approved European products with the 150 mg/day cap. NOW Foods third-party testing found 70% of Amazon-sold resveratrol products were below labeled potency. Synthetic or pharmaceutical-grade is the better choice if supplementing.

The signal is narrow and inconsistent. Crandall 2012 (PMC3670158) in older adults with impaired glucose tolerance (IGT) showed improved insulin sensitivity at 1-2 g/day over 4 weeks, but the same group's Poulsen 2013 (PMID 23193181) tested obese men and saw no metabolic benefit. Yoshino 2012 (PMC3496026) was negative in healthy non-obese postmenopausal women. The hypertension meta-analysis meta-analysis (n=491) found resveratrol null on triglycerides, total cholesterol, HbA1c, fasting insulin, and liver enzymes. Timmers 2011 was the celebrated positive metabolic trial in obese men, but the same research group's NCT01638780 follow-up reversed the finding. The pattern: resveratrol may help glucose homeostasis in already-metabolically-compromised populations but does not act as a preventive metabolic optimizer in healthy people. NAFLD is fully null across NAFLD trial, Heeboll, Kantartzis, and Poulsen.

GlaxoSmithKline acquired Sirtris Pharmaceuticals from David Sinclair and team for 720 million USD, betting on SIRT1 activator development for diabetes and metabolic disease. The bet collapsed in stages. a 2010 falsification report on SIRT1 fluorophore artifact (Pfizer/Amgen demonstrated that SRT1720 and resveratrol's apparent SIRT1 activation was an artifact of the fluorophore peptide substrate used in Sirtris assays; with native peptide substrates the activation disappeared. SRT501 (micronized resveratrol) was halted after Popat catastrophic renal failure. SRT2104, the lead synthetic SIRT1 activator, completed several Phase II trials with disappointing or null results across psoriasis, ulcerative colitis, type 2 diabetes, and elderly cardiovascular endpoints. GSK quietly discontinued the Sirtris program. The 2025 GRADE meta-analysis (PMID 40158656) closed the question: resveratrol does not raise human SIRT1 at gene expression, protein, or serum level. The Sirtris collapse is one of the most expensive negative results in 21st-century pharma.