STUDresearch · Non-peptide
Fisetin
Also known as
3,3',4',7-tetrahydroxyflavone · 3,3′,4′,7-Tetrahydroxyflavone · Fisetin flavonoid · Natural fisetin · Senolytic fisetin (discussion label) · Novusetin (branded ~95% fisetin extract, often Rhus-derived) · Cognisetin (marketing / memory-branded fisetin label) · FF-20 / hybrid-hydrogel fisetin (enhanced-bioavailability research form)
Community talk. May be wrong. Not medical advice. Not a protocol. Not for human or animal use.
Systemic oral flavonoid for whole-body senescent-cell, SASP, and aging-inflammation talk—not a local injury inject, peptide, or tissue-targeted therapy.
A study-design amount in older adults, not a published general anti-aging result.
Forum arithmetic and self-experiment calendars copied from trial-registration language; some discussions extend the pulse to 2–3 days. This is not proof of efficacy or safety for self-treatment.
Continuous consumer use framed as a polyphenol habit, not the intermittent senolytic model.
Lower-dose community and educational-guide context, far below 20 mg/kg for most adults and not a validated alternative regimen.
Anecdotal self-experiment outliers, not trial registration, dose finding, or evidence of safety or efficacy.
Crossover PK context showing that formulation and stated product amount can diverge from delivered fisetin and measured exposure.
Half-life & effect duration
- Half-life in the body
- Abdominal-cavity injection · mice · rapid phaseAbout 5.4 minutes
- Same study · terminal phaseAbout 3.1 hours
- Felt duration people report
- Some accountsFatigue or muscle weakness lasting days; vivid dreams over weeks
- Other accountsNo noticeable effect or no fatigue
- Joint-change accountImprovement only after 4–5 treatments
Tap a line to jump into the full notes. Research only — may be wrong.
Timing context & sources
Half-life in the body
A mouse study using 223 mg/kg intraperitoneal fisetin found biphasic parent-plasma decline with a 0.09-hour rapid phase and 3.1-hour terminal phase.
Peak parent fisetin occurred at 15 minutes, and metabolites included glucuronides plus the methylated metabolite geraldol.
Mouse intraperitoneal high-dose kinetics cannot establish human oral half-life. Parent fisetin, conjugates and geraldol are different analytes, and oral formulations can change exposure.
- Touil et al. — Fisetin disposition and metabolism in mice (opens in a new tab)Abstract: 223 mg/kg intraperitoneal fisetin in mice; Cmax at 15 minutes; biphasic decline with 0.09-hour rapid and 3.1-hour terminal half-lives; glucuronides and geraldol identified.High-dose mouse intraperitoneal experiment; not human oral pharmacokinetics and not a comparison of consumer formulations.
Felt duration people report
Inspected reports range from no noticeable effect to profound fatigue or muscle weakness lasting days, vivid dreams over weeks, and perceived joint changes after repeated exposures.
One fatigue report combined about 1,000 mg fisetin with other ingredients and possible viral illness. Another user linked weakness to 25–40 mg/kg multi-agent exposures. Other posters reported no fatigue, and a separate pure-fisetin user described shoulder improvement only after four or five treatments.
Products, amounts, forms and co-agents varied; illness and expectation are strong confounders. These reports do not measure clearance, prove senolysis or establish symptom prevalence.
- Rapamycin.news — Fisetin dosing: 1,500 mg for 2 days every 4–8 weeks (opens in a new tab)Original post and replies distinguish AI-derived text from users describing weight-based two-day fisetin, quercetin combinations, capsule products and monthly calendars.Unverified products, arithmetic and co-agents; discussion contains copied protocol language and no objective outcome adjudication.
- Rapamycin.news — Fatigue after taking senolytic (opens in a new tab)Posts report profound fatigue after a multi-ingredient exposure containing about 1,000 mg fisetin, weakness after 25–40 mg/kg combinations, other users with no fatigue, and vivid dreams during a separate two-week fisetin product course.Strong product, co-agent and illness confounding; no verified identity, blinded assessment or measured pharmacokinetics.
- Rapamycin.news — Do senolytics decrease lifespan? (opens in a new tab)Replies include a user reporting pure fisetin 30–40 mg/kg with oil and black pepper, shoulder-function change after four or five treatments and only brief libido change; others stopped after no perceived benefit.Uncontrolled self-reports, uncertain products and subjective outcomes; same-day additives and repeated exposure prevent a single-agent felt-duration estimate.
Other context in this card
- Yousefzadeh et al. — Fisetin is a senotherapeutic that extends health and lifespan (opens in a new tab)Abstract and figure information: 10 flavonoids screened in senescent murine and human fibroblasts; fisetin was most potent, then tested in progeroid and aged mice and human adipose explants.Cell, mouse and ex-vivo human-tissue evidence; it does not establish clinical anti-aging efficacy, dose or felt duration in people.
- ClinicalTrials.gov — AFFIRM fisetin intervention study (NCT03430037) (opens in a new tab)Study record: older women; oral fisetin 20 mg/kg/day on two consecutive days for two consecutive months; record showed no posted results at review.Registry design, not a result; population and endpoints do not establish general healthy-user efficacy or a universal regimen.
What people say
- Subjective longevity logs: After high-dose pulses, some self-experimenters report less joint/stiffness noise, clearer sinuses/nasal inflammation, less BPH-like night voiding urgency, modest cognitive “word-finding” ease, or higher training drive—highly confounded and not trial hard endpoints. anecdote
- Mild post-pulse “illness-like” feel: A subset describes low-grade feverishness, fatigue, appetite bump, or transient aches for 1–4 days after gram-range pulses and interpret it as immune clearance of senescent debris—unproven mechanism story, not diagnostic of senolysis. anecdote
- Mouse flavonoid ranking (Yousefzadeh 2018): Among ~10 flavonoids screened (incl. quercetin, luteolin, curcumin, resveratrol, apigenin, EGCG-class neighbors), fisetin was the most potent senolytic in senescent fibroblast assays. animal
- Senescent-cell burden (mice): Acute or intermittent oral fisetin cut senescence markers across multiple tissues—commonly summarized as roughly mid-range clearance (~25–50% by organ/method depending on readout). animal
- Acute aged-mouse pulse: ~100 mg/kg/day oral gavage for ~5 consecutive days in old wild-type mice reduced senescence markers when tissues were sampled days after the last dose. animal
- Late-life continuous diet (mice): Diet containing ~500 ppm (~500 mg/kg feed) fisetin started late (~85 weeks) restored tissue-homeostasis signals, reduced age-pathology markers, and extended median and maximum lifespan in wild-type mice. animal
- Hit-and-run logic: Benefits after brief exposure despite terminal plasma half-life on the order of hours is cited as more consistent with senescent-cell removal than with continuous enzyme/receptor occupancy. animal
- Human tissue / ex-vivo: Reduced senescence signals in a subset of cells in human adipose explants—supports translational interest, not proof of in-body whole-organism clearance. lab
- Physical function (newer mouse intermittent work): Intermittent late-life oral fisetin schedules (trial-mimicking on/off blocks) improved age-related physical-function endpoints and frailty-related measures in old mice in 2020s Aging Cell–class work. animal
- Mayo / multi-site human programs: Intermittent oral fisetin trials target frailty, inflammation, bone/metabolic aging, diabetic CKD, COVID-era skilled-nursing complications, and healthy-volunteer safety—flagship frailty programs (e.g. AFFIRM-LITE NCT03675724; related NCT03430037) used ~20 mg/kg/day × 2 days as the template many forums copy; peer-reviewed definitive efficacy packages for those frailty arms were still widely described as incomplete/unpublished in 2025 community tracking. trial
- D+Q contrast: Dasatinib + quercetin has more published human tissue senescent-cell reduction evidence; fisetin is cast as the accessible “natural single-agent” hope—not a proven head-to-head replacement. trial
- Allergy / mast-cell adjacency: Older mouse and cell work on mast-cell and late-phase allergic inflammation is sometimes cited when users log nasal comfort on daily low-dose or after pulses. animal
- Metabolic / vascular inflammation (preclinical): Mouse and cell lines show high-glucose vascular-inflammation and diabetes-adjacent endpoint signals; human clinical translation for metabolic disease is still trial-stage, not settled. animal
- Stroke adjunct pilot (specialty): A randomized human pilot explored fisetin with rt-PA for extending treatment window in ischemic stroke—disease-context, not a longevity protocol. trial
- Neuroprotection interest: Preclinical neuroprotective / geroneuroprotector framing (memory, stroke-window, dementia-adjacent models) drives Cognisetin-style marketing; human cognition RCTs as a stand-alone anti-aging claim remain weak. animal
Doses people talk about
- ~70 kg adult math: ~1,400 mg/day × 2 days is the most-copied forum conversion from the 20 mg/kg trial template. forum
- ~60–80 kg practical band: Roughly ~1,200–1,600 mg/day × 2 consecutive days appears repeatedly in self-experiment write-ups tracking Mayo registration language. forum
- Mouse→human scaling debate: Simple HED from 100 mg/kg × 5 days is often blog-scaled near ~500 mg/day × 5 days for a ~60 kg adult; Mayo trial arms instead used higher short pulses (~20 mg/kg × 2 days)—self-experimenters argue both ways. forum
- 100 mg twice daily × 2 days: Appears in some lower-dose intermittent write-ups and educational dosing guides as a gentler calendar; far below full 20 mg/kg for most adults. forum
- Community high-pulse cluster: ~1,000–1,800 mg/day × 2 days monthly or quarterly is the dense self-experiment band post-2018. forum
- Extended multi-day high-dose logs: Some Fight Aging / Longecity-style logs describe ~1 g/day for ~10–15 days, or multi-day 1.2 g/day “senolytic weeks”—anecdotal only, not Mayo registration text. anecdote
- Extreme outlier logs: Multi-gram single days (e.g. ~3 g once) or multi-week multi-gram cumulative courses appear in open self-experiment threads; not evidence of safety or efficacy and not trial-standard. anecdote
- With dietary fat / oil: Olive oil, MCT oil, or a fat-containing meal is commonly co-administered to chase higher oral exposure for lipophilic flavonols. forum
- Empty stomach vs with food: Split opinions—some pulse empty for “maximum hit,” many educational sources prefer with meals/fat for absorption and GI comfort. forum
- Split vs bolus same day: Whether the full 20 mg/kg is taken once or split BID/TID on pulse days is not standardized in public registration blurbs; users do both for pill-count and stomach reasons. forum
- Daily consumer / label band: ~100–500 mg/day continuous from common capsule products—marketed antioxidant/healthy-aging use, not the mg/kg pulse model. forum
- Novusetin / 95% extract products: Common retail path (e.g. Doctor’s Best, Swanson-style labels); “more soluble/stable” marketing is frequent—independent human BA packages are thinner than the brand claims. forum
- Liposomal / nano oral products: Marketed as higher bioavailability; one cited animal liposomal study reported ~47-fold relative bioavailability vs free fisetin (IV liposomal context in the original PK paper—do not treat as a proven human oral multiplier for every brand). animal
- Enhanced oral complex (human PK): A randomized crossover in healthy volunteers compared 1000 mg unformulated fisetin vs 1000 mg FF-20 hybrid-hydrogel product delivering ~192 mg fisetin and reported ~26.9-fold higher plasma AUC0–12h for the formulated arm—labeled bottle mg ≠ free fisetin mg. trial
- PPI hold note (trial operational detail): Some Mayo-linked protocols ask participants on proton-pump inhibitors to reduce or hold PPI ~2 days before and during the 2-day fisetin window when possible—flagged as a drug-interaction / absorption operational detail in community reads of eligibility text. trial
- Food vs supplement reality: Strawberries ~160 µg/g fisetin (highest common produce); average dietary intake often cited ~0.4 mg/day in Japanese diet surveys; a cup of strawberries is milligram-fraction vs multi-hundred-mg to gram pulses—food cannot practically match trial pulse totals. trial
- Framing: Discussed community, trial-registration, and animal-scaling ranges for research education only—not medical advice, not a prescription, not a proven human anti-aging regimen. forum
- Mayo-style pulse (dominant template): ~20 mg/kg body weight oral per day for 2 consecutive days. trial
- Trial registration language (examples): AFFIRM-LITE-class frailty work and healthy-volunteer pilots list fisetin ~20 mg/kg/day orally for 2 consecutive days (± placebo arms); some programs repeat courses on monthly-style calendars. trial
- Alternate trial-style lengths: Community and secondary summaries also mention 2–3 consecutive days at weight-based high dose, or multi-month intermittent repeats; exact schedules differ by NCT and are not one universal label. trial
- Mouse acute senolytic pulse (source paper): ~100 mg/kg/day oral for ~5 days in aged mice—blog “human equivalent” translations vary (surface-area HED vs higher trial-style mg) and are a major forum fight. animal
- Uncertainty: Low oral bioavailability + rapid conjugation mean labeled capsule mg is a poor proxy for free plasma exposure; product form and co-admin dominate real-world “dose.” trial
How it may feel
- Pulse day 1 (high oral total): Most report little “drug-like” buzz; minority note mild GI, light-headedness, facial warmth/itch, or chalky aftertaste if powder is dumped in water/oil. forum
- Pulse day 2 / same evening: Second consecutive high-dose day; same quiet acute profile for many; some stack fat/oil or split capsules across the day for stomach tolerance. forum
- Days 3–7 after pulse: Main “did anything change?” window—subtle joint, sinus, energy, or recovery shifts if claimed; also the window some describe mild fatigue or feverishness. anecdote
- Weeks 2–4: Checkpoint before the next monthly/bimonthly run; nasal/joint anecdotes sometimes fade and return weeks later in logs that retake on a calendar. forum
- Months 1–3 (multi-pulse calendars): Reassess schedule frequency (monthly vs quarterly), form (plain vs liposomal), and whether subjective wins justify another multi-gram bottle spend. forum
- Daily low-dose (100–500 mg): Even subtler than pulses; framed as polyphenol/antioxidant habit rather than hit-and-run senolysis—users often report “no feel” for weeks. forum
- No change after 1–2 pulses: Community advice usually rechecks form (fat/liposomal), purity/third-party testing, body-weight math, and expectations—not automatic megadose escalation into multi-gram extremes. forum
- Younger healthy users: Forums often note risk/benefit may be weaker if senescent-cell burden is low; many still copy Mayo math for prevention narratives without hard proof. forum
Cycles people discuss
- Pulse model (dominant longevity talk): Short high-dose blocks—most often 2 consecutive days—then weeks to months off (hit-and-run senolytic logic). forum
- Mayo-copy spacing: Second course often discussed ~1 month later; many self-experimenters run monthly × ~3 months then reassess, or stretch to every 2–3 months / quarterly. forum
- No fixed lifelong healthy-adult cadence: Restarts after gaps are common; there is no consensus lifelong prevention schedule backed by published human longevity outcomes. forum
- Stack calendars: Some alternate fisetin pulse months with D+Q pulse months, or keep fisetin as the “natural” pulse and reserve dasatinib for separate supervised contexts—ratios/schedules vary widely. forum
- Trial-style intermittent: Registration and secondary sources describe 2-day pulses with multi-week or monthly spacing, sometimes repeated across multi-month windows in older adults. trial
- Mouse intermittent function schedules: Newer physical-function work used intermittent on/off blocks (e.g. week-on / weeks-off style patterns summarized as trial-mimicking)—not identical to every human self-protocol. animal
- Daily alternative: Open-ended ~100–500 mg/day as a polyphenol habit—different goal framing than intermittent senolysis; no settled “must cycle off” rule in consumer use. forum
- Daily vs bolus research question: At least one dosing-equivalence trial design explicitly compares daily administration vs short bolus (≈2-day) for SASP biomarkers and tolerability—reflects the real community fork. trial
Timing
- Feel lag: Subjective changes, if any, are often logged days to weeks after a pulse—not minutes after the capsule. anecdote
- Not a multi-day depot: Even enhanced oral forms are not long-acting injectables; pulse logic still assumes brief systemic presence. forum
- With-fat timing: Fat meal or oil co-admin is a same-day exposure tactic, not a half-life extension depot. forum
- Mouse plasma PK (classic cite): After efficacious i.p. dosing, biphasic decline with rapid half-life ~0.09 h and terminal half-life ~3.1 h; free fisetin clears quickly. animal
- Metabolite geraldol: Methylated metabolite identified as active/discussed contributor; free parent alone understates total flavonoid-related exposure. animal
- Human / general PK summary: Rapid absorption, extensive phase-II conjugation (sulfates/glucuronides), short free half-life across species—reviews emphasize rapid metabolism and low free bioavailability. trial
- Why pulses still make sense in theory: Yousefzadeh-linked commentary notes healthspan signals despite short elimination half-lives are more consistent with senescent-cell removal (cells take days–weeks to reaccumulate after insult) than with continuous target occupancy. animal
- Formulation changes Cmax/AUC: Liposomal and hydrogel/complex products aim at higher exposure and sometimes longer measurable plasma windows; brand multipliers are not interchangeable. trial
More on what it is
- What it is: Plant flavonol (highest common food source: strawberries; also apples, persimmon, onions, smoke bush / *Rhus* extracts used in many supplements). Chemically 3,3',4',7-tetrahydroxyflavone. trial
- Why people care: 2018 Yousefzadeh/Mayo–linked mouse work ranked it the strongest of ~10 flavonoids tested as a senolytic and showed late-life lifespan extension—then Mayo intermittent oral trials made “Mayo fisetin protocol” a default longevity-forum template. animal
- Mechanism talk: Intermittent high doses framed as hit-and-run clearance of senescent (“zombie”) cells and SASP burden; short plasma half-life is used as an argument that durable effects (if real) are clearance/downstream tissue change, not continuous receptor occupancy. animal
- Evidence honesty: Strong mouse/tissue ranking and lifespan/function signals; human adipose explants support translation interest; large definitive RCTs proving clinical senolysis, frailty reversal, or human lifespan gain are still thin / largely unpublished for the flagship Mayo frailty programs as of mid-late 2020s discussion. trial
- Bioavailability wall: Poor water solubility, rapid phase-II metabolism, and low free oral exposure are the main practical fights—liposomal, hydrogel/complex, and fat co-admin products exist because plain powder mg often under-delivers free plasma. trial
- Not this: Not a peptide, not dasatinib, not navitoclax, not food-strawberry-equivalent at gram-range pulses, and not an approved anti-aging drug. trial
Stacks
- vs D+Q (main comparison): Fisetin alone as a natural pulse alternative to dasatinib + quercetin; some run both on separate months rather than same days. forum
- Fisetin + quercetin: Flavonoid co-stack or “senolytic weekend” logs; ratios informal (often gram-range fisetin pulse + ~500–1,250 mg quercetin-class on pulse days)—not a validated fixed ratio. forum
- Fisetin + luteolin (± resveratrol): Commercial “senolytic blend” products (often liposomal) pair these polyphenols; marketing ahead of combination RCTs. forum
- Absorption aids: Dietary fat/oil, piperine/black-pepper extracts, or liposomal carriers as bioavailability boosters. forum
- Longevity backbone adjacency: Stacked in calendars with NMN/NR, resveratrol, spermidine, metformin interest, or weekly rapamycin—different mechanisms; no standard multi-agent RCT for the full cocktail. forum
- Life Extension–style “Senolytic Activator” days: Some pulse logs combine fisetin oil mixes with commercial quercetin-heavy senolytic formulas on a third day or same weekend—product contents vary by SKU/year. forum
- Piperlongumine combo talk: Advanced self-experiment threads sometimes add piperlongumine as another natural senolytic candidate alongside fisetin—dose culture is sparse and experimental. forum
- FOXO4-DRI adjacency (research-only lore): Named in multi-mechanism “kitchen sink” senolytic wish-lists with fisetin + D+Q; FOXO4-DRI is a separate research peptide with its own risk profile—not a retail fisetin partner. forum
- Lifestyle confounds: Sleep, resistance training, protein, and fasting windows are often co-credited when a pulse “works.” forum
- Immune-season polyphenol stacks: Lower daily fisetin sometimes sits next to quercetin + zinc + C style stacks—goal is seasonal comfort, not Mayo mg/kg math. forum
Storage notes
- No mix instructions here: STUDresearch does not list reconstitution, diluent volumes, or syringe unit charts. People reconstitute many different ways and vial labels differ — that content creates more confusion than clarity. forum
- Storage (general talk only): Unopened research products are usually kept cool, dry, and away from light per the seller label. Anything after first use is product-specific — follow the label, not a universal forum SOP. forum
Watch for
- GI (most common high-dose complaint): Nausea, stomach upset, loose stool on multi-hundred-mg to gram pulse days—dose and empty-stomach use may worsen. forum
- Usually quiet acute profile: Many pulse logs report no dramatic sides; quiet acute use ≠ long-term high-dose safety proof. forum
- Mild fatigue / feverishness / appetite bump: Post-pulse 1–4 day “flu-ish” feel in a minority of high-dose logs; mechanism (true clearance vs placebo vs other) unproven. anecdote
- Headache / light-headedness: Occasional same-day or next-day reports at high oral totals. forum
- Skin warmth / itch / transient rash-like feel: Minority high-dose anecdotes; forums sometimes speculate residual plant-source irritants vs fisetin itself. anecdote
- Sleep disruption on multi-day high courses: Some extended gram-range courses log trouble falling asleep or early waking that settles after stopping. anecdote
- Bleeding / antiplatelet caution: Educational sources flag potential antiplatelet effects and extra care with anticoagulants/antiplatelets or before procedures—systematic interaction tables are still thin. forum
- Drug-metabolism caveats: As a flavonoid, theoretical CYP/transporter interactions apply; concurrent multi-drug regimens warrant caution even without a full fisetin interaction encyclopedia. forum
- Senolytic theory risk: Debate on clearing contextually useful senescence (e.g. wound healing, tumor suppression roles)—human risk magnitude unquantified. forum
- Young / low-burden users: Lower expected senescent-cell load may mean less benefit and still full product/megadose risk—community risk/benefit talk is age-skewed toward middle-age+. forum
- Source quality: Mislabeling, under-assay, contaminants, and extract-source variability are real supplement-market risks at pulse bottle volumes. forum
- PPI / acid-suppression operational flag: Some trial eligibility text asks to hold or reduce PPIs around the 2-day dosing window—suggests absorption/interaction concern operationalized in study design. trial
- Topoisomerase inhibition (in-vitro discussion): Cell papers on dual topo I/II inhibition appear in cautious forum threads; large mouse high-dose arms did not report leukemia-like signals in the flagship lifespan paper, but this remains a theoretical worry for megadose self-experimenters. lab
- Underdosing / false confidence: Low free oral bioavailability means many “protocol” powder mg may deliver little free exposure—especially plain capsules without fat or enhanced forms. trial
- Not proven anti-aging Rx: Mayo-linked and independent commentary stresses commercial fisetin products are not validated as proven senolytics for the general public; D+Q still has clearer published human clearance data. trial
- Pregnancy / pediatric / complex disease: Not characterized for high-dose intermittent use in these groups in the longevity literature—outside research framing. forum
- Long-term intermittent safety gap: Human trial data remain limited especially for years of repeated gram-range pulses; “no adverse effects reported” summaries reflect sparse published AEs, not a completed lifetime safety dossier. trial
