{
  "slug": "fisetin",
  "name": "Fisetin (3,3',4',7-tetrahydroxyflavone)",
  "alternate_names": [
    "Fisetin",
    "3,3',4',7-tetrahydroxyflavone",
    "Flavonol polyphenol"
  ],
  "mechanism": [
    "Senolytic signaling in preclinical models (p53/p21/Bcl-2 pathway; mouse + human-tissue-explant only, not human-validated in vivo)",
    "Sirtuin (SIRT1/SIRT3) activation in research models",
    "NF-kB pathway suppression (mechanistic)",
    "Direct ROS scavenging / free-radical quenching",
    "mTOR modulation (preclinical)",
    "MMP (matrix metalloproteinase) inhibition — observed as reduced MMP-7 in one human RCT"
  ],
  "target": [
    "p53 / p21 / Bcl-2 (senescence axis)",
    "SIRT1 / SIRT3",
    "NF-kB",
    "Nrf2",
    "mTOR",
    "Matrix metalloproteinases (MMP-7)",
    "Inflammatory markers (hs-CRP, IL-8)"
  ],
  "use_case": [
    "antioxidant / inflammatory-marker support (research-context · disease-population RCT only)",
    "cellular-senescence / healthy-aging biology (research-context · preclinical + early-phase trials, no human efficacy RCT)",
    "oral bioavailability / formulation pharmacokinetics (educational context)"
  ],
  "body_system": [
    "CELL",
    "MITO",
    "IMMUNE",
    "NEURO",
    "EPIGEN"
  ],
  "evidence_tier": "B",
  "evidence_anchor_pmid_count": 3,
  "dosage_range": "100 mg/day x 7 weeks was used in the single human efficacy RCT (Farsad-Naeimi 2018, colorectal-cancer patients · inflammation markers, not a healthy-population study). Intermittent senolytic research dosing (~20 mg/kg/day x 2 days/month, i.e. ~1400 mg x 2 days) appears ONLY in early-phase clinical trials and is not a consumer regimen. Oral bioavailability is very low (<5%); a hybrid-hydrogel formulation raised AUC in a healthy-volunteer PK crossover (Krishnakumar 2022). Educational reference only — not a dosing recommendation; no established efficacy dose in healthy people.",
  "safety_notes": "No formal upper limit established. Short-term human exposure (100 mg/day x 7 wk; and intermittent high-dose 20 mg/kg x 2 days in trials) reported as tolerable with occasional mild GI discomfort, but long-term daily safety beyond ~8 weeks is not established. Very low oral bioavailability (<5%) means actual systemic exposure is limited even at high doses. Not recommended for pregnant/lactating women, children, or people with hepatic/renal impairment (safety data absent). Educational, not medical advice — not a treatment for any disease.",
  "regulatory": {
    "fda": "Marketed as a dietary supplement (multiple brands) but NO published NDI notification or GRAS determination on record — regulatory grey zone under DSHEA; structure/function language only",
    "efsa": "No EFSA authorized health claim. Concentrated/purified fisetin extract may trigger the Novel Food Regulation (EU 2015/2283) absent demonstrated pre-1997 EU food-use history; member-state market status varies",
    "anvisa": "NOT on the ANVISA dietary-supplement positive list (IN 28/2018) — market entry would require an innovative-ingredient application (12-24 months); currently not marketable in Brazil"
  },
  "authorized_claims": [],
  "ingredient_hub_url": "https://asxan.ai/ingredients/fisetin/",
  "related_goal_slugs": [
    "longevity-stack"
  ],
  "related_lifestyle_slugs": [
    "senior-60-plus"
  ],
  "last_evidence_review": "2026-06-13",
  "schema_version": "nc-public-v0.2",
  "api_version": "nc-public-v0.3",
  "_meta": {
    "last_evidence_review": "2026-06-13",
    "ip_axes_disclosed": {
      "public_axes": [
        "mechanism",
        "target",
        "use_case",
        "body_system",
        "evidence_tier",
        "dosage_range",
        "safety_notes",
        "regulatory",
        "authorized_claims"
      ],
      "ip_axes_not_exposed": [
        "proprietary_formula_ratios",
        "clinical_protocol_internals",
        "rnd_pipeline_compounds",
        "supplier_specific_grade_specifications",
        "unpublished_endpoint_data"
      ],
      "rationale": "asxan.ai surfaces the educational, evidence-tier-disclosed slice. Formula composition, clinical-protocol internals, and RnD pipeline data are intentionally outside this public surface."
    }
  }
}