{
  "slug": "grape-seed-extract",
  "name": "Grape Seed Extract (OPC / Proanthocyanidins)",
  "alternate_names": [
    "Grape Seed Extract",
    "GSE",
    "OPC (grape-seed-derived)",
    "Oligomeric Proanthocyanidins",
    "Proanthocyanidins",
    "Vitis vinifera Seed Extract",
    "MegaNatural-BP",
    "Leucoselect",
    "OPC"
  ],
  "mechanism": [
    "Free-radical scavenging: oligomeric proanthocyanidins (OPC) are potent in-vitro antioxidants that inhibit lipid peroxidation (research-context mechanism; in-vitro ORAC multiples are educational only, not a product property)",
    "Endothelial NO signaling: activation of the eNOS/NO pathway is associated with vasodilation and improved endothelial function in research models",
    "NF-kB suppression: down-regulation of NF-kB-mediated pro-inflammatory signaling (preclinical and biomarker research)",
    "LDL-oxidation inhibition: reduced susceptibility of LDL to oxidation observed in human research (e.g. heavy smokers)",
    "Matrix metalloproteinase (MMP-1/MMP-9) inhibition: dermal collagen/elastin-protective mechanism studied in skin research"
  ],
  "target": [
    "NF-kB",
    "eNOS",
    "MMP-1",
    "MMP-9",
    "SOD",
    "PON1 (paraoxonase)",
    "ox-LDL"
  ],
  "use_case": [
    "blood-pressure research direction (strongest; meta-analytic evidence concentrated in prehypertensive, hypertensive, metabolic-syndrome and obese populations, not healthy normotensives)",
    "antioxidant / oxidative-stress research direction (MDA and ox-LDL reduction; A-grade meta support)",
    "cardiovascular-risk-marker research direction (lipid / LDL-oxidation endpoints in at-risk populations)",
    "inflammatory-marker research direction (hs-CRP; effect is selective — CRP and WBC were null in meta-analysis)",
    "venous-circulation / leg-comfort research direction (research-context only; limited high-quality RCTs)",
    "skin research direction (oral chloasma/elasticity and topical wound research; research-context only, not a cosmetic claim)"
  ],
  "body_system": [
    "CARDIO",
    "BLOOD",
    "CELL",
    "SKIN",
    "VISION"
  ],
  "evidence_tier": "A",
  "evidence_anchor_pmid_count": 303,
  "evidence_breakdown": {
    "meta_sr": 17,
    "human_rct": 52,
    "total_indexed": 303
  },
  "dosage_range": "RCT-validated oral doses are 150-300 mg/day of standardized extract (>=95% proanthocyanidins); MegaNatural-BP 300 mg/day is the most-validated blood-pressure dose, and lipid/metabolic trials extend to ~400 mg/day. No formal Upper Limit established. Branded raw materials (MegaNatural-BP, Leucoselect) drove most trials, so efficacy extrapolation to generic GSE warrants caution. Educational reference, not a dosing recommendation.",
  "safety_notes": "Excellent tolerability — across RCTs adverse-event rates were not significantly different from placebo; rare mild headache, dizziness or nausea. FDA self-affirmed GRAS with no-objection notices. OPC has mild antiplatelet activity (Shenoy 2007), so people taking anticoagulants/antiplatelets (warfarin, aspirin) should consult a professional, and discontinuation ~2 weeks before surgery is commonly advised. A controlled trial found no clinically significant effect on CYP2D6-substrate pharmacokinetics (Goey 2013, dextromethorphan probe). Safety data in pregnancy/lactation are insufficient; people with grape allergy should avoid it. This page describes scientific evidence, not medical advice; people treated for hypertension or on blood thinners should not self-substitute it for medical care.",
  "regulatory": {
    "fda": "Legal dietary-supplement ingredient: pre-DSHEA Old Dietary Ingredient and self-affirmed GRAS (FDA no-objection). DSHEA structure/function claims (e.g. antioxidant support, supports healthy blood pressure already within the normal range) permitted with the mandatory FDA disclaimer; disease claims prohibited. No FDA-authorized health claim.",
    "efsa": "Marketable as a food-supplement ingredient (long history of use, not a Novel Food); traditional-herbal (THR) registrations exist in France/Italy for venous function. EFSA has authorized 0 health claims — antioxidant and cardiovascular Article 13 claims (incl. proanthocyanidins ID 1334) were rejected for insufficient evidence.",
    "anvisa": "Brazil ANVISA: legal botanical food-supplement ingredient under RDC 240/2018; claims must follow ANVISA-recognized wording; no single-ingredient authorized functional claim. [China NMPA: listed health-food raw material; multiple OPC blue-hat health foods approved for the authorized function 'helps with antioxidation' — the only function approved for grape-seed OPC in China; also a conventional-food ingredient per GB/T 22250-2008.]"
  },
  "regulatory_markets": [
    {
      "market": "US",
      "status": "GRAS",
      "tier": "permitted"
    },
    {
      "market": "EU",
      "status": "Authorized claim",
      "tier": "authorized"
    },
    {
      "market": "CN",
      "status": "Supplement (CBEC)",
      "tier": "permitted"
    },
    {
      "market": "BR",
      "status": "ANVISA supplement",
      "tier": "permitted"
    }
  ],
  "ingredient_hub_url": "https://asxan.ai/ingredients/grape-seed-extract/",
  "related_goal_slugs": [],
  "related_lifestyle_slugs": [],
  "last_evidence_review": "2026-06-27",
  "schema_version": "nc-public-v0.2",
  "api_version": "nc-public-v0.3",
  "_meta": {
    "last_evidence_review": "2026-06-27",
    "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",
        "proprietary_research_compounds",
        "supplier_specific_grade_specifications",
        "unpublished_endpoint_data"
      ],
      "rationale": "asxan.ai surfaces the educational, evidence-tier-disclosed slice. Formula composition and clinical-protocol internals are intentionally outside this public surface."
    }
  }
}