{
  "slug": "guarana",
  "name": "Guaraná (Paullinia cupana)",
  "alternate_names": [
    "Paullinia cupana",
    "Guarana",
    "Guaranine",
    "Brazilian cocoa",
    "Amazon natural caffeine",
    "PC-18 (purified dry extract)"
  ],
  "mechanism": [
    "Caffeine antagonizes A1/A2A adenosine receptors, reducing the sleep-promoting / fatigue signaling that lowers alertness (research-context mechanism)",
    "Phosphodiesterase inhibition by methylxanthines (caffeine, theobromine, theophylline) raising intracellular cAMP (mechanistic)",
    "Polyphenol matrix (procyanidins B1-B4, catechin, epicatechin) forms a slow-release complex with caffeine, proposed to flatten the peak-and-crash curve seen with isolated caffeine (mechanism / pharmacokinetic hypothesis)",
    "Free-radical scavenging / antioxidant activity of catechins and procyanidins in mechanistic and ex-vivo work (e.g., reduced LDL oxidation)",
    "Promotion of fat oxidation and thermogenesis, studied mainly in caffeine + green-tea co-formulations (research-context)",
    "Platelet-aggregation inhibition and MAO modulation reported in preclinical / mechanistic studies"
  ],
  "target": [
    "A1 / A2A adenosine receptors",
    "Phosphodiesterase (PDE)",
    "MAO-A / MAO-B",
    "Oxidative-stress markers (LDL oxidation, antioxidant enzymes)",
    "Fatigue / mental-performance scales (research endpoints)"
  ],
  "use_case": [
    "fatigue / mental alertness markers (research-context · strongest direct-guarana RCT+meta evidence is in cancer chemotherapy/radiation-related fatigue populations, NOT general healthy fatigue)",
    "attention / working-memory and acute cognitive-task performance (research-context · low-dose acute RCTs)",
    "exercise performance markers (research-context · cycling time-trial RCTs where guarana but not low-dose caffeine outperformed placebo, suggesting a non-caffeine polyphenol contribution)",
    "thermogenesis / energy-expenditure and weight-management markers (research-context · evidence mostly from green-tea/caffeine co-formulations, not guarana monotherapy)",
    "antioxidant / oxidative-stress and LDL-oxidation markers (research-context · single elderly RCT + ex-vivo)",
    "mood / psychological-wellbeing markers (research-context · single small trial of a commercial product)",
    "metabolic markers (research-context · habitual-intake epidemiological cohort, association not causation)"
  ],
  "body_system": [
    "NEURO",
    "MOOD",
    "MUSCULO",
    "CARDIO",
    "ENDO",
    "IMMUNE"
  ],
  "evidence_tier": "B",
  "evidence_anchor_pmid_count": 70,
  "evidence_breakdown": {
    "meta_sr": 5,
    "human_rct": 20,
    "total_indexed": 70
  },
  "dosage_range": "Research-context dosing varies by endpoint and form. Cancer-related fatigue RCTs used 50-75 mg/day of standardized purified dry extract (PC-18 / ~22% caffeine; ≈11-16 mg caffeine) over ~21 days. Acute cognitive RCTs used 37.5-300 mg full-spectrum extract (≈8-66 mg caffeine), where low doses were as or more effective than high doses — suggesting a non-caffeine (procyanidin/catechin) contribution. Thermogenesis/weight studies used 200-400 mg/day, usually combined with green tea. Cycling-performance RCTs used ~200-300 mg pre-exercise. Traditional Brazilian use is 0.5-2 g/day seed powder brewed in water. Total caffeine from ALL sources should stay <400 mg/day (adults) / <200 mg/day (pregnancy) — guarana carries 2-3x the caffeine of coffee beans, so the dose must always be converted to total caffeine. Educational reference only, not a dosing recommendation.",
  "safety_notes": "Generally well tolerated within studied ranges; decades of population-level consumption in Brazil (Guaraná Antarctica is the country's #2 soft-drink brand). Adverse effects are caffeine-mediated — insomnia, palpitations, jitteriness, GI upset — and become more likely at high extract doses (>500 mg/day). Two HARD safety limits apply across markets: (1) total caffeine <400 mg/day for adults and <200 mg/day in pregnancy (FDA/EFSA/Health Canada/ACOG consensus); products must convert the guarana dose to total caffeine and disclose it; (2) concentrated guarana extract is contraindicated in children (<18). Caution in hypertension, arrhythmia, and cardiovascular disease (additive stimulant risk). Documented interactions: MAO inhibitors, other CNS stimulants, warfarin/CYP1A2 substrates, and lithium (caffeine diuresis can affect lithium levels) — all caffeine-mediated. Stacking with coffee, tea, energy drinks, or cola can exceed the daily caffeine ceiling. Not for pregnant/breastfeeding women without medical guidance.",
  "regulatory": {
    "fda": "Lawful dietary-supplement ingredient under DSHEA (pre-DSHEA use history — marketed in the US before 1994, so no NDI notification required) and a self-affirmed GRAS natural caffeine source for food/beverage use; never 'FDA approved'. Structure/function claims only, with the mandatory DSHEA disclaimer and 30-day FDA notification. No disease claims. FDA warning-letter precedent against marketing high-caffeine products to children.",
    "efsa": "Traditional food ingredient, NOT a Novel Food (long EU use history); Paullinia cupana seed is on the BELFRIT (Belgium-France-Italy) botanical list and is marketable as a food supplement under Directive 2002/46/EC (member-state botanical lists vary). Guarana itself has NO authorized Article 13/14 health claim. However, products delivering ≥75 mg caffeine per serving may use the EFSA-authorized caffeine claims ('Caffeine contributes to increased alertness' / 'to an increase in endurance performance'). Beverages with caffeine ≥150 mg/L must carry the 'High caffeine content. Not recommended for children or pregnant or breast-feeding women' label (Reg (EU) 1169/2011). EFSA 2015 caffeine safe upper limit: 400 mg/day adults, 200 mg/day pregnancy.",
    "anvisa": "Fully established in Brazil (origin country): a traditional food ingredient and an authorized dietary-supplement constituent under RDC 243/2018 + IN 28/2018 (Paullinia cupana seed), and a Traditional Herbal Product under RDC 240/2018 Annex I. Dietary-supplement caffeine cap is 420 mg per daily serving (all sources). Mandatory caffeine-content labeling plus the warning 'Contém cafeína. Não recomendado para crianças, gestantes, lactantes e pessoas sensíveis à cafeína'. Traditional-use claims only (no disease claims). No Anexo V functional health claim specific to guarana. [China NMPA, for reference: not approved — absent from novel-food, health-food, and medicine-food-homology lists; only compliant C-end channel is cross-border e-commerce with no functional claims and mandatory caffeine declaration on the Chinese label.]"
  },
  "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/guarana/",
  "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."
    }
  }
}