{
  "slug": "caffeine",
  "name": "Caffeine (1,3,7-Trimethylxanthine)",
  "alternate_names": [
    "1,3,7-trimethylxanthine",
    "Caffeine anhydrous",
    "Guaranine"
  ],
  "mechanism": [
    "Non-selective adenosine A1/A2A receptor antagonism (relieves central adenosine-mediated inhibition)",
    "Phosphodiesterase inhibition (raises intracellular cAMP)",
    "Catecholamine release promotion",
    "Enhanced fatty-acid oxidation during exercise",
    "Sarcoplasmic-reticulum Ca2+ release facilitation"
  ],
  "target": [
    "Adenosine A1 receptor (A1R)",
    "Adenosine A2A receptor (A2AR)",
    "Phosphodiesterase (PDE)",
    "Ryanodine receptor / sarcoplasmic-reticulum Ca2+ channel"
  ],
  "use_case": [
    "alertness / vigilance support (research context)",
    "attention and reaction-time performance (research context)",
    "endurance exercise performance (research context)",
    "strength and power output (research context)",
    "exercise fat-oxidation and metabolic rate (research context)",
    "subjective energy and positive mood (research context)"
  ],
  "body_system": [
    "NEURO",
    "MUSCULO",
    "MITO",
    "WEIGHT",
    "MOOD"
  ],
  "evidence_tier": "S",
  "evidence_anchor_pmid_count": 1381,
  "evidence_breakdown": {
    "meta_sr": 144,
    "human_rct": 420,
    "total_indexed": 1381
  },
  "dosage_range": "75-200 mg single acute dose for alertness/attention; 3-6 mg/kg body weight 30-60 min pre-exercise for endurance and strength/power; safety ceiling ≤400 mg/day for healthy adults and ≤200 mg/day in pregnancy (EFSA 2015 / FDA); single doses ≤200 mg raise no safety concern. Educational reference, not a dosing recommendation.",
  "safety_notes": "Common adverse effects at higher intakes: anxiety, insomnia, palpitations, tremor, GI/acid reflux. Withdrawal symptoms (headache, fatigue, irritability) appear 12-24 h after cessation, peaking ~20-51 h. Wide CYP1A2-driven inter-individual variability (~50% slow metabolizers; cardiovascular sensitivity may rise at high doses). Tolerance to alertness/metabolic effects develops over ~7-12 days. Afternoon/evening intake shortens and degrades sleep (Gardiner 2023 meta PMID 36870101). Not for children/adolescents; pregnancy ≤200 mg/day. High-purity bulk caffeine powder carries fatal-overdose risk (FDA 2018). Do not combine with ephedrine/synephrine/DMAA. WADA-monitored (not banned).",
  "regulatory": {
    "fda": "GRAS (21 CFR 182.1180; cola-type beverages limited to 0.02% / 200 ppm) and a lawful dietary-supplement ingredient under DSHEA 1994; structure/function claims permitted with 30-day FDA notification. FDA recommends ≤400 mg/day for healthy adults. 2018 guidance restricts pure/highly-concentrated bulk caffeine sold direct to consumers (overdose risk).",
    "efsa": "Four authorized Reg 432/2012 / Reg (EU) 2017/676 health claims: alertness and attention (Art. 13.1, ≥75 mg/serving) and endurance performance + endurance capacity (Art. 13.5, 3 mg/kg pre-exercise). EFSA 2011 REJECTED fat-oxidation/body-fat-reduction (ID 735, 1484) and energy-expenditure/weight-reduction (ID 1487) claims. EFSA 2015 safety: ≤400 mg/day adults, ≤200 mg/day pregnancy, single dose ≤200 mg of no concern.",
    "anvisa": "Permitted in food supplements under the RDC 243/2018 framework (IN 28/2018 authorized-constituent list); energy drinks limited to ≤350 mg/L (RDC 273/2005); mandatory 'CONTÉM CAFEÍNA' label warning plus pregnancy/child cautions. Weight-loss and fatigue-treatment claims are not permitted."
  },
  "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/caffeine/",
  "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."
    }
  }
}