{
  "slug": "hmb",
  "name": "HMB (β-Hydroxy β-Methylbutyrate)",
  "alternate_names": [
    "HMB",
    "β-Hydroxy β-Methylbutyrate",
    "Beta-hydroxy-beta-methylbutyrate",
    "3-Hydroxyisovaleric acid",
    "Calcium HMB (HMB-Ca)",
    "HMB free acid (HMB-FA)",
    "β--β-"
  ],
  "mechanism": [
    "Leucine metabolite (~5% of dietary leucine is converted to HMB via the KIC intermediate); supplementation is used to reach research-level intakes (research-context)",
    "Stimulation of muscle protein synthesis via the mTOR/p70S6K signaling pathway (research model)",
    "Attenuation of muscle protein breakdown by downregulating the ubiquitin-proteasome system and caspase-3 apoptotic pathway (preclinical / mechanistic)",
    "Support of skeletal-muscle mitochondrial biogenesis (Standley 2017 RCT mechanistic readout)"
  ],
  "target": [
    "mTORC1 / p70S6K",
    "Ubiquitin-proteasome system (Atrogin-1 / MuRF-1)",
    "Caspase-3 apoptotic pathway",
    "IGF-1 axis",
    "Skeletal-muscle mitochondria"
  ],
  "use_case": [
    "age-related muscle loss / lean-mass preservation (research context)",
    "muscle preservation during bed rest or reduced mobility (research context)",
    "post-exercise recovery / exercise-induced muscle-damage markers (research context)",
    "resistance-training lean-mass and strength outcomes (research context)",
    "nutritional management of clinical muscle wasting (research context · clinical populations)"
  ],
  "body_system": [
    "MUSCULO",
    "MITO",
    "CELL"
  ],
  "evidence_tier": "S",
  "evidence_anchor_pmid_count": 399,
  "evidence_breakdown": {
    "meta_sr": 50,
    "human_rct": 152,
    "total_indexed": 399
  },
  "dosage_range": "3 g/day, typically split into 3 × 1 g doses (the dose used in nearly all positive RCTs · educational reference); intervention windows of 8–24 weeks for muscle-mass outcomes and over the full immobilization period for disuse protection · 6 g/day studied short-term without added benefit · HMB-Ca is the predominant form in long-term trials, HMB-FA reaches a faster plasma peak (~30 min vs ~60 min)",
  "safety_notes": "3 g/day has been used long-term (12 months+) in adults without serious adverse events reported; occasional mild GI discomfort (nausea), usually linked to fasted dosing. Human RCTs report no adverse effect on liver/kidney function, blood counts, lipids or glucose, and no clinically significant drug interactions are documented. No adequate safety data in pregnancy or lactation, and trials were conducted in adults — not recommended for pregnant/breastfeeding women or individuals under 18. Educational information only; consult a healthcare professional. Not intended to diagnose, treat, cure or prevent any disease.",
  "regulatory": {
    "fda": "Lawful dietary-supplement ingredient under DSHEA · HMB-Ca self-affirmed GRAS (Metabolic Technologies / TSI Group) and treated as a pre-1994 Old Dietary Ingredient; HMB-FA (free acid) may require an NDI notification. Structure/function claims only (no FDA-authorized health claim); the FDA disclaimer is mandatory. ('FDA GRAS self-affirmed' — GRAS is a self-determination with no FDA objection, not an FDA approval/certification.)",
    "efsa": "Lawful to market as a food-supplement ingredient (HMB-Ca sold in the EU since the 2000s). NO authorized health claim: the EFSA NDA Panel (EFSA Journal 2011;9(6):2227) concluded that a cause-and-effect relationship was not established for the 'maintenance of normal muscle function' claim. EU material may state composition/source only — no efficacy wording.",
    "anvisa": "Authorized as a food-supplement constituent (Suplemento Alimentar) under RDC 243/2018; β-hidroxi-β-metilbutirato is listed in IN 28/2018 permitted-constituents annex (HMB-Ca as the principal form). Functional claims permitted only within the ANVISA framework; no disease-treatment claims."
  },
  "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/hmb/",
  "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."
    }
  }
}