{ "$schema_version": "5.3", "review_mode": "fresh", "claim_restatement": { "index_wording": "Laetrile or amygdalin provides clinically meaningful anticancer benefit through selective tumour toxicity at regimens promoted for human treatment.", "entry_form": "claim", "gradeable_restatement": "Laetrile/amygdalin treatment provides clinically meaningful anticancer benefit through selective tumour toxicity at regimens promoted for human treatment.", "restatement_required": true, "split_into": [], "parent_claim": null, "scope_qualifiers": [ { "qualifier": "Chemical formulation, dose, route, cancer type/stage, coingestions, concurrent care and observation horizon fixed before outcomes", "determinable_before_outcome": true, "determined_from": "Enrollment and experimental design, before results; no responder-defined scope.", "action": "retained" } ], "original_claim": "Laetrile or amygdalin provides clinically meaningful anticancer benefit through selective tumour toxicity at regimens promoted for human treatment.", "restatement_note": "The original registered wording, including \"laetrile or amygdalin\", is retained above and in preregistration. The slash denotes the registered treatment family, with chemical formulation, route and dose still assessed separately. This is a grammatical restatement, without changing the claim or broadening evidence across formulations." }, "hypothesis": { "name": "Laetrile / Amygdalin as Cancer Treatment", "central_claim": "Laetrile/amygdalin treatment provides clinically meaningful anticancer benefit through selective tumour toxicity at regimens promoted for human treatment.", "proposed_mechanism": "Laetrile or amygdalin provides clinically meaningful anticancer benefit through selective tumour toxicity at regimens promoted for human treatment.", "claimed_scope": "Promoted human laetrile/amygdalin cancer regimens, with chemical formulation, dose, route, cancer stage and concurrent treatment specified; engineered experimental carriers are separate contexts", "claimed_level": [ "maintenance", "progression", "response" ], "is_conjunctive": true, "conjunctive_note": "Primary SC2 is the registered clinical policy/benefit claim. Etiologic mechanisms and separately stated harms are reported at their own scope; proof of harm does not itself assign the nominal benefit level." }, "rubric_routing": { "primary_rubric": "02-cancer-biology.md", "secondary_rubrics": [], "index_notes_applied": [ "Primary SC2 is the registered clinical policy/benefit claim. Etiologic mechanisms and separately stated harms are reported at their own scope; proof of harm does not itself assign the nominal benefit level." ], "rubric_fit_note": "Rubric02 directly governs tumour control and clinical survival. Its literal endogenous-driver/lineage definitions are designed mainly for cancer mechanisms, so an explicit exposure-treatment adaptation is used: a field-valid drug-benefit test requires measured cancer response/control or survival under a specified exposure, with a credible comparator, not merely marker shifts. Toxicology SC3 separately concerns clinical symptoms and measured exposure under routes/coingestions with specificity, dechallenge/antidote and controlled model contrasts. SC4 concerns actual treatment receipt and clinical survival, while observational coding and selection prevent a laetrile-specific causal estimate. Original rubric quotes are preserved; this adaptation does not amend v5.3." }, "subclaim_matrix": { "subclaims": [ { "id": "SC1", "statement": "Amygdalin produces tumour-selective cytotoxicity that spares normal tissue.", "subclaim_type": "mechanism", "scope": "Chemical formulation, route, metabolic enzymes and achievable exposure stated", "claimed_scope": "Chemical formulation, route, metabolic enzymes and achievable exposure stated", "governing_rubric": "02-cancer-biology.md", "key_evidence_anchor": "Matched tumour/normal systems and in vivo exposure/toxicology", "hsef_level": "Γ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Some matched malignant/normal cell comparisons and engineered activation systems show differential effects. Other matched marrow studies show no selective killing, and high culture concentrations, tissue-mismatched controls and enzyme/carrier additions prevent a general human therapeutic window. Partial system selectivity is retained atΓ, not promoted to clinical efficacy.", "rubric_adaptation": "For a drug-selectivity mechanism, matched malignant and normal systems plus clinically anchored tumour/normal exposure and in vivo confirmation are the applied criterion. Cell death in vitro or a tumour-only marker shift cannot establish a human therapeutic window." }, { "id": "SC2", "statement": "Promoted human laetrile regimens improve tumour control or survival.", "subclaim_type": "generalization", "scope": "Baseline cancer type/stage, treatment, dose and cointerventions specified", "claimed_scope": "Baseline cancer type/stage, treatment, dose and cointerventions specified", "governing_rubric": "02-cancer-biology.md", "key_evidence_anchor": "Original clinical tumour response, progression, survival and comparator evidence", "hsef_level": "Α", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "The registered human-regimen benefit claim has no credible, reproducible positive clinical support in the examined set. The 178-patient nonrandomized treatment programme reported no substantive benefit. Six judged responses in solicited favorable historical records lack a credible counterfactual and reliable attribution. Laboratory activity and new-platform animal effects remain SC1 support and do not establish SC2. Α is evidence-derived unsupported clinical benefit, rather than a penalty for the absence of an RCT or a claim of zero biological activity.", "rubric_adaptation": "For a treatment-benefit claim, the applied field-valid criterion is objective tumour response/control or survival under the specified regimen with a credible counterfactual, clinically relevant exposure and interpretable concurrent therapy. The negative uncontrolled study is a discriminator, not a positive causal crossing or randomized effect size." }, { "id": "SC3", "statement": "Promoted laetrile regimens avoid clinically important systemic cyanide toxicity.", "subclaim_type": "generalization", "scope": "Oral versus intravenous exposure and interacting foods/cointerventions separated", "claimed_scope": "Oral versus intravenous exposure and interacting foods/cointerventions separated", "governing_rubric": "02-cancer-biology.md", "key_evidence_anchor": "Clinical toxicology, blood exposure and documented poisoning cases", "hsef_level": "Α", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "The blanket claim of avoiding clinically important systemic cyanide toxicity is directly challenged by prescribed oral-regimen poisoning, measured cyanide, food interactions and animal rescue/exposure tests. Some small IV pharmacology settings lack observed toxicity, but that cannot establish safety across promoted regimens. The positive avoidance claim is unsupported atΑ; the opposite route-dependent poisoning model scores separately and higher.", "rubric_adaptation": "For the avoidance-of-toxicity claim, the applied criterion is route/dose-specific clinical safety with measured exposure, interacting-food controls and a meaningful observation horizon. Clinical poisoning with timing, cyanide or antidote/dechallenge supports the opposite harm proposition; it does not cross the positive avoidance threshold." }, { "id": "SC4", "statement": "Replacing effective cancer care with unproven alternative treatment can worsen clinical survival.", "subclaim_type": "mechanism", "scope": "Treatable nonmetastatic cancer and actual treatment receipt/refusal; not every complementary use", "claimed_scope": "Treatable nonmetastatic cancer and actual treatment receipt/refusal; not every complementary use", "governing_rubric": "02-cancer-biology.md", "key_evidence_anchor": "Treatment substitution cohorts with confounding, selection and modality specificity retained", "hsef_level": "Β", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Treatment substitution/refusal cohorts associate with worse survival and treatment-refusal adjustment attenuates the complementary-use association. These are clinically important warnings, but the retrieved cohorts are nonrandomized and not laetrile-specific. This separate broad causal proposition is held atΒ under the association-only cap; the observed hazard ratios are not randomized causal estimates.", "rubric_adaptation": "For treatment-substitution harm, compare actual treatment receipt/refusal with survival in predefined cancers while controlling selection and treatment indication. The retrieved association-only cohorts do not establish a laetrile-specific or randomized effect." } ], "aggregation_rule": "primary-subclaim", "aggregation_preregistered": true, "aggregation_rationale": "Primary SC2 is the registered clinical policy/benefit claim. Etiologic mechanisms and separately stated harms are reported at their own scope; proof of harm does not itself assign the nominal benefit level.", "primary_subclaim_id": "SC2", "aggregation_derivation": "Overall Α follows the preregistered primary SC2 human-regimen clinical-benefit gate. Partial selectivity and experimental activity remain Γ in SC1; they cannot be transferred into the clinical-benefit score. Toxicity avoidance is separately contradicted at Α, and generic care-substitution survival associations remain Β. Route-dependent cyanide harm has its own Ζ model assessment. No finding of toxicity alone determines the benefit grade.", "aggregation_alternatives": { "weakest_link_would_return": "Α", "primary_subclaim_would_return": "Α", "scope_matched_would_return": "Α", "note": "Separate narrow successes do not replace the preregistered full-scope gate." }, "index_rule_deviation": "" }, "competing_models": { "models_evaluated": [ { "rank_in_tournament": 1, "model_id": "M2", "is_nominal": false, "name": "Route-dependent nonselective cyanide toxicity", "core_claim": "Microbial or food-enzyme activation and coingestions generate systemic cyanide rather than a reliably tumour-selective clinical exposure.", "explains_what_nominal_does_not": "Microbial or food-enzyme activation and coingestions generate systemic cyanide rather than a reliably tumour-selective clinical exposure.", "strongest_supporting_evidence": [ "Human route pharmacology, prescribed-dose poisoning, food crossover, gut-flora manipulations and animal thiosulfate rescue constrain distinct errors and converge on harm." ], "strongest_contradictory_evidence": [ "Not every route or dose causes poisoning; small IV settings and some chronic series show little clinical toxicity. Cases cannot determine population incidence." ], "hsef_level_for_this_model": "Ζ", "rationale": "Human route pharmacology, prescribed-dose poisoning, food crossover, gut-flora manipulations and animal thiosulfate rescue constrain distinct errors and converge on harm. Not every route or dose causes poisoning; small IV settings and some chronic series show little clinical toxicity. Cases cannot determine population incidence." }, { "rank_in_tournament": 2, "model_id": "M3", "is_nominal": false, "name": "Contextual cell activity without a clinical exposure bridge", "core_claim": "Culture effects and engineered delivery can be real without being achievable as a safe effective promoted human regimen.", "explains_what_nominal_does_not": "Culture effects and engineered delivery can be real without being achievable as a safe effective promoted human regimen.", "strongest_supporting_evidence": [ "Matched normal-cell positives, drug-combination effects and targeted enzyme/nanocarrier models support restricted activity; human plasma and culture exposure contexts differ." ], "strongest_contradictory_evidence": [ "Some native animal tumour models report activity, so it would be wrong to assert the molecule is biologically inactive in every setting." ], "hsef_level_for_this_model": "Γ", "rationale": "Matched normal-cell positives, drug-combination effects and targeted enzyme/nanocarrier models support restricted activity; human plasma and culture exposure contexts differ. Some native animal tumour models report activity, so it would be wrong to assert the molecule is biologically inactive in every setting." }, { "rank_in_tournament": 3, "model_id": "M4", "is_nominal": false, "name": "Selection and concurrent treatment explain apparent clinical benefit", "core_claim": "Solicited favorable cases and provider impressions can reflect selection, prior treatment and subjective endpoints rather than drug efficacy.", "explains_what_nominal_does_not": "Solicited favorable cases and provider impressions can reflect selection, prior treatment and subjective endpoints rather than drug efficacy.", "strongest_supporting_evidence": [ "The1978case-record design solicits only perceived successes; modern provider survey uses impressions and limited monitoring, and substitution cohorts show treatment-refusal differences." ], "strongest_contradictory_evidence": [ "This does not prove every individual response is attributable to prior treatment or quantify confounding in every testimonial." ], "hsef_level_for_this_model": "Β", "rationale": "The1978case-record design solicits only perceived successes; modern provider survey uses impressions and limited monitoring, and substitution cohorts show treatment-refusal differences. This does not prove every individual response is attributable to prior treatment or quantify confounding in every testimonial." }, { "rank_in_tournament": 4, "model_id": "M1", "is_nominal": true, "name": "Selective tumour toxicity produces clinical benefit", "core_claim": "Promoted laetrile exposure safely targets tumour cells and improves human disease control.", "explains_what_nominal_does_not": "Promoted laetrile exposure safely targets tumour cells and improves human disease control.", "strongest_supporting_evidence": [ "Selected cell-pair sparing, engineered antibody-enzyme activation and newer animal delivery studies provide its strongest good-faith support." ], "strongest_contradictory_evidence": [ "Human regimen benefit lacks a credible positive comparator, matched marrow shows no selectivity, and systemic oral poisoning directly opposes a broad safe selective mechanism." ], "hsef_level_for_this_model": "Α", "rationale": "Selected cell-pair sparing, engineered antibody-enzyme activation and newer animal delivery studies provide its strongest good-faith support. Human regimen benefit lacks a credible positive comparator, matched marrow shows no selectivity, and systemic oral poisoning directly opposes a broad safe selective mechanism." } ], "tournament_summary": "Descriptive comparison; does not modify the nominal score. Human oral/IV parent and cyanide pharmacology (7005480;7273266), intestinal-versus-tumour glucosidase assays (6796962), and controlled mouse activation measurements (7448350) distinguish systemic activation from a consistently selective tumour mechanism. Engineered magnetic activation (32636623) changes that delivery problem experimentally, but its formulation is different and its body retains cardiac/liver biomarker effects.", "study_separating_rank1_from_rank2": "Human oral/IV parent and cyanide pharmacology (7005480;7273266), intestinal-versus-tumour glucosidase assays (6796962), and controlled mouse activation measurements (7448350) distinguish systemic activation from a consistently selective tumour mechanism. Engineered magnetic activation (32636623) changes that delivery problem experimentally, but its formulation is different and its body retains cardiac/liver biomarker effects.", "nominal_wins_only_by_funding_artifact": false, "level_unchanged_by_tournament": true }, "evidence_inventory": [ { "n": 1, "pmid": "7033783", "title": "A clinical trial of amygdalin (Laetrile) in the treatment of human cancer.", "citation": "Moertel CG, Fleming TR, Rubin J et al. A clinical trial of amygdalin (Laetrile) in the treatment of human cancer. The New England journal of medicine. 1982.", "doi": "10.1056/NEJM198201283060403", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/7033783/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/7033783/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID7033783", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "contradicts", "what_it_shows": "The original nonrandomized study treated 178 patients and reports no substantive cancer benefit with cyanide hazards.", "what_it_does_not_show": "Uncontrolled heterogeneous trial, not an RCT; exact response numbers were unavailable in the original abstract/body.", "confounders_present": [ "Uncontrolled heterogeneous trial, not an RCT; exact response numbers were unavailable in the original abstract/body." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 2, "pmid": "7005480", "title": "A pharmacologic and toxicological study of amygdalin.", "citation": "Moertel CG, Ames MM, Kovach JS et al. A pharmacologic and toxicological study of amygdalin. JAMA. 1981.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/7005480/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/7005480/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "NCI_CLINICAL_PHARMACOLOGY_PROGRAMME", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "Six cancer patients show route differences: IV parent excretion with little toxicity, oral cyanide and almond-related symptoms.", "what_it_does_not_show": "Small safety study does not establish clinical benefit or safety of every IV regimen.", "confounders_present": [ "Small safety study does not establish clinical benefit or safety of every IV regimen." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 3, "pmid": "7273266", "title": "Pharmacology of amygdalin (laetrile) in cancer patients.", "citation": "Ames MM, Moyer TP, Kovach JS et al. Pharmacology of amygdalin (laetrile) in cancer patients. Cancer chemotherapy and pharmacology. 1981.", "doi": "10.1007/BF00253010", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/7273266/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/7273266/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "NCI_CLINICAL_PHARMACOLOGY_PROGRAMME", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "IV parent exposure is high and rapidly cleared; oral parent exposure is low while cyanide rises and almonds amplify it.", "what_it_does_not_show": "Related pharmacology programme; plasma parent drug is not tumour exposure or an efficacy endpoint.", "confounders_present": [ "Related pharmacology programme; plasma parent drug is not tumour exposure or an efficacy endpoint." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 4, "pmid": "7092570", "title": "The pharmacokinetics of amygdalin.", "citation": "Rauws AG, Olling M, Timmerman A. The pharmacokinetics of amygdalin. Archives of toxicology. 1982.", "doi": "10.1007/BF00347879", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/7092570/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/7092570/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID7092570", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal in vivo", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Dog and rat pharmacokinetics demonstrate renal elimination and limited oral parent bioavailability with prunasin formation.", "what_it_does_not_show": "Species limits; no efficacy trial or equivalence of oral and IV toxicity.", "confounders_present": [ "Species limits; no efficacy trial or equivalence of oral and IV toxicity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 5, "pmid": "30935547", "title": "Cyanide and lactate levels in patients during chronic oral amygdalin intake followed by intravenous amygdalin administration.", "citation": "Mani J, Rutz J, Maxeiner S et al. Cyanide and lactate levels in patients during chronic oral amygdalin intake followed by intravenous amygdalin administration. Complementary therapies in medicine. 2019.", "doi": "10.1016/j.ctim.2019.03.002", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/30935547/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30935547/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID30935547", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Retrospective oral-plus-IV exposure in 55 patients shows increased cyanide but decreased lactate around infusion.", "what_it_does_not_show": "Biomarkers without comparator or objective tumour outcome; printed dose units require body verification.", "confounders_present": [ "Biomarkers without comparator or objective tumour outcome; printed dose units require body verification." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 6, "pmid": "38999817", "title": "Survey of Physicians and Healers Using Amygdalin to Treat Cancer Patients.", "citation": "Markowitsch SD, Binali S, Rutz J et al. Survey of Physicians and Healers Using Amygdalin to Treat Cancer Patients. Nutrients. 2024.", "doi": "10.3390/nu16132068", "pmcid": "PMC11243289", "url": "https://pubmed.ncbi.nlm.nih.gov/38999817/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38999817/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID38999817", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:2. Materials and Methods:paragraph0, 1:2. Materials and Methods:paragraph6. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [], "evidence_class": "Weak", "system": "human provider survey", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Providers report perceived progression delay and few adverse effects, with variable dosing and little cyanide monitoring.", "what_it_does_not_show": "Selected 38 of 76 providers; impressions are not audited patient outcomes or evidence of safety.", "confounders_present": [ "Selected 38 of 76 providers; impressions are not audited patient outcomes or evidence of safety." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 7, "pmid": "627001", "title": "Pharmaceutical assessment of amygdalin (Laetrile) products.", "citation": "Davignon JP, Trissel LA, Kleinman LM. Pharmaceutical assessment of amygdalin (Laetrile) products. Cancer treatment reports. 1978.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/627001/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/627001/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID627001", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "pharmaceutical analytic", "decisive_perturbation": false, "endogenous": false, "direction": "contradicts", "what_it_shows": "Selected historical commercial products were subpotent, mislabeled, contaminated or pyrogenic.", "what_it_does_not_show": "Manufacturer and batch findings cannot describe every modern preparation or determine cancer efficacy.", "confounders_present": [ "Manufacturer and batch findings cannot describe every modern preparation or determine cancer efficacy." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 8, "pmid": "6796962", "title": "Amygdalin (Laetrile) and prunasin beta-glucosidases: distribution in germ-free rat and in human tumor tissue.", "citation": "Newmark J, Brady RO, Grimley PM et al. Amygdalin (Laetrile) and prunasin beta-glucosidases: distribution in germ-free rat and in human tumor tissue. Proceedings of the National Academy of Sciences of the United States of America. 1981.", "doi": "10.1073/pnas.78.10.6513", "pmcid": "PMC349070", "url": "https://pubmed.ncbi.nlm.nih.gov/6796962/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/6796962/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID6796962", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human and animal tissue biochemical", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "Intestinal mucosa has activating glucosidase activity not detected in the human tumour tissues tested.", "what_it_does_not_show": "Specific tissue panel challenges selective activation but cannot exclude every alternate cellular mechanism.", "confounders_present": [ "Specific tissue panel challenges selective activation but cannot exclude every alternate cellular mechanism." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 9, "pmid": "14281087", "title": "LAETRILE: A STUDY OF ITS PHYSICOCHEMICAL AND BIOCHEMICAL PROPERTIES.", "citation": "LEVI L, FRENCH WN, BICKIS IJ et al. LAETRILE: A STUDY OF ITS PHYSICOCHEMICAL AND BIOCHEMICAL PROPERTIES. Canadian Medical Association journal. 1965.", "doi": "", "pmcid": "PMC1928277", "url": "https://pubmed.ncbi.nlm.nih.gov/14281087/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/14281087/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID14281087", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "pharmaceutical biochemical", "decisive_perturbation": false, "endogenous": false, "direction": "contradicts", "what_it_shows": "Canadian and US formulations differ; tested preparations do not support the manufacturers' biological rationale.", "what_it_does_not_show": "Historic chemical and biological tests are not clinical endpoints or universal product identification.", "confounders_present": [ "Historic chemical and biological tests are not clinical endpoints or universal product identification." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 10, "pmid": "16014371", "title": "Life-threatening interaction between complementary medicines: cyanide toxicity following ingestion of amygdalin and vitamin C.", "citation": "Bromley J, Hughes BG, Leong DC et al. Life-threatening interaction between complementary medicines: cyanide toxicity following ingestion of amygdalin and vitamin C. The Annals of pharmacotherapy. 2005.", "doi": "10.1345/aph.1E634", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/16014371/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/16014371/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID16014371", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human clinical case", "decisive_perturbation": false, "endogenous": false, "direction": "contradicts", "what_it_shows": "Oral amygdalin with high-dose vitamin C precedes severe neurological and acidosis symptoms with rapid antidote response.", "what_it_does_not_show": "Single case; exact interaction magnitude and population incidence are not determined.", "confounders_present": [ "Single case; exact interaction magnitude and population incidence are not determined." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 11, "pmid": "25605411", "title": "Severe cyanide poisoning from an alternative medicine treatment with amygdalin and apricot kernels in a 4-year-old child.", "citation": "Sauer H, Wollny C, Oster I et al. Severe cyanide poisoning from an alternative medicine treatment with amygdalin and apricot kernels in a 4-year-old child. Wiener medizinische Wochenschrift (1946). 2015.", "doi": "10.1007/s10354-014-0340-7", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/25605411/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/25605411/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID25605411", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human clinical case", "decisive_perturbation": false, "endogenous": false, "direction": "contradicts", "what_it_shows": "A child receiving oral/IV amygdalin and kernels develops encephalopathy, acidosis and elevated cyanide, improving after antidote.", "what_it_does_not_show": "Combined exposure prevents assignment to each component; case supports harm, not an incidence estimate.", "confounders_present": [ "Combined exposure prevents assignment to each component; case supports harm, not an incidence estimate." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 12, "pmid": "30399062", "title": "Role of Hemodialysis in the Management of Cyanide Intoxication From Apricot Kernels in a 3-Year-Old Child.", "citation": "Dalkıran T, Kandur Y, Ozaslan M et al. Role of Hemodialysis in the Management of Cyanide Intoxication From Apricot Kernels in a 3-Year-Old Child. Pediatric emergency care. 2020.", "doi": "10.1097/PEC.0000000000001644", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/30399062/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30399062/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID30399062", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human clinical case", "decisive_perturbation": false, "endogenous": false, "direction": "contradicts", "what_it_shows": "Kernel ingestion precedes pediatric coma and measured cyanide, followed by recovery with antidote and dialysis.", "what_it_does_not_show": "Small-child kernel exposure differs from an IV regimen; combined rescue does not isolate dialysis efficacy.", "confounders_present": [ "Small-child kernel exposure differs from an IV regimen; combined rescue does not isolate dialysis efficacy." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 13, "pmid": "28912981", "title": "Physician Beware: Severe Cyanide Toxicity from Amygdalin Tablets Ingestion.", "citation": "Dang T, Nguyen C, Tran PN. Physician Beware: Severe Cyanide Toxicity from Amygdalin Tablets Ingestion. Case reports in emergency medicine. 2017.", "doi": "10.1155/2017/4289527", "pmcid": "PMC5587935", "url": "https://pubmed.ncbi.nlm.nih.gov/28912981/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28912981/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID28912981", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:2. Case Report:paragraph0, 1:2. Case Report:paragraph1. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human clinical case", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "Prescribed oral tablets precede hypotension, acidosis and altered consciousness with rapid antidote response in a cancer patient.", "what_it_does_not_show": "Selected body does not report a measured cyanide value; temporal clinical attribution is not a poisoning-rate estimate.", "confounders_present": [ "Selected body does not report a measured cyanide value; temporal clinical attribution is not a poisoning-rate estimate." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 14, "pmid": "31322009", "title": "Rebound metabolic acidosis following intentional amygdalin supplement overdose.", "citation": "Shively RM, Harding SA, Hoffman RS et al. Rebound metabolic acidosis following intentional amygdalin supplement overdose. Clinical toxicology (Philadelphia, Pa.). 2020.", "doi": "10.1080/15563650.2019.1640369", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/31322009/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31322009/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID31322009", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human clinical case", "decisive_perturbation": false, "endogenous": false, "direction": "contradicts", "what_it_shows": "Intentional massive amygdalin overdose causes recurrent acidosis and hypotension requiring repeated antidotal treatment.", "what_it_does_not_show": "A 20 g overdose is not a standard promoted regimen; severity must not be generalized to all dosing.", "confounders_present": [ "A 20 g overdose is not a standard promoted regimen; severity must not be generalized to all dosing." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 15, "pmid": "28893740", "title": "An unusual presentation of chronic cyanide toxicity from self-prescribed apricot kernel extract.", "citation": "Konstantatos A, Shiv Kumar M, Burrell A et al. An unusual presentation of chronic cyanide toxicity from self-prescribed apricot kernel extract. BMJ case reports. 2017.", "doi": "10.1136/bcr-2017-220814", "pmcid": "PMC5623210", "url": "https://pubmed.ncbi.nlm.nih.gov/28893740/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28893740/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID28893740", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human clinical case", "decisive_perturbation": false, "endogenous": false, "direction": "contradicts", "what_it_shows": "Chronic kernel extract is associated with measured cyanide and abnormal oximetry normalizing after cessation.", "what_it_does_not_show": "Oximeter-interference explanation is inferred; single case and unavailable body limit broader attribution.", "confounders_present": [ "Oximeter-interference explanation is inferred; single case and unavailable body limit broader attribution." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 16, "pmid": "20196932", "title": "Cyanide poisoning caused by ingestion of apricot seeds.", "citation": "Akyildiz BN, Kurtoğlu S, Kondolot M et al. Cyanide poisoning caused by ingestion of apricot seeds. Annals of tropical paediatrics. 2010.", "doi": "10.1179/146532810X12637745451951", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/20196932/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/20196932/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID20196932", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human clinical case series", "decisive_perturbation": false, "endogenous": false, "direction": "contradicts", "what_it_shows": "Thirteen pediatric seed-ingestion cases include ventilation, coma and acidosis with recovery after treatment.", "what_it_does_not_show": "Selected intensive-care series has no population denominator and does not test isolated IV products.", "confounders_present": [ "Selected intensive-care series has no population denominator and does not test isolated IV products." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 17, "pmid": "6301673", "title": "Neuromyopathy of cyanide intoxication due to \"laetrile\" (amygdalin). A clinicopathologic study.", "citation": "Kalyanaraman UP, Kalyanaraman K, Cullinan SA et al. Neuromyopathy of cyanide intoxication due to \"laetrile\" (amygdalin). A clinicopathologic study. Cancer. 1983.", "doi": "10.1002/1097-0142(19830601)51:11<2126::aid-cncr2820511129>3.0.co;2-l", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/6301673/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/6301673/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID6301673", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human clinical case", "decisive_perturbation": false, "endogenous": false, "direction": "contradicts", "what_it_shows": "Neuromyopathy after laetrile has elevated cyanide/thiocyanate and improves after discontinuation, with alternatives assessed.", "what_it_does_not_show": "Nutritional deficiency contributes; single-patient evidence does not quantify risk or establish cancer efficacy.", "confounders_present": [ "Nutritional deficiency contributes; single-patient evidence does not quantify risk or establish cancer efficacy." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 18, "pmid": "25708890", "title": "Bioavailability of cyanide after consumption of a single meal of foods containing high levels of cyanogenic glycosides: a crossover study in humans.", "citation": "Abraham K, Buhrke T, Lampen A. Bioavailability of cyanide after consumption of a single meal of foods containing high levels of cyanogenic glycosides: a crossover study in humans. Archives of toxicology. 2016.", "doi": "10.1007/s00204-015-1479-8", "pmcid": "PMC4754328", "url": "https://pubmed.ncbi.nlm.nih.gov/25708890/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/25708890/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID25708890", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Materials and methods:paragraph2, 1:Materials and methods:paragraph6, 1:Materials and methods:paragraph8. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Healthy-adult crossover demonstrates different cyanide peaks from foods with equal cyanide-equivalent doses.", "what_it_does_not_show": "Small healthy sample and limited challenge measure exposure, not cancer efficacy or poisoning incidence.", "confounders_present": [ "Small healthy sample and limited challenge measure exposure, not cancer efficacy or poisoning incidence." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 19, "pmid": "6098693", "title": "The cyanide content of laetrile preparations, apricot, peach and apple seeds.", "citation": "Holzbecher MD, Moss MA, Ellenberger HA. The cyanide content of laetrile preparations, apricot, peach and apple seeds. Journal of toxicology. Clinical toxicology. 1984.", "doi": "10.3109/15563658408992565", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/6098693/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/6098693/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID6098693", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "pharmaceutical analytic", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Preparations from an intoxicated patient and fruit seeds contain measurable cyanide.", "what_it_does_not_show": "Product analysis complements clinical cases but is not a complete dose-risk or causation model.", "confounders_present": [ "Product analysis complements clinical cases but is not a complete dose-risk or causation model." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 20, "pmid": "7222669", "title": "Amygdalin toxicity studies in rats predict chronic cyanide poisoning in humans.", "citation": "Newton GW, Schmidt ES, Lewis JP et al. Amygdalin toxicity studies in rats predict chronic cyanide poisoning in humans. The Western journal of medicine. 1981.", "doi": "", "pmcid": "PMC1272529", "url": "https://pubmed.ncbi.nlm.nih.gov/7222669/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/7222669/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID7222669", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal in vivo and human microbial ex vivo", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Rat antibiotic/gut-flora comparisons and human fecal bacteria show microbial cyanide release from amygdalin.", "what_it_does_not_show": "Animal dosing and ex vivo activity do not specify human incidence or remove formulation/route differences.", "confounders_present": [ "Animal dosing and ex vivo activity do not specify human incidence or remove formulation/route differences." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 21, "pmid": "448892", "title": "Studies of amygdalin (laetrile) toxicity in rodents.", "citation": "Khandekar JD, Edelman H. Studies of amygdalin (laetrile) toxicity in rodents. JAMA. 1979.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/448892/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/448892/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID448892", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal in vivo", "decisive_perturbation": false, "endogenous": false, "direction": "contradicts", "what_it_shows": "Repeated high intraperitoneal doses produce rat mortality with cyanide signals.", "what_it_does_not_show": "High-dose animal route is not a direct human-regimen risk estimate; nonselective toxicity is retained.", "confounders_present": [ "High-dose animal route is not a direct human-regimen risk estimate; nonselective toxicity is retained." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 22, "pmid": "7448350", "title": "Blood cyanide levels in mice after administration of amygdalin.", "citation": "Hill HZ, Backer R, Hill GJ. Blood cyanide levels in mice after administration of amygdalin. Biopharmaceutics & drug disposition. 1980.", "doi": "10.1002/bdd.2510010409", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/7448350/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/7448350/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID7448350", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal in vivo", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Oral mouse dosing produces cyanide and distress; gut contents activate drug whereas tumour tissue releases little; parenteral exposure differs.", "what_it_does_not_show": "Species, individual variability and near-lethal doses limit clinical extrapolation.", "confounders_present": [ "Species, individual variability and near-lethal doses limit clinical extrapolation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 23, "pmid": "6661693", "title": "High-dose ascorbic acid decreases detoxification of cyanide derived from amygdalin (laetrile): studies in guinea pigs.", "citation": "Basu TK. High-dose ascorbic acid decreases detoxification of cyanide derived from amygdalin (laetrile): studies in guinea pigs. Canadian journal of physiology and pharmacology. 1983.", "doi": "10.1139/y83-203", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/6661693/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/6661693/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID6661693", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal in vivo", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Vitamin C coadministration decreases cyanide detoxification through reduced cysteine availability in guinea pigs.", "what_it_does_not_show": "Specific metabolic model does not quantify the interaction at every human dose.", "confounders_present": [ "Specific metabolic model does not quantify the interaction at every human dose." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 24, "pmid": "7063858", "title": "Congenital malformations induced by laetrile.", "citation": "Willhite CC. Congenital malformations induced by laetrile. Science (New York, N.Y.). 1982.", "doi": "10.1126/science.7063858", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/7063858/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/7063858/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID7063858", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal in vivo", "decisive_perturbation": false, "endogenous": true, "direction": "contradicts", "what_it_shows": "Oral but not IV hamster exposure causes malformations with cyanide increase; thiosulfate protects embryos.", "what_it_does_not_show": "Pregnancy and species scope retained; not a measured human teratogenic incidence.", "confounders_present": [ "Pregnancy and species scope retained; not a measured human teratogenic incidence." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 25, "pmid": "203726", "title": "Laetrile toxicity studies in dogs.", "citation": "Schmidt ES, Newton GW, Sanders SM et al. Laetrile toxicity studies in dogs. JAMA. 1978.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/203726/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/203726/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID203726", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal in vivo", "decisive_perturbation": false, "endogenous": true, "direction": "contradicts", "what_it_shows": "Oral laetrile with almonds causes death or neurological impairment in dogs at proposed human-equivalent doses.", "what_it_does_not_show": "Food, dose and species limits; this does not describe every IV formulation.", "confounders_present": [ "Food, dose and species limits; this does not describe every IV formulation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 26, "pmid": "1060511", "title": "Experimental studies of the antitumor activity of amygdalin MF (NSC-15780) alone and in combination with beta-glucosidase (NSC-128056).", "citation": "Laster WR, Schabel FM. Experimental studies of the antitumor activity of amygdalin MF (NSC-15780) alone and in combination with beta-glucosidase (NSC-128056). Cancer chemotherapy reports. 1975.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/1060511/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/1060511/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "NCI_RODENT_TEST_PROGRAMME", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal in vivo tumour models", "decisive_perturbation": true, "endogenous": true, "direction": "contradicts", "what_it_shows": "Drug alone and enzyme combination fail tumour tests near tolerated-dose limits; enzyme potentiates lethality.", "what_it_does_not_show": "Three transplantable models are restricted contexts; negative contrasts earn no positive efficacy crossing.", "confounders_present": [ "Three transplantable models are restricted contexts; negative contrasts earn no positive efficacy crossing." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 27, "pmid": "1203898", "title": "Antitumor activity of amygdalin MF (NSC-15780) as a single agent and with beta-glucosidase (NSC-128056) on a spectrum of transplantable rodent tumors.", "citation": "Wodinsky I, Swiniarski JK. Antitumor activity of amygdalin MF (NSC-15780) as a single agent and with beta-glucosidase (NSC-128056) on a spectrum of transplantable rodent tumors. Cancer chemotherapy reports. 1975.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/1203898/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/1203898/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "NCI_RODENT_TEST_PROGRAMME", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal in vivo tumour models", "decisive_perturbation": false, "endogenous": false, "direction": "contradicts", "what_it_shows": "Four rodent tumours show no activity under drug/enzyme schedules, with increased combination toxicity.", "what_it_does_not_show": "Models share a testing programme and are not four independent studies or all human cancers.", "confounders_present": [ "Models share a testing programme and are not four independent studies or all human cancers." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 28, "pmid": "347176", "title": "Antitumor tests of amygdalin in spontaneous animal tumor systems.", "citation": "Stock CC, Martin DS, Sugiura K et al. Antitumor tests of amygdalin in spontaneous animal tumor systems. Journal of surgical oncology. 1978.", "doi": "10.1002/jso.2930100203", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/347176/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/347176/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID347176", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal in vivo spontaneous tumours", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "Early visual metastasis benefits fail independent, cooperative and blinded assessments; leukemia/prevention tests are negative.", "what_it_does_not_show": "Disputed positive observations are retained with replication limits, not erased or generalized to new delivery platforms.", "confounders_present": [ "Disputed positive observations are retained with replication limits, not erased or generalized to new delivery platforms." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 29, "pmid": "642516", "title": "Antitumor tests of amygdalin in transplantable animal tumor systems.", "citation": "Stock CC, Tarnowski GS, Schmid FA et al. Antitumor tests of amygdalin in transplantable animal tumor systems. Journal of surgical oncology. 1978.", "doi": "10.1002/jso.2930100202", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/642516/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/642516/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "NCI_RODENT_TEST_PROGRAMME", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal in vivo tumour models", "decisive_perturbation": false, "endogenous": false, "direction": "contradicts", "what_it_shows": "Broad rodent tumour panels show no effect from high-dose amygdalin, including chemotherapy interaction tests.", "what_it_does_not_show": "Many models share a programme; this does not exclude distinct engineered delivery.", "confounders_present": [ "Many models share a programme; this does not exclude distinct engineered delivery." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 30, "pmid": "1268862", "title": "Failure of amygdalin to arrest B16 melanoma and BW5147 AKR leukemia.", "citation": "Hill GJ, Shine TE, Hill HZ et al. Failure of amygdalin to arrest B16 melanoma and BW5147 AKR leukemia. Cancer research. 1976.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/1268862/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/1268862/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID1268862", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal in vivo tumour models", "decisive_perturbation": false, "endogenous": false, "direction": "contradicts", "what_it_shows": "Parenteral amygdalin does not arrest two specified murine tumours across a dose range.", "what_it_does_not_show": "Model and route-specific negative, not a human randomized trial.", "confounders_present": [ "Model and route-specific negative, not a human randomized trial." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 31, "pmid": "4008516", "title": "Studies on high-dose chemotherapy of amygdalin in murine P388 lymphocytic leukaemia and P815 mast cell leukaemia.", "citation": "Chitnis MP, Adwankar MK, Amonkar AJ. Studies on high-dose chemotherapy of amygdalin in murine P388 lymphocytic leukaemia and P815 mast cell leukaemia. Journal of cancer research and clinical oncology. 1985.", "doi": "10.1007/BF00390359", "pmcid": "PMC12252541", "url": "https://pubmed.ncbi.nlm.nih.gov/4008516/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/4008516/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID4008516", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal in vivo tumour models", "decisive_perturbation": false, "endogenous": false, "direction": "null", "what_it_shows": "High-dose schedules do not prolong survival in two leukemia-bearing mouse models.", "what_it_does_not_show": "No inference to an exact human hazard ratio or every formulation.", "confounders_present": [ "No inference to an exact human hazard ratio or every formulation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 32, "pmid": "32122873", "title": "Potential therapy of vitamin B17 against Ehrlich solid tumor induced changes in Interferon gamma, Nuclear factor kappa B, DNA fragmentation, p53, Bcl2, survivin, VEGF and TNF-α Expressions in mice.", "citation": "El-Masry T, Al-Shaalan N, Tousson E et al. Potential therapy of vitamin B17 against Ehrlich solid tumor induced changes in Interferon gamma, Nuclear factor kappa B, DNA fragmentation, p53, Bcl2, survivin, VEGF and TNF-α Expressions in mice. Pakistan journal of pharmaceutical sciences. 2020.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/32122873/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32122873/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID32122873", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "animal in vivo transplanted tumour", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Amygdalin changes apoptosis, inflammatory and organ-function markers in Ehrlich tumour-bearing mice.", "what_it_does_not_show": "Marker-heavy abstract does not show durable human tumour control; B17 terminology is not a validated vitamin status.", "confounders_present": [ "Marker-heavy abstract does not show durable human tumour control; B17 terminology is not a validated vitamin status." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 33, "pmid": "35444229", "title": "Amygdalin potentiates the anti-cancer effect of Sorafenib on Ehrlich ascites carcinoma and ameliorates the associated liver damage.", "citation": "Attia AA, Salama AF, Eldiasty JG et al. Amygdalin potentiates the anti-cancer effect of Sorafenib on Ehrlich ascites carcinoma and ameliorates the associated liver damage. Scientific reports. 2022.", "doi": "10.1038/s41598-022-10517-0", "pmcid": "PMC9021277", "url": "https://pubmed.ncbi.nlm.nih.gov/35444229/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35444229/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID35444229", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal in vivo transplanted tumour", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Amygdalin with sorafenib reduces Ehrlich tumour burden and liver injury measures in mice.", "what_it_does_not_show": "Combination and route context, not clinical benefit or a proved selective cyanide mechanism.", "confounders_present": [ "Combination and route context, not clinical benefit or a proved selective cyanide mechanism." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 34, "pmid": "32510292", "title": "Prunus Armeniaca L. Seed Extract and Its Amygdalin Containing Fraction Induced Mitochondrial-Mediated Apoptosis and Autophagy in Liver Carcinogenesis.", "citation": "Hosny S, Sahyon H, Youssef M et al. Prunus Armeniaca L. Seed Extract and Its Amygdalin Containing Fraction Induced Mitochondrial-Mediated Apoptosis and Autophagy in Liver Carcinogenesis. Anti-cancer agents in medicinal chemistry. 2021.", "doi": "10.2174/1871520620666200608124003", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/32510292/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32510292/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID32510292", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "animal in vivo and cellular", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Apricot extract and amygdalin-containing fraction alter apoptosis/autophagy and proliferation in a chemically induced liver model.", "what_it_does_not_show": "Mixed extract and molecular endpoints cannot establish pure-drug clinical efficacy.", "confounders_present": [ "Mixed extract and molecular endpoints cannot establish pure-drug clinical efficacy." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 35, "pmid": "40097629", "title": "The protective and chemotherapeutical role of amygdalin in induced mammary cancer in experimental mice and upregulation of related genes.", "citation": "Mageid ADA, Abdel-Wadoud IM, Salim EI et al. The protective and chemotherapeutical role of amygdalin in induced mammary cancer in experimental mice and upregulation of related genes. Scientific reports. 2025.", "doi": "10.1038/s41598-025-93620-2", "pmcid": "PMC11914690", "url": "https://pubmed.ncbi.nlm.nih.gov/40097629/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40097629/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID40097629", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal in vivo chemically induced tumour", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Amygdalin alone or with tamoxifen changes mammary histology and molecular/biochemical tumour measures.", "what_it_does_not_show": "Induction, combination and marker limits; no human treatment outcome or selective exposure bridge.", "confounders_present": [ "Induction, combination and marker limits; no human treatment outcome or selective exposure bridge." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 36, "pmid": "35681261", "title": "Amygdalin Induced Mitochondria-Mediated Apoptosis of Lung Cancer Cells via Regulating NF[Formula: see text]B-1/NF[Formula: see text]B Signaling Cascade in Vitro and in Vivo.", "citation": "Lin S, Wen J, Xu X et al. 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In vitro cytotoxicity following specific activation of amygdalin by beta-glucosidase conjugated to a bladder cancer-associated monoclonal antibody. International journal of cancer. 1998.", "doi": "10.1002/(sici)1097-0215(19981209)78:6<712::aid-ijc8>3.0.co;2-d", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/9833764/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/9833764/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID9833764", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Amygdalin (Laetrile): effect on clonogenic cells from human myeloid leukemia cell lines and normal human marrow. Cancer treatment reports. 1980.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/6929726/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/6929726/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID6929726", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Role of Amygdalin in Blocking DNA Replication in Breast Cancer In Vitro. Current pharmaceutical biotechnology. 2021.", "doi": "10.2174/1389201022666210203123803", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33535947/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33535947/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID33535947", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Effect of amygdalin on oral cancer cell line: An in vitro study. Journal of oral and maxillofacial pathology : JOMFP. 2019.", "doi": "10.4103/jomfp.JOMFP_281_18", "pmcid": "PMC6503803", "url": "https://pubmed.ncbi.nlm.nih.gov/31110425/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31110425/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID31110425", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Amygdalin inhibits genes related to cell cycle in SNU-C4 human colon cancer cells. World journal of gastroenterology. 2005.", "doi": "10.3748/wjg.v11.i33.5156", "pmcid": "PMC4320388", "url": "https://pubmed.ncbi.nlm.nih.gov/16127745/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/16127745/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID16127745", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Amygdalin Regulates Apoptosis and Adhesion in Hs578T Triple-Negative Breast Cancer Cells. Biomolecules & therapeutics. 2016.", "doi": "10.4062/biomolther.2015.172", "pmcid": "PMC4703354", "url": "https://pubmed.ncbi.nlm.nih.gov/26759703/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26759703/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID26759703", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Amygdalin Decreases Adhesion and Migration of MDA-MB-231 and MCF-7 Breast Cancer Cell Lines. Current molecular pharmacology. 2021.", "doi": "10.2174/1874467213666200810141251", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/32778045/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32778045/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID32778045", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Amygdalin inhibits the growth of renal cell carcinoma cells in vitro. International journal of molecular medicine. 2016.", "doi": "10.3892/ijmm.2015.2439", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/26709398/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26709398/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID26709398", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "cellular in vitro", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Renal cancer cells exposed to 10 mg/mL show growth and cell-cycle effects with cdk1/cyclin B tests.", "what_it_does_not_show": "Blockade phenocopy is not a drug-specific rescue; human exposure and normal-organ selectivity remain untested.", "confounders_present": [ "Blockade phenocopy is not a drug-specific rescue; human exposure and normal-organ selectivity remain untested." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [ "Related renal/prostate culture programme with common exposure and growth-assay limits." ] }, { "n": 46, "pmid": "26827990", "title": "Amygdalin delays cell cycle progression and blocks growth of prostate cancer cells in vitro.", "citation": "Makarević J, Tsaur I, Juengel E et al. Amygdalin delays cell cycle progression and blocks growth of prostate cancer cells in vitro. Life sciences. 2016.", "doi": "10.1016/j.lfs.2016.01.039", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/26827990/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26827990/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID26827990", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Amygdalin Exerts Antitumor Activity in Taxane-Resistant Prostate Cancer Cells. Cancers. 2022.", "doi": "10.3390/cancers14133111", "pmcid": "PMC9265127", "url": "https://pubmed.ncbi.nlm.nih.gov/35804883/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35804883/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID35804883", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Antitumor Action of Amygdalin on Human Breast Cancer Cells by Selective Sensitization to Oxidative Stress. Nutrition and cancer. 2019.", "doi": "10.1080/01635581.2018.1508731", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/30407870/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30407870/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID30407870", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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In vitro and in silico anticancer activity of amygdalin on the SK-BR-3 human breast cancer cell line. Molecular biology reports. 2019.", "doi": "10.1007/s11033-019-05080-3", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/31583572/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31583572/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID31583572", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Growth of Renal Cancer Cell Lines Is Strongly Inhibited by Synergistic Activity of Low-Dosed Amygdalin and Sulforaphane. Nutrients. 2024.", "doi": "10.3390/nu16213750", "pmcid": "PMC11547972", "url": "https://pubmed.ncbi.nlm.nih.gov/39519581/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39519581/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID39519581", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 2:3. Results:paragraph0, 2:3. Results:paragraph1, 2:3. Results:paragraph3. 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Magnetically Directed Enzyme/Prodrug Prostate Cancer Therapy Based on β-Glucosidase/Amygdalin. International journal of nanomedicine. 2020.", "doi": "10.2147/IJN.S242359", "pmcid": "PMC7334483", "url": "https://pubmed.ncbi.nlm.nih.gov/32636623/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32636623/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID32636623", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 2:Results:paragraph7, 2:Results:paragraph21, 2:Results:paragraph28. 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Targeted nanocomposite delivery system of amygdalin using chitosan/reduced graphene oxide-zinc oxide/hyaluronic acid for treatment of head and neck squamous cell carcinoma. BMC oral health. 2026.", "doi": "10.1186/s12903-026-07943-1", "pmcid": "PMC13063543", "url": "https://pubmed.ncbi.nlm.nih.gov/41882653/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41882653/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID41882653", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Formation of amygdalin/β-cyclodextrin derivatives inclusion complexes for anticancer activity assessment in human cervical carcinoma HeLa cell line. International journal of pharmaceutics. 2024.", "doi": "10.1016/j.ijpharm.2024.124293", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38823468/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38823468/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID38823468", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Weak", "system": "engineered formulation cellular", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Cyclodextrin complexes improve HeLa MTT cytotoxicity compared with free compound.", "what_it_does_not_show": "Formulation culture assay does not establish a human therapeutic window or clinical benefit.", "confounders_present": [ "Formulation culture assay does not establish a human therapeutic window or clinical benefit." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 55, "pmid": "38027646", "title": "Amygdalin/chitosan-polyvinyl alcohol/cerium-tannic acid hydrogel as biodegradable long-time implant for cancer recurrence care applications: An in vitro study.", "citation": "Hakimi F, Sharifyrad M, Safari H et al. Amygdalin/chitosan-polyvinyl alcohol/cerium-tannic acid hydrogel as biodegradable long-time implant for cancer recurrence care applications: An in vitro study. Heliyon. 2023.", "doi": "10.1016/j.heliyon.2023.e21835", "pmcid": "PMC10658248", "url": "https://pubmed.ncbi.nlm.nih.gov/38027646/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38027646/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID38027646", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Weak", "system": "engineered hydrogel cellular", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Amygdalin hydrogel causes colorectal-cell apoptosis alongside material/biocompatibility tests.", "what_it_does_not_show": "Proposed implant has no demonstrated postoperative recurrence-prevention or clinical safety outcome.", "confounders_present": [ "Proposed implant has no demonstrated postoperative recurrence-prevention or clinical safety outcome." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 56, "pmid": "36204233", "title": "Amygdalin as a chemoprotective agent in co-treatment with cisplatin.", "citation": "Christodoulou P, Boutsikos P, Neophytou CM et al. Amygdalin as a chemoprotective agent in co-treatment with cisplatin. Frontiers in pharmacology. 2022.", "doi": "10.3389/fphar.2022.1013692", "pmcid": "PMC9531591", "url": "https://pubmed.ncbi.nlm.nih.gov/36204233/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36204233/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID36204233", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "cellular in vitro matched normal", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Combination with cisplatin protects selected normal cells while enhancing cancer-cell inhibition.", "what_it_does_not_show": "Specific cell types and schedules, not organismal safety or patient quality-of-life trial.", "confounders_present": [ "Specific cell types and schedules, not organismal safety or patient quality-of-life trial." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 57, "pmid": "28146364", "title": "Antimutagenic, Antirecombinogenic, and Antitumor Effect of Amygdalin in a Yeast Cell-Based Test and Mammalian Cell Lines.", "citation": "Todorova A, Pesheva M, Iliev I et al. Antimutagenic, Antirecombinogenic, and Antitumor Effect of Amygdalin in a Yeast Cell-Based Test and Mammalian Cell Lines. Journal of medicinal food. 2017.", "doi": "10.1089/jmf.2016.0108", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/28146364/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28146364/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID28146364", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Weak", "system": "yeast and mammalian cellular", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Yeast recombination/genotoxicity and mammalian cell comparisons suggest context-specific effects.", "what_it_does_not_show": "Yeast surrogates are not human cancer prevention; native organism dependency and exposure bridge absent.", "confounders_present": [ "Yeast surrogates are not human cancer prevention; native organism dependency and exposure bridge absent." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 58, "pmid": "34146630", "title": "Phytochemical characterization and biological activity of apricot kernels' extract in yeast-cell based tests and hepatocellular and colorectal carcinoma cell lines.", "citation": "Dimitrov M, Iliev I, Bardarov K et al. Phytochemical characterization and biological activity of apricot kernels' extract in yeast-cell based tests and hepatocellular and colorectal carcinoma cell lines. Journal of ethnopharmacology. 2021.", "doi": "10.1016/j.jep.2021.114333", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/34146630/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34146630/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID34146630", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Weak", "system": "extract cellular and yeast", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Characterized kernel extract shows different toxicity in cancer and selected normal lines.", "what_it_does_not_show": "Thousands of constituents and multiple cyanogenic glycosides prevent assigning all activity to pure amygdalin.", "confounders_present": [ "Thousands of constituents and multiple cyanogenic glycosides prevent assigning all activity to pure amygdalin." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 59, "pmid": "37299029", "title": "Antioxidant, Anti-Inflammatory, and Anti-Cancer Properties of Amygdalin Extracted from Three Cassava Varieties Cultivated in Benin.", "citation": "Lehmane H, Kohonou AN, Tchogou AP et al. Antioxidant, Anti-Inflammatory, and Anti-Cancer Properties of Amygdalin Extracted from Three Cassava Varieties Cultivated in Benin. Molecules (Basel, Switzerland). 2023.", "doi": "10.3390/molecules28114548", "pmcid": "PMC10254302", "url": "https://pubmed.ncbi.nlm.nih.gov/37299029/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37299029/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID37299029", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Weak", "system": "extract animal and cellular", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Cassava extract tests report antioxidant, inflammatory and limited rat cancer-model changes.", "what_it_does_not_show": "Mixed ingredients and chemical identity need scrutiny; no isolated human amygdalin therapeutic effect.", "confounders_present": [ "Mixed ingredients and chemical identity need scrutiny; no isolated human amygdalin therapeutic effect." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 60, "pmid": "38908223", "title": "Evaluating the therapeutic potential of amygdalin: Cytotoxic and antimicrobial properties.", "citation": "Abdel-Gawad DRI, Ibrahim MA, El-Banna HA et al. Evaluating the therapeutic potential of amygdalin: Cytotoxic and antimicrobial properties. Tissue & cell. 2024.", "doi": "10.1016/j.tice.2024.102443", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38908223/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38908223/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID38908223", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Use of Alternative Medicine for Cancer and Its Impact on Survival. Journal of the National Cancer Institute. 2018.", "doi": "10.1093/jnci/djx145", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/28922780/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28922780/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID28922780", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Matched NCDB patients using alternative treatment without conventional care have higher mortality association.", "what_it_does_not_show": "Selection, residual confounding and coarse modality coding; not a laetrile-specific randomized hazard ratio.", "confounders_present": [ "Selection, residual confounding and coarse modality coding; not a laetrile-specific randomized hazard ratio." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [ "NCDB alternative-modality coding and selection also constrain complementary-use report30027204." ] }, { "n": 62, "pmid": "30027204", "title": "Complementary Medicine, Refusal of Conventional Cancer Therapy, and Survival Among Patients With Curable Cancers.", "citation": "Johnson SB, Park HS, Gross CP et al. Complementary Medicine, Refusal of Conventional Cancer Therapy, and Survival Among Patients With Curable Cancers. JAMA oncology. 2018.", "doi": "10.1001/jamaoncol.2018.2487", "pmcid": "PMC6233773", "url": "https://pubmed.ncbi.nlm.nih.gov/30027204/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30027204/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID30027204", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Complementary-use mortality association attenuates and becomes nonsignificant after treatment refusal/delay adjustment.", "what_it_does_not_show": "Shared NCDB and observational mediation; not proof every complementary use causes death.", "confounders_present": [ "Shared NCDB and observational mediation; not proof every complementary use causes death." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [ "SharedNCDBcoding; adjusting refusal is observational, not randomized mediation." ] }, { "n": 63, "pmid": "22734852", "title": "Outcome analysis of breast cancer patients who declined evidence-based treatment.", "citation": "Joseph K, Vrouwe S, Kamruzzaman A et al. Outcome analysis of breast cancer patients who declined evidence-based treatment. World journal of surgical oncology. 2012.", "doi": "10.1186/1477-7819-10-118", "pmcid": "PMC3438047", "url": "https://pubmed.ncbi.nlm.nih.gov/22734852/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/22734852/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID22734852", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Methods:paragraph0, 1:Methods:paragraph1. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Matched breast-cancer primary-treatment refusal is associated with worse survival.", "what_it_does_not_show": "Body confirms age, year and stage matching without full TNM; not laetrile-specific and selection remains.", "confounders_present": [ "Body confirms age, year and stage matching without full TNM; not laetrile-specific and selection remains." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 64, "pmid": "16978951", "title": "Outcomes of breast cancer in patients who use alternative therapies as primary treatment.", "citation": "Chang EY, Glissmeyer M, Tonnes S et al. Outcomes of breast cancer in patients who use alternative therapies as primary treatment. American journal of surgery. 2006.", "doi": "10.1016/j.amjsurg.2006.05.013", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/16978951/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/16978951/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID16978951", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational case series", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Patients delaying or refusing standard breast-cancer care frequently progress or relapse.", "what_it_does_not_show": "Small chart series; some mortality figures are projections rather than observed causal deaths and modalities differ.", "confounders_present": [ "Small chart series; some mortality figures are projections rather than observed causal deaths and modalities differ." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 65, "pmid": "683212", "title": "Special report on Laetrile: the NCI Laetrile Review. Results of the National Cancer Institute's retrospective Laetrile analysis.", "citation": "Ellison NM, Byar DP, Newell GR. Special report on Laetrile: the NCI Laetrile Review. Results of the National Cancer Institute's retrospective Laetrile analysis. The New England journal of medicine. 1978.", "doi": "10.1056/NEJM197809072991013", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/683212/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/683212/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID683212", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human selected retrospective records", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Blinded oncologists judge six responses in solicited favorable laetrile treatment courses.", "what_it_does_not_show": "Only claimed-benefit cases solicited; nonrandomized courses, incomplete records and cointerventions prevent definite attribution.", "confounders_present": [ "Only claimed-benefit cases solicited; nonrandomized courses, incomplete records and cointerventions prevent definite attribution." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 66, "pmid": "36355478", "title": "In Vitro and In Vivo Evaluation of the Effectiveness and Safety of Amygdalin as a Cancer Therapy.", "citation": "El-Ela FIA, Gamal A, Elbanna HA et al. In Vitro and In Vivo Evaluation of the Effectiveness and Safety of Amygdalin as a Cancer Therapy. Pharmaceuticals (Basel, Switzerland). 2022.", "doi": "10.3390/ph15111306", "pmcid": "PMC9697812", "url": "https://pubmed.ncbi.nlm.nih.gov/36355478/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36355478/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID36355478", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:2. Results and Discussion:paragraph8, 1:2. Results and Discussion:paragraph9, 1:2. Results and Discussion:paragraph10, 2:3. Materials and Methods:paragraph13, 2:3. Materials and Methods:paragraph14, 2:3. Materials and Methods:paragraph15, 2:3. Materials and Methods:paragraph16, 2:3. Materials and Methods:paragraph17, 2:3. Materials and Methods:paragraph18, 2:3. Materials and Methods:paragraph19, 2:3. Materials and Methods:paragraph20, 2:3. Materials and Methods:paragraph21. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "engineered delivery animal", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Original body compares topical loaded niosomal gel, blank gel, oral free compound and tamoxifen in small DMBA skin-tumour rat groups.", "what_it_does_not_show": "Formulation/route differ, and selected local histology does not establish systemic cyanide safety, tumour pharmacokinetics or human benefit.", "confounders_present": [ "Formulation/route differ, and selected local histology does not establish systemic cyanide safety, tumour pharmacokinetics or human benefit." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 67, "pmid": "32097740", "title": "Evaluation of amygdalin-loaded alginate-chitosan nanoparticles as biocompatible drug delivery carriers for anticancerous efficacy.", "citation": "Sohail R, Abbas SR. Evaluation of amygdalin-loaded alginate-chitosan nanoparticles as biocompatible drug delivery carriers for anticancerous efficacy. International journal of biological macromolecules. 2020.", "doi": "10.1016/j.ijbiomac.2020.02.191", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/32097740/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32097740/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID32097740", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "engineered nanodelivery cellular", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Alginate-chitosan particles sustain release and increase H1299 cell cytotoxicity compared with free drug.", "what_it_does_not_show": "Abstract claims normal-tissue protection but supplied results do not detail an independent normal-tissue clinical endpoint; no whole-paper audit.", "confounders_present": [ "Abstract claims normal-tissue protection but supplied results do not detail an independent normal-tissue clinical endpoint; no whole-paper audit." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] } ], "verification_summary": { "load_bearing_claims_checked": 72, "verified": 72, "unverified": 0, "contradicted": 0, "note": "Verified attribution is distinct from mechanism truth or complete body access." }, "factual_issues_found": [], "cap_rules_applied": [ { "subclaim_id": "SC1", "cap": "Γ", "cap_source": "universal", "triggered": true, "trigger_text_quoted": "In vitro evidence alone cannot exceed Γ.", "specific_trigger": "Some matched malignant/normal cell comparisons and engineered activation systems show differential effects. Other matched marrow studies show no selective killing, and high culture concentrations, tissue-mismatched controls and enzyme/carrier additions prevent a general human therapeutic window. Partial system selectivity is retained atΓ, not promoted to clinical efficacy.", "resulting_ceiling": "Γ" }, { "subclaim_id": "SC4", "cap": "Β", "cap_source": "universal", "triggered": true, "trigger_text_quoted": "Pure association evidence — however large, however replicated — cannot exceed Β.", "specific_trigger": "Treatment substitution/refusal cohorts associate with worse survival and treatment-refusal adjustment attenuates the complementary-use association. These are clinically important warnings, but the retrieved cohorts are nonrandomized and not laetrile-specific. This separate broad causal proposition is held atΒ under the association-only cap; the observed hazard ratios are not randomized causal estimates.", "resulting_ceiling": "Β" } ], "cap_precedence_resolutions": [ { "collision": "Perturbation in a defined setting versus broader inference", "subclaim_scope_cap_binds_on": "Laetrile or amygdalin provides clinically meaningful anticancer benefit through selective tumour toxicity at regimens promoted for human treatment.", "subclaim_scope_threshold_binds_on": "The precise experimentally tested subclaim scope", "resolution": "SC1 retains partial-system Γ support from matched-cell and experimental delivery findings. The preregistered SC2 gate asks about benefit of promoted human regimens; different experimental platforms cannot supply that clinical result. The uncontrolled negative treatment programme is informative without being a randomized causal effect. SC3 poisoning contradicts toxicity avoidance; it supports the opposite harm model rather than an efficacy crossing. SC4 remains a non-drug-specific survival association.", "note": "Convergent lines are assessed as a set; one weak leg is not re-capped over the assembled case." } ], "boundary_check_BGD": [ { "subclaim_id": "SC1", "field_valid_perturbation_quote": "\n- Endogenous genetic manipulation in autochthonous models\n- Patient-derived system perturbation with matched rescue AND in vivo confirmation\n- Clonal tracking demonstrating persistence of dependency through selection pressure", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "", "gamma_hard_rules_triggered": [ "Cell death, apoptosis markers and docking do not establish a clinically attainable tumour-selective exposure.", "The old human study is nonrandomized and its abstract says no substantive benefit; clinical toxicity is not proof of anticancer efficacy.", "New enzyme/nanocarrier/gel platforms are distinct interventions, not confirmations of historical formulations.", "Matched normal-cell positives are retained, but normal marrow negative and systemic poisoning limit generalization.", "Substitution cohorts lack laetrile-specific identification and causal randomization." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Some matched malignant/normal cell comparisons and engineered activation systems show differential effects. Other matched marrow studies show no selective killing, and high culture concentrations, tissue-mismatched controls and enzyme/carrier additions prevent a general human therapeutic window. Partial system selectivity is retained atΓ, not promoted to clinical efficacy.", "ceiling_from_boundary_check": "Γ" }, { "subclaim_id": "SC2", "field_valid_perturbation_quote": "\n- Endogenous genetic manipulation in autochthonous models\n- Patient-derived system perturbation with matched rescue AND in vivo confirmation\n- Clonal tracking demonstrating persistence of dependency through selection pressure", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "", "gamma_hard_rules_triggered": [ "Cell death, apoptosis markers and docking do not establish a clinically attainable tumour-selective exposure.", "The old human study is nonrandomized and its abstract says no substantive benefit; clinical toxicity is not proof of anticancer efficacy.", "New enzyme/nanocarrier/gel platforms are distinct interventions, not confirmations of historical formulations.", "Matched normal-cell positives are retained, but normal marrow negative and systemic poisoning limit generalization.", "Substitution cohorts lack laetrile-specific identification and causal randomization." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "The registered human-regimen benefit claim has no credible, reproducible positive clinical support in the examined set. The 178-patient nonrandomized treatment programme reported no substantive benefit. Six judged responses in solicited favorable historical records lack a credible counterfactual and reliable attribution. Laboratory activity and new-platform animal effects remain SC1 support and do not establish SC2. Α is evidence-derived unsupported clinical benefit, rather than a penalty for the absence of an RCT or a claim of zero biological activity.", "ceiling_from_boundary_check": "Γ" }, { "subclaim_id": "SC3", "field_valid_perturbation_quote": "\n- Endogenous genetic manipulation in autochthonous models\n- Patient-derived system perturbation with matched rescue AND in vivo confirmation\n- Clonal tracking demonstrating persistence of dependency through selection pressure", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "", "gamma_hard_rules_triggered": [ "Cell death, apoptosis markers and docking do not establish a clinically attainable tumour-selective exposure.", "The old human study is nonrandomized and its abstract says no substantive benefit; clinical toxicity is not proof of anticancer efficacy.", "New enzyme/nanocarrier/gel platforms are distinct interventions, not confirmations of historical formulations.", "Matched normal-cell positives are retained, but normal marrow negative and systemic poisoning limit generalization.", "Substitution cohorts lack laetrile-specific identification and causal randomization." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "The blanket claim of avoiding clinically important systemic cyanide toxicity is directly challenged by prescribed oral-regimen poisoning, measured cyanide, food interactions and animal rescue/exposure tests. Some small IV pharmacology settings lack observed toxicity, but that cannot establish safety across promoted regimens. The positive avoidance claim is unsupported atΑ; the opposite route-dependent poisoning model scores separately and higher.", "ceiling_from_boundary_check": "Γ" }, { "subclaim_id": "SC4", "field_valid_perturbation_quote": "\n- Endogenous genetic manipulation in autochthonous models\n- Patient-derived system perturbation with matched rescue AND in vivo confirmation\n- Clonal tracking demonstrating persistence of dependency through selection pressure", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "", "gamma_hard_rules_triggered": [ "Cell death, apoptosis markers and docking do not establish a clinically attainable tumour-selective exposure.", "The old human study is nonrandomized and its abstract says no substantive benefit; clinical toxicity is not proof of anticancer efficacy.", "New enzyme/nanocarrier/gel platforms are distinct interventions, not confirmations of historical formulations.", "Matched normal-cell positives are retained, but normal marrow negative and systemic poisoning limit generalization.", "Substitution cohorts lack laetrile-specific identification and causal randomization." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Treatment substitution/refusal cohorts associate with worse survival and treatment-refusal adjustment attenuates the complementary-use association. These are clinically important warnings, but the retrieved cohorts are nonrandomized and not laetrile-specific. This separate broad causal proposition is held atΒ under the association-only cap; the observed hazard ratios are not randomized causal estimates.", "ceiling_from_boundary_check": "Γ" } ], "thresholds_tested": [ { "subclaim_id": "SC1", "threshold": "Δ", "requirement_quoted": "Requires at least one meaningful causal perturbation showing the proposed mechanism contributes to initiation, maintenance, or relapse.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "Demonstrate tumour-selective functional activity at measured, clinically attainable parent/metabolite exposure in matched normal and malignant systems with orthogonal death/readout assays and in vivo pharmacokinetics; establish a benefit-to-toxic-exposure margin." }, { "subclaim_id": "SC2", "threshold": "Δ", "requirement_quoted": "Requires at least one meaningful causal perturbation showing the proposed mechanism contributes to initiation, maintenance, or relapse.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "First validate formulation identity, achievable selective exposure and systemic toxicology in relevant controlled models. Only a new platform meeting those conditions could justify an independently reviewed add-on clinical study with objective cancer endpoints; the historical regimen should not be assumed worth retesting or substituted for effective care." }, { "subclaim_id": "SC3", "threshold": "Δ", "requirement_quoted": "Requires at least one meaningful causal perturbation showing the proposed mechanism contributes to initiation, maintenance, or relapse.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "Define route, dose, formulation, coingestions and monitoring prospectively; quantify clinical toxic events and parent/cyanide/thiocyanate exposure over time. A few symptom-free IV administrations do not establish broad-regimen safety." }, { "subclaim_id": "SC4", "threshold": "Δ", "requirement_quoted": "Requires at least one meaningful causal perturbation showing the proposed mechanism contributes to initiation, maintenance, or relapse.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "Use stronger counterfactual treatment-receipt designs and validated alternative-modality identification, with indication, stage, prognosis and refusal reasons retained. Do not infer a laetrile-specific hazard ratio from coarse alternative-care categories." } ], "generalization_check": { "generalization_tested": "yes", "context_boundary_mapped": "yes", "internal_negative_controls": [ "Matched normal marrow is inhibited comparably to leukemia clonogens (6929726).", "Human tested tumour tissues lack detectable activating glucosidase despite intestinal activity (6796962).", "Drug alone and enzyme combination fail several historical tumour models near tolerated dose; enzyme increases toxicity (1060511;1203898).", "Early visual spontaneous-tumour benefits are not retained under independent/blind assessments (347176).", "Amygdalin1 mg/mL alone does not inhibit the examined renal lines, while a sulforaphane combination does (39519581).", "Without magnetic targeting, several enzyme/nanoparticle arms do not reproduce the mouse growth effect; cardiac/liver biomarkers rise (32636623).", "Complementary-use mortality association becomes nonsignificant after refusal/delay adjustment (30027204)." ], "note": "Antecedent boundaries are chemical product, oral/IV/topical route, dose, duration, coingested foods/vitaminC, tumour model and concurrent therapy. Modern engineered activation is not a post-hoc rescue of the historical regimen: it is a new platform requiring its own efficacy and safety evidence. Rare clinical responses and symptom-free exposures are retained without redefining responders as the whole scope." }, "falsification_patterns_met": [ { "pattern": "Broad toxicity-avoidance prediction fails under promoted oral exposure", "evidence": "Prescribed tablets, food interactions, measuredcyanide cases and controlled animal comparisons contradictSC3. The sparse apparent-benignassociational safety case is downgraded fromΒtoΑ; the opposite harm model is graded independently.", "downgrade_applied": true } ], "pitfalls_flagged": [ { "pitfall": "Historical human trial labeled randomized", "where": "7033783is nonrandomized; exact response denominator must not be invented from its abstract." }, { "pitfall": "Positive culture activity equated with clinical exposure", "where": "mg/mL and engineered activation do not establish a safe patient tumour concentration." }, { "pitfall": "Every route assigned the same toxicity", "where": "Oral/IVand interacting-food differences are original findings." }, { "pitfall": "Generic alternative-care mortality assigned to laetrile", "where": "NCDBcoding and refusal cohorts do not identify the compound." }, { "pitfall": "Unmonitored provider impressions treated as safety", "where": "Mostsurveyproviders do not monitorcyanide." } ], "causal_tally_audit": { "tally_claimed_by_document": 0, "tally_after_audit": 0, "tally_unit": "Positive qualifying study units across scoped subclaims, not independent causal lines or full-claim necessity/sufficiency.", "screened_discriminating_contrasts": 54, "items_rejected": [ "Null and negative contrasts are discriminators, not positive threshold crossings. Reports and replications are not independent causal lines.", "The zero positive crossing tally concerns the stated benefit/safety propositions; it does not count or negate causal support for the separately scored opposite cyanide-harm model.", "Pivotal nulls and poisoning events do not become positive clinical benefit or harmlessness crossings.", "Cell assays, engineered platforms and repeated reports are not independent human efficacy studies." ] }, "steelman": { "case_one_rung_higher": "One rung above, Β: six judged responses in the selected 1978 case records and clinical testimonials offer a possible clinical association. Favorable-case solicitation, incomplete records, concurrent treatments and no credible comparator prevent a reproducible benefit association attributable to the eligible regimen. Γ would require importing laboratory or new-platform activity into a different clinical scope; that evidence is retained in SC1 instead.", "case_one_rung_lower": "Α is the lowest HSEF rung, so no lower letter exists. A stronger dismissal asserting that amygdalin is biologically inactive in all systems is rejected: matched-cell and animal delivery positives are real within their examined contexts. The nominal clinical score does not erase Γ mechanistic support or the separate cyanide-harm model.", "which_rejected": "Retain Α for the registered human-regimen benefit gate and Γ for partial-system selectivity. The selected clinical responses cannot establish replicated attribution; the 178-patient negative human course is not an RCT or a universal zero-effect proof. New delivery platforms retain their own evidence and would require a new clinical scope and justified exposure bridge.", "blocking_cap_threshold_or_missing_experiment": "Missing experiment: First characterize formulation identity, parent/metabolite kinetics and cyanide generation with clinically anchored exposure in matched malignant and normal systems. Establish selective functional activity, normal-organ margin and pharmacodynamic tumour exposure in controlled relevant models using carrier/enzyme-only and route-matched controls. A future new-platform add-on trial would require those preclinical criteria and independent review; it must preserve effective cancer care and is not a recommendation to revive the historical unbeneficial regimen." }, "final_score": { "hsef_level": "Α", "hsef_descriptor": "Speculative / narrative", "confidence": "Moderate", "confidence_rationale": "67 primary reports with 8 selected partial-body examinations; evidence density and the near-absence of replicated clinical tests set the confidence, not correctness and not reviewer access depth.", "rests_on_non_peer_reviewed_work": false, "rationale": "Overall Α follows the preregistered primary SC2 human-regimen clinical-benefit gate. Partial selectivity and experimental activity remain Γ in SC1; they cannot be transferred into the clinical-benefit score. Toxicity avoidance is separately contradicted at Α, and generic care-substitution survival associations remain Β. Route-dependent cyanide harm has its own Ζ model assessment. No finding of toxicity alone determines the benefit grade." }, "role_of_mechanism": { "classification": "epiphenomenon", "derivation_step_matched": 2, "derivation": "For the registered clinical anticancer benefit, no demonstrated disease-control dependency in either direction is established, so step2 applies to purported human benefit. This classification is not a description of cyanide poisoning: administered exposure, metabolism and antidote/dechallenge demonstrate genuine harm causation, which is graded in the opposite model. Nor does it deny laboratory cytotoxicity; that is a different scoped phenotype.", "tournament_used_as_tiebreaker": false, "note": "Derived from causal direction, not tournament rank." }, "extended_scoring_MSD": { "momentum": { "value": "Mechanistic only", "artifact": "The 2020 magnetic enzyme platform (32636623),2022 niosomal gel (36355478),2024 renal combination (39519581) and2026 nanocomposite (41882653) test preclinical delivery/activity. The 2024 provider survey (38999817) supplies use patterns, not a verified clinical efficacy trial underway.", "justification": "The 2020 magnetic enzyme platform (32636623),2022 niosomal gel (36355478),2024 renal combination (39519581) and2026 nanocomposite (41882653) test preclinical delivery/activity. The 2024 provider survey (38999817) supplies use patterns, not a verified clinical efficacy trial underway." }, "stability": { "value": "Stable", "trigger": "No verified named pending result was identified that demonstrably determines the full-scope letter; this is a bounded search finding, not proof that none exists.", "justification": "No verified named pending result was identified that demonstrably determines the full-scope letter; this is a bounded search finding, not proof that none exists." }, "divergence": { "implied_level": null, "implied_level_basis": "No single field-implied level is defensible from conflicting framings.", "assessed_level": "Α", "gap_in_rungs": null, "value": "Contested", "justification": "No manufactured field consensus or arithmetic gap." }, "calibration_note": "M/S/D never modify HSEF level or confidence." }, "change_record": { "applies": false, "prior_level": "none assigned", "prior_confidence": null, "prior_source": null, "derived_before_consulting_prior": true, "new_level": "Α", "direction": "newly assigned", "what_moved_it": "Fresh primary evidence appraisal; not blinded.", "divergence_from_other_reviewers": null }, "proposed_decisive_experiments": [ { "name": "Registered boundary experiment", "experiment": "First characterize formulation identity, parent/metabolite kinetics and cyanide generation with clinically anchored exposure in matched malignant and normal systems. Establish selective functional activity, normal-organ margin and pharmacodynamic tumour exposure in controlled relevant models using carrier/enzyme-only and route-matched controls. A future new-platform add-on trial would require those preclinical criteria and independent review; it must preserve effective cancer care and is not a recommendation to revive the historical unbeneficial regimen.", "readout": "Measured parent, cyanide and thiocyanate in tumour and normal compartments; objective tumour function/control and systemic injury; conditional later clinical progression/survival", "critical_control": "Formulation/purity, free drug versus carrier/enzyme, oral/IV/topical route, microbiota/foods, normal tissue proliferation, delivered tumour exposure, systemic toxicity, concurrent standard therapy and prespecified endpoints", "supporting_result": "A new platform produces replicated selective functional tumour control at attainable exposure with verified normal-organ safety and then, only if justified, an add-on clinical endpoint benefit", "falsifying_result": "Cell activity requires unachievable or toxic exposure, disappears against normal tissue/carrier controls, or delivery improves markers without tumour control and systemic safety" } ], "knowledge_gaps": [ { "name": "Gap 1", "statement": "Bridge cell concentrations to measured tumour and normal-organ exposure rather than equating plasma peak with sustained tumour concentration.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 2", "statement": "Separate free compound, historical products and new carrier/enzyme platforms.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 3", "statement": "Verify actual normal-tissue comparators and systemic cyanide margins for modern selectivity claims.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 4", "statement": "Resolve route, foods and microbial activation without assuming everyIVdose is safe or everyoral exposure is lethal.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 5", "statement": "Retain the difference between178 treated and175 evaluable, and label the temporary response detail as secondary-source verification until original body is obtained.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 6", "statement": "Do not use generic alternative-care mortality coding as a laetrile-specific causal estimate.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 7", "statement": "Audit current retractions before reusing older positive cell papers.", "relevance": "Limits mechanism identification or scope." } ], "review_metadata": { "review_date": "2026-10-12", "reviewer": "Codex", "evidence_base_note": "67 primary reports; literature cutoff 2026-10-12; source examination UTC date 2026-10-12; bounded critical review, not exhaustive systematic review.", "literature_tools_available": true, "literature_tools_note": "Life Sciences Literature PubMed/Entrez, separately logged public original-body retrieval, and Consensus Pro browser searches. Provider output retained as observed browser text with citation-link mappings, or as previously exported connector documents where present. AI synthesis is not primary full-text verification. Consensus retrieved/included counts are not examined-primary counts. Scite monthly limit was reached earlier in this session; no new Scite query or incoming citation-context audit is claimed for these cases. Tool receipts record actual use. Supplementary discovery outputs do not earn primary-count credit. No independent blinded review.", "skill_version": "5.3", "validator_run": "PASS: exact archived HSEF v5.3 validator rerun after final sealing.", "validator_warnings_addressed": "No warnings.", "limits": "Bounded source-based critical review; no complete-paper/supplement audit, independent scientific peer review or blinded calibration. Revision cases retain original prose outside the three framework output blocks and have explicit correction logs." }, "is_calibration_entry": { "value": false, "entry_role": "not_calibration", "blind_graded": null, "completed_blinded_calibration": false, "expected_band_sealed_at": "", "target_sha256": "", "target_authorship": "not applicable", "target_author_saw_review": null, "future_run_status": "not prepared", "unblinded_reason": "The cases were selected because the user asked for historically promoted claims challenged by evidence. This selection context was visible; no blind calibration is claimed and no negative score was preregistered." }, "upper_ladder_check": { "final_level_below_zeta": true, "equivalents_considered": [ { "kind": "mendelian_randomization", "available": true, "why_not_sufficient": "Therapeutic cancer endpoints, exposure pharmacology, controlled tumour-model panels, objective case-record review and matched-cell selectivity were considered. No positive controlled clinical benefit at the promoted regimen scope was verified; the absence of an RCT is not itself the blocker. Existing human tumour-course evidence and failure to bridge safe exposure are substantive limits. The opposite route-dependent harm case has convergent independent classes and can score above the nominal without reapplying association caps to all its clinical cases. Complementary-use mortality cohorts alone remain association evidence." }, { "kind": "natural_experiment", "available": true, "why_not_sufficient": "Therapeutic cancer endpoints, exposure pharmacology, controlled tumour-model panels, objective case-record review and matched-cell selectivity were considered. No positive controlled clinical benefit at the promoted regimen scope was verified; the absence of an RCT is not itself the blocker. Existing human tumour-course evidence and failure to bridge safe exposure are substantive limits. The opposite route-dependent harm case has convergent independent classes and can score above the nominal without reapplying association caps to all its clinical cases. Complementary-use mortality cohorts alone remain association evidence." }, { "kind": "dose_response_across_populations", "available": false, "why_not_sufficient": "Therapeutic cancer endpoints, exposure pharmacology, controlled tumour-model panels, objective case-record review and matched-cell selectivity were considered. No positive controlled clinical benefit at the promoted regimen scope was verified; the absence of an RCT is not itself the blocker. Existing human tumour-course evidence and failure to bridge safe exposure are substantive limits. The opposite route-dependent harm case has convergent independent classes and can score above the nominal without reapplying association caps to all its clinical cases. Complementary-use mortality cohorts alone remain association evidence." }, { "kind": "withdrawal_rechallenge", "available": false, "why_not_sufficient": "Therapeutic cancer endpoints, exposure pharmacology, controlled tumour-model panels, objective case-record review and matched-cell selectivity were considered. No positive controlled clinical benefit at the promoted regimen scope was verified; the absence of an RCT is not itself the blocker. Existing human tumour-course evidence and failure to bridge safe exposure are substantive limits. The opposite route-dependent harm case has convergent independent classes and can score above the nominal without reapplying association caps to all its clinical cases. Complementary-use mortality cohorts alone remain association evidence." }, { "kind": "therapeutic_perturbation_hard_endpoint", "available": false, "why_not_sufficient": "Therapeutic cancer endpoints, exposure pharmacology, controlled tumour-model panels, objective case-record review and matched-cell selectivity were considered. No positive controlled clinical benefit at the promoted regimen scope was verified; the absence of an RCT is not itself the blocker. Existing human tumour-course evidence and failure to bridge safe exposure are substantive limits. The opposite route-dependent harm case has convergent independent classes and can score above the nominal without reapplying association caps to all its clinical cases. Complementary-use mortality cohorts alone remain association evidence." } ], "convergence_present": false, "cap_reapplied_to_convergent_set": false }, "provenance_header": { "sources_total": 67, "claims_total": 72, "claims_verified": 72, "claims_unverified": 0, "claims_contradicted": 0, "tier_a_sources": 67, "generated_by": "Codex; HSEF v5.3", "gate_passed": true }, "claims": [ { "id": "C1", "text": "The original nonrandomized study treated 178 patients and reports no substantive cancer benefit with cyanide hazards. Uncontrolled heterogeneous trial, not an RCT; exact response numbers were unavailable in the original abstract/body.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 1 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C2", "text": "Six cancer patients show route differences: IV parent excretion with little toxicity, oral cyanide and almond-related symptoms. Small safety study does not establish clinical benefit or safety of every IV regimen.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 2 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C3", "text": "IV parent exposure is high and rapidly cleared; oral parent exposure is low while cyanide rises and almonds amplify it. Related pharmacology programme; plasma parent drug is not tumour exposure or an efficacy endpoint.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 3 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C4", "text": "Dog and rat pharmacokinetics demonstrate renal elimination and limited oral parent bioavailability with prunasin formation. Species limits; no efficacy trial or equivalence of oral and IV toxicity.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 4 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C5", "text": "Retrospective oral-plus-IV exposure in 55 patients shows increased cyanide but decreased lactate around infusion. Biomarkers without comparator or objective tumour outcome; printed dose units require body verification.", "carries_number": true, "load_bearing_for": [ "SC3" ], "source_ns": [ 5 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C6", "text": "Providers report perceived progression delay and few adverse effects, with variable dosing and little cyanide monitoring. Selected 38 of 76 providers; impressions are not audited patient outcomes or evidence of safety.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 6 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:2. Materials and Methods:paragraph0, 1:2. Materials and Methods:paragraph6. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C7", "text": "Selected historical commercial products were subpotent, mislabeled, contaminated or pyrogenic. Manufacturer and batch findings cannot describe every modern preparation or determine cancer efficacy.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 7 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C8", "text": "Intestinal mucosa has activating glucosidase activity not detected in the human tumour tissues tested. Specific tissue panel challenges selective activation but cannot exclude every alternate cellular mechanism.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 8 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C9", "text": "Canadian and US formulations differ; tested preparations do not support the manufacturers' biological rationale. Historic chemical and biological tests are not clinical endpoints or universal product identification.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 9 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C10", "text": "Oral amygdalin with high-dose vitamin C precedes severe neurological and acidosis symptoms with rapid antidote response. Single case; exact interaction magnitude and population incidence are not determined.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 10 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C11", "text": "A child receiving oral/IV amygdalin and kernels develops encephalopathy, acidosis and elevated cyanide, improving after antidote. Combined exposure prevents assignment to each component; case supports harm, not an incidence estimate.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 11 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C12", "text": "Kernel ingestion precedes pediatric coma and measured cyanide, followed by recovery with antidote and dialysis. Small-child kernel exposure differs from an IV regimen; combined rescue does not isolate dialysis efficacy.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 12 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C13", "text": "Prescribed oral tablets precede hypotension, acidosis and altered consciousness with rapid antidote response in a cancer patient. Selected body does not report a measured cyanide value; temporal clinical attribution is not a poisoning-rate estimate.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 13 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:2. Case Report:paragraph0, 1:2. Case Report:paragraph1. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C14", "text": "Intentional massive amygdalin overdose causes recurrent acidosis and hypotension requiring repeated antidotal treatment. A 20 g overdose is not a standard promoted regimen; severity must not be generalized to all dosing.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 14 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C15", "text": "Chronic kernel extract is associated with measured cyanide and abnormal oximetry normalizing after cessation. Oximeter-interference explanation is inferred; single case and unavailable body limit broader attribution.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 15 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C16", "text": "Thirteen pediatric seed-ingestion cases include ventilation, coma and acidosis with recovery after treatment. Selected intensive-care series has no population denominator and does not test isolated IV products.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 16 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C17", "text": "Neuromyopathy after laetrile has elevated cyanide/thiocyanate and improves after discontinuation, with alternatives assessed. Nutritional deficiency contributes; single-patient evidence does not quantify risk or establish cancer efficacy.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 17 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C18", "text": "Healthy-adult crossover demonstrates different cyanide peaks from foods with equal cyanide-equivalent doses. Small healthy sample and limited challenge measure exposure, not cancer efficacy or poisoning incidence.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 18 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Materials and methods:paragraph2, 1:Materials and methods:paragraph6, 1:Materials and methods:paragraph8. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C19", "text": "Preparations from an intoxicated patient and fruit seeds contain measurable cyanide. Product analysis complements clinical cases but is not a complete dose-risk or causation model.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 19 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C20", "text": "Rat antibiotic/gut-flora comparisons and human fecal bacteria show microbial cyanide release from amygdalin. Animal dosing and ex vivo activity do not specify human incidence or remove formulation/route differences.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 20 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C21", "text": "Repeated high intraperitoneal doses produce rat mortality with cyanide signals. High-dose animal route is not a direct human-regimen risk estimate; nonselective toxicity is retained.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 21 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C22", "text": "Oral mouse dosing produces cyanide and distress; gut contents activate drug whereas tumour tissue releases little; parenteral exposure differs. Species, individual variability and near-lethal doses limit clinical extrapolation.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 22 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C23", "text": "Vitamin C coadministration decreases cyanide detoxification through reduced cysteine availability in guinea pigs. Specific metabolic model does not quantify the interaction at every human dose.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 23 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C24", "text": "Oral but not IV hamster exposure causes malformations with cyanide increase; thiosulfate protects embryos. Pregnancy and species scope retained; not a measured human teratogenic incidence.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 24 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C25", "text": "Oral laetrile with almonds causes death or neurological impairment in dogs at proposed human-equivalent doses. Food, dose and species limits; this does not describe every IV formulation.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 25 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C26", "text": "Drug alone and enzyme combination fail tumour tests near tolerated-dose limits; enzyme potentiates lethality. Three transplantable models are restricted contexts; negative contrasts earn no positive efficacy crossing.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 26 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C27", "text": "Four rodent tumours show no activity under drug/enzyme schedules, with increased combination toxicity. Models share a testing programme and are not four independent studies or all human cancers.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 27 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C28", "text": "Early visual metastasis benefits fail independent, cooperative and blinded assessments; leukemia/prevention tests are negative. Disputed positive observations are retained with replication limits, not erased or generalized to new delivery platforms.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 28 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C29", "text": "Broad rodent tumour panels show no effect from high-dose amygdalin, including chemotherapy interaction tests. Many models share a programme; this does not exclude distinct engineered delivery.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 29 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C30", "text": "Parenteral amygdalin does not arrest two specified murine tumours across a dose range. Model and route-specific negative, not a human randomized trial.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 30 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C31", "text": "High-dose schedules do not prolong survival in two leukemia-bearing mouse models. No inference to an exact human hazard ratio or every formulation.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 31 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C32", "text": "Amygdalin changes apoptosis, inflammatory and organ-function markers in Ehrlich tumour-bearing mice. Marker-heavy abstract does not show durable human tumour control; B17 terminology is not a validated vitamin status.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 32 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C33", "text": "Amygdalin with sorafenib reduces Ehrlich tumour burden and liver injury measures in mice. Combination and route context, not clinical benefit or a proved selective cyanide mechanism.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 33 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C34", "text": "Apricot extract and amygdalin-containing fraction alter apoptosis/autophagy and proliferation in a chemically induced liver model. Mixed extract and molecular endpoints cannot establish pure-drug clinical efficacy.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 34 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C35", "text": "Amygdalin alone or with tamoxifen changes mammary histology and molecular/biochemical tumour measures. Induction, combination and marker limits; no human treatment outcome or selective exposure bridge.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 35 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C36", "text": "Lung cell apoptosis and NFkB1 studies with xenograft findings support restricted model activity. No promoted human-dose selectivity; original abstract only and supplements unexamined.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 36 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C37", "text": "Antibody-directed glucosidase activation produces antigen-specific killing with mismatched-antibody and coculture controls. Engineered activation differs from ordinary laetrile; two cancer lines do not establish systemic normal-tissue safety.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 37 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C38", "text": "Matched marrow and myeloid leukemia clonogenic tests find no selective killing, including enzyme activation. Specific assay cannot exclude every cell-pair effect, while normal-tissue cost is directly retained.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 38 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C39", "text": "Drug inhibits migration/invasion in selected lung cancer lines below concentrations needed for growth inhibition. No actual metastatic disease endpoint or matched normal-tissue/exposure test.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 39 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C40", "text": "Treatment at the line's IC50 downregulates DNA-replication genes in MCF7 cells. Expression after cytotoxic exposure can be secondary; no matched normal or exposure validation.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 40 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C41", "text": "Apricot and almond ethanolic extracts reduce KB cell viability in an MTT assay. Extract identity and cell-line assay do not establish pure-drug oral-cancer clinical response.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 41 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C42", "text": "Amygdalin at 5 mg/mL changes cell-cycle gene expression in colon cancer cells. High concentration and transcript readout do not prove clinically achievable selectivity or tumour control.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 42 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C43", "text": "Breast cancer lines show apoptosis and adhesion changes with caspase, Bax/Bcl2 and p38 signals. Cancer-only culture findings lack normal-organ exposure and human prevention endpoints.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 43 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C44", "text": "Cancer growth and migration decrease while selected normal skin fibroblasts are spared at the tested concentrations. One normal comparator and culture context cannot define a systemic therapeutic window.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 44 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C45", "text": "Renal cancer cells exposed to 10 mg/mL show growth and cell-cycle effects with cdk1/cyclin B tests. Blockade phenocopy is not a drug-specific rescue; human exposure and normal-organ selectivity remain untested.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 45 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C46", "text": "Dose-dependent prostate cell growth/clonogenic inhibition accompanies cell-cycle changes. High mg/mL exposure and cell-specific apoptosis effects limit clinical translation.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 46 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C47", "text": "Drug inhibits parental and taxane-resistant prostate lines at 10 mg/mL. Related cell programme, not independent clinical trials; exposure and safety bridge absent.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 47 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C48", "text": "Breast line growth inhibition correlates with oxidative stress at 39–45 mM IC50. Tumour-only correlations and high concentrations do not demonstrate normal-tissue sparing or mediator necessity.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 48 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C49", "text": "SKBR3 viability/apoptotic proteins change; docking proposes target interactions. Docking is not measured binding or necessity, and culture lacks a human-dose selective window.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 49 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C50", "text": "Original body reports HepG2/WI38 IC50 differences and synergy with sorafenib. mg/mL exposure and unmatched tissue/proliferation contexts limit selectivity; the source's outdated HCC-treatment assertion is not adopted.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 50 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 2:Results:paragraph0, 2:Results:paragraph15, 2:Results:paragraph25. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C51", "text": "Body shows little monodrug growth effect at 1 mg/mL but stronger sulforaphane combinations, without induced apoptosis. Low dose is relative to culture, not verified patient exposure; no in vivo clinical feasibility result.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 51 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 2:3. Results:paragraph0, 2:3. Results:paragraph1, 2:3. Results:paragraph3. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C52", "text": "Magnetic enzyme-loaded nanoparticles permit targeted activation and mouse tumour-growth inhibition. Different experimental platform; body reports AST, CK and LDH increases despite no obvious histological organ injury.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 52 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 2:Results:paragraph7, 2:Results:paragraph21, 2:Results:paragraph28. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C53", "text": "Loaded nanocomposite improves uptake and viability/migration assays in selected HNSCC cells. Carrier components and release may contribute; in vitro platform is not clinical free-drug benefit or complete systemic safety.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 53 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C54", "text": "Cyclodextrin complexes improve HeLa MTT cytotoxicity compared with free compound. Formulation culture assay does not establish a human therapeutic window or clinical benefit.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 54 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C55", "text": "Amygdalin hydrogel causes colorectal-cell apoptosis alongside material/biocompatibility tests. Proposed implant has no demonstrated postoperative recurrence-prevention or clinical safety outcome.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 55 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C56", "text": "Combination with cisplatin protects selected normal cells while enhancing cancer-cell inhibition. Specific cell types and schedules, not organismal safety or patient quality-of-life trial.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 56 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C57", "text": "Yeast recombination/genotoxicity and mammalian cell comparisons suggest context-specific effects. Yeast surrogates are not human cancer prevention; native organism dependency and exposure bridge absent.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 57 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C58", "text": "Characterized kernel extract shows different toxicity in cancer and selected normal lines. Thousands of constituents and multiple cyanogenic glycosides prevent assigning all activity to pure amygdalin.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 58 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C59", "text": "Cassava extract tests report antioxidant, inflammatory and limited rat cancer-model changes. Mixed ingredients and chemical identity need scrutiny; no isolated human amygdalin therapeutic effect.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 59 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C60", "text": "Monocytic leukemia line shows concentration/time-dependent viability and apoptosis changes. No matched normal/exposure comparison; broad claims about incurable leukemia and clinical application are not adopted.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 60 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C61", "text": "Matched NCDB patients using alternative treatment without conventional care have higher mortality association. Selection, residual confounding and coarse modality coding; not a laetrile-specific randomized hazard ratio.", "carries_number": false, "load_bearing_for": [ "SC4" ], "source_ns": [ 61 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C62", "text": "Complementary-use mortality association attenuates and becomes nonsignificant after treatment refusal/delay adjustment. Shared NCDB and observational mediation; not proof every complementary use causes death.", "carries_number": false, "load_bearing_for": [ "SC4" ], "source_ns": [ 62 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C63", "text": "Matched breast-cancer primary-treatment refusal is associated with worse survival. Body confirms age, year and stage matching without full TNM; not laetrile-specific and selection remains.", "carries_number": false, "load_bearing_for": [ "SC4" ], "source_ns": [ 63 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Methods:paragraph0, 1:Methods:paragraph1. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C64", "text": "Patients delaying or refusing standard breast-cancer care frequently progress or relapse. Small chart series; some mortality figures are projections rather than observed causal deaths and modalities differ.", "carries_number": false, "load_bearing_for": [ "SC4" ], "source_ns": [ 64 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C65", "text": "Blinded oncologists judge six responses in solicited favorable laetrile treatment courses. Only claimed-benefit cases solicited; nonrandomized courses, incomplete records and cointerventions prevent definite attribution.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 65 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C66", "text": "Original body compares topical loaded niosomal gel, blank gel, oral free compound and tamoxifen in small DMBA skin-tumour rat groups. Formulation/route differ, and selected local histology does not establish systemic cyanide safety, tumour pharmacokinetics or human benefit.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 66 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:2. Results and Discussion:paragraph8, 1:2. Results and Discussion:paragraph9, 1:2. Results and Discussion:paragraph10, 2:3. Materials and Methods:paragraph13, 2:3. Materials and Methods:paragraph14, 2:3. Materials and Methods:paragraph15, 2:3. Materials and Methods:paragraph16, 2:3. Materials and Methods:paragraph17, 2:3. Materials and Methods:paragraph18, 2:3. Materials and Methods:paragraph19, 2:3. Materials and Methods:paragraph20, 2:3. Materials and Methods:paragraph21. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "C67", "text": "Alginate-chitosan particles sustain release and increase H1299 cell cytotoxicity compared with free drug. Abstract claims normal-tissue protection but supplied results do not detail an independent normal-tissue clinical endpoint; no whole-paper audit.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 67 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-12", "note": "" }, { "id": "CSC1", "text": "Some matched malignant/normal cell comparisons and engineered activation systems show differential effects. Other matched marrow studies show no selective killing, and high culture concentrations, tissue-mismatched controls and enzyme/carrier additions prevent a general human therapeutic window. Partial system selectivity is retained atΓ, not promoted to clinical efficacy.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 2, 3, 4, 7, 8, 9, 18, 20, 22, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 66, 67 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-12", "note": "" }, { "id": "CSC2", "text": "The registered human-regimen benefit claim has no credible, reproducible positive clinical support in the examined set. The 178-patient nonrandomized treatment programme reported no substantive benefit. Six judged responses in solicited favorable historical records lack a credible counterfactual and reliable attribution. Laboratory activity and new-platform animal effects remain SC1 support and do not establish SC2. Α is evidence-derived unsupported clinical benefit, rather than a penalty for the absence of an RCT or a claim of zero biological activity.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 1, 6, 9, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 65 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-12", "note": "" }, { "id": "CSC3", "text": "The blanket claim of avoiding clinically important systemic cyanide toxicity is directly challenged by prescribed oral-regimen poisoning, measured cyanide, food interactions and animal rescue/exposure tests. Some small IV pharmacology settings lack observed toxicity, but that cannot establish safety across promoted regimens. The positive avoidance claim is unsupported atΑ; the opposite route-dependent poisoning model scores separately and higher.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-12", "note": "" }, { "id": "CSC4", "text": "Treatment substitution/refusal cohorts associate with worse survival and treatment-refusal adjustment attenuates the complementary-use association. These are clinically important warnings, but the retrieved cohorts are nonrandomized and not laetrile-specific. This separate broad causal proposition is held atΒ under the association-only cap; the observed hazard ratios are not randomized causal estimates.", "carries_number": false, "load_bearing_for": [ "SC4" ], "source_ns": [ 61, 62, 63, 64 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-12", "note": "" }, { "id": "CH", "text": "Laetrile has no demonstrated clinically meaningful benefit in the examined human cancer regimens; oral use can cause serious cyanide poisoning, while newer preclinical delivery studies remain experimental.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 1, 2, 13, 50, 52, 66 ], "verification": "verified", "verified_against": "Bounded synthesis of examined sources; score is adjudication.", "verified_on": "2026-10-12", "note": "" } ], "citation_ledger": [ { "n": 1, "citation": "Moertel CG, Fleming TR, Rubin J et al. A clinical trial of amygdalin (Laetrile) in the treatment of human cancer. The New England journal of medicine. 1982.", "tier": "A", "kind": "primary", "pmid": "7033783", "doi": "10.1056/NEJM198201283060403", "url": "https://pubmed.ncbi.nlm.nih.gov/7033783/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID7033783", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C1", "CSC2", "CSC3", "CH" ] }, { "n": 2, "citation": "Moertel CG, Ames MM, Kovach JS et al. A pharmacologic and toxicological study of amygdalin. JAMA. 1981.", "tier": "A", "kind": "primary", "pmid": "7005480", "doi": "", "url": "https://pubmed.ncbi.nlm.nih.gov/7005480/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "NCI_CLINICAL_PHARMACOLOGY_PROGRAMME", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C2", "CSC1", "CSC3", "CH" ] }, { "n": 3, "citation": "Ames MM, Moyer TP, Kovach JS et al. Pharmacology of amygdalin (laetrile) in cancer patients. Cancer chemotherapy and pharmacology. 1981.", "tier": "A", "kind": "primary", "pmid": "7273266", "doi": "10.1007/BF00253010", "url": "https://pubmed.ncbi.nlm.nih.gov/7273266/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "NCI_CLINICAL_PHARMACOLOGY_PROGRAMME", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C3", "CSC1", "CSC3" ] }, { "n": 4, "citation": "Rauws AG, Olling M, Timmerman A. The pharmacokinetics of amygdalin. Archives of toxicology. 1982.", "tier": "A", "kind": "primary", "pmid": "7092570", "doi": "10.1007/BF00347879", "url": "https://pubmed.ncbi.nlm.nih.gov/7092570/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID7092570", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C4", "CSC1", "CSC3" ] }, { "n": 5, "citation": "Mani J, Rutz J, Maxeiner S et al. Cyanide and lactate levels in patients during chronic oral amygdalin intake followed by intravenous amygdalin administration. Complementary therapies in medicine. 2019.", "tier": "A", "kind": "primary", "pmid": "30935547", "doi": "10.1016/j.ctim.2019.03.002", "url": "https://pubmed.ncbi.nlm.nih.gov/30935547/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID30935547", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C5", "CSC3" ] }, { "n": 6, "citation": "Markowitsch SD, Binali S, Rutz J et al. Survey of Physicians and Healers Using Amygdalin to Treat Cancer Patients. Nutrients. 2024.", "tier": "A", "kind": "primary", "pmid": "38999817", "doi": "10.3390/nu16132068", "url": "https://pubmed.ncbi.nlm.nih.gov/38999817/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID38999817", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:2. Materials and Methods:paragraph0, 1:2. Materials and Methods:paragraph6. No complete-paper or supplement audit claimed.", "carries_claims": [ "C6", "CSC2", "CSC3" ] }, { "n": 7, "citation": "Davignon JP, Trissel LA, Kleinman LM. Pharmaceutical assessment of amygdalin (Laetrile) products. Cancer treatment reports. 1978.", "tier": "A", "kind": "primary", "pmid": "627001", "doi": "", "url": "https://pubmed.ncbi.nlm.nih.gov/627001/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-12", "status_checked_on": "2026-10-12", "study_id": "PMID627001", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C7", "CSC1", "CSC3" ] }, { "n": 8, "citation": "Newmark J, Brady RO, Grimley PM et al. Amygdalin (Laetrile) and prunasin beta-glucosidases: distribution in germ-free rat and in human tumor tissue. 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No complete-paper or supplement audit claimed.", "carries_claims": [ "C67", "CSC1" ] } ], "independence_basis": { "required": true, "lines": [ { "label": "Human route and exposure pharmacology", "sources": [ 2, 3, 18 ], "excludes_error": "Measures systemic parent/cyanide and food-matrix differences, reducing uncertainty about exposure; some studies share a programme and healthy challenges do not measure cancer efficacy." }, { "label": "Clinical poisoning and reversal", "sources": [ 10, 13, 11, 17 ], "excludes_error": "Independent temporal exposure, symptoms and antidote/dechallenge reduce a culture-only explanation, while selection and interacting exposures prevent incidence estimates." }, { "label": "Controlled activation and toxic rescue", "sources": [ 20, 22, 24 ], "excludes_error": "Microbial/route interventions and thiosulfate rescue constrain cyanide mediation against nonspecific illness; species limits remain." }, { "label": "Restricted experimental tumour activity", "sources": [ 50, 52, 66 ], "excludes_error": "Matched cells and altered delivery test biological activity, but share preclinical exposure/specificity translation limits and do not converge on human regimen benefit." } ], "shared_failure_mode_checked": true, "note": "The causal convergence atΖbelongs to the opposite route-dependent poisoning model, not to clinical anticancer benefit or harmlessness. Human pharmacology papers from the NCI programme are not automatically separate lines. Historical tumour panels share laboratories/regimens; many renal/prostate cell reports share lines and assays. Multiple death/apoptosis markers from one exposure are not independent tests. Cases across settings plus controlled metabolism/route/rescue and direct exposure measurements constrain different failure modes, without producing a population poisoning rate. NCDB substitution/complementary reports share a database and coarse coding." }, "gamma_hard_rules_considered": [ { "subclaim_id": "SC1", "rule_quoted": "Sphere formation alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC1", "rule_quoted": "Marker enrichment alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC1", "rule_quoted": "Xenograft tumor-initiation without lineage-resolved endogenous evidence", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC1", "rule_quoted": "In vitro-only mechanistic studies, however elegant", "trigger_status": "Applies to the uncontrolled or cell-only positive support class, with ceiling Γ; it does not upgrade that class or describe the whole source set." }, { "subclaim_id": "SC2", "rule_quoted": "Sphere formation alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC2", "rule_quoted": "Marker enrichment alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC2", "rule_quoted": "Xenograft tumor-initiation without lineage-resolved endogenous evidence", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC2", "rule_quoted": "In vitro-only mechanistic studies, however elegant", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC3", "rule_quoted": "Sphere formation alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC3", "rule_quoted": "Marker enrichment alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC3", "rule_quoted": "Xenograft tumor-initiation without lineage-resolved endogenous evidence", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC3", "rule_quoted": "In vitro-only mechanistic studies, however elegant", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC4", "rule_quoted": "Sphere formation alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC4", "rule_quoted": "Marker enrichment alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC4", "rule_quoted": "Xenograft tumor-initiation without lineage-resolved endogenous evidence", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC4", "rule_quoted": "In vitro-only mechanistic studies, however elegant", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." } ], "consensus_validation": { "completed": true, "status": "completed_original_source_reconciliation", "provider_mode": "Consensus Pro signed-in browser; observed output and citation link mappings", "queries": [ "https://consensus.app/search/laetrile-amygdalin-cancer-treatment/r2qpQ4-GS1mql46fgAIFzg/" ], "query_record_note": "Exact visible question/response retained privately in raw browser receipt.", "primary_comparison_count": 11, "primary_comparisons": [ { "pmid": "7033783", "doi": "10.1056/NEJM198201283060403", "source_type": "primary study report", "study_group": "PMID7033783", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus reports the178-patient nonrandomized regimen and explicitly limits original access to its abstract.", "result_comparison": "Our original abstract check agrees: practitioner-like metabolic programme, no substantive benefit and cyanide hazards. The175 evaluable/one temporary partial response detail is supplied by a later review in Consensus and by auxiliaryNCIcontext in our check; it is not directly verified in an original trial body. Do not call this an RCT or zero responses.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/7033783/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_20_22_2026-10-12\\laetrile-cancer-treatment\\examinations\\original-0-15-4000.json" ], "body_receipts": [] }, { "pmid": "683212", "doi": "10.1056/NEJM197809072991013", "source_type": "primary study report", "study_group": "PMID683212", "access_depth": "abstract_metadata", "consensus_aspect": "Provider emphasizes negative clinical evidence but does not detail the original favorable case-record submission analysis.", "result_comparison": "The original1978 abstract retains six responses judged by a blinded oncology panel, while only presumed-success cases were solicited and incomplete records excluded. These observations justify interest without proving a treatment effect or becoming an independent controlled trial.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/683212/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_20_22_2026-10-12\\laetrile-cancer-treatment\\examinations\\original-64-65-6000.json" ], "body_receipts": [] }, { "pmid": "7005480", "doi": "", "source_type": "primary study report", "study_group": "NCI_CLINICAL_PHARMACOLOGY_PROGRAMME", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus correctly reports oral/IV differences and the raw-almond interaction from the original pharmacology abstract.", "result_comparison": "Original six-patient abstract confirms low observed toxicity withIVadministration, increased oral cyanide and transient symptoms in one almond-challenged patient. Small route-specific observations cannot prove safety of every IV dose or efficacy.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/7005480/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_20_22_2026-10-12\\laetrile-cancer-treatment\\examinations\\original-0-15-4000.json" ], "body_receipts": [] }, { "pmid": "7273266", "doi": "10.1007/BF00253010", "source_type": "primary study report", "study_group": "NCI_CLINICAL_PHARMACOLOGY_PROGRAMME", "access_depth": "abstract_metadata", "consensus_aspect": "Provider discusses clinically attainable exposure and oral versusIV activation.", "result_comparison": "Original pharmacology distinguishes high, briefIVparent plasma levels from very low oral parent levels with cyanide increase. These are parent plasma measurements, not sustained tumour concentration. Culturemg/mL activity cannot be equated to the same human exposure.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/7273266/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_20_22_2026-10-12\\laetrile-cancer-treatment\\examinations\\original-0-15-4000.json" ], "body_receipts": [] }, { "pmid": "37726740", "doi": "10.1186/s12906-023-04142-1", "source_type": "primary study report", "study_group": "PMID37726740", "access_depth": "full_text_partial", "consensus_aspect": "Consensus acknowledges matched-normal positive studies but does not report the examined original cell-pair dose limits.", "result_comparison": "Original Results verifies HepG2 versusWI38 differentialIC50 and sorafenib synergy atmg/mL concentrations. Unmatched tissue types, cell proliferation and missing whole-organ exposure still limit a human therapeutic window; the positive comparator is retained.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/37726740/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_20_22_2026-10-12\\laetrile-cancer-treatment\\examinations\\original-45-65-3600.json" ], "body_receipts": [ "deliverables\\hsef_v53_remaining_priority_20_22_2026-10-12\\laetrile-cancer-treatment\\body-presentation-receipts\\37726740-s2-p0-15-25.json" ] }, { "pmid": "39519581", "doi": "10.3390/nu16213750", "source_type": "primary study report", "study_group": "PMID39519581", "access_depth": "full_text_partial", "consensus_aspect": "Provider's preclinical summary could be read as broad monodrug activity.", "result_comparison": "Original body distinguishes minimal growth effect from1 mg/mLalone from strong sulforaphane-combination effects, and reports no induced apoptosis in those assays. A low dose in that protocol is not verified patient exposure.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/39519581/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_20_22_2026-10-12\\laetrile-cancer-treatment\\examinations\\original-45-65-3600.json" ], "body_receipts": [ "deliverables\\hsef_v53_remaining_priority_20_22_2026-10-12\\laetrile-cancer-treatment\\body-presentation-receipts\\39519581-s2-p0-1-3.json" ] }, { "pmid": "32636623", "doi": "10.2147/IJN.S242359", "source_type": "primary study report", "study_group": "PMID32636623", "access_depth": "full_text_partial", "consensus_aspect": "Provider emphasizes nanocarriers as a technical advance rather than clinical validation.", "result_comparison": "Original magnetic-enzyme Results agree with a restricted delivery benefit and retain inactive targeting controls. AST, CK and LDHincrease despite no obvious organ histology injury. Neither the carrier norenzyme addition is historical free-drug therapy, and limited histology cannot be labeled complete safety.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/32636623/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_20_22_2026-10-12\\laetrile-cancer-treatment\\examinations\\original-45-65-3600.json" ], "body_receipts": [ "deliverables\\hsef_v53_remaining_priority_20_22_2026-10-12\\laetrile-cancer-treatment\\body-presentation-receipts\\32636623-s2-p7-21-28.json" ] }, { "pmid": "36355478", "doi": "10.3390/ph15111306", "source_type": "primary study report", "study_group": "PMID36355478", "access_depth": "full_text_partial", "consensus_aspect": "Consensus supplies a new niosomal-gel animal lead and a provider release graphic.", "result_comparison": "Original record and selected Methods/Results were examined: thirty rats in small DMBA groups, topical loaded gel versus blank gel/oral free compound, reduced local carcinoma volume and skin pathology. These results remain positive in their context, but do not measure a human regimen, systemic cyanide margin or complete normal-organ safety. Provider graphics are not republished.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/36355478/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_20_22_2026-10-12\\laetrile-cancer-treatment\\examinations\\original-65-67-6000.json" ], "body_receipts": [ "deliverables\\hsef_v53_remaining_priority_20_22_2026-10-12\\laetrile-cancer-treatment\\body-presentation-receipts\\36355478-s1-p8-9-10.json", "deliverables\\hsef_v53_remaining_priority_20_22_2026-10-12\\laetrile-cancer-treatment\\body-presentation-receipts\\36355478-s2-p13-14-15-16-17-18-19-20-21.json" ] }, { "pmid": "32097740", "doi": "10.1016/j.ijbiomac.2020.02.191", "source_type": "primary study report", "study_group": "PMID32097740", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus says alginate-chitosan carriers protect normal cells and tissues.", "result_comparison": "The original abstract reports release, mucin/flow and H1299 cell activity, then makes a broad protection conclusion. Our original-body access is unavailable, so an independent normal-tissue endpoint was not verified. Its abstract supports a delivery lead, not clinical proof of protection.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/32097740/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_20_22_2026-10-12\\laetrile-cancer-treatment\\examinations\\original-65-67-6000.json" ], "body_receipts": [] }, { "pmid": "30027204", "doi": "10.1001/jamaoncol.2018.2487", "source_type": "primary study report", "study_group": "PMID30027204", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus separates alternative/complementary-care survival cohorts from laetrile-specific efficacy.", "result_comparison": "Original abstract agrees that refusal is important: mortality association becomes nonsignificant after refusal/delay adjustment. This observational attenuation is not randomized mediation proof, not a compound-specific hazard ratio and not evidence that every complementary use causes death.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/30027204/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_20_22_2026-10-12\\laetrile-cancer-treatment\\examinations\\original-45-65-3600.json" ], "body_receipts": [] }, { "pmid": "22734852", "doi": "10.1186/1477-7819-10-118", "source_type": "primary study report", "study_group": "PMID22734852", "access_depth": "full_text_partial", "consensus_aspect": "Provider uses refusal cohorts as separate evidence about treatment substitution.", "result_comparison": "OriginalMethods confirms retrospective primary-treatment refusal, limited age/year/stage matching and exclusion of older patients. The association is clinically relevant but cannot identify laetrile exposure or remove every selection factor.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/22734852/", "source_examination_receipts": [ "deliverables\\hsef_v53_remaining_priority_20_22_2026-10-12\\laetrile-cancer-treatment\\examinations\\original-45-65-3600.json" ], "body_receipts": [ "deliverables\\hsef_v53_remaining_priority_20_22_2026-10-12\\laetrile-cancer-treatment\\body-presentation-receipts\\22734852-s1-p0-1.json" ] } ], "grade_changed": false, "grade_change_note": "Source-based adjudication; no independent blinded regrade claimed.", "raw_receipts": [ { "path": "deliverables\\hsef_v53_remaining_priority_20_22_2026-10-12\\laetrile-cancer-treatment\\consensus-browser-2026-10-12.json", "sha256": "499362c3b58d147054cb575d8239a72da8dc7ca1b0722f34d3cd9ff65e5973fa" } ], "independent_blinded_audit": false, "cutoff": "2026-10-12", "completed_utc": "2026-10-12T21:01:18.842067+00:00", "conclusion": "Endpoint hierarchy, experimental scope and original-source limits determine the evidence cards; provider wording does not override them." } }