{ "$schema_version": "5.3", "review_mode": "fresh", "claim_restatement": { "index_wording": "Replacing dietary saturated fat with linoleic-acid-rich oils reduces coronary heart disease events in adults.", "entry_form": "claim", "gradeable_restatement": "Replacing dietary saturated fat with linoleic-acid-rich oils reduces coronary heart disease events in adults.", "restatement_required": true, "split_into": [], "parent_claim": null, "scope_qualifiers": [ { "qualifier": "Adult baseline disease and coronary risk, specified oil and replacement food, energy balance, allocation, endpoint and minimum one-year follow-up fixed before outcomes", "determinable_before_outcome": true, "determined_from": "Enrollment and experimental design, before results; no responder-defined scope.", "action": "retained" } ] }, "hypothesis": { "name": "Replacing Saturated Fat with Linoleic-Acid-Rich Oils", "central_claim": "Replacing dietary saturated fat with linoleic-acid-rich oils reduces coronary heart disease events in adults.", "proposed_mechanism": "Replacing dietary saturated fat with linoleic-acid-rich oils reduces coronary heart disease events in adults.", "claimed_scope": "Adults with baseline coronary risk specified; isocaloric saturated-fat replacement by specified linoleic-acid-rich oils; randomized allocation and coronary events over at least one year", "claimed_level": [ "response", "maintenance", "progression" ], "is_conjunctive": false, "conjunctive_note": "The precise lead clinical proposition is SC2. Mechanism, competing-cause, generalization and safety companions remain separately reported; they do not replace the primary clinical endpoint." }, "rubric_routing": { "primary_rubric": "06-metabolism-aging.md", "secondary_rubrics": [], "index_notes_applied": [ "The precise lead clinical proposition is SC2. Mechanism, competing-cause, generalization and safety companions remain separately reported; they do not replace the primary clinical endpoint." ], "rubric_fit_note": "The frozen framework has no dedicated clinical nutrition or cardiovascular-prevention rubric. Rubric06's lifespan-specific wording is quoted unchanged, with an explicit clinical adaptation to controlled dietary replacement and adjudicated coronary events. Lipid markers, ectopic fat, inflammation, plaque surrogates, symptoms, coronary mortality and nonfatal coronary events remain distinct. The human clinical sources are not capped merely for involving one species; the literal single-species rule concerns animal-to-human inference. Genuine independently failing causal sets are not re-capped using their observational leg." }, "subclaim_matrix": { "subclaims": [ { "id": "SC1", "statement": "Replacing saturated fat with linoleic-acid-rich oils lowers LDL-related lipid exposure.", "subclaim_type": "mechanism", "scope": "Isocaloric replacement; oil composition and comparator specified", "claimed_scope": "Isocaloric replacement; oil composition and comparator specified", "governing_rubric": "06-metabolism-aging.md", "key_evidence_anchor": "Controlled feeding and lipid experiments", "hsef_level": "Γ", "confidence": "High", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Controlled replacement trials, including DIVAS and Minnesota, establish lipid lowering in their experimental contexts. The proposed LDL-related exposure is an intermediate marker for coronary events, so its downstream clinical inference retains Γ. This does not imply that the directly measured lipid change is doubtful or that LDL causality elsewhere is refuted.", "rubric_adaptation": "Controlled isoenergetic feeding can identify a lipid-exposure response, but the registered clinical event is assessed separately; marker change is not itself a clinical threshold crossing." }, { "id": "SC2", "statement": "The replacement reduces coronary heart disease events.", "subclaim_type": "sufficiency", "scope": "Adults with baseline risk specified; randomized allocation; clinical coronary events over at least one year", "claimed_scope": "Adults with baseline risk specified; randomized allocation; clinical coronary events over at least one year", "governing_rubric": "06-metabolism-aging.md", "key_evidence_anchor": "Clinical dietary replacement trials", "hsef_level": "Γ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "In the actually examined exact clinical sources, Minnesota reports no cardiovascular-event benefit and Sydney reports increased coronary mortality. Positive Finnish hospital-period observations and bundled Oslo or Lyon programmes retain their allocation and composition limits. The older VA and Oslo Diet-Heart primary clinical scans could not be accessed, so their reported positive results are explicitly unverified here. No verified positive allocated oil-replacement coronary-event crossing was identified at this evidence-access depth; the Step9 unclear-positive boundary holds the precise registered claim at Γ rather than promoting lipid changes or second-hand trial summaries. This is a bounded verification verdict, not proof that LA-rich oils have no benefit.", "rubric_adaptation": "The field-valid clinical equivalent is allocated saturated-fat replacement by specified LA-rich oil against a retained comparator with a positive adjudicated coronary-event difference over at least one year. Oil mixtures are legitimate specified exposures; unrelated diet, smoking or medication changes cannot be silently assigned to oil substitution. Accessible primary results and actual endpoint hierarchy are required." }, { "id": "SC3", "statement": "Linoleic-acid-rich seed oils cause clinically important inflammatory cardiovascular harm at usual dietary exposures.", "subclaim_type": "sufficiency", "scope": "Usual food exposures; food matrix and saturated-fat comparator retained", "claimed_scope": "Usual food exposures; food matrix and saturated-fat comparator retained", "governing_rubric": "06-metabolism-aging.md", "key_evidence_anchor": "Direct clinical inflammatory-harm tests", "hsef_level": "Γ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "The usual-exposure inflammatory-harm claim lacks a verified clinical inflammatory coronary endpoint. Controlled omega6 feeding has neutral or favourable inflammatory markers in several experiments; FADSDIET shows genotype-dependent short marker responses without randomized saturated-fat comparison. Sydney's historical high-dose intervention harm does not isolate inflammation or establish toxicity of all modern seed oils. Biomarker-only inference cannot exceed Γ.", "rubric_adaptation": "The phenotype is clinically important inflammatory cardiovascular harm at ordinary food exposures, requiring a direct clinical outcome and evidence that inflammation mediates it. Acute signalling, CRP, oxidative markers and extreme historical oil diets remain separate inference classes." }, { "id": "SC4", "statement": "Carnivore diets have established long-term cardiovascular superiority over balanced dietary patterns.", "subclaim_type": "primacy", "scope": "Exact diet, baseline health and clinically measured long-term outcomes", "claimed_scope": "Exact diet, baseline health and clinically measured long-term outcomes", "governing_rubric": "06-metabolism-aging.md", "key_evidence_anchor": "Controlled clinical diet comparisons", "hsef_level": "Α", "confidence": "Low", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "No examined controlled long-term cardiovascular comparison establishes carnivore superiority. Two original carnivore empirical reports contain self-selected perceived benefits and lipid changes, without adjudicated event comparisons; extrapolating these to established long-term superiority remains Α. Positive subjective experiences are retained, not dismissed as fabricated.", "rubric_adaptation": "The clinical primacy claim requires defined carnivore and balanced patterns compared on long-term adjudicated cardiovascular outcomes. Survey satisfaction, uncontrolled weight loss and selected laboratory values cannot establish superiority." } ], "aggregation_rule": "primary-subclaim", "aggregation_preregistered": true, "aggregation_rationale": "The precise lead clinical proposition is SC2. Mechanism, competing-cause, generalization and safety companions remain separately reported; they do not replace the primary clinical endpoint.", "primary_subclaim_id": "SC2", "aggregation_derivation": "The preregistered primary-subclaim rule returns Γ from SC2. Sixty original reports provide strong experimental lipid effects and a substantial but conflicting clinical and prognostic context. The accessible exact trial evidence does not verify a positive oil-replacement coronary-event crossing; older positive trial reports remain inaccessible at primary-result depth. LA-rich oils were not silently redefined as chemically pure LA, and ALA-containing oils are not excluded simply because they contain ALA. Whole-diet or smoking cointerventions and shared metabolic instruments retain explicit limits. Weakest-link returns Α for carnivore superiority; primary-subclaim and scope-matched return Γ. The verdict does not endorse a blanket seed-oil-harm claim or suggest saturated fat or carnivore diets are clinically superior.", "aggregation_alternatives": { "weakest_link_would_return": "Α", "primary_subclaim_would_return": "Γ", "scope_matched_would_return": "Γ", "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": "M4", "is_nominal": false, "name": "Food-pattern and cointervention programmes improve coronary outcomes", "core_claim": "A dietary pattern together with relevant behaviour change can reduce coronary events without demonstrating an isolated LA-rich oil mechanism.", "explains_what_nominal_does_not": "A dietary pattern together with relevant behaviour change can reduce coronary events without demonstrating an isolated LA-rich oil mechanism.", "strongest_supporting_evidence": [ "Randomized Lyon (PMID7911176) and Oslo diet-antismoking (PMID6118715) programmes show clinical event reductions in their baseline-defined populations, with long-term follow-up PMID26924204." ], "strongest_contradictory_evidence": [ "These programmes alter multiple foods or smoking, and their clinical success cannot identify the oil replacement component or a universal diet optimum." ], "hsef_level_for_this_model": "Ε", "rationale": "Randomized Lyon (PMID7911176) and Oslo diet-antismoking (PMID6118715) programmes show clinical event reductions in their baseline-defined populations, with long-term follow-up PMID26924204. These programmes alter multiple foods or smoking, and their clinical success cannot identify the oil replacement component or a universal diet optimum." }, { "rank_in_tournament": 2, "model_id": "M3", "is_nominal": false, "name": "Other lipid species and non-LDL pathways affect clinical response", "core_claim": "Specific non-LA lipid exposures can modify coronary outcomes even when LDLchanges do not differ, providing an alternative explanation for mixed-oil programme results.", "explains_what_nominal_does_not": "Specific non-LA lipid exposures can modify coronary outcomes even when LDLchanges do not differ, providing an alternative explanation for mixed-oil programme results.", "strongest_supporting_evidence": [ "JELIS (PMID17398308) provides a positive allocated EPAclinical adjunct with the same statin-associated LDLfall, while Lyon's multi-fat diet (PMID7911176) reduced events without a serum-lipid difference." ], "strongest_contradictory_evidence": [ "The inference is restricted to defined EPAadjunct and bundled diet contexts; it does not prove that ALA rather than LA explains every older trial or that LDLis causally irrelevant." ], "hsef_level_for_this_model": "Ε", "rationale": "JELIS (PMID17398308) provides a positive allocated EPAclinical adjunct with the same statin-associated LDLfall, while Lyon's multi-fat diet (PMID7911176) reduced events without a serum-lipid difference. The inference is restricted to defined EPAadjunct and bundled diet contexts; it does not prove that ALA rather than LA explains every older trial or that LDLis causally irrelevant." }, { "rank_in_tournament": 3, "model_id": "M2", "is_nominal": false, "name": "Composition, implementation and baseline context explain discordance", "core_claim": "Oil constituents, food matrices, trans fat, adherence and baseline disease affect the net result of a nominal fat replacement.", "explains_what_nominal_does_not": "Oil constituents, food matrices, trans fat, adherence and baseline disease affect the net result of a nominal fat replacement.", "strongest_supporting_evidence": [ "Minnesota and Sydney original Methods identify different historical exposures and implementation, DIVASdocuments achieved replacement (PMID24717370), and coconut-butter-olive and rice-bran-sunflower trials (PMID29511019,16483027) show composition-sensitive markers." ], "strongest_contradictory_evidence": [ "These explanatory factors were not factorially isolated against coronary outcomes across the old trials; retrospective explanations cannot erase their null or adverse results." ], "hsef_level_for_this_model": "Γ", "rationale": "Minnesota and Sydney original Methods identify different historical exposures and implementation, DIVASdocuments achieved replacement (PMID24717370), and coconut-butter-olive and rice-bran-sunflower trials (PMID29511019,16483027) show composition-sensitive markers. These explanatory factors were not factorially isolated against coronary outcomes across the old trials; retrospective explanations cannot erase their null or adverse results." }, { "rank_in_tournament": 4, "model_id": "M1", "is_nominal": true, "name": "LA-rich oil replacement reduces coronary events", "core_claim": "Replacing saturated fat with specified LA-rich oil causally lowers coronary-event incidence over at least one year.", "explains_what_nominal_does_not": "Replacing saturated fat with specified LA-rich oil causally lowers coronary-event incidence over at least one year.", "strongest_supporting_evidence": [ "Controlled feeding lipid changes (PMID26016869), positive substitution associations (PMID26429077), and some genetic support (PMID33924952) favour the hypothesis." ], "strongest_contradictory_evidence": [ "Accessible exact clinical trials are null or adverse, and old positive clinical scans were inaccessible; nonrandomized hospital periods and bundled diet programmes cannot silently supply exact-source verification." ], "hsef_level_for_this_model": "Γ", "rationale": "Controlled feeding lipid changes (PMID26016869), positive substitution associations (PMID26429077), and some genetic support (PMID33924952) favour the hypothesis. Accessible exact clinical trials are null or adverse, and old positive clinical scans were inaccessible; nonrandomized hospital periods and bundled diet programmes cannot silently supply exact-source verification." } ], "tournament_summary": "Descriptive comparison; does not modify the nominal score. Lyon's randomized clinical report (PMID7911176) separates a documented whole-pattern clinical benefit from an assumed LDL-mediated LA-rich oil benefit: events decreased while serum lipids stayed similar and LAintake fell. It does not prove LAharm, because other food and fatty-acid components changed simultaneously.", "study_separating_rank1_from_rank2": "Lyon's randomized clinical report (PMID7911176) separates a documented whole-pattern clinical benefit from an assumed LDL-mediated LA-rich oil benefit: events decreased while serum lipids stayed similar and LAintake fell. It does not prove LAharm, because other food and fatty-acid components changed simultaneously.", "nominal_wins_only_by_funding_artifact": false, "level_unchanged_by_tournament": true }, "evidence_inventory": [ { "n": 1, "pmid": "7754988", "title": "Cretan Mediterranean diet for prevention of coronary heart disease.", "citation": "Renaud S, de Lorgeril M, Delaye J et al. Cretan Mediterranean diet for prevention of coronary heart disease. The American journal of clinical nutrition. 1995.", "doi": "10.1093/ajcn/61.6.1360S", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/7754988/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/7754988/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Lyon_Diet_Heart_605", "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": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "The Lyon secondary-prevention randomized dietary programme substantially reduced recurrent coronary events while lowering saturated fat and linoleic acid and increasing oleic and alpha-linolenic acids.", "what_it_does_not_show": "This is a multicomponent Mediterranean dietary contrast, not isocaloric saturated-fat replacement by linoleic-rich oils; it overlaps the parent trial reported in PMID7911176.", "confounders_present": [ "This is a multicomponent Mediterranean dietary contrast, not isocaloric saturated-fat replacement by linoleic-rich oils; it overlaps the parent trial reported in PMID7911176." ], "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": 2, "pmid": "7911176", "title": "Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease.", "citation": "de Lorgeril M, Renaud S, Mamelle N et al. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet (London, England). 1994.", "doi": "10.1016/s0140-6736(94)92580-1", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/7911176/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/7911176/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "ErratumIn: PMID not supplied" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Lyon_Diet_Heart_605", "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": [ "M4", "M3" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "In605post-infarct patients, the randomized Mediterranean alpha-linolenic-rich diet reduced cardiac death or nonfatal infarction over about27months without a serum-lipid difference.", "what_it_does_not_show": "Linoleic intake was lower, not higher, and many food and fatty-acid changes were bundled; the attached erratum's identifier and details were not supplied, and this is the same Lyon trial as PMID7754988.", "confounders_present": [ "Linoleic intake was lower, not higher, and many food and fatty-acid changes were bundled; the attached erratum's identifier and details were not supplied, and this is the same Lyon trial as PMID7754988." ], "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": 3, "pmid": "30571417", "title": "APOE and the Association of Fatty Acids With the Risk of Stroke, Coronary Heart Disease, and Mortality.", "citation": "Satizabal CL, Samieri C, Davis-Plourde KL et al. APOE and the Association of Fatty Acids With the Risk of Stroke, Coronary Heart Disease, and Mortality. Stroke. 2018.", "doi": "10.1161/STROKEAHA.118.022132", "pmcid": "PMC6310220", "url": "https://pubmed.ncbi.nlm.nih.gov/30571417/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30571417/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Framingham_and_3C_fatty_acid_cohorts", "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 observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Prospective fatty-acid measurements in two older-adult cohorts associated higher linoleic acid with lower stroke and mortality among APOEepsilon4carriers.", "what_it_does_not_show": "The exploratory genotype subgroup and measured plasma exposure are not randomized isocaloric replacement; the reported linoleic benefits were stroke and mortality rather than isolated coronary events.", "confounders_present": [ "The exploratory genotype subgroup and measured plasma exposure are not randomized isocaloric replacement; the reported linoleic benefits were stroke and mortality rather than isolated coronary events." ], "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": 4, "pmid": "1973470", "title": "Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial.", "citation": "Ornish D, Brown SE, Scherwitz LW et al. Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial. Lancet (London, England). 1990.", "doi": "10.1016/0140-6736(90)91656-u", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/1973470/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/1973470/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID1973470", "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", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "A48-patient randomized comprehensive lifestyle programme showed coronary-angiographic regression after one year compared with usual care.", "what_it_does_not_show": "Vegetarian diet, smoking cessation, exercise and stress management were bundled; angiographic lesions are not coronary events and no carnivore comparator or isolated linoleic replacement was tested.", "confounders_present": [ "Vegetarian diet, smoking cessation, exercise and stress management were bundled; angiographic lesions are not coronary events and no carnivore comparator or isolated linoleic replacement was tested." ], "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": 5, "pmid": "17398308", "title": "Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.", "citation": "Yokoyama M, Origasa H, Matsuzaki M et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet (London, England). 2007.", "doi": "10.1016/S0140-6736(07)60527-3", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/17398308/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/17398308/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "ErratumIn: PMID not supplied" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID17398308", "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": [ "M3" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "JELIS randomized18645Japanese hypercholesterolemic patients to EPA plus statin or statin alone and reduced the composite major-coronary endpoint over4.6years.", "what_it_does_not_show": "This omega3 pharmacological adjunct is a composition-confounding comparator, not saturated-fat replacement by linoleic oils; coronary mortality did not differ, open-label treatment matters, and an attached unspecified erratum is flagged.", "confounders_present": [ "This omega3 pharmacological adjunct is a composition-confounding comparator, not saturated-fat replacement by linoleic oils; coronary mortality did not differ, open-label treatment matters, and an attached unspecified erratum is flagged." ], "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": 6, "pmid": "34372670", "title": "Mediterranean Diet Reduces Atherosclerosis Progression in Coronary Heart Disease: An Analysis of the CORDIOPREV Randomized Controlled Trial.", "citation": "Jimenez-Torres J, Alcalá-Diaz JF, Torres-Peña JD et al. Mediterranean Diet Reduces Atherosclerosis Progression in Coronary Heart Disease: An Analysis of the CORDIOPREV Randomized Controlled Trial. Stroke. 2021.", "doi": "10.1161/STROKEAHA.120.033214", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/34372670/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34372670/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "ErratumIn: PMID34694867" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID34372670", "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", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "CORDIOPREV secondary analysis associated Mediterranean allocation with improved carotid thickness and plaque measures versus low-fat allocation over five to seven years.", "what_it_does_not_show": "Carotid morphology is a surrogate and extra-virgin olive oil is predominantly monounsaturated; this does not isolate linoleic replacement or establish carnivore superiority, and erratum PMID34694867 attaches to the parent report.", "confounders_present": [ "Carotid morphology is a surrogate and extra-virgin olive oil is predominantly monounsaturated; this does not isolate linoleic replacement or establish carnivore superiority, and erratum PMID34694867 attaches to the parent report." ], "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": "29511019", "title": "Randomised trial of coconut oil, olive oil or butter on blood lipids and other cardiovascular risk factors in healthy men and women.", "citation": "Khaw KT, Sharp SJ, Finikarides L et al. Randomised trial of coconut oil, olive oil or butter on blood lipids and other cardiovascular risk factors in healthy men and women. BMJ open. 2018.", "doi": "10.1136/bmjopen-2017-020167", "pmcid": "PMC5855206", "url": "https://pubmed.ncbi.nlm.nih.gov/29511019/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29511019/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID29511019", "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": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "A94-person randomized four-week butter, coconut or olive-oil study found higher LDLcholesterol with butter, while coconut and olive oils did not differ significantly.", "what_it_does_not_show": "These oils were not linoleic-rich and consumption could supplement rather than replace food isocalorically; food-specific biomarker effects cannot substitute for coronary-event benefit.", "confounders_present": [ "These oils were not linoleic-rich and consumption could supplement rather than replace food isocalorically; food-specific biomarker effects cannot substitute for coronary-event 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": false, "decisive_test_note": "", "shared_components": [] }, { "n": 8, "pmid": "32209700", "title": "Dietary Fats and Atherosclerosis From Childhood to Adulthood.", "citation": "Laitinen TT, Nuotio J, Rovio SP et al. Dietary Fats and Atherosclerosis From Childhood to Adulthood. Pediatrics. 2020.", "doi": "10.1542/peds.2019-2786", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/32209700/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32209700/", "tier": "A", "source_tier": "A", "kind": "secondary_analysis", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "STRIP_NCT00223600", "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": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "A secondary STRIP analysis linked achieving a childhood dietary-fat target with more favourable aortic thickness and distensibility through young adulthood.", "what_it_does_not_show": "The analysed exposure was achieved diet rather than randomized allocation, with a surrogate endpoint and mostly pediatric horizon; it does not establish adult coronary-event causation or isolated linoleic replacement.", "confounders_present": [ "The analysed exposure was achieved diet rather than randomized allocation, with a surrogate endpoint and mostly pediatric horizon; it does not establish adult coronary-event causation or isolated linoleic replacement." ], "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": 9, "pmid": "1484945", "title": "Dietary management of patients with familial hypercholesterolaemia treated with simvastatin.", "citation": "Chisholm A, Mann J, Sutherland W et al. Dietary management of patients with familial hypercholesterolaemia treated with simvastatin. The Quarterly journal of medicine. 1992.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/1484945/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/1484945/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID1484945", "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": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "A19-person randomized crossover found lower LDL-related plasma cholesterol under a lower-fat diet despite concurrent simvastatin for familial hypercholesterolemia.", "what_it_does_not_show": "The dietary contrast was not isolated isocaloric linoleic substitution; lipid lowering in a familial clinical population is not an observed coronary-event endpoint.", "confounders_present": [ "The dietary contrast was not isolated isocaloric linoleic substitution; lipid lowering in a familial clinical population is not an observed coronary-event 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": false, "decisive_test_note": "", "shared_components": [] }, { "n": 10, "pmid": "1431574", "title": "Effect of dietary cis and trans fatty acids on serum lipoprotein[a] levels in humans.", "citation": "Mensink RP, Zock PL, Katan MB et al. Effect of dietary cis and trans fatty acids on serum lipoprotein[a] levels in humans. Journal of lipid research. 1992.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/1431574/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/1431574/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID1431574", "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": "Three controlled feeding experiments compared saturated, cis-unsaturated and trans-unsaturated fat effects on lipoproteina, with markedly higher values under trans exposure.", "what_it_does_not_show": "The abstract is publisher-truncated before the linoleic arm's full results; the exposure was short and a lipid marker, so results cannot demonstrate long-term coronary harm from usual linoleic oils.", "confounders_present": [ "The abstract is publisher-truncated before the linoleic arm's full results; the exposure was short and a lipid marker, so results cannot demonstrate long-term coronary harm from usual linoleic oils." ], "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": 11, "pmid": "28864332", "title": "Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study.", "citation": "Dehghan M, Mente A, Zhang X et al. Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study. Lancet (London, England). 2017.", "doi": "10.1016/S0140-6736(17)32252-3", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/28864332/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28864332/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID28864332", "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", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "PURE associated higher carbohydrate intake with mortality while fat classes were not significantly associated with myocardial infarction or cardiovascular mortality across18countries.", "what_it_does_not_show": "Diet was observational and nutritional adequacy, socioeconomic context and replacement foods differ; neither a null saturated-fat association nor lower all-cause mortality establishes carnivore superiority or a randomized linoleic substitution effect.", "confounders_present": [ "Diet was observational and nutritional adequacy, socioeconomic context and replacement foods differ; neither a null saturated-fat association nor lower all-cause mortality establishes carnivore superiority or a randomized linoleic substitution 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": false, "decisive_test_note": "", "shared_components": [] }, { "n": 12, "pmid": "32188587", "title": "Associations of fat and carbohydrate intake with cardiovascular disease and mortality: prospective cohort study of UK Biobank participants.", "citation": "Ho FK, Gray SR, Welsh P et al. Associations of fat and carbohydrate intake with cardiovascular disease and mortality: prospective cohort study of UK Biobank participants. BMJ (Clinical research ed.). 2020.", "doi": "10.1136/bmj.m688", "pmcid": "PMC7190059", "url": "https://pubmed.ncbi.nlm.nih.gov/32188587/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32188587/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "ErratumIn: PMID32371385" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "UKBiobank_dietary_analysis", "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 observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "UKBiobank dietary analysis found nonlinear macronutrient-mortality associations, including different estimated risks at moderate versus high polyunsaturated-fat intakes.", "what_it_does_not_show": "Diet questionnaires, selection and residual confounding prevent treating macronutrient curves as causal replacement-dose rules; erratum PMID32371385 attaches and coronary events differ from total mortality.", "confounders_present": [ "Diet questionnaires, selection and residual confounding prevent treating macronutrient curves as causal replacement-dose rules; erratum PMID32371385 attaches and coronary events differ from total mortality." ], "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": 13, "pmid": "26429077", "title": "Saturated Fats Compared With Unsaturated Fats and Sources of Carbohydrates in Relation to Risk of Coronary Heart Disease: A Prospective Cohort Study.", "citation": "Li Y, Hruby A, Bernstein AM et al. Saturated Fats Compared With Unsaturated Fats and Sources of Carbohydrates in Relation to Risk of Coronary Heart Disease: A Prospective Cohort Study. Journal of the American College of Cardiology. 2015.", "doi": "10.1016/j.jacc.2015.07.055", "pmcid": "PMC4593072", "url": "https://pubmed.ncbi.nlm.nih.gov/26429077/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26429077/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID26429077", "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": [ "M1" ], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "NHS and HPFS prospective substitution models associated replacing5%energy saturated fat with PUFA with25%lower coronary risk; refined carbohydrate replacement was not beneficial.", "what_it_does_not_show": "Modelled substitution is not assigned isocaloric replacement and PUFA composition and healthy-behaviour confounding remain; these repeated cohorts are not independent randomized fatty-acid lines.", "confounders_present": [ "Modelled substitution is not assigned isocaloric replacement and PUFA composition and healthy-behaviour confounding remain; these repeated cohorts are not independent randomized fatty-acid lines." ], "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": 14, "pmid": "35422138", "title": "Deep Lipidomics in Human Plasma: Cardiometabolic Disease Risk and Effect of Dietary Fat Modulation.", "citation": "Eichelmann F, Sellem L, Wittenbecher C et al. Deep Lipidomics in Human Plasma: Cardiometabolic Disease Risk and Effect of Dietary Fat Modulation. Circulation. 2022.", "doi": "10.1161/CIRCULATIONAHA.121.056805", "pmcid": "PMC9241667", "url": "https://pubmed.ncbi.nlm.nih.gov/35422138/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35422138/", "tier": "A", "source_tier": "A", "kind": "trial_and_cohort_original_lipidomics", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "DIVAS_NCT01478958_EPICPotsdam", "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": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "EPICPotsdam lipidomics associated selected lipids with incident disease, and the16-week DIVAS randomized dietary-fat modification changed several risk-associated lipid species favourably.", "what_it_does_not_show": "The diet contained mixed monounsaturated and omega6fats; connecting biomarker changes to a separate cohort's events does not demonstrate coronary-event prevention or mediator necessity.", "confounders_present": [ "The diet contained mixed monounsaturated and omega6fats; connecting biomarker changes to a separate cohort's events does not demonstrate coronary-event prevention or mediator necessity." ], "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": [ "Shared DIVAS lipidomic subgroup and EPICPotsdam event case-cohorts with PMID37062359." ] }, { "n": 15, "pmid": "38578269", "title": "Higher ratio of plasma omega-6/omega-3 fatty acids is associated with greater risk of all-cause, cancer, and cardiovascular mortality: A population-based cohort study in UK Biobank.", "citation": "Zhang Y, Sun Y, Yu Q et al. Higher ratio of plasma omega-6/omega-3 fatty acids is associated with greater risk of all-cause, cancer, and cardiovascular mortality: A population-based cohort study in UK Biobank. eLife. 2024.", "doi": "10.7554/eLife.90132", "pmcid": "PMC10997328", "url": "https://pubmed.ncbi.nlm.nih.gov/38578269/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38578269/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "UpdateOf: PMID36711941" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "UKBiobank_PUFA_biomarkers", "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 observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "UKBiobank associated a higher plasma omega6-to-omega3ratio with mortality, while each fatty-acid class individually associated inversely with mortality and omega3had the stronger association.", "what_it_does_not_show": "A ratio can rise through reduced omega3and does not identify omega6toxicity; circulating proportions and mortality are not randomized usual-exposure inflammatory harm, and UpdateOf PMID36711941 is attached without an extra primary row.", "confounders_present": [ "A ratio can rise through reduced omega3and does not identify omega6toxicity; circulating proportions and mortality are not randomized usual-exposure inflammatory harm, and UpdateOf PMID36711941 is attached without an extra primary row." ], "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": 16, "pmid": "27234460", "title": "Polyunsaturated fats, carbohydrates and carotid disease: The Atherosclerosis Risk in Communities (ARIC) Carotid MRI study.", "citation": "Dearborn JL, Qiao Y, Guallar E et al. Polyunsaturated fats, carbohydrates and carotid disease: The Atherosclerosis Risk in Communities (ARIC) Carotid MRI study. Atherosclerosis. 2016.", "doi": "10.1016/j.atherosclerosis.2016.05.024", "pmcid": "PMC5094848", "url": "https://pubmed.ncbi.nlm.nih.gov/27234460/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/27234460/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID27234460", "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 observational", "decisive_perturbation": false, "endogenous": false, "direction": "null", "what_it_shows": "The ARIC carotidMRI study found no independent association of PUFA intake or glycemic index with high-risk plaque features after vascular-risk adjustment.", "what_it_does_not_show": "Questionnaire exposure, selected attendees and surrogate plaques do not test randomized coronary events; a surrogate null does not refute every dietary replacement effect.", "confounders_present": [ "Questionnaire exposure, selected attendees and surrogate plaques do not test randomized coronary events; a surrogate null does not refute every dietary replacement 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": false, "decisive_test_note": "", "shared_components": [] }, { "n": 17, "pmid": "29397160", "title": "Effect of Dietary Counseling on a Comprehensive Metabolic Profile from Childhood to Adulthood.", "citation": "Lehtovirta M, Pahkala K, Niinikoski H et al. Effect of Dietary Counseling on a Comprehensive Metabolic Profile from Childhood to Adulthood. The Journal of pediatrics. 2018.", "doi": "10.1016/j.jpeds.2017.11.057", "pmcid": "PMC5864506", "url": "https://pubmed.ncbi.nlm.nih.gov/29397160/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29397160/", "tier": "A", "source_tier": "A", "kind": "secondary_analysis", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "STRIP_NCT00223600", "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": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Repeated randomized STRIP counselling lowered saturated intake and LDL-related lipid measures while increasing circulating omega3and omega6proportions from childhood through young adulthood.", "what_it_does_not_show": "Multiple dietary changes and a pediatric horizon limit isolated adult linoleic-oil inference; the shared STRIP cohort and biomarkers are not a separate coronary-event trial.", "confounders_present": [ "Multiple dietary changes and a pediatric horizon limit isolated adult linoleic-oil inference; the shared STRIP cohort and biomarkers are not a separate coronary-event 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": false, "decisive_test_note": "", "shared_components": [] }, { "n": 18, "pmid": "2643423", "title": "Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota Coronary Survey.", "citation": "Frantz ID, Dawson EA, Ashman PL et al. Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota Coronary Survey. Arteriosclerosis (Dallas, Tex.). 1989.", "doi": "10.1161/01.atv.9.1.129", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/2643423/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/2643423/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Minnesota_Coronary_Experiment", "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": [ "M2" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "null", "what_it_shows": "The original Minnesota randomized institutional trial lowered serum cholesterol but found no overall cardiovascular-event, cardiovascular-death or total-mortality difference.", "what_it_does_not_show": "Mean dietary exposure was384days despite a4.5-year trial and many short stays; intervention changed dietary cholesterol and historical fat sources, and later recovered reports share this trial.", "confounders_present": [ "Mean dietary exposure was384days despite a4.5-year trial and many short stays; intervention changed dietary cholesterol and historical fat sources, and later recovered reports share this 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": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 19, "pmid": "8506889", "title": "Response to a cholesterol-lowering diet: efficacy is greater in hypercholesterolemic subjects even after adjustment for regression to the mean.", "citation": "Denke MA, Frantz ID. Response to a cholesterol-lowering diet: efficacy is greater in hypercholesterolemic subjects even after adjustment for regression to the mean. The American journal of medicine. 1993.", "doi": "10.1016/0002-9343(93)90215-b", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/8506889/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/8506889/", "tier": "A", "source_tier": "A", "kind": "secondary_analysis", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Minnesota_Coronary_Experiment", "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": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "A Minnesota subgroup analysis using repeated measurements found greater cholesterol reduction with higher baseline cholesterol after adjusting for regression to the mean.", "what_it_does_not_show": "This same-trial lipid response does not demonstrate coronary benefit or identify outcome-defined responders; single baseline measurements can exaggerate apparent subgroup response.", "confounders_present": [ "This same-trial lipid response does not demonstrate coronary benefit or identify outcome-defined responders; single baseline measurements can exaggerate apparent subgroup response." ], "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": "758101", "title": "Effect of cholesterol-lowering diet on mortality from coronary heart disease and other causes.", "citation": "Turpeinen O. Effect of cholesterol-lowering diet on mortality from coronary heart disease and other causes. Circulation. 1979.", "doi": "10.1161/01.cir.59.1.1", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/758101/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/758101/", "tier": "A", "source_tier": "A", "kind": "secondary_report", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Finnish_Mental_Hospital_periods", "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": "natural experiment", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "The Finnish two-hospital dietary intervention associated replacement of dairy fats with vegetable oils with lower male coronary mortality over its12-year crossover.", "what_it_does_not_show": "Hospital-period allocation, institutional medication and population changes can confound the result; this is a report from the same Finnish study as PMID393644 and6840954 rather than individual randomization.", "confounders_present": [ "Hospital-period allocation, institutional medication and population changes can confound the result; this is a report from the same Finnish study as PMID393644 and6840954 rather than individual randomization." ], "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": "393644", "title": "Dietary prevention of coronary heart disease: the Finnish Mental Hospital Study.", "citation": "Turpeinen O, Karvonen MJ, Pekkarinen M et al. Dietary prevention of coronary heart disease: the Finnish Mental Hospital Study. International journal of epidemiology. 1979.", "doi": "10.1093/ije/8.2.99", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/393644/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/393644/", "tier": "A", "source_tier": "A", "kind": "controlled_hospital_period_intervention", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Finnish_Mental_Hospital_periods", "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": [ "M1", "M2" ], "evidence_class": "Moderate", "system": "natural experiment", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "The Finnish two-hospital crossover found about half the male electrocardiographic-coronary or coronary-death incidence during lower-saturated higher-polyunsaturated dietary periods.", "what_it_does_not_show": "Although metadata labels randomized trial, the described allocation is hospital-period diet reversal and should not be treated as patient randomization; mixed dietary changes and historical context restrict isolated linoleic inference.", "confounders_present": [ "Although metadata labels randomized trial, the described allocation is hospital-period diet reversal and should not be treated as patient randomization; mixed dietary changes and historical context restrict isolated linoleic inference." ], "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": 22, "pmid": "6840954", "title": "Dietary prevention of coronary heart disease in women: the Finnish mental hospital study.", "citation": "Miettinen M, Turpeinen O, Karvonen MJ et al. Dietary prevention of coronary heart disease in women: the Finnish mental hospital study. International journal of epidemiology. 1983.", "doi": "10.1093/ije/12.1.17", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/6840954/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/6840954/", "tier": "A", "source_tier": "A", "kind": "controlled_hospital_period_intervention", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Finnish_Mental_Hospital_periods", "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": "natural experiment", "decisive_perturbation": true, "endogenous": true, "direction": "null", "what_it_shows": "The Finnish women's hospital-period intervention lowered cholesterol and coronary incidence estimates, but the coronary difference was not statistically significant.", "what_it_does_not_show": "Shared hospital-period design and possible medication or population changes limit inference; nonsignificance is not proof of equivalence, and male/female reports are grouped under one parent study.", "confounders_present": [ "Shared hospital-period design and possible medication or population changes limit inference; nonsignificance is not proof of equivalence, and male/female reports are grouped under one parent study." ], "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": 23, "pmid": "38714425", "title": "Dietary n-3 alpha-linolenic and n-6 linoleic acids modestly lower serum lipoprotein(a) concentration but differentially influence other atherogenic lipoprotein traits: A randomized trial.", "citation": "Nuotio P, Lankinen MA, Meuronen T et al. Dietary n-3 alpha-linolenic and n-6 linoleic acids modestly lower serum lipoprotein(a) concentration but differentially influence other atherogenic lipoprotein traits: A randomized trial. Atherosclerosis. 2024.", "doi": "10.1016/j.atherosclerosis.2024.117562", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38714425/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38714425/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID38714425", "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": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "An118-man randomized oil comparison lowered lipoproteina under both linoleic-rich sunflower and alpha-linolenic-rich Camelina diets, with larger LDL-related reductions under the latter.", "what_it_does_not_show": "There was no retained saturated-fat comparator and no coronary outcomes; FADSgenotype did not modify the lipid response, so metabolic genotype assumptions cannot be treated as established mediation.", "confounders_present": [ "There was no retained saturated-fat comparator and no coronary outcomes; FADSgenotype did not modify the lipid response, so metabolic genotype assumptions cannot be treated as established mediation." ], "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": 24, "pmid": "24550191", "title": "Overfeeding polyunsaturated and saturated fat causes distinct effects on liver and visceral fat accumulation in humans.", "citation": "Rosqvist F, Iggman D, Kullberg J et al. Overfeeding polyunsaturated and saturated fat causes distinct effects on liver and visceral fat accumulation in humans. Diabetes. 2014.", "doi": "10.2337/db13-1622", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/24550191/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/24550191/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "LIPOGAIN_NCT01427140", "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": "contradicts", "what_it_shows": "The39-person LIPOGAIN randomized overfeeding trial found greater liver and visceral-fat accumulation with palm-oil muffins than sunflower-oil muffins despite similar weight gain.", "what_it_does_not_show": "This is an excess-energy context and ectopic-fat or body-composition outcomes, not usual-intake inflammatory coronary harm or an isocaloric clinical-event trial.", "confounders_present": [ "This is an excess-energy context and ectopic-fat or body-composition outcomes, not usual-intake inflammatory coronary harm or an isocaloric clinical-event 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": false, "decisive_test_note": "", "shared_components": [] }, { "n": 25, "pmid": "33693945", "title": "Glu298Asp (rs1799983) Polymorphism Influences Postprandial Vascular Reactivity and the Insulin Response to Meals of Varying Fat Composition in Postmenopausal Women: Findings from the Randomized, Controlled Dietary Intervention and VAScular function (DIVAS)-2 Study.", "citation": "Rathnayake KM, Weech M, Lovegrove JA et al. Glu298Asp (rs1799983) Polymorphism Influences Postprandial Vascular Reactivity and the Insulin Response to Meals of Varying Fat Composition in Postmenopausal Women: Findings from the Randomized, Controlled Dietary Intervention and VAScular function (DIVAS)-2 Study. The Journal of nutrition. 2021.", "doi": "10.1093/jn/nxaa394", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33693945/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33693945/", "tier": "A", "source_tier": "A", "kind": "secondary_analysis", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "DIVAS2_NCT02144454", "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 interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "A32-woman DIVAS2postprandial crossover found selected genotype-dependent vascular and insulin responses to saturated, monounsaturated and omega6meals.", "what_it_does_not_show": "Genotyping was retrospective, the interaction was not consistent across absolute and incremental vascular measures, and acute biomarkers do not establish clinically important inflammatory cardiovascular harm.", "confounders_present": [ "Genotyping was retrospective, the interaction was not consistent across absolute and incremental vascular measures, and acute biomarkers do not establish clinically important inflammatory cardiovascular harm." ], "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": 26, "pmid": "28275132", "title": "Impact of polyunsaturated and saturated fat overfeeding on the DNA-methylation pattern in human adipose tissue: a randomized controlled trial.", "citation": "Perfilyev A, Dahlman I, Gillberg L et al. Impact of polyunsaturated and saturated fat overfeeding on the DNA-methylation pattern in human adipose tissue: a randomized controlled trial. The American journal of clinical nutrition. 2017.", "doi": "10.3945/ajcn.116.143164", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/28275132/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28275132/", "tier": "A", "source_tier": "A", "kind": "secondary_analysis", "status_flags": [ "ErratumIn: PMID28673906" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "LIPOGAIN_NCT01427140", "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 interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "A LIPOGAIN secondary randomized-overfeeding analysis found distinct adipose methylation changes after saturated and omega6fat excess, including shared overfeeding effects.", "what_it_does_not_show": "Gene methylation is not evidence of clinical inflammation or coronary injury; the same parent trial is grouped and erratum PMID28673906 attaches without another primary row.", "confounders_present": [ "Gene methylation is not evidence of clinical inflammation or coronary injury; the same parent trial is grouped and erratum PMID28673906 attaches without another primary row." ], "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": 27, "pmid": "29741564", "title": "Replacement of dietary saturated fat with unsaturated fats increases numbers of circulating endothelial progenitor cells and decreases numbers of microparticles: findings from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study.", "citation": "Weech M, Altowaijri H, Mayneris-Perxachs J et al. Replacement of dietary saturated fat with unsaturated fats increases numbers of circulating endothelial progenitor cells and decreases numbers of microparticles: findings from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study. The American journal of clinical nutrition. 2018.", "doi": "10.1093/ajcn/nqy018", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/29741564/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29741564/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "DIVAS_NCT01478958", "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": "contradicts", "what_it_shows": "Sixteen-week isoenergetic DIVASreplacement with omega6or monounsaturated fats lowered selected circulating endothelial and platelet microparticles compared with saturated fat.", "what_it_does_not_show": "Novel vascular markers are not clinical events and endothelial-progenitor increases were confined to the monounsaturated arm; this is the same DIVASparent as its lipid and vascular reports.", "confounders_present": [ "Novel vascular markers are not clinical events and endothelial-progenitor increases were confined to the monounsaturated arm; this is the same DIVASparent as its lipid and vascular reports." ], "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": 28, "pmid": "33344496", "title": "Abdominal Fat and Metabolic Health Markers but Not PNPLA3 Genotype Predicts Liver Fat Accumulation in Response to Excess Intake of Energy and Saturated Fat in Healthy Individuals.", "citation": "Rosqvist F, Orho-Melander M, Kullberg J et al. Abdominal Fat and Metabolic Health Markers but Not PNPLA3 Genotype Predicts Liver Fat Accumulation in Response to Excess Intake of Energy and Saturated Fat in Healthy Individuals. Frontiers in nutrition. 2020.", "doi": "10.3389/fnut.2020.606004", "pmcid": "PMC7744344", "url": "https://pubmed.ncbi.nlm.nih.gov/33344496/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33344496/", "tier": "A", "source_tier": "A", "kind": "pooled_secondary_analysis", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "LIPOGAIN1_and2_pooled_SFA_arms", "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": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "A pooled LIPOGAIN1and2secondary analysis associated baseline metabolic characteristics with liver-fat response to saturated-fat overfeeding.", "what_it_does_not_show": "Only the saturated-fat arms were pooled and predictors were observational; overlapping parent trials and hypercaloric exposure do not demonstrate usual linoleic-oil inflammation or harm.", "confounders_present": [ "Only the saturated-fat arms were pooled and predictors were observational; overlapping parent trials and hypercaloric exposure do not demonstrate usual linoleic-oil inflammation or harm." ], "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": [ "Pools only saturated-fat arms from two previous LIPOGAIN studies." ] }, { "n": 29, "pmid": "31369090", "title": "Overeating Saturated Fat Promotes Fatty Liver and Ceramides Compared With Polyunsaturated Fat: A Randomized Trial.", "citation": "Rosqvist F, Kullberg J, Ståhlman M et al. Overeating Saturated Fat Promotes Fatty Liver and Ceramides Compared With Polyunsaturated Fat: A Randomized Trial. The Journal of clinical endocrinology and metabolism. 2019.", "doi": "10.1210/jc.2019-00160", "pmcid": "PMC6839433", "url": "https://pubmed.ncbi.nlm.nih.gov/31369090/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31369090/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "LIPOGAIN2_NCT02211612", "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": "contradicts", "what_it_shows": "LIPOGAIN2randomized61adults to excess-energy palm or sunflower muffins and found higher liver fat, ceramides and atherogenic lipids with saturated fat despite similar weight gain.", "what_it_does_not_show": "The report centres on secondary or exploratory outcomes and excess calories; biomarker and liver-fat differences do not establish coronary-event reduction or universally harmless linoleic oils.", "confounders_present": [ "The report centres on secondary or exploratory outcomes and excess calories; biomarker and liver-fat differences do not establish coronary-event reduction or universally harmless linoleic oils." ], "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": 30, "pmid": "29546297", "title": "Meal Fatty Acids Have Differential Effects on Postprandial Blood Pressure and Biomarkers of Endothelial Function but Not Vascular Reactivity in Postmenopausal Women in the Randomized Controlled Dietary Intervention and VAScular function (DIVAS)-2 Study.", "citation": "Rathnayake KM, Weech M, Jackson KG et al. Meal Fatty Acids Have Differential Effects on Postprandial Blood Pressure and Biomarkers of Endothelial Function but Not Vascular Reactivity in Postmenopausal Women in the Randomized Controlled Dietary Intervention and VAScular function (DIVAS)-2 Study. The Journal of nutrition. 2018.", "doi": "10.1093/jn/nxx042", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/29546297/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29546297/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "DIVAS2_NCT02144454", "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 interventional", "decisive_perturbation": false, "endogenous": true, "direction": "contradicts", "what_it_shows": "DIVAS2randomized meal fat composition produced lower solubleICAM1after omega6meals but no primary flow-mediated-dilatation difference.", "what_it_does_not_show": "An acute endothelial activation marker does not establish long-term clinical inflammation or safety; the primary vascular null and same-trial genotype reanalysis are retained.", "confounders_present": [ "An acute endothelial activation marker does not establish long-term clinical inflammation or safety; the primary vascular null and same-trial genotype reanalysis are 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": false, "decisive_test_note": "", "shared_components": [] }, { "n": 31, "pmid": "26016869", "title": "Replacement of saturated with unsaturated fats had no impact on vascular function but beneficial effects on lipid biomarkers, E-selectin, and blood pressure: results from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study.", "citation": "Vafeiadou K, Weech M, Altowaijri H et al. Replacement of saturated with unsaturated fats had no impact on vascular function but beneficial effects on lipid biomarkers, E-selectin, and blood pressure: results from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study. The American journal of clinical nutrition. 2015.", "doi": "10.3945/ajcn.114.097089", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/26016869/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26016869/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "DIVAS_NCT01478958", "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": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "The195-person16-week isoenergetic DIVAStrial lowered LDLcholesterol with saturated-fat replacement by omega6PUFA, but its primary flow-mediated-dilatation endpoint was null.", "what_it_does_not_show": "Its estimated17-20%mortality reduction was extrapolated from lipid change and was not an observed mortality or coronary-event result; mixed monounsaturated replacement and short follow-up retain scope.", "confounders_present": [ "Its estimated17-20%mortality reduction was extrapolated from lipid change and was not an observed mortality or coronary-event result; mixed monounsaturated replacement and short follow-up retain scope." ], "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": 32, "pmid": "29169396", "title": "Apolipoprotein E gene polymorphism modifies fasting total cholesterol concentrations in response to replacement of dietary saturated with monounsaturated fatty acids in adults at moderate cardiovascular disease risk.", "citation": "Shatwan IM, Weech M, Jackson KG et al. Apolipoprotein E gene polymorphism modifies fasting total cholesterol concentrations in response to replacement of dietary saturated with monounsaturated fatty acids in adults at moderate cardiovascular disease risk. Lipids in health and disease. 2017.", "doi": "10.1186/s12944-017-0606-3", "pmcid": "PMC5701425", "url": "https://pubmed.ncbi.nlm.nih.gov/29169396/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29169396/", "tier": "A", "source_tier": "A", "kind": "secondary_analysis", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "DIVAS_NCT01478958", "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": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "A retrospective DIVASgenotype analysis found one APOEinteraction with cholesterol response under monounsaturated replacement, with other variants null.", "what_it_does_not_show": "Small genotype subgroups and retrospective interactions do not define baseline-validated linoleic responders or add an independent causal line to the shared trial.", "confounders_present": [ "Small genotype subgroups and retrospective interactions do not define baseline-validated linoleic responders or add an independent causal line to the shared 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": false, "decisive_test_note": "", "shared_components": [] }, { "n": 33, "pmid": "26479316", "title": "NMR-based metabolic profiling in healthy individuals overfed different types of fat: links to changes in liver fat accumulation and lean tissue mass.", "citation": "Elmsjö A, Rosqvist F, Engskog MK et al. NMR-based metabolic profiling in healthy individuals overfed different types of fat: links to changes in liver fat accumulation and lean tissue mass. Nutrition & diabetes. 2015.", "doi": "10.1038/nutd.2015.31", "pmcid": "PMC4631933", "url": "https://pubmed.ncbi.nlm.nih.gov/26479316/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26479316/", "tier": "A", "source_tier": "A", "kind": "secondary_analysis", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "LIPOGAIN_NCT01427140", "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": "LIPOGAIN metabolomic reanalysis found a few differential plasma metabolites under saturated versus omega6overfeeding and correlations with fat compartments.", "what_it_does_not_show": "These are candidate metabolic markers, not proven mediators or coronary outcomes; the39participants overlap the original overfeeding report.", "confounders_present": [ "These are candidate metabolic markers, not proven mediators or coronary outcomes; the39participants overlap the original overfeeding report." ], "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": 34, "pmid": "25319187", "title": "Role of dietary fats in modulating cardiometabolic risk during moderate weight gain: a randomized double-blind overfeeding trial (LIPOGAIN study).", "citation": "Iggman D, Rosqvist F, Larsson A et al. Role of dietary fats in modulating cardiometabolic risk during moderate weight gain: a randomized double-blind overfeeding trial (LIPOGAIN study). Journal of the American Heart Association. 2014.", "doi": "10.1161/JAHA.114.001095", "pmcid": "PMC4323808", "url": "https://pubmed.ncbi.nlm.nih.gov/25319187/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/25319187/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "LIPOGAIN_NCT01427140", "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": "LIPOGAIN sunflower versus palm overfeeding improved selected atherogenic lipid ratios, while endothelial activation markers increased with weight gain across both fat arms.", "what_it_does_not_show": "The common excess-energy response cannot be attributed specifically to linoleic acid; shared-trial lipid ratios and acute-risk biomarkers do not establish long-term coronary harm or benefit.", "confounders_present": [ "The common excess-energy response cannot be attributed specifically to linoleic acid; shared-trial lipid ratios and acute-risk biomarkers do not establish long-term coronary harm or 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": false, "decisive_test_note": "", "shared_components": [] }, { "n": 35, "pmid": "37062359", "title": "Replacement of dietary saturated with unsaturated fatty acids is associated with beneficial effects on lipidome metabolites: a secondary analysis of a randomized trial.", "citation": "Sellem L, Eichelmann F, Jackson KG et al. Replacement of dietary saturated with unsaturated fatty acids is associated with beneficial effects on lipidome metabolites: a secondary analysis of a randomized trial. The American journal of clinical nutrition. 2023.", "doi": "10.1016/j.ajcnut.2023.03.024", "pmcid": "PMC10315407", "url": "https://pubmed.ncbi.nlm.nih.gov/37062359/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37062359/", "tier": "A", "source_tier": "A", "kind": "secondary_analysis", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "DIVAS_NCT01478958_EPICPotsdam", "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": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "A DIVASsecondary lipidomic analysis linked dietary-fat-responsive plasma species to incident disease associations in EPICPotsdam.", "what_it_does_not_show": "Different trial and cohort populations and multiple fat changes prevent an identified mediator claim; the same113DIVASsubset and EPICPotsdamcase-cohorts overlap PMID35422138.", "confounders_present": [ "Different trial and cohort populations and multiple fat changes prevent an identified mediator claim; the same113DIVASsubset and EPICPotsdamcase-cohorts overlap PMID35422138." ], "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": 36, "pmid": "31480637", "title": "Impact of the Apolipoprotein E (epsilon) Genotype on Cardiometabolic Risk Markers and Responsiveness to Acute and Chronic Dietary Fat Manipulation.", "citation": "Rathnayake KM, Weech M, Jackson KG et al. Impact of the Apolipoprotein E (epsilon) Genotype on Cardiometabolic Risk Markers and Responsiveness to Acute and Chronic Dietary Fat Manipulation. Nutrients. 2019.", "doi": "10.3390/nu11092044", "pmcid": "PMC6770634", "url": "https://pubmed.ncbi.nlm.nih.gov/31480637/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31480637/", "tier": "A", "source_tier": "A", "kind": "secondary_analysis", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "DIVAS_and_DIVAS2_genotype_reanalysis", "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": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Retrospective DIVASandDIVAS2genotyping associated APOEwith selected baseline markers and exploratory responses, especially under monounsaturated exposure.", "what_it_does_not_show": "Genetic stratification of a shared trial is not Mendelian randomization and requires prospective replication; genotype-marker correlations do not establish linoleic inflammatory harm.", "confounders_present": [ "Genetic stratification of a shared trial is not Mendelian randomization and requires prospective replication; genotype-marker correlations do not establish linoleic inflammatory harm." ], "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": [ "Retrospective combination of DIVAS and DIVAS2 participants, not a new allocation trial." ] }, { "n": 37, "pmid": "28372558", "title": "Fatty acid composition in serum cholesterol esters and phospholipids is linked to visceral and subcutaneous adipose tissue content in elderly individuals: a cross-sectional study.", "citation": "Rosqvist F, Bjermo H, Kullberg J et al. Fatty acid composition in serum cholesterol esters and phospholipids is linked to visceral and subcutaneous adipose tissue content in elderly individuals: a cross-sectional study. Lipids in health and disease. 2017.", "doi": "10.1186/s12944-017-0445-2", "pmcid": "PMC5379570", "url": "https://pubmed.ncbi.nlm.nih.gov/28372558/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28372558/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID28372558", "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": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "contradicts", "what_it_shows": "In287PIVUSolder adults, serum linoleic proportions associated inversely with visceral and other fat depots after covariate adjustment.", "what_it_does_not_show": "Cross-sectional fatty-acid proportions and body-fat surrogates can reflect metabolism and diet, not causal replacement or clinical inflammatory cardiovascular effects.", "confounders_present": [ "Cross-sectional fatty-acid proportions and body-fat surrogates can reflect metabolism and diet, not causal replacement or clinical inflammatory cardiovascular effects." ], "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": 38, "pmid": "24717370", "title": "Development of a food-exchange model to replace saturated fat with MUFAs and n-6 PUFAs in adults at moderate cardiovascular risk.", "citation": "Weech M, Vafeiadou K, Hasaj M et al. Development of a food-exchange model to replace saturated fat with MUFAs and n-6 PUFAs in adults at moderate cardiovascular risk. The Journal of nutrition. 2014.", "doi": "10.3945/jn.114.190645", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/24717370/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/24717370/", "tier": "A", "source_tier": "A", "kind": "original_trial_exposure_adherence_report", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "DIVAS_NCT01478958", "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": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "The195-person DIVASfood-exchange report verified broadly achieved isoenergetic fat-composition targets with little change in other macronutrients or anthropometrics.", "what_it_does_not_show": "This is original adherence and exposure data from the same randomized parent, not a separate coronary-event trial or proof that every individual met the prescription.", "confounders_present": [ "This is original adherence and exposure data from the same randomized parent, not a separate coronary-event trial or proof that every individual met the prescription." ], "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": 39, "pmid": "22492369", "title": "Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial.", "citation": "Bjermo H, Iggman D, Kullberg J et al. Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial. The American journal of clinical nutrition. 2012.", "doi": "10.3945/ajcn.111.030114", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/22492369/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/22492369/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID22492369", "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": [ "M1" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "contradicts", "what_it_shows": "A67-person10-week isocaloric randomized vegetableomega6versus butter trial found lower liver fat and selected inflammatory signalling markers with PUFA, without a proinflammatory or oxidative-stress signal.", "what_it_does_not_show": "Some favourable lipid estimates were restricted to postrandomization compliant participants and cannot define clinical beneficiaries; markers and liver fat are not coronary outcomes or universal safety proof.", "confounders_present": [ "Some favourable lipid estimates were restricted to postrandomization compliant participants and cannot define clinical beneficiaries; markers and liver fat are not coronary outcomes or universal safety proof." ], "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": 40, "pmid": "34934897", "title": "Behavioral Characteristics and Self-Reported Health Status among 2029 Adults Consuming a \"Carnivore Diet\".", "citation": "Lennerz BS, Mey JT, Henn OH et al. Behavioral Characteristics and Self-Reported Health Status among 2029 Adults Consuming a \"Carnivore Diet\". Current developments in nutrition. 2021.", "doi": "10.1093/cdn/nzab133", "pmcid": "PMC8684475", "url": "https://pubmed.ncbi.nlm.nih.gov/34934897/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34934897/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID34934897", "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, 1:Methods:paragraph2, 1:Methods:paragraph3, 1:Methods:paragraph5, 2:Results:paragraph7, 2:Results:paragraph12, 2:Results:paragraph18. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC4" ], "favors_models": [ "M4" ], "evidence_class": "Weak", "system": "human observational", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "A2029-person social-media carnivore survey reported perceived symptom and weight improvements alongside high satisfaction and high LDLcholesterol in a laboratory-reporting subset.", "what_it_does_not_show": "Maintainer recruitment, self-report, missing measurements and no concurrent comparison prevent long-term cardiovascular superiority or clinical event safety conclusions.", "confounders_present": [ "Maintainer recruitment, self-report, missing measurements and no concurrent comparison prevent long-term cardiovascular superiority or clinical event safety conclusions." ], "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": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 41, "pmid": "40385902", "title": "Subjective Experiences and Blood Parameter Changes in Individuals From Germany Following a Self-Conceived \"Carnivore Diet\": An Explorative Study.", "citation": "Klement RJ, Matzat JS. Subjective Experiences and Blood Parameter Changes in Individuals From Germany Following a Self-Conceived \"Carnivore Diet\": An Explorative Study. Cureus. 2025.", "doi": "10.7759/cureus.82521", "pmcid": "PMC12085909", "url": "https://pubmed.ncbi.nlm.nih.gov/40385902/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40385902/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID40385902", "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": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "A24-person exploratory German carnivore study collected before-and-after laboratory reports and perceived benefits, with significantly higher total and LDLcholesterol after adoption.", "what_it_does_not_show": "Self-selected participants, varied diet definitions, short eligibility and uncontrolled cointerventions cannot establish long-term event superiority; favourable triglycerides or HbA1c do not cancel LDL-related uncertainty.", "confounders_present": [ "Self-selected participants, varied diet definitions, short eligibility and uncontrolled cointerventions cannot establish long-term event superiority; favourable triglycerides or HbA1c do not cancel LDL-related uncertainty." ], "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": 42, "pmid": "27071971", "title": "Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73).", "citation": "Ramsden CE, Zamora D, Majchrzak-Hong S et al. Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73). BMJ (Clinical research ed.). 2016.", "doi": "10.1136/bmj.i1246", "pmcid": "PMC4836695", "url": "https://pubmed.ncbi.nlm.nih.gov/27071971/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/27071971/", "tier": "A", "source_tier": "A", "kind": "original_recovered_trial_data", "status_flags": [ "ErratumIn: PMID38942429" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Minnesota_Coronary_Experiment", "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:paragraph6, 1:Methods:paragraph9, 1:Methods:paragraph12, 1:Methods:paragraph18, 1:Methods:paragraph19, 1:Methods:paragraph20, 1:Methods:paragraph30, 1:Methods:paragraph32, 1:Methods:paragraph35, 2:Results:paragraph5, 2:Results:paragraph8, 2:Results:paragraph17, 2:Results:paragraph18, 2:Results:paragraph19, 2:Results:paragraph22. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "Original recovered Minnesotatrial analyses confirmed cholesterol lowering without a reported mortality benefit; selected autopsy files and longitudinal cholesterol-mortality associations challenged a simple marker-to-benefit prediction.", "what_it_does_not_show": "Only the original recovered-data component earns primary credit: full randomized raw data were unavailable and autopsies partly recovered; cholesterol-death association in both arms is not randomized mediator harm, and the examined2024erratumPMID38942429 updates a thesis link rather than study numbers.", "confounders_present": [ "Only the original recovered-data component earns primary credit: full randomized raw data were unavailable and autopsies partly recovered; cholesterol-death association in both arms is not randomized mediator harm, and the examined2024erratumPMID38942429 updates a thesis link rather than study numbers." ], "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": [ "New original recovered analyses share the same Minnesota parent; its meta-analysis is not counted as original evidence." ] }, { "n": 43, "pmid": "23386268", "title": "Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis.", "citation": "Ramsden CE, Zamora D, Leelarthaepin B et al. Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. BMJ (Clinical research ed.). 2013.", "doi": "10.1136/bmj.e8707", "pmcid": "PMC4688426", "url": "https://pubmed.ncbi.nlm.nih.gov/23386268/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/23386268/", "tier": "A", "source_tier": "A", "kind": "original_recovered_trial_data", "status_flags": [ "ErratumIn: PMID not supplied" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID23386268", "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:paragraph1, 1:Methods:paragraph2, 1:Methods:paragraph4, 1:Methods:paragraph5, 1:Methods:paragraph7, 2:Results:paragraph0, 2:Results:paragraph12, 2:Results:paragraph13, 2:Results:paragraph17, 2:Results:paragraph19. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [ "M2" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "contradicts", "what_it_shows": "Original recovered Sydneydata from458post-coronary-event men showed lower cholesterol but higher coronary and cardiovascular mortality under safflower-oil and margarine substitution over median39months.", "what_it_does_not_show": "Only recovered original trial data earns credit, not its meta-analysis; actual all-causeP=.051 was borderline, historical margarine and highLAexposure constrain usual-modern-oil inference, and an unspecified erratum attaches.", "confounders_present": [ "Only recovered original trial data earns credit, not its meta-analysis; actual all-causeP=.051 was borderline, historical margarine and highLAexposure constrain usual-modern-oil inference, and an unspecified erratum attaches." ], "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": [ "New original recovered Sydney participant data are counted; the accompanying meta-analysis is not." ] }, { "n": 44, "pmid": "8192728", "title": "Can linoleic acid contribute to coronary artery disease?", "citation": "Hodgson JM, Wahlqvist ML, Boxall JA et al. Can linoleic acid contribute to coronary artery disease? The American journal of clinical nutrition. 1993.", "doi": "10.1093/ajcn/58.2.228", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/8192728/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/8192728/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID8192728", "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": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "A226-patient coronary-angiography series associated higher adipose and platelet linoleic proportions with more extensive coronary disease.", "what_it_does_not_show": "Cross-sectional referred-patient selection, residual confounding and reverse causation prevent treating this adverse association as randomized oil harm or an identified inflammatory mechanism.", "confounders_present": [ "Cross-sectional referred-patient selection, residual confounding and reverse causation prevent treating this adverse association as randomized oil harm or an identified inflammatory 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": false, "decisive_test_note": "", "shared_components": [] }, { "n": 45, "pmid": "16483027", "title": "Use of rice bran oil in patients with hyperlipidaemia.", "citation": "Kuriyan R, Gopinath N, Vaz M et al. Use of rice bran oil in patients with hyperlipidaemia. The National medical journal of India. 2005.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/16483027/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/16483027/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID16483027", "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": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "A14-person randomized home-use crossover found lower total cholesterol and triglycerides with rice-bran than sunflower oil, while the LDLdifference was nonsignificant.", "what_it_does_not_show": "An oil-versus-oil food-matrix comparison has no saturated-fat arm or coronary endpoint; small unblinded home-use periods cannot attribute differences solely to linoleic content or establish risk reduction.", "confounders_present": [ "An oil-versus-oil food-matrix comparison has no saturated-fat arm or coronary endpoint; small unblinded home-use periods cannot attribute differences solely to linoleic content or establish risk reduction." ], "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": 46, "pmid": "21816117", "title": "Linoleic acid intake, plasma cholesterol and 10-year incidence of CHD in 20,000 middle-aged men and women in the Netherlands.", "citation": "de Goede J, Geleijnse JM, Boer JM et al. Linoleic acid intake, plasma cholesterol and 10-year incidence of CHD in 20,000 middle-aged men and women in the Netherlands. The British journal of nutrition. 2012.", "doi": "10.1017/S0007114511003837", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/21816117/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/21816117/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID21816117", "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 observational", "decisive_perturbation": false, "endogenous": false, "direction": "null", "what_it_shows": "A20069-person Dutch prospective cohort found no linoleic-intake association with coronary incidence over ten years despite a4-5%energy LA-versus-carbohydrate difference.", "what_it_does_not_show": "The replacement comparator was largely carbohydrate rather than saturated fat, and questionnaire exposure and280events limit precision; the null does not establish clinical equivalence of oil replacement.", "confounders_present": [ "The replacement comparator was largely carbohydrate rather than saturated fat, and questionnaire exposure and280events limit precision; the null does not establish clinical equivalence of oil replacement." ], "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": 47, "pmid": "22802735", "title": "Plasma phospholipid fatty acid concentration and incident coronary heart disease in men and women: the EPIC-Norfolk prospective study.", "citation": "Khaw KT, Friesen MD, Riboli E et al. Plasma phospholipid fatty acid concentration and incident coronary heart disease in men and women: the EPIC-Norfolk prospective study. PLoS medicine. 2012.", "doi": "10.1371/journal.pmed.1001255", "pmcid": "PMC3389034", "url": "https://pubmed.ncbi.nlm.nih.gov/22802735/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/22802735/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID22802735", "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 observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "EPICNorfolk baseline plasma phospholipid measurements associated higher omega6fatty-acid concentrations with lower subsequent coronary risk after adjustment.", "what_it_does_not_show": "Measured circulating fats reflect metabolism as well as intake, and heterogeneous individual fatty-acid associations prevent equating totalomega6with a randomized linoleic-rich oil substitution.", "confounders_present": [ "Measured circulating fats reflect metabolism as well as intake, and heterogeneous individual fatty-acid associations prevent equating totalomega6with a randomized linoleic-rich oil substitution." ], "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": 48, "pmid": "5900208", "title": "Composition of lipids in human serum and adipose tissue during prolonged feeding of a diet high in unsaturated fat.", "citation": "Dayton S, Hashimoto S, Dixon W et al. Composition of lipids in human serum and adipose tissue during prolonged feeding of a diet high in unsaturated fat. Journal of lipid research. 1966.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/5900208/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/5900208/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "LA_Veterans_unsaturated_diet", "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": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "The randomized Veterans prolonged-feeding cohort showed lower serum cholesterol and substantial sustained tissue-linoleic enrichment under unsaturated-fat replacement over up to five years.", "what_it_does_not_show": "This original exposure and lipid report does not itself give coronary-event counts; it belongs to the same Veterans parent as its clinical reports and cannot verify a clinical crossing from markers alone.", "confounders_present": [ "This original exposure and lipid report does not itself give coronary-event counts; it belongs to the same Veterans parent as its clinical reports and cannot verify a clinical crossing from markers alone." ], "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": 49, "pmid": "6118715", "title": "Effect of diet and smoking intervention on the incidence of coronary heart disease. Report from the Oslo Study Group of a randomised trial in healthy men.", "citation": "Hjermann I, Velve Byre K, Holme I et al. Effect of diet and smoking intervention on the incidence of coronary heart disease. Report from the Oslo Study Group of a randomised trial in healthy men. Lancet (London, England). 1981.", "doi": "10.1016/s0140-6736(81)91338-6", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/6118715/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/6118715/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Oslo_primary_prevention_diet_antismoking_1232", "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": [ "M4" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "The1232-man randomized Oslo primary-prevention programme reduced first infarction or sudden-death incidence by47%over five years with diet and antismoking advice.", "what_it_does_not_show": "Diet composition, fish, weight control and smoking changes were bundled, so this positive cannot identify the effect of isolated linoleic-rich oil replacement; later follow-up is the same study.", "confounders_present": [ "Diet composition, fish, weight control and smoking changes were bundled, so this positive cannot identify the effect of isolated linoleic-rich oil replacement; later follow-up is the same study." ], "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": 50, "pmid": "26924204", "title": "Lifelong benefits on myocardial infarction mortality: 40-year follow-up of the randomized Oslo diet and antismoking study.", "citation": "Holme I, Retterstøl K, Norum KR et al. Lifelong benefits on myocardial infarction mortality: 40-year follow-up of the randomized Oslo diet and antismoking study. Journal of internal medicine. 2016.", "doi": "10.1111/joim.12485", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/26924204/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26924204/", "tier": "A", "source_tier": "A", "kind": "trial_long_term_followup", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Oslo_primary_prevention_diet_antismoking_1232", "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": [ "M4" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Forty-year follow-up of the randomized Oslo diet-and-antismoking programme found a borderline reduction in first-infarction mortality, with all-cause benefit limited to earlier follow-up.", "what_it_does_not_show": "Long-term events reflect the same bundled intervention and subsequent exposures; it is not an independent oil trial or evidence of lifelong universal mortality benefit.", "confounders_present": [ "Long-term events reflect the same bundled intervention and subsequent exposures; it is not an independent oil trial or evidence of lifelong universal mortality 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": false, "decisive_test_note": "", "shared_components": [ "Forty-year follow-up of the same randomized Oslo diet-antismoking participants." ] }, { "n": 51, "pmid": "33687534", "title": "Linoleic acid in adipose tissue and the risk of myocardial infarction: a case-cohort study.", "citation": "Nielsen MH, Frydenberg M, Bork CS et al. Linoleic acid in adipose tissue and the risk of myocardial infarction: a case-cohort study. European journal of nutrition. 2021.", "doi": "10.1007/s00394-021-02526-y", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33687534/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33687534/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID33687534", "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 observational", "decisive_perturbation": false, "endogenous": false, "direction": "null", "what_it_shows": "A Danish case-cohort study with2819incident infarctions found no association between baseline adipose linoleic acid and infarction risk over16years, including shorter-horizon analyses.", "what_it_does_not_show": "A tissue biomarker reflects long-term exposure and metabolism rather than randomized replacement; null associations do not prove equivalence or inflammatory harm.", "confounders_present": [ "A tissue biomarker reflects long-term exposure and metabolism rather than randomized replacement; null associations do not prove equivalence or inflammatory harm." ], "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": 52, "pmid": "40199060", "title": "Circulating polyunsaturated fatty acids percentages and coronary artery disease incidence and mortality: Observational and Mendelian randomization analyses.", "citation": "Liu Q, Kong Y, Kang H et al. Circulating polyunsaturated fatty acids percentages and coronary artery disease incidence and mortality: Observational and Mendelian randomization analyses. Clinical nutrition (Edinburgh, Scotland). 2025.", "doi": "10.1016/j.clnu.2025.03.020", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/40199060/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40199060/", "tier": "A", "source_tier": "A", "kind": "observational_and_mendelian_randomization", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "UKBiobank_PUFA_observational_and_genetic", "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 observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "A203373-person UKBiobank study found inverse observational PUFA-percentage associations with coronary outcomes and genetically proxied omega6support for lower coronary incidence, with sex differences.", "what_it_does_not_show": "The abstract's causal positive is totalomega6percentage rather than isolated LA-rich oil intake or isocaloric replacement; composition scaling, pleiotropy and subgroup precision remain relevant.", "confounders_present": [ "The abstract's causal positive is totalomega6percentage rather than isolated LA-rich oil intake or isocaloric replacement; composition scaling, pleiotropy and subgroup precision remain relevant." ], "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": 53, "pmid": "25124495", "title": "Circulating omega-6 polyunsaturated fatty acids and total and cause-specific mortality: the Cardiovascular Health Study.", "citation": "Wu JH, Lemaitre RN, King IB et al. Circulating omega-6 polyunsaturated fatty acids and total and cause-specific mortality: the Cardiovascular Health Study. Circulation. 2014.", "doi": "10.1161/CIRCULATIONAHA.114.011590", "pmcid": "PMC4189990", "url": "https://pubmed.ncbi.nlm.nih.gov/25124495/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/25124495/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID25124495", "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 observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "The Cardiovascular Health Study associated higher circulating linoleic acid with lower total and especially nonarrhythmic coronary mortality in older adults.", "what_it_does_not_show": "Prospective biomarker associations challenge a blanket harm narrative but retain residual confounding and metabolic-exposure ambiguity; they are not assigned saturated-fat substitution.", "confounders_present": [ "Prospective biomarker associations challenge a blanket harm narrative but retain residual confounding and metabolic-exposure ambiguity; they are not assigned saturated-fat substitution." ], "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": 54, "pmid": "24351702", "title": "Circulating and dietary omega-3 and omega-6 polyunsaturated fatty acids and incidence of CVD in the Multi-Ethnic Study of Atherosclerosis.", "citation": "de Oliveira Otto MC, Wu JH, Baylin A et al. Circulating and dietary omega-3 and omega-6 polyunsaturated fatty acids and incidence of CVD in the Multi-Ethnic Study of Atherosclerosis. Journal of the American Heart Association. 2013.", "doi": "10.1161/JAHA.113.000506", "pmcid": "PMC3886748", "url": "https://pubmed.ncbi.nlm.nih.gov/24351702/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/24351702/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID24351702", "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 observational", "decisive_perturbation": false, "endogenous": false, "direction": "null", "what_it_shows": "MESA found no significant association of dietary or circulating linoleic acid with incident composite cardiovascular disease, whereas marine omega3associations were inverse.", "what_it_does_not_show": "Only189composite events limit precision, and exposure biomarkers and dietary estimates do not implement isocaloric replacement; a class-level PUFA benefit cannot be assigned automatically to every species.", "confounders_present": [ "Only189composite events limit precision, and exposure biomarkers and dietary estimates do not implement isocaloric replacement; a class-level PUFA benefit cannot be assigned automatically to every species." ], "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": 55, "pmid": "28647413", "title": "Omega-6 fatty acids: Opposing associations with risk-The Ludwigshafen Risk and Cardiovascular Health Study.", "citation": "Delgado GE, März W, Lorkowski S et al. Omega-6 fatty acids: Opposing associations with risk-The Ludwigshafen Risk and Cardiovascular Health Study. Journal of clinical lipidology. 2017.", "doi": "10.1016/j.jacl.2017.05.003", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/28647413/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28647413/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID28647413", "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 observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "The Ludwigshafen angiography cohort reported opposing mortality associations across individualomega6species, with linoleic acid and gamma-linolenic acid described as favourable.", "what_it_does_not_show": "Referral selection, baseline disease and circulating metabolism confound interpretation; the abstract contains an internally inconsistent interval for one non-LAresult, which is not used numerically here.", "confounders_present": [ "Referral selection, baseline disease and circulating metabolism confound interpretation; the abstract contains an internally inconsistent interval for one non-LAresult, which is not used numerically here." ], "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": 56, "pmid": "35692035", "title": "Role of circulating polyunsaturated fatty acids on cardiovascular diseases risk: analysis using Mendelian randomization and fatty acid genetic association data from over 114,000 UK Biobank participants.", "citation": "Borges MC, Haycock PC, Zheng J et al. Role of circulating polyunsaturated fatty acids on cardiovascular diseases risk: analysis using Mendelian randomization and fatty acid genetic association data from over 114,000 UK Biobank participants. BMC medicine. 2022.", "doi": "10.1186/s12916-022-02399-w", "pmcid": "PMC9190170", "url": "https://pubmed.ncbi.nlm.nih.gov/35692035/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35692035/", "tier": "A", "source_tier": "A", "kind": "mendelian_randomization", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "UKBiobank_PUFA_GWAS_instrument", "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": [ "M2" ], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "A large fatty-acid GWASand MR analysis found inconsistent linoleic estimates across cardiovascular endpoints and methods, with lipoprotein and FADSlocus sensitivity.", "what_it_does_not_show": "Genetically proxied circulating concentration is not dietary isocaloric replacement; horizontal pleiotropy and shared lipid pathways restrict interpretation rather than proving either clinical benefit or inflammatory harm.", "confounders_present": [ "Genetically proxied circulating concentration is not dietary isocaloric replacement; horizontal pleiotropy and shared lipid pathways restrict interpretation rather than proving either clinical benefit or inflammatory harm." ], "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": 57, "pmid": "37738352", "title": "Circulating fatty acids, genetic risk, and incident coronary artery disease: A prospective, longitudinal cohort study.", "citation": "Zhuang P, Liu X, Li Y et al. Circulating fatty acids, genetic risk, and incident coronary artery disease: A prospective, longitudinal cohort study. Science advances. 2023.", "doi": "10.1126/sciadv.adf9037", "pmcid": "PMC10881029", "url": "https://pubmed.ncbi.nlm.nih.gov/37738352/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37738352/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "UKBiobank_PUFA_genetic_risk_cohort", "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 observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "A UKBiobank cohort associated higher circulating linoleic acid with increased coronary risk within a high-genetic-risk subgroup, while other PUFAassociations differed.", "what_it_does_not_show": "A baseline genetic stratum is measurable before outcomes but an observational subgroup result does not establish a causal LA-risk interaction or justify universal toxicity; circulating composition and residual confounding remain.", "confounders_present": [ "A baseline genetic stratum is measurable before outcomes but an observational subgroup result does not establish a causal LA-risk interaction or justify universal toxicity; circulating composition and residual confounding remain." ], "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": 58, "pmid": "33924952", "title": "Causal Effects of Serum Levels of n-3 or n-6 Polyunsaturated Fatty Acids on Coronary Artery Disease: Mendelian Randomization Study.", "citation": "Park S, Lee S, Kim Y et al. Causal Effects of Serum Levels of n-3 or n-6 Polyunsaturated Fatty Acids on Coronary Artery Disease: Mendelian Randomization Study. Nutrients. 2021.", "doi": "10.3390/nu13051490", "pmcid": "PMC8145894", "url": "https://pubmed.ncbi.nlm.nih.gov/33924952/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33924952/", "tier": "A", "source_tier": "A", "kind": "mendelian_randomization", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "UKBiobank_and_CARDIoGRAM_fatty_acid_instruments", "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": [ "M1" ], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Allele-score and summary-level MR supported lower coronary risk with genetically predicted linoleic acid, while other fatty acids showed different directions.", "what_it_does_not_show": "Instruments perturb endogenous metabolism rather than assigned dietary replacement, may affect multiple lipids and share cohorts or loci with other MRpapers; this is genuine causal-inference support with scope and validity limits.", "confounders_present": [ "Instruments perturb endogenous metabolism rather than assigned dietary replacement, may affect multiple lipids and share cohorts or loci with other MRpapers; this is genuine causal-inference support with scope and validity limits." ], "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": [ "Circulating-fatty-acid instruments may share metabolic loci or outcome cohorts with other MRreports; they do not randomly assign dietary oil replacement." ] }, { "n": 59, "pmid": "30572606", "title": "Erythrocyte n-6 Fatty Acids and Risk for Cardiovascular Outcomes and Total Mortality in the Framingham Heart Study.", "citation": "Harris WS, Tintle NL, Ramachandran VS. Erythrocyte n-6 Fatty Acids and Risk for Cardiovascular Outcomes and Total Mortality in the Framingham Heart Study. Nutrients. 2018.", "doi": "10.3390/nu10122012", "pmcid": "PMC6316092", "url": "https://pubmed.ncbi.nlm.nih.gov/30572606/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30572606/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Framingham_Offspring_fatty_acids", "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 observational", "decisive_perturbation": false, "endogenous": false, "direction": "null", "what_it_shows": "Framingham offspring erythrocyteomega6measurements showed little independent association with cardiovascular outcomes or mortality after marineomega3adjustment.", "what_it_does_not_show": "The same cohort contributes to other fatty-acid analyses, and biomarker covariance and limited event counts prevent interpreting the null as equivalence or oil-swap causation.", "confounders_present": [ "The same cohort contributes to other fatty-acid analyses, and biomarker covariance and limited event counts prevent interpreting the null as equivalence or oil-swap causation." ], "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": 60, "pmid": "30624587", "title": "Inflammatory response to dietary linoleic acid depends on FADS1 genotype.", "citation": "Lankinen MA, Fauland A, Shimizu BI et al. Inflammatory response to dietary linoleic acid depends on FADS1 genotype. The American journal of clinical nutrition. 2019.", "doi": "10.1093/ajcn/nqy287", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/30624587/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30624587/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID30624587", "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 interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "FADSDIET exposed62genotype-selected healthy men to a four-week linoleic-enriched diet and found differing CRPand fatty-acid responses by FADS1genotype.", "what_it_does_not_show": "Both genotype groups received enrichment without a randomized saturated-fat comparator, and short marker changes or correlations do not demonstrate clinically important inflammatory coronary harm at usual intake.", "confounders_present": [ "Both genotype groups received enrichment without a randomized saturated-fat comparator, and short marker changes or correlations do not demonstrate clinically important inflammatory coronary harm at usual intake." ], "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": [] } ], "verification_summary": { "load_bearing_claims_checked": 65, "verified": 65, "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": "Biomarker change without functional/phenotypic change caps at Γ.", "specific_trigger": "Controlled replacement trials, including DIVAS and Minnesota, establish lipid lowering in their experimental contexts. The proposed LDL-related exposure is an intermediate marker for coronary events, so its downstream clinical inference retains Γ. This does not imply that the directly measured lipid change is doubtful or that LDL causality elsewhere is refuted.", "resulting_ceiling": "Γ" }, { "subclaim_id": "SC3", "cap": "Γ", "cap_source": "universal", "triggered": true, "trigger_text_quoted": "Biomarker change without functional/phenotypic change caps at Γ.", "specific_trigger": "The usual-exposure inflammatory-harm claim lacks a verified clinical inflammatory coronary endpoint. Controlled omega6 feeding has neutral or favourable inflammatory markers in several experiments; FADSDIET shows genotype-dependent short marker responses without randomized saturated-fat comparison. Sydney's historical high-dose intervention harm does not isolate inflammation or establish toxicity of all modern seed oils. Biomarker-only inference cannot exceed Γ.", "resulting_ceiling": "Γ" }, { "subclaim_id": "SC4", "cap": "Α", "cap_source": "rubric", "triggered": true, "trigger_text_quoted": "Use when the hypothesis is mostly a grand narrative with weak intervention support.", "specific_trigger": "No examined controlled long-term cardiovascular comparison establishes carnivore superiority. Two original carnivore empirical reports contain self-selected perceived benefits and lipid changes, without adjudicated event comparisons; extrapolating these to established long-term superiority remains Α. Positive subjective experiences are retained, not dismissed as fabricated.", "resulting_ceiling": "Α" } ], "cap_precedence_resolutions": [ { "collision": "Perturbation in a defined setting versus broader inference", "subclaim_scope_cap_binds_on": "Replacing dietary saturated fat with linoleic-acid-rich oils reduces coronary heart disease events in adults.", "subclaim_scope_threshold_binds_on": "The precise experimentally tested subclaim scope", "resolution": "Clinical or natural-experiment evidence is assessed within its actual dietary package, allocation and endpoint scope. The marker cap binds feeding-derived predictions rather than automatically downgrading a genuinely convergent exact-scope set. Here the missing bridge is a verified positive clinical oil-swap crossing, not a rule that all nutrition or all human-only work must remain low. Mixed ALA-containing LA-rich oils stay eligible; pure-LAmolecular specificity is a separate question.", "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- Genetic or pharmacologic intervention producing reproducible lifespan/healthspan extension\n- Must separate developmental effects from true aging effects\n- Biomarker change alone does NOT satisfy this threshold", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "", "gamma_hard_rules_triggered": [ "Biomarker-only improvement without organismal benefit" ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Controlled replacement trials, including DIVAS and Minnesota, establish lipid lowering in their experimental contexts. The proposed LDL-related exposure is an intermediate marker for coronary events, so its downstream clinical inference retains Γ. This does not imply that the directly measured lipid change is doubtful or that LDL causality elsewhere is refuted.", "ceiling_from_boundary_check": "Γ" }, { "subclaim_id": "SC2", "field_valid_perturbation_quote": "\n- Genetic or pharmacologic intervention producing reproducible lifespan/healthspan extension\n- Must separate developmental effects from true aging effects\n- Biomarker change alone does NOT satisfy this threshold", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "", "gamma_hard_rules_triggered": [ "No verified positive exact allocated clinical crossing at the recorded access depth; missing primary-result verification cannot be supplied by AI or a review." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "In the actually examined exact clinical sources, Minnesota reports no cardiovascular-event benefit and Sydney reports increased coronary mortality. Positive Finnish hospital-period observations and bundled Oslo or Lyon programmes retain their allocation and composition limits. The older VA and Oslo Diet-Heart primary clinical scans could not be accessed, so their reported positive results are explicitly unverified here. No verified positive allocated oil-replacement coronary-event crossing was identified at this evidence-access depth; the Step9 unclear-positive boundary holds the precise registered claim at Γ rather than promoting lipid changes or second-hand trial summaries. This is a bounded verification verdict, not proof that LA-rich oils have no benefit.", "ceiling_from_boundary_check": "Γ" }, { "subclaim_id": "SC3", "field_valid_perturbation_quote": "\n- Genetic or pharmacologic intervention producing reproducible lifespan/healthspan extension\n- Must separate developmental effects from true aging effects\n- Biomarker change alone does NOT satisfy this threshold", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "", "gamma_hard_rules_triggered": [ "Biomarker-only improvement without organismal benefit" ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "The usual-exposure inflammatory-harm claim lacks a verified clinical inflammatory coronary endpoint. Controlled omega6 feeding has neutral or favourable inflammatory markers in several experiments; FADSDIET shows genotype-dependent short marker responses without randomized saturated-fat comparison. Sydney's historical high-dose intervention harm does not isolate inflammation or establish toxicity of all modern seed oils. Biomarker-only inference cannot exceed Γ.", "ceiling_from_boundary_check": "Γ" }, { "subclaim_id": "SC4", "field_valid_perturbation_quote": "\n- Genetic or pharmacologic intervention producing reproducible lifespan/healthspan extension\n- Must separate developmental effects from true aging effects\n- Biomarker change alone does NOT satisfy this threshold", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "", "gamma_hard_rules_triggered": [ "Self-report and marker changes do not establish long-term clinical superiority." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "No examined controlled long-term cardiovascular comparison establishes carnivore superiority. Two original carnivore empirical reports contain self-selected perceived benefits and lipid changes, without adjudicated event comparisons; extrapolating these to established long-term superiority remains Α. Positive subjective experiences are retained, not dismissed as fabricated.", "ceiling_from_boundary_check": "Γ" } ], "thresholds_tested": [ { "subclaim_id": "SC1", "threshold": "Δ", "requirement_quoted": "Requires at least one intervention changing lifespan or healthspan in a way consistent with the hypothesis.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "Link the allocated lipid response to a functional clinical endpoint or independently identify its mediation; marker reproducibility alone does not cross the registered clinical threshold." }, { "subclaim_id": "SC2", "threshold": "Δ", "requirement_quoted": "Requires at least one intervention changing lifespan or healthspan in a way consistent with the hypothesis.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "Obtain and verify original positive historical oil-trial results with their exact endpoint and composition, then test modern specified oil replacement with adjudicated coronary outcomes over a prespecified horizon. The clinical inference must survive implementation, competing exposures and allocation limitations." }, { "subclaim_id": "SC3", "threshold": "Δ", "requirement_quoted": "Requires at least one intervention changing lifespan or healthspan in a way consistent with the hypothesis.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "Directly demonstrate clinically important inflammatory coronary harm under usual LA-rich food replacement, with mediator dissociation and a retained comparator rather than short marker correlations or historical product extrapolation." }, { "subclaim_id": "SC4", "threshold": "Δ", "requirement_quoted": "Requires at least one intervention changing lifespan or healthspan in a way consistent with the hypothesis.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "A controlled, baseline-defined, long-term comparison of an exact carnivore pattern against a specified balanced pattern must show superior adjudicated cardiovascular outcomes, with comparable energy, support and medication management." } ], "generalization_check": { "generalization_tested": "yes", "context_boundary_mapped": "yes", "internal_negative_controls": [ "Minnesota randomized cardiovascular-event null, PMID2643423", "Sydney allocated coronary-mortality adverse result, PMID23386268", "DIVASprimary flow-mediated-dilatation null despite lipid improvement, PMID26016869", "Finnish women's nonsignificant coronary contrast, PMID6840954", "Dutch dietary LAcohort null, PMID21816117", "Danish adiposeLAinfarction null, PMID33687534", "MESAand Framingham LAassociation nulls, PMID24351702 and30572606", "Conflicting circulating-PUFAMR sensitivity results, PMID35692035" ], "note": "Clinical and biomarker contexts were tested in different baseline-defined groups, but a positive exact randomized clinical crossing was not verified from accessible primary results. Thus divergent contexts do not themselves promote the exact claim to Ε. Cohort diet replacement models, circulating fatty-acid instruments, high-dose historical foods and hypercaloric muffin studies are labelled individually. No adherent or symptom-benefiting group is defined after outcomes to remove negative results." }, "falsification_patterns_met": [], "pitfalls_flagged": [ { "pitfall": "Confirmation by biomarker", "where": "Observed LDLlowering and a predicted mortality reduction in DIVASare not measured coronary-event prevention." }, { "pitfall": "Mechanism conflation", "where": "LA-rich oil substitution is not identical to pureLA, totalPUFA, an omega6-to-omega3ratio, repeated frying, Mediterranean patterns or carnivore diets." }, { "pitfall": "Therapeutic effect misread as mechanistic proof", "where": "Whole-pattern or EPAadjunct benefit does not identify a single LAorLDLmediator." }, { "pitfall": "Scope fitted to the result", "where": "Postrandom compliance, long-stay survivor cohorts and diet maintainers do not define baseline clinical beneficiaries." }, { "pitfall": "Negative field-valid perturbation read as a crossed threshold", "where": "Minnesota nulls, Sydney adverse results and conflicting MRdo not become positive evidence merely because their design is informative." }, { "pitfall": "Replication confused with reproduction", "where": "Minnesota, Finnish hospital periods, DIVAS, LIPOGAIN, STRIPand Oslo follow-ups are grouped by study; molecular-resolution and follow-up reports are not independent causal lines." }, { "pitfall": "Association dressed as mechanism", "where": "Cholesterol-death covariance pooled across both Minnesotaarms and circulating-fatty-acid percentages do not constitute randomized mediator harm or food-replacement exposure." } ], "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": 8, "items_rejected": [ "Null and negative contrasts are discriminators, not positive threshold crossings. Reports and replications are not independent causal lines.", "No positive exact allocated oil-replacement coronary-event unit is counted at the recorded primary-access depth; this is a verification boundary, not evidence that inaccessible historical results do not exist.", "Positive whole-pattern, smoking and EPAclinical contrasts retain their intervention scope and do not inflate SC2's oil-specific tally.", "Original recovered-data reports count as reports of their parent studies; meta-analysis components, corrections, protocols and inaccessible abstract-free scans do not add original examination credit.", "Primary source count includes controlled feeding, mechanistic context, prospective cohorts and companion carnivore reports; it is not a count of sixty clinical oil trials." ] }, "steelman": { "case_one_rung_higher": "The strongest Δcase combines predictable lipid lowering, positive cohort substitution estimates, favourable fatty-acid genetic studies and historically reported positive VAor Oslo Diet-Heart outcomes. Because the claim concerns LA-rich oils rather than pureLA, an ALA-containing oil is not disqualified. A verified positive clinical oil replacement result could cross the first clinical threshold even if its mechanism is mixed.", "case_one_rung_lower": "The strongest Βcase notes that accessible randomized exact clinical oil-replacement data are null or harmful and many positive sources are marker or association studies. If the proposal were only a correlation-based clinical narrative, Βwould describe it. However, controlled feeding provides partial experimental system support and the broader mixed clinical evidence cannot be discarded as no intervention science at all.", "which_rejected": "The higher case is blocked by missing original-result verification for the older positive clinical anchors and by uncontrolled component attribution in the available bundled positives, as required by Step9's positive exact-scope test. The lower case is rejected because the proposed mechanism has genuine controlled physiological support and clinically informative perturbations, even though the positive coronary crossing is not verified here. This access-constrained grade is revisable and does not declare the broad oil-benefit literature refuted.", "blocking_cap_threshold_or_missing_experiment": "Missing experiment: Randomize adults with prospectively defined coronary risk to isocaloric replacement of a specified saturated-fat food source with a chemically characterized LA-rich oil, versus retained saturated-fat food and an independently specified unsaturated-oil comparator. Prespecify adjudicated fatal and nonfatal coronary events over multiple years, achieved dietary intake, trans-fat exposure, background omega3, medication stability and analysis. Use LDL/apoBand inflammatory measurements as candidate mediators, not as substituted clinical outcomes." }, "final_score": { "hsef_level": "Γ", "hsef_descriptor": "Mechanistically plausible, partial system support", "confidence": "Moderate", "confidence_rationale": "Evidence density and reproducibility set the band: 60 primary reports, but the exact clinical question is carried by a handful of allocated trials whose results conflict (null in Minnesota, adverse in Sydney, favourable in the Finnish hospital periods and in bundled dietary programmes), and the cohort and genetic estimates disagree with each other. Access depth is reported separately and is not a determinant of confidence (rationale corrected 2026-10-14 in adversarial review; band unchanged).", "rests_on_non_peer_reviewed_work": false, "rationale": "The preregistered primary-subclaim rule returns Γ from SC2. Sixty original reports provide strong experimental lipid effects and a substantial but conflicting clinical and prognostic context. The accessible exact trial evidence does not verify a positive oil-replacement coronary-event crossing; older positive trial reports remain inaccessible at primary-result depth. LA-rich oils were not silently redefined as chemically pure LA, and ALA-containing oils are not excluded simply because they contain ALA. Whole-diet or smoking cointerventions and shared metabolic instruments retain explicit limits. Weakest-link returns Α for carnivore superiority; primary-subclaim and scope-matched return Γ. The verdict does not endorse a blanket seed-oil-harm claim or suggest saturated fat or carnivore diets are clinically superior." }, "role_of_mechanism": { "classification": "epiphenomenon", "derivation_step_matched": 2, "derivation": "For the precise beneficial-coronary-trajectory account, the examined exact-scope evidence does not demonstrate the proposed positive causal dependency in either direction; Step2therefore returns epiphenomenon for that account. This label is not an assertion that oils are biologically inert: allocated feeding effects, adverse historical clinical contrasts and broader dietary benefits remain explicitly reported. It names the unisolated proposed benefit mechanism, not all physiology of the exposure.", "tournament_used_as_tiebreaker": false, "note": "Derived from causal direction, not tournament rank." }, "extended_scoring_MSD": { "momentum": { "value": "Mechanistic only", "artifact": "Modern DIVASlipidomic analyses (PMID37062359), FADS-response work (PMID30624587,38714425) and circulating-PUFAMR(PMID40199060,35692035) investigate mechanisms or genetic proxies; no verified pending modern exact oil-swap coronary-event trial was identified.", "justification": "Modern DIVASlipidomic analyses (PMID37062359), FADS-response work (PMID30624587,38714425) and circulating-PUFAMR(PMID40199060,35692035) investigate mechanisms or genetic proxies; no verified pending modern exact oil-swap coronary-event trial was identified." }, "stability": { "value": "Stable", "trigger": "No named verified pending exact clinical result was identified. The concrete upward trigger is primary verification of a positive old oil trial or a new allocated event trial; an access gap alone does not establish that the result will be positive.", "justification": "No named verified pending exact clinical result was identified. The concrete upward trigger is primary verification of a positive old oil trial or a new allocated event trial; an access gap alone does not establish that the result will be positive." }, "divergence": { "implied_level": null, "implied_level_basis": "No single field-implied level is defensible from conflicting framings.", "assessed_level": "Γ", "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": "Γ", "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": "Randomize adults with prospectively defined coronary risk to isocaloric replacement of a specified saturated-fat food source with a chemically characterized LA-rich oil, versus retained saturated-fat food and an independently specified unsaturated-oil comparator. Prespecify adjudicated fatal and nonfatal coronary events over multiple years, achieved dietary intake, trans-fat exposure, background omega3, medication stability and analysis. Use LDL/apoBand inflammatory measurements as candidate mediators, not as substituted clinical outcomes.", "readout": "Adjudicated coronary events with prespecified endpoint hierarchy, intention-to-treat effect estimates and intervals; achieved energy and fatty-acid composition; apoB/LDL, inflammatory signals and safety outcomes", "critical_control": "Comparable energy, dietary support, cointerventions and modern prevention care; characterized oils; explicit ALAand trans-fat content; stable medication; complete participant follow-up", "supporting_result": "A positive allocated oil-replacement coronary-event contrast that replicates and maps baseline-defined boundaries; independently informative mediation supports a higher mechanistic claim", "falsifying_result": "No clinical benefit despite adequate verified substitution and follow-up, or benefit confined to other cointerventions; adverse events must remain in the analysis and cannot be removed by defining responders" } ], "knowledge_gaps": [ { "name": "Gap 1", "statement": "Accessible primary-result verification of the old VA, Oslo Diet-Heart, MRCsoybean and Rose clinical studies, with actual composition and endpoint hierarchy", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 2", "statement": "Modern long-term allocated oil-swap coronary-event trials with contemporary prevention care", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 3", "statement": "Distinct causal identification of dietary LA-rich oil exposure versus circulating fatty-acid metabolism and shared FADSor lipoprotein instrument pathways", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 4", "statement": "Usual-intake inflammatory coronary harm versus high-dose historical margarine, repeated heating and short biomarker changes", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 5", "statement": "Food-matrix and comparator effects, including saturated-fat sources, refined carbohydrate replacement and mixedomega3/omega6oils", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 6", "statement": "Defined carnivore patterns assessed against an active balanced comparator on actual cardiovascular events rather than maintainer surveys", "relevance": "Limits mechanism identification or scope." } ], "review_metadata": { "review_date": "2026-10-13", "reviewer": "Codex", "evidence_base_note": "60 primary reports; literature cutoff 2026-10-13; source examination UTC date 2026-10-13; 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": "These topic families were selected from an editorial traffic-priority list. Selection was visible; no blind calibration or predetermined clinical verdict was preregistered." }, "upper_ladder_check": { "final_level_below_zeta": true, "equivalents_considered": [ { "kind": "mendelian_randomization", "available": true, "why_not_sufficient": "Genetic LAand omega6analyses and Finnish hospital-period natural experiments were evaluated as real evidence with distinct confounders. They do not automatically form a positive exact-scope set: circulating metabolic instruments differ from assigned dietary replacement, results and pleiotropy sensitivity conflict, and historical hospital periods can confound diet with other changes. No universal association cap is reapplied to an independently convergent same-scope case; the positive exact clinical bridge was not verified at this access depth." }, { "kind": "natural_experiment", "available": true, "why_not_sufficient": "Genetic LAand omega6analyses and Finnish hospital-period natural experiments were evaluated as real evidence with distinct confounders. They do not automatically form a positive exact-scope set: circulating metabolic instruments differ from assigned dietary replacement, results and pleiotropy sensitivity conflict, and historical hospital periods can confound diet with other changes. No universal association cap is reapplied to an independently convergent same-scope case; the positive exact clinical bridge was not verified at this access depth." }, { "kind": "dose_response_across_populations", "available": false, "why_not_sufficient": "Genetic LAand omega6analyses and Finnish hospital-period natural experiments were evaluated as real evidence with distinct confounders. They do not automatically form a positive exact-scope set: circulating metabolic instruments differ from assigned dietary replacement, results and pleiotropy sensitivity conflict, and historical hospital periods can confound diet with other changes. No universal association cap is reapplied to an independently convergent same-scope case; the positive exact clinical bridge was not verified at this access depth." }, { "kind": "withdrawal_rechallenge", "available": false, "why_not_sufficient": "Genetic LAand omega6analyses and Finnish hospital-period natural experiments were evaluated as real evidence with distinct confounders. They do not automatically form a positive exact-scope set: circulating metabolic instruments differ from assigned dietary replacement, results and pleiotropy sensitivity conflict, and historical hospital periods can confound diet with other changes. No universal association cap is reapplied to an independently convergent same-scope case; the positive exact clinical bridge was not verified at this access depth." }, { "kind": "therapeutic_perturbation_hard_endpoint", "available": false, "why_not_sufficient": "Genetic LAand omega6analyses and Finnish hospital-period natural experiments were evaluated as real evidence with distinct confounders. They do not automatically form a positive exact-scope set: circulating metabolic instruments differ from assigned dietary replacement, results and pleiotropy sensitivity conflict, and historical hospital periods can confound diet with other changes. No universal association cap is reapplied to an independently convergent same-scope case; the positive exact clinical bridge was not verified at this access depth." } ], "convergence_present": false, "cap_reapplied_to_convergent_set": false }, "provenance_header": { "sources_total": 60, "claims_total": 65, "claims_verified": 65, "claims_unverified": 0, "claims_contradicted": 0, "tier_a_sources": 60, "generated_by": "Codex; HSEF v5.3", "gate_passed": true }, "claims": [ { "id": "C1", "text": "The Lyon secondary-prevention randomized dietary programme substantially reduced recurrent coronary events while lowering saturated fat and linoleic acid and increasing oleic and alpha-linolenic acids. This is a multicomponent Mediterranean dietary contrast, not isocaloric saturated-fat replacement by linoleic-rich oils; it overlaps the parent trial reported in PMID7911176.", "carries_number": false, "load_bearing_for": [ "SC2" ], "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": "2026-10-13", "note": "" }, { "id": "C2", "text": "In605post-infarct patients, the randomized Mediterranean alpha-linolenic-rich diet reduced cardiac death or nonfatal infarction over about27months without a serum-lipid difference. Linoleic intake was lower, not higher, and many food and fatty-acid changes were bundled; the attached erratum's identifier and details were not supplied, and this is the same Lyon trial as PMID7754988.", "carries_number": true, "load_bearing_for": [ "SC2" ], "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": "2026-10-13", "note": "" }, { "id": "C3", "text": "Prospective fatty-acid measurements in two older-adult cohorts associated higher linoleic acid with lower stroke and mortality among APOEepsilon4carriers. The exploratory genotype subgroup and measured plasma exposure are not randomized isocaloric replacement; the reported linoleic benefits were stroke and mortality rather than isolated coronary events.", "carries_number": true, "load_bearing_for": [ "SC2", "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": "2026-10-13", "note": "" }, { "id": "C4", "text": "A48-patient randomized comprehensive lifestyle programme showed coronary-angiographic regression after one year compared with usual care. Vegetarian diet, smoking cessation, exercise and stress management were bundled; angiographic lesions are not coronary events and no carnivore comparator or isolated linoleic replacement was tested.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "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": "2026-10-13", "note": "" }, { "id": "C5", "text": "JELIS randomized18645Japanese hypercholesterolemic patients to EPA plus statin or statin alone and reduced the composite major-coronary endpoint over4.6years. This omega3 pharmacological adjunct is a composition-confounding comparator, not saturated-fat replacement by linoleic oils; coronary mortality did not differ, open-label treatment matters, and an attached unspecified erratum is flagged.", "carries_number": true, "load_bearing_for": [ "SC2" ], "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": "2026-10-13", "note": "" }, { "id": "C6", "text": "CORDIOPREV secondary analysis associated Mediterranean allocation with improved carotid thickness and plaque measures versus low-fat allocation over five to seven years. Carotid morphology is a surrogate and extra-virgin olive oil is predominantly monounsaturated; this does not isolate linoleic replacement or establish carnivore superiority, and erratum PMID34694867 attaches to the parent report.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "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. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C7", "text": "A94-person randomized four-week butter, coconut or olive-oil study found higher LDLcholesterol with butter, while coconut and olive oils did not differ significantly. These oils were not linoleic-rich and consumption could supplement rather than replace food isocalorically; food-specific biomarker effects cannot substitute for coronary-event benefit.", "carries_number": true, "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": "2026-10-13", "note": "" }, { "id": "C8", "text": "A secondary STRIP analysis linked achieving a childhood dietary-fat target with more favourable aortic thickness and distensibility through young adulthood. The analysed exposure was achieved diet rather than randomized allocation, with a surrogate endpoint and mostly pediatric horizon; it does not establish adult coronary-event causation or isolated linoleic replacement.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "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": "2026-10-13", "note": "" }, { "id": "C9", "text": "A19-person randomized crossover found lower LDL-related plasma cholesterol under a lower-fat diet despite concurrent simvastatin for familial hypercholesterolemia. The dietary contrast was not isolated isocaloric linoleic substitution; lipid lowering in a familial clinical population is not an observed coronary-event endpoint.", "carries_number": true, "load_bearing_for": [ "SC1" ], "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": "2026-10-13", "note": "" }, { "id": "C10", "text": "Three controlled feeding experiments compared saturated, cis-unsaturated and trans-unsaturated fat effects on lipoproteina, with markedly higher values under trans exposure. The abstract is publisher-truncated before the linoleic arm's full results; the exposure was short and a lipid marker, so results cannot demonstrate long-term coronary harm from usual linoleic oils.", "carries_number": false, "load_bearing_for": [ "SC1", "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": "2026-10-13", "note": "" }, { "id": "C11", "text": "PURE associated higher carbohydrate intake with mortality while fat classes were not significantly associated with myocardial infarction or cardiovascular mortality across18countries. Diet was observational and nutritional adequacy, socioeconomic context and replacement foods differ; neither a null saturated-fat association nor lower all-cause mortality establishes carnivore superiority or a randomized linoleic substitution effect.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "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": "2026-10-13", "note": "" }, { "id": "C12", "text": "UKBiobank dietary analysis found nonlinear macronutrient-mortality associations, including different estimated risks at moderate versus high polyunsaturated-fat intakes. Diet questionnaires, selection and residual confounding prevent treating macronutrient curves as causal replacement-dose rules; erratum PMID32371385 attaches and coronary events differ from total mortality.", "carries_number": false, "load_bearing_for": [ "SC2", "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": "2026-10-13", "note": "" }, { "id": "C13", "text": "NHS and HPFS prospective substitution models associated replacing5%energy saturated fat with PUFA with25%lower coronary risk; refined carbohydrate replacement was not beneficial. Modelled substitution is not assigned isocaloric replacement and PUFA composition and healthy-behaviour confounding remain; these repeated cohorts are not independent randomized fatty-acid lines.", "carries_number": true, "load_bearing_for": [ "SC2" ], "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. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C14", "text": "EPICPotsdam lipidomics associated selected lipids with incident disease, and the16-week DIVAS randomized dietary-fat modification changed several risk-associated lipid species favourably. The diet contained mixed monounsaturated and omega6fats; connecting biomarker changes to a separate cohort's events does not demonstrate coronary-event prevention or mediator necessity.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "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": "2026-10-13", "note": "" }, { "id": "C15", "text": "UKBiobank associated a higher plasma omega6-to-omega3ratio with mortality, while each fatty-acid class individually associated inversely with mortality and omega3had the stronger association. A ratio can rise through reduced omega3and does not identify omega6toxicity; circulating proportions and mortality are not randomized usual-exposure inflammatory harm, and UpdateOf PMID36711941 is attached without an extra primary row.", "carries_number": true, "load_bearing_for": [ "SC2", "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": "2026-10-13", "note": "" }, { "id": "C16", "text": "The ARIC carotidMRI study found no independent association of PUFA intake or glycemic index with high-risk plaque features after vascular-risk adjustment. Questionnaire exposure, selected attendees and surrogate plaques do not test randomized coronary events; a surrogate null does not refute every dietary replacement effect.", "carries_number": false, "load_bearing_for": [ "SC2" ], "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": "2026-10-13", "note": "" }, { "id": "C17", "text": "Repeated randomized STRIP counselling lowered saturated intake and LDL-related lipid measures while increasing circulating omega3and omega6proportions from childhood through young adulthood. Multiple dietary changes and a pediatric horizon limit isolated adult linoleic-oil inference; the shared STRIP cohort and biomarkers are not a separate coronary-event trial.", "carries_number": true, "load_bearing_for": [ "SC1" ], "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": "2026-10-13", "note": "" }, { "id": "C18", "text": "The original Minnesota randomized institutional trial lowered serum cholesterol but found no overall cardiovascular-event, cardiovascular-death or total-mortality difference. Mean dietary exposure was384days despite a4.5-year trial and many short stays; intervention changed dietary cholesterol and historical fat sources, and later recovered reports share this trial.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "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. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C19", "text": "A Minnesota subgroup analysis using repeated measurements found greater cholesterol reduction with higher baseline cholesterol after adjusting for regression to the mean. This same-trial lipid response does not demonstrate coronary benefit or identify outcome-defined responders; single baseline measurements can exaggerate apparent subgroup response.", "carries_number": false, "load_bearing_for": [ "SC1" ], "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": "2026-10-13", "note": "" }, { "id": "C20", "text": "The Finnish two-hospital dietary intervention associated replacement of dairy fats with vegetable oils with lower male coronary mortality over its12-year crossover. Hospital-period allocation, institutional medication and population changes can confound the result; this is a report from the same Finnish study as PMID393644 and6840954 rather than individual randomization.", "carries_number": true, "load_bearing_for": [ "SC2" ], "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": "2026-10-13", "note": "" }, { "id": "C21", "text": "The Finnish two-hospital crossover found about half the male electrocardiographic-coronary or coronary-death incidence during lower-saturated higher-polyunsaturated dietary periods. Although metadata labels randomized trial, the described allocation is hospital-period diet reversal and should not be treated as patient randomization; mixed dietary changes and historical context restrict isolated linoleic inference.", "carries_number": false, "load_bearing_for": [ "SC2" ], "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": "2026-10-13", "note": "" }, { "id": "C22", "text": "The Finnish women's hospital-period intervention lowered cholesterol and coronary incidence estimates, but the coronary difference was not statistically significant. Shared hospital-period design and possible medication or population changes limit inference; nonsignificance is not proof of equivalence, and male/female reports are grouped under one parent study.", "carries_number": false, "load_bearing_for": [ "SC2" ], "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": "2026-10-13", "note": "" }, { "id": "C23", "text": "An118-man randomized oil comparison lowered lipoproteina under both linoleic-rich sunflower and alpha-linolenic-rich Camelina diets, with larger LDL-related reductions under the latter. There was no retained saturated-fat comparator and no coronary outcomes; FADSgenotype did not modify the lipid response, so metabolic genotype assumptions cannot be treated as established mediation.", "carries_number": true, "load_bearing_for": [ "SC1" ], "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": "2026-10-13", "note": "" }, { "id": "C24", "text": "The39-person LIPOGAIN randomized overfeeding trial found greater liver and visceral-fat accumulation with palm-oil muffins than sunflower-oil muffins despite similar weight gain. This is an excess-energy context and ectopic-fat or body-composition outcomes, not usual-intake inflammatory coronary harm or an isocaloric clinical-event trial.", "carries_number": true, "load_bearing_for": [ "SC1", "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": "2026-10-13", "note": "" }, { "id": "C25", "text": "A32-woman DIVAS2postprandial crossover found selected genotype-dependent vascular and insulin responses to saturated, monounsaturated and omega6meals. Genotyping was retrospective, the interaction was not consistent across absolute and incremental vascular measures, and acute biomarkers do not establish clinically important inflammatory cardiovascular harm.", "carries_number": true, "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": "2026-10-13", "note": "" }, { "id": "C26", "text": "A LIPOGAIN secondary randomized-overfeeding analysis found distinct adipose methylation changes after saturated and omega6fat excess, including shared overfeeding effects. Gene methylation is not evidence of clinical inflammation or coronary injury; the same parent trial is grouped and erratum PMID28673906 attaches without another primary row.", "carries_number": true, "load_bearing_for": [ "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": "2026-10-13", "note": "" }, { "id": "C27", "text": "Sixteen-week isoenergetic DIVASreplacement with omega6or monounsaturated fats lowered selected circulating endothelial and platelet microparticles compared with saturated fat. Novel vascular markers are not clinical events and endothelial-progenitor increases were confined to the monounsaturated arm; this is the same DIVASparent as its lipid and vascular reports.", "carries_number": true, "load_bearing_for": [ "SC1", "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": "2026-10-13", "note": "" }, { "id": "C28", "text": "A pooled LIPOGAIN1and2secondary analysis associated baseline metabolic characteristics with liver-fat response to saturated-fat overfeeding. Only the saturated-fat arms were pooled and predictors were observational; overlapping parent trials and hypercaloric exposure do not demonstrate usual linoleic-oil inflammation or harm.", "carries_number": true, "load_bearing_for": [ "SC3" ], "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": "2026-10-13", "note": "" }, { "id": "C29", "text": "LIPOGAIN2randomized61adults to excess-energy palm or sunflower muffins and found higher liver fat, ceramides and atherogenic lipids with saturated fat despite similar weight gain. The report centres on secondary or exploratory outcomes and excess calories; biomarker and liver-fat differences do not establish coronary-event reduction or universally harmless linoleic oils.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "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": "2026-10-13", "note": "" }, { "id": "C30", "text": "DIVAS2randomized meal fat composition produced lower solubleICAM1after omega6meals but no primary flow-mediated-dilatation difference. An acute endothelial activation marker does not establish long-term clinical inflammation or safety; the primary vascular null and same-trial genotype reanalysis are retained.", "carries_number": true, "load_bearing_for": [ "SC3" ], "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": "2026-10-13", "note": "" }, { "id": "C31", "text": "The195-person16-week isoenergetic DIVAStrial lowered LDLcholesterol with saturated-fat replacement by omega6PUFA, but its primary flow-mediated-dilatation endpoint was null. Its estimated17-20%mortality reduction was extrapolated from lipid change and was not an observed mortality or coronary-event result; mixed monounsaturated replacement and short follow-up retain scope.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "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": "2026-10-13", "note": "" }, { "id": "C32", "text": "A retrospective DIVASgenotype analysis found one APOEinteraction with cholesterol response under monounsaturated replacement, with other variants null. Small genotype subgroups and retrospective interactions do not define baseline-validated linoleic responders or add an independent causal line to the shared trial.", "carries_number": false, "load_bearing_for": [ "SC1" ], "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": "2026-10-13", "note": "" }, { "id": "C33", "text": "LIPOGAIN metabolomic reanalysis found a few differential plasma metabolites under saturated versus omega6overfeeding and correlations with fat compartments. These are candidate metabolic markers, not proven mediators or coronary outcomes; the39participants overlap the original overfeeding report.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "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": "2026-10-13", "note": "" }, { "id": "C34", "text": "LIPOGAIN sunflower versus palm overfeeding improved selected atherogenic lipid ratios, while endothelial activation markers increased with weight gain across both fat arms. The common excess-energy response cannot be attributed specifically to linoleic acid; shared-trial lipid ratios and acute-risk biomarkers do not establish long-term coronary harm or benefit.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "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": "2026-10-13", "note": "" }, { "id": "C35", "text": "A DIVASsecondary lipidomic analysis linked dietary-fat-responsive plasma species to incident disease associations in EPICPotsdam. Different trial and cohort populations and multiple fat changes prevent an identified mediator claim; the same113DIVASsubset and EPICPotsdamcase-cohorts overlap PMID35422138.", "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": "2026-10-13", "note": "" }, { "id": "C36", "text": "Retrospective DIVASandDIVAS2genotyping associated APOEwith selected baseline markers and exploratory responses, especially under monounsaturated exposure. Genetic stratification of a shared trial is not Mendelian randomization and requires prospective replication; genotype-marker correlations do not establish linoleic inflammatory harm.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "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": "2026-10-13", "note": "" }, { "id": "C37", "text": "In287PIVUSolder adults, serum linoleic proportions associated inversely with visceral and other fat depots after covariate adjustment. Cross-sectional fatty-acid proportions and body-fat surrogates can reflect metabolism and diet, not causal replacement or clinical inflammatory cardiovascular effects.", "carries_number": true, "load_bearing_for": [ "SC3" ], "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": "2026-10-13", "note": "" }, { "id": "C38", "text": "The195-person DIVASfood-exchange report verified broadly achieved isoenergetic fat-composition targets with little change in other macronutrients or anthropometrics. This is original adherence and exposure data from the same randomized parent, not a separate coronary-event trial or proof that every individual met the prescription.", "carries_number": true, "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": "2026-10-13", "note": "" }, { "id": "C39", "text": "A67-person10-week isocaloric randomized vegetableomega6versus butter trial found lower liver fat and selected inflammatory signalling markers with PUFA, without a proinflammatory or oxidative-stress signal. Some favourable lipid estimates were restricted to postrandomization compliant participants and cannot define clinical beneficiaries; markers and liver fat are not coronary outcomes or universal safety proof.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "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": "2026-10-13", "note": "" }, { "id": "C40", "text": "A2029-person social-media carnivore survey reported perceived symptom and weight improvements alongside high satisfaction and high LDLcholesterol in a laboratory-reporting subset. Maintainer recruitment, self-report, missing measurements and no concurrent comparison prevent long-term cardiovascular superiority or clinical event safety conclusions.", "carries_number": true, "load_bearing_for": [ "SC4" ], "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. Selected body sections: 1:Methods:paragraph0, 1:Methods:paragraph1, 1:Methods:paragraph2, 1:Methods:paragraph3, 1:Methods:paragraph5, 2:Results:paragraph7, 2:Results:paragraph12, 2:Results:paragraph18. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C41", "text": "A24-person exploratory German carnivore study collected before-and-after laboratory reports and perceived benefits, with significantly higher total and LDLcholesterol after adoption. Self-selected participants, varied diet definitions, short eligibility and uncontrolled cointerventions cannot establish long-term event superiority; favourable triglycerides or HbA1c do not cancel LDL-related uncertainty.", "carries_number": true, "load_bearing_for": [ "SC4" ], "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": "2026-10-13", "note": "" }, { "id": "C42", "text": "Original recovered Minnesotatrial analyses confirmed cholesterol lowering without a reported mortality benefit; selected autopsy files and longitudinal cholesterol-mortality associations challenged a simple marker-to-benefit prediction. Only the original recovered-data component earns primary credit: full randomized raw data were unavailable and autopsies partly recovered; cholesterol-death association in both arms is not randomized mediator harm, and the examined2024erratumPMID38942429 updates a thesis link rather than study numbers.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "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. Selected body sections: 1:Methods:paragraph0, 1:Methods:paragraph6, 1:Methods:paragraph9, 1:Methods:paragraph12, 1:Methods:paragraph18, 1:Methods:paragraph19, 1:Methods:paragraph20, 1:Methods:paragraph30, 1:Methods:paragraph32, 1:Methods:paragraph35, 2:Results:paragraph5, 2:Results:paragraph8, 2:Results:paragraph17, 2:Results:paragraph18, 2:Results:paragraph19, 2:Results:paragraph22. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C43", "text": "Original recovered Sydneydata from458post-coronary-event men showed lower cholesterol but higher coronary and cardiovascular mortality under safflower-oil and margarine substitution over median39months. Only recovered original trial data earns credit, not its meta-analysis; actual all-causeP=.051 was borderline, historical margarine and highLAexposure constrain usual-modern-oil inference, and an unspecified erratum attaches.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "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. Selected body sections: 1:Methods:paragraph1, 1:Methods:paragraph2, 1:Methods:paragraph4, 1:Methods:paragraph5, 1:Methods:paragraph7, 2:Results:paragraph0, 2:Results:paragraph12, 2:Results:paragraph13, 2:Results:paragraph17, 2:Results:paragraph19. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C44", "text": "A226-patient coronary-angiography series associated higher adipose and platelet linoleic proportions with more extensive coronary disease. Cross-sectional referred-patient selection, residual confounding and reverse causation prevent treating this adverse association as randomized oil harm or an identified inflammatory mechanism.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "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": "2026-10-13", "note": "" }, { "id": "C45", "text": "A14-person randomized home-use crossover found lower total cholesterol and triglycerides with rice-bran than sunflower oil, while the LDLdifference was nonsignificant. An oil-versus-oil food-matrix comparison has no saturated-fat arm or coronary endpoint; small unblinded home-use periods cannot attribute differences solely to linoleic content or establish risk reduction.", "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": "2026-10-13", "note": "" }, { "id": "C46", "text": "A20069-person Dutch prospective cohort found no linoleic-intake association with coronary incidence over ten years despite a4-5%energy LA-versus-carbohydrate difference. The replacement comparator was largely carbohydrate rather than saturated fat, and questionnaire exposure and280events limit precision; the null does not establish clinical equivalence of oil replacement.", "carries_number": true, "load_bearing_for": [ "SC2" ], "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": "2026-10-13", "note": "" }, { "id": "C47", "text": "EPICNorfolk baseline plasma phospholipid measurements associated higher omega6fatty-acid concentrations with lower subsequent coronary risk after adjustment. Measured circulating fats reflect metabolism as well as intake, and heterogeneous individual fatty-acid associations prevent equating totalomega6with a randomized linoleic-rich oil substitution.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "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": "2026-10-13", "note": "" }, { "id": "C48", "text": "The randomized Veterans prolonged-feeding cohort showed lower serum cholesterol and substantial sustained tissue-linoleic enrichment under unsaturated-fat replacement over up to five years. This original exposure and lipid report does not itself give coronary-event counts; it belongs to the same Veterans parent as its clinical reports and cannot verify a clinical crossing from markers alone.", "carries_number": false, "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": "2026-10-13", "note": "" }, { "id": "C49", "text": "The1232-man randomized Oslo primary-prevention programme reduced first infarction or sudden-death incidence by47%over five years with diet and antismoking advice. Diet composition, fish, weight control and smoking changes were bundled, so this positive cannot identify the effect of isolated linoleic-rich oil replacement; later follow-up is the same study.", "carries_number": true, "load_bearing_for": [ "SC2" ], "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": "2026-10-13", "note": "" }, { "id": "C50", "text": "Forty-year follow-up of the randomized Oslo diet-and-antismoking programme found a borderline reduction in first-infarction mortality, with all-cause benefit limited to earlier follow-up. Long-term events reflect the same bundled intervention and subsequent exposures; it is not an independent oil trial or evidence of lifelong universal mortality benefit.", "carries_number": false, "load_bearing_for": [ "SC2" ], "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. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C51", "text": "A Danish case-cohort study with2819incident infarctions found no association between baseline adipose linoleic acid and infarction risk over16years, including shorter-horizon analyses. A tissue biomarker reflects long-term exposure and metabolism rather than randomized replacement; null associations do not prove equivalence or inflammatory harm.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "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. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C52", "text": "A203373-person UKBiobank study found inverse observational PUFA-percentage associations with coronary outcomes and genetically proxied omega6support for lower coronary incidence, with sex differences. The abstract's causal positive is totalomega6percentage rather than isolated LA-rich oil intake or isocaloric replacement; composition scaling, pleiotropy and subgroup precision remain relevant.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "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. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C53", "text": "The Cardiovascular Health Study associated higher circulating linoleic acid with lower total and especially nonarrhythmic coronary mortality in older adults. Prospective biomarker associations challenge a blanket harm narrative but retain residual confounding and metabolic-exposure ambiguity; they are not assigned saturated-fat substitution.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "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": "2026-10-13", "note": "" }, { "id": "C54", "text": "MESA found no significant association of dietary or circulating linoleic acid with incident composite cardiovascular disease, whereas marine omega3associations were inverse. Only189composite events limit precision, and exposure biomarkers and dietary estimates do not implement isocaloric replacement; a class-level PUFA benefit cannot be assigned automatically to every species.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "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": "2026-10-13", "note": "" }, { "id": "C55", "text": "The Ludwigshafen angiography cohort reported opposing mortality associations across individualomega6species, with linoleic acid and gamma-linolenic acid described as favourable. Referral selection, baseline disease and circulating metabolism confound interpretation; the abstract contains an internally inconsistent interval for one non-LAresult, which is not used numerically here.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "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": "2026-10-13", "note": "" }, { "id": "C56", "text": "A large fatty-acid GWASand MR analysis found inconsistent linoleic estimates across cardiovascular endpoints and methods, with lipoprotein and FADSlocus sensitivity. Genetically proxied circulating concentration is not dietary isocaloric replacement; horizontal pleiotropy and shared lipid pathways restrict interpretation rather than proving either clinical benefit or inflammatory harm.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "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": "2026-10-13", "note": "" }, { "id": "C57", "text": "A UKBiobank cohort associated higher circulating linoleic acid with increased coronary risk within a high-genetic-risk subgroup, while other PUFAassociations differed. A baseline genetic stratum is measurable before outcomes but an observational subgroup result does not establish a causal LA-risk interaction or justify universal toxicity; circulating composition and residual confounding remain.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3" ], "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": "2026-10-13", "note": "" }, { "id": "C58", "text": "Allele-score and summary-level MR supported lower coronary risk with genetically predicted linoleic acid, while other fatty acids showed different directions. Instruments perturb endogenous metabolism rather than assigned dietary replacement, may affect multiple lipids and share cohorts or loci with other MRpapers; this is genuine causal-inference support with scope and validity limits.", "carries_number": false, "load_bearing_for": [ "SC2" ], "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": "2026-10-13", "note": "" }, { "id": "C59", "text": "Framingham offspring erythrocyteomega6measurements showed little independent association with cardiovascular outcomes or mortality after marineomega3adjustment. The same cohort contributes to other fatty-acid analyses, and biomarker covariance and limited event counts prevent interpreting the null as equivalence or oil-swap causation.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "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": "2026-10-13", "note": "" }, { "id": "C60", "text": "FADSDIET exposed62genotype-selected healthy men to a four-week linoleic-enriched diet and found differing CRPand fatty-acid responses by FADS1genotype. Both genotype groups received enrichment without a randomized saturated-fat comparator, and short marker changes or correlations do not demonstrate clinically important inflammatory coronary harm at usual intake.", "carries_number": true, "load_bearing_for": [ "SC3" ], "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": "2026-10-13", "note": "" }, { "id": "CSC1", "text": "Controlled replacement trials, including DIVAS and Minnesota, establish lipid lowering in their experimental contexts. The proposed LDL-related exposure is an intermediate marker for coronary events, so its downstream clinical inference retains Γ. This does not imply that the directly measured lipid change is doubtful or that LDL causality elsewhere is refuted.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 7, 8, 9, 10, 14, 17, 18, 19, 23, 24, 27, 29, 31, 32, 33, 34, 35, 36, 38, 39, 42, 43, 45, 48 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-13", "note": "" }, { "id": "CSC2", "text": "In the actually examined exact clinical sources, Minnesota reports no cardiovascular-event benefit and Sydney reports increased coronary mortality. Positive Finnish hospital-period observations and bundled Oslo or Lyon programmes retain their allocation and composition limits. The older VA and Oslo Diet-Heart primary clinical scans could not be accessed, so their reported positive results are explicitly unverified here. No verified positive allocated oil-replacement coronary-event crossing was identified at this evidence-access depth; the Step9 unclear-positive boundary holds the precise registered claim at Γ rather than promoting lipid changes or second-hand trial summaries. This is a bounded verification verdict, not proof that LA-rich oils have no benefit.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 1, 2, 3, 4, 5, 6, 8, 11, 12, 13, 14, 15, 16, 18, 20, 21, 22, 31, 35, 42, 43, 44, 46, 47, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-13", "note": "" }, { "id": "CSC3", "text": "The usual-exposure inflammatory-harm claim lacks a verified clinical inflammatory coronary endpoint. Controlled omega6 feeding has neutral or favourable inflammatory markers in several experiments; FADSDIET shows genotype-dependent short marker responses without randomized saturated-fat comparison. Sydney's historical high-dose intervention harm does not isolate inflammation or establish toxicity of all modern seed oils. Biomarker-only inference cannot exceed Γ.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 3, 7, 10, 12, 15, 24, 25, 26, 27, 28, 29, 30, 31, 33, 34, 36, 37, 39, 42, 43, 44, 47, 51, 52, 53, 54, 55, 56, 57, 59, 60 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-13", "note": "" }, { "id": "CSC4", "text": "No examined controlled long-term cardiovascular comparison establishes carnivore superiority. Two original carnivore empirical reports contain self-selected perceived benefits and lipid changes, without adjudicated event comparisons; extrapolating these to established long-term superiority remains Α. Positive subjective experiences are retained, not dismissed as fabricated.", "carries_number": false, "load_bearing_for": [ "SC4" ], "source_ns": [ 4, 6, 11, 40, 41 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-13", "note": "" }, { "id": "CH", "text": "LA-rich oil replacement reliably changes lipid markers; exact coronary-event benefit needs more careful source and intervention separation, while blanket inflammatory harm and carnivore superiority remain unproved.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 31, 18, 43, 39, 40 ], "verification": "verified", "verified_against": "Bounded synthesis of examined sources; score is adjudication.", "verified_on": "2026-10-13", "note": "" } ], "citation_ledger": [ { "n": 1, "citation": "Renaud S, de Lorgeril M, Delaye J et al. Cretan Mediterranean diet for prevention of coronary heart disease. The American journal of clinical nutrition. 1995.", "tier": "A", "kind": "rct", "pmid": "7754988", "doi": "10.1093/ajcn/61.6.1360S", "url": "https://pubmed.ncbi.nlm.nih.gov/7754988/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Lyon_Diet_Heart_605", "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" ] }, { "n": 2, "citation": "de Lorgeril M, Renaud S, Mamelle N et al. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet (London, England). 1994.", "tier": "A", "kind": "rct", "pmid": "7911176", "doi": "10.1016/s0140-6736(94)92580-1", "url": "https://pubmed.ncbi.nlm.nih.gov/7911176/", "status_flags": [ "ErratumIn: PMID not supplied" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Lyon_Diet_Heart_605", "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", "CSC2" ] }, { "n": 3, "citation": "Satizabal CL, Samieri C, Davis-Plourde KL et al. APOE and the Association of Fatty Acids With the Risk of Stroke, Coronary Heart Disease, and Mortality. Stroke. 2018.", "tier": "A", "kind": "primary", "pmid": "30571417", "doi": "10.1161/STROKEAHA.118.022132", "url": "https://pubmed.ncbi.nlm.nih.gov/30571417/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Framingham_and_3C_fatty_acid_cohorts", "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", "CSC2", "CSC3" ] }, { "n": 4, "citation": "Ornish D, Brown SE, Scherwitz LW et al. Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial. Lancet (London, England). 1990.", "tier": "A", "kind": "rct", "pmid": "1973470", "doi": "10.1016/0140-6736(90)91656-u", "url": "https://pubmed.ncbi.nlm.nih.gov/1973470/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID1973470", "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", "CSC2", "CSC4" ] }, { "n": 5, "citation": "Yokoyama M, Origasa H, Matsuzaki M et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet (London, England). 2007.", "tier": "A", "kind": "rct", "pmid": "17398308", "doi": "10.1016/S0140-6736(07)60527-3", "url": "https://pubmed.ncbi.nlm.nih.gov/17398308/", "status_flags": [ "ErratumIn: PMID not supplied" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID17398308", "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", "CSC2" ] }, { "n": 6, "citation": "Jimenez-Torres J, Alcalá-Diaz JF, Torres-Peña JD et al. Mediterranean Diet Reduces Atherosclerosis Progression in Coronary Heart Disease: An Analysis of the CORDIOPREV Randomized Controlled Trial. Stroke. 2021.", "tier": "A", "kind": "rct", "pmid": "34372670", "doi": "10.1161/STROKEAHA.120.033214", "url": "https://pubmed.ncbi.nlm.nih.gov/34372670/", "status_flags": [ "ErratumIn: PMID34694867" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID34372670", "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": [ "C6", "CSC2", "CSC4" ] }, { "n": 7, "citation": "Khaw KT, Sharp SJ, Finikarides L et al. Randomised trial of coconut oil, olive oil or butter on blood lipids and other cardiovascular risk factors in healthy men and women. 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The clinical dietary adaptation is explicit; the boundary fails because a positive exact clinical crossing was not verified, not because only humans were studied." }, { "subclaim_id": "SC2", "rule_quoted": "Biomarker-only improvement without organismal benefit", "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": "ROS change measurements 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": "NAD level change measurements 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": "Mitochondrial metrics 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": "Senescence marker changes 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": "Single-species or single-strain 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": "Biomarker-only improvement without organismal benefit", "trigger_status": "Triggered for the claimed inference from CRP, eicosanoids or oxidative signals to inflammatory coronary harm at usual exposures." }, { "subclaim_id": "SC4", "rule_quoted": "ROS change measurements 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": "NAD level change measurements 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": "Mitochondrial metrics 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": "Senescence marker changes 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": "Single-species or single-strain 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": "Biomarker-only improvement without organismal benefit", "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/linoleic-acid-coronary-events/z5pSNnvhSnqeayH8Sk6nzA/" ], "query_record_note": "Exact provider question/response retained privately in its retrieval receipt.", "primary_comparison_count": 13, "primary_comparisons": [ { "pmid": "27071971", "doi": "10.1136/bmj.i1246", "source_type": "primary study report", "study_group": "Minnesota_Coronary_Experiment", "access_depth": "full_text_partial", "consensus_aspect": "Consensus calls the cholesterol-death association within-arm and describes9423participants without adequately separating the recovered analyses.", "result_comparison": "Actual original Methods/Results show that the detailed longitudinal cohort comprised2355people exposed for at least one year, full randomized raw data were not recovered, and the adjusted cholesterol-death association pooled both arms with no detected cholesterol-by-arm interaction. This is observational mediator covariance, not randomized proof that cholesterol lowering causes death. The broader9423cohort's mortality graphs and the149partially recovered autopsies are separate evidence components.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/27071971/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\saturated-fat-linoleic-coronary\\examinations\\original-33-43-10000.json" ], "body_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\saturated-fat-linoleic-coronary\\body-presentation-receipts\\27071971-s1-p0-6-9-12-18-19-20-30-32-35.json", "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\saturated-fat-linoleic-coronary\\body-presentation-receipts\\27071971-s2-p5-8-17-18-19-22.json" ] }, { "pmid": "23386268", "doi": "10.1136/bmj.e8707", "source_type": "primary study report", "study_group": "PMID23386268", "access_depth": "full_text_partial", "consensus_aspect": "Consensus says Sydney significantly increased all-cause mortality along with coronary mortality.", "result_comparison": "Actual selected original Results give all-causeP=.051, a borderline result rounded in the abstract; coronary and cardiovascular mortality contrasts were significant. The458men, median39-month horizon and highLA safflower-oil/margarine intervention are verified, while usual-modern-oil toxicity and an inflammatory mediator are not demonstrated.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/23386268/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\saturated-fat-linoleic-coronary\\examinations\\original-33-43-10000.json" ], "body_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\saturated-fat-linoleic-coronary\\body-presentation-receipts\\23386268-s1-p1-2-4-5-7.json", "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\saturated-fat-linoleic-coronary\\body-presentation-receipts\\23386268-s2-p0-12-13-17-19.json" ] }, { "pmid": "2643423", "doi": "10.1161/01.atv.9.1.129", "source_type": "primary study report", "study_group": "Minnesota_Coronary_Experiment", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus describes Minnesota as lipid lowering without clinical benefit.", "result_comparison": "The original1989trial abstract agrees for overall cardiovascular events and mortality. It also reports a mean dietary exposure of384days despite the longer trial, and the institutional food replacement changed several lipid-related features. The1989and2016reports belong to one parent trial; the recovered report's meta-analysis does not count as an additional original clinical experiment.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/2643423/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\saturated-fat-linoleic-coronary\\examinations\\original-17-25-10000.json" ], "body_receipts": [] }, { "pmid": "393644", "doi": "10.1093/ije/8.2.99", "source_type": "primary study report", "study_group": "Finnish_Mental_Hospital_periods", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus groups classic historical diets as randomized clinical oil trials and mentions their design limitations.", "result_comparison": "The actual Finnish abstract describes one hospital on the diet, the other as control, then reversal after six years. Despite anRCTmetadata tag, this is treated as a controlled hospital-period natural experiment, with the male favourable result retained and the women's nonsignificant report grouped under the same parent programme.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/393644/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\saturated-fat-linoleic-coronary\\examinations\\original-17-25-10000.json" ], "body_receipts": [] }, { "pmid": "26016869", "doi": "10.3945/ajcn.114.097089", "source_type": "primary study report", "study_group": "DIVAS_NCT01478958", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus says vegetable-oil substitution reliably lowers LDLand warns that biomarkers do not guarantee survival benefit.", "result_comparison": "The originalDIVAStrial confirms16-week isoenergetic replacement and lower LDLbut a null primary flow-mediated-dilatation endpoint. Its17-20%mortality reduction was estimated from lipid change, not observed. This source supports experimental lipid response, not a coronary-event crossing.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/26016869/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\saturated-fat-linoleic-coronary\\examinations\\original-25-33-10000.json" ], "body_receipts": [] }, { "pmid": "22492369", "doi": "10.3945/ajcn.111.030114", "source_type": "primary study report", "study_group": "PMID22492369", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus says human feeding studies largely contradict a blanket LA-induced systemic-inflammation claim.", "result_comparison": "The original67-person randomized isocaloric trial found lower liver fat and selected inflammatory signals with vegetableomega6versus butter and no reported oxidative-stress or proinflammatory signal. Some lipid findings were restricted to postrandomization compliant participants. Short markers cannot prove universal safety or long-term event protection, but the unfavourable-inflammation prediction did not hold in this experiment.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/22492369/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\saturated-fat-linoleic-coronary\\examinations\\original-33-43-10000.json" ], "body_receipts": [] }, { "pmid": "34934897", "doi": "10.1093/cdn/nzab133", "source_type": "primary study report", "study_group": "PMID34934897", "access_depth": "full_text_partial", "consensus_aspect": "Consensus correctly identifies a self-selected2029-person carnivore survey with perceived benefits and elevated median LDLin a subset.", "result_comparison": "Actual original Methods confirm recruitment through existing carnivore social-media communities and at least six months of diet maintenance, with self-reported measurements and no balanced-diet control. Selected Results retain perceived benefits, improved glycemic reports and high LDLwithout converting these into adjudicated long-term cardiovascular superiority.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/34934897/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\saturated-fat-linoleic-coronary\\examinations\\original-33-43-10000.json" ], "body_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\saturated-fat-linoleic-coronary\\body-presentation-receipts\\34934897-s1-p0-1-2-3-5.json", "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\saturated-fat-linoleic-coronary\\body-presentation-receipts\\34934897-s2-p7-12-18.json" ] }, { "pmid": "7911176", "doi": "10.1016/s0140-6736(94)92580-1", "source_type": "primary study report", "study_group": "Lyon_Diet_Heart_605", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus discusses mixedomega3/omega6diets separately from pureLAand notes composition confounding.", "result_comparison": "The originalLyonallocated programme lowered coronary events while LAintake decreased and ALA/oleic exposure increased, with similar serum lipids. It is a positive whole-pattern result and does not prove LAharm. More generally, our registered claim is LA-rich oils, not pureLA, so anALA-containing oil is not excluded merely for containingALA.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/7911176/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\saturated-fat-linoleic-coronary\\examinations\\original-0-8-10000.json" ], "body_receipts": [] }, { "pmid": "33924952", "doi": "10.3390/nu13051490", "source_type": "primary study report", "study_group": "UKBiobank_and_CARDIoGRAM_fatty_acid_instruments", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus's brief clinical summary does not resolve the differing circulating-fatty-acid MRresults.", "result_comparison": "The examined originalMRreports favourable linoleic-CAD estimates using allele scores and pleiotropy-robust summary methods. It is retained as causal-inference support, while the exposure is lifelong circulating metabolism rather than assigned isocaloric oil replacement. It does not independently verify the clinical dietary bridge.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/33924952/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\saturated-fat-linoleic-coronary\\examinations\\original-53-60-10000.json" ], "body_receipts": [] }, { "pmid": "35692035", "doi": "10.1186/s12916-022-02399-w", "source_type": "primary study report", "study_group": "UKBiobank_PUFA_GWAS_instrument", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus emphasizes heterogeneous trial and biomarker evidence but does not identify this conflicting largeMRanalysis in its brief response.", "result_comparison": "The originallargePUFAGWAS/MRreport found inconsistent linoleic estimates across methods and endpoints and important LDL/FADSlocus sensitivity. Those assumptions and shared metabolic pathways are examined rather than treating everyMRpaper as either simple association or independently convergent proof.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/35692035/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\saturated-fat-linoleic-coronary\\examinations\\original-53-60-10000.json" ], "body_receipts": [] }, { "pmid": "30624587", "doi": "10.1093/ajcn/nqy287", "source_type": "primary study report", "study_group": "PMID30624587", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus says controlled interventions do not elevate systemic inflammatory biomarkers in general.", "result_comparison": "FADSDIETprovides a relevant qualification: short CRPand fatty-acid responses differed byFADS1genotype among62men receiving enrichment. There was no randomized saturated-fat comparator and no clinical coronary inflammatory endpoint. The result narrows a universal no-marker-response claim without establishing usual-intake clinical harm.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/30624587/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\saturated-fat-linoleic-coronary\\examinations\\original-53-60-10000.json" ], "body_receipts": [] }, { "pmid": "33687534", "doi": "10.1007/s00394-021-02526-y", "source_type": "primary study report", "study_group": "PMID33687534", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus's brief overview calls the evidence conflicting but highlights recovered clinical trials more than prospective adipose-exposure nulls.", "result_comparison": "The originalDanishcase-cohort study found no adiposeLAassociation with infarction after16years or shorter horizons. That null is retained alongside favourableCHSandEPICNorfolkassociations, preventing selective citation of only positive or adverse cohorts.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/33687534/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\saturated-fat-linoleic-coronary\\examinations\\original-45-53-10000.json" ], "body_receipts": [] }, { "pmid": "21816117", "doi": "10.1017/S0007114511003837", "source_type": "primary study report", "study_group": "PMID21816117", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus identifies replacement-comparator and dietary-context gaps.", "result_comparison": "The originalDutch20,069-person study found no coronary incidence association across LAintake differences mainly replacing carbohydrate. It is not a randomized saturated-fat replacement trial, so its null cannot directly refute the registered oil-swap proposition.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/21816117/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\saturated-fat-linoleic-coronary\\examinations\\original-45-53-10000.json" ], "body_receipts": [] } ], "grade_changed": false, "grade_change_note": "Source-based adjudication; no independent blinded regrade claimed.", "raw_receipts": [ { "path": "deliverables\\hsef_v53_traffic_ranks_11_15_2026-10-13\\saturated-fat-linoleic-coronary\\consensus-browser-2026-10-13.json", "sha256": "c4936f3bef62a2f9f30a774c8462d6288cb30560389205092dc319e4b78fe430" } ], "independent_blinded_audit": false, "cutoff": "2026-10-13", "completed_utc": "2026-10-13T17:02:52.583019+00:00", "conclusion": "Endpoint hierarchy, experimental scope and original-source limits determine the evidence cards; provider wording does not override them." } }