{ "$schema_version": "5.3", "review_mode": "fresh", "claim_restatement": { "index_wording": "Vitamin D Deficiency and Non-skeletal Disease", "entry_form": "claim", "gradeable_restatement": "Low circulating 25-hydroxyvitamin D is a causal contributor to non-skeletal disease, such that supplementation reduces incidence.", "restatement_required": true, "split_into": [], "parent_claim": null, "scope_qualifiers": [ { "qualifier": "Enrollment, product identity, disease, species, baseline state and treatment timing", "determinable_before_outcome": true, "determined_from": "Enrollment and experimental design, before results; no responder-defined scope.", "action": "retained" } ] }, "hypothesis": { "name": "Vitamin D Deficiency and Non-skeletal Disease", "central_claim": "Low circulating 25-hydroxyvitamin D is a causal contributor to non-skeletal disease, such that supplementation reduces incidence.", "proposed_mechanism": "Low circulating 25-hydroxyvitamin D is a causal contributor to non-skeletal disease, such that supplementation reduces incidence.", "claimed_scope": "Correcting low vitamin D prevents incidence across broad nonskeletal disease categories", "claimed_level": [ "progression" ], "is_conjunctive": true, "conjunctive_note": "The website claim hinges on SC3 at its stated scope; SC1 and SC2 are reported separately and cannot substitute for that claim." }, "rubric_routing": { "primary_rubric": "06-metabolism-aging.md", "secondary_rubrics": [ "05-immunology-inflammation.md" ], "index_notes_applied": [ "The website claim hinges on SC3 at its stated scope; SC1 and SC2 are reported separately and cannot substitute for that claim." ], "rubric_fit_note": "06-metabolism-aging is a partial fit for broad healthspan inference; 05-immunology-inflammation covers immune subclaims. Aging/lifespan requirements are not used to deny disease-specific prevention. The full claim requires causal incidence changes across its stated nonskeletal scope, not vitamin-D concentration or immune biomarkers alone." }, "subclaim_matrix": { "subclaims": [ { "id": "SC1", "statement": "Low vitamin D predicts non-skeletal disease risk.", "subclaim_type": "existence", "scope": "Cancer, cardiovascular, metabolic, autoimmune and infectious endpoints", "claimed_scope": "Cancer, cardiovascular, metabolic, autoimmune and infectious endpoints", "governing_rubric": "06-metabolism-aging.md", "key_evidence_anchor": "Prospective observational studies", "hsef_level": "Β", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Low vitamin D predicts selected disease risks but illness, adiposity, exposure and behavior can confound those associations." }, { "id": "SC2", "statement": "Vitamin D signaling causally modifies specific non-skeletal pathways.", "subclaim_type": "mechanism", "scope": "Defined experimental and human disease contexts", "claimed_scope": "Defined experimental and human disease contexts", "governing_rubric": "05-immunology-inflammation.md", "key_evidence_anchor": "Pathway perturbation or prospective genetic inference", "hsef_level": "Γ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Biological signaling, immune-cell changes and selected genetic/disease-specific findings support plausibility; broad nonskeletal causal pathways are not established by biomarkers alone." }, { "id": "SC3", "statement": "Supplementation reduces non-skeletal disease incidence across disease categories.", "subclaim_type": "generalization", "scope": "Baseline vitamin D measured before randomization; disease-specific results reported separately", "claimed_scope": "Baseline vitamin D measured before randomization; disease-specific results reported separately", "governing_rubric": "06-metabolism-aging.md", "key_evidence_anchor": "Randomized incidence trials with baseline-deficiency strata", "hsef_level": "Γ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Large randomized trials do not show a consistent broad prevention effect. Positive disease-specific or original secondary findings do not establish the registered across-category claim." } ], "aggregation_rule": "primary-subclaim", "aggregation_preregistered": true, "aggregation_rationale": "The website claim hinges on SC3 at its stated scope; SC1 and SC2 are reported separately and cannot substitute for that claim.", "primary_subclaim_id": "SC3", "aggregation_derivation": "Overall Γ is a partial-mechanism assessment for the registered broad prevention claim, not a denial of vitamin-D biology or skeletal indications. Robust null trials and attenuated secondary evidence prevent a broad positive causal crossing; genetic and disease-specific findings keep this above a purely associational interpretation.", "aggregation_alternatives": { "weakest_link_would_return": "Β", "primary_subclaim_would_return": "Γ", "scope_matched_would_return": "Γ", "note": "Separate narrow successes do not replace the preregistered gate." }, "index_rule_deviation": "" }, "competing_models": { "models_evaluated": [ { "rank_in_tournament": 1, "model_id": "M2", "is_nominal": false, "name": "Risk marker with selective causal effects", "core_claim": "Low vitamin D is often a marker of shared causes, with possible disease- and deficiency-specific causal contributions.", "explains_what_nominal_does_not": "Low vitamin D is often a marker of shared causes, with possible disease- and deficiency-specific causal contributions.", "strongest_supporting_evidence": [ "Broad trial nulls coexist with selected genetic and clinical signals." ], "strongest_contradictory_evidence": [ "This mixed explanation does not resolve the size of every severe-deficiency effect." ], "hsef_level_for_this_model": "Γ", "rationale": "Broad trial nulls coexist with selected genetic and clinical signals. This mixed explanation does not resolve the size of every severe-deficiency effect." }, { "rank_in_tournament": 2, "model_id": "M1", "is_nominal": true, "name": "Broad deficiency-driven nonskeletal disease", "core_claim": "Low vitamin D is an upstream common cause whose correction prevents multiple disease categories.", "explains_what_nominal_does_not": "Low vitamin D is an upstream common cause whose correction prevents multiple disease categories.", "strongest_supporting_evidence": [ "Observational gradients, immune biology and original autoimmune-trial findings support a plausible rationale." ], "strongest_contradictory_evidence": [ "Large cancer, cardiovascular, respiratory and other trials do not provide consistent broad incidence benefit." ], "hsef_level_for_this_model": "Γ", "rationale": "Observational gradients, immune biology and original autoimmune-trial findings support a plausible rationale. Large cancer, cardiovascular, respiratory and other trials do not provide consistent broad incidence benefit." }, { "rank_in_tournament": 3, "model_id": "M3", "is_nominal": false, "name": "Predominantly reverse causation/confounding", "core_claim": "Illness, adiposity, sun exposure and behavior influence both vitamin-D levels and risk.", "explains_what_nominal_does_not": "Illness, adiposity, sun exposure and behavior influence both vitamin-D levels and risk.", "strongest_supporting_evidence": [ "Associations are often stronger than randomized correction effects." ], "strongest_contradictory_evidence": [ "Selected genetic and clinical findings prevent concluding all effects are noncausal." ], "hsef_level_for_this_model": "Β", "rationale": "Associations are often stronger than randomized correction effects. Selected genetic and clinical findings prevent concluding all effects are noncausal." }, { "rank_in_tournament": 4, "model_id": "M4", "is_nominal": false, "name": "Baseline-dependent immune modulation", "core_claim": "Effects may be concentrated in prespecified deficient or disease-specific strata.", "explains_what_nominal_does_not": "Effects may be concentrated in prespecified deficient or disease-specific strata.", "strongest_supporting_evidence": [ "Selected low-baseline and psoriasis genetic findings support testing this possibility." ], "strongest_contradictory_evidence": [ "Postrandomization achieved levels and unreplicated subgroup signals do not establish the boundary." ], "hsef_level_for_this_model": "Γ", "rationale": "Selected low-baseline and psoriasis genetic findings support testing this possibility. Postrandomization achieved levels and unreplicated subgroup signals do not establish the boundary." } ], "tournament_summary": "Descriptive comparison; does not modify the nominal score. Prespecified baseline deficiency and disease category, verified correction and randomized incidence endpoints separate a causal deficiency effect from shared-cause associations; defining responders afterward cannot supply the scope.", "study_separating_rank1_from_rank2": "Prespecified baseline deficiency and disease category, verified correction and randomized incidence endpoints separate a causal deficiency effect from shared-cause associations; defining responders afterward cannot supply the scope.", "nominal_wins_only_by_funding_artifact": false, "level_unchanged_by_tournament": true }, "evidence_inventory": [ { "n": 1, "pmid": "30415629", "title": "Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease.", "citation": "Manson JE, Cook NR, Lee IM et al. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. The New England journal of medicine. 2019.", "doi": "10.1056/NEJMoa1809944", "pmcid": "PMC6425757", "url": "https://pubmed.ncbi.nlm.nih.gov/30415629/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30415629/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "VITAL", "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:RESULTS:paragraph2, 1:RESULTS:paragraph5. 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": "null", "what_it_shows": "VITAL did not significantly reduce its primary invasive-cancer or major-cardiovascular endpoints with vitamin D.", "what_it_does_not_show": "This constrains broad prevention in the enrolled population, not every severely deficient or disease-specific subgroup.", "confounders_present": [ "This constrains broad prevention in the enrolled population, not every severely deficient or disease-specific subgroup." ], "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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: VITAL" ] }, { "n": 2, "pmid": "32749491", "title": "Effect of Long-term Vitamin D3 Supplementation vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial.", "citation": "Okereke OI, Reynolds CF, Mischoulon D et al. Effect of Long-term Vitamin D3 Supplementation vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial. JAMA. 2020.", "doi": "10.1001/jama.2020.10224", "pmcid": "PMC7403921", "url": "https://pubmed.ncbi.nlm.nih.gov/32749491/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32749491/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "VITAL", "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": "null", "what_it_shows": "VITAL-DEP did not significantly prevent depression outcomes.", "what_it_does_not_show": "This is not a trial of treating every existing depressive disorder or severe deficiency.", "confounders_present": [ "This is not a trial of treating every existing depressive disorder or severe deficiency." ], "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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: VITAL" ] }, { "n": 3, "pmid": "36098968", "title": "Effect of Vitamin D3 and Omega-3 Fatty Acid Supplementation on Risk of Frailty: An Ancillary Study of a Randomized Clinical Trial.", "citation": "Orkaby AR, Dushkes R, Ward R et al. Effect of Vitamin D3 and Omega-3 Fatty Acid Supplementation on Risk of Frailty: An Ancillary Study of a Randomized Clinical Trial. JAMA network open. 2022.", "doi": "10.1001/jamanetworkopen.2022.31206", "pmcid": "PMC9471979", "url": "https://pubmed.ncbi.nlm.nih.gov/36098968/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36098968/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "VITAL", "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": "null", "what_it_shows": "VITAL frailty analyses found no clear preventive benefit.", "what_it_does_not_show": "Frailty analysis does not establish all possible skeletal or functional effects.", "confounders_present": [ "Frailty analysis does not establish all possible skeletal or functional 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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: VITAL" ] }, { "n": 4, "pmid": "37378490", "title": "Effects of Vitamin D3 and Marine Omega-3 Fatty Acids Supplementation on Indicated and Selective Prevention of Depression in Older Adults: Results From the Clinical Center Sub-Cohort of the VITamin D and OmegA-3 TriaL (VITAL).", "citation": "Vyas CM, Mischoulon D, Chang G et al. Effects of Vitamin D3 and Marine Omega-3 Fatty Acids Supplementation on Indicated and Selective Prevention of Depression in Older Adults: Results From the Clinical Center Sub-Cohort of the VITamin D and OmegA-3 TriaL (VITAL). The Journal of clinical psychiatry. 2023.", "doi": "10.4088/JCP.22m14629", "pmcid": "PMC10328718", "url": "https://pubmed.ncbi.nlm.nih.gov/37378490/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37378490/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "VITAL", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "A smaller VITAL subgroup did not demonstrate depression prevention.", "what_it_does_not_show": "Limited subgroup power and shared parent cohort do not create independent replication.", "confounders_present": [ "Limited subgroup power and shared parent cohort do not create independent replication." ], "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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: VITAL" ] }, { "n": 5, "pmid": "36591342", "title": "Effects of Vitamin D3 Supplementation on Cardiovascular and Cancer Outcomes by eGFR in VITAL.", "citation": "Limonte CP, Zelnick LR, Hoofnagle AN et al. Effects of Vitamin D3 Supplementation on Cardiovascular and Cancer Outcomes by eGFR in VITAL. Kidney360. 2022.", "doi": "10.34067/KID.0006472022", "pmcid": "PMC9802543", "url": "https://pubmed.ncbi.nlm.nih.gov/36591342/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36591342/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "VITAL", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "VITAL kidney strata showed biochemical vitamin-D/PTH effects without differential cancer/CV benefit.", "what_it_does_not_show": "Biochemical target response is not broad disease-incidence reduction.", "confounders_present": [ "Biochemical target response is not broad disease-incidence 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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: VITAL" ] }, { "n": 6, "pmid": "37380191", "title": "Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial.", "citation": "Thompson B, Waterhouse M, English DR et al. Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial. BMJ (Clinical research ed.). 2023.", "doi": "10.1136/bmj-2023-075230", "pmcid": "PMC10302209", "url": "https://pubmed.ncbi.nlm.nih.gov/37380191/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37380191/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D_HEALTH", "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": "supports", "what_it_shows": "D-Health cardiovascular analyses suggested a modest signal with an overall confidence interval including no effect.", "what_it_does_not_show": "Nominal secondary/subgroup findings are not definitive broad cardiovascular prevention.", "confounders_present": [ "Nominal secondary/subgroup findings are not definitive broad cardiovascular prevention." ], "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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: D_HEALTH" ] }, { "n": 7, "pmid": "36715270", "title": "Vitamin D supplementation and cognition-Results from analyses of the D-Health trial.", "citation": "Pham H, Waterhouse M, Rahman S et al. Vitamin D supplementation and cognition-Results from analyses of the D-Health trial. Journal of the American Geriatrics Society. 2023.", "doi": "10.1111/jgs.18247", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/36715270/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36715270/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D_HEALTH", "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": "null", "what_it_shows": "D-Health cognitive analyses found no benefit on tested cognition.", "what_it_does_not_show": "Same parent trial, selected measures and enrollment restrict scope.", "confounders_present": [ "Same parent trial, selected measures and enrollment restrict 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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: D_HEALTH" ] }, { "n": 8, "pmid": "24108783", "title": "Effect of vitamin D supplementation on antibiotic use: a randomized controlled trial.", "citation": "Tran B, Armstrong BK, Ebeling PR et al. Effect of vitamin D supplementation on antibiotic use: a randomized controlled trial. The American journal of clinical nutrition. 2014.", "doi": "10.3945/ajcn.113.063271", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/24108783/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/24108783/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D_HEALTH_PILOT", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Pilot supplementation did not clearly reduce overall antibiotic use.", "what_it_does_not_show": "An exploratory older subgroup and nonsignificant interaction cannot establish a reliable subgroup effect.", "confounders_present": [ "An exploratory older subgroup and nonsignificant interaction cannot establish a reliable subgroup 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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: D_HEALTH_PILOT" ] }, { "n": 9, "pmid": "37698908", "title": "The Effect of Vitamin D Supplementation on Hypothyroidism in the Randomized Controlled D-Health Trial.", "citation": "Waterhouse M, Pham H, Rahman ST et al. The Effect of Vitamin D Supplementation on Hypothyroidism in the Randomized Controlled D-Health Trial. Thyroid : official journal of the American Thyroid Association. 2023.", "doi": "10.1089/thy.2023.0317", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/37698908/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37698908/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D_HEALTH", "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": "null", "what_it_shows": "D-Health tertiary analyses did not reduce incident hypothyroidism.", "what_it_does_not_show": "A tertiary endpoint is not independent confirmation of autoimmune prevention.", "confounders_present": [ "A tertiary endpoint is not independent confirmation of autoimmune prevention." ], "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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: D_HEALTH" ] }, { "n": 10, "pmid": "40096917", "title": "The effect of vitamin D supplementation on cancer incidence in the randomised controlled D-Health Trial: Implications for policy and practice.", "citation": "Neale RE, English DR, McLeod DS et al. The effect of vitamin D supplementation on cancer incidence in the randomised controlled D-Health Trial: Implications for policy and practice. The Journal of steroid biochemistry and molecular biology. 2025.", "doi": "10.1016/j.jsbmb.2025.106738", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/40096917/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40096917/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D_HEALTH", "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": "null", "what_it_shows": "D-Health did not reduce overall cancer incidence.", "what_it_does_not_show": "Not all cancer subtypes or severely deficient populations are separately resolved.", "confounders_present": [ "Not all cancer subtypes or severely deficient populations are separately resolved." ], "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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: D_HEALTH" ] }, { "n": 11, "pmid": "23066119", "title": "Recruitment and results of a pilot trial of vitamin D supplementation in the general population of Australia.", "citation": "Tran B, Armstrong BK, Carlin JB et al. Recruitment and results of a pilot trial of vitamin D supplementation in the general population of Australia. The Journal of clinical endocrinology and metabolism. 2012.", "doi": "10.1210/jc.2012-2682", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/23066119/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/23066119/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D_HEALTH_PILOT", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "A pilot showed feasible supplementation and increased vitamin-D levels.", "what_it_does_not_show": "Feasibility and biochemical correction are not clinical prevention.", "confounders_present": [ "Feasibility and biochemical correction are not clinical prevention." ], "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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: D_HEALTH_PILOT" ] }, { "n": 12, "pmid": "35026158", "title": "The D-Health Trial: a randomised controlled trial of the effect of vitamin D on mortality.", "citation": "Neale RE, Baxter C, Romero BD et al. The D-Health Trial: a randomised controlled trial of the effect of vitamin D on mortality. The lancet. Diabetes & endocrinology. 2022.", "doi": "10.1016/S2213-8587(21)00345-4", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/35026158/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35026158/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "ErratumIn: PMID35325597" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D_HEALTH", "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": "null", "what_it_shows": "D-Health did not reduce all-cause mortality.", "what_it_does_not_show": "Exploratory cancer-mortality analyses do not establish generalized harm; an erratum is attached.", "confounders_present": [ "Exploratory cancer-mortality analyses do not establish generalized harm; an erratum is attached." ], "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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: D_HEALTH" ] }, { "n": 13, "pmid": "33444565", "title": "The effect of vitamin D supplementation on acute respiratory tract infection in older Australian adults: an analysis of data from the D-Health Trial.", "citation": "Pham H, Waterhouse M, Baxter C et al. The effect of vitamin D supplementation on acute respiratory tract infection in older Australian adults: an analysis of data from the D-Health Trial. The lancet. Diabetes & endocrinology. 2021.", "doi": "10.1016/S2213-8587(20)30380-6", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33444565/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33444565/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D_HEALTH", "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": "null", "what_it_shows": "D-Health did not reduce acute respiratory infection incidence, with limited duration findings.", "what_it_does_not_show": "Episode duration is distinct from prevention incidence and from severe-deficiency effects.", "confounders_present": [ "Episode duration is distinct from prevention incidence and from severe-deficiency 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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: D_HEALTH" ] }, { "n": 14, "pmid": "26206095", "title": "Effect of vitamin D supplementation on selected inflammatory biomarkers in older adults: a secondary analysis of data from a randomised, placebo-controlled trial.", "citation": "Waterhouse M, Tran B, Ebeling PR et al. Effect of vitamin D supplementation on selected inflammatory biomarkers in older adults: a secondary analysis of data from a randomised, placebo-controlled trial. The British journal of nutrition. 2015.", "doi": "10.1017/S0007114515002366", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/26206095/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26206095/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D_HEALTH_PILOT", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Pilot D-Health work found no clear broad inflammatory-marker improvement.", "what_it_does_not_show": "A biomarker null does not establish every clinical outcome.", "confounders_present": [ "A biomarker null does not establish every clinical outcome." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: D_HEALTH_PILOT" ] }, { "n": 15, "pmid": "37702332", "title": "Effects of Vitamin D Supplementation on Telomere Length: An Analysis of Data from the Randomised Controlled D-Health Trial.", "citation": "Rahman ST, Waterhouse M, Pham H et al. Effects of Vitamin D Supplementation on Telomere Length: An Analysis of Data from the Randomised Controlled D-Health Trial. The journal of nutrition, health & aging. 2023.", "doi": "10.1007/s12603-023-1948-3", "pmcid": "PMC12877696", "url": "https://pubmed.ncbi.nlm.nih.gov/37702332/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37702332/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D_HEALTH", "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": "null", "what_it_shows": "D-Health did not change the tested telomere-length endpoint.", "what_it_does_not_show": "Telomere length is not a validated substitute for organismal aging or disease prevention.", "confounders_present": [ "Telomere length is not a validated substitute for organismal aging or disease prevention." ], "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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: D_HEALTH" ] }, { "n": 16, "pmid": "31173679", "title": "Vitamin D Supplementation and Prevention of Type 2 Diabetes.", "citation": "Pittas AG, Dawson-Hughes B, Sheehan P et al. Vitamin D Supplementation and Prevention of Type 2 Diabetes. The New England journal of medicine. 2019.", "doi": "10.1056/NEJMoa1900906", "pmcid": "PMC6993875", "url": "https://pubmed.ncbi.nlm.nih.gov/31173679/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31173679/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D2D", "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": "null", "what_it_shows": "D2d's primary diabetes endpoint favored supplementation numerically but did not reach statistical significance.", "what_it_does_not_show": "Participants were not selected for vitamin-D deficiency; the result does not prove benefit or exclude a modest effect.", "confounders_present": [ "Participants were not selected for vitamin-D deficiency; the result does not prove benefit or exclude a modest 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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: D2D" ] }, { "n": 17, "pmid": "34473295", "title": "Effects of Vitamin D Supplementation on Insulin Sensitivity and Secretion in Prediabetes.", "citation": "Rasouli N, Brodsky IG, Chatterjee R et al. Effects of Vitamin D Supplementation on Insulin Sensitivity and Secretion in Prediabetes. The Journal of clinical endocrinology and metabolism. 2022.", "doi": "10.1210/clinem/dgab649", "pmcid": "PMC8684490", "url": "https://pubmed.ncbi.nlm.nih.gov/34473295/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34473295/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D2D", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "D2d beta-cell measures were null overall with a low-baseline-D subgroup signal.", "what_it_does_not_show": "Biomarker subgroup results require replication and cannot establish broad diabetes prevention.", "confounders_present": [ "Biomarker subgroup results require replication and cannot establish broad diabetes prevention." ], "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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: D2D" ] }, { "n": 18, "pmid": "33693713", "title": "Vitamin D Supplementation for Prevention of Cancer: The D2d Cancer Outcomes (D2dCA) Ancillary Study.", "citation": "Chatterjee R, Fuss P, Vickery EM et al. Vitamin D Supplementation for Prevention of Cancer: The D2d Cancer Outcomes (D2dCA) Ancillary Study. The Journal of clinical endocrinology and metabolism. 2021.", "doi": "10.1210/clinem/dgab153", "pmcid": "PMC8372641", "url": "https://pubmed.ncbi.nlm.nih.gov/33693713/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33693713/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D2D", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "D2d did not clearly reduce cancer/polyps in its secondary analysis.", "what_it_does_not_show": "Shared cohort and limited event counts restrict precision.", "confounders_present": [ "Shared cohort and limited event counts restrict precision." ], "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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: D2D" ] }, { "n": 19, "pmid": "42024385", "title": "Vitamin D Receptor Polymorphisms and the Effect of Vitamin D Supplementation on Diabetes Risk Among Adults With Prediabetes.", "citation": "Dawson-Hughes B, Huggins GS, Nelson J et al. Vitamin D Receptor Polymorphisms and the Effect of Vitamin D Supplementation on Diabetes Risk Among Adults With Prediabetes. JAMA network open. 2026.", "doi": "10.1001/jamanetworkopen.2026.7332", "pmcid": "PMC13107228", "url": "https://pubmed.ncbi.nlm.nih.gov/42024385/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/42024385/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D2D", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "D2d genotype analyses suggested differential diabetes response.", "what_it_does_not_show": "Baseline genotype is prespecifiable but exploratory interaction requires independent replication.", "confounders_present": [ "Baseline genotype is prespecifiable but exploratory interaction requires independent replication." ], "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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: D2D" ] }, { "n": 20, "pmid": "34362787", "title": "Effect of Vitamin D Supplementation on Kidney Function in Adults with Prediabetes: A Secondary Analysis of a Randomized Trial.", "citation": "Kim SH, Brodsky IG, Chatterjee R et al. Effect of Vitamin D Supplementation on Kidney Function in Adults with Prediabetes: A Secondary Analysis of a Randomized Trial. Clinical journal of the American Society of Nephrology : CJASN. 2021.", "doi": "10.2215/CJN.00420121", "pmcid": "PMC8455038", "url": "https://pubmed.ncbi.nlm.nih.gov/34362787/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34362787/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D2D", "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": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "D2d kidney outcomes showed no clear benefit.", "what_it_does_not_show": "Secondary renal endpoints do not establish universal absence of vitamin-D effects.", "confounders_present": [ "Secondary renal endpoints do not establish universal absence of vitamin-D 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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: D2D" ] }, { "n": 21, "pmid": "37001590", "title": "Effect of intratrial mean 25(OH)D concentration on diabetes risk, by race and weight: an ancillary analysis in the D2d study.", "citation": "Chatterjee R, Davenport CA, Vickery EM et al. Effect of intratrial mean 25(OH)D concentration on diabetes risk, by race and weight: an ancillary analysis in the D2d study. The American journal of clinical nutrition. 2023.", "doi": "10.1016/j.ajcnut.2023.03.021", "pmcid": "PMC10447481", "url": "https://pubmed.ncbi.nlm.nih.gov/37001590/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37001590/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D2D", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Higher achieved vitamin-D levels in D2d associated with lower diabetes risk.", "what_it_does_not_show": "Conditioning on postrandomization levels does not retain randomized assignment of those levels.", "confounders_present": [ "Conditioning on postrandomization levels does not retain randomized assignment of those levels." ], "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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: D2D" ] }, { "n": 22, "pmid": "35753926", "title": "The effect of vitamin D supplementation on cardiovascular risk in patients with prediabetes: A secondary analysis of the D2d study.", "citation": "Desouza C, Chatterjee R, Vickery EM et al. The effect of vitamin D supplementation on cardiovascular risk in patients with prediabetes: A secondary analysis of the D2d study. Journal of diabetes and its complications. 2022.", "doi": "10.1016/j.jdiacomp.2022.108230", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/35753926/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35753926/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D2D", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "D2d cardiovascular events were not clearly reduced despite selected risk-score changes.", "what_it_does_not_show": "Surrogate change and limited events do not establish clinical prevention.", "confounders_present": [ "Surrogate change and limited events do not establish clinical prevention." ], "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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: D2D" ] }, { "n": 23, "pmid": "35140313", "title": "Safety and tolerability of high-dose daily vitamin D3 supplementation in the vitamin D and type 2 diabetes (D2d) study-a randomized trial in persons with prediabetes.", "citation": "Johnson KC, Pittas AG, Margolis KL et al. Safety and tolerability of high-dose daily vitamin D3 supplementation in the vitamin D and type 2 diabetes (D2d) study-a randomized trial in persons with prediabetes. European journal of clinical nutrition. 2022.", "doi": "10.1038/s41430-022-01068-8", "pmcid": "PMC9352576", "url": "https://pubmed.ncbi.nlm.nih.gov/35140313/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35140313/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "ErratumIn: PMID35418608" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D2D", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "D2d monitored supplementation without a clear major safety difference.", "what_it_does_not_show": "Safety under trial monitoring is not proof of efficacy or universal safety; an erratum is attached.", "confounders_present": [ "Safety under trial monitoring is not proof of efficacy or universal safety; an erratum is attached." ], "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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: D2D" ] }, { "n": 24, "pmid": "35082139", "title": "Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial.", "citation": "Hahn J, Cook NR, Alexander EK et al. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial. BMJ (Clinical research ed.). 2022.", "doi": "10.1136/bmj-2021-066452", "pmcid": "PMC8791065", "url": "https://pubmed.ncbi.nlm.nih.gov/35082139/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35082139/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "VITAL", "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": "supports", "what_it_shows": "The original VITAL autoimmune report found a statistically significant reduction in confirmed incident autoimmune disease.", "what_it_does_not_show": "The same cohort's later case confirmation attenuated the estimate; it is not an independently replicated broad signal.", "confounders_present": [ "The same cohort's later case confirmation attenuated the estimate; it is not an independently replicated broad signal." ], "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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: VITAL" ] }, { "n": 25, "pmid": "38272846", "title": "Vitamin D and Marine n-3 Fatty Acids for Autoimmune Disease Prevention: Outcomes Two Years After Completion of a Double-Blind, Placebo-Controlled Trial.", "citation": "Costenbader KH, Cook NR, Lee IM et al. Vitamin D and Marine n-3 Fatty Acids for Autoimmune Disease Prevention: Outcomes Two Years After Completion of a Double-Blind, Placebo-Controlled Trial. Arthritis & rheumatology (Hoboken, N.J.). 2024.", "doi": "10.1002/art.42811", "pmcid": "PMC11565399", "url": "https://pubmed.ncbi.nlm.nih.gov/38272846/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38272846/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "VITAL", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 2:RESULTS:paragraph4. 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": "supports", "what_it_shows": "Updated VITAL cases weakened the randomized vitamin-D autoimmune estimate and follow-up showed no overall sustained vitamin-D difference.", "what_it_does_not_show": "Observational post-trial follow-up is not continued randomized supplementation; attenuation does not exclude all disease-specific effects.", "confounders_present": [ "Observational post-trial follow-up is not continued randomized supplementation; attenuation does not exclude all disease-specific 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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: VITAL" ] }, { "n": 26, "pmid": "36278483", "title": "Randomized phase I trial of antigen-specific tolerizing immunotherapy with peptide/calcitriol liposomes in ACPA+ rheumatoid arthritis.", "citation": "Sonigra A, Nel HJ, Wehr P et al. Randomized phase I trial of antigen-specific tolerizing immunotherapy with peptide/calcitriol liposomes in ACPA+ rheumatoid arthritis. JCI insight. 2022.", "doi": "10.1172/jci.insight.160964", "pmcid": "PMC9714780", "url": "https://pubmed.ncbi.nlm.nih.gov/36278483/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36278483/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID36278483", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "DEN-181 altered immune measures in a small rheumatoid-arthritis phase 1 trial.", "what_it_does_not_show": "A peptide/calcitriol combination is not oral vitamin-D population prevention or isolated vitamin-D efficacy.", "confounders_present": [ "A peptide/calcitriol combination is not oral vitamin-D population prevention or isolated vitamin-D efficacy." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 27, "pmid": "18279374", "title": "Association of vitamin D receptor gene 3'-variants with Hashimoto's thyroiditis in the Croatian population.", "citation": "Stefanić M, Papić S, Suver M et al. Association of vitamin D receptor gene 3'-variants with Hashimoto's thyroiditis in the Croatian population. International journal of immunogenetics. 2008.", "doi": "10.1111/j.1744-313X.2008.00748.x", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/18279374/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/18279374/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID18279374", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Vitamin-D receptor variants associated with Hashimoto thyroiditis.", "what_it_does_not_show": "Association is not a validated exposure instrument or randomized supplementation effect.", "confounders_present": [ "Association is not a validated exposure instrument or randomized supplementation 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": [] }, "shared_components": [] }, { "n": 28, "pmid": "32043288", "title": "Adding vitamin D3 to the dipeptidyl peptidase-4 inhibitor saxagliptin has the potential to protect β-cell function in LADA patients: A 1-year pilot study.", "citation": "Zhang Z, Yan X, Wu C et al. Adding vitamin D3 to the dipeptidyl peptidase-4 inhibitor saxagliptin has the potential to protect β-cell function in LADA patients: A 1-year pilot study. Diabetes/metabolism research and reviews. 2020.", "doi": "10.1002/dmrr.3298", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/32043288/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32043288/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID32043288", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "LADA combination-treatment arms had selected within-group beta-cell findings.", "what_it_does_not_show": "No significant between-group difference on the listed measures; saxagliptin prevents isolating vitamin D.", "confounders_present": [ "No significant between-group difference on the listed measures; saxagliptin prevents isolating vitamin D." ], "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": [] }, "shared_components": [] }, { "n": 29, "pmid": "31766063", "title": "Vitamin D Status and Thyroid Autoantibodies in Autoimmune Thyroiditis.", "citation": "Koehler VF, Filmann N, Mann WA. Vitamin D Status and Thyroid Autoantibodies in Autoimmune Thyroiditis. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2019.", "doi": "10.1055/a-1023-4181", "pmcid": "PMC8873028", "url": "https://pubmed.ncbi.nlm.nih.gov/31766063/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31766063/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID31766063", "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": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "A retrospective Hashimoto study associated supplementation/level changes with antibody trajectories.", "what_it_does_not_show": "Nonrandomized groups and antibody surrogates do not establish clinical prevention.", "confounders_present": [ "Nonrandomized groups and antibody surrogates do not establish clinical prevention." ], "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": [] }, "shared_components": [] }, { "n": 30, "pmid": "37076476", "title": "Combination therapy with saxagliptin and vitamin D for the preservation of β-cell function in adult-onset type 1 diabetes: a multi-center, randomized, controlled trial.", "citation": "Yan X, Li X, Liu B et al. Combination therapy with saxagliptin and vitamin D for the preservation of β-cell function in adult-onset type 1 diabetes: a multi-center, randomized, controlled trial. Signal transduction and targeted therapy. 2023.", "doi": "10.1038/s41392-023-01369-9", "pmcid": "PMC10115841", "url": "https://pubmed.ncbi.nlm.nih.gov/37076476/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37076476/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "NCT02407899", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "A saxagliptin/vitamin-D type 1 diabetes trial missed its primary fasting C-peptide endpoint with a secondary signal.", "what_it_does_not_show": "Combination attribution and secondary analysis cannot establish vitamin-D-alone prevention.", "confounders_present": [ "Combination attribution and secondary analysis cannot establish vitamin-D-alone prevention." ], "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": [] }, "shared_components": [] }, { "n": 31, "pmid": "33759075", "title": "Vitamin D deficiency is associated with thyroid autoimmunity: results from an epidemiological survey in Tianjin, China.", "citation": "Fang F, Chai Y, Wei H et al. Vitamin D deficiency is associated with thyroid autoimmunity: results from an epidemiological survey in Tianjin, China. Endocrine. 2021.", "doi": "10.1007/s12020-021-02688-z", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33759075/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33759075/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID33759075", "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": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Low vitamin D associated with thyroid autoantibodies.", "what_it_does_not_show": "Reverse causation and common causes remain; antibody presence is not disease-incidence reduction.", "confounders_present": [ "Reverse causation and common causes remain; antibody presence is not disease-incidence 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": [] }, "shared_components": [] }, { "n": 32, "pmid": "32414130", "title": "Low Vitamin D Levels Predict Mortality in Ankylosing Spondylitis Patients: A Nationwide Population-Based Cohort Study.", "citation": "Ben-Shabat N, Watad A, Shabat A et al. Low Vitamin D Levels Predict Mortality in Ankylosing Spondylitis Patients: A Nationwide Population-Based Cohort Study. Nutrients. 2020.", "doi": "10.3390/nu12051400", "pmcid": "PMC7285142", "url": "https://pubmed.ncbi.nlm.nih.gov/32414130/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32414130/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID32414130", "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": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Low vitamin D associated with mortality in ankylosing spondylitis.", "what_it_does_not_show": "Disease-related confounding and subgroup context preclude a supplementation causal claim.", "confounders_present": [ "Disease-related confounding and subgroup context preclude a supplementation causal claim." ], "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": [] }, "shared_components": [] }, { "n": 33, "pmid": "37437450", "title": "Associations between vitamin D and autoimmune diseases: Mendelian randomization analysis.", "citation": "Zhao SS, Mason A, Gjekmarkaj E et al. Associations between vitamin D and autoimmune diseases: Mendelian randomization analysis. Seminars in arthritis and rheumatism. 2023.", "doi": "10.1016/j.semarthrit.2023.152238", "pmcid": "PMC7614794", "url": "https://pubmed.ncbi.nlm.nih.gov/37437450/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37437450/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID37437450", "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": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Mendelian randomization supported a disease-specific psoriasis signal and weaker lupus findings.", "what_it_does_not_show": "Instrument assumptions and disease heterogeneity do not establish broad autoimmune prevention.", "confounders_present": [ "Instrument assumptions and disease heterogeneity do not establish broad autoimmune prevention." ], "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": [] }, "shared_components": [] }, { "n": 34, "pmid": "22069289", "title": "The effect of vitamin D supplementation on peripheral regulatory T cells and β cell function in healthy humans: a randomized controlled trial.", "citation": "Bock G, Prietl B, Mader JK et al. The effect of vitamin D supplementation on peripheral regulatory T cells and β cell function in healthy humans: a randomized controlled trial. Diabetes/metabolism research and reviews. 2011.", "doi": "10.1002/dmrr.1276", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/22069289/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/22069289/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID22069289", "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": "supports", "what_it_shows": "Supplementation increased a T-regulatory-cell measure in a controlled study.", "what_it_does_not_show": "Immune-cell percentage change did not demonstrate beta-cell function or disease-incidence benefit.", "confounders_present": [ "Immune-cell percentage change did not demonstrate beta-cell function or disease-incidence 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": [] }, "shared_components": [] }, { "n": 35, "pmid": "20122848", "title": "No effect of supplementation with cholecalciferol on cytokines and markers of inflammation in overweight and obese subjects.", "citation": "Jorde R, Sneve M, Torjesen PA et al. No effect of supplementation with cholecalciferol on cytokines and markers of inflammation in overweight and obese subjects. Cytokine. 2010.", "doi": "10.1016/j.cyto.2009.12.006", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/20122848/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/20122848/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID20122848", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Supplementation in obesity did not change the tested cytokine markers.", "what_it_does_not_show": "A selected cytokine null does not exclude all vitamin-D pathways.", "confounders_present": [ "A selected cytokine null does not exclude all vitamin-D pathways." ], "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": [] }, "shared_components": [] }, { "n": 36, "pmid": "35198149", "title": "Effects of Vitamin D supplementation on resolution of fever and cough in children with pulmonary tuberculosis: A randomized double-blind controlled trial in Indonesia.", "citation": "Tamara L, Kartasasmita CB, Alam A et al. Effects of Vitamin D supplementation on resolution of fever and cough in children with pulmonary tuberculosis: A randomized double-blind controlled trial in Indonesia. Journal of global health. 2022.", "doi": "10.7189/jogh.12.04015", "pmcid": "PMC8855907", "url": "https://pubmed.ncbi.nlm.nih.gov/35198149/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35198149/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "NCT05073965", "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": "supports", "what_it_shows": "Adjunct vitamin D improved selected symptom-resolution outcomes in children treated for tuberculosis.", "what_it_does_not_show": "Treatment response is not prevention of tuberculosis infection or broad disease incidence.", "confounders_present": [ "Treatment response is not prevention of tuberculosis infection or broad disease incidence." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 37, "pmid": "35639792", "title": "High-dose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial.", "citation": "Annweiler C, Beaudenon M, Gautier J et al. High-dose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial. PLoS medicine. 2022.", "doi": "10.1371/journal.pmed.1003999", "pmcid": "PMC9154122", "url": "https://pubmed.ncbi.nlm.nih.gov/35639792/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35639792/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "NCT04344041", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "COVIT reported an early adjusted mortality signal in older patients treated for acute COVID-19.", "what_it_does_not_show": "Open-label acute treatment, short-term endpoint and adjustment do not establish prevention or a durable universal effect.", "confounders_present": [ "Open-label acute treatment, short-term endpoint and adjustment do not establish prevention or a durable universal 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": [] }, "shared_components": [] }, { "n": 38, "pmid": "39861434", "title": "Vitamins K2 and D3 Improve Long COVID, Fungal Translocation, and Inflammation: Randomized Controlled Trial.", "citation": "Atieh O, Daher J, Durieux JC et al. Vitamins K2 and D3 Improve Long COVID, Fungal Translocation, and Inflammation: Randomized Controlled Trial. Nutrients. 2025.", "doi": "10.3390/nu17020304", "pmcid": "PMC11767688", "url": "https://pubmed.ncbi.nlm.nih.gov/39861434/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39861434/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID39861434", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "A vitamin-K2/D3 Long-COVID combination reported clinical-index improvement.", "what_it_does_not_show": "Combination and comparator conditions do not isolate vitamin D or test disease prevention.", "confounders_present": [ "Combination and comparator conditions do not isolate vitamin D or test disease prevention." ], "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": [] }, "shared_components": [] }, { "n": 39, "pmid": "32706534", "title": "Vitamin D Supplements for Prevention of Tuberculosis Infection and Disease.", "citation": "Ganmaa D, Uyanga B, Zhou X et al. Vitamin D Supplements for Prevention of Tuberculosis Infection and Disease. The New England journal of medicine. 2020.", "doi": "10.1056/NEJMoa1915176", "pmcid": "PMC7476371", "url": "https://pubmed.ncbi.nlm.nih.gov/32706534/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32706534/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "NCT02276755", "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:Results:paragraph2, 1:Results:paragraph4. 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": "null", "what_it_shows": "Supplementation raised vitamin-D levels but did not prevent tuberculosis infection or disease in a largely deficient child population.", "what_it_does_not_show": "Specific population and outcome; null disease incidence is not proof of every vitamin-D mechanism's absence.", "confounders_present": [ "Specific population and outcome; null disease incidence is not proof of every vitamin-D mechanism's absence." ], "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": [] }, "shared_components": [] }, { "n": 40, "pmid": "38113446", "title": "Effect of Daily Vitamin D Supplementation on Risk of Upper Respiratory Infection in Older Adults: A Randomized Controlled Trial.", "citation": "Camargo CA, Schaumberg DA, Friedenberg G et al. Effect of Daily Vitamin D Supplementation on Risk of Upper Respiratory Infection in Older Adults: A Randomized Controlled Trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2024.", "doi": "10.1093/cid/ciad770", "pmcid": "PMC11093666", "url": "https://pubmed.ncbi.nlm.nih.gov/38113446/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38113446/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "VITAL", "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": "null", "what_it_shows": "VITAL found no overall reduction in upper-respiratory infection.", "what_it_does_not_show": "The very-low-baseline subgroup was small and uncertain, so not all severe-deficiency effects are resolved.", "confounders_present": [ "The very-low-baseline subgroup was small and uncertain, so not all severe-deficiency effects are resolved." ], "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": [] }, "shared_components": [ "Shared parent randomization/recruitment and outcome ascertainment: VITAL" ] }, { "n": 41, "pmid": "33714594", "title": "Vitamin D Status Is Associated With In-Hospital Mortality and Mechanical Ventilation: A Cohort of COVID-19 Hospitalized Patients.", "citation": "Angelidi AM, Belanger MJ, Lorinsky MK et al. Vitamin D Status Is Associated With In-Hospital Mortality and Mechanical Ventilation: A Cohort of COVID-19 Hospitalized Patients. Mayo Clinic proceedings. 2021.", "doi": "10.1016/j.mayocp.2021.01.001", "pmcid": "PMC7834253", "url": "https://pubmed.ncbi.nlm.nih.gov/33714594/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33714594/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID33714594", "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": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Hospital COVID-19 vitamin-D measurements associated with mortality.", "what_it_does_not_show": "Acute illness can change measured levels; association does not establish correction benefit.", "confounders_present": [ "Acute illness can change measured levels; association does not establish correction 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": [] }, "shared_components": [] }, { "n": 42, "pmid": "29089348", "title": "Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study.", "citation": "Dimitrakopoulou VI, Tsilidis KK, Haycock PC et al. Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study. BMJ (Clinical research ed.). 2017.", "doi": "10.1136/bmj.j4761", "pmcid": "PMC5666592", "url": "https://pubmed.ncbi.nlm.nih.gov/29089348/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29089348/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID29089348", "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": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Mendelian randomization did not support moderate causal effects across seven cancers.", "what_it_does_not_show": "Instrument validity and power for small or nonlinear effects remain limitations.", "confounders_present": [ "Instrument validity and power for small or nonlinear effects remain limitations." ], "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": [] }, "shared_components": [] }, { "n": 43, "pmid": "33596318", "title": "Metabolic Signatures of Genetically Elevated Vitamin D Among Chinese: Observational and Mendelian Randomization Study.", "citation": "Zhuang Z, Yu C, Guo Y et al. Metabolic Signatures of Genetically Elevated Vitamin D Among Chinese: Observational and Mendelian Randomization Study. The Journal of clinical endocrinology and metabolism. 2021.", "doi": "10.1210/clinem/dgab097", "pmcid": "PMC7612493", "url": "https://pubmed.ncbi.nlm.nih.gov/33596318/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33596318/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID33596318", "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": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Lipid Mendelian randomization lacked strong multiple-testing-corrected findings.", "what_it_does_not_show": "Nominal lipid signals are neither robust causal evidence nor hard clinical outcomes.", "confounders_present": [ "Nominal lipid signals are neither robust causal evidence nor hard clinical outcomes." ], "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": [] }, "shared_components": [] }, { "n": 44, "pmid": "25406188", "title": "Genetically low vitamin D concentrations and increased mortality: Mendelian randomisation analysis in three large cohorts.", "citation": "Afzal S, Brøndum-Jacobsen P, Bojesen SE et al. Genetically low vitamin D concentrations and increased mortality: Mendelian randomisation analysis in three large cohorts. BMJ (Clinical research ed.). 2014.", "doi": "10.1136/bmj.g6330", "pmcid": "PMC4238742", "url": "https://pubmed.ncbi.nlm.nih.gov/25406188/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/25406188/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID25406188", "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": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Genetic analysis supported selected mortality associations, differing by cause.", "what_it_does_not_show": "Pleiotropy and instrument assumptions remain; genetic lifelong exposure is not an oral supplement trial.", "confounders_present": [ "Pleiotropy and instrument assumptions remain; genetic lifelong exposure is not an oral supplement 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": [] }, "shared_components": [] }, { "n": 45, "pmid": "30597039", "title": "Circulating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study.", "citation": "Jiang X, Dimou NL, Al-Dabhani K et al. Circulating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study. International journal of epidemiology. 2019.", "doi": "10.1093/ije/dyy284", "pmcid": "PMC6934026", "url": "https://pubmed.ncbi.nlm.nih.gov/30597039/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30597039/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID30597039", "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": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Large Mendelian randomization found no convincing breast/prostate cancer effect.", "what_it_does_not_show": "Does not exclude all small, nonlinear or population-specific effects.", "confounders_present": [ "Does not exclude all small, nonlinear or population-specific 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": [] }, "shared_components": [] }, { "n": 46, "pmid": "32918767", "title": "A comprehensive genetic and epidemiological association analysis of vitamin D with common diseases/traits in the UK Biobank.", "citation": "Ye Y, Yang H, Wang Y et al. A comprehensive genetic and epidemiological association analysis of vitamin D with common diseases/traits in the UK Biobank. Genetic epidemiology. 2021.", "doi": "10.1002/gepi.22357", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/32918767/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32918767/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID32918767", "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": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "A phenome-wide genetic study supported selected disease-specific possibilities including multiple sclerosis.", "what_it_does_not_show": "Multiple comparisons and instruments do not establish that all low-D associations are causal.", "confounders_present": [ "Multiple comparisons and instruments do not establish that all low-D associations are causal." ], "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": [] }, "shared_components": [] }, { "n": 47, "pmid": "29315215", "title": "Association between Vitamin D Genetic Risk Score and Cancer Risk in a Large Cohort of U.S. Women.", "citation": "Chandler PD, Tobias DK, Wang L et al. Association between Vitamin D Genetic Risk Score and Cancer Risk in a Large Cohort of U.S. Women. Nutrients. 2018.", "doi": "10.3390/nu10010055", "pmcid": "PMC5793283", "url": "https://pubmed.ncbi.nlm.nih.gov/29315215/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29315215/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID29315215", "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": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "A genetic vitamin-D score did not predict the tested cancers in the women's cohort.", "what_it_does_not_show": "Population and instrument limitations constrain small/nonlinear effects.", "confounders_present": [ "Population and instrument limitations constrain small/nonlinear 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": [] }, "shared_components": [] }, { "n": 48, "pmid": "36279545", "title": "Vitamin D Deficiency Increases Mortality Risk in the UK Biobank : A Nonlinear Mendelian Randomization Study.", "citation": "Sutherland JP, Zhou A, Hyppönen E. Vitamin D Deficiency Increases Mortality Risk in the UK Biobank : A Nonlinear Mendelian Randomization Study. Annals of internal medicine. 2022.", "doi": "10.7326/M21-3324", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/36279545/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36279545/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID36279545", "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": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Nonlinear Mendelian randomization suggested a low-level mortality relationship.", "what_it_does_not_show": "Stratification/instrument assumptions require caution; this is not randomized correction of severe deficiency.", "confounders_present": [ "Stratification/instrument assumptions require caution; this is not randomized correction of severe deficiency." ], "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": [] }, "shared_components": [] }, { "n": 49, "pmid": "33420236", "title": "The causal role of circulating vitamin D concentrations in human complex traits and diseases: a large-scale Mendelian randomization study.", "citation": "Jiang X, Ge T, Chen CY. The causal role of circulating vitamin D concentrations in human complex traits and diseases: a large-scale Mendelian randomization study. Scientific reports. 2021.", "doi": "10.1038/s41598-020-80655-w", "pmcid": "PMC7794542", "url": "https://pubmed.ncbi.nlm.nih.gov/33420236/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33420236/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID33420236", "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": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Multi-trait Mendelian randomization supported selected outcomes, including multiple sclerosis, while most traits were null.", "what_it_does_not_show": "A selective genetic association pattern does not prove broad supplement-preventable disease.", "confounders_present": [ "A selective genetic association pattern does not prove broad supplement-preventable disease." ], "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": [] }, "shared_components": [] }, { "n": 50, "pmid": "28384800", "title": "Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study : A Randomized Clinical Trial.", "citation": "Scragg R, Stewart AW, Waayer D et al. Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study : A Randomized Clinical Trial. JAMA cardiology. 2017.", "doi": "10.1001/jamacardio.2017.0175", "pmcid": "PMC5815022", "url": "https://pubmed.ncbi.nlm.nih.gov/28384800/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28384800/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID28384800", "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": "null", "what_it_shows": "ViDA did not reduce cardiovascular events with its tested supplementation regimen.", "what_it_does_not_show": "Regimen and population context matter; no inference to all possible dosing or severe deficiency.", "confounders_present": [ "Regimen and population context matter; no inference to all possible dosing or severe deficiency." ], "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": [] }, "shared_components": [] } ], "verification_summary": { "load_bearing_claims_checked": 54, "verified": 54, "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": "Β", "cap_source": "universal", "triggered": true, "trigger_text_quoted": "Pure association evidence — however large, however replicated — cannot exceed Β.", "specific_trigger": "Low vitamin D predicts selected disease risks but illness, adiposity, exposure and behavior can confound those associations.", "resulting_ceiling": "Β" } ], "cap_precedence_resolutions": [ { "collision": "Perturbation in a defined setting versus broader inference", "subclaim_scope_cap_binds_on": "Low circulating 25-hydroxyvitamin D is a causal contributor to non-skeletal disease, such that supplementation reduces incidence.", "subclaim_scope_threshold_binds_on": "The precise experimentally tested subclaim scope", "resolution": "Biochemical correction confirms exposure but does not itself cross a clinical prevention threshold. Positive immune-pathway or disease-specific results retain their scopes; null broad prevention does not negate skeletal biology. The nominal Γ is an unmet causal threshold assessment, not a claim that all trials or all mechanisms are biomarker-only.", "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": [ "Human associations and biomarker-only changes do not establish the broad causal claim.", "Model perturbations bind their tested species and phenotype, not an untested human scope.", "Positive treatment effects are checked for specific mechanism attribution; negative trials require target engagement before mechanistic falsification." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Low vitamin D predicts selected disease risks but illness, adiposity, exposure and behavior can confound those associations.", "ceiling_from_boundary_check": "Γ" }, { "subclaim_id": "SC2", "field_valid_perturbation_quote": "\n- Cell-type-specific conditional knockout or depletion\n- Pathway-specific blockade (not broad immunosuppression) changing disease course\n- Human targeted therapy with mechanistic alignment showing disease-modifying effect", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "", "gamma_hard_rules_triggered": [ "Human associations and biomarker-only changes do not establish the broad causal claim.", "Model perturbations bind their tested species and phenotype, not an untested human scope.", "Positive treatment effects are checked for specific mechanism attribution; negative trials require target engagement before mechanistic falsification." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Biological signaling, immune-cell changes and selected genetic/disease-specific findings support plausibility; broad nonskeletal causal pathways are not established by biomarkers alone.", "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": [ "Human associations and biomarker-only changes do not establish the broad causal claim.", "Model perturbations bind their tested species and phenotype, not an untested human scope.", "Positive treatment effects are checked for specific mechanism attribution; negative trials require target engagement before mechanistic falsification." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Large randomized trials do not show a consistent broad prevention effect. Positive disease-specific or original secondary findings do not establish the registered across-category claim.", "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": "A valid genetic/natural-experiment or randomized correction must establish outcome causality beyond the association." }, { "subclaim_id": "SC2", "threshold": "Δ", "requirement_quoted": "Requires pathway- or cell-type-resolved causal perturbation affecting disease or phenotype.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "Pathway-specific manipulation must affect the relevant disease course, rather than only immune-cell or serum measures." }, { "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": "Prespecified deficiency-defined randomized correction must reduce the specified clinical incidences with biochemical engagement and appropriate disease-specific controls." } ], "generalization_check": { "generalization_tested": "no", "context_boundary_mapped": "yes", "internal_negative_controls": [ "VITAL primary cancer and cardiovascular outcomes were null despite biochemical exposure.", "Mongolian children had largely deficient baseline levels yet tuberculosis infection/disease prevention was null.", "Achieved levels are postrandomization variables, not randomized subgroup definitions." ], "note": "Regimens, ages, diseases and baseline levels differ. The largely deficient Mongolian childhood trial is an important counterexample to explaining every null by vitamin-D-replete recruitment. Severe deficiency in other outcomes remains incompletely tested." }, "falsification_patterns_met": [], "pitfalls_flagged": [ { "pitfall": "Superseded estimate", "where": "Later VITAL case confirmation attenuated the originally significant autoimmune estimate; both reports are one trial." }, { "pitfall": "Surrogate substitution", "where": "Concentration, T-cell changes and telomere measures are not disease-incidence benefit." }, { "pitfall": "Post-outcome scope", "where": "Achieved vitamin-D concentrations cannot retrospectively define a randomized responsive group." }, { "pitfall": "Combination attribution", "where": "Saxagliptin, peptide/calcitriol and K2/D3 combinations do not isolate vitamin D." } ], "causal_tally_audit": { "tally_claimed_by_document": 18, "tally_after_audit": 18, "items_rejected": [ "Null and negative contrasts are discriminators, not positive threshold crossings. Reports and replications are not independent causal lines.", "The tally counts reports with discriminating intervention contrasts, including negative results; it is not a count of positive causal crossings.", "Shared parent trials and multiple manipulations within a study remain grouped." ] }, "steelman": { "case_one_rung_higher": "Case for Δ: original VITAL autoimmune prevention, selected genetic findings and deficiency-related subgroup signals supply credible causal leads. However, updated randomized-period case confirmation weakened the autoimmune estimate; tuberculosis treatment response is not prevention, and no coherent across-category incidence crossing is established.", "case_one_rung_lower": "Case for Β: strong associations are frequently confounded and broad prevention trials are null. Experimental signaling and selected genetic/disease-specific evidence still supply partial mechanistic support, so a purely association-only classification discards relevant causal leads.", "which_rejected": "Retain Γ for the exact broad claim; neither original secondary significance nor broad nulls resolve every disease-specific effect. Do not count VITAL follow-ups as independent replication.", "blocking_cap_threshold_or_missing_experiment": "Missing experiment: Randomize correction within prespecified, safely enrolled baseline-deficiency strata, using registered disease-specific incidence endpoints and measured biochemical engagement; compare across strata without conditioning on achieved levels." }, "final_score": { "hsef_level": "Γ", "hsef_descriptor": "Mechanistically plausible, partial system support", "confidence": "Moderate", "confidence_rationale": "Several large independent randomized trials on different continents converge on the broad null, which is substantial density, but substantive evidence-quality reservations remain and are documented in the review itself: the registered exposure is deficiency while the large trials supplemented broad populations with mostly modest baseline deficiency, so they are indirect for the registered estimand; the one trial recruited in a genuinely deficient population tests a single disease in children; the secondary and tertiary reports share parent-trial participants rather than replicating independently; achieved-concentration analyses condition on a postrandomization variable; subgroup and genotype signals are unreplicated; and the Mendelian-randomization evidence carries instrument and nonlinear-stratification assumptions. Evidence density and reproducibility set the Moderate band, not the reviewer's access depth and not correctness.", "rests_on_non_peer_reviewed_work": false, "rationale": "Overall Γ is a partial-mechanism assessment for the registered broad prevention claim, not a denial of vitamin-D biology or skeletal indications. Robust null trials and attenuated secondary evidence prevent a broad positive causal crossing; genetic and disease-specific findings keep this above a purely associational interpretation." }, "role_of_mechanism": { "classification": "epiphenomenon", "derivation_step_matched": 2, "derivation": "For the registered across-category prevention claim, a general dependency on deficiency is not established. Step 2 records this unresolved general role; it does not assert vitamin D is biologically incidental in every disease or in skeletal physiology.", "tournament_used_as_tiebreaker": false, "note": "Derived from causal direction, not tournament rank." }, "extended_scoring_MSD": { "momentum": { "value": "Mechanistic only", "artifact": "D-Health cancer incidence (PMID40096917), updated VITAL autoimmune outcomes (PMID38272846) and D2d genotype analyses (PMID42024385) refine disease-specific boundaries. These are completed reports; no verified named pending broad deficiency-correction result was found.", "justification": "D-Health cancer incidence (PMID40096917), updated VITAL autoimmune outcomes (PMID38272846) and D2d genotype analyses (PMID42024385) refine disease-specific boundaries. These are completed reports; no verified named pending broad deficiency-correction result was found." }, "stability": { "value": "Stable", "trigger": "No specific pending result with a verified completion trigger was identified in this bounded search; Stable follows the framework definition, not a forecast of permanent truth.", "justification": "No specific pending result with a verified completion trigger was identified in this bounded search; Stable follows the framework definition, not a forecast of permanent truth." }, "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. Artifact for the split: supplement marketing, much of the observational literature and parts of clinical practice frame vitamin-D correction as broadly preventive, implying a high rung, while the field's own large randomized trials are read by trialists as showing no broad prevention effect, implying the bottom of the ladder for the registered claim (PMID30415629,35026158,40096917,32706534)." }, "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 correction within prespecified, safely enrolled baseline-deficiency strata, using registered disease-specific incidence endpoints and measured biochemical engagement; compare across strata without conditioning on achieved levels.", "readout": "Confirmed disease incidence and function, biochemical engagement and treatment adherence", "critical_control": "Baseline definition before outcomes, ethical deficiency treatment rules, adjudication blinded to allocation and multiplicity control", "supporting_result": "Reproducible clinically meaningful prevention in the registered deficiency/disease scope", "falsifying_result": "Verified correction without the prespecified incidence effect at adequate precision and follow-up" } ], "knowledge_gaps": [ { "name": "Gap 1", "statement": "Severe deficiency remains incompletely represented for several outcomes.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 2", "statement": "Disease-specific effect sizes and nonlinear exposure assumptions need independent tests.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 3", "statement": "Genetic instrument validity and pleiotropy remain assumptions.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 4", "statement": "Some apparent vitamin-D benefits involve combinations or secondary endpoints.", "relevance": "Limits mechanism identification or scope." } ], "review_metadata": { "review_date": "2026-10-09", "reviewer": "Codex", "evidence_base_note": "50 primary reports; literature cutoff 2026-10-09; source examination UTC date 2026-10-10; 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; No Consensus or Scite calls used; PubMed primary records and separately logged public original-body retrieval only.", "skill_version": "5.3", "validator_run": "Exact package-bundled v5.3 validator: PASS, zero FAIL findings; rerun after sealing.", "validator_warnings_addressed": "No warnings.", "limits": "Bounded critical review; not systematic review, complete-abstract audit, complete-paper audit, blind calibration or independent peer review.", "consensus_consistency_audit": "2026-10-09; supplementary provenance/source reconciliation; original grading retained; prior grades visible." }, "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": "Ranking categorical verdict and index guidance were visible. No completed blinded calibration claimed." }, "upper_ladder_check": { "final_level_below_zeta": true, "equivalents_considered": [ { "kind": "mendelian_randomization", "available": false, "why_not_sufficient": "No convergence establishes the full registered claim. Positive narrower results are retained without re-capping an assembled causal set; their scopes and distinct failure modes are stated separately." }, { "kind": "natural_experiment", "available": false, "why_not_sufficient": "No convergence establishes the full registered claim. Positive narrower results are retained without re-capping an assembled causal set; their scopes and distinct failure modes are stated separately." }, { "kind": "dose_response_across_populations", "available": false, "why_not_sufficient": "No convergence establishes the full registered claim. Positive narrower results are retained without re-capping an assembled causal set; their scopes and distinct failure modes are stated separately." }, { "kind": "withdrawal_rechallenge", "available": false, "why_not_sufficient": "No convergence establishes the full registered claim. Positive narrower results are retained without re-capping an assembled causal set; their scopes and distinct failure modes are stated separately." }, { "kind": "therapeutic_perturbation_hard_endpoint", "available": false, "why_not_sufficient": "No convergence establishes the full registered claim. Positive narrower results are retained without re-capping an assembled causal set; their scopes and distinct failure modes are stated separately." } ], "convergence_present": false, "cap_reapplied_to_convergent_set": false }, "provenance_header": { "sources_total": 50, "claims_total": 54, "claims_verified": 54, "claims_unverified": 0, "claims_contradicted": 0, "tier_a_sources": 50, "generated_by": "Codex; HSEF v5.3", "gate_passed": true }, "claims": [ { "id": "C1", "text": "VITAL did not significantly reduce its primary invasive-cancer or major-cardiovascular endpoints with vitamin D. This constrains broad prevention in the enrolled population, not every severely deficient or disease-specific subgroup.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 1 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:RESULTS:paragraph2, 1:RESULTS:paragraph5. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C2", "text": "VITAL-DEP did not significantly prevent depression outcomes. This is not a trial of treating every existing depressive disorder or severe deficiency.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 2 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C3", "text": "VITAL frailty analyses found no clear preventive benefit. Frailty analysis does not establish all possible skeletal or functional effects.", "carries_number": false, "load_bearing_for": [ "SC1", "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": "2026-10-10", "note": "" }, { "id": "C4", "text": "A smaller VITAL subgroup did not demonstrate depression prevention. Limited subgroup power and shared parent cohort do not create independent replication.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 4 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C5", "text": "VITAL kidney strata showed biochemical vitamin-D/PTH effects without differential cancer/CV benefit. Biochemical target response is not broad disease-incidence reduction.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 5 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C6", "text": "D-Health cardiovascular analyses suggested a modest signal with an overall confidence interval including no effect. Nominal secondary/subgroup findings are not definitive broad cardiovascular prevention.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 6 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C7", "text": "D-Health cognitive analyses found no benefit on tested cognition. Same parent trial, selected measures and enrollment restrict scope.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "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": "2026-10-10", "note": "" }, { "id": "C8", "text": "Pilot supplementation did not clearly reduce overall antibiotic use. An exploratory older subgroup and nonsignificant interaction cannot establish a reliable subgroup effect.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 8 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C9", "text": "D-Health tertiary analyses did not reduce incident hypothyroidism. A tertiary endpoint is not independent confirmation of autoimmune prevention.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "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": "2026-10-10", "note": "" }, { "id": "C10", "text": "D-Health did not reduce overall cancer incidence. Not all cancer subtypes or severely deficient populations are separately resolved.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "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": "2026-10-10", "note": "" }, { "id": "C11", "text": "A pilot showed feasible supplementation and increased vitamin-D levels. Feasibility and biochemical correction are not clinical prevention.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 11 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C12", "text": "D-Health did not reduce all-cause mortality. Exploratory cancer-mortality analyses do not establish generalized harm; an erratum is attached.", "carries_number": false, "load_bearing_for": [ "SC1", "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": "2026-10-10", "note": "" }, { "id": "C13", "text": "D-Health did not reduce acute respiratory infection incidence, with limited duration findings. Episode duration is distinct from prevention incidence and from severe-deficiency effects.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 13 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C14", "text": "Pilot D-Health work found no clear broad inflammatory-marker improvement. A biomarker null does not establish every clinical outcome.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 14 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C15", "text": "D-Health did not change the tested telomere-length endpoint. Telomere length is not a validated substitute for organismal aging or disease prevention.", "carries_number": false, "load_bearing_for": [ "SC1", "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": "2026-10-10", "note": "" }, { "id": "C16", "text": "D2d's primary diabetes endpoint favored supplementation numerically but did not reach statistical significance. Participants were not selected for vitamin-D deficiency; the result does not prove benefit or exclude a modest effect.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 16 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C17", "text": "D2d beta-cell measures were null overall with a low-baseline-D subgroup signal. Biomarker subgroup results require replication and cannot establish broad diabetes prevention.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 17 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C18", "text": "D2d did not clearly reduce cancer/polyps in its secondary analysis. Shared cohort and limited event counts restrict precision.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 18 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C19", "text": "D2d genotype analyses suggested differential diabetes response. Baseline genotype is prespecifiable but exploratory interaction requires independent replication.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 19 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C20", "text": "D2d kidney outcomes showed no clear benefit. Secondary renal endpoints do not establish universal absence of vitamin-D effects.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 20 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C21", "text": "Higher achieved vitamin-D levels in D2d associated with lower diabetes risk. Conditioning on postrandomization levels does not retain randomized assignment of those levels.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 21 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C22", "text": "D2d cardiovascular events were not clearly reduced despite selected risk-score changes. Surrogate change and limited events do not establish clinical prevention.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 22 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C23", "text": "D2d monitored supplementation without a clear major safety difference. Safety under trial monitoring is not proof of efficacy or universal safety; an erratum is attached.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 23 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C24", "text": "The original VITAL autoimmune report found a statistically significant reduction in confirmed incident autoimmune disease. The same cohort's later case confirmation attenuated the estimate; it is not an independently replicated broad signal.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "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": "2026-10-10", "note": "" }, { "id": "C25", "text": "Updated VITAL cases weakened the randomized vitamin-D autoimmune estimate and follow-up showed no overall sustained vitamin-D difference. Observational post-trial follow-up is not continued randomized supplementation; attenuation does not exclude all disease-specific effects.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "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. Selected body sections: 2:RESULTS:paragraph4. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C26", "text": "DEN-181 altered immune measures in a small rheumatoid-arthritis phase 1 trial. A peptide/calcitriol combination is not oral vitamin-D population prevention or isolated vitamin-D efficacy.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 26 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C27", "text": "Vitamin-D receptor variants associated with Hashimoto thyroiditis. Association is not a validated exposure instrument or randomized supplementation effect.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 27 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C28", "text": "LADA combination-treatment arms had selected within-group beta-cell findings. No significant between-group difference on the listed measures; saxagliptin prevents isolating vitamin D.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "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": "2026-10-10", "note": "" }, { "id": "C29", "text": "A retrospective Hashimoto study associated supplementation/level changes with antibody trajectories. Nonrandomized groups and antibody surrogates do not establish clinical prevention.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "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": "2026-10-10", "note": "" }, { "id": "C30", "text": "A saxagliptin/vitamin-D type 1 diabetes trial missed its primary fasting C-peptide endpoint with a secondary signal. Combination attribution and secondary analysis cannot establish vitamin-D-alone prevention.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "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": "2026-10-10", "note": "" }, { "id": "C31", "text": "Low vitamin D associated with thyroid autoantibodies. Reverse causation and common causes remain; antibody presence is not disease-incidence reduction.", "carries_number": false, "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": "2026-10-10", "note": "" }, { "id": "C32", "text": "Low vitamin D associated with mortality in ankylosing spondylitis. Disease-related confounding and subgroup context preclude a supplementation causal claim.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "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": "2026-10-10", "note": "" }, { "id": "C33", "text": "Mendelian randomization supported a disease-specific psoriasis signal and weaker lupus findings. Instrument assumptions and disease heterogeneity do not establish broad autoimmune prevention.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "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": "2026-10-10", "note": "" }, { "id": "C34", "text": "Supplementation increased a T-regulatory-cell measure in a controlled study. Immune-cell percentage change did not demonstrate beta-cell function or disease-incidence benefit.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "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": "2026-10-10", "note": "" }, { "id": "C35", "text": "Supplementation in obesity did not change the tested cytokine markers. A selected cytokine null does not exclude all vitamin-D pathways.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "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": "2026-10-10", "note": "" }, { "id": "C36", "text": "Adjunct vitamin D improved selected symptom-resolution outcomes in children treated for tuberculosis. Treatment response is not prevention of tuberculosis infection or broad disease incidence.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "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": "2026-10-10", "note": "" }, { "id": "C37", "text": "COVIT reported an early adjusted mortality signal in older patients treated for acute COVID-19. Open-label acute treatment, short-term endpoint and adjustment do not establish prevention or a durable universal effect.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "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": "2026-10-10", "note": "" }, { "id": "C38", "text": "A vitamin-K2/D3 Long-COVID combination reported clinical-index improvement. Combination and comparator conditions do not isolate vitamin D or test disease prevention.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "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": "2026-10-10", "note": "" }, { "id": "C39", "text": "Supplementation raised vitamin-D levels but did not prevent tuberculosis infection or disease in a largely deficient child population. Specific population and outcome; null disease incidence is not proof of every vitamin-D mechanism's absence.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "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. Selected body sections: 1:Results:paragraph2, 1:Results:paragraph4. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C40", "text": "VITAL found no overall reduction in upper-respiratory infection. The very-low-baseline subgroup was small and uncertain, so not all severe-deficiency effects are resolved.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 40 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C41", "text": "Hospital COVID-19 vitamin-D measurements associated with mortality. Acute illness can change measured levels; association does not establish correction benefit.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "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": "2026-10-10", "note": "" }, { "id": "C42", "text": "Mendelian randomization did not support moderate causal effects across seven cancers. Instrument validity and power for small or nonlinear effects remain limitations.", "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. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C43", "text": "Lipid Mendelian randomization lacked strong multiple-testing-corrected findings. Nominal lipid signals are neither robust causal evidence nor hard clinical outcomes.", "carries_number": false, "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. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-10", "note": "" }, { "id": "C44", "text": "Genetic analysis supported selected mortality associations, differing by cause. Pleiotropy and instrument assumptions remain; genetic lifelong exposure is not an oral supplement trial.", "carries_number": false, "load_bearing_for": [ "SC1", "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": "2026-10-10", "note": "" }, { "id": "C45", "text": "Large Mendelian randomization found no convincing breast/prostate cancer effect. Does not exclude all small, nonlinear or population-specific effects.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "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": "2026-10-10", "note": "" }, { "id": "C46", "text": "A phenome-wide genetic study supported selected disease-specific possibilities including multiple sclerosis. Multiple comparisons and instruments do not establish that all low-D associations are causal.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "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": "2026-10-10", "note": "" }, { "id": "C47", "text": "A genetic vitamin-D score did not predict the tested cancers in the women's cohort. Population and instrument limitations constrain small/nonlinear effects.", "carries_number": false, "load_bearing_for": [ "SC1", "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": "2026-10-10", "note": "" }, { "id": "C48", "text": "Nonlinear Mendelian randomization suggested a low-level mortality relationship. Stratification/instrument assumptions require caution; this is not randomized correction of severe deficiency.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "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": "2026-10-10", "note": "" }, { "id": "C49", "text": "Multi-trait Mendelian randomization supported selected outcomes, including multiple sclerosis, while most traits were null. A selective genetic association pattern does not prove broad supplement-preventable disease.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "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": "2026-10-10", "note": "" }, { "id": "C50", "text": "ViDA did not reduce cardiovascular events with its tested supplementation regimen. Regimen and population context matter; no inference to all possible dosing or severe deficiency.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "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": "2026-10-10", "note": "" }, { "id": "CSC1", "text": "Low vitamin D predicts selected disease risks but illness, adiposity, exposure and behavior can confound those associations.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-10", "note": "" }, { "id": "CSC2", "text": "Biological signaling, immune-cell changes and selected genetic/disease-specific findings support plausibility; broad nonskeletal causal pathways are not established by biomarkers alone.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-10", "note": "" }, { "id": "CSC3", "text": "Large randomized trials do not show a consistent broad prevention effect. Positive disease-specific or original secondary findings do not establish the registered across-category claim.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-10", "note": "" }, { "id": "CH", "text": "Broad nonskeletal disease prevention by vitamin-D correction is not established; narrower deficiency and disease-specific questions remain open.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 1, 39, 24, 25, 33 ], "verification": "verified", "verified_against": "Bounded synthesis of examined sources; score is adjudication.", "verified_on": "2026-10-10", "note": "" } ], "citation_ledger": [ { "n": 1, "citation": "Manson JE, Cook NR, Lee IM et al. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. The New England journal of medicine. 2019.", "tier": "A", "kind": "rct", "pmid": "30415629", "doi": "10.1056/NEJMoa1809944", "url": "https://pubmed.ncbi.nlm.nih.gov/30415629/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "VITAL", "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:RESULTS:paragraph2, 1:RESULTS:paragraph5. No complete-paper or supplement audit claimed.", "carries_claims": [ "C1", "CSC1", "CSC2", "CSC3", "CH" ] }, { "n": 2, "citation": "Okereke OI, Reynolds CF, Mischoulon D et al. Effect of Long-term Vitamin D3 Supplementation vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial. JAMA. 2020.", "tier": "A", "kind": "rct", "pmid": "32749491", "doi": "10.1001/jama.2020.10224", "url": "https://pubmed.ncbi.nlm.nih.gov/32749491/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "VITAL", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C2", "CSC1", "CSC2", "CSC3" ] }, { "n": 3, "citation": "Orkaby AR, Dushkes R, Ward R et al. Effect of Vitamin D3 and Omega-3 Fatty Acid Supplementation on Risk of Frailty: An Ancillary Study of a Randomized Clinical Trial. JAMA network open. 2022.", "tier": "A", "kind": "rct", "pmid": "36098968", "doi": "10.1001/jamanetworkopen.2022.31206", "url": "https://pubmed.ncbi.nlm.nih.gov/36098968/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "VITAL", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C3", "CSC1", "CSC2", "CSC3" ] }, { "n": 4, "citation": "Vyas CM, Mischoulon D, Chang G et al. Effects of Vitamin D3 and Marine Omega-3 Fatty Acids Supplementation on Indicated and Selective Prevention of Depression in Older Adults: Results From the Clinical Center Sub-Cohort of the VITamin D and OmegA-3 TriaL (VITAL). The Journal of clinical psychiatry. 2023.", "tier": "A", "kind": "rct", "pmid": "37378490", "doi": "10.4088/JCP.22m14629", "url": "https://pubmed.ncbi.nlm.nih.gov/37378490/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "VITAL", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C4", "CSC1", "CSC2", "CSC3" ] }, { "n": 5, "citation": "Limonte CP, Zelnick LR, Hoofnagle AN et al. Effects of Vitamin D3 Supplementation on Cardiovascular and Cancer Outcomes by eGFR in VITAL. Kidney360. 2022.", "tier": "A", "kind": "rct", "pmid": "36591342", "doi": "10.34067/KID.0006472022", "url": "https://pubmed.ncbi.nlm.nih.gov/36591342/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "VITAL", "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", "CSC1", "CSC2", "CSC3" ] }, { "n": 6, "citation": "Thompson B, Waterhouse M, English DR et al. Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial. BMJ (Clinical research ed.). 2023.", "tier": "A", "kind": "rct", "pmid": "37380191", "doi": "10.1136/bmj-2023-075230", "url": "https://pubmed.ncbi.nlm.nih.gov/37380191/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D_HEALTH", "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", "CSC1", "CSC2", "CSC3" ] }, { "n": 7, "citation": "Pham H, Waterhouse M, Rahman S et al. Vitamin D supplementation and cognition-Results from analyses of the D-Health trial. Journal of the American Geriatrics Society. 2023.", "tier": "A", "kind": "primary", "pmid": "36715270", "doi": "10.1111/jgs.18247", "url": "https://pubmed.ncbi.nlm.nih.gov/36715270/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D_HEALTH", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C7", "CSC1", "CSC2", "CSC3" ] }, { "n": 8, "citation": "Tran B, Armstrong BK, Ebeling PR et al. Effect of vitamin D supplementation on antibiotic use: a randomized controlled trial. The American journal of clinical nutrition. 2014.", "tier": "A", "kind": "rct", "pmid": "24108783", "doi": "10.3945/ajcn.113.063271", "url": "https://pubmed.ncbi.nlm.nih.gov/24108783/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D_HEALTH_PILOT", "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": [ "C8", "CSC1", "CSC2", "CSC3" ] }, { "n": 9, "citation": "Waterhouse M, Pham H, Rahman ST et al. The Effect of Vitamin D Supplementation on Hypothyroidism in the Randomized Controlled D-Health Trial. Thyroid : official journal of the American Thyroid Association. 2023.", "tier": "A", "kind": "primary", "pmid": "37698908", "doi": "10.1089/thy.2023.0317", "url": "https://pubmed.ncbi.nlm.nih.gov/37698908/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D_HEALTH", "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": [ "C9", "CSC1", "CSC2", "CSC3" ] }, { "n": 10, "citation": "Neale RE, English DR, McLeod DS et al. The effect of vitamin D supplementation on cancer incidence in the randomised controlled D-Health Trial: Implications for policy and practice. The Journal of steroid biochemistry and molecular biology. 2025.", "tier": "A", "kind": "rct", "pmid": "40096917", "doi": "10.1016/j.jsbmb.2025.106738", "url": "https://pubmed.ncbi.nlm.nih.gov/40096917/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D_HEALTH", "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": [ "C10", "CSC1", "CSC2", "CSC3" ] }, { "n": 11, "citation": "Tran B, Armstrong BK, Carlin JB et al. Recruitment and results of a pilot trial of vitamin D supplementation in the general population of Australia. The Journal of clinical endocrinology and metabolism. 2012.", "tier": "A", "kind": "rct", "pmid": "23066119", "doi": "10.1210/jc.2012-2682", "url": "https://pubmed.ncbi.nlm.nih.gov/23066119/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D_HEALTH_PILOT", "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": [ "C11", "CSC1", "CSC2", "CSC3" ] }, { "n": 12, "citation": "Neale RE, Baxter C, Romero BD et al. The D-Health Trial: a randomised controlled trial of the effect of vitamin D on mortality. The lancet. Diabetes & endocrinology. 2022.", "tier": "A", "kind": "rct", "pmid": "35026158", "doi": "10.1016/S2213-8587(21)00345-4", "url": "https://pubmed.ncbi.nlm.nih.gov/35026158/", "status_flags": [ "ErratumIn: PMID35325597" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "D_HEALTH", "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": [ "C12", "CSC1", "CSC2", "CSC3" ] }, { "n": 13, "citation": "Pham H, Waterhouse M, Baxter C et al. The effect of vitamin D supplementation on acute respiratory tract infection in older Australian adults: an analysis of data from the D-Health Trial. The lancet. 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BMJ (Clinical research ed.). 2014.", "tier": "A", "kind": "primary", "pmid": "25406188", "doi": "10.1136/bmj.g6330", "url": "https://pubmed.ncbi.nlm.nih.gov/25406188/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-10", "status_checked_on": "2026-10-10", "study_id": "PMID25406188", "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": [ "C44", "CSC1", "CSC2", "CSC3" ] }, { "n": 45, "citation": "Jiang X, Dimou NL, Al-Dabhani K et al. Circulating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study. 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