{ "$schema_version": "5.3", "review_mode": "fresh", "claim_restatement": { "index_wording": "Oral magnesium supplementation improves sleep in adults with poor sleep or insomnia.", "entry_form": "claim", "gradeable_restatement": "Oral magnesium supplementation improves sleep in adults meeting the registered poor-sleep eligibility criteria.", "restatement_required": true, "split_into": [], "parent_claim": null, "scope_qualifiers": [ { "qualifier": "Age, baseline sleep symptoms/diagnosis, measured magnesium status or dietary assessment, renal function, formulation, dose and duration are enrollment facts; no responder-defined scope.", "determinable_before_outcome": true, "determined_from": "Enrollment and experimental design, before results; no responder-defined scope.", "action": "retained" } ], "original_claim": "Oral magnesium supplementation improves sleep in adults with poor sleep or insomnia.", "restatement_note": "The original poor-sleep/insomnia population is retained in preregistration. This grammatical restatement denotes the same baseline-defined sleep eligibility and does not exclude null outcomes, change the tested formulations or redefine eligibility by treatment response." }, "hypothesis": { "name": "Magnesium Forms, Sleep and Stress", "central_claim": "Oral magnesium supplementation improves sleep in adults meeting the registered poor-sleep eligibility criteria.", "proposed_mechanism": "Oral magnesium supplementation improves sleep in adults with poor sleep or insomnia.", "claimed_scope": "Oral magnesium formulations in adults with baseline poor sleep or insomnia, with formulation, elemental dose, baseline magnesium status, renal function, coingredients and a 2–24-week horizon specified before outcomes.", "claimed_level": [ "response", "maintenance" ], "is_conjunctive": false, "conjunctive_note": "The nominal is the clinical sufficiency proposition represented by SC2. Mechanism, superiority, additional indication and safety subclaims are separately reported and do not gate the registered efficacy claim. The original topic family and this narrower gradeable restatement are retained; no response-based exclusions are allowed." }, "rubric_routing": { "primary_rubric": "07-psychiatry-neuromodulation.md", "secondary_rubrics": [ "06-metabolism-aging.md" ], "index_notes_applied": [ "The nominal is the clinical sufficiency proposition represented by SC2. Mechanism, superiority, additional indication and safety subclaims are separately reported and do not gate the registered efficacy claim. The original topic family and this narrower gradeable restatement are retained; no response-based exclusions are allowed." ], "rubric_fit_note": "The frozen framework has no dedicated nutrition/sleep rubric. Rubric 07 is the closest clinical comparator route and 06 covers metabolic availability. Explicit adaptation: an ordinary non-hallucinogenic oral formulation versus a credible identical placebo can cross the clinical threshold for a prespecified validated sleep-symptom outcome. Psychedelic-specific subjective-effect matching is not imposed without evidence of unmistakable acute effects. Rating scales are accepted only for the registered symptom claim, not for objective architecture or functional recovery. Original rubric wording, universal caps and clinical mediator-manipulation requirements remain visible and unchanged." }, "subclaim_matrix": { "subclaims": [ { "id": "SC1", "statement": "Oral magnesium supplementation changes magnesium availability relevant to neural physiology.", "subclaim_type": "mechanism", "scope": "Chemical form, elemental dose, baseline deficiency, renal function and exposure specified", "claimed_scope": "Chemical form, elemental dose, baseline deficiency, renal function and exposure specified", "governing_rubric": "06-metabolism-aging.md", "key_evidence_anchor": "Original bioavailability, compartment and physiological studies", "hsef_level": "Γ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Controlled oral exposure and isotope studies demonstrate systemic absorption. Rodent central exposure and neural effects retain their experimental scope. Peripheral status changes and rodent cognition cannot establish human brain delivery or a sleep-relevant neural dependency at the studied exposure; the target-availability inference retains Γ. The separately controlled clinical formulation effect is assessed in SC2.", "rubric_adaptation": "Systemic absorption and measured exposure can establish availability under their defined conditions; central functional effects need actual brain or neural physiology evidence. Human urine/plasma measures alone do not establish brain delivery or sleep efficacy." }, { "id": "SC2", "statement": "Oral magnesium improves validated sleep outcomes against a credible comparator in adults with poor sleep or insomnia.", "subclaim_type": "sufficiency", "scope": "Baseline poor sleep or insomnia; age, deficiency, formulation, coingredients and 2–24-week horizon fixed", "claimed_scope": "Baseline poor sleep or insomnia; age, deficiency, formulation, coingredients and 2–24-week horizon fixed", "governing_rubric": "07-psychiatry-neuromodulation.md", "key_evidence_anchor": "Controlled sleep studies with objective or validated outcomes and nulls", "hsef_level": "Δ", "confidence": "Low", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "The prospectively registered, blinded 2025 bisglycinate trial supports a small improvement on the validated primary ISI outcome over four weeks. Older and newer studies contain additional positive, null and mixed sleep findings. A clean, reproducible baseline-deficiency effect boundary has not been mapped, clinically important responder contrasts are incompletely established and objective replication is limited. The first causal threshold is retained atΔ without elevating a small formulation effect to broad reliable insomnia treatment.", "rubric_adaptation": "The registered endpoint is validated sleep symptom improvement or objective sleep over 2–24 weeks, with a credible blinded comparison and prespecified outcomes. Do not equate a small statistical ISI change with remission or meaningful objective sleep restoration." }, { "id": "SC3", "statement": "Magnesium glycinate or threonate produces superior sleep benefit to other magnesium salts.", "subclaim_type": "generalization", "scope": "Matched elemental dose, population, duration and coingredients; no superiority inferred solely from absorption", "claimed_scope": "Matched elemental dose, population, duration and coingredients; no superiority inferred solely from absorption", "governing_rubric": "07-psychiatry-neuromodulation.md", "key_evidence_anchor": "Direct form-comparison sleep trials", "hsef_level": "Α", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "No directly examined, matched-elemental-dose human sleep trial establishes that glycinate or threonate is superior to other salts. Absorption comparisons and rodent cognitive/anxiety studies are not direct clinical sleep comparisons. This positive comparative sleep proposition remains unsupported atΑ, rather than being inferred from popularity or formulation branding.", "rubric_adaptation": "Clinical salt superiority requires direct matched elemental-dose and coingredient comparison in baseline-defined poor sleepers, with the same sleep endpoint and horizon. Pharmacokinetic rankings cannot substitute." }, { "id": "SC4", "statement": "Magnesium-mediated neural changes explain clinical sleep or stress improvement.", "subclaim_type": "mechanism", "scope": "Physiological mediator and relevant behaviour measured; rodent anxiety does not equal human insomnia", "claimed_scope": "Physiological mediator and relevant behaviour measured; rodent anxiety does not equal human insomnia", "governing_rubric": "07-psychiatry-neuromodulation.md", "key_evidence_anchor": "Manipulation, paired measurements and separating deficiency correction from supplementation", "hsef_level": "Γ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "NMDA structural/mutational studies, deficiency/repletion models and mouse ligand experiments support plausible neural mechanisms. Human sleep/stress studies generally measure hormones, magnesium or neural signals alongside symptoms without manipulating the candidate mediator while retaining treatment. Coingredients and glycine ligand exposure remain unpartitioned, so the human mediation claim does not crossΔ.", "rubric_adaptation": "Clinical mediation requires manipulating the proposed magnesium-dependent mediator while retaining treatment or another valid dissociation, with a sleep/stress trajectory readout. Correlation, animal proxies and EEG/hormone shifts alone do not qualify." } ], "aggregation_rule": "primary-subclaim", "aggregation_preregistered": true, "aggregation_rationale": "The nominal is the clinical sufficiency proposition represented by SC2. Mechanism, superiority, additional indication and safety subclaims are separately reported and do not gate the registered efficacy claim. The original topic family and this narrower gradeable restatement are retained; no response-based exclusions are allowed.", "primary_subclaim_id": "SC2", "aggregation_derivation": "The registered clinical subclaim SC2 supports Δ with Low confidence. A prospectively registered (DRKS00031494, registered 12 April 2023, before first enrolment on 20 April 2023), double-blind, placebo-controlled bisglycinate trial found a small improvement on its validated primary insomnia score. The studied formulation effect does not establish a large clinically meaningful benefit, a deficiency-only response boundary, salt superiority or magnesium-ion mediation. Mixed and null findings, plus limited objective replication, prevent a stronger clinical claim.", "aggregation_alternatives": { "weakest_link_would_return": "Α", "primary_subclaim_would_return": "Δ", "scope_matched_would_return": "Δ", "note": "Separate narrow successes do not replace the preregistered full-scope gate." }, "index_rule_deviation": "" }, "competing_models": { "models_evaluated": [ { "rank_in_tournament": 1, "model_id": "M1", "is_nominal": true, "name": "An oral magnesium formulation modestly improves selected sleep symptoms", "core_claim": "Some studied oral formulations cause a small sleep-symptom improvement under controlled conditions.", "explains_what_nominal_does_not": "Some studied oral formulations cause a small sleep-symptom improvement under controlled conditions.", "strongest_supporting_evidence": [ "Prospective bisglycinate trial supplies a positive validated primary ISI contrast; older oxide and some threonate outcomes provide qualified corroboration." ], "strongest_contradictory_evidence": [ "Citrate PSQI and newer threonate objective sleep are null; the ion-specific mechanism and broad clinical importance remain unresolved." ], "hsef_level_for_this_model": "Δ", "rationale": "Prospective bisglycinate trial supplies a positive validated primary ISI contrast; older oxide and some threonate outcomes provide qualified corroboration. Citrate PSQI and newer threonate objective sleep are null; the ion-specific mechanism and broad clinical importance remain unresolved." }, { "rank_in_tournament": 2, "model_id": "M2", "is_nominal": false, "name": "Nutritional deficiency correction restores physiology in selected contexts", "core_claim": "Low magnesium can impair physiology and sleep in restricted experimental settings; correcting it can restore them.", "explains_what_nominal_does_not": "Low magnesium can impair physiology and sleep in restricted experimental settings; correcting it can restore them.", "strongest_supporting_evidence": [ "Deficiency/repletion rat sleep experiments provide a causal nutritional context and human low-status subgroup biomarkers respond." ], "strongest_contradictory_evidence": [ "Deficiency-dependent human sleep responsiveness has not been cleanly established; low-status serum/RBC correction does not by itself improve sleep." ], "hsef_level_for_this_model": "Δ", "rationale": "Deficiency/repletion rat sleep experiments provide a causal nutritional context and human low-status subgroup biomarkers respond. Deficiency-dependent human sleep responsiveness has not been cleanly established; low-status serum/RBC correction does not by itself improve sleep." }, { "rank_in_tournament": 3, "model_id": "M3", "is_nominal": false, "name": "Coingredients and the treatment package can explain some improvement", "core_claim": "Ligands, melatonin, botanicals and expectancy can alter reported sleep independently of a demonstrated magnesium-ion mediator.", "explains_what_nominal_does_not": "Ligands, melatonin, botanicals and expectancy can alter reported sleep independently of a demonstrated magnesium-ion mediator.", "strongest_supporting_evidence": [ "Factorial melatonin/PCOS results and equal citrate-placebo PSQI improvement show alternatives; multiingredient trials leave component effects bundled." ], "strongest_contradictory_evidence": [ "This does not prove every magnesium formulation benefit is placebo, glycine or melatonin, and the bisglycinate comparison is blinded." ], "hsef_level_for_this_model": "Δ", "rationale": "Factorial melatonin/PCOS results and equal citrate-placebo PSQI improvement show alternatives; multiingredient trials leave component effects bundled. This does not prove every magnesium formulation benefit is placebo, glycine or melatonin, and the bisglycinate comparison is blinded." }, { "rank_in_tournament": 4, "model_id": "M4", "is_nominal": false, "name": "Absorption or neural biomarkers change without sleep improvement", "core_claim": "Magnesium exposure can shift measured physiology without a corresponding clinical sleep benefit.", "explains_what_nominal_does_not": "Magnesium exposure can shift measured physiology without a corresponding clinical sleep benefit.", "strongest_supporting_evidence": [ "Citrate low-status changes with equal PSQI, newer threonate physiological changes with null objective sleep, and PK studies constrain the bridge." ], "strongest_contradictory_evidence": [ "Some validated symptoms do improve; this rival cannot explain away every positive controlled result." ], "hsef_level_for_this_model": "Δ", "rationale": "Citrate low-status changes with equal PSQI, newer threonate physiological changes with null objective sleep, and PK studies constrain the bridge. Some validated symptoms do improve; this rival cannot explain away every positive controlled result." } ], "tournament_summary": "Descriptive comparison; does not modify the nominal score. A factorial trial separating elemental magnesium, the glycine/threonate ligand and their formulation while stratifying baseline status would distinguish nutrient correction, ligand effects and nonspecific improvement. Objective and clinically meaningful sleep endpoints must be assessed alongside exposure.", "study_separating_rank1_from_rank2": "A factorial trial separating elemental magnesium, the glycine/threonate ligand and their formulation while stratifying baseline status would distinguish nutrient correction, ligand effects and nonspecific improvement. Objective and clinically meaningful sleep endpoints must be assessed alongside exposure.", "nominal_wins_only_by_funding_artifact": false, "level_unchanged_by_tournament": true }, "evidence_inventory": [ { "n": 1, "pmid": "39252819", "title": "Magnesium-L-threonate improves sleep quality and daytime functioning in adults with self-reported sleep problems: A randomized controlled trial.", "citation": "Hausenblas HA, Lynch T, Hooper S et al. Magnesium-L-threonate improves sleep quality and daytime functioning in adults with self-reported sleep problems: A randomized controlled trial. Sleep medicine: X. 2024.", "doi": "10.1016/j.sleepx.2024.100121", "pmcid": "PMC11381753", "url": "https://pubmed.ncbi.nlm.nih.gov/39252819/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39252819/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "ErratumIn: PMID40567408" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MG-THREONATE-ISRCTN14728094", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Materials and methods:paragraph0, 1:Materials and methods:paragraph6, 1:Materials and methods:paragraph7, 1:Materials and methods:paragraph14, 1:Materials and methods:paragraph32, 11:Declaration of competing interest:paragraph0, 2:Results:paragraph3, 2:Results:paragraph7, 2:Results:paragraph15. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [ "M3", "M4" ], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "The 21-day threonate trial reports selected wearable scores and awakening/daytime benefits.", "what_it_does_not_show": "Overall ISI interaction is null (p=0.39); correction 40567408 adds retrospective registration and conflicts. Wearable scores are not polysomnography.", "confounders_present": [ "Overall ISI interaction is null (p=0.39); correction 40567408 adds retrospective registration and conflicts. Wearable scores are not polysomnography." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 2, "pmid": "23853635", "title": "The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial.", "citation": "Abbasi B, Kimiagar M, Sadeghniiat K et al. The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences. 2012.", "doi": "", "pmcid": "PMC3703169", "url": "https://pubmed.ncbi.nlm.nih.gov/23853635/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/23853635/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID23853635", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:MATERIALS AND METHODS:paragraph0, 1:MATERIALS AND METHODS:paragraph1, 2:RESULTS:paragraph0, 2:RESULTS:paragraph3, 2:RESULTS:paragraph5. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [ "M1" ], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "An eight-week oxide trial in older adults improves ISI and selected sleep-log outcomes.", "what_it_does_not_show": "46 randomized and 43 completed; sample powered on renin, not sleep. Total sleep time is null; low dietary intake is not proof of clinical deficiency.", "confounders_present": [ "46 randomized and 43 completed; sample powered on renin, not sleep. Total sleep time is null; low dietary intake is not proof of clinical 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": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 3, "pmid": "40918053", "title": "Magnesium Bisglycinate Supplementation in Healthy Adults Reporting Poor Sleep: A Randomized, Placebo-Controlled Trial.", "citation": "Schuster J, Cycelskij I, Lopresti A et al. Magnesium Bisglycinate Supplementation in Healthy Adults Reporting Poor Sleep: A Randomized, Placebo-Controlled Trial. Nature and science of sleep. 2025.", "doi": "10.2147/NSS.S524348", "pmcid": "PMC12412596", "url": "https://pubmed.ncbi.nlm.nih.gov/40918053/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40918053/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MG-BISGLYCINATE-DRKS00031494", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Materials and Methods:paragraph0, 1:Materials and Methods:paragraph4, 1:Materials and Methods:paragraph12, 1:Materials and Methods:paragraph14, 1:Materials and Methods:paragraph15, 1:Materials and Methods:paragraph17, 2:Results:paragraph0, 2:Results:paragraph8, 2:Results:paragraph10, 2:Results:paragraph13, 2:Results:paragraph16, 2:Results:paragraph18. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [ "M1" ], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "A prospectively registered (DRKS00031494, registered 12 April 2023, before first enrolment on 20 April 2023) four-week bisglycinate trial shows a small primary ISI benefit.", "what_it_does_not_show": "155 randomized, 153 baseline analyzed and 134 completed; d=0.2, p=0.049. Glycine ligand exposure is not isolated and objective sleep is absent.", "confounders_present": [ "155 randomized, 153 baseline analyzed and 134 completed; d=0.2, p=0.049. Glycine ligand exposure is not isolated and objective sleep is absent." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 4, "pmid": "39534260", "title": "Effects of magnesium and potassium supplementation on insomnia and sleep hormones in patients with diabetes mellitus.", "citation": "Khalid S, Bashir S, Mehboob R et al. Effects of magnesium and potassium supplementation on insomnia and sleep hormones in patients with diabetes mellitus. Frontiers in endocrinology. 2024.", "doi": "10.3389/fendo.2024.1370733", "pmcid": "PMC11554482", "url": "https://pubmed.ncbi.nlm.nih.gov/39534260/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39534260/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MG-K-INSOMNIA-NCT04642313", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Materials and methods:paragraph0, 1:Materials and methods:paragraph13, 2:Results:paragraph0, 2:Results:paragraph1, 2:Results:paragraph2. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [ "M3", "M4" ], "evidence_class": "Weak", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "A diabetic-insomnia four-arm trial reports ISI and hormone changes after Mg/K supplementation.", "what_it_does_not_show": "Baseline ISI categories differ substantially (p=0.0001); post-group associations are not adjusted change effects. Single blinding and restricted diet limit inference.", "confounders_present": [ "Baseline ISI categories differ substantially (p=0.0001); post-group associations are not adjusted change effects. Single blinding and restricted diet limit inference." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 5, "pmid": "40923590", "title": "Effects of magnesium and potassium on insulin resistance and blood sugar level among insomniac patients with diabetes mellitus-A randomized controlled trial.", "citation": "Khalid S, Bashir S, Mehboob R et al. Effects of magnesium and potassium on insulin resistance and blood sugar level among insomniac patients with diabetes mellitus-A randomized controlled trial. Journal of investigative medicine : the official publication of the American Federation for Clinical Research. 2026.", "doi": "10.1177/10815589251378179", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/40923590/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40923590/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MG-K-INSOMNIA-NCT04642313", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC4" ], "favors_models": [], "evidence_class": "Weak", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "An original follow-up of the diabetic-insomnia trial reports glucose and HOMA changes.", "what_it_does_not_show": "Same NCT04642313 participants as 39534260; metabolic proxies are not sleep mediation or an independent trial.", "confounders_present": [ "Same NCT04642313 participants as 39534260; metabolic proxies are not sleep mediation or an independent trial." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 6, "pmid": "41561890", "title": "Comparison of Diabetic Nephropathy Markers in Diabetic Patients With Insomnia Before and After Potassium and Magnesium Supplementation: A Randomized Controlled Trial.", "citation": "Khalid S, Bashir S, Mehboob R et al. Comparison of Diabetic Nephropathy Markers in Diabetic Patients With Insomnia Before and After Potassium and Magnesium Supplementation: A Randomized Controlled Trial. Health science reports. 2026.", "doi": "10.1002/hsr2.71738", "pmcid": "PMC12813270", "url": "https://pubmed.ncbi.nlm.nih.gov/41561890/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41561890/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MG-K-INSOMNIA-NCT04642313", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC4" ], "favors_models": [], "evidence_class": "Weak", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "An original follow-up of the diabetic-insomnia trial reports renal and liver marker changes.", "what_it_does_not_show": "Same320/290 cohort; these markers are not neural mediators or new clinical sleep evidence.", "confounders_present": [ "Same320/290 cohort; these markers are not neural mediators or new clinical sleep evidence." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 7, "pmid": "21199787", "title": "Magnesium supplementation improves indicators of low magnesium status and inflammatory stress in adults older than 51 years with poor quality sleep.", "citation": "Nielsen FH, Johnson LK, Zeng H. Magnesium supplementation improves indicators of low magnesium status and inflammatory stress in adults older than 51 years with poor quality sleep. Magnesium research. 2010.", "doi": "10.1684/mrh.2010.0220", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/21199787/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/21199787/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID21199787", "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", "SC4" ], "favors_models": [ "M3", "M4" ], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "null", "what_it_shows": "Citrate improves selected low-magnesium and inflammatory indicators in a seven-week randomized trial.", "what_it_does_not_show": "Global PSQI improves equally with magnesium and placebo. Nutritional biomarker response does not establish a sleep-responsive deficiency subgroup.", "confounders_present": [ "Global PSQI improves equally with magnesium and placebo. Nutritional biomarker response does not establish a sleep-responsive deficiency 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": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 8, "pmid": "11777170", "title": "Magnesium involvement in sleep: genetic and nutritional models.", "citation": "Chollet D, Franken P, Raffin Y et al. Magnesium involvement in sleep: genetic and nutritional models. Behavior genetics. 2001.", "doi": "10.1023/a:1012790321071", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/11777170/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/11777170/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID11777170", "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", "SC4" ], "favors_models": [ "M2" ], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Genetic RBC-magnesium lines and dietary deficiency alter mouse sleep and EEG patterns.", "what_it_does_not_show": "Central/peripheral regulation and correlation directions differ; optimal balance is distinct from a universal more-magnesium model.", "confounders_present": [ "Central/peripheral regulation and correlation directions differ; optimal balance is distinct from a universal more-magnesium model." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 9, "pmid": "8232845", "title": "Effects of a magnesium-deficient diet on sleep organization in rats.", "citation": "Depoortere H, Françon D, Llopis J. Effects of a magnesium-deficient diet on sleep organization in rats. Neuropsychobiology. 1993.", "doi": "10.1159/000118988", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/8232845/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/8232845/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID8232845", "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", "SC4" ], "favors_models": [ "M2" ], "evidence_class": "Strong", "system": "animal model", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "Prolonged dietary deficiency disrupts rat sleep/ECoG and repletion restores patterns.", "what_it_does_not_show": "Small groups and a deficiency/recovery context do not establish supplementation benefits in replete adults.", "confounders_present": [ "Small groups and a deficiency/recovery context do not establish supplementation benefits in replete adults." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 10, "pmid": "41554599", "title": "Magnesium deficiency differentially modulates hippocampal and prefrontal oscillations and cardiac rhythms.", "citation": "Inoue S, Ikegaya Y, Matsumoto N et al. Magnesium deficiency differentially modulates hippocampal and prefrontal oscillations and cardiac rhythms. Journal of pharmacological sciences. 2026.", "doi": "10.1016/j.jphs.2025.12.002", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/41554599/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41554599/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID41554599", "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", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Three-week deficiency alters rat hippocampal/prefrontal oscillations.", "what_it_does_not_show": "Sleep architecture is unchanged; neural signals cannot be relabeled an insomnia phenotype.", "confounders_present": [ "Sleep architecture is unchanged; neural signals cannot be relabeled an insomnia phenotype." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 11, "pmid": "6083421", "title": "Vigilance states and cerebral monoamine metabolism in experimental magnesium deficiency.", "citation": "Poenaru S, Rouhani S, Durlach J et al. Vigilance states and cerebral monoamine metabolism in experimental magnesium deficiency. Magnesium. 1984.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/6083421/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/6083421/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID6083421", "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", "SC4" ], "favors_models": [ "M2" ], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "A restricted-magnesium diet changes rat monoamine concentrations and increases wakefulness.", "what_it_does_not_show": "Terminal neurochemical correlations do not isolate a mediator; species and deficiency scope differ from supplementation for human insomnia.", "confounders_present": [ "Terminal neurochemical correlations do not isolate a mediator; species and deficiency scope differ from supplementation for human insomnia." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 12, "pmid": "33864354", "title": "Effect of magnesium and vitamin B6 supplementation on mental health and quality of life in stressed healthy adults: Post-hoc analysis of a randomised controlled trial.", "citation": "Noah L, Dye L, Bois De Fer B et al. Effect of magnesium and vitamin B6 supplementation on mental health and quality of life in stressed healthy adults: Post-hoc analysis of a randomised controlled trial. Stress and health : journal of the International Society for the Investigation of Stress. 2021.", "doi": "10.1002/smi.3051", "pmcid": "PMC9292249", "url": "https://pubmed.ncbi.nlm.nih.gov/33864354/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33864354/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MG-B6-EUDRACT2015-003749-24", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC4" ], "favors_models": [], "evidence_class": "Weak", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "A secondary low-magnesemia stress trial analysis reports mood/QoL improvements in both treatment arms.", "what_it_does_not_show": "No magnesium-free control and shared2015-003749-24 participants; post-hoc change does not identify magnesium causality.", "confounders_present": [ "No magnesium-free control and shared2015-003749-24 participants; post-hoc change does not identify magnesium causality." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 13, "pmid": "30562392", "title": "Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial.", "citation": "Pouteau E, Kabir-Ahmadi M, Noah L et al. Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial. PloS one. 2018.", "doi": "10.1371/journal.pone.0208454", "pmcid": "PMC6298677", "url": "https://pubmed.ncbi.nlm.nih.gov/30562392/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30562392/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MG-B6-EUDRACT2015-003749-24", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "An investigator-blind stress trial compares Mg+B6 with Mg and finds no overall primary superiority.", "what_it_does_not_show": "Both arms contain magnesium; a severe-stress subgroup advantage concerns added B6, not magnesium necessity.", "confounders_present": [ "Both arms contain magnesium; a severe-stress subgroup advantage concerns added B6, not magnesium necessity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 14, "pmid": "41194549", "title": "Effects of a Scutellaria baicalensis/Crataegus laevigata, magnesium and chromium supplement on stressed individuals: A randomised, double-blind, placebo-controlled, crossover trial.", "citation": "Dodd F, Weishaupt R, Katumba PKM et al. Effects of a Scutellaria baicalensis/Crataegus laevigata, magnesium and chromium supplement on stressed individuals: A randomised, double-blind, placebo-controlled, crossover trial. Journal of psychopharmacology (Oxford, England). 2025.", "doi": "10.1177/02698811251381261", "pmcid": "PMC12672942", "url": "https://pubmed.ncbi.nlm.nih.gov/41194549/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41194549/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID41194549", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "A herbal/Mg/chromium crossover trial reports selected mood and cognitive benefits.", "what_it_does_not_show": "35 analyzed of 43 enrolled, short periods and a multiingredient bundle; no isolated magnesium sleep effect.", "confounders_present": [ "35 analyzed of 43 enrolled, short periods and a multiingredient bundle; no isolated magnesium sleep effect." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 15, "pmid": "33896388", "title": "A combination of green tea, rhodiola, magnesium and B vitamins modulates brain activity and protects against the effects of induced social stress in healthy volunteers.", "citation": "Boyle NB, Billington J, Lawton C et al. A combination of green tea, rhodiola, magnesium and B vitamins modulates brain activity and protects against the effects of induced social stress in healthy volunteers. Nutritional neuroscience. 2022.", "doi": "10.1080/1028415X.2021.1909204", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33896388/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33896388/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "TEADIOLA-NCT03262376", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "A randomized botanical/Mg/B-vitamin experiment changes EEG theta and selected subjective stress responses.", "what_it_does_not_show": "The ingredient bundle and absent magnesium-only factorial control leave magnesium mediation unidentified.", "confounders_present": [ "The ingredient bundle and absent magnesium-only factorial control leave magnesium mediation unidentified." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 16, "pmid": "33210604", "title": "Impact of magnesium supplementation, in combination with vitamin B6, on stress and magnesium status: secondary data from a randomized controlled trial.", "citation": "Noah L, Pickering G, Mazur A et al. Impact of magnesium supplementation, in combination with vitamin B6, on stress and magnesium status: secondary data from a randomized controlled trial. Magnesium research. 2020.", "doi": "10.1684/mrh.2020.0468", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33210604/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33210604/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MG-B6-EUDRACT2015-003749-24", "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", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "A secondary stress-trial report finds RBC-magnesium increases in low-status subgroups without extra B6 benefit.", "what_it_does_not_show": "Shared trial participants; RBC change and within-group stress improvement are not causal sleep efficacy.", "confounders_present": [ "Shared trial participants; RBC change and within-group stress improvement are not causal sleep efficacy." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 17, "pmid": "35938130", "title": "A Combination of Green Tea, Rhodiola, Magnesium, and B Vitamins Increases Electroencephalogram Theta Activity During Attentional Task Performance Under Conditions of Induced Social Stress.", "citation": "Boyle NB, Dye L, Lawton CL et al. A Combination of Green Tea, Rhodiola, Magnesium, and B Vitamins Increases Electroencephalogram Theta Activity During Attentional Task Performance Under Conditions of Induced Social Stress. Frontiers in nutrition. 2022.", "doi": "10.3389/fnut.2022.935001", "pmcid": "PMC9355406", "url": "https://pubmed.ncbi.nlm.nih.gov/35938130/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35938130/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "TEADIOLA-NCT03262376", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "An original EEG analysis finds greater task theta under stress with the combined supplement.", "what_it_does_not_show": "Behavioral performance and ERP outcomes are null; same NCT03262376 trial, and neural signals do not establish functional benefit.", "confounders_present": [ "Behavioral performance and ERP outcomes are null; same NCT03262376 trial, and neural signals do not establish functional benefit." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 18, "pmid": "37662591", "title": "Assessing brain function in stressed healthy individuals following the use of a combination of green tea, Rhodiola, magnesium, and B vitamins: an fMRI study.", "citation": "Pickering G, Noah L, Pereira B et al. Assessing brain function in stressed healthy individuals following the use of a combination of green tea, Rhodiola, magnesium, and B vitamins: an fMRI study. Frontiers in nutrition. 2023.", "doi": "10.3389/fnut.2023.1211321", "pmcid": "PMC10469327", "url": "https://pubmed.ncbi.nlm.nih.gov/37662591/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37662591/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID37662591", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "A40-person supplement/placebo trial reports stress-rating and BOLD changes.", "what_it_does_not_show": "Multiple ingredients, single blinding and correlated imaging/rating changes do not isolate magnesium; thermal stress is not insomnia.", "confounders_present": [ "Multiple ingredients, single blinding and correlated imaging/rating changes do not isolate magnesium; thermal stress is not insomnia." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 19, "pmid": "41601871", "title": "The effects of magnesium L-threonate (Magtein®) on cognitive performance and sleep quality in adults: a randomised, double-blind, placebo-controlled trial.", "citation": "Lopresti AL, Smith SJ. The effects of magnesium L-threonate (Magtein®) on cognitive performance and sleep quality in adults: a randomised, double-blind, placebo-controlled trial. Frontiers in nutrition. 2025.", "doi": "10.3389/fnut.2025.1729164", "pmcid": "PMC12832366", "url": "https://pubmed.ncbi.nlm.nih.gov/41601871/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41601871/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MG-THREONATE-ACTRN12624000379516", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Materials and methods:paragraph0, 2:Results:paragraph20, 2:Results:paragraph29, 2:Results:paragraph30, 2:Results:paragraph32, 2:Results:paragraph39. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [ "M1" ], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "A prospective six-week threonate trial improves sleep-related impairment and checks allocation guesses.", "what_it_does_not_show": "Sleep disturbance, restorative sleep and all ring sleep outcomes are null. Severe subgroups are exploratory and cognitive-age estimates are not rejuvenation.", "confounders_present": [ "Sleep disturbance, restorative sleep and all ring sleep outcomes are null. Severe subgroups are exploratory and cognitive-age estimates are not rejuvenation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 20, "pmid": "38738598", "title": "Magnesium citrate monotherapy improves restless legs syndrome symptoms and multiple suggested immobilization test scores in an open-label pilot study.", "citation": "Gorantla S, Ravisankar A, Trotti LM. Magnesium citrate monotherapy improves restless legs syndrome symptoms and multiple suggested immobilization test scores in an open-label pilot study. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2024.", "doi": "10.5664/jcsm.11206", "pmcid": "PMC11294134", "url": "https://pubmed.ncbi.nlm.nih.gov/38738598/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38738598/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID38738598", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Weak", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "An open-label 12-person citrate pilot improves RLS symptoms and immobilization readouts.", "what_it_does_not_show": "No placebo, different clinical condition and unchanged serum magnesium; expectancy and regression remain.", "confounders_present": [ "No placebo, different clinical condition and unchanged serum magnesium; expectancy and regression remain." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 21, "pmid": "28241153", "title": "Effect of Magnesium Oxide Supplementation on Nocturnal Leg Cramps: A Randomized Clinical Trial.", "citation": "Roguin Maor N, Alperin M, Shturman E et al. Effect of Magnesium Oxide Supplementation on Nocturnal Leg Cramps: A Randomized Clinical Trial. JAMA internal medicine. 2017.", "doi": "10.1001/jamainternmed.2016.9261", "pmcid": "PMC5818780", "url": "https://pubmed.ncbi.nlm.nih.gov/28241153/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28241153/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID28241153", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "A randomized oxide trial finds no benefit for nocturnal cramps or sleep quality over placebo.", "what_it_does_not_show": "The cramp population differs from primary insomnia; improvement in both arms does not identify an intervention effect.", "confounders_present": [ "The cramp population differs from primary insomnia; improvement in both arms does not identify an intervention effect." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 22, "pmid": "42829807", "title": "Modulating stress and sleep through a multi-compound dietary supplement: a randomized, double-blind, placebo-controlled trial.", "citation": "Mastrofini GF, Romersi RF, Lombardi MG et al. Modulating stress and sleep through a multi-compound dietary supplement: a randomized, double-blind, placebo-controlled trial. Journal of the International Society of Sports Nutrition. 2026.", "doi": "10.1080/15502783.2026.2740227", "pmcid": "PMC13644447", "url": "https://pubmed.ncbi.nlm.nih.gov/42829807/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/42829807/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID42829807", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [ "M3", "M4" ], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "A four-arm morning/evening supplement trial finds selected morning botanical stress/sleep improvements.", "what_it_does_not_show": "The evening threonate/theanine/apigenin bundle shows minimal effects; healthy active participants and multiple ingredients limit magnesium attribution.", "confounders_present": [ "The evening threonate/theanine/apigenin bundle shows minimal effects; healthy active participants and multiple ingredients limit magnesium attribution." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 23, "pmid": "12163983", "title": "Oral Mg(2+) supplementation reverses age-related neuroendocrine and sleep EEG changes in humans.", "citation": "Held K, Antonijevic IA, Künzel H et al. Oral Mg(2+) supplementation reverses age-related neuroendocrine and sleep EEG changes in humans. Pharmacopsychiatry. 2002.", "doi": "10.1055/s-2002-33195", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/12163983/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/12163983/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID12163983", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [ "M1" ], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "A12-person elderly crossover increases slow-wave sleep/EEG power with endocrine shifts.", "what_it_does_not_show": "Small short study and unclear indexed insomnia eligibility; hormone association does not prove mediation or salt superiority.", "confounders_present": [ "Small short study and unclear indexed insomnia eligibility; hormone association does not prove mediation or salt superiority." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 24, "pmid": "34092248", "title": "Metabolic and hormonal effects of melatonin and/or magnesium supplementation in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial.", "citation": "Alizadeh M, Karandish M, Asghari Jafarabadi M et al. Metabolic and hormonal effects of melatonin and/or magnesium supplementation in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Nutrition & metabolism. 2021.", "doi": "10.1186/s12986-021-00586-9", "pmcid": "PMC8183043", "url": "https://pubmed.ncbi.nlm.nih.gov/34092248/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34092248/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID34092248", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [ "M3", "M4" ], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "A PCOS factorial trial reports PSQI improvement with melatonin and melatonin+Mg.", "what_it_does_not_show": "The magnesium-only sleep benefit is not established by those positive arms; combination efficacy cannot be assigned to magnesium.", "confounders_present": [ "The magnesium-only sleep benefit is not established by those positive arms; combination efficacy cannot be assigned to magnesium." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 25, "pmid": "30761462", "title": "Dose-Dependent Absorption Profile of Different Magnesium Compounds.", "citation": "Ates M, Kizildag S, Yuksel O et al. Dose-Dependent Absorption Profile of Different Magnesium Compounds. Biological trace element research. 2019.", "doi": "10.1007/s12011-019-01663-0", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/30761462/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30761462/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID30761462", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "Rodent dose/form comparisons find salt-dependent brain, muscle and serum magnesium patterns.", "what_it_does_not_show": "Tissue concentrations do not demonstrate clinical sleep benefit; divided dosing does not uniformly improve availability.", "confounders_present": [ "Tissue concentrations do not demonstrate clinical sleep benefit; divided dosing does not uniformly improve availability." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 26, "pmid": "29679349", "title": "Timeline (Bioavailability) of Magnesium Compounds in Hours: Which Magnesium Compound Works Best?", "citation": "Uysal N, Kizildag S, Yuce Z et al. Timeline (Bioavailability) of Magnesium Compounds in Hours: Which Magnesium Compound Works Best? Biological trace element research. 2019.", "doi": "10.1007/s12011-018-1351-9", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/29679349/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29679349/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID29679349", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Single-dose rat pharmacokinetics finds acetyl-taurate brain penetration and anxiety-related changes.", "what_it_does_not_show": "These are preclinical malate/taurate results, not glycinate/threonate superiority for human sleep.", "confounders_present": [ "These are preclinical malate/taurate results, not glycinate/threonate superiority for human sleep." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 27, "pmid": "31330811", "title": "Predicting and Testing Bioavailability of Magnesium Supplements.", "citation": "Blancquaert L, Vervaet C, Derave W. Predicting and Testing Bioavailability of Magnesium Supplements. Nutrients. 2019.", "doi": "10.3390/nu11071663", "pmcid": "PMC6683096", "url": "https://pubmed.ncbi.nlm.nih.gov/31330811/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31330811/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID31330811", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 2:3. Results:paragraph9, 2:3. Results:paragraph12, 2:3. Results:paragraph13, 2:3. Results:paragraph15, 2:3. Results:paragraph17. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "Original digestion models and controlled human testing identify serum absorption differences between formulations.", "what_it_does_not_show": "Urinary comparisons are null and elemental doses differ; absorption does not establish brain delivery or sleep superiority.", "confounders_present": [ "Urinary comparisons are null and elemental doses differ; absorption does not establish brain delivery or sleep superiority." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 28, "pmid": "2407766", "title": "Magnesium bioavailability from magnesium citrate and magnesium oxide.", "citation": "Lindberg JS, Zobitz MM, Poindexter JR et al. Magnesium bioavailability from magnesium citrate and magnesium oxide. Journal of the American College of Nutrition. 1990.", "doi": "10.1080/07315724.1990.10720349", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/2407766/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/2407766/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID2407766", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Citrate is more soluble and produces greater urinary magnesium loading than oxide in volunteers.", "what_it_does_not_show": "Acute excretion, gastric acidity and renal handling are distinct from clinical sleep efficacy.", "confounders_present": [ "Acute excretion, gastric acidity and renal handling are distinct from clinical sleep efficacy." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 29, "pmid": "7815675", "title": "Bioavailability of magnesium diglycinate vs magnesium oxide in patients with ileal resection.", "citation": "Schuette SA, Lashner BA, Janghorbani M. Bioavailability of magnesium diglycinate vs magnesium oxide in patients with ileal resection. JPEN. Journal of parenteral and enteral nutrition. 1994.", "doi": "10.1177/0148607194018005430", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/7815675/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/7815675/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID7815675", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Stable-isotope crossover in 12 ileal-resection patients compares diglycinate with oxide.", "what_it_does_not_show": "Overall absorption does not differ; four most impaired patients show an advantage, which cannot define a general sleep benefit.", "confounders_present": [ "Overall absorption does not differ; four most impaired patients show an advantage, which cannot define a general sleep benefit." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 30, "pmid": "35253448", "title": "Effects of Magnesium Citrate, Magnesium Oxide, and Magnesium Sulfate Supplementation on Arterial Stiffness: A Randomized, Double-Blind, Placebo-Controlled Intervention Trial.", "citation": "Schutten JC, Joris PJ, Groendijk I et al. Effects of Magnesium Citrate, Magnesium Oxide, and Magnesium Sulfate Supplementation on Arterial Stiffness: A Randomized, Double-Blind, Placebo-Controlled Intervention Trial. Journal of the American Heart Association. 2022.", "doi": "10.1161/JAHA.121.021783", "pmcid": "PMC9075273", "url": "https://pubmed.ncbi.nlm.nih.gov/35253448/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35253448/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID35253448", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3", "SC4" ], "favors_models": [ "M3", "M4" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "A24-week matched-salt trial in 164 adults raises plasma and urinary magnesium.", "what_it_does_not_show": "Arterial stiffness and blood pressure remain null; excretion differences do not establish sleep benefit.", "confounders_present": [ "Arterial stiffness and blood pressure remain null; excretion differences do not establish sleep benefit." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 31, "pmid": "16548135", "title": "Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach.", "citation": "Coudray C, Rambeau M, Feillet-Coudray C et al. Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach. Magnesium research. 2005.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/16548135/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/16548135/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID16548135", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Stable-isotope randomized repletion in depleted rats compares absorption/retention from ten salts.", "what_it_does_not_show": "All forms are bioavailable, with context-dependent differences; depleted male rats are not replete human poor sleepers.", "confounders_present": [ "All forms are bioavailable, with context-dependent differences; depleted male rats are not replete human poor sleepers." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 32, "pmid": "29630135", "title": "Magnesium bioavailability after administration of sucrosomial® magnesium: results of an ex-vivo study and a comparative, double-blinded, cross-over study in healthy subjects.", "citation": "Brilli E, Khadge S, Fabiano A et al. Magnesium bioavailability after administration of sucrosomial® magnesium: results of an ex-vivo study and a comparative, double-blinded, cross-over study in healthy subjects. European review for medical and pharmacological sciences. 2018.", "doi": "10.26355/eurrev_201803_14605", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/29630135/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29630135/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID29630135", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Human crossover and ex vivo testing compare sucrosomial magnesium with several salts.", "what_it_does_not_show": "Compartment-specific availability differences do not establish sleep efficacy; branded delivery differs from ligand chemistry.", "confounders_present": [ "Compartment-specific availability differences do not establish sleep efficacy; branded delivery differs from ligand chemistry." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 33, "pmid": "39770988", "title": "Comparative Clinical Study on Magnesium Absorption and Side Effects After Oral Intake of Microencapsulated Magnesium (MAGSHAPETM Microcapsules) Versus Other Magnesium Sources.", "citation": "Pajuelo D, Meissner JM, Negra T et al. Comparative Clinical Study on Magnesium Absorption and Side Effects After Oral Intake of Microencapsulated Magnesium (MAGSHAPETM Microcapsules) Versus Other Magnesium Sources. Nutrients. 2024.", "doi": "10.3390/nu16244367", "pmcid": "PMC11677548", "url": "https://pubmed.ncbi.nlm.nih.gov/39770988/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39770988/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID39770988", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "A40-person crossover finds sustained plasma rises with microencapsulation compared with several forms.", "what_it_does_not_show": "Acute plasma and GI outcomes are not brain or sleep measures; bisglycinate is not a uniform plasma winner.", "confounders_present": [ "Acute plasma and GI outcomes are not brain or sleep measures; bisglycinate is not a uniform plasma winner." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 34, "pmid": "40955524", "title": "Comparing the Bioavailability of Two Seawater-Derived Magnesium Preparations.", "citation": "McFarlin BK, Paschall AL, Kelly ME et al. Comparing the Bioavailability of Two Seawater-Derived Magnesium Preparations. Journal of medicinal food. 2025.", "doi": "10.1177/1096620X251380191", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/40955524/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40955524/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID40955524", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "A matched-dose crossover finds both seawater preparations increase magnesium uptake versus placebo.", "what_it_does_not_show": "The two forms do not differ at matched elemental dose; serum/urinary measures are not sleep endpoints.", "confounders_present": [ "The two forms do not differ at matched elemental dose; serum/urinary measures are not sleep endpoints." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 35, "pmid": "42084749", "title": "Enhanced Neurophysiological Benefits of Magnesium-Acetyl-Taurate Over Magnesium-L-Threonate: A Comparative pre-clinical Study on Bioavailability, Synaptic Plasticity and Cognitive Functions.", "citation": "Kumar A, Mehan S, Gupta S et al. Enhanced Neurophysiological Benefits of Magnesium-Acetyl-Taurate Over Magnesium-L-Threonate: A Comparative pre-clinical Study on Bioavailability, Synaptic Plasticity and Cognitive Functions. Neuromolecular medicine. 2026.", "doi": "10.1007/s12017-026-08929-6", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/42084749/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/42084749/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID42084749", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Rat acetyl-taurate/threonate comparison reports brain-magnesium and cognitive/anxiety patterns.", "what_it_does_not_show": "Salt mass doses, many markers and rodent behaviors are not a direct matched human sleep comparison.", "confounders_present": [ "Salt mass doses, many markers and rodent behaviors are not a direct matched human sleep comparison." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 36, "pmid": "31606725", "title": "Comparative study of the bioavailability of magnesium salts.", "citation": "Eremenko NN, Shikh EV, Serebrova SY et al. Comparative study of the bioavailability of magnesium salts. Drug metabolism and personalized therapy. 2019.", "doi": "10.1515/dmpt-2019-0004", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/31606725/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31606725/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID31606725", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Volunteer/heart-failure work finds comparable magnesium-orotate±potassium blood/RBC profiles.", "what_it_does_not_show": "Serum homeostasis complicates AUC interpretation; human neural and sleep outcomes were not measured.", "confounders_present": [ "Serum homeostasis complicates AUC interpretation; human neural and sleep outcomes were not measured." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 37, "pmid": "27412366", "title": "Pharmacokinetic Profile of Oral Magnesium Hydroxide.", "citation": "Dolberg MK, Nielsen LP, Dahl R. Pharmacokinetic Profile of Oral Magnesium Hydroxide. Basic & clinical pharmacology & toxicology. 2017.", "doi": "10.1111/bcpt.12642", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/27412366/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/27412366/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID27412366", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Oral-versus-IV testing estimates hydroxide bioavailability in ten healthy men.", "what_it_does_not_show": "Small acute pharmacokinetics does not establish brain exposure, sleep benefit or safety across renal contexts.", "confounders_present": [ "Small acute pharmacokinetics does not establish brain exposure, sleep benefit or safety across renal contexts." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 38, "pmid": "30018220", "title": "Bioaccessibility and Bioavailability of a Marine-Derived Multimineral, Aquamin-Magnesium.", "citation": "Felice VD, O'Gorman DM, O'Brien NM et al. Bioaccessibility and Bioavailability of a Marine-Derived Multimineral, Aquamin-Magnesium. Nutrients. 2018.", "doi": "10.3390/nu10070912", "pmcid": "PMC6073474", "url": "https://pubmed.ncbi.nlm.nih.gov/30018220/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30018220/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID30018220", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Weak", "system": "in vitro", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "INFOGEST/Caco2 testing compares a marine multimineral with magnesium chloride and oxide.", "what_it_does_not_show": "Digestion/epithelial transport is not living brain exposure or clinical sleep efficacy; additional minerals are bundled.", "confounders_present": [ "Digestion/epithelial transport is not living brain exposure or clinical sleep efficacy; additional minerals are bundled." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 39, "pmid": "11794633", "title": "Bioavailability of US commercial magnesium preparations.", "citation": "Firoz M, Graber M. Bioavailability of US commercial magnesium preparations. Magnesium research. 2001.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/11794633/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/11794633/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID11794633", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Volunteer urinary testing finds oxide less absorbed and chloride/lactate/aspartate comparable.", "what_it_does_not_show": "Some inorganic salts match organic salts; chemical class labels cannot establish clinical sleep rankings.", "confounders_present": [ "Some inorganic salts match organic salts; chemical class labels cannot establish clinical sleep rankings." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 40, "pmid": "30829204", "title": "Neurobehavioral and biochemical effects of magnesium chloride (MgCl2), magnesium sulphate (MgSO4) and magnesium-L-threonate (MgT) supplementation in rats: A dose dependent comparative study.", "citation": "Sadir S, Tabassum S, Emad S et al. Neurobehavioral and biochemical effects of magnesium chloride (MgCl2), magnesium sulphate (MgSO4) and magnesium-L-threonate (MgT) supplementation in rats: A dose dependent comparative study. Pakistan journal of pharmaceutical sciences. 2019.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/30829204/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30829204/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID30829204", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Weak", "system": "animal model", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Rat salt/dose comparisons report memory and depression-related behavior differences.", "what_it_does_not_show": "Forced-swim/maze proxies, salt-mass doses and biomarkers do not demonstrate human insomnia or form superiority.", "confounders_present": [ "Forced-swim/maze proxies, salt-mass doses and biomarkers do not demonstrate human insomnia or form superiority." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 41, "pmid": "20862466", "title": "Bioavailability of magnesium from different pharmaceutical formulations.", "citation": "Siener R, Jahnen A, Hesse A. Bioavailability of magnesium from different pharmaceutical formulations. Urological research. 2011.", "doi": "10.1007/s00240-010-0309-y", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/20862466/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/20862466/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID20862466", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "An oxide effervescent/capsule crossover under standardized diet produces different urinary uptake.", "what_it_does_not_show": "Delivery formulation matters within one salt; no brain or sleep function endpoint was measured.", "confounders_present": [ "Delivery formulation matters within one salt; no brain or sleep function endpoint was measured." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 42, "pmid": "31230494", "title": "Magnesium Bioavailability and Tolerability Do Not Differ between Two Supplements with Different Release Properties.", "citation": "Greupner T, Schneider I, Gellert S et al. Magnesium Bioavailability and Tolerability Do Not Differ between Two Supplements with Different Release Properties. Journal of dietary supplements. 2020.", "doi": "10.1080/19390211.2019.1629146", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/31230494/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31230494/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID31230494", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "Controlled crossover finds no availability/tolerability difference between immediate and delayed release.", "what_it_does_not_show": "Open-label acute pharmacokinetics is not sleep comparative efficacy; the null is retained.", "confounders_present": [ "Open-label acute pharmacokinetics is not sleep comparative efficacy; the null is retained." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 43, "pmid": "12001016", "title": "Magnesium bioavailability from mineral water. A study in adult men.", "citation": "Verhas M, de la Guéronnière V, Grognet JM et al. Magnesium bioavailability from mineral water. A study in adult men. European journal of clinical nutrition. 2002.", "doi": "10.1038/sj.ejcn.1601333", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/12001016/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/12001016/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID12001016", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Oral/IV mineral-water radiotracing quantifies enteral absorption in men.", "what_it_does_not_show": "Ten participants and acute tracers; no sleep endpoint. Age correlation is not a randomized age effect.", "confounders_present": [ "Ten participants and acute tracers; no sleep endpoint. Age correlation is not a randomized age effect." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 44, "pmid": "1864954", "title": "Intestinal absorption of magnesium from food and supplements.", "citation": "Fine KD, Santa Ana CA, Porter JL et al. Intestinal absorption of magnesium from food and supplements. The Journal of clinical investigation. 1991.", "doi": "10.1172/JCI115317", "pmcid": "PMC295344", "url": "https://pubmed.ncbi.nlm.nih.gov/1864954/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/1864954/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID1864954", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Controlled magnesium loading shows curvilinear absorption and lower fractions at larger doses; enteric coating lowers uptake.", "what_it_does_not_show": "Intestinal or food effects do not establish central exposure or hypnotic efficacy.", "confounders_present": [ "Intestinal or food effects do not establish central exposure or hypnotic efficacy." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 45, "pmid": "1468087", "title": "Blood and urinary magnesium kinetics after oral magnesium supplements.", "citation": "White J, Massey L, Gales SK et al. Blood and urinary magnesium kinetics after oral magnesium supplements. Clinical therapeutics. 1992.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/1468087/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/1468087/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID1468087", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "A12-person crossover finds some salt-specific blood/urine time-profile differences.", "what_it_does_not_show": "Overall blood compartment changes are mostly nonsignificant; there is no general salt winner or sleep comparison.", "confounders_present": [ "Overall blood compartment changes are mostly nonsignificant; there is no general salt winner or sleep comparison." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 46, "pmid": "3430654", "title": "Absorption of magnesium from orally administered magnesium sulfate in man.", "citation": "Morris ME, LeRoy S, Sutton SC. Absorption of magnesium from orally administered magnesium sulfate in man. Journal of toxicology. Clinical toxicology. 1987.", "doi": "10.3109/15563658708992640", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/3430654/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/3430654/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID3430654", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "A six-volunteer sulfate study measures limited variable absorption and diarrhea after a cathartic dose.", "what_it_does_not_show": "Cathartic exposure and normal kidneys differ from sleep regimens; no dosing recommendation is inferred.", "confounders_present": [ "Cathartic exposure and normal kidneys differ from sleep regimens; no dosing recommendation is inferred." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 47, "pmid": "11756061", "title": "Meal effect on magnesium bioavailability from mineral water in healthy women.", "citation": "Sabatier M, Arnaud MJ, Kastenmayer P et al. Meal effect on magnesium bioavailability from mineral water in healthy women. The American journal of clinical nutrition. 2002.", "doi": "10.1093/ajcn/75.1.65", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/11756061/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/11756061/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID11756061", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Stable-isotope crossover finds meal-enhanced mineral-water absorption/retention in ten women.", "what_it_does_not_show": "Meal effects change availability without demonstrating a neural sleep mechanism or salt superiority.", "confounders_present": [ "Meal effects change availability without demonstrating a neural sleep mechanism or salt superiority." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 48, "pmid": "35041150", "title": "Effects of short-term magnesium supplementation on ionized, total magnesium and other relevant electrolytes levels.", "citation": "Ivanovic ND, Radosavljevic B, Zekovic M et al. Effects of short-term magnesium supplementation on ionized, total magnesium and other relevant electrolytes levels. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine. 2022.", "doi": "10.1007/s10534-022-00363-y", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/35041150/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/35041150/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID35041150", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Short supplementation finds discordant ionized/total magnesium patterns and oxide advantage on selected indices.", "what_it_does_not_show": "Compartment changes are not brain availability; no insomnia endpoint or glycinate superiority was tested.", "confounders_present": [ "Compartment changes are not brain availability; no insomnia endpoint or glycinate superiority was tested." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 49, "pmid": "20152124", "title": "Enhancement of learning and memory by elevating brain magnesium.", "citation": "Slutsky I, Abumaria N, Wu LJ et al. Enhancement of learning and memory by elevating brain magnesium. Neuron. 2010.", "doi": "10.1016/j.neuron.2009.12.026", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/20152124/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/20152124/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID20152124", "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", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Threonate increases rat brain magnesium and enhances memory/synaptic physiology.", "what_it_does_not_show": "Memory and plasticity are not human insomnia; central-model findings do not predict every clinical sleep measure.", "confounders_present": [ "Memory and plasticity are not human insomnia; central-model findings do not predict every clinical sleep measure." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 50, "pmid": "34883514", "title": "Association of magnesium intake with sleep duration and sleep quality: findings from the CARDIA study.", "citation": "Zhang Y, Chen C, Lu L et al. Association of magnesium intake with sleep duration and sleep quality: findings from the CARDIA study. Sleep. 2022.", "doi": "10.1093/sleep/zsab276", "pmcid": "PMC8996025", "url": "https://pubmed.ncbi.nlm.nih.gov/34883514/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34883514/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID34883514", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "CARDIA intake associates with less short sleep and borderline sleep-quality improvement.", "what_it_does_not_show": "Diet/lifestyle confounding, self-report and depression interaction remain; no randomized salt-specific efficacy.", "confounders_present": [ "Diet/lifestyle confounding, self-report and depression interaction remain; no randomized salt-specific efficacy." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 51, "pmid": "36354243", "title": "Effect of short-term magnesium supplementation on anxiety, depression and sleep quality in patients after open-heart surgery.", "citation": "Saba S, Faizi F, Sepandi M et al. Effect of short-term magnesium supplementation on anxiety, depression and sleep quality in patients after open-heart surgery. Magnesium research. 2022.", "doi": "10.1684/mrh.2022.0503", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/36354243/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36354243/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID36354243", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Weak", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Post-heart-surgery magnesium versus routine care suggests lower PSQI/anxiety scores.", "what_it_does_not_show": "Five days is outside the registered2–24-week horizon; no blinded placebo and postoperative recovery confound interpretation.", "confounders_present": [ "Five days is outside the registered2–24-week horizon; no blinded placebo and postoperative recovery confound interpretation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 52, "pmid": "38745424", "title": "The effects of melatonin and magnesium in a novel supplement delivery system on sleep scores, body composition and metabolism in otherwise healthy individuals with sleep disturbances.", "citation": "Carlos RM, Matias CN, Cavaca ML et al. The effects of melatonin and magnesium in a novel supplement delivery system on sleep scores, body composition and metabolism in otherwise healthy individuals with sleep disturbances. Chronobiology international. 2024.", "doi": "10.1080/07420528.2024.2353225", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38745424/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38745424/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID38745424", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Melatonin/Mg coffee-pod crossover improves several sleep measures over placebo.", "what_it_does_not_show": "No single-ingredient arms and final average PSQI remains poor; combination efficacy does not establish magnesium mediation.", "confounders_present": [ "No single-ingredient arms and final average PSQI remains poor; combination efficacy does not establish magnesium mediation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 53, "pmid": "19066411", "title": "NMDA/glutamate mechanism of magnesium-induced anxiolytic-like behavior in mice.", "citation": "Poleszak E, Wlaź P, Wróbel A et al. NMDA/glutamate mechanism of magnesium-induced anxiolytic-like behavior in mice. Pharmacological reports : PR. 2008.", "doi": "", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/19066411/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/19066411/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID19066411", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "NMDA/glycine-site ligand manipulations enhance or antagonize magnesium-related mouse anxiety-like behavior.", "what_it_does_not_show": "Elevated-plus-maze and nonclinical exposure are not oral human insomnia; glycine-site binding is not glycinate comparative efficacy.", "confounders_present": [ "Elevated-plus-maze and nonclinical exposure are not oral human insomnia; glycine-site binding is not glycinate comparative efficacy." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 54, "pmid": "41515231", "title": "Magnesium and Zinc Are Associated with Sleep Quality in Saudi Adults: Evidence from a Cross-Sectional Study.", "citation": "Al-Musharaf S, Aldhwayan MM, Mazi TA et al. Magnesium and Zinc Are Associated with Sleep Quality in Saudi Adults: Evidence from a Cross-Sectional Study. Nutrients. 2025.", "doi": "10.3390/nu18010114", "pmcid": "PMC12787342", "url": "https://pubmed.ncbi.nlm.nih.gov/41515231/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41515231/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID41515231", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Saudi cross-sectional data associate serum/dietary magnesium with poor PSQI quality.", "what_it_does_not_show": "Confounding and model variation remain; nutrient association is not a causal deficiency-response trial.", "confounders_present": [ "Confounding and model variation remain; nutrient association is not a causal deficiency-response trial." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 55, "pmid": "38703902", "title": "Association between magnesium deficiency score and sleep quality in adults: A population-based cross-sectional study.", "citation": "Luo X, Tang M, Wei X et al. Association between magnesium deficiency score and sleep quality in adults: A population-based cross-sectional study. Journal of affective disorders. 2024.", "doi": "10.1016/j.jad.2024.05.002", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38703902/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38703902/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID38703902", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "mixed", "what_it_shows": "NHANES depletion-score analysis associates sleep trouble/apnea with a higher score.", "what_it_does_not_show": "No association with insomnia or insufficient sleep; renal-risk proxies and reverse causation remain.", "confounders_present": [ "No association with insomnia or insufficient sleep; renal-risk proxies and reverse causation remain." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 56, "pmid": "24807818", "title": "Dietary magnesium restriction reduces amygdala-hypothalamic GluN1 receptor complex levels in mice.", "citation": "Ghafari M, Whittle N, Miklósi AG et al. Dietary magnesium restriction reduces amygdala-hypothalamic GluN1 receptor complex levels in mice. Brain structure & function. 2015.", "doi": "10.1007/s00429-014-0779-8", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/24807818/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/24807818/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "ErratumIn: PMID24965486" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID24807818", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "animal model", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Dietary restriction alters mouse NMDA-complex proteins alongside depression-related behavior.", "what_it_does_not_show": "Paroxetine restores behavior without protein restoration; correlation is not necessity. Author-name correction 24965486 is attached.", "confounders_present": [ "Paroxetine restores behavior without protein restoration; correlation is not necessity. Author-name correction 24965486 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": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 57, "pmid": "40010346", "title": "Structural insights into the diverse actions of magnesium on NMDA receptors.", "citation": "Huang X, Sun X, Wang Q et al. Structural insights into the diverse actions of magnesium on NMDA receptors. Neuron. 2025.", "doi": "10.1016/j.neuron.2025.01.021", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/40010346/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40010346/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID40010346", "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", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "in vitro", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Structural/mutational work identifies magnesium-specific NMDA sites for block, potentiation and inhibition.", "what_it_does_not_show": "Engineered receptors are not human sleep; these diverse effects are not a simple universal sedative mechanism.", "confounders_present": [ "Engineered receptors are not human sleep; these diverse effects are not a simple universal sedative mechanism." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 58, "pmid": "41916937", "title": "Magnesium supplementation as an adjunct to fluoxetine therapy for depression.", "citation": "Walyddaini AS, Lisal ST, Ilhamuddin et al. Magnesium supplementation as an adjunct to fluoxetine therapy for depression. East Asian archives of psychiatry : official journal of the Hong Kong College of Psychiatrists = Dong Ya jing shen ke xue zhi : Xianggang jing shen ke yi xue yuan qi kan. 2026.", "doi": "10.12809/eaap25122", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/41916937/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41916937/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID41916937", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Weak", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Magnesium added to fluoxetine produces a larger HDRS change including insomnia items.", "what_it_does_not_show": "Alternating allocation is not concealed randomization; no blinded magnesium placebo and a depression composite is not a sleep primary.", "confounders_present": [ "Alternating allocation is not concealed randomization; no blinded magnesium placebo and a depression composite is not a sleep primary." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 59, "pmid": "37520407", "title": "A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Therapeutic Effect of Magnesium-L-Threonate Supplementation for Persistent Pain After Breast Cancer Surgery.", "citation": "Ni Y, Deng F, Yu S et al. A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Therapeutic Effect of Magnesium-L-Threonate Supplementation for Persistent Pain After Breast Cancer Surgery. Breast cancer (Dove Medical Press). 2023.", "doi": "10.2147/BCTT.S413435", "pmcid": "PMC10386839", "url": "https://pubmed.ncbi.nlm.nih.gov/37520407/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37520407/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID37520407", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [ "M4" ], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "Twelve-week randomized magnesium-threonate trial in 109 breast-surgery patients finds no between-arm PSQI mood cognition or pain benefit", "what_it_does_not_show": "Pain-prevention cohort was not enrolled for primary insomnia; secondary sleep endpoint and postoperative context limit transfer to poor-sleep eligibility", "confounders_present": [ "Pain-prevention cohort was not enrolled for primary insomnia; secondary sleep endpoint and postoperative context limit transfer to poor-sleep eligibility" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 60, "pmid": "42661485", "title": "Magnesium Supplementation for Sleep in Adults: A Systematic Review of Randomized Controlled Trials.", "citation": "Lopresti AL, Smith SJ, Drummond PD. Magnesium Supplementation for Sleep in Adults: A Systematic Review of Randomized Controlled Trials. Journal of dietary supplements. 2026.", "doi": "10.1080/19390211.2026.2719670", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/42661485/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/42661485/", "tier": "B", "source_tier": "B", "kind": "systematic_review", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-11-02", "status_checked_on": "2026-11-02", "study_id": "PMID42661485", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata checked in the 2026-11-02 adversarial pass (finding m7); context item outside the 59 examined primary reports; no primary-report or threshold credit.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "A systematic review of twelve stand-alone-magnesium RCTs finds inconsistent sleep effects at low to very-low certainty and does not support routine insomnia treatment.", "what_it_does_not_show": "A secondary synthesis earns no primary-report credit; it shares authors with refs 3 and 19.", "confounders_present": [ "A secondary synthesis earns no primary-report credit; it shares authors with refs 3 and 19." ], "verification": "verified", "verification_note": "Added by the 2026-11-02 adversarial pass as context; PMID and DOI verified in PubMed.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 61, "pmid": "33865376", "title": "Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis.", "citation": "Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis. BMC complementary medicine and therapies. 2021.", "doi": "10.1186/s12906-021-03297-z", "pmcid": "PMC8053283", "url": "https://pubmed.ncbi.nlm.nih.gov/33865376/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33865376/", "tier": "B", "source_tier": "B", "kind": "meta_analysis", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-11-02", "status_checked_on": "2026-11-02", "study_id": "PMID33865376", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata checked in the 2026-11-02 adversarial pass (finding m7); context item outside the 59 examined primary reports; no primary-report or threshold credit.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "A meta-analysis of three small older-adult RCTs reports shorter sleep-onset latency on low to very-low-quality evidence.", "what_it_does_not_show": "A secondary synthesis of moderate-to-high risk-of-bias trials earns no primary-report credit and does not establish a clinically important effect.", "confounders_present": [ "A secondary synthesis of moderate-to-high risk-of-bias trials earns no primary-report credit and does not establish a clinically important effect." ], "verification": "verified", "verification_note": "Added by the 2026-11-02 adversarial pass as context; PMID and DOI verified in PubMed.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 62, "pmid": "36620514", "title": "Effect of magnesium supplementation in improving hyperandrogenism, hirsutism, and sleep quality in women with polycystic ovary syndrome: A randomized, placebo-controlled clinical trial.", "citation": "Gholizadeh-Moghaddam M, Ghasemi-Tehrani H, Askari G et al. Effect of magnesium supplementation in improving hyperandrogenism, hirsutism, and sleep quality in women with polycystic ovary syndrome: A randomized, placebo-controlled clinical trial. Health science reports. 2023.", "doi": "10.1002/hsr2.1013", "pmcid": "PMC9798963", "url": "https://pubmed.ncbi.nlm.nih.gov/36620514/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36620514/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-11-02", "status_checked_on": "2026-11-02", "study_id": "PMID36620514", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata checked in the 2026-11-02 adversarial pass (finding m7); context item outside the 59 examined primary reports; no primary-report or threshold credit.", "relates_to_subclaims": [ "SC2" ], "favors_models": [ "M4" ], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "A ten-week magnesium oxide versus placebo trial in women with PCOS finds no sleep-quality effect.", "what_it_does_not_show": "Participants were not enrolled for poor sleep; this is a population boundary, not a direct test of the registered claim.", "confounders_present": [ "Participants were not enrolled for poor sleep; this is a population boundary, not a direct test of the registered claim." ], "verification": "verified", "verification_note": "Added by the 2026-11-02 adversarial pass as context; PMID and DOI verified in PubMed.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] } ], "verification_summary": { "load_bearing_claims_checked": 64, "verified": 64, "unverified": 0, "contradicted": 0, "note": "Verified attribution is distinct from mechanism truth or complete body access." }, "factual_issues_found": [], "cap_rules_applied": [ { "subclaim_id": "SC1", "cap": "Γ", "cap_source": "universal", "triggered": true, "trigger_text_quoted": "Biomarker change without functional/phenotypic change caps at Γ.", "specific_trigger": "Controlled oral exposure and isotope studies demonstrate systemic absorption. Rodent central exposure and neural effects retain their experimental scope. Peripheral status changes and rodent cognition cannot establish human brain delivery or a sleep-relevant neural dependency at the studied exposure; the target-availability inference retains Γ. The separately controlled clinical formulation effect is assessed in SC2.", "resulting_ceiling": "Γ" }, { "subclaim_id": "SC4", "cap": "Γ", "cap_source": "rubric", "triggered": true, "trigger_text_quoted": "Candidate mediator correlated with outcome, never manipulated.", "specific_trigger": "NMDA structural/mutational studies, deficiency/repletion models and mouse ligand experiments support plausible neural mechanisms. Human sleep/stress studies generally measure hormones, magnesium or neural signals alongside symptoms without manipulating the candidate mediator while retaining treatment. Coingredients and glycine ligand exposure remain unpartitioned, so the human mediation claim does not crossΔ.", "resulting_ceiling": "Γ" } ], "cap_precedence_resolutions": [ { "collision": "Perturbation in a defined setting versus broader inference", "subclaim_scope_cap_binds_on": "Oral magnesium supplementation improves sleep in adults with poor sleep or insomnia.", "subclaim_scope_threshold_binds_on": "The precise experimentally tested subclaim scope", "resolution": "The small positive primary symptom contrast in a prospectively registered, blinded ordinary-supplement trial crosses the explicitly adapted clinical threshold for SC2. It does not cross a human neural-mediation threshold or establish meaningful objective architecture recovery. Peripheral biomarker and rodent findings retain their exact scope; correlations areΓ-capped for human mediation. Absence of a direct salt comparison leavesSC3unsupported without recapping clinical efficacy.", "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 peripheral exposure and rodent neural function are scoped separately." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Controlled oral exposure and isotope studies demonstrate systemic absorption. Rodent central exposure and neural effects retain their experimental scope. Peripheral status changes and rodent cognition cannot establish human brain delivery or a sleep-relevant neural dependency at the studied exposure; the target-availability inference retains Γ. The separately controlled clinical formulation effect is assessed in SC2.", "ceiling_from_boundary_check": "Γ" }, { "subclaim_id": "SC2", "field_valid_perturbation_quote": "at least one of:\n- Active comparator matched for acute subjective effect, blinding integrity measured and reported\n- Blinded on/off, staggered-onset, or randomized-withdrawal neuromodulation, reversible and within-subject\n- Mediator manipulation with the intervention intact: antagonist blockade of the acute experience with the drug still given, or dosing under general anaesthesia\n- Depletion or challenge experiment in humans whose outcome is symptom trajectory, not a biomarker\n- Psychotherapy component dismantling, or scaffold removal from a drug arm, with blinded assessors\n\nRating-scale or biomarker change alone does NOT satisfy this threshold when the claim is functional, and statistical mediation alone never satisfies it.", "qualifying_evidence_present": "yes", "qualifying_evidence_citation": "PMID40918053", "gamma_hard_rules_triggered": [ "Credible identical-placebo, prospectively registered primary ISI contrast retained; older unblinded, biomarker and exploratory findings do not earn this crossing." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "yes", "perturbation_result_note": "The prospectively registered, blinded 2025 bisglycinate trial supports a small improvement on the validated primary ISI outcome over four weeks. Older and newer studies contain additional positive, null and mixed sleep findings. A clean, reproducible baseline-deficiency effect boundary has not been mapped, clinically important responder contrasts are incompletely established and objective replication is limited. The first causal threshold is retained atΔ without elevating a small formulation effect to broad reliable insomnia treatment.", "ceiling_from_boundary_check": "Δ or higher" }, { "subclaim_id": "SC3", "field_valid_perturbation_quote": "at least one of:\n- Active comparator matched for acute subjective effect, blinding integrity measured and reported\n- Blinded on/off, staggered-onset, or randomized-withdrawal neuromodulation, reversible and within-subject\n- Mediator manipulation with the intervention intact: antagonist blockade of the acute experience with the drug still given, or dosing under general anaesthesia\n- Depletion or challenge experiment in humans whose outcome is symptom trajectory, not a biomarker\n- Psychotherapy component dismantling, or scaffold removal from a drug arm, with blinded assessors\n\nRating-scale or biomarker change alone does NOT satisfy this threshold when the claim is functional, and statistical mediation alone never satisfies it.", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "", "gamma_hard_rules_triggered": [ "No direct comparative clinical sleep test was examined." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "No directly examined, matched-elemental-dose human sleep trial establishes that glycinate or threonate is superior to other salts. Absorption comparisons and rodent cognitive/anxiety studies are not direct clinical sleep comparisons. This positive comparative sleep proposition remains unsupported atΑ, rather than being inferred from popularity or formulation branding.", "ceiling_from_boundary_check": "Γ" }, { "subclaim_id": "SC4", "field_valid_perturbation_quote": "at least one of:\n- Active comparator matched for acute subjective effect, blinding integrity measured and reported\n- Blinded on/off, staggered-onset, or randomized-withdrawal neuromodulation, reversible and within-subject\n- Mediator manipulation with the intervention intact: antagonist blockade of the acute experience with the drug still given, or dosing under general anaesthesia\n- Depletion or challenge experiment in humans whose outcome is symptom trajectory, not a biomarker\n- Psychotherapy component dismantling, or scaffold removal from a drug arm, with blinded assessors\n\nRating-scale or biomarker change alone does NOT satisfy this threshold when the claim is functional, and statistical mediation alone never satisfies it.", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "", "gamma_hard_rules_triggered": [ "Candidate mediator correlated with outcome, never manipulated in the examined human clinical sleep setting. Rodent effects do not establish human mediation." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "NMDA structural/mutational studies, deficiency/repletion models and mouse ligand experiments support plausible neural mechanisms. Human sleep/stress studies generally measure hormones, magnesium or neural signals alongside symptoms without manipulating the candidate mediator while retaining treatment. Coingredients and glycine ligand exposure remain unpartitioned, so the human mediation claim does not crossΔ.", "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": "Confirm central exposure and neural functional relevance in people at the studied oral doses with robust compartment measurements rather than urinary/plasma surrogates alone." }, { "subclaim_id": "SC2", "threshold": "Δ", "requirement_quoted": "Requires a controlled human interventional study with a credible active comparator, or a mediator manipulation in humans, with a pre-registered primary outcome.", "satisfied": "yes", "supporting_evidence": [ "[3] A prospectively registered (DRKS00031494, registered 12 April 2023, before first enrolment on 20 April 2023) four-week bisglycinate trial shows a small primary ISI benefit." ], "what_would_cross_it": "" }, { "subclaim_id": "SC2", "threshold": "Ε", "requirement_quoted": "Requires causal support restricted to a defined context — one diagnosis, one severity stratum, one treatment-resistant subgroup, or only with the accompanying psychotherapeutic scaffold.", "satisfied": "no", "supporting_evidence": [ "[3] A prospectively registered (DRKS00031494, registered 12 April 2023, before first enrolment on 20 April 2023) four-week bisglycinate trial shows a small primary ISI benefit." ], "what_would_cross_it": "Replicate the prespecified sleep benefit in an independent blinded trial with clinically meaningful responder thresholds, objective sleep and prospectively stratified baseline magnesium status. Map where benefit stops rather than select responders afterward." }, { "subclaim_id": "SC3", "threshold": "Δ", "requirement_quoted": "Requires a controlled human interventional study with a credible active comparator, or a mediator manipulation in humans, with a pre-registered primary outcome.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "Directly compare matched elemental-dose glycinate, threonate and another salt with matched ligand/coingredients, credible blinding and prespecified sleep outcomes." }, { "subclaim_id": "SC4", "threshold": "Δ", "requirement_quoted": "Requires a controlled human interventional study with a credible active comparator, or a mediator manipulation in humans, with a pre-registered primary outcome.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "Dissociate magnesium-ion, ligand and candidate neural pathway effects under the same treatment and measure the clinically relevant sleep/stress trajectory." } ], "generalization_check": { "generalization_tested": "yes", "context_boundary_mapped": "yes", "internal_negative_controls": [ "Nielsen citrate and placebo improve PSQI equally despite some status/inflammation differences.", "2024 threonate overall ISI interaction and several LSEQ sleep subscales are null; post-hoc positives do not erase them.", "The 2025/2026 threonate trial reports no ring-derived sleep difference and null sleep disturbance/restorative sleep alongside a positive sleep-related-impairment measure.", "PCOS magnesium-only sleep effect is not the melatonin or combination result; stress Mg-versus-Mg+B6 comparisons lack a magnesium-free arm.", "Three-week rodent deficiency changes neural oscillations without changing sleep architecture; longer deficiency/repletion has different effects." ], "note": "The evidence includes varied formulations, ages, clinical conditions, dietary/serum status, doses and short horizons. These are not interchangeable replications. A consistent human deficiency-dependent benefit boundary has not been mapped: Nielsen has no supplement-specific global PSQI effect, and the bisglycinate dietary interaction is exploratory and based on a non-validated question. The older trial selected low dietary intake and serum Mg <0.95 mmol/L, which is not a definition proving every participant had clinical hypomagnesemia. Salt superiority, brain delivery and long-term functional recovery remain separate." }, "falsification_patterns_met": [ { "pattern": "More peripheral magnesium does not consistently yield better sleep", "evidence": "Nielsen status/inflammation changes coexist with equal placebo/globalPSQI; newer threonate physiological shifts coexist with null objective sleep.", "downgrade_applied": false }, { "pattern": "Human mediator and salt-superiority predictions remain untested or unpartitioned", "evidence": "No matched clinical salt comparison or human mediator manipulation was examined; ligand/coingredient exposures remain present.", "downgrade_applied": false } ], "pitfalls_flagged": [ { "name": "Confirmation by biomarker", "evidence": "Absorption, hormone, EEG or HRV change is not proof of clinically meaningful sleep benefit.", "pitfall": "Confirmation by biomarker", "where": "Absorption, hormone, EEG or HRV change is not proof of clinically meaningful sleep benefit." }, { "name": "Mechanism conflation", "evidence": "Formulation efficacy, magnesium-ion mediation and relative salt efficacy are separate claims.", "pitfall": "Mechanism conflation", "where": "Formulation efficacy, magnesium-ion mediation and relative salt efficacy are separate claims." }, { "name": "Scope fitted to the result", "evidence": "Exploratory dietary correlations/severe subgroups cannot redefine the enrolled population as established responders.", "pitfall": "Scope fitted to the result", "where": "Exploratory dietary correlations/severe subgroups cannot redefine the enrolled population as established responders." }, { "name": "Selective generalization", "evidence": "Rodent deficiency rescue and brain uptake do not demonstrate benefit in magnesium-replete adult poor sleepers.", "pitfall": "Selective generalization", "where": "Rodent deficiency rescue and brain uptake do not demonstrate benefit in magnesium-replete adult poor sleepers." }, { "name": "Replication confused with independence", "evidence": "Several metabolic/mental-health publications share underlying trial participants.", "pitfall": "Replication confused with independence", "where": "Several metabolic/mental-health publications share underlying trial participants." } ], "causal_tally_audit": { "tally_claimed_by_document": 1, "tally_after_audit": 1, "tally_unit": "Positive qualifying study units across scoped subclaims, not independent causal lines or full-claim necessity/sufficiency.", "screened_discriminating_contrasts": 18, "items_rejected": [ "Null and negative contrasts are discriminators, not positive threshold crossings. Reports and replications are not independent causal lines.", "Only positive qualifying scoped studies earn threshold credit; original nulls and exploratory subgroup contrasts remain discriminating evidence.", "Three diabetic-insomnia reports share one trial, three stress reports share another, and two EEG stress papers share another.", "Availability studies and rodent stress/cognition papers are not clinical insomnia trials; the 59 original reports must not be marketed as 59 sleep RCTs." ] }, "steelman": { "case_one_rung_higher": "Ε could be defended from positive selected older-adult outcomes, the recent bisglycinate primary symptom result and a small positive sleep-related-impairment contrast in the newer threonate trial. The stronger case would require a mapped baseline-defined response boundary with credible replication rather than different endpoints, populations or post-hoc subgroup claims.", "case_one_rung_lower": "Γ could be defended because clinical effects are small and formulation ligands, missing objective confirmation and old trial reporting complicate mechanism. That would improperly erase the prespecified placebo-controlled symptom contribution of the ordinary formulation; exact ion mediation is a separate SC4 claim.", "which_rejected": "Reject Ε because a stable clinical response boundary and robust matched replication are not established; mixed/null objective and broad sleep outcomes remain. Reject Γ for SC2 because the registered clinical symptom claim has a credible prospectively registered primary placebo contrast. Retain Δ Low; SC4 human mechanism stays Γ.", "blocking_cap_threshold_or_missing_experiment": "Missing experiment: An independently sponsored, prospectively registered blinded factorial trial in adults with baseline poor sleep, stratified by validated measured magnesium status before randomization. Compare matched elemental-dose magnesium salts with ligand-matched controls, including glycine/threonate-only and visually identical placebo conditions. Use a prespecified clinically meaningful ISI responder threshold plus actigraphy/polysomnography and daytime function over 8–12 weeks, with allocation guesses, adherence and missingness sensitivity." }, "final_score": { "hsef_level": "Δ", "hsef_descriptor": "First field-valid causal perturbation crossed", "confidence": "Low", "confidence_rationale": "One positive qualifying study unit (PMID 40918053; d=0.2, p=0.049) without independent replication of that endpoint and formulation; the other controlled sleep trials differ in salt, dose, population and endpoint and include primary or global nulls (PMIDs 21199787, 39252819, 37520407). Evidence density and reproducibility set the band at Low, the framework's (Δ, low) pattern.", "rests_on_non_peer_reviewed_work": false, "rationale": "The registered clinical subclaim SC2 supports Δ with Low confidence. A prospectively registered (DRKS00031494, registered 12 April 2023, before first enrolment on 20 April 2023), double-blind, placebo-controlled bisglycinate trial found a small improvement on its validated primary insomnia score. The studied formulation effect does not establish a large clinically meaningful benefit, a deficiency-only response boundary, salt superiority or magnesium-ion mediation. Mixed and null findings, plus limited objective replication, prevent a stronger clinical claim." }, "role_of_mechanism": { "classification": "reinforcing / stabilizing factor", "derivation_step_matched": 5, "derivation": "The positive primary controlled formulation contrast supports a contribution to sleep symptom response, so mere epiphenomenon is inappropriate. Requiredness, withdrawal prevention and rate limitation have not all been demonstrated for oral magnesium in humans; other sleep-active components and interventions work without it. The remaining mandatory role class is a reinforcing/stabilizing contribution to sleep regulation, with its precise ion-specific mediator unresolved.", "tournament_used_as_tiebreaker": false, "note": "Derived from causal direction, not tournament rank." }, "extended_scoring_MSD": { "momentum": { "value": "Mechanistic only", "artifact": "Recent controlled clinical work exists — the prospectively registered bisglycinate trial DRKS00031494 used a controlled validated symptom endpoint without objective sleep measurement, and the newer threonate trial ACTRN12624000379516 added ring-derived wearables and an allocation-guess check — but both are completed, and no registered independent form/ligand or status-stratified trial addressing the named boundary was identified in this bounded search.", "justification": "Recent controlled clinical work exists — the prospectively registered bisglycinate trial DRKS00031494 used a controlled validated symptom endpoint without objective sleep measurement, and the newer threonate trial ACTRN12624000379516 added ring-derived wearables and an allocation-guess check — but both are completed, and no registered independent form/ligand or status-stratified trial addressing the named boundary was identified in this bounded search." }, "stability": { "value": "Stable", "trigger": "No verified named pending trial specifically addressing the required ligand-matched, status-stratified objective sleep boundary was identified in this bounded search. New independent trials could change the assessment, but no unverified pending result is invented.", "justification": "No verified named pending trial specifically addressing the required ligand-matched, status-stratified objective sleep boundary was identified in this bounded search. New independent trials could change the assessment, but no unverified pending result is invented." }, "divergence": { "implied_level": null, "implied_level_basis": "Marketing formulations, clinical papers and systematic summaries defend different propositions; no single field-wide inferred HSEFlevel was measured.", "assessed_level": "Δ", "gap_in_rungs": null, "value": "Contested", "justification": "No manufactured causal percentage or global belief-to-evidence arithmetic." }, "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": "Δ", "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": "An independently sponsored, prospectively registered blinded factorial trial in adults with baseline poor sleep, stratified by validated measured magnesium status before randomization. Compare matched elemental-dose magnesium salts with ligand-matched controls, including glycine/threonate-only and visually identical placebo conditions. Use a prespecified clinically meaningful ISI responder threshold plus actigraphy/polysomnography and daytime function over 8–12 weeks, with allocation guesses, adherence and missingness sensitivity.", "readout": "Between-arm validated insomnia symptoms, prespecified meaningful responder rates, objective sleep continuity/architecture and daytime function; exposure measured separately.", "critical_control": "Matched elemental magnesium, chemical ligands, other sleep-active ingredients and contact; prospective baseline status strata, renal eligibility, blinded allocation and missingness sensitivity. Do not select post-treatment responders.", "supporting_result": "A reproducible clinically meaningful sleep benefit that persists against ligand-matched control and maps to a predefined status/context boundary would strengthen clinical causality and form-specific attribution.", "falsifying_result": "No matched-control benefit or effects confined to coingredients/expectancy would weaken the broad magnesium formulation attribution; an objective null does not automatically erase a replicated symptom-only effect." } ], "knowledge_gaps": [ { "name": "Gap 1", "statement": "Independent replication of a clinically meaningful sleep benefit rather than only borderline small symptom differences.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 2", "statement": "A prospectively tested magnesium-deficient versus replete response boundary using validated assessment, not post-hoc non-validated dietary questions.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 3", "statement": "Matched elemental-dose and ligand-controlled direct salt comparisons for sleep.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 4", "statement": "Human brain/mediator measurements with genuine mediator dissociation while maintaining treatment.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 5", "statement": "Polysomnography/actigraphy, daytime function and longer-term safety/adherence beyond short consumer wearable scores.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 6", "statement": "Transparent prospective registration, outcome hierarchy, sponsorship and corrections; the threonate correction changes confidence in prespecification.", "relevance": "Limits mechanism identification or scope." } ], "review_metadata": { "review_date": "2026-10-12", "reviewer": "Codex", "evidence_base_note": "59 primary reports; literature cutoff 2026-10-12; source examination UTC date 2026-10-13; bounded critical review, not exhaustive systematic review.", "literature_tools_available": true, "literature_tools_note": "Life Sciences Literature PubMed/Entrez, separately logged public original-body retrieval, and Consensus Pro browser searches. Provider output retained as observed browser text with citation-link mappings, or as previously exported connector documents where present. AI synthesis is not primary full-text verification. Consensus retrieved/included counts are not examined-primary counts. Scite monthly limit was reached earlier in this session; no new Scite query or incoming citation-context audit is claimed for these cases. Tool receipts record actual use. Supplementary discovery outputs do not earn primary-count credit. No independent blinded review.", "skill_version": "5.3", "validator_run": "PASS: exact archived HSEF v5.3 validator rerun after final sealing.", "validator_warnings_addressed": "No warnings.", "limits": "Bounded source-based critical review; no complete-paper/supplement audit, independent scientific peer review or blinded calibration. Revision cases retain original prose outside the three framework output blocks and have explicit correction logs.", "adversarial_reviews": [ { "reviewer": "Claude Opus 5.5 (Anthropic)", "date": "2026-10-14", "findings_applied": [ "A1", "A2", "A3", "A4", "A5" ], "record": "ADVERSARIAL REVIEW AND APPROVAL section of magnesium-sleep.review.md" }, { "reviewer": "Claude Opus 5.5 (Anthropic)", "date": "2026-11-02", "findings_applied": [ "M1", "M2", "m3", "m4", "m5", "m6", "m7", "m8", "E9", "E10" ], "record": "ADVERSARIAL_REVIEW.magnesium-sleep.md; adversarial-findings.magnesium-sleep.json; validation-round3-2026-11-02.json", "level_before": "Δ", "level_after": "Δ", "confidence_before": "Moderate", "confidence_after": "Low", "registration_verification": "WHO ICTRP record DRKS00031494 (last refreshed 7 April 2025): date of registration 12/04/2023, date of first enrolment 20/04/2023, prospective registration Yes, primary outcome ISI; retrieved 2026-11-02." } ] }, "is_calibration_entry": { "value": false, "entry_role": "not_calibration", "blind_graded": null, "completed_blinded_calibration": false, "expected_band_sealed_at": "", "target_sha256": "", "target_authorship": "not applicable", "target_author_saw_review": null, "future_run_status": "not prepared", "unblinded_reason": "These topic families were selected from an editorial traffic-priority list. Selection was visible; no blind calibration or predetermined clinical verdict was preregistered." }, "upper_ladder_check": { "final_level_below_zeta": true, "equivalents_considered": [ { "kind": "mendelian_randomization", "available": false, "why_not_sufficient": "Ordinary placebo-controlled supplementation and objective EEG are available; one newer threonate trial reports allocation guessing. However, substantial endpoint heterogeneity, incomplete prespecification in older trials, small effects, ligand/coingredient confounding and mixed objective outcomes remain (one small positive EEG crossover, null ring-derived outcomes in the newer threonate trial). No independent human mediator manipulation, discontinuation/rechallenge or validated genetic line establishes the registered sleep claim. Repetition of the same supplement modality and shared secondary analyses do not create independent causal lines." }, { "kind": "natural_experiment", "available": false, "why_not_sufficient": "Ordinary placebo-controlled supplementation and objective EEG are available; one newer threonate trial reports allocation guessing. However, substantial endpoint heterogeneity, incomplete prespecification in older trials, small effects, ligand/coingredient confounding and mixed objective outcomes remain (one small positive EEG crossover, null ring-derived outcomes in the newer threonate trial). No independent human mediator manipulation, discontinuation/rechallenge or validated genetic line establishes the registered sleep claim. Repetition of the same supplement modality and shared secondary analyses do not create independent causal lines." }, { "kind": "dose_response_across_populations", "available": false, "why_not_sufficient": "Ordinary placebo-controlled supplementation and objective EEG are available; one newer threonate trial reports allocation guessing. However, substantial endpoint heterogeneity, incomplete prespecification in older trials, small effects, ligand/coingredient confounding and mixed objective outcomes remain (one small positive EEG crossover, null ring-derived outcomes in the newer threonate trial). No independent human mediator manipulation, discontinuation/rechallenge or validated genetic line establishes the registered sleep claim. Repetition of the same supplement modality and shared secondary analyses do not create independent causal lines." }, { "kind": "withdrawal_rechallenge", "available": false, "why_not_sufficient": "Ordinary placebo-controlled supplementation and objective EEG are available; one newer threonate trial reports allocation guessing. However, substantial endpoint heterogeneity, incomplete prespecification in older trials, small effects, ligand/coingredient confounding and mixed objective outcomes remain (one small positive EEG crossover, null ring-derived outcomes in the newer threonate trial). No independent human mediator manipulation, discontinuation/rechallenge or validated genetic line establishes the registered sleep claim. Repetition of the same supplement modality and shared secondary analyses do not create independent causal lines." }, { "kind": "therapeutic_perturbation_hard_endpoint", "available": false, "why_not_sufficient": "Ordinary placebo-controlled supplementation and objective EEG are available; one newer threonate trial reports allocation guessing. However, substantial endpoint heterogeneity, incomplete prespecification in older trials, small effects, ligand/coingredient confounding and mixed objective outcomes remain (one small positive EEG crossover, null ring-derived outcomes in the newer threonate trial). No independent human mediator manipulation, discontinuation/rechallenge or validated genetic line establishes the registered sleep claim. Repetition of the same supplement modality and shared secondary analyses do not create independent causal lines." } ], "convergence_present": false, "cap_reapplied_to_convergent_set": false }, "provenance_header": { "sources_total": 59, "claims_total": 64, "claims_verified": 64, "claims_unverified": 0, "claims_contradicted": 0, "tier_a_sources": 59, "generated_by": "Codex; HSEF v5.3", "gate_passed": true }, "claims": [ { "id": "C1", "text": "The 21-day threonate trial reports selected wearable scores and awakening/daytime benefits. Overall ISI interaction is null (p=0.39); correction 40567408 adds retrospective registration and conflicts. Wearable scores are not polysomnography.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "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:Materials and methods:paragraph0, 1:Materials and methods:paragraph6, 1:Materials and methods:paragraph7, 1:Materials and methods:paragraph14, 1:Materials and methods:paragraph32, 11:Declaration of competing interest:paragraph0, 2:Results:paragraph3, 2:Results:paragraph7, 2:Results:paragraph15. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C2", "text": "An eight-week oxide trial in older adults improves ISI and selected sleep-log outcomes. 46 randomized and 43 completed; sample powered on renin, not sleep. Total sleep time is null; low dietary intake is not proof of clinical deficiency.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "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. Selected body sections: 1:MATERIALS AND METHODS:paragraph0, 1:MATERIALS AND METHODS:paragraph1, 2:RESULTS:paragraph0, 2:RESULTS:paragraph3, 2:RESULTS:paragraph5. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C3", "text": "A prospectively registered (DRKS00031494, registered 12 April 2023, before first enrolment on 20 April 2023) four-week bisglycinate trial shows a small primary ISI benefit. 155 randomized, 153 baseline analyzed and 134 completed; d=0.2, p=0.049. Glycine ligand exposure is not isolated and objective sleep is absent.", "carries_number": false, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "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. Selected body sections: 1:Materials and Methods:paragraph0, 1:Materials and Methods:paragraph4, 1:Materials and Methods:paragraph12, 1:Materials and Methods:paragraph14, 1:Materials and Methods:paragraph15, 1:Materials and Methods:paragraph17, 2:Results:paragraph0, 2:Results:paragraph8, 2:Results:paragraph10, 2:Results:paragraph13, 2:Results:paragraph16, 2:Results:paragraph18. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C4", "text": "A diabetic-insomnia four-arm trial reports ISI and hormone changes after Mg/K supplementation. Baseline ISI categories differ substantially (p=0.0001); post-group associations are not adjusted change effects. Single blinding and restricted diet limit inference.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 4 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Materials and methods:paragraph0, 1:Materials and methods:paragraph13, 2:Results:paragraph0, 2:Results:paragraph1, 2:Results:paragraph2. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C5", "text": "An original follow-up of the diabetic-insomnia trial reports glucose and HOMA changes. Same NCT04642313 participants as 39534260; metabolic proxies are not sleep mediation or an independent trial.", "carries_number": false, "load_bearing_for": [ "SC4" ], "source_ns": [ 5 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C6", "text": "An original follow-up of the diabetic-insomnia trial reports renal and liver marker changes. Same320/290 cohort; these markers are not neural mediators or new clinical sleep evidence.", "carries_number": false, "load_bearing_for": [ "SC4" ], "source_ns": [ 6 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C7", "text": "Citrate improves selected low-magnesium and inflammatory indicators in a seven-week randomized trial. Global PSQI improves equally with magnesium and placebo. Nutritional biomarker response does not establish a sleep-responsive deficiency subgroup.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 7 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C8", "text": "Genetic RBC-magnesium lines and dietary deficiency alter mouse sleep and EEG patterns. Central/peripheral regulation and correlation directions differ; optimal balance is distinct from a universal more-magnesium model.", "carries_number": false, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 8 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C9", "text": "Prolonged dietary deficiency disrupts rat sleep/ECoG and repletion restores patterns. Small groups and a deficiency/recovery context do not establish supplementation benefits in replete adults.", "carries_number": false, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 9 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C10", "text": "Three-week deficiency alters rat hippocampal/prefrontal oscillations. Sleep architecture is unchanged; neural signals cannot be relabeled an insomnia phenotype.", "carries_number": false, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 10 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C11", "text": "A restricted-magnesium diet changes rat monoamine concentrations and increases wakefulness. Terminal neurochemical correlations do not isolate a mediator; species and deficiency scope differ from supplementation for human insomnia.", "carries_number": false, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 11 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C12", "text": "A secondary low-magnesemia stress trial analysis reports mood/QoL improvements in both treatment arms. No magnesium-free control and shared2015-003749-24 participants; post-hoc change does not identify magnesium causality.", "carries_number": false, "load_bearing_for": [ "SC4" ], "source_ns": [ 12 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C13", "text": "An investigator-blind stress trial compares Mg+B6 with Mg and finds no overall primary superiority. Both arms contain magnesium; a severe-stress subgroup advantage concerns added B6, not magnesium necessity.", "carries_number": true, "load_bearing_for": [ "SC4" ], "source_ns": [ 13 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C14", "text": "A herbal/Mg/chromium crossover trial reports selected mood and cognitive benefits. 35 analyzed of 43 enrolled, short periods and a multiingredient bundle; no isolated magnesium sleep effect.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 14 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C15", "text": "A randomized botanical/Mg/B-vitamin experiment changes EEG theta and selected subjective stress responses. The ingredient bundle and absent magnesium-only factorial control leave magnesium mediation unidentified.", "carries_number": false, "load_bearing_for": [ "SC4" ], "source_ns": [ 15 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C16", "text": "A secondary stress-trial report finds RBC-magnesium increases in low-status subgroups without extra B6 benefit. Shared trial participants; RBC change and within-group stress improvement are not causal sleep efficacy.", "carries_number": true, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 16 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C17", "text": "An original EEG analysis finds greater task theta under stress with the combined supplement. Behavioral performance and ERP outcomes are null; same NCT03262376 trial, and neural signals do not establish functional benefit.", "carries_number": false, "load_bearing_for": [ "SC4" ], "source_ns": [ 17 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C18", "text": "A40-person supplement/placebo trial reports stress-rating and BOLD changes. Multiple ingredients, single blinding and correlated imaging/rating changes do not isolate magnesium; thermal stress is not insomnia.", "carries_number": true, "load_bearing_for": [ "SC4" ], "source_ns": [ 18 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C19", "text": "A prospective six-week threonate trial improves sleep-related impairment and checks allocation guesses. Sleep disturbance, restorative sleep and all ring sleep outcomes are null. Severe subgroups are exploratory and cognitive-age estimates are not rejuvenation.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "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. Selected body sections: 1:Materials and methods:paragraph0, 2:Results:paragraph20, 2:Results:paragraph29, 2:Results:paragraph30, 2:Results:paragraph32, 2:Results:paragraph39. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C20", "text": "An open-label 12-person citrate pilot improves RLS symptoms and immobilization readouts. No placebo, different clinical condition and unchanged serum magnesium; expectancy and regression remain.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 20 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C21", "text": "A randomized oxide trial finds no benefit for nocturnal cramps or sleep quality over placebo. The cramp population differs from primary insomnia; improvement in both arms does not identify an intervention effect.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 21 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C22", "text": "A four-arm morning/evening supplement trial finds selected morning botanical stress/sleep improvements. The evening threonate/theanine/apigenin bundle shows minimal effects; healthy active participants and multiple ingredients limit magnesium attribution.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 22 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C23", "text": "A12-person elderly crossover increases slow-wave sleep/EEG power with endocrine shifts. Small short study and unclear indexed insomnia eligibility; hormone association does not prove mediation or salt superiority.", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 23 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C24", "text": "A PCOS factorial trial reports PSQI improvement with melatonin and melatonin+Mg. The magnesium-only sleep benefit is not established by those positive arms; combination efficacy cannot be assigned to magnesium.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 24 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C25", "text": "Rodent dose/form comparisons find salt-dependent brain, muscle and serum magnesium patterns. Tissue concentrations do not demonstrate clinical sleep benefit; divided dosing does not uniformly improve availability.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 25 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C26", "text": "Single-dose rat pharmacokinetics finds acetyl-taurate brain penetration and anxiety-related changes. These are preclinical malate/taurate results, not glycinate/threonate superiority for human sleep.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3", "SC4" ], "source_ns": [ 26 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C27", "text": "Original digestion models and controlled human testing identify serum absorption differences between formulations. Urinary comparisons are null and elemental doses differ; absorption does not establish brain delivery or sleep superiority.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 27 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 2:3. Results:paragraph9, 2:3. Results:paragraph12, 2:3. Results:paragraph13, 2:3. Results:paragraph15, 2:3. Results:paragraph17. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C28", "text": "Citrate is more soluble and produces greater urinary magnesium loading than oxide in volunteers. Acute excretion, gastric acidity and renal handling are distinct from clinical sleep efficacy.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 28 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C29", "text": "Stable-isotope crossover in 12 ileal-resection patients compares diglycinate with oxide. Overall absorption does not differ; four most impaired patients show an advantage, which cannot define a general sleep benefit.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 29 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C30", "text": "A24-week matched-salt trial in 164 adults raises plasma and urinary magnesium. Arterial stiffness and blood pressure remain null; excretion differences do not establish sleep benefit.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3", "SC4" ], "source_ns": [ 30 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C31", "text": "Stable-isotope randomized repletion in depleted rats compares absorption/retention from ten salts. All forms are bioavailable, with context-dependent differences; depleted male rats are not replete human poor sleepers.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 31 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C32", "text": "Human crossover and ex vivo testing compare sucrosomial magnesium with several salts. Compartment-specific availability differences do not establish sleep efficacy; branded delivery differs from ligand chemistry.", "carries_number": false, "load_bearing_for": [ "SC1", "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": "2026-10-13", "note": "" }, { "id": "C33", "text": "A40-person crossover finds sustained plasma rises with microencapsulation compared with several forms. Acute plasma and GI outcomes are not brain or sleep measures; bisglycinate is not a uniform plasma winner.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 33 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C34", "text": "A matched-dose crossover finds both seawater preparations increase magnesium uptake versus placebo. The two forms do not differ at matched elemental dose; serum/urinary measures are not sleep endpoints.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 34 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C35", "text": "Rat acetyl-taurate/threonate comparison reports brain-magnesium and cognitive/anxiety patterns. Salt mass doses, many markers and rodent behaviors are not a direct matched human sleep comparison.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3", "SC4" ], "source_ns": [ 35 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C36", "text": "Volunteer/heart-failure work finds comparable magnesium-orotate±potassium blood/RBC profiles. Serum homeostasis complicates AUC interpretation; human neural and sleep outcomes were not measured.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 36 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C37", "text": "Oral-versus-IV testing estimates hydroxide bioavailability in ten healthy men. Small acute pharmacokinetics does not establish brain exposure, sleep benefit or safety across renal contexts.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 37 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C38", "text": "INFOGEST/Caco2 testing compares a marine multimineral with magnesium chloride and oxide. Digestion/epithelial transport is not living brain exposure or clinical sleep efficacy; additional minerals are bundled.", "carries_number": true, "load_bearing_for": [ "SC1", "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": "2026-10-13", "note": "" }, { "id": "C39", "text": "Volunteer urinary testing finds oxide less absorbed and chloride/lactate/aspartate comparable. Some inorganic salts match organic salts; chemical class labels cannot establish clinical sleep rankings.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 39 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C40", "text": "Rat salt/dose comparisons report memory and depression-related behavior differences. Forced-swim/maze proxies, salt-mass doses and biomarkers do not demonstrate human insomnia or form superiority.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3", "SC4" ], "source_ns": [ 40 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C41", "text": "An oxide effervescent/capsule crossover under standardized diet produces different urinary uptake. Delivery formulation matters within one salt; no brain or sleep function endpoint was measured.", "carries_number": false, "load_bearing_for": [ "SC1", "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": "2026-10-13", "note": "" }, { "id": "C42", "text": "Controlled crossover finds no availability/tolerability difference between immediate and delayed release. Open-label acute pharmacokinetics is not sleep comparative efficacy; the null is retained.", "carries_number": false, "load_bearing_for": [ "SC1", "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": "2026-10-13", "note": "" }, { "id": "C43", "text": "Oral/IV mineral-water radiotracing quantifies enteral absorption in men. Ten participants and acute tracers; no sleep endpoint. Age correlation is not a randomized age effect.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 43 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C44", "text": "Controlled magnesium loading shows curvilinear absorption and lower fractions at larger doses; enteric coating lowers uptake. Intestinal or food effects do not establish central exposure or hypnotic efficacy.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 44 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C45", "text": "A12-person crossover finds some salt-specific blood/urine time-profile differences. Overall blood compartment changes are mostly nonsignificant; there is no general salt winner or sleep comparison.", "carries_number": true, "load_bearing_for": [ "SC1", "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": "2026-10-13", "note": "" }, { "id": "C46", "text": "A six-volunteer sulfate study measures limited variable absorption and diarrhea after a cathartic dose. Cathartic exposure and normal kidneys differ from sleep regimens; no dosing recommendation is inferred.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 46 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C47", "text": "Stable-isotope crossover finds meal-enhanced mineral-water absorption/retention in ten women. Meal effects change availability without demonstrating a neural sleep mechanism or salt superiority.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 47 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C48", "text": "Short supplementation finds discordant ionized/total magnesium patterns and oxide advantage on selected indices. Compartment changes are not brain availability; no insomnia endpoint or glycinate superiority was tested.", "carries_number": false, "load_bearing_for": [ "SC1", "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": "2026-10-13", "note": "" }, { "id": "C49", "text": "Threonate increases rat brain magnesium and enhances memory/synaptic physiology. Memory and plasticity are not human insomnia; central-model findings do not predict every clinical sleep measure.", "carries_number": false, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 49 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C50", "text": "CARDIA intake associates with less short sleep and borderline sleep-quality improvement. Diet/lifestyle confounding, self-report and depression interaction remain; no randomized salt-specific efficacy.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 50 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C51", "text": "Post-heart-surgery magnesium versus routine care suggests lower PSQI/anxiety scores. Five days is outside the registered2–24-week horizon; no blinded placebo and postoperative recovery confound interpretation.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 51 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C52", "text": "Melatonin/Mg coffee-pod crossover improves several sleep measures over placebo. No single-ingredient arms and final average PSQI remains poor; combination efficacy does not establish magnesium mediation.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 52 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C53", "text": "NMDA/glycine-site ligand manipulations enhance or antagonize magnesium-related mouse anxiety-like behavior. Elevated-plus-maze and nonclinical exposure are not oral human insomnia; glycine-site binding is not glycinate comparative efficacy.", "carries_number": false, "load_bearing_for": [ "SC4" ], "source_ns": [ 53 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C54", "text": "Saudi cross-sectional data associate serum/dietary magnesium with poor PSQI quality. Confounding and model variation remain; nutrient association is not a causal deficiency-response trial.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 54 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C55", "text": "NHANES depletion-score analysis associates sleep trouble/apnea with a higher score. No association with insomnia or insufficient sleep; renal-risk proxies and reverse causation remain.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 55 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C56", "text": "Dietary restriction alters mouse NMDA-complex proteins alongside depression-related behavior. Paroxetine restores behavior without protein restoration; correlation is not necessity. Author-name correction 24965486 is attached.", "carries_number": false, "load_bearing_for": [ "SC4" ], "source_ns": [ 56 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C57", "text": "Structural/mutational work identifies magnesium-specific NMDA sites for block, potentiation and inhibition. Engineered receptors are not human sleep; these diverse effects are not a simple universal sedative mechanism.", "carries_number": false, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 57 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C58", "text": "Magnesium added to fluoxetine produces a larger HDRS change including insomnia items. Alternating allocation is not concealed randomization; no blinded magnesium placebo and a depression composite is not a sleep primary.", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 58 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C59", "text": "Twelve-week randomized magnesium-threonate trial in 109 breast-surgery patients finds no between-arm PSQI mood cognition or pain benefit Pain-prevention cohort was not enrolled for primary insomnia; secondary sleep endpoint and postoperative context limit transfer to poor-sleep eligibility", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 59 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "CSC1", "text": "Controlled oral exposure and isotope studies demonstrate systemic absorption. Rodent central exposure and neural effects retain their experimental scope. Peripheral status changes and rodent cognition cannot establish human brain delivery or a sleep-relevant neural dependency at the studied exposure; the target-availability inference retains Γ. The separately controlled clinical formulation effect is assessed in SC2.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 7, 8, 9, 10, 11, 16, 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, 57 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-13", "note": "" }, { "id": "CSC2", "text": "The prospectively registered, blinded 2025 bisglycinate trial supports a small improvement on the validated primary ISI outcome over four weeks. Older and newer studies contain additional positive, null and mixed sleep findings. A clean, reproducible baseline-deficiency effect boundary has not been mapped, clinically important responder contrasts are incompletely established and objective replication is limited. The first causal threshold is retained atΔ without elevating a small formulation effect to broad reliable insomnia treatment.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 1, 2, 3, 4, 7, 14, 19, 20, 21, 22, 23, 24, 50, 51, 52, 54, 55, 58, 59 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-13", "note": "" }, { "id": "CSC3", "text": "No directly examined, matched-elemental-dose human sleep trial establishes that glycinate or threonate is superior to other salts. Absorption comparisons and rodent cognitive/anxiety studies are not direct clinical sleep comparisons. This positive comparative sleep proposition remains unsupported atΑ, rather than being inferred from popularity or formulation branding.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 1, 3, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 38, 39, 40, 41, 42, 44, 45, 48, 59 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-13", "note": "" }, { "id": "CSC4", "text": "NMDA structural/mutational studies, deficiency/repletion models and mouse ligand experiments support plausible neural mechanisms. Human sleep/stress studies generally measure hormones, magnesium or neural signals alongside symptoms without manipulating the candidate mediator while retaining treatment. Coingredients and glycine ligand exposure remain unpartitioned, so the human mediation claim does not crossΔ.", "carries_number": false, "load_bearing_for": [ "SC4" ], "source_ns": [ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 23, 24, 26, 30, 35, 40, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-13", "note": "" }, { "id": "CH", "text": "Magnesium has small, inconsistent sleep benefits in controlled studies; glycinate/threonate superiority and a proven human neural mediator are not established.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 3, 7, 1, 19, 2, 27 ], "verification": "verified", "verified_against": "Bounded synthesis of examined sources; score is adjudication.", "verified_on": "2026-10-13", "note": "" } ], "citation_ledger": [ { "n": 1, "citation": "Hausenblas HA, Lynch T, Hooper S et al. Magnesium-L-threonate improves sleep quality and daytime functioning in adults with self-reported sleep problems: A randomized controlled trial. Sleep medicine: X. 2024.", "tier": "A", "kind": "rct", "pmid": "39252819", "doi": "10.1016/j.sleepx.2024.100121", "url": "https://pubmed.ncbi.nlm.nih.gov/39252819/", "status_flags": [ "ErratumIn: PMID40567408" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MG-THREONATE-ISRCTN14728094", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Materials and methods:paragraph0, 1:Materials and methods:paragraph6, 1:Materials and methods:paragraph7, 1:Materials and methods:paragraph14, 1:Materials and methods:paragraph32, 11:Declaration of competing interest:paragraph0, 2:Results:paragraph3, 2:Results:paragraph7, 2:Results:paragraph15. No complete-paper or supplement audit claimed.", "carries_claims": [ "C1", "CSC2", "CSC3", "CSC4", "CH" ] }, { "n": 2, "citation": "Abbasi B, Kimiagar M, Sadeghniiat K et al. The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences. 2012.", "tier": "A", "kind": "primary", "pmid": "23853635", "doi": "", "url": "https://pubmed.ncbi.nlm.nih.gov/23853635/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID23853635", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:MATERIALS AND METHODS:paragraph0, 1:MATERIALS AND METHODS:paragraph1, 2:RESULTS:paragraph0, 2:RESULTS:paragraph3, 2:RESULTS:paragraph5. No complete-paper or supplement audit claimed.", "carries_claims": [ "C2", "CSC2", "CSC4", "CH" ] }, { "n": 3, "citation": "Schuster J, Cycelskij I, Lopresti A et al. Magnesium Bisglycinate Supplementation in Healthy Adults Reporting Poor Sleep: A Randomized, Placebo-Controlled Trial. Nature and science of sleep. 2025.", "tier": "A", "kind": "rct", "pmid": "40918053", "doi": "10.2147/NSS.S524348", "url": "https://pubmed.ncbi.nlm.nih.gov/40918053/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MG-BISGLYCINATE-DRKS00031494", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Materials and Methods:paragraph0, 1:Materials and Methods:paragraph4, 1:Materials and Methods:paragraph12, 1:Materials and Methods:paragraph14, 1:Materials and Methods:paragraph15, 1:Materials and Methods:paragraph17, 2:Results:paragraph0, 2:Results:paragraph8, 2:Results:paragraph10, 2:Results:paragraph13, 2:Results:paragraph16, 2:Results:paragraph18. No complete-paper or supplement audit claimed.", "carries_claims": [ "C3", "CSC2", "CSC3", "CSC4", "CH" ] }, { "n": 4, "citation": "Khalid S, Bashir S, Mehboob R et al. Effects of magnesium and potassium supplementation on insomnia and sleep hormones in patients with diabetes mellitus. Frontiers in endocrinology. 2024.", "tier": "A", "kind": "rct", "pmid": "39534260", "doi": "10.3389/fendo.2024.1370733", "url": "https://pubmed.ncbi.nlm.nih.gov/39534260/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MG-K-INSOMNIA-NCT04642313", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Materials and methods:paragraph0, 1:Materials and methods:paragraph13, 2:Results:paragraph0, 2:Results:paragraph1, 2:Results:paragraph2. No complete-paper or supplement audit claimed.", "carries_claims": [ "C4", "CSC2", "CSC4" ] }, { "n": 5, "citation": "Khalid S, Bashir S, Mehboob R et al. Effects of magnesium and potassium on insulin resistance and blood sugar level among insomniac patients with diabetes mellitus-A randomized controlled trial. Journal of investigative medicine : the official publication of the American Federation for Clinical Research. 2026.", "tier": "A", "kind": "rct", "pmid": "40923590", "doi": "10.1177/10815589251378179", "url": "https://pubmed.ncbi.nlm.nih.gov/40923590/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MG-K-INSOMNIA-NCT04642313", "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", "CSC4" ] }, { "n": 6, "citation": "Khalid S, Bashir S, Mehboob R et al. Comparison of Diabetic Nephropathy Markers in Diabetic Patients With Insomnia Before and After Potassium and Magnesium Supplementation: A Randomized Controlled Trial. Health science reports. 2026.", "tier": "A", "kind": "primary", "pmid": "41561890", "doi": "10.1002/hsr2.71738", "url": "https://pubmed.ncbi.nlm.nih.gov/41561890/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MG-K-INSOMNIA-NCT04642313", "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", "CSC4" ] }, { "n": 7, "citation": "Nielsen FH, Johnson LK, Zeng H. Magnesium supplementation improves indicators of low magnesium status and inflammatory stress in adults older than 51 years with poor quality sleep. Magnesium research. 2010.", "tier": "A", "kind": "rct", "pmid": "21199787", "doi": "10.1684/mrh.2010.0220", "url": "https://pubmed.ncbi.nlm.nih.gov/21199787/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID21199787", "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", "CSC4", "CH" ] }, { "n": 8, "citation": "Chollet D, Franken P, Raffin Y et al. Magnesium involvement in sleep: genetic and nutritional models. Behavior genetics. 2001.", "tier": "A", "kind": "primary", "pmid": "11777170", "doi": "10.1023/a:1012790321071", "url": "https://pubmed.ncbi.nlm.nih.gov/11777170/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID11777170", "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", "CSC4" ] }, { "n": 9, "citation": "Depoortere H, Françon D, Llopis J. Effects of a magnesium-deficient diet on sleep organization in rats. Neuropsychobiology. 1993.", "tier": "A", "kind": "primary", "pmid": "8232845", "doi": "10.1159/000118988", "url": "https://pubmed.ncbi.nlm.nih.gov/8232845/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID8232845", "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", "CSC4" ] }, { "n": 10, "citation": "Inoue S, Ikegaya Y, Matsumoto N et al. Magnesium deficiency differentially modulates hippocampal and prefrontal oscillations and cardiac rhythms. Journal of pharmacological sciences. 2026.", "tier": "A", "kind": "primary", "pmid": "41554599", "doi": "10.1016/j.jphs.2025.12.002", "url": "https://pubmed.ncbi.nlm.nih.gov/41554599/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID41554599", "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", "CSC4" ] }, { "n": 11, "citation": "Poenaru S, Rouhani S, Durlach J et al. Vigilance states and cerebral monoamine metabolism in experimental magnesium deficiency. Magnesium. 1984.", "tier": "A", "kind": "primary", "pmid": "6083421", "doi": "", "url": "https://pubmed.ncbi.nlm.nih.gov/6083421/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID6083421", "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", "CSC4" ] }, { "n": 12, "citation": "Noah L, Dye L, Bois De Fer B et al. Effect of magnesium and vitamin B6 supplementation on mental health and quality of life in stressed healthy adults: Post-hoc analysis of a randomised controlled trial. Stress and health : journal of the International Society for the Investigation of Stress. 2021.", "tier": "A", "kind": "rct", "pmid": "33864354", "doi": "10.1002/smi.3051", "url": "https://pubmed.ncbi.nlm.nih.gov/33864354/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MG-B6-EUDRACT2015-003749-24", "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", "CSC4" ] }, { "n": 13, "citation": "Pouteau E, Kabir-Ahmadi M, Noah L et al. Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial. PloS one. 2018.", "tier": "A", "kind": "rct", "pmid": "30562392", "doi": "10.1371/journal.pone.0208454", "url": "https://pubmed.ncbi.nlm.nih.gov/30562392/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MG-B6-EUDRACT2015-003749-24", "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": [ "C13", "CSC4" ] }, { "n": 14, "citation": "Dodd F, Weishaupt R, Katumba PKM et al. Effects of a Scutellaria baicalensis/Crataegus laevigata, magnesium and chromium supplement on stressed individuals: A randomised, double-blind, placebo-controlled, crossover trial. Journal of psychopharmacology (Oxford, England). 2025.", "tier": "A", "kind": "rct", "pmid": "41194549", "doi": "10.1177/02698811251381261", "url": "https://pubmed.ncbi.nlm.nih.gov/41194549/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID41194549", "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": [ "C14", "CSC2", "CSC4" ] }, { "n": 15, "citation": "Boyle NB, Billington J, Lawton C et al. A combination of green tea, rhodiola, magnesium and B vitamins modulates brain activity and protects against the effects of induced social stress in healthy volunteers. Nutritional neuroscience. 2022.", "tier": "A", "kind": "rct", "pmid": "33896388", "doi": "10.1080/1028415X.2021.1909204", "url": "https://pubmed.ncbi.nlm.nih.gov/33896388/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "TEADIOLA-NCT03262376", "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": [ "C15", "CSC4" ] }, { "n": 16, "citation": "Noah L, Pickering G, Mazur A et al. Impact of magnesium supplementation, in combination with vitamin B6, on stress and magnesium status: secondary data from a randomized controlled trial. Magnesium research. 2020.", "tier": "A", "kind": "rct", "pmid": "33210604", "doi": "10.1684/mrh.2020.0468", "url": "https://pubmed.ncbi.nlm.nih.gov/33210604/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MG-B6-EUDRACT2015-003749-24", "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": [ "C16", "CSC1", "CSC4" ] }, { "n": 17, "citation": "Boyle NB, Dye L, Lawton CL et al. A Combination of Green Tea, Rhodiola, Magnesium, and B Vitamins Increases Electroencephalogram Theta Activity During Attentional Task Performance Under Conditions of Induced Social Stress. Frontiers in nutrition. 2022.", "tier": "A", "kind": "primary", "pmid": "35938130", "doi": "10.3389/fnut.2022.935001", "url": "https://pubmed.ncbi.nlm.nih.gov/35938130/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "TEADIOLA-NCT03262376", "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": [ "C17", "CSC4" ] }, { "n": 18, "citation": "Pickering G, Noah L, Pereira B et al. Assessing brain function in stressed healthy individuals following the use of a combination of green tea, Rhodiola, magnesium, and B vitamins: an fMRI study. Frontiers in nutrition. 2023.", "tier": "A", "kind": "primary", "pmid": "37662591", "doi": "10.3389/fnut.2023.1211321", "url": "https://pubmed.ncbi.nlm.nih.gov/37662591/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID37662591", "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": [ "C18", "CSC4" ] }, { "n": 19, "citation": "Lopresti AL, Smith SJ. The effects of magnesium L-threonate (Magtein®) on cognitive performance and sleep quality in adults: a randomised, double-blind, placebo-controlled trial. Frontiers in nutrition. 2025.", "tier": "A", "kind": "rct", "pmid": "41601871", "doi": "10.3389/fnut.2025.1729164", "url": "https://pubmed.ncbi.nlm.nih.gov/41601871/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "MG-THREONATE-ACTRN12624000379516", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Materials and methods:paragraph0, 2:Results:paragraph20, 2:Results:paragraph29, 2:Results:paragraph30, 2:Results:paragraph32, 2:Results:paragraph39. No complete-paper or supplement audit claimed.", "carries_claims": [ "C19", "CSC2", "CSC4", "CH" ] }, { "n": 20, "citation": "Gorantla S, Ravisankar A, Trotti LM. Magnesium citrate monotherapy improves restless legs syndrome symptoms and multiple suggested immobilization test scores in an open-label pilot study. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2024.", "tier": "A", "kind": "primary", "pmid": "38738598", "doi": "10.5664/jcsm.11206", "url": "https://pubmed.ncbi.nlm.nih.gov/38738598/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID38738598", "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": [ "C20", "CSC2", "CSC4" ] }, { "n": 21, "citation": "Roguin Maor N, Alperin M, Shturman E et al. Effect of Magnesium Oxide Supplementation on Nocturnal Leg Cramps: A Randomized Clinical Trial. JAMA internal medicine. 2017.", "tier": "A", "kind": "rct", "pmid": "28241153", "doi": "10.1001/jamainternmed.2016.9261", "url": "https://pubmed.ncbi.nlm.nih.gov/28241153/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID28241153", "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": [ "C21", "CSC2" ] }, { "n": 22, "citation": "Mastrofini GF, Romersi RF, Lombardi MG et al. Modulating stress and sleep through a multi-compound dietary supplement: a randomized, double-blind, placebo-controlled trial. Journal of the International Society of Sports Nutrition. 2026.", "tier": "A", "kind": "rct", "pmid": "42829807", "doi": "10.1080/15502783.2026.2740227", "url": "https://pubmed.ncbi.nlm.nih.gov/42829807/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID42829807", "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": [ "C22", "CSC2", "CSC4" ] }, { "n": 23, "citation": "Held K, Antonijevic IA, Künzel H et al. Oral Mg(2+) supplementation reverses age-related neuroendocrine and sleep EEG changes in humans. Pharmacopsychiatry. 2002.", "tier": "A", "kind": "rct", "pmid": "12163983", "doi": "10.1055/s-2002-33195", "url": "https://pubmed.ncbi.nlm.nih.gov/12163983/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID12163983", "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": [ "C23", "CSC2", "CSC4" ] }, { "n": 24, "citation": "Alizadeh M, Karandish M, Asghari Jafarabadi M et al. Metabolic and hormonal effects of melatonin and/or magnesium supplementation in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Nutrition & metabolism. 2021.", "tier": "A", "kind": "primary", "pmid": "34092248", "doi": "10.1186/s12986-021-00586-9", "url": "https://pubmed.ncbi.nlm.nih.gov/34092248/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID34092248", "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": [ "C24", "CSC2", "CSC4" ] }, { "n": 25, "citation": "Ates M, Kizildag S, Yuksel O et al. Dose-Dependent Absorption Profile of Different Magnesium Compounds. Biological trace element research. 2019.", "tier": "A", "kind": "primary", "pmid": "30761462", "doi": "10.1007/s12011-019-01663-0", "url": "https://pubmed.ncbi.nlm.nih.gov/30761462/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID30761462", "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": [ "C25", "CSC1", "CSC3" ] }, { "n": 26, "citation": "Uysal N, Kizildag S, Yuce Z et al. Timeline (Bioavailability) of Magnesium Compounds in Hours: Which Magnesium Compound Works Best? Biological trace element research. 2019.", "tier": "A", "kind": "primary", "pmid": "29679349", "doi": "10.1007/s12011-018-1351-9", "url": "https://pubmed.ncbi.nlm.nih.gov/29679349/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID29679349", "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": [ "C26", "CSC1", "CSC3", "CSC4" ] }, { "n": 27, "citation": "Blancquaert L, Vervaet C, Derave W. Predicting and Testing Bioavailability of Magnesium Supplements. Nutrients. 2019.", "tier": "A", "kind": "primary", "pmid": "31330811", "doi": "10.3390/nu11071663", "url": "https://pubmed.ncbi.nlm.nih.gov/31330811/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID31330811", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 2:3. Results:paragraph9, 2:3. Results:paragraph12, 2:3. Results:paragraph13, 2:3. Results:paragraph15, 2:3. Results:paragraph17. No complete-paper or supplement audit claimed.", "carries_claims": [ "C27", "CSC1", "CSC3", "CH" ] }, { "n": 28, "citation": "Lindberg JS, Zobitz MM, Poindexter JR et al. Magnesium bioavailability from magnesium citrate and magnesium oxide. Journal of the American College of Nutrition. 1990.", "tier": "A", "kind": "primary", "pmid": "2407766", "doi": "10.1080/07315724.1990.10720349", "url": "https://pubmed.ncbi.nlm.nih.gov/2407766/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID2407766", "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": [ "C28", "CSC1", "CSC3" ] }, { "n": 29, "citation": "Schuette SA, Lashner BA, Janghorbani M. Bioavailability of magnesium diglycinate vs magnesium oxide in patients with ileal resection. JPEN. Journal of parenteral and enteral nutrition. 1994.", "tier": "A", "kind": "rct", "pmid": "7815675", "doi": "10.1177/0148607194018005430", "url": "https://pubmed.ncbi.nlm.nih.gov/7815675/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID7815675", "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": [ "C29", "CSC1", "CSC3" ] }, { "n": 30, "citation": "Schutten JC, Joris PJ, Groendijk I et al. Effects of Magnesium Citrate, Magnesium Oxide, and Magnesium Sulfate Supplementation on Arterial Stiffness: A Randomized, Double-Blind, Placebo-Controlled Intervention Trial. Journal of the American Heart Association. 2022.", "tier": "A", "kind": "rct", "pmid": "35253448", "doi": "10.1161/JAHA.121.021783", "url": "https://pubmed.ncbi.nlm.nih.gov/35253448/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID35253448", "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": [ "C30", "CSC1", "CSC3", "CSC4" ] }, { "n": 31, "citation": "Coudray C, Rambeau M, Feillet-Coudray C et al. Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach. Magnesium research. 2005.", "tier": "A", "kind": "primary", "pmid": "16548135", "doi": "", "url": "https://pubmed.ncbi.nlm.nih.gov/16548135/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID16548135", "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": [ "C31", "CSC1", "CSC3" ] }, { "n": 32, "citation": "Brilli E, Khadge S, Fabiano A et al. Magnesium bioavailability after administration of sucrosomial® magnesium: results of an ex-vivo study and a comparative, double-blinded, cross-over study in healthy subjects. European review for medical and pharmacological sciences. 2018.", "tier": "A", "kind": "primary", "pmid": "29630135", "doi": "10.26355/eurrev_201803_14605", "url": "https://pubmed.ncbi.nlm.nih.gov/29630135/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID29630135", "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": [ "C32", "CSC1", "CSC3" ] }, { "n": 33, "citation": "Pajuelo D, Meissner JM, Negra T et al. Comparative Clinical Study on Magnesium Absorption and Side Effects After Oral Intake of Microencapsulated Magnesium (MAGSHAPETM Microcapsules) Versus Other Magnesium Sources. Nutrients. 2024.", "tier": "A", "kind": "rct", "pmid": "39770988", "doi": "10.3390/nu16244367", "url": "https://pubmed.ncbi.nlm.nih.gov/39770988/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID39770988", "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": [ "C33", "CSC1", "CSC3" ] }, { "n": 34, "citation": "McFarlin BK, Paschall AL, Kelly ME et al. Comparing the Bioavailability of Two Seawater-Derived Magnesium Preparations. Journal of medicinal food. 2025.", "tier": "A", "kind": "rct", "pmid": "40955524", "doi": "10.1177/1096620X251380191", "url": "https://pubmed.ncbi.nlm.nih.gov/40955524/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID40955524", "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": [ "C34", "CSC1", "CSC3" ] }, { "n": 35, "citation": "Kumar A, Mehan S, Gupta S et al. Enhanced Neurophysiological Benefits of Magnesium-Acetyl-Taurate Over Magnesium-L-Threonate: A Comparative pre-clinical Study on Bioavailability, Synaptic Plasticity and Cognitive Functions. Neuromolecular medicine. 2026.", "tier": "A", "kind": "primary", "pmid": "42084749", "doi": "10.1007/s12017-026-08929-6", "url": "https://pubmed.ncbi.nlm.nih.gov/42084749/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID42084749", "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": [ "C35", "CSC1", "CSC3", "CSC4" ] }, { "n": 36, "citation": "Eremenko NN, Shikh EV, Serebrova SY et al. Comparative study of the bioavailability of magnesium salts. Drug metabolism and personalized therapy. 2019.", "tier": "A", "kind": "primary", "pmid": "31606725", "doi": "10.1515/dmpt-2019-0004", "url": "https://pubmed.ncbi.nlm.nih.gov/31606725/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID31606725", "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": [ "C36", "CSC1", "CSC3" ] }, { "n": 37, "citation": "Dolberg MK, Nielsen LP, Dahl R. Pharmacokinetic Profile of Oral Magnesium Hydroxide. Basic & clinical pharmacology & toxicology. 2017.", "tier": "A", "kind": "primary", "pmid": "27412366", "doi": "10.1111/bcpt.12642", "url": "https://pubmed.ncbi.nlm.nih.gov/27412366/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID27412366", "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": [ "C37", "CSC1" ] }, { "n": 38, "citation": "Felice VD, O'Gorman DM, O'Brien NM et al. Bioaccessibility and Bioavailability of a Marine-Derived Multimineral, Aquamin-Magnesium. Nutrients. 2018.", "tier": "A", "kind": "primary", "pmid": "30018220", "doi": "10.3390/nu10070912", "url": "https://pubmed.ncbi.nlm.nih.gov/30018220/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID30018220", "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": [ "C38", "CSC1", "CSC3" ] }, { "n": 39, "citation": "Firoz M, Graber M. Bioavailability of US commercial magnesium preparations. Magnesium research. 2001.", "tier": "A", "kind": "primary", "pmid": "11794633", "doi": "", "url": "https://pubmed.ncbi.nlm.nih.gov/11794633/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID11794633", "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": [ "C39", "CSC1", "CSC3" ] }, { "n": 40, "citation": "Sadir S, Tabassum S, Emad S et al. Neurobehavioral and biochemical effects of magnesium chloride (MgCl2), magnesium sulphate (MgSO4) and magnesium-L-threonate (MgT) supplementation in rats: A dose dependent comparative study. Pakistan journal of pharmaceutical sciences. 2019.", "tier": "A", "kind": "primary", "pmid": "30829204", "doi": "", "url": "https://pubmed.ncbi.nlm.nih.gov/30829204/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID30829204", "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": [ "C40", "CSC1", "CSC3", "CSC4" ] }, { "n": 41, "citation": "Siener R, Jahnen A, Hesse A. Bioavailability of magnesium from different pharmaceutical formulations. Urological research. 2011.", "tier": "A", "kind": "primary", "pmid": "20862466", "doi": "10.1007/s00240-010-0309-y", "url": "https://pubmed.ncbi.nlm.nih.gov/20862466/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID20862466", "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": [ "C41", "CSC1", "CSC3" ] }, { "n": 42, "citation": "Greupner T, Schneider I, Gellert S et al. Magnesium Bioavailability and Tolerability Do Not Differ between Two Supplements with Different Release Properties. Journal of dietary supplements. 2020.", "tier": "A", "kind": "primary", "pmid": "31230494", "doi": "10.1080/19390211.2019.1629146", "url": "https://pubmed.ncbi.nlm.nih.gov/31230494/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID31230494", "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": [ "C42", "CSC1", "CSC3" ] }, { "n": 43, "citation": "Verhas M, de la Guéronnière V, Grognet JM et al. Magnesium bioavailability from mineral water. A study in adult men. European journal of clinical nutrition. 2002.", "tier": "A", "kind": "rct", "pmid": "12001016", "doi": "10.1038/sj.ejcn.1601333", "url": "https://pubmed.ncbi.nlm.nih.gov/12001016/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID12001016", "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": [ "C43", "CSC1" ] }, { "n": 44, "citation": "Fine KD, Santa Ana CA, Porter JL et al. Intestinal absorption of magnesium from food and supplements. The Journal of clinical investigation. 1991.", "tier": "A", "kind": "primary", "pmid": "1864954", "doi": "10.1172/JCI115317", "url": "https://pubmed.ncbi.nlm.nih.gov/1864954/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID1864954", "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", "CSC3" ] }, { "n": 45, "citation": "White J, Massey L, Gales SK et al. Blood and urinary magnesium kinetics after oral magnesium supplements. Clinical therapeutics. 1992.", "tier": "A", "kind": "rct", "pmid": "1468087", "doi": "", "url": "https://pubmed.ncbi.nlm.nih.gov/1468087/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID1468087", "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": [ "C45", "CSC1", "CSC3" ] }, { "n": 46, "citation": "Morris ME, LeRoy S, Sutton SC. Absorption of magnesium from orally administered magnesium sulfate in man. Journal of toxicology. Clinical toxicology. 1987.", "tier": "A", "kind": "primary", "pmid": "3430654", "doi": "10.3109/15563658708992640", "url": "https://pubmed.ncbi.nlm.nih.gov/3430654/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID3430654", "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": [ "C46", "CSC1" ] }, { "n": 47, "citation": "Sabatier M, Arnaud MJ, Kastenmayer P et al. Meal effect on magnesium bioavailability from mineral water in healthy women. The American journal of clinical nutrition. 2002.", "tier": "A", "kind": "primary", "pmid": "11756061", "doi": "10.1093/ajcn/75.1.65", "url": "https://pubmed.ncbi.nlm.nih.gov/11756061/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID11756061", "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": [ "C47", "CSC1" ] }, { "n": 48, "citation": "Ivanovic ND, Radosavljevic B, Zekovic M et al. Effects of short-term magnesium supplementation on ionized, total magnesium and other relevant electrolytes levels. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine. 2022.", "tier": "A", "kind": "primary", "pmid": "35041150", "doi": "10.1007/s10534-022-00363-y", "url": "https://pubmed.ncbi.nlm.nih.gov/35041150/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID35041150", "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": [ "C48", "CSC1", "CSC3" ] }, { "n": 49, "citation": "Slutsky I, Abumaria N, Wu LJ et al. Enhancement of learning and memory by elevating brain magnesium. Neuron. 2010.", "tier": "A", "kind": "primary", "pmid": "20152124", "doi": "10.1016/j.neuron.2009.12.026", "url": "https://pubmed.ncbi.nlm.nih.gov/20152124/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID20152124", "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": [ "C49", "CSC1", "CSC4" ] }, { "n": 50, "citation": "Zhang Y, Chen C, Lu L et al. Association of magnesium intake with sleep duration and sleep quality: findings from the CARDIA study. Sleep. 2022.", "tier": "A", "kind": "primary", "pmid": "34883514", "doi": "10.1093/sleep/zsab276", "url": "https://pubmed.ncbi.nlm.nih.gov/34883514/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID34883514", "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": [ "C50", "CSC2", "CSC4" ] }, { "n": 51, "citation": "Saba S, Faizi F, Sepandi M et al. Effect of short-term magnesium supplementation on anxiety, depression and sleep quality in patients after open-heart surgery. Magnesium research. 2022.", "tier": "A", "kind": "primary", "pmid": "36354243", "doi": "10.1684/mrh.2022.0503", "url": "https://pubmed.ncbi.nlm.nih.gov/36354243/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID36354243", "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": [ "C51", "CSC2", "CSC4" ] }, { "n": 52, "citation": "Carlos RM, Matias CN, Cavaca ML et al. The effects of melatonin and magnesium in a novel supplement delivery system on sleep scores, body composition and metabolism in otherwise healthy individuals with sleep disturbances. Chronobiology international. 2024.", "tier": "A", "kind": "rct", "pmid": "38745424", "doi": "10.1080/07420528.2024.2353225", "url": "https://pubmed.ncbi.nlm.nih.gov/38745424/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID38745424", "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": [ "C52", "CSC2", "CSC4" ] }, { "n": 53, "citation": "Poleszak E, Wlaź P, Wróbel A et al. NMDA/glutamate mechanism of magnesium-induced anxiolytic-like behavior in mice. Pharmacological reports : PR. 2008.", "tier": "A", "kind": "primary", "pmid": "19066411", "doi": "", "url": "https://pubmed.ncbi.nlm.nih.gov/19066411/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID19066411", "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": [ "C53", "CSC4" ] }, { "n": 54, "citation": "Al-Musharaf S, Aldhwayan MM, Mazi TA et al. Magnesium and Zinc Are Associated with Sleep Quality in Saudi Adults: Evidence from a Cross-Sectional Study. Nutrients. 2025.", "tier": "A", "kind": "primary", "pmid": "41515231", "doi": "10.3390/nu18010114", "url": "https://pubmed.ncbi.nlm.nih.gov/41515231/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID41515231", "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": [ "C54", "CSC2", "CSC4" ] }, { "n": 55, "citation": "Luo X, Tang M, Wei X et al. Association between magnesium deficiency score and sleep quality in adults: A population-based cross-sectional study. Journal of affective disorders. 2024.", "tier": "A", "kind": "primary", "pmid": "38703902", "doi": "10.1016/j.jad.2024.05.002", "url": "https://pubmed.ncbi.nlm.nih.gov/38703902/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID38703902", "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": [ "C55", "CSC2", "CSC4" ] }, { "n": 56, "citation": "Ghafari M, Whittle N, Miklósi AG et al. Dietary magnesium restriction reduces amygdala-hypothalamic GluN1 receptor complex levels in mice. Brain structure & function. 2015.", "tier": "A", "kind": "primary", "pmid": "24807818", "doi": "10.1007/s00429-014-0779-8", "url": "https://pubmed.ncbi.nlm.nih.gov/24807818/", "status_flags": [ "ErratumIn: PMID24965486" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID24807818", "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": [ "C56", "CSC4" ] }, { "n": 57, "citation": "Huang X, Sun X, Wang Q et al. Structural insights into the diverse actions of magnesium on NMDA receptors. Neuron. 2025.", "tier": "A", "kind": "primary", "pmid": "40010346", "doi": "10.1016/j.neuron.2025.01.021", "url": "https://pubmed.ncbi.nlm.nih.gov/40010346/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID40010346", "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": [ "C57", "CSC1", "CSC4" ] }, { "n": 58, "citation": "Walyddaini AS, Lisal ST, Ilhamuddin et al. Magnesium supplementation as an adjunct to fluoxetine therapy for depression. East Asian archives of psychiatry : official journal of the Hong Kong College of Psychiatrists = Dong Ya jing shen ke xue zhi : Xianggang jing shen ke yi xue yuan qi kan. 2026.", "tier": "A", "kind": "primary", "pmid": "41916937", "doi": "10.12809/eaap25122", "url": "https://pubmed.ncbi.nlm.nih.gov/41916937/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID41916937", "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": [ "C58", "CSC2", "CSC4" ] }, { "n": 59, "citation": "Ni Y, Deng F, Yu S et al. A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Therapeutic Effect of Magnesium-L-Threonate Supplementation for Persistent Pain After Breast Cancer Surgery. Breast cancer (Dove Medical Press). 2023.", "tier": "A", "kind": "rct", "pmid": "37520407", "doi": "10.2147/BCTT.S413435", "url": "https://pubmed.ncbi.nlm.nih.gov/37520407/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID37520407", "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": [ "C59", "CSC2", "CSC3", "CSC4" ] } ], "independence_basis": { "required": false, "lines": [], "shared_failure_mode_checked": true, "note": "All models/subclaims remain belowΖ. Human supplementation trials form a repeated pharmacological/nutritional modality and share expectancy, missingness and endpoint-selection risks. Animal dietary rescue is valid in deficiency but does not independently prove the broad human supplementation claim. Isotope and receptor assays exclude measurement errors in availability/structure; they are not independent clinical sleep causal lines." }, "gamma_hard_rules_considered": [ { "subclaim_id": "SC1", "rule_quoted": "ROS change measurements alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC1", "rule_quoted": "NAD level change measurements alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC1", "rule_quoted": "Mitochondrial metrics alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC1", "rule_quoted": "Senescence marker changes alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC1", "rule_quoted": "Single-species or single-strain evidence", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC1", "rule_quoted": "Biomarker-only improvement without organismal benefit", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC2", "rule_quoted": "**Functional-unblinding rule.** Inert-placebo trial of an intervention with unmistakable acute subjective effects — psychedelics, ketamine, entactogens, suprathreshold stimulation, ECT — with no blinding-integrity check reported. Such a trial did not control what it claims to control.", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC2", "rule_quoted": "**Mediation-by-correlation rule.** Candidate mediator correlated with outcome, never manipulated.", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC2", "rule_quoted": "**Open-label rule.** Open-label, single-arm, retrospective, or naturalistic evidence alone. A positive open-label result never crosses Δ, however large.", "trigger_status": "Applies to the uncontrolled or cell-only positive support class, with ceiling Γ; it does not upgrade that class or describe the whole source set." }, { "subclaim_id": "SC2", "rule_quoted": "**Unblinded-rater rule.** Outcomes rated by clinicians who delivered the intervention or knew allocation.", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC2", "rule_quoted": "**Acute-pharmacodynamic rule.** Acute molecular, occupancy, or imaging change with no link to symptom trajectory.", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC2", "rule_quoted": "**Rodent-proxy rule.** Forced-swim, tail-suspension, sucrose-preference, or head-twitch alone; head-twitch is pharmacodynamic, not therapeutic.", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC3", "rule_quoted": "**Functional-unblinding rule.** Inert-placebo trial of an intervention with unmistakable acute subjective effects — psychedelics, ketamine, entactogens, suprathreshold stimulation, ECT — with no blinding-integrity check reported. Such a trial did not control what it claims to control.", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC3", "rule_quoted": "**Mediation-by-correlation rule.** Candidate mediator correlated with outcome, never manipulated.", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC3", "rule_quoted": "**Open-label rule.** Open-label, single-arm, retrospective, or naturalistic evidence alone. A positive open-label result never crosses Δ, however large.", "trigger_status": "Applies to the uncontrolled or cell-only positive support class, with ceiling Γ; it does not upgrade that class or describe the whole source set." }, { "subclaim_id": "SC3", "rule_quoted": "**Unblinded-rater rule.** Outcomes rated by clinicians who delivered the intervention or knew allocation.", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC3", "rule_quoted": "**Acute-pharmacodynamic rule.** Acute molecular, occupancy, or imaging change with no link to symptom trajectory.", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC3", "rule_quoted": "**Rodent-proxy rule.** Forced-swim, tail-suspension, sucrose-preference, or head-twitch alone; head-twitch is pharmacodynamic, not therapeutic.", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC4", "rule_quoted": "**Functional-unblinding rule.** Inert-placebo trial of an intervention with unmistakable acute subjective effects — psychedelics, ketamine, entactogens, suprathreshold stimulation, ECT — with no blinding-integrity check reported. Such a trial did not control what it claims to control.", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC4", "rule_quoted": "**Mediation-by-correlation rule.** Candidate mediator correlated with outcome, never manipulated.", "trigger_status": "Triggered for the offered human magnesium/ligand mediator inference; no mediator-specific intervention retaining the formulation was examined." }, { "subclaim_id": "SC4", "rule_quoted": "**Open-label rule.** Open-label, single-arm, retrospective, or naturalistic evidence alone. A positive open-label result never crosses Δ, however large.", "trigger_status": "Applies to the uncontrolled or cell-only positive support class, with ceiling Γ; it does not upgrade that class or describe the whole source set." }, { "subclaim_id": "SC4", "rule_quoted": "**Unblinded-rater rule.** Outcomes rated by clinicians who delivered the intervention or knew allocation.", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC4", "rule_quoted": "**Acute-pharmacodynamic rule.** Acute molecular, occupancy, or imaging change with no link to symptom trajectory.", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC4", "rule_quoted": "**Rodent-proxy rule.** Forced-swim, tail-suspension, sucrose-preference, or head-twitch alone; head-twitch is pharmacodynamic, not therapeutic.", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." } ], "consensus_validation": { "completed": true, "status": "completed_original_source_reconciliation", "provider_mode": "Consensus Pro signed-in browser; observed output and citation link mappings", "queries": [ "https://consensus.app/search/oral-magnesium-effects-sleep/UIuYDhmHQv2mJ_Q4YU-JMw/" ], "query_record_note": "Exact visible question/response retained privately in raw browser receipt.", "primary_comparison_count": 11, "primary_comparisons": [ { "pmid": "40918053", "doi": "10.2147/NSS.S524348", "source_type": "primary study report", "study_group": "MG-BISGLYCINATE-DRKS00031494", "access_depth": "full_text_partial", "consensus_aspect": "Consensus describes a modest bisglycinate effect and 1523 mg glycine coingredient.", "result_comparison": "Selected original Methods confirm the studied bisglycinate salt supplies 250 mg Mg and 1523 mg glycine daily; this is ligand exposure, not necessarily separately added free glycine. Original Results show small primary ISI benefit, d=.2, p=.049, 153 baseline analyzed and 134 completed. There is no ligand-matched control, objective sleep or established clinically important between-arm responder result.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/40918053/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\examinations\\original-0-10-6000.json" ], "body_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\body-presentation-receipts\\40918053-s1-p0-4-12-14-15-17.json", "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\body-presentation-receipts\\40918053-s2-p0-8-10-13-16-18.json" ] }, { "pmid": "21199787", "doi": "10.1684/mrh.2010.0220", "source_type": "primary study report", "study_group": "PMID21199787", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus reports equal global PSQI improvements with citrate and placebo but suggests deficient responders.", "result_comparison": "Original abstract confirms no supplement-specific global PSQI effect. Low-status serum and CRP responses occur in selected baseline groups, yet they do not establish sleep responsiveness or a deficiency-only causal boundary.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/21199787/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\examinations\\original-0-10-6000.json" ], "body_receipts": [] }, { "pmid": "23853635", "doi": "", "source_type": "primary study report", "study_group": "PMID23853635", "access_depth": "full_text_partial", "consensus_aspect": "Provider emphasizes subjective improvements and low nutritional status in the older-adult trial.", "result_comparison": "Selected original Methods show dietary Mg <75% RDA and serum Mg <0.95 mmol/L; this does not prove every participant had clinical hypomagnesemia. Sample power used renin; 46 entered and 43 completed. Selected Results retain total-sleep-time null alongside positive ISI/log/hormone measures.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/23853635/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\examinations\\original-0-10-6000.json" ], "body_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\body-presentation-receipts\\23853635-s1-p0-1.json", "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\body-presentation-receipts\\23853635-s2-p0-3-5.json" ] }, { "pmid": "39252819", "doi": "10.1016/j.sleepx.2024.100121", "source_type": "primary study report", "study_group": "MG-THREONATE-ISRCTN14728094", "access_depth": "full_text_partial", "consensus_aspect": "Provider mentions selected wearable and awakening benefits but understates prespecification limits.", "result_comparison": "Original body has null overall ISI time×group (p=.39) and several LSEQ sleep subscales. Correction 40567408 adds retrospective-registration and competing-interest disclosures, attached to the parent rather than counted as another study. Wearable scores are not direct polysomnographic architecture.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/39252819/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\examinations\\original-0-10-6000.json" ], "body_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\body-presentation-receipts\\39252819-s1-p0-6-7-14-32.json", "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\body-presentation-receipts\\39252819-s11-p0.json", "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\body-presentation-receipts\\39252819-s2-p3-7-15.json" ] }, { "pmid": "41601871", "doi": "10.3389/fnut.2025.1729164", "source_type": "primary study report", "study_group": "MG-THREONATE-ACTRN12624000379516", "access_depth": "full_text_partial", "consensus_aspect": "Consensus synthesis does not fully detail the newer threonate endpoint nulls.", "result_comparison": "Selected original body confirms prospective registration and allocation-guess assessment; sleep-related-impairment improves, while sleep disturbance, restorative sleep and all ring-derived sleep outcomes are null. The severe subgroup is exploratory. Cognitive-age transformation is not observed brain rejuvenation.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/41601871/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\examinations\\original-10-20-6000.json" ], "body_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\body-presentation-receipts\\41601871-s1-p0.json", "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\body-presentation-receipts\\41601871-s2-p20-29-30-32-39.json" ] }, { "pmid": "39534260", "doi": "10.3389/fendo.2024.1370733", "source_type": "primary study report", "study_group": "MG-K-INSOMNIA-NCT04642313", "access_depth": "full_text_partial", "consensus_aspect": "Provider general sleep narrative could obscure trial-specific baseline comparability.", "result_comparison": "Selected original Results report baseline ISI category imbalance p=.0001, with post-treatment between-group association also p=.0001. Without an adjusted change contrast this is a weaker causal anchor; selected Methods also impose a Mg/K-restricted diet. The two metabolic/renal followups share the same trial.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/39534260/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\examinations\\original-0-10-6000.json" ], "body_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\body-presentation-receipts\\39534260-s1-p0-13.json", "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\body-presentation-receipts\\39534260-s2-p0-1-2.json" ] }, { "pmid": "30562392", "doi": "10.1371/journal.pone.0208454", "source_type": "primary study report", "study_group": "MG-B6-EUDRACT2015-003749-24", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus sometimes treats stress improvement with Mg as isolated nutrient efficacy.", "result_comparison": "Original randomization compares Mg+B6 to Mg, with no Mg-free arm. The overall primary comparison is null; severe-stress subgroup advantage concerns added B6. Improvements within both arms do not identify Mg causality.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/30562392/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\examinations\\original-10-20-6000.json" ], "body_receipts": [] }, { "pmid": "31330811", "doi": "10.3390/nu11071663", "source_type": "primary study report", "study_group": "PMID31330811", "access_depth": "full_text_partial", "consensus_aspect": "Provider correctly separates form absorption from direct sleep comparisons.", "result_comparison": "Original body confirms serum-profile differences alongside null urinary contrasts and unequal elemental doses across formulations. These findings measure availability, not superiority of glycinate/threonate for sleep.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/31330811/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\examinations\\original-20-30-6000.json" ], "body_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\body-presentation-receipts\\31330811-s2-p9-12-13-15-17.json" ] }, { "pmid": "8232845", "doi": "10.1159/000118988", "source_type": "primary study report", "study_group": "PMID8232845", "access_depth": "abstract_metadata", "consensus_aspect": "Provider attributes plausibility to deficiency/neural models.", "result_comparison": "Original rat experiment shows long-deficiency sleep disruption and restoration on Mg repletion. Its restricted nutritional/species context cannot establish a broad hypnotic effect in replete adults.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/8232845/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\examinations\\original-0-10-6000.json" ], "body_receipts": [] }, { "pmid": "34092248", "doi": "10.1186/s12986-021-00586-9", "source_type": "primary study report", "study_group": "PMID34092248", "access_depth": "abstract_metadata", "consensus_aspect": "Provider discusses multiingredient contamination of sleep results.", "result_comparison": "Original factorial PCOS trial reports PSQI improvements in melatonin and melatonin+Mg groups, not a demonstrated Mg-only advantage. Component attribution must retain the actual arms rather than transfer the combined result.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/34092248/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\examinations\\original-20-30-6000.json" ], "body_receipts": [] }, { "pmid": "37520407", "doi": "10.2147/BCTT.S413435", "source_type": "primary study report", "study_group": "PMID37520407", "access_depth": "abstract_metadata", "consensus_aspect": "Completeness of the provider formulation outline", "result_comparison": "The original 2023 trial randomized 109 postoperative breast-cancer patients and found no between-arm PSQI, mood or cognitive benefit. It supplies a relevant null formulation result omitted from the provider outline. Enrollment was for pain prevention, so it cannot be treated as a direct falsification of the registered primary-insomnia claim. Search omissions and limited coverage do not establish literature-wide absence.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/37520407/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\examinations\\original-58-59-6000.json" ], "body_receipts": [] } ], "grade_changed": false, "grade_change_note": "Source-based adjudication; no independent blinded regrade claimed.", "raw_receipts": [ { "path": "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\magnesium-sleep\\consensus-browser-2026-10-12.json", "sha256": "f6de31a86abb6d2d56781dde9c59c9840f6a633b2f5f100723cd2f82a5f589e6" } ], "independent_blinded_audit": false, "cutoff": "2026-10-12", "completed_utc": "2026-10-13T06:25:02.142837+00:00", "conclusion": "Endpoint hierarchy, experimental scope and original-source limits determine the evidence cards; provider wording does not override them." } }