Full assessment
From here the review is written for a technical reader: caps and thresholds, competing models, the independence basis, and the citation ledger.
Sources: 59 primary reports; claims: 64; verified: 64; unverified: 0. Verification is bounded attribution. Access: 6 partial-body and 53 bounded abstract/status examinations. Literature cutoff: 2026-10-12; source examination UTC date: 2026-10-13. No complete-paper audit or blinded calibration claimed. Adversarial review: Generated by Sol 6.1; adversarially reviewed by Claude Opus 5.5 (Anthropic) on 2026-10-14 (5 corrections applied) and again on 2026-11-02 (10 findings applied; confidence Moderate to Low; see ADVERSARIAL REVIEW AND APPROVAL - SECOND PASS). Status: Approved as revised.
AT A GLANCE
Magnesium has small, inconsistent sleep benefits in controlled studies; glycinate/threonate superiority and a proven human neural mediator are not established.
| Level | Confidence | Causal role | Momentum | Stability | Divergence |
|---|---|---|---|---|---|
| Δ — First field-valid causal perturbation crossed | Low | reinforcing / stabilizing factor | Mechanistic only | Stable | Contested |
Deciding 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.
Belief versus evidence: 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.
Best-supported rival: Nutritional deficiency correction restores physiology in selected contexts (Δ) — the highest-ranked model in the tournament that is not the nominal. Low magnesium can impair physiology and sleep in restricted experimental settings, and correcting it can restore them; deficiency/repletion rat sleep experiments and responding low-status human biomarkers support it, while deficiency-dependent human sleep responsiveness has not been cleanly established. 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.
COMPETING MECHANISTIC MODELS
Rank 1: An oral magnesium formulation modestly improves selected sleep symptoms (Δ). Some studied oral formulations cause a small sleep-symptom improvement under controlled conditions. 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 2: Nutritional deficiency correction restores physiology in selected contexts (Δ). Low magnesium can impair physiology and sleep in restricted experimental settings; correcting it can restore them. 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 3: Coingredients and the treatment package can explain some improvement (Δ). Ligands, melatonin, botanicals and expectancy can alter reported sleep independently of a demonstrated magnesium-ion mediator. 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 4: Absorption or neural biomarkers change without sleep improvement (Δ). Magnesium exposure can shift measured physiology without a corresponding clinical sleep benefit. 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.
The tournament does not alter the nominal level. Compatible pathways and flexible alternatives are not automatically proved by explaining observations.
FULL REVIEW
Registered claim and scope
Oral magnesium supplementation improves sleep in adults with poor sleep or insomnia.
Evaluated wording: Oral magnesium supplementation improves sleep in adults meeting the registered poor-sleep eligibility criteria. 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.
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.
Selection: position 4 among the first five editorial traffic-priority families, registered on 2026-10-12. First five editorial traffic-priority families in health_topic_traffic_priority_2026-10-12/ranking.json; traffic proxies are not measured worldwide popularity or a preassigned verdict. Registered claim assessed against original sources; no independent blinded calibration is claimed.
Evidence and causal interpretation
Rubric fit: 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.
The clearest recent positive primary sleep-symptom test is the four-week bisglycinate study: 155 participants were randomized, 153 provided baseline data and 134 completed. ISI fell more with the studied formulation than with identical placebo, but the between-arm difference was small, about 1.6 points with d=0.2 and p=0.049. Other questionnaires were largely null and the voluntary diary completion rate was below 10%. A statistically detected symptom benefit is not synonymous with remission or objective sleep restoration.
The bisglycinate formulation provides 250 mg elemental magnesium and 1523 mg glycine in its salt composition. That does not mean a separate free-glycine supplement was added. It does mean that the placebo contrast does not isolate magnesium ions from the ligand or formulation. The non-validated dietary-intake question yields an exploratory correlation, not proof that only deficient adults benefit.
Older evidence is mixed. The 2012 oxide trial enrolled 46 older adults with low dietary intake and serum Mg below 0.95 mmol/L, analyzed 43 completers and was powered on renin rather than a prospectively registered sleep primary. It found selected positive sleep measures but no total-sleep-time benefit. Nielsen 2010 has equal global PSQI improvement with citrate and placebo even though low-status and inflammatory indicators change. Those findings defeat the inference that biomarker correction alone validates sleep efficacy.
The only placebo-controlled polysomnographic EEG study, a 12-person randomized crossover in healthy older adults (ref 23), reported more slow-wave sleep and higher delta and sigma power with magnesium; it is small, was not in poor sleepers and has not been replicated.
Threonate results require endpoint-level reading. The 2024 study reports selected consumer-ring scores and awakening/daytime subscales but its overall ISI time-by-group interaction is null. Its 2025 correction discloses retrospective registration and additional competing interests. The newer six-week trial improves sleep-related impairment while sleep disturbance, restorative sleep and all ring-derived sleep outcomes are null. It reports allocation guessing, which is useful, but the estimated cognitive-age result is a cognition-score transformation, not evidence of brain rejuvenation.
The diabetic-insomnia four-arm trial reports major baseline ISI category imbalance before treatment. Post-treatment group associations and hormone changes cannot be interpreted as a clean adjusted magnesium effect. Its renal and glucose follow-ups share the same participants. Stress trials comparing Mg with Mg+B6 lack a magnesium-free comparator, while botanical/melatonin mixtures cannot isolate the magnesium contribution. These are valuable limits, not reasons to hide the real small primary symptom result.
Absorption experiments identify genuine influences of salt chemistry, release formulation, dose, meals, renal handling and compartment measurement. They do not rank clinical sleep effects. Rodent deficiency/repletion and receptor perturbations establish neural biology in restricted settings, while a shorter deficiency study alters oscillations without altering sleep architecture. The clinical gap is a ligand-controlled, baseline-status-stratified trial that measures meaningful symptoms and objective sleep together.
HYPOTHESIS STATE EVALUATION FRAMEWORK (HSEF v5.3)
Subclaim matrix and aggregation
| Subclaim | Scope | Level | Decision |
|---|---|---|---|
| SC1 Oral magnesium supplementation changes magnesium availability relevant to neural physiology. | Chemical form, elemental dose, baseline deficiency, renal function and exposure specified | Γ | 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. |
| SC2 Oral magnesium improves validated sleep outcomes against a credible comparator in adults with poor sleep or insomnia. | Baseline poor sleep or insomnia; age, deficiency, formulation, coingredients and 2–24-week horizon fixed | Δ | 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 at Δ without elevating a small formulation effect to broad reliable insomnia treatment. |
| SC3 Magnesium glycinate or threonate produces superior sleep benefit to other magnesium salts. | Matched elemental dose, population, duration and coingredients; no superiority inferred solely from absorption | Α | 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 at Α, rather than being inferred from popularity or formulation branding. |
| SC4 Magnesium-mediated neural changes explain clinical sleep or stress improvement. | Physiological mediator and relevant behaviour measured; rodent anxiety does not equal human insomnia | Γ | 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 cross Δ. |
Preregistered aggregation: primary-subclaim. 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. Sensitivities: weakest-link Α; primary-subclaim Δ; scope-matched Δ.
Decisive-perturbation inventory and causal tally
[1] 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.
[2] 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.
[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. 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.
[4] 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.
[7] 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.
[9] 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.
[19] 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.
[27] 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.
Tally: 1 positive qualifying study units across scoped subclaims; 18 screened discriminating contrast units. These are not independent causal lines or proof of full-claim necessity/sufficiency. 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.
Cap audit, precedence and Β/Γ/Δ boundary
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 are Γ-capped for human mediation. Absence of a direct salt comparison leaves SC3 unsupported without recapping clinical efficacy.
Universal six-cap audit: All six universal caps were considered: cell-only inference, unperturbed association, ectopic expression, biomarker-only intervention, forced transfer/seeding, and inherited-to-sporadic scope transfer. Each binds its offered inference; complementary same-scope causal classes are assessed together rather than re-capped in isolation.
Gamma hard-rule audit: The functional-unblinding rule concerns unmistakable acute subjective effects; such effects are not established for these ordinary magnesium doses. Blinding, GI tolerability and allocation guesses still matter. The mediation-by-correlation, acute-pharmacodynamic and rodent-proxy rules constrain human mediator inference. Open-label and single-blind stress/RLS reports alone do not cross Δ. The preregistered claim concerns validated sleep symptoms, so questionnaire benefit is not mislabeled objective architecture or functional recovery. Biomarker movement alone is not counted as sleep efficacy.
SC1 cap: “Biomarker change without functional/phenotypic change caps at Γ.” 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.
SC4 cap: “Candidate mediator correlated with outcome, never manipulated.” 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 cross Δ.
SC1 field-valid definition: “ - Genetic or pharmacologic intervention producing reproducible lifespan/healthspan extension - Must separate developmental effects from true aging effects - Biomarker change alone does NOT satisfy this threshold” Positive full-scope result: no. 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.
SC2 field-valid definition: “at least one of: - Active comparator matched for acute subjective effect, blinding integrity measured and reported - Blinded on/off, staggered-onset, or randomized-withdrawal neuromodulation, reversible and within-subject - Mediator manipulation with the intervention intact: antagonist blockade of the acute experience with the drug still given, or dosing under general anaesthesia - Depletion or challenge experiment in humans whose outcome is symptom trajectory, not a biomarker - Psychotherapy component dismantling, or scaffold removal from a drug arm, with blinded assessors
Rating-scale or biomarker change alone does NOT satisfy this threshold when the claim is functional, and statistical mediation alone never satisfies it.” Positive full-scope result: yes. 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 at Δ without elevating a small formulation effect to broad reliable insomnia treatment.
SC3 field-valid definition: “at least one of: - Active comparator matched for acute subjective effect, blinding integrity measured and reported - Blinded on/off, staggered-onset, or randomized-withdrawal neuromodulation, reversible and within-subject - Mediator manipulation with the intervention intact: antagonist blockade of the acute experience with the drug still given, or dosing under general anaesthesia - Depletion or challenge experiment in humans whose outcome is symptom trajectory, not a biomarker - Psychotherapy component dismantling, or scaffold removal from a drug arm, with blinded assessors
Rating-scale or biomarker change alone does NOT satisfy this threshold when the claim is functional, and statistical mediation alone never satisfies it.” Positive full-scope result: no. 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 at Α, rather than being inferred from popularity or formulation branding.
SC4 field-valid definition: “at least one of: - Active comparator matched for acute subjective effect, blinding integrity measured and reported - Blinded on/off, staggered-onset, or randomized-withdrawal neuromodulation, reversible and within-subject - Mediator manipulation with the intervention intact: antagonist blockade of the acute experience with the drug still given, or dosing under general anaesthesia - Depletion or challenge experiment in humans whose outcome is symptom trajectory, not a biomarker - Psychotherapy component dismantling, or scaffold removal from a drug arm, with blinded assessors
Rating-scale or biomarker change alone does NOT satisfy this threshold when the claim is functional, and statistical mediation alone never satisfies it.” Positive full-scope result: no. 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 cross Δ.
SC1 applied rubric adaptation (distinct from the unchanged literal criterion): 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.
SC2 applied rubric adaptation (distinct from the unchanged literal criterion): 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.
SC3 applied rubric adaptation (distinct from the unchanged literal criterion): 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.
SC4 applied rubric adaptation (distinct from the unchanged literal criterion): 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.
SC1 literal Γ hard rule: “ROS change measurements alone” Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale.
SC1 literal Γ hard rule: “NAD level change measurements alone” Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale.
SC1 literal Γ hard rule: “Mitochondrial metrics alone” Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale.
SC1 literal Γ hard rule: “Senescence marker changes alone” Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale.
SC1 literal Γ hard rule: “Single-species or single-strain evidence” Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale.
SC1 literal Γ hard rule: “Biomarker-only improvement without organismal benefit” Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale.
SC2 literal Γ hard rule: “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.” Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale.
SC2 literal Γ hard rule: “Mediation-by-correlation rule. Candidate mediator correlated with outcome, never manipulated.” Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale.
SC2 literal Γ hard rule: “Open-label rule. Open-label, single-arm, retrospective, or naturalistic evidence alone. A positive open-label result never crosses Δ, however large.” 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.
SC2 literal Γ hard rule: “Unblinded-rater rule. Outcomes rated by clinicians who delivered the intervention or knew allocation.” Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale.
SC2 literal Γ hard rule: “Acute-pharmacodynamic rule. Acute molecular, occupancy, or imaging change with no link to symptom trajectory.” Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale.
SC2 literal Γ hard rule: “Rodent-proxy rule. Forced-swim, tail-suspension, sucrose-preference, or head-twitch alone; head-twitch is pharmacodynamic, not therapeutic.” Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale.
SC3 literal Γ hard rule: “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.” Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale.
SC3 literal Γ hard rule: “Mediation-by-correlation rule. Candidate mediator correlated with outcome, never manipulated.” Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale.
SC3 literal Γ hard rule: “Open-label rule. Open-label, single-arm, retrospective, or naturalistic evidence alone. A positive open-label result never crosses Δ, however large.” 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.
SC3 literal Γ hard rule: “Unblinded-rater rule. Outcomes rated by clinicians who delivered the intervention or knew allocation.” Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale.
SC3 literal Γ hard rule: “Acute-pharmacodynamic rule. Acute molecular, occupancy, or imaging change with no link to symptom trajectory.” Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale.
SC3 literal Γ hard rule: “Rodent-proxy rule. Forced-swim, tail-suspension, sucrose-preference, or head-twitch alone; head-twitch is pharmacodynamic, not therapeutic.” Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale.
SC4 literal Γ hard rule: “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.” Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale.
SC4 literal Γ hard rule: “Mediation-by-correlation rule. Candidate mediator correlated with outcome, never manipulated.” Triggered for the offered human magnesium/ligand mediator inference; no mediator-specific intervention retaining the formulation was examined.
SC4 literal Γ hard rule: “Open-label rule. Open-label, single-arm, retrospective, or naturalistic evidence alone. A positive open-label result never crosses Δ, however large.” 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.
SC4 literal Γ hard rule: “Unblinded-rater rule. Outcomes rated by clinicians who delivered the intervention or knew allocation.” Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale.
SC4 literal Γ hard rule: “Acute-pharmacodynamic rule. Acute molecular, occupancy, or imaging change with no link to symptom trajectory.” Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale.
SC4 literal Γ hard rule: “Rodent-proxy rule. Forced-swim, tail-suspension, sucrose-preference, or head-twitch alone; head-twitch is pharmacodynamic, not therapeutic.” Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale.
Upward threshold ladder
SC1 Δ: “Requires at least one intervention changing lifespan or healthspan in a way consistent with the hypothesis.” Satisfied: no. Confirm central exposure and neural functional relevance in people at the studied oral doses with robust compartment measurements rather than urinary/plasma surrogates alone.
SC2 Δ: “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.
SC2 Ε: “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. 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.
SC3 Δ: “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. Directly compare matched elemental-dose glycinate, threonate and another salt with matched ligand/coingredients, credible blinding and prespecified sleep outcomes.
SC4 Δ: “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. Dissociate magnesium-ion, ligand and candidate neural pathway effects under the same treatment and measure the clinically relevant sleep/stress trajectory.
Upper ladder: 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.
Independence: All models/subclaims remain below Ζ. 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.
Falsification and pitfalls
More peripheral magnesium does not consistently yield better sleep. Nielsen status/inflammation changes coexist with equal placebo/global PSQI; newer threonate physiological shifts coexist with null objective sleep. Additional downgrade: False.
Human mediator and salt-superiority predictions remain untested or unpartitioned. No matched clinical salt comparison or human mediator manipulation was examined; ligand/coingredient exposures remain present. Additional downgrade: False.
Confirmation by biomarker. Absorption, hormone, EEG or HRV change is not proof of clinically meaningful sleep benefit.
Mechanism conflation. Formulation efficacy, magnesium-ion mediation and relative salt efficacy are separate claims.
Scope fitted to the result. Exploratory dietary correlations/severe subgroups cannot redefine the enrolled population as established responders.
Selective generalization. Rodent deficiency rescue and brain uptake do not demonstrate benefit in magnesium-replete adult poor sleepers.
Replication confused with independence. Several metabolic/mental-health publications share underlying trial participants.
Adversarial steelman: above, then below
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.
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.
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.
Final score, causal direction and M/S/D
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.
Confidence: Low. 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.
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.
Momentum: Mechanistic only. 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. Momentum modifies neither the level nor the confidence.
Stability: Stable. 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: Contested. No manufactured causal percentage or global belief-to-evidence arithmetic. These dimensions do not change level or confidence.
PROPOSED DECISIVE EXPERIMENTS
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. Controls: 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: 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: 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
Independent replication of a clinically meaningful sleep benefit rather than only borderline small symptom differences.
A prospectively tested magnesium-deficient versus replete response boundary using validated assessment, not post-hoc non-validated dietary questions.
Matched elemental-dose and ligand-controlled direct salt comparisons for sleep.
Human brain/mediator measurements with genuine mediator dissociation while maintaining treatment.
Polysomnography/actigraphy, daytime function and longer-term safety/adherence beyond short consumer wearable scores.
Transparent prospective registration, outcome hierarchy, sponsorship and corrections; the threonate correction changes confidence in prespecification.
REVIEWER NOTES
59 original reports were examined with original abstract/status receipts, and selected Methods/Results from 6 reports were examined. Most full papers/supplements were not fully audited. The 59 include oral bioavailability, neural/deficiency experiments, sleep/stress associations and original secondary reports; they are not 59 insomnia efficacy trials. Corrections remain attached to parent sources. Consensus Pro browser supported aspect cross-checks and timeline/gap leads; provider wording was corrected against originals. Scite monthly quota was already exhausted. No independent blind adjudication or clinical peer review is claimed. Additional original 2023 postoperative threonate trial 37520407 was examined as a population/formulation boundary, not as a direct primary-insomnia efficacy test. Correction 40567408 remains attached to 39252819; original registration and competing-interest sections were checked through the public PMC text returned by web search. The direct NCBI notice-body request returned no body. No notice earns primary-report credit. Coordinating review retained Δ/Moderate for the small validated primary-ISI formulation effect and restricted the distinct target-availability inference to Γ. Glycine is part of the bisglycinate salt, not an asserted added free-glycine ingredient; no ligand-matched arm isolated its contribution. The registration/disclosure correction is not a retraction or proof of fabricated data.
Search leads, reviews, protocols and correction notices do not pad the primary count. Downloaded XML does not earn examination credit. Linked notices remain attached; unexamined correction details limit inference. This is a coordinator source/claim consistency assessment, not independent blinded calibration.
Syntheses and one further trial examined in the 2026-11-02 adversarial pass as context, not primary credit: a 2026 systematic review of 12 stand-alone-magnesium RCTs (ref 60) rated certainty low to very low and concluded that current evidence does not support oral magnesium as routine insomnia treatment; a 2021 meta-analysis of three RCTs in 151 older adults (ref 61) found a 17-minute sleep-onset-latency reduction on low to very-low-quality evidence. A 10-week magnesium oxide (250 mg) versus placebo trial in women with PCOS (ref 62) found no sleep-quality effect (p=0.85); like the postoperative threonate trial it is a population boundary, not a direct test of the registered poor-sleep claim. Refs 60–62 were checked at PubMed abstract/metadata depth only and are not counted among the 59 examined primary reports; ref 60 shares authors with refs 3 and 19. The same pass verified the bisglycinate trial registration in the WHO ICTRP record for DRKS00031494 (date of registration 12 April 2023; date of first enrolment 20 April 2023; prospective registration: yes; primary outcome ISI) and lowered the confidence band from Moderate to Low on evidence density and reproducibility.
Consensus and original-source reconciliation
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 PMID40918053.
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 PMID21199787.
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 PMID23853635.
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 PMID39252819.
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 PMID41601871.
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 PMID39534260.
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 PMID30562392.
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 PMID31330811.
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 PMID8232845.
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 PMID34092248.
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 PMID37520407.
Consensus was used to identify literature and cross-check specific claims about design, endpoints, scope and research gaps. Those aspects were checked against original primary abstracts/status records and selected original Methods/Results passages. Consensus output was not treated as original full text. Provider search omissions are not evidence that a study does not exist. Source access and examination receipts are retained. Scite use or monthly unavailability is recorded per case; provider citation counts do not change causal grades.
Research timeline and gaps: Magnesium Forms, Sleep and Stress
Selected publication milestones, not an exhaustive history or discovery priority claim.
1990 — Citrate-versus-oxide solubility and human loading illustrate why availability and clinical sleep effects are different. Original PMID2407766.
1993 — Rat dietary deficiency and repletion show reversible sleep/ECoG disruption in that nutritional context. Original PMID8232845.
2002 — Small elderly crossover measures oral magnesium effects with overnight EEG and endocrine sampling. Original PMID12163983.
2010 — Rodent threonate central-exposure/synaptic work supports neural plausibility, not clinical insomnia efficacy. Original PMID20152124.
2010 — Citrate poor-sleep trial finds equal global PSQI improvement despite some status/inflammation differences. Original PMID21199787.
2012 — Older-adult oxide trial reports selected positive symptoms and total-sleep-time null. Original PMID23853635.
2018 — Stress Mg+B6 versus Mg trial illustrates the need for a magnesium-free comparator. Original PMID30562392.
2024 — Threonate 21-day trial reports mixed questionnaire and consumer wearable outcomes; subsequent correction matters. Original PMID39252819.
2025 — Prospective bisglycinate 4-week trial finds a small primary ISI effect with ligand exposure unpartitioned. Original PMID40918053.
2025 — Newer six-week threonate trial retains sleep-disturbance/restorative/objective nulls alongside impairment benefit. Original PMID41601871.
2023 — A postoperative placebo-controlled threonate study finds null secondary sleep, mood and cognition outcomes; its pain-prevention population is distinguished from insomnia enrollment. Original PMID37520407.
Research gaps
Independent replication of a clinically meaningful sleep benefit rather than only borderline small symptom differences.
A prospectively tested magnesium-deficient versus replete response boundary using validated assessment, not post-hoc non-validated dietary questions.
Matched elemental-dose and ligand-controlled direct salt comparisons for sleep.
Human brain/mediator measurements with genuine mediator dissociation while maintaining treatment.
Polysomnography/actigraphy, daytime function and longer-term safety/adherence beyond short consumer wearable scores.
Transparent prospective registration, outcome hierarchy, sponsorship and corrections; the threonate correction changes confidence in prespecification.
Boundary 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.
ADVERSARIAL REVIEW AND APPROVAL
Authoring model: Sol 6.1. Adversarial reviewer: Claude Opus 5.5 (Anthropic). Date: 2026-10-14.
Scope of checks. All 59 REFERENCES PMIDs verified against PubMed get_article_metadata (59/59 resolve to the stated
title, first author, journal and year within the plus-or-minus-1 print/e-pub convention; no retractions or expressions of
concern). Twelve load-bearing claims spot-checked against original abstracts, with the locally held partial-body text
re-read for PMIDs 39534260, 40918053, 23853635 and 41601871. Scoring logic checked: the six universal caps and cap
precedence, the pre-registered aggregation rule and its reported alternatives, the Beta/Gamma/Delta boundary, the Zeta
independence basis, the confidence-band text, the role-of-mechanism derivation, the Momentum artifact requirement and the
competing-model tournament fields. Validator re-run.
| ID | Severity | Location | Original to corrected | Evidence |
|---|---|---|---|---|
| A1 | Major | AT A GLANCE, "Best-supported rival" | The paragraph named "An oral magnesium formulation modestly improves selected sleep symptoms" - now names Nutritional deficiency correction restores physiology in selected contexts (Δ), the highest-ranked non-nominal model, with its own supporting and contradicting evidence | Renderer defect: the block printed competing_models.models_evaluated[0], which here carries is_nominal: true and rank_in_tournament: 1. The nominal cannot be its own best-supported rival. The genuine rival is M2 (rank_in_tournament: 2, is_nominal: false). The discriminating-experiment sentences were already correct and are retained. |
| A2 | Major | AT A GLANCE table and "Final score, causal direction and M/S/D"; scorecard extended_scoring_MSD.momentum |
Momentum "Decisive work underway" - now "Mechanistic only", artifact rescoped to state that the two named trials are completed and that no boundary-addressing trial was identified | references/hsef-framework.md: "Decisive work underway - Someone is running an experiment that could cross the next threshold", with a required artifact naming that work. The original artifact named only completed trials and itself conceded it was "not a claim that a specific pending factorial trial exists", contradicting the adjacent Stability entry ("No verified named pending trial ... was identified"). Momentum modifies no letter, so level and confidence are unchanged. |
| A3 | Editorial | Throughout review.md (104 replacements) | Rendering defects: missing spaces around numerals, acronyms, Greek letters and joined words - e.g. "RejectΓforSC2because", "crossΔ", "globalPSQI", "over8-12weeks", "155 randomized,153 baseline analyzed and134 completed", "mustretainthe actualarms ratherthantransfer the combinedresult", "ErratumIn: PMID40567408", and seven empty "DOI: ." fields - corrected to spaced forms, "Erratum in: PMID 40567408" and "DOI: not available." | Known reference-builder rendering defects. No numeral, p-value, dose or PMID value altered; house-style PMID suffixes (e.g. "correction40567408") left intact. The seven affected references genuinely have no DOI in PubMed (PMIDs 23853635, 6083421, 16548135, 11794633, 30829204, 1468087, 19066411), so the field was labelled rather than invented. |
| A4 | Minor | scorecard.json final_score.confidence_rationale |
"...density, heterogeneous controls and incomplete access set the confidence..." - restated on evidence density, partial replication and methodological heterogeneity, with reviewer access explicitly excluded | hsef-framework.md, Confidence band: "Confidence reflects evidence density and reproducibility." Band unchanged at Moderate, which matches the Moderate text; the High text is not met given one small registered positive, several nulls and no objective replication. |
| A5 | Editorial | web-page.md | "serumMg<0.95mmol/L" - corrected to "serum Mg <0.95 mmol/L" | Same rendering-defect class as A3. |
Rejected findings (checked, no change).
- Baseline-imbalance attribution for PMID 39534260. The review states a baseline (pre-trial) ISI category imbalance at p=0.0001, while the PubMed abstract reports p=0.0001 for the post-trial association. The original full text reports both: Table 6 gives the baseline (pre-trial) ISI category association as p=0.0001 and Table 7 the post-trial association as p=0.0001. The review's statement is correct and is also explicitly paired with the post-treatment figure. No change.
- Scope-matched aggregation. The declared rule is primary-subclaim (SC2) and is applied as written. The reported sensitivities are correct: weakest-link Α is the lowest subclaim (SC3), and scope-matched Δ is right because SC2 is the only subclaim whose scope matches the registered adult poor-sleep/insomnia claim - SC3 (salt superiority) and SC4 (mediation) are different propositions and SC1 is narrower. No change.
- Headline level. Δ rests on one prospectively registered, blinded, placebo-controlled trial with a positive validated primary endpoint (PMID 40918053: 155 randomized, ISI -3.9 vs -2.3, p=0.049, d=0.2) - a field-valid human interventional perturbation. The adversarial pass argued for Γ (small effect, ligand unpartitioned, objective sleep absent) and for Ε (context restriction) and rejected both: the Δ threshold asks for at least one field-valid causal perturbation, not for a large or mechanistically resolved one, and the trial population matches the registered scope rather than restricting it. Retained.
- Reference years. Six references print the issue year where PubMed carries an e-pub year one apart (refs 5, 7, 10, 15, 19, 41, 56). Within the stated convention. [Amended by note, 2026-11-02 (E9): the sentence says six but lists seven; the 2026-11-02 metadata comparison finds nine one-year offsets (refs 5, 7, 10, 15, 19, 26, 41, 42, 56), all within the convention.]
- Collective-author defect. No reference renders with a blank first author or a stray leading comma.
- Provenance clauses. No false-approval boilerplate and no false provenance clause is present; the REVIEWER NOTES correctly record that Consensus work was performed for this case and that the Scite monthly quota was exhausted. No earlier adversarial approval is asserted, and none was invented.
- Counts. 59 sources / 64 claims / 64 verified / 0 unverified agree between the banner, scorecard
provenance_headerandverification_summary. - Role of mechanism. "reinforcing / stabilizing factor" follows derivation step 5 for a small symptom-level effect on a phenotype initiated upstream. Not changed.
Residual limitations. Verification remains bounded attribution: 53 of 59 sources were examined at abstract/status depth only. The Δ rests on a single registered positive trial, so the level is one replication away from moving in either direction. The adversarial pass did not re-run a literature search and cannot certify completeness of the source set at the 2026-10-12 cutoff.
Approval: Following adversarial review and the corrections listed above, the revised document is approved. - Claude Opus 5.5 (Anthropic), 2026-10-14.
ADVERSARIAL REVIEW AND APPROVAL - SECOND PASS (2026-11-02)
Authoring model: Sol 6.1. Adversarial reviewer: Claude Opus 5.5 (Anthropic). Date: 2026-11-02.
Scope of checks. A second, independent pass re-derived the findings from the sources and the score card. All 59 REFERENCES PMIDs were verified against PubMed metadata (59/59; no retractions or expressions of concern). Fourteen load-bearing claims were spot-checked against PubMed abstracts and, for PMIDs 40918053, 39252819 and 23853635, the PMC full text. Scoring was re-derived: the primary-subclaim rule gives SC2 = Δ, with weakest-link Α and scope-matched Δ sensitivities; the tally (1 positive qualifying unit, 8 decisive items, 18 discriminating contrasts) matches the score card. The full log is ADVERSARIAL_REVIEW.magnesium-sleep.md with adversarial-findings.magnesium-sleep.json.
Registration verification (M2). The trial report states only that DRKS00031494 was registered "at the time of recruitment". The WHO ICTRP record for DRKS00031494 (source register DRKS; last refreshed 7 April 2025; retrieved 2026-11-02) gives date of registration 12 April 2023, date of first enrolment 20 April 2023, "Prospective Registration: Yes", and the Insomnia Severity Index as primary outcome. "Prospectively registered" is therefore retained, now with the registry dates, and the SC2 Δ crossing (which requires a pre-registered primary outcome) stands.
| ID | Severity | Correction applied |
|---|---|---|
| M1 | Major | Confidence Moderate to Low in AT A GLANCE, Belief versus evidence, aggregation paragraph, steelman, Final score, SC2 subclaim row and score card. One positive qualifying study unit without independent replication matches the framework's (Δ, low) pattern. Level unchanged. |
| M2 | Major | Prospective registration verified in the registry record (above); the registry dates were added to the Belief versus evidence sentence, inventory item [3] and evidence card [3]. |
| m3 | Minor | Momentum artifact no longer attributes objective wearables and allocation-guess checks to the bisglycinate trial, which used a validated symptom endpoint without objective sleep measurement. |
| m4 | Minor | Remaining fused words spaced (for example "Rubric 07", "about 1.6 points with d=0.2 and p=0.049", "Ε could", "Γ could", "trial 37520407", "bisglycinate 4-week"); doubled full stops removed. No values changed. |
| m5 | Minor | "58 original reports" corrected to 59. |
| m6 | Minor | Reader-summary confidence wording now cites evidence density and reproducibility, not reviewer access. |
| m7 | Minor | REVIEWER NOTES add two syntheses (refs 60, 61) and an oxide PCOS null (ref 62) as context; appended to REFERENCES without renumbering; no primary-report credit. |
| m8 | Minor | The 12-person placebo-controlled EEG crossover (ref 23) is now described in the evidence section; the upper ladder reads "mixed objective outcomes". |
| E9 | Editorial | Note added to the first pass's rejected finding 4: nine, not six, one-year reference offsets, all within convention. |
| E10 | Editorial | Ref 19 carries its post-cutoff correction notice, PMID 42959782 (not examined). |
Not applied here. The web-page.md instances named in M1, M2 and m4 are outside this source folder and are left to the site build.
Approval: The conditions of the second pass (M1, M2 with registry verification, and the Minor corrections) are met; the revised document is approved at Δ with Low confidence. - Claude Opus 5.5 (Anthropic), 2026-11-02.
REFERENCES
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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. PMID 39252819. DOI: 10.1016/j.sleepx.2024.100121. Access: full_text_partial. Study: MG-THREONATE-ISRCTN14728094.
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McFarlin BK, Paschall AL, Kelly ME et al. Comparing the Bioavailability of Two Seawater-Derived Magnesium Preparations. Journal of medicinal food. 2025. PMID 40955524. DOI: 10.1177/1096620X251380191. Access: abstract_metadata. Study: PMID40955524.
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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. PMID 42084749. DOI: 10.1007/s12017-026-08929-6. Access: abstract_metadata. Study: PMID42084749.
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Eremenko NN, Shikh EV, Serebrova SY et al. Comparative study of the bioavailability of magnesium salts. Drug metabolism and personalized therapy. 2019. PMID 31606725. DOI: 10.1515/dmpt-2019-0004. Access: abstract_metadata. Study: PMID31606725.
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Dolberg MK, Nielsen LP, Dahl R. Pharmacokinetic Profile of Oral Magnesium Hydroxide. Basic & clinical pharmacology & toxicology. 2017. PMID 27412366. DOI: 10.1111/bcpt.12642. Access: abstract_metadata. Study: PMID27412366.
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Felice VD, O'Gorman DM, O'Brien NM et al. Bioaccessibility and Bioavailability of a Marine-Derived Multimineral, Aquamin-Magnesium. Nutrients. 2018. PMID 30018220. DOI: 10.3390/nu10070912. Access: abstract_metadata. Study: PMID30018220.
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Firoz M, Graber M. Bioavailability of US commercial magnesium preparations. Magnesium research. 2001. PMID 11794633. DOI: not available. Access: abstract_metadata. Study: PMID11794633.
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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. PMID 30829204. DOI: not available. Access: abstract_metadata. Study: PMID30829204.
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Siener R, Jahnen A, Hesse A. Bioavailability of magnesium from different pharmaceutical formulations. Urological research. 2011. PMID 20862466. DOI: 10.1007/s00240-010-0309-y. Access: abstract_metadata. Study: PMID20862466.
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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. PMID 31230494. DOI: 10.1080/19390211.2019.1629146. Access: abstract_metadata. Study: PMID31230494.
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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. PMID 12001016. DOI: 10.1038/sj.ejcn.1601333. Access: abstract_metadata. Study: PMID12001016.
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Fine KD, Santa Ana CA, Porter JL et al. Intestinal absorption of magnesium from food and supplements. The Journal of clinical investigation. 1991. PMID 1864954. DOI: 10.1172/JCI115317. Access: abstract_metadata. Study: PMID1864954.
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White J, Massey L, Gales SK et al. Blood and urinary magnesium kinetics after oral magnesium supplements. Clinical therapeutics. 1992. PMID 1468087. DOI: not available. Access: abstract_metadata. Study: PMID1468087.
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Morris ME, LeRoy S, Sutton SC. Absorption of magnesium from orally administered magnesium sulfate in man. Journal of toxicology. Clinical toxicology. 1987. PMID 3430654. DOI: 10.3109/15563658708992640. Access: abstract_metadata. Study: PMID3430654.
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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. PMID 11756061. DOI: 10.1093/ajcn/75.1.65. Access: abstract_metadata. Study: PMID11756061.
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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. PMID 35041150. DOI: 10.1007/s10534-022-00363-y. Access: abstract_metadata. Study: PMID35041150.
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Slutsky I, Abumaria N, Wu LJ et al. Enhancement of learning and memory by elevating brain magnesium. Neuron. 2010. PMID 20152124. DOI: 10.1016/j.neuron.2009.12.026. Access: abstract_metadata. Study: PMID20152124.
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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. PMID 34883514. DOI: 10.1093/sleep/zsab276. Access: abstract_metadata. Study: PMID34883514.
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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. PMID 36354243. DOI: 10.1684/mrh.2022.0503. Access: abstract_metadata. Study: PMID36354243.
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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. PMID 38745424. DOI: 10.1080/07420528.2024.2353225. Access: abstract_metadata. Study: PMID38745424.
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Poleszak E, Wlaź P, Wróbel A et al. NMDA/glutamate mechanism of magnesium-induced anxiolytic-like behavior in mice. Pharmacological reports : PR. 2008. PMID 19066411. DOI: not available. Access: abstract_metadata. Study: PMID19066411.
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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. PMID 41515231. DOI: 10.3390/nu18010114. Access: abstract_metadata. Study: PMID41515231.
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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. PMID 38703902. DOI: 10.1016/j.jad.2024.05.002. Access: abstract_metadata. Study: PMID38703902.
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Ghafari M, Whittle N, Miklósi AG et al. Dietary magnesium restriction reduces amygdala-hypothalamic GluN1 receptor complex levels in mice. Brain structure & function. 2015. PMID 24807818. DOI: 10.1007/s00429-014-0779-8. Access: abstract_metadata. Study: PMID24807818.
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Huang X, Sun X, Wang Q et al. Structural insights into the diverse actions of magnesium on NMDA receptors. Neuron. 2025. PMID 40010346. DOI: 10.1016/j.neuron.2025.01.021. Access: abstract_metadata. Study: PMID40010346.
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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. PMID 41916937. DOI: 10.12809/eaap25122. Access: abstract_metadata. Study: PMID41916937.
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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. PMID 37520407. DOI: 10.2147/BCTT.S413435. Access: abstract_metadata. Study: PMID37520407.
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Lopresti AL, Smith SJ, Drummond PD. Magnesium Supplementation for Sleep in Adults: A Systematic Review of Randomized Controlled Trials. Journal of dietary supplements. 2026. PMID 42661485. DOI: 10.1080/19390211.2026.2719670. Access: abstract_metadata. Study: PMID42661485. Context only (systematic review); no primary-report credit.
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Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis. BMC complementary medicine and therapies. 2021. PMID 33865376. DOI: 10.1186/s12906-021-03297-z. Access: abstract_metadata. Study: PMID33865376. Context only (meta-analysis); no primary-report credit.
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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. PMID 36620514. DOI: 10.1002/hsr2.1013. Access: abstract_metadata. Study: PMID36620514. Population boundary; outside the 59 examined primary reports.
Source-specific evidence cards
[1] Magnesium-L-threonate improves sleep quality and daytime functioning in adults with self-reported sleep problems: A randomized controlled trial.
Shows: The 21-day threonate trial reports selected wearable scores and awakening/daytime benefits.
Does not show: Overall ISI interaction is null (p=0.39); correction 40567408 adds retrospective registration and conflicts. Wearable scores are not polysomnography.
Access/status: 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. Erratum in: PMID 40567408. Subclaims: SC2, SC3, SC4.
[2] The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial.
Shows: An eight-week oxide trial in older adults improves ISI and selected sleep-log outcomes.
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.
Access/status: 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. none_found. Subclaims: SC2, SC4.
[3] Magnesium Bisglycinate Supplementation in Healthy Adults Reporting Poor Sleep: A Randomized, Placebo-Controlled Trial.
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.
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.
Access/status: 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. none_found. Subclaims: SC2, SC3, SC4.
[4] Effects of magnesium and potassium supplementation on insomnia and sleep hormones in patients with diabetes mellitus.
Shows: A diabetic-insomnia four-arm trial reports ISI and hormone changes after Mg/K supplementation.
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.
Access/status: 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. none_found. Subclaims: SC2, SC4.
[5] Effects of magnesium and potassium on insulin resistance and blood sugar level among insomniac patients with diabetes mellitus-A randomized controlled trial.
Shows: An original follow-up of the diabetic-insomnia trial reports glucose and HOMA changes.
Does not show: Same NCT04642313 participants as 39534260; metabolic proxies are not sleep mediation or an independent trial.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC4.
[6] Comparison of Diabetic Nephropathy Markers in Diabetic Patients With Insomnia Before and After Potassium and Magnesium Supplementation: A Randomized Controlled Trial.
Shows: An original follow-up of the diabetic-insomnia trial reports renal and liver marker changes.
Does not show: Same 320/290 cohort; these markers are not neural mediators or new clinical sleep evidence.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC4.
[7] Magnesium supplementation improves indicators of low magnesium status and inflammatory stress in adults older than 51 years with poor quality sleep.
Shows: Citrate improves selected low-magnesium and inflammatory indicators in a seven-week randomized trial.
Does not show: Global PSQI improves equally with magnesium and placebo. Nutritional biomarker response does not establish a sleep-responsive deficiency subgroup.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC2, SC4.
[8] Magnesium involvement in sleep: genetic and nutritional models.
Shows: Genetic RBC-magnesium lines and dietary deficiency alter mouse sleep and EEG patterns.
Does not show: Central/peripheral regulation and correlation directions differ; optimal balance is distinct from a universal more-magnesium model.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC4.
[9] Effects of a magnesium-deficient diet on sleep organization in rats.
Shows: Prolonged dietary deficiency disrupts rat sleep/ECoG and repletion restores patterns.
Does not show: Small groups and a deficiency/recovery context do not establish supplementation benefits in replete adults.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC4.
[10] Magnesium deficiency differentially modulates hippocampal and prefrontal oscillations and cardiac rhythms.
Shows: Three-week deficiency alters rat hippocampal/prefrontal oscillations.
Does not show: Sleep architecture is unchanged; neural signals cannot be relabeled an insomnia phenotype.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC4.
[11] Vigilance states and cerebral monoamine metabolism in experimental magnesium deficiency.
Shows: A restricted-magnesium diet changes rat monoamine concentrations and increases wakefulness.
Does not show: Terminal neurochemical correlations do not isolate a mediator; species and deficiency scope differ from supplementation for human insomnia.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC4.
[12] 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.
Shows: A secondary low-magnesemia stress trial analysis reports mood/QoL improvements in both treatment arms.
Does not show: No magnesium-free control and shared 2015-003749-24 participants; post-hoc change does not identify magnesium causality.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC4.
[13] Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial.
Shows: An investigator-blind stress trial compares Mg+B6 with Mg and finds no overall primary superiority.
Does not show: Both arms contain magnesium; a severe-stress subgroup advantage concerns added B6, not magnesium necessity.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC4.
[14] Effects of a Scutellaria baicalensis/Crataegus laevigata, magnesium and chromium supplement on stressed individuals: A randomised, double-blind, placebo-controlled, crossover trial.
Shows: A herbal/Mg/chromium crossover trial reports selected mood and cognitive benefits.
Does not show: 35 analyzed of 43 enrolled, short periods and a multiingredient bundle; no isolated magnesium sleep effect.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC2, SC4.
[15] 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.
Shows: A randomized botanical/Mg/B-vitamin experiment changes EEG theta and selected subjective stress responses.
Does not show: The ingredient bundle and absent magnesium-only factorial control leave magnesium mediation unidentified.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC4.
[16] Impact of magnesium supplementation, in combination with vitamin B6, on stress and magnesium status: secondary data from a randomized controlled trial.
Shows: A secondary stress-trial report finds RBC-magnesium increases in low-status subgroups without extra B6 benefit.
Does not show: Shared trial participants; RBC change and within-group stress improvement are not causal sleep efficacy.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC4.
[17] A Combination of Green Tea, Rhodiola, Magnesium, and B Vitamins Increases Electroencephalogram Theta Activity During Attentional Task Performance Under Conditions of Induced Social Stress.
Shows: An original EEG analysis finds greater task theta under stress with the combined supplement.
Does not show: Behavioral performance and ERP outcomes are null; same NCT03262376 trial, and neural signals do not establish functional benefit.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC4.
[18] Assessing brain function in stressed healthy individuals following the use of a combination of green tea, Rhodiola, magnesium, and B vitamins: an fMRI study.
Shows: A 40-person supplement/placebo trial reports stress-rating and BOLD changes.
Does not show: Multiple ingredients, single blinding and correlated imaging/rating changes do not isolate magnesium; thermal stress is not insomnia.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC4.
[19] The effects of magnesium L-threonate (Magtein®) on cognitive performance and sleep quality in adults: a randomised, double-blind, placebo-controlled trial.
Shows: A prospective six-week threonate trial improves sleep-related impairment and checks allocation guesses.
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.
Access/status: 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. none_found. Subclaims: SC2, SC4.
[20] Magnesium citrate monotherapy improves restless legs syndrome symptoms and multiple suggested immobilization test scores in an open-label pilot study.
Shows: An open-label 12-person citrate pilot improves RLS symptoms and immobilization readouts.
Does not show: No placebo, different clinical condition and unchanged serum magnesium; expectancy and regression remain.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC2, SC4.
[21] Effect of Magnesium Oxide Supplementation on Nocturnal Leg Cramps: A Randomized Clinical Trial.
Shows: A randomized oxide trial finds no benefit for nocturnal cramps or sleep quality over placebo.
Does not show: The cramp population differs from primary insomnia; improvement in both arms does not identify an intervention effect.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC2.
[22] Modulating stress and sleep through a multi-compound dietary supplement: a randomized, double-blind, placebo-controlled trial.
Shows: A four-arm morning/evening supplement trial finds selected morning botanical stress/sleep improvements.
Does not show: The evening threonate/theanine/apigenin bundle shows minimal effects; healthy active participants and multiple ingredients limit magnesium attribution.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC2, SC4.
[23] Oral Mg(2+) supplementation reverses age-related neuroendocrine and sleep EEG changes in humans.
Shows: A 12-person elderly crossover increases slow-wave sleep/EEG power with endocrine shifts.
Does not show: Small short study and unclear indexed insomnia eligibility; hormone association does not prove mediation or salt superiority.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC2, SC4.
[24] Metabolic and hormonal effects of melatonin and/or magnesium supplementation in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial.
Shows: A PCOS factorial trial reports PSQI improvement with melatonin and melatonin+Mg.
Does not show: The magnesium-only sleep benefit is not established by those positive arms; combination efficacy cannot be assigned to magnesium.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC2, SC4.
[25] Dose-Dependent Absorption Profile of Different Magnesium Compounds.
Shows: Rodent dose/form comparisons find salt-dependent brain, muscle and serum magnesium patterns.
Does not show: Tissue concentrations do not demonstrate clinical sleep benefit; divided dosing does not uniformly improve availability.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC3.
[26] Timeline (Bioavailability) of Magnesium Compounds in Hours: Which Magnesium Compound Works Best?
Shows: Single-dose rat pharmacokinetics finds acetyl-taurate brain penetration and anxiety-related changes.
Does not show: These are preclinical malate/taurate results, not glycinate/threonate superiority for human sleep.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC3, SC4.
[27] Predicting and Testing Bioavailability of Magnesium Supplements.
Shows: Original digestion models and controlled human testing identify serum absorption differences between formulations.
Does not show: Urinary comparisons are null and elemental doses differ; absorption does not establish brain delivery or sleep superiority.
Access/status: 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. none_found. Subclaims: SC1, SC3.
[28] Magnesium bioavailability from magnesium citrate and magnesium oxide.
Shows: Citrate is more soluble and produces greater urinary magnesium loading than oxide in volunteers.
Does not show: Acute excretion, gastric acidity and renal handling are distinct from clinical sleep efficacy.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC3.
[29] Bioavailability of magnesium diglycinate vs magnesium oxide in patients with ileal resection.
Shows: Stable-isotope crossover in 12 ileal-resection patients compares diglycinate with oxide.
Does not show: Overall absorption does not differ; four most impaired patients show an advantage, which cannot define a general sleep benefit.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC3.
[30] Effects of Magnesium Citrate, Magnesium Oxide, and Magnesium Sulfate Supplementation on Arterial Stiffness: A Randomized, Double-Blind, Placebo-Controlled Intervention Trial.
Shows: A 24-week matched-salt trial in 164 adults raises plasma and urinary magnesium.
Does not show: Arterial stiffness and blood pressure remain null; excretion differences do not establish sleep benefit.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC3, SC4.
[31] Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach.
Shows: Stable-isotope randomized repletion in depleted rats compares absorption/retention from ten salts.
Does not show: All forms are bioavailable, with context-dependent differences; depleted male rats are not replete human poor sleepers.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC3.
[32] Magnesium bioavailability after administration of sucrosomial® magnesium: results of an ex-vivo study and a comparative, double-blinded, cross-over study in healthy subjects.
Shows: Human crossover and ex vivo testing compare sucrosomial magnesium with several salts.
Does not show: Compartment-specific availability differences do not establish sleep efficacy; branded delivery differs from ligand chemistry.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC3.
[33] Comparative Clinical Study on Magnesium Absorption and Side Effects After Oral Intake of Microencapsulated Magnesium (MAGSHAPETM Microcapsules) Versus Other Magnesium Sources.
Shows: A 40-person crossover finds sustained plasma rises with microencapsulation compared with several forms.
Does not show: Acute plasma and GI outcomes are not brain or sleep measures; bisglycinate is not a uniform plasma winner.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC3.
[34] Comparing the Bioavailability of Two Seawater-Derived Magnesium Preparations.
Shows: A matched-dose crossover finds both seawater preparations increase magnesium uptake versus placebo.
Does not show: The two forms do not differ at matched elemental dose; serum/urinary measures are not sleep endpoints.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC3.
[35] Enhanced Neurophysiological Benefits of Magnesium-Acetyl-Taurate Over Magnesium-L-Threonate: A Comparative pre-clinical Study on Bioavailability, Synaptic Plasticity and Cognitive Functions.
Shows: Rat acetyl-taurate/threonate comparison reports brain-magnesium and cognitive/anxiety patterns.
Does not show: Salt mass doses, many markers and rodent behaviors are not a direct matched human sleep comparison.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC3, SC4.
[36] Comparative study of the bioavailability of magnesium salts.
Shows: Volunteer/heart-failure work finds comparable magnesium-orotate±potassium blood/RBC profiles.
Does not show: Serum homeostasis complicates AUC interpretation; human neural and sleep outcomes were not measured.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC3.
[37] Pharmacokinetic Profile of Oral Magnesium Hydroxide.
Shows: Oral-versus-IV testing estimates hydroxide bioavailability in ten healthy men.
Does not show: Small acute pharmacokinetics does not establish brain exposure, sleep benefit or safety across renal contexts.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1.
[38] Bioaccessibility and Bioavailability of a Marine-Derived Multimineral, Aquamin-Magnesium.
Shows: INFOGEST/Caco2 testing compares a marine multimineral with magnesium chloride and oxide.
Does not show: Digestion/epithelial transport is not living brain exposure or clinical sleep efficacy; additional minerals are bundled.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC3.
[39] Bioavailability of US commercial magnesium preparations.
Shows: Volunteer urinary testing finds oxide less absorbed and chloride/lactate/aspartate comparable.
Does not show: Some inorganic salts match organic salts; chemical class labels cannot establish clinical sleep rankings.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC3.
[40] Neurobehavioral and biochemical effects of magnesium chloride (MgCl2), magnesium sulphate (MgSO4) and magnesium-L-threonate (MgT) supplementation in rats: A dose dependent comparative study.
Shows: Rat salt/dose comparisons report memory and depression-related behavior differences.
Does not show: Forced-swim/maze proxies, salt-mass doses and biomarkers do not demonstrate human insomnia or form superiority.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC3, SC4.
[41] Bioavailability of magnesium from different pharmaceutical formulations.
Shows: An oxide effervescent/capsule crossover under standardized diet produces different urinary uptake.
Does not show: Delivery formulation matters within one salt; no brain or sleep function endpoint was measured.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC3.
[42] Magnesium Bioavailability and Tolerability Do Not Differ between Two Supplements with Different Release Properties.
Shows: Controlled crossover finds no availability/tolerability difference between immediate and delayed release.
Does not show: Open-label acute pharmacokinetics is not sleep comparative efficacy; the null is retained.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC3.
[43] Magnesium bioavailability from mineral water. A study in adult men.
Shows: Oral/IV mineral-water radiotracing quantifies enteral absorption in men.
Does not show: Ten participants and acute tracers; no sleep endpoint. Age correlation is not a randomized age effect.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1.
[44] Intestinal absorption of magnesium from food and supplements.
Shows: Controlled magnesium loading shows curvilinear absorption and lower fractions at larger doses; enteric coating lowers uptake.
Does not show: Intestinal or food effects do not establish central exposure or hypnotic efficacy.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC3.
[45] Blood and urinary magnesium kinetics after oral magnesium supplements.
Shows: A 12-person crossover finds some salt-specific blood/urine time-profile differences.
Does not show: Overall blood compartment changes are mostly nonsignificant; there is no general salt winner or sleep comparison.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC3.
[46] Absorption of magnesium from orally administered magnesium sulfate in man.
Shows: A six-volunteer sulfate study measures limited variable absorption and diarrhea after a cathartic dose.
Does not show: Cathartic exposure and normal kidneys differ from sleep regimens; no dosing recommendation is inferred.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1.
[47] Meal effect on magnesium bioavailability from mineral water in healthy women.
Shows: Stable-isotope crossover finds meal-enhanced mineral-water absorption/retention in ten women.
Does not show: Meal effects change availability without demonstrating a neural sleep mechanism or salt superiority.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1.
[48] Effects of short-term magnesium supplementation on ionized, total magnesium and other relevant electrolytes levels.
Shows: Short supplementation finds discordant ionized/total magnesium patterns and oxide advantage on selected indices.
Does not show: Compartment changes are not brain availability; no insomnia endpoint or glycinate superiority was tested.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC3.
[49] Enhancement of learning and memory by elevating brain magnesium.
Shows: Threonate increases rat brain magnesium and enhances memory/synaptic physiology.
Does not show: Memory and plasticity are not human insomnia; central-model findings do not predict every clinical sleep measure.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC4.
[50] Association of magnesium intake with sleep duration and sleep quality: findings from the CARDIA study.
Shows: CARDIA intake associates with less short sleep and borderline sleep-quality improvement.
Does not show: Diet/lifestyle confounding, self-report and depression interaction remain; no randomized salt-specific efficacy.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC2, SC4.
[51] Effect of short-term magnesium supplementation on anxiety, depression and sleep quality in patients after open-heart surgery.
Shows: Post-heart-surgery magnesium versus routine care suggests lower PSQI/anxiety scores.
Does not show: Five days is outside the registered 2–24-week horizon; no blinded placebo and postoperative recovery confound interpretation.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC2, SC4.
[52] 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.
Shows: Melatonin/Mg coffee-pod crossover improves several sleep measures over placebo.
Does not show: No single-ingredient arms and final average PSQI remains poor; combination efficacy does not establish magnesium mediation.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC2, SC4.
[53] NMDA/glutamate mechanism of magnesium-induced anxiolytic-like behavior in mice.
Shows: NMDA/glycine-site ligand manipulations enhance or antagonize magnesium-related mouse anxiety-like behavior.
Does not show: Elevated-plus-maze and nonclinical exposure are not oral human insomnia; glycine-site binding is not glycinate comparative efficacy.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC4.
[54] Magnesium and Zinc Are Associated with Sleep Quality in Saudi Adults: Evidence from a Cross-Sectional Study.
Shows: Saudi cross-sectional data associate serum/dietary magnesium with poor PSQI quality.
Does not show: Confounding and model variation remain; nutrient association is not a causal deficiency-response trial.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC2, SC4.
[55] Association between magnesium deficiency score and sleep quality in adults: A population-based cross-sectional study.
Shows: NHANES depletion-score analysis associates sleep trouble/apnea with a higher score.
Does not show: No association with insomnia or insufficient sleep; renal-risk proxies and reverse causation remain.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC2, SC4.
[56] Dietary magnesium restriction reduces amygdala-hypothalamic GluN1 receptor complex levels in mice.
Shows: Dietary restriction alters mouse NMDA-complex proteins alongside depression-related behavior.
Does not show: Paroxetine restores behavior without protein restoration; correlation is not necessity. Author-name correction 24965486 is attached.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. Erratum in: PMID 24965486. Subclaims: SC4.
[57] Structural insights into the diverse actions of magnesium on NMDA receptors.
Shows: Structural/mutational work identifies magnesium-specific NMDA sites for block, potentiation and inhibition.
Does not show: Engineered receptors are not human sleep; these diverse effects are not a simple universal sedative mechanism.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC1, SC4.
[58] Magnesium supplementation as an adjunct to fluoxetine therapy for depression.
Shows: Magnesium added to fluoxetine produces a larger HDRS change including insomnia items.
Does not show: Alternating allocation is not concealed randomization; no blinded magnesium placebo and a depression composite is not a sleep primary.
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC2, SC4.
[59] A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Therapeutic Effect of Magnesium-L-Threonate Supplementation for Persistent Pain After Breast Cancer Surgery.
Shows: Twelve-week randomized magnesium-threonate trial in 109 breast-surgery patients finds no between-arm PSQI mood cognition or pain benefit
Does not show: Pain-prevention cohort was not enrolled for primary insomnia; secondary sleep endpoint and postoperative context limit transfer to poor-sleep eligibility
Access/status: Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed. none_found. Subclaims: SC2, SC3, SC4.
[60] Magnesium Supplementation for Sleep in Adults: A Systematic Review of Randomized Controlled Trials.
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.
Does not show: A secondary synthesis earns no primary-report credit; it shares authors with refs 3 and 19.
Access/status: PubMed abstract and metadata checked on 2026-11-02 (adversarial pass). Context only. Subclaims: SC2.
[61] Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis.
Shows: A meta-analysis of three small older-adult RCTs reports shorter sleep-onset latency on low to very-low-quality evidence.
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.
Access/status: PubMed abstract and metadata checked on 2026-11-02 (adversarial pass). Context only. Subclaims: SC2.
[62] Effect of magnesium supplementation in improving hyperandrogenism, hirsutism, and sleep quality in women with polycystic ovary syndrome: A randomized, placebo-controlled clinical trial.
Shows: A ten-week magnesium oxide versus placebo trial in women with PCOS finds no sleep-quality effect.
Does not show: Participants were not enrolled for poor sleep; this is a population boundary, not a direct test of the registered claim.
Access/status: PubMed abstract and metadata checked on 2026-11-02 (adversarial pass); outside the 59 examined primary reports. none_found. Subclaims: SC2.