{
  "cutoff": "2026-10-12",
  "note": "Selected publication milestones, not an exhaustive history or discovery priority claim.",
  "milestones": [
    {
      "pmid": "2407766",
      "year": "1990",
      "title": "Magnesium bioavailability from magnesium citrate and magnesium oxide.",
      "doi": "10.1080/07315724.1990.10720349",
      "url": "https://pubmed.ncbi.nlm.nih.gov/2407766/",
      "interpretation": "Citrate-versus-oxide solubility and human loading illustrate why availability and clinical sleep effects are different."
    },
    {
      "pmid": "8232845",
      "year": "1993",
      "title": "Effects of a magnesium-deficient diet on sleep organization in rats.",
      "doi": "10.1159/000118988",
      "url": "https://pubmed.ncbi.nlm.nih.gov/8232845/",
      "interpretation": "Rat dietary deficiency and repletion show reversible sleep/ECoG disruption in that nutritional context."
    },
    {
      "pmid": "12163983",
      "year": "2002",
      "title": "Oral Mg(2+) supplementation reverses age-related neuroendocrine and sleep EEG changes in humans.",
      "doi": "10.1055/s-2002-33195",
      "url": "https://pubmed.ncbi.nlm.nih.gov/12163983/",
      "interpretation": "Small elderly crossover measures oral magnesium effects with overnight EEG and endocrine sampling."
    },
    {
      "pmid": "20152124",
      "year": "2010",
      "title": "Enhancement of learning and memory by elevating brain magnesium.",
      "doi": "10.1016/j.neuron.2009.12.026",
      "url": "https://pubmed.ncbi.nlm.nih.gov/20152124/",
      "interpretation": "Rodent threonate central-exposure/synaptic work supports neural plausibility, not clinical insomnia efficacy."
    },
    {
      "pmid": "21199787",
      "year": "2010",
      "title": "Magnesium supplementation improves indicators of low magnesium status and inflammatory stress in adults older than 51 years with poor quality sleep.",
      "doi": "10.1684/mrh.2010.0220",
      "url": "https://pubmed.ncbi.nlm.nih.gov/21199787/",
      "interpretation": "Citrate poor-sleep trial finds equal globalPSQI improvement despite some status/inflammation differences."
    },
    {
      "pmid": "23853635",
      "year": "2012",
      "title": "The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial.",
      "doi": "",
      "url": "https://pubmed.ncbi.nlm.nih.gov/23853635/",
      "interpretation": "Older-adult oxide trial reports selected positive symptoms and total-sleep-time null."
    },
    {
      "pmid": "30562392",
      "year": "2018",
      "title": "Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial.",
      "doi": "10.1371/journal.pone.0208454",
      "url": "https://pubmed.ncbi.nlm.nih.gov/30562392/",
      "interpretation": "StressMg+B6versusMg trial illustrates the need for a magnesium-free comparator."
    },
    {
      "pmid": "39252819",
      "year": "2024",
      "title": "Magnesium-L-threonate improves sleep quality and daytime functioning in adults with self-reported sleep problems: A randomized controlled trial.",
      "doi": "10.1016/j.sleepx.2024.100121",
      "url": "https://pubmed.ncbi.nlm.nih.gov/39252819/",
      "interpretation": "Threonate21-day trial reports mixed questionnaire and consumer wearable outcomes; subsequent correction matters."
    },
    {
      "pmid": "40918053",
      "year": "2025",
      "title": "Magnesium Bisglycinate Supplementation in Healthy Adults Reporting Poor Sleep: A Randomized, Placebo-Controlled Trial.",
      "doi": "10.2147/NSS.S524348",
      "url": "https://pubmed.ncbi.nlm.nih.gov/40918053/",
      "interpretation": "Prospective bisglycinate4-week trial finds a small primaryISI effect with ligand exposure unpartitioned."
    },
    {
      "pmid": "41601871",
      "year": "2025",
      "title": "The effects of magnesium L-threonate (Magtein®) on cognitive performance and sleep quality in adults: a randomised, double-blind, placebo-controlled trial.",
      "doi": "10.3389/fnut.2025.1729164",
      "url": "https://pubmed.ncbi.nlm.nih.gov/41601871/",
      "interpretation": "Newer six-week threonate trial retains sleep-disturbance/restorative/objective nulls alongside impairment benefit."
    },
    {
      "pmid": "37520407",
      "year": "2023",
      "title": "A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Therapeutic Effect of Magnesium-L-Threonate Supplementation for Persistent Pain After Breast Cancer Surgery.",
      "doi": "10.2147/BCTT.S413435",
      "url": "https://pubmed.ncbi.nlm.nih.gov/37520407/",
      "interpretation": "A postoperative placebo-controlled threonate study finds null secondary sleep, mood and cognition outcomes; its pain-prevention population is distinguished from insomnia enrollment."
    }
  ],
  "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."
  ],
  "decisive_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 over8–12weeks, with allocation guesses, adherence and missingness sensitivity."
}