A reference work, not a recommendation to use: this profile describes mechanism and evidence and does not replace medical advice. The claims come from marketing and forums and are tested here, not endorsed.

Claims checked

  • Better sleep

    Small benefit

    Sleep · healthy (self-reported poor sleep) · Human, randomised

    One large RCT with 155 adults: ISI decrease somewhat greater than under placebo (p = 0.049, d = 0.2), sleep quality and other endpoints without difference [7]. No objective sleep measurement, no comparison with other forms of magnesium. A meta-analysis of three small RCTs in older adults with insomnia (low to very low quality of evidence) used oxide and citrate and does not count toward the rating [12].

  • Stress ↓, calming

    No benefit

    Mood & stress · healthy (self-reported poor sleep) · Human, randomised

    In the glycinate RCT, questionnaires on stress and mood (secondary endpoints) did not differ from placebo [7]. A systematic review with weak signs of less anxiety in anxiety-prone groups pools other forms of magnesium and does not count toward the rating [11]. The addition “through glycine” is tested as a separate promise.

  • The glycine adds a calming, sleep-promoting effect (better than other forms of magnesium)

    Not studied

    Sleep · healthy · No data

    No study has compared glycinate with another form of magnesium with the same magnesium content; the glycinate RCT had only placebo as a comparison [7]. The glycine content is about half the amount in glycine sleep studies, which come mostly from a manufacturer group [7][8]. Split off from the earlier promise “Stress ↓, calming through glycine.”[8]

  • Fewer muscle cramps

    Single unconfirmed finding

    Muscle & performance · Patients: pregnant women with calf cramps · Human, randomised small studiesEvery study behind this level and result had fewer than 100 participants. Small studies report larger effects on average than large ones, so the result is less certain.

    One RCT with magnesium bisglycinate chelate and 80 evaluated pregnant women found fewer and milder cramps than under placebo [9]. The Cochrane review (contradictory in pregnant women, no relevant benefit in older people with nocturnal cramps) pools different forms of magnesium and does not count toward the rating [10].

small studies: Every study behind this level and result had fewer than 100 participants. Small studies report larger effects on average than large ones, so the result is less certain.

Mechanism of action

Evidence map: Magnesium glycinate

Each line stands for a published finding; line style and color show where it comes from. The filter hides weaker evidence levels. Sources: see references.

After potassium, magnesium is the second most abundant cation in cells and is involved in more than 600 enzymatic reactions; the gut, kidney and bone regulate its levels [1]. In nerve cells, Mg2+ blocks the NMDA receptor channel in a voltage-dependent manner: at rest it interrupts the ion current, and on depolarization the block is relieved [2]. This underlies the idea that magnesium protects against excessive excitation; a review sees the strongest evidence in migraine and depression, with thinner data for other neurological questions [3]. These effects belong to magnesium in general, not specifically to the glycinate form.

In magnesium bisglycinate, magnesium is bound to two glycine molecules. The only isotope study found in humans compared it with magnesium oxide in a double-blind crossover design in 12 people after removal of parts of the small intestine (ileal resection): overall, the same amount was absorbed from both forms (23.5 vs. 22.8%); only in the four people with the poorest absorption from oxide was glycinate superior (23.5 vs. 11.8%), and it was better tolerated [4]. The authors suspect that part of it is absorbed as an intact dipeptide; this has not been demonstrated in humans. A systematic review found organic forms overall more available than inorganic ones, with the absorbed fraction depending on the amount [5]. In a randomized study of 46 healthy people, an amino acid chelate and citrate raised urinary magnesium excretion after 60 days more than oxide, but serum levels were raised most by citrate [6]; the abstract does not say which amino acid ligand was in the chelate. No study directly comparing glycinate with citrate in healthy people was found.

The largest placebo-controlled study with magnesium bisglycinate (155 adults with poor sleep, 4 weeks) found a somewhat greater reduction in insomnia severity (ISI −3.9 vs. −2.3 points) with a small effect size (d = 0.2); questionnaires on stress and mood did not differ [7]. The study did not compare with another form of magnesium, so a contribution of the glycine cannot be separated out; the glycine content was about half the amount used in sleep studies with glycine alone [7]. These glycine sleep studies come mostly from a research group of the manufacturer Ajinomoto [8]. In 80 evaluated pregnant women with calf cramps, more women under bisglycinate than under placebo achieved a halving of cramp frequency (86.0 vs. 60.5%) [9]; a Cochrane review, however, rates the studies in pregnant women as contradictory and found no relevant benefit of magnesium in older people with nocturnal cramps [10].

Synaptik serves solely to explain biochemistry and pharmacology and is not medical advice or a recommendation to take anything.

Mechanism of action only. Schematic section through an excitatory synapse, not to scale: of the NMDA receptor (a tetramer of two GluN1 and two GluN2B subunits) the two rear subunits are drawn and the front two are cut away to expose the pore. The sequence repeats in three beats: glutamate with depolarisation, glutamate alone, depolarisation alone. Particle numbers, timings, openings and the Ca²⁺ influx are outputs of this figure's model, not measurements, and are not shown as numbers. The numbers in the bottom-right readout come from laboratory and animal experiments and are not comparable with each other.
Drug
View

Glutamate  Glycine / D-serine  Mg²⁺  Ca²⁺  Na⁺  K⁺  red = drug, shown in the scene as a miniature skeletal formula · shapes as in the figure

Magnesium glycinate supplies Mg²⁺, the natural pore blocker [3], and glycine, the co-agonist at GluN1 [16]. Both sites are highlighted; the model stays at baseline because whether the salt raises magnesium or glycine at the receptor in the brain has not been studied. The effect at the channel belongs to magnesium in general, not to the glycinate form.

Tap or focus a labelled part for a one-line explanation.

Also acting here, not drawn

  • CX-717: ampakine; NMDA effect only indirect, no action on the receptor itself
  • Huperzine A: NMDA inhibition only in a review by the developers’ group, without a binding site
  • L-theanine: only very weak binding to glutamate receptors
  • Phenylpiracetam: no displacement of ligands at NMDA receptors
  • Piracetam: only changed receptor numbers (mice)
  • Selank: only changed numbers of binding sites (mice)

What the figure shows, and how sure we are

Mechanism-of-action explainer only. Not medical advice, and no statement about benefit, risk, amount or use. Ketamine, esketamine, memantine and atomoxetine are medicines; most of the other substances have been studied at the NMDA receptor only in the lab or in animals.

What was simplified. One receptor stands for many; sizes, cleft width, membrane thickness, ion numbers and all timings are illustrative. The rear two subunits of a GluN1-GluN2B receptor are drawn; NMDA receptors with GluN2A and other subunits, and the AMPA receptors that help produce the depolarisation, are left out. The positions of Mg²⁺ in the filter and of ketamine in the vestibule follow [2] and [8]; for atomoxetine and crocetin the position in the pore has not been determined, and for agmatine the binding site at all. The numbers in [3], [4], [9], [11] to [18], [20] to [22], [24] and [26] to [32] come from the Synaptik drug profiles, where they were checked against the abstracts; [1], [5] to [8], [19], [23] and [25] were checked against their PubMed abstracts (25 Oct 2026), and the statements taken from the review [2] (M1, M3, M4 and the pore loop M2, M3 as the gate, the Mg²⁺ site at the tip of M2, Na⁺, K⁺ and Ca²⁺ as charge carriers, kinases and scaffold proteins at the C-terminal domain of GluN2B) against the relevant sections of the full text.

If medicines, alcohol or other substances are causing problems, a GP or a local addiction counselling service can help.

Assigned to the site of action GABA-A receptor (benzodiazepine, GABA and membrane sites), GABA-B with GIRK, glycine receptor; not drawn in its figure: concerns only the glycine part; the only evidence is a review on glycine.

Assigned to the site of action Enterocyte brush border (microvilli with enzymes and transporters); not drawn in its figure: uptake via the dipeptide route is only presumed in the profile.

Targets

TargetTypeActionKey dataEvidence
NMDA receptor, channel poreIon channelInhibitorvoltage-dependent block by Mg2+ (mouse neurons, patch clamp) Laboratory[2]
NMDA receptor, glycine binding site (glycine moiety)ReceptorAgonistco-agonist Laboratory[8]
Glycine receptor (chloride channel, glycine moiety)Ion channelAgonist Laboratory[8]
Dipeptide transport in the small intestine (suspected)TransporterBindingHypothesis from the earlier isotope peak Human, non-randomised[4]

Effect profile

Which signaling systems the compound affects according to current data. ↑ enhanced, ↓ dampened, ≈ modulated, ○ no effect; dots = evidence level.

  • Dopamineno data
  • Noradrenalineno data
  • Serotoninno data
  • Acetylcholineno data
  • Glutamate · AMPAno data
  • Glutamate · NMDAmodulated · Mg2+ blocks the NMDA channel (laboratory), glycine is a co-agonist at the same receptor; net effect in the brain after intake unknown[2][8]
  • GABAno data
  • Histamineno data
  • Orexinno data
  • Adenosineno data
  • Opioidsno data
  • Melatoninno data
  • Neurotrophinsno data
  • Blood flowno data
  • Nitric oxideno data
  • Energy metabolismno data
  • Insulin · glucoseno data
  • Inflammation · oxidativeno data
  • Stress axisno data
  • Testosterone axisno data
  • Endocannabinoidsno data
  • Autophagy · senescenceno data
  • Immune systemno data
  • Lipid metabolismno data
  • Coagulation · fibrinolysisno data
  • Methylationno data

Routes of administration and bioavailability

How much of a compound reaches the blood or target tissue depends on the route into the body and on the dosage form. All routes of administration explained

  • Oral (swallowed) · Bisglycinate (chelate)

    ≈ 23.5% (isotope magnesium-26, patients after ileal resection; oxide 22.8%)

    Double-blind crossover study with 12 patients: same overall absorption as oxide, earlier peak and larger area under the isotope curve, better tolerated; benefit only in the four people with the poorest oxide absorption [4]. Data in healthy people are lacking.

    Human, randomised

  • Oral (swallowed) · Amino acid chelate (ligand not stated)

    In 46 healthy people, higher urinary excretion than under oxide after 60 days, but serum level lower than under citrate [6]. According to a systematic review, organic forms are overall more available than inorganic ones [5].

    Human, randomised

Human studies

  • Sleep in adults with poor sleep

    RCT, double-blind, placebo-controlled · healthy (self-reported poor sleep) · n = 155 · 4 weeks

    Measured: Insomnia Severity Index (ISI)

    Result: ISI −3.9 vs. −2.3 points (p = 0.049, d = 0.2); other psychological endpoints without difference.[7]

    Human, randomised

  • Calf cramps in pregnancy

    RCT, double-blind, placebo-controlled · Patients: pregnant women (weeks 14–34) with calf cramps · n = 86 · 4 weeks

    Measured: Halving of cramp frequency and intensity

    Result: Halving of frequency in 86.0 vs. 60.5% (p = 0.007), of intensity in 69.8 vs. 48.8% (p = 0.048); 80 evaluated.[9]

    Human, randomised

  • Isotope study glycinate vs. oxide

    RCT, double-blind, crossover · Patients: after ileal resection · n = 12 · single doses

    Measured: Absorption of the isotope magnesium-26

    Result: 23.5 vs. 22.8% overall; in four people with poor absorption 23.5 vs. 11.8% (p < 0.05).[4]

    Human, randomised

  • Comparison of amino acid chelate, citrate, oxide

    RCT, double-blind, placebo-controlled, parallel · healthy · n = 46 · 60 days

    Measured: Magnesium in urine, serum, erythrocytes, saliva

    Result: Organic forms higher urinary excretion than oxide (p = 0.033); highest serum level under citrate.[6]

    Human, randomised

Risks and warnings

  • Hypermagnesemia in impaired kidney function

    The kidney regulates the magnesium balance [1]. In a hospital cohort receiving magnesium oxide, 23% had an elevated magnesium concentration; risk factors were impaired kidney function, larger amounts and longer use [13]. Data specifically on glycinate are lacking; that the principle applies to all magnesium salts is an inference.

    Human, non-randomised

  • Gastrointestinal complaints

    In the Cochrane analysis, oral magnesium mainly caused gastrointestinal complaints such as diarrhea [10]. In the glycinate studies, side effects were not more frequent than under placebo [7][9]; in comparison with oxide, glycinate was better tolerated (12 patients) [4].

    Human, randomised

Interactions

  • Tetracyclines and fluoroquinolones: Polyvalent cations such as Mg2+ form poorly soluble chelates with these antibiotics and reduce their absorption; clinically shown for magnesium-containing antacids [14]. Not studied specifically for glycinate.
  • Bisphosphonates: Same chelate mechanism according to prescribing information, quantitative data lacking [14].

Fact check: common claims

  • not supported

    “Magnesium glycinate is absorbed better than all other forms”

    The only isotope study in humans found no overall difference from oxide, an advantage only in four patients with impaired absorption [4]. A comparison with citrate in healthy people is lacking; an unspecified amino acid chelate reached lower serum levels than citrate [6].

  • not supported

    “The glycine in glycinate adds a calming, sleep-promoting effect”

    No experiment has compared glycinate with another form of magnesium [7]. The glycine content is below the amounts in the glycine sleep studies, which almost all come from one manufacturer group [7][8].

  • partly supported

    “Glycinate is gentle on the stomach and barely laxative”

    Better tolerated than oxide in 12 patients [4]; in two RCTs no more frequent side effects than under placebo [7][9]. A direct comparison with citrate on tolerability is lacking.

  • partly supported

    “Glycinate is absorbed as an intact dipeptide”

    The authors of the isotope study infer this from laboratory data and the earlier isotope peak; it was not measured directly in humans [4].

Pharmacokinetics

Absorption
By mouth. In patients after ileal resection, same total absorption as oxide, isotope peak on average 3.2 hours earlier [4].
Half-life
Cannot meaningfully be stated for an endogenous mineral; not verified.
Metabolism
Breaks down into magnesium and glycine; how much is absorbed as an intact chelate is unresolved in humans [4]. The kidney regulates excretion [1].
Entry into the brain
No evidence that glycinate brings more magnesium into the brain than other forms.

Legal status

Germany
Not verified.
EU
Annex II Part B of Directive 2002/46/EC (“magnesium bisglycinate”); thus authorized as a magnesium source in food supplements [15].
USA
Not verified.

Authorised EU health claims

EU claim authorised An authorised health claim is a legal statement about the nutrient, not about this form, and not a level of evidence. The evidence for this form is reported separately under the main claim and in the human studies.

  • “contributes to normal psychological function”

    Nutrient
    Magnesium
    Legal basis
    Regulation (EU) No 432/2012[16]
    Reading
    legally permitted for magnesium in general, no statement about magnesium glycinate; for stress and mood with glycinate, see the promise “Stress ↓, calming” (no benefit in one RCT)
  • “contributes to normal muscle function”

    Nutrient
    Magnesium
    Legal basis
    Regulation (EU) No 432/2012[16]
    Reading
    legally permitted for magnesium in general, no statement about magnesium glycinate; for calf cramps, see the promise “Fewer muscle cramps” (tested only in pregnant women)

Related compounds

Open questions

  • Is glycinate more available than citrate in healthy people, measured by urinary excretion after the stores are saturated?
  • Does the glycine measurably contribute to the sleep effect when glycinate is tested against another form of magnesium with the same magnesium content?
  • Do mainly people with low magnesium intake benefit, as an exploratory analysis suggests?

References

  1. de Baaij JH, Hoenderop JG, Bindels RJ. Magnesium in man: implications for health and disease. Physiol Rev. 2015;95(1):1–46. doi:10.1152/physrev.00012.2014 · PubMed
  2. Nowak L, Bregestovski P, Ascher P, Herbet A, Prochiantz A. Magnesium gates glutamate-activated channels in mouse central neurones. Nature. 1984;307(5950):462–5. doi:10.1038/307462a0 · PubMed
  3. Kirkland AE, Sarlo GL, Holton KF. The role of magnesium in neurological disorders. Nutrients. 2018;10(6):730. doi:10.3390/nu10060730 · PubMed
  4. Schuette SA, Lashner BA, Janghorbani M. Bioavailability of magnesium diglycinate vs magnesium oxide in patients with ileal resection. JPEN J Parenter Enteral Nutr. 1994;18(5):430–5. doi:10.1177/0148607194018005430 · PubMed
  5. Pardo MR, Garicano Vilar E, San Mauro Martín I, Camina Martín MA. Bioavailability of magnesium food supplements: a systematic review. Nutrition. 2021;89:111294. doi:10.1016/j.nut.2021.111294 · PubMed
  6. Walker AF, Marakis G, Christie S, Byng M. Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study. Magnes Res. 2003;16(3):183–91. PubMed
  7. Schuster J, Cycelskij I, Lopresti A, Hahn A. Magnesium bisglycinate supplementation in healthy adults reporting poor sleep: a randomized, placebo-controlled trial. Nat Sci Sleep. 2025;17:2027–40. doi:10.2147/NSS.S524348 · PubMed
  8. Bannai M, Kawai N. New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. J Pharmacol Sci. 2012;118(2):145–8. doi:10.1254/jphs.11r04fm · PubMed
  9. Supakatisant C, Phupong V. Oral magnesium for relief in pregnancy-induced leg cramps: a randomised controlled trial. Matern Child Nutr. 2015;11(2):139–45. doi:10.1111/j.1740-8709.2012.00440.x · PubMed
  10. Garrison SR, Korownyk CS, Kolber MR, Allan GM, Musini VM, Sekhon RK, et al. Magnesium for skeletal muscle cramps. Cochrane Database Syst Rev. 2020;9(9):CD009402. doi:10.1002/14651858.CD009402.pub3 · PubMed
  11. Boyle NB, Lawton C, Dye L. The effects of magnesium supplementation on subjective anxiety and stress – a systematic review. Nutrients. 2017;9(5):429. doi:10.3390/nu9050429 · PubMed
  12. Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a systematic review & meta-analysis. BMC Complement Med Ther. 2021;21(1):125. doi:10.1186/s12906-021-03297-z · PubMed
  13. Wakai E, Ikemura K, Sugimoto H, Iwamoto T, Okuda M. Risk factors for the development of hypermagnesemia in patients prescribed magnesium oxide: a retrospective cohort study. J Pharm Health Care Sci. 2019;5:4. doi:10.1186/s40780-019-0133-7 · PubMed
  14. Ogawa R, Echizen H. Clinically significant drug interactions with antacids: an update. Drugs. 2011;71(14):1839–64. doi:10.2165/11593990-000000000-00000 · PubMed
  15. Richtlinie 2002/46/EG des Europäischen Parlaments und des Rates vom 10. Juni 2002 zur Angleichung der Rechtsvorschriften der Mitgliedstaaten über Nahrungsergänzungsmittel. ABl. L 183 vom 12.7.2002, S. 51. Konsolidierte Fassung vom 26.11.2025 (CELEX 02002L0046-20251126).
  16. Verordnung (EU) Nr. 432/2012 der Kommission vom 16. Mai 2012 zur Festlegung einer Liste zulässiger anderer gesundheitsbezogener Angaben über Lebensmittel als Angaben über die Reduzierung eines Krankheitsrisikos sowie die Entwicklung und die Gesundheit von Kindern. ABl. L 136 vom 25.5.2012, S. 1. Konsolidierte Fassung vom 20.08.2025 (CELEX 02012R0432-20250820).
How this profile was checked

Last reviewed: 2026-10-24. All sources with a DOI or PMID were resolved automatically via Crossref or doi.org and PubMed.

Translated from the German profile (version of 2026-10-24); translation checked on 2026-10-26.

Checked

  • DOIs via Crossref and PMIDs via PubMed (checking script).
  • Checked against the abstracts: 12 patients, 23.5 vs. 22.8%, subgroup 23.5 vs. 11.8%, peak 3.2 h earlier [4]; 14 studies, organic better than inorganic, depending on the amount [5]; 46 healthy people, 60 days, p = 0.033, citrate highest serum level [6]; 155 people, ISI −3.9 vs. −2.3, p = 0.049, d = 0.2 [7]; 86 pregnant women, 80 evaluated, 86.0 vs. 60.5% and 69.8 vs. 48.8% [9]; Cochrane: 11 studies, no benefit in idiopathic cramps, pregnancy contradictory [10]; 18 studies, weak signs in anxiety [11]; 23% hypermagnesemia, risk factors [13]; chelate interactions [14].
  • In the full text of [7]: product from Biogena, glycine content about half the amount cited in glycine sleep studies; no comparison with another form of magnesium.
  • Ajinomoto affiliation in [8] checked against the abstract.
  • ClinicalTrials.gov: 20 hits for “magnesium glycinate,” 6 hits for “magnesium bisglycinate” (October 23, 2026).
  • October 24, 2026 (rule decisions K1–K8): Annex II Part B of Directive 2002/46/EC (CELEX 02002L0046-20251126, Cellar XHTML) contains “magnesium bisglycinate.” Wording of the two magnesium claims in Regulation (EU) No 432/2012, base version (CELEX 32012R0432) and consolidated version of August 20, 2025 (CELEX 02012R0432-20250820), found unchanged.
  • Form-specific check (K2): abstract [9] names “magnesium bisglycinate chelate” (41 vs. 39 evaluated, no conflicts of interest); [7] bisglycinate according to the full text. Meta-analysis [12], Cochrane review [10] and anxiety review [11] mix forms and do not count toward the ratings.
  • Precision flags (m004, implemented by Claude on October 26, 2026, for confirmation by Tilman): “Fewer muscle cramps” → “kleine_studien”: [9] 86 included, 80 evaluated (abstract); [10] does not count according to the rationale.

Not verified

  • Legal status in Germany and the US not checked in registers.
  • Funding of the sleep study [7] not clearly found in the full text (product from Biogena).
  • Which amino acid ligand was used in the chelate of [6] (full text not accessible).

No dosages, no sources of supply. This information does not replace medical advice.

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