Magnesium Glycinate for Anxiety

Table of Contents

1. Magnesium and Anxiety: What the Evidence Shows
2. Proposed Mechanisms: NMDA, GABA-A, HPA Axis, Calcium
3. How Common Low Magnesium Intake Is
4. Magnesium Forms Compared: What Absorption Studies Show
5. What Is Claimed for the Glycinate Form
6. Clinical Evidence for Anxiety and Depression
7. Doses Used in Trials and Reference Intakes
8. Tests of Magnesium Status
9. Combinations With Other Supplements
10. Safety and Drug Interactions
11. Key Research Papers
12. Connections
13. Featured Videos

Magnesium and Anxiety: What the Evidence Shows

Three kinds of evidence connect magnesium and anxiety, and they differ in strength:

• Population studies — in the Hordaland Health Study of 5,708 community-dwelling adults in Western Norway, aged 46–49 or 70–74, higher energy-adjusted magnesium intake was associated with lower depression scores; the association was attenuated after adjustment for socioeconomic and lifestyle factors but remained statistically significant. The inverse relationship between magnesium intake and anxiety was weaker and not statistically significant in the fully adjusted models (Jacka 2009). A cross-sectional study shows association, not cause.
• Animal studies — mice fed a magnesium-deficient diet showed enhanced anxiety-related behaviour in a battery of established anxiety tests, together with increased transcription of corticotropin-releasing hormone in the paraventricular hypothalamic nucleus and raised plasma ACTH. The anxiety-like behaviour responded to chronic desipramine and acute diazepam, and chronic desipramine reversed the stress-axis abnormalities (Sartori 2012). In another mouse study, the anxiolytic-like effect of magnesium in the elevated plus maze was blocked by flumazenil, a benzodiazepine-receptor antagonist (Poleszak 2008). These are animal results.
• Supplementation trials in people — a 2017 systematic review of the effects of magnesium supplementation on subjective anxiety and stress included 18 studies, all in groups with an existing vulnerability to anxiety: mildly anxious people, premenstrual syndrome, postpartum women and people with hypertension. Four of eight studies in anxious samples, four of seven in premenstrual samples and one of two in hypertensive samples reported positive effects on subjective anxiety; magnesium had no effect on postpartum anxiety, and no study used a validated measure of stress. The authors concluded that the evidence is suggestive of a beneficial effect in anxiety-vulnerable samples but that its quality is poor, and called for well-designed randomised trials (Boyle 2017). The review did not single out the glycinate form. An open-label trial of magnesium chloride for depression also measured anxiety scores; it is described below (Tarleton 2017).

A 2020 review describes the relationship between magnesium and stress as a two-way "vicious circle": stress could increase magnesium loss, and magnesium deficiency could enhance the body's susceptibility to stress (Pickering 2020). Several of its authors were employees of a consumer-healthcare company. A 2011 review similarly describes stress and low blood magnesium as potentiating each other's negative effects, while noting that the role of magnesium in stress-related conditions is unclear (Cuciureanu 2011).

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Proposed Mechanisms: NMDA, GABA-A, HPA Axis, Calcium

The mechanisms below are those proposed in reviews and laboratory research. How strongly oral magnesium supplements engage them in people has not been measured in the studies cited here.

1. NMDA receptor — at resting membrane potential, a magnesium ion sits in the channel of the NMDA glutamate receptor and blocks calcium entry; the block is voltage-dependent and lifts when the neuron is depolarised. Magnesium is described as a natural NMDA antagonist (Abbasi 2012), and a 2018 review describes magnesium's protective role against excessive excitation that can lead to neuronal cell death (excitotoxicity), reporting strong data for a role of magnesium in migraine and depression and emerging data for chronic pain, anxiety and stroke (Kirkland 2018). A 2010 review-and-hypothesis paper proposes that magnesium deficiency biases NMDA-coupled calcium channels towards opening, which may appear as major depression (Eby 2010); this is a hypothesis.
2. GABA-A receptor — magnesium is described as having GABA-agonist activity (Abbasi 2012). The evidence for an interaction with benzodiazepine/GABA-A receptors comes from mouse studies such as the flumazenil experiment above (Poleszak 2008).
3. HPA stress axis — in magnesium-deficient mice, corticotropin-releasing hormone transcription and plasma ACTH were raised (Sartori 2012). A 2020 review states that magnesium plays an inhibitory key role in the regulation and neurotransmission of the normal stress response (Pickering 2020). In one human trial, in 46 elderly people with primary insomnia, 500 mg elemental magnesium a day as magnesium oxide for 8 weeks lowered serum cortisol compared with placebo (Abbasi 2012).
4. Calcium and nerve–muscle excitability — magnesium is involved in nerve transmission and neuromuscular conduction (Kirkland 2018), and an imbalance in magnesium status, mainly low magnesium, can result in neuromuscular, cardiac or nervous disorders (Jahnen-Dechent 2012). A 2011 review lists the glutamatergic, serotonergic and adrenergic neurotransmitter systems and several neurohormones as potential routes for magnesium's action in stress (Cuciureanu 2011).

Glycine, the amino acid in magnesium glycinate, acts in both inhibitory and excitatory neurotransmission, through glycine receptors and as a co-agonist at NMDA receptors (Bannai and Kawai 2012). Whether the glycine in a magnesium glycinate supplement adds to any effect of the magnesium has not been tested in the trials cited here.

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How Common Low Magnesium Intake Is

In the United States, a 2012 review reported that almost half (48%) of the population consumed less than the required amount of magnesium from food in 2005–2006, down from 56% in 2001–2002 (Rosanoff 2012). A 2025 review estimates that about 2.4 billion people, roughly 31% of the world's population, fail to meet recommended magnesium intake levels (Zhang 2025). The US recommended dietary allowance (RDA) is about 420 mg a day for adult men and 320 mg a day for adult women (Zhang 2025).

Factors described in the reviews include:

• Diet and food processing — the 2025 review lists modern dietary patterns low in whole grains and vegetables, soil nutrient depletion from intensive agriculture, losses in food processing, ageing populations, chronic diseases and socioeconomic disparities (Zhang 2025). Whole grains, legumes, leafy greens, nuts and seeds are the main dietary sources of magnesium.
• Stress — the "vicious circle" review proposes that stress increases magnesium loss (Pickering 2020).
• Medicines — low blood magnesium can be a consequence of certain drugs, including diuretics, epidermal growth factor receptor inhibitors, calcineurin inhibitors and proton pump inhibitors (de Baaij 2015).

Serum magnesium does not reflect the magnesium inside cells, which makes up more than 99% of total body magnesium, so low status can go undetected by a standard blood test (DiNicolantonio 2018). The tests are described below.

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Magnesium Forms Compared: What Absorption Studies Show

Magnesium supplements differ in how much elemental magnesium they carry and in how well they dissolve. A 2019 study concluded that a supplement's solubility is of greater relevance for absorption than its elemental magnesium loading: inorganic salts such as oxide carry a lot of magnesium but dissolve poorly, while organic salts dissolve well but carry less (Blancquaert 2019). The human absorption studies measured different things and are not on one scale.

Widely circulated single-number absorption percentages for each magnesium form were not found in these studies, and none of them measured magnesium glycinate alongside all the other forms. Supplement labels in the US state the elemental magnesium content (for example "Magnesium (as magnesium bisglycinate) ... mg"), not the weight of the whole compound; because glycine makes up most of the weight of magnesium bisglycinate, the compound carries much less magnesium per gram than magnesium oxide. The studies are described in detail on the Magnesium Glycinate Bioavailability page in the Minerals section.

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What Is Claimed for the Glycinate Form

Magnesium glycinate (magnesium bisglycinate) is one Mg²⁺ ion bound by two glycine molecules, each forming a ring with the metal. What is claimed for the form, and what the studies show:

1. Absorption through amino-acid transporters — supplement marketing often claims that the chelate is absorbed intact through amino-acid transporters and is protected from stomach acid. The authors of the one human isotope trial concluded that "some portion" of magnesium diglycinate is absorbed intact, probably through a dipeptide transport pathway (Schuette 1994); how large that portion is in people has not been measured. Claims that the chelate is protected from phytates and oxalates, or absorbed equally well regardless of meal composition or stomach acid, were not found in the studies cited here.
2. Gut tolerability — the isotope trial found the chelate better tolerated than oxide by all patients (Schuette 1994). Diarrhoea is a known effect of oral magnesium in general, and magnesium citrate and oxide are both used as laxatives. No large trial measuring side-effect rates specifically for magnesium glycinate was found for this page.
3. The glycine itself — glycine acts as an inhibitory neurotransmitter through glycine receptors (Bannai and Kawai 2012). Glycine on its own has been studied for sleep in small trials from an amino-acid manufacturer's research group: a review by that group reports that glycine taken before bedtime improved subjective sleep quality in people with insomniac tendencies (Bannai and Kawai 2012), and in one of their trials 3 g of glycine before bed reduced next-day fatigue in healthy volunteers after three nights of restricted sleep (Bannai 2012). These studies tested glycine, not magnesium glycinate, and the amount of glycine in a magnesium glycinate supplement depends on the product.

Whether magnesium and glycine taken together as magnesium glycinate produce a greater effect on anxiety than either alone has not been tested in the trials cited here.

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Clinical Evidence for Anxiety and Depression

The 2017 systematic review described above remains the main summary of magnesium trials for anxiety: suggestive of a benefit in anxiety-vulnerable groups, with evidence of poor quality (Boyle 2017). Individual studies:

• Tarleton 2017 (PLoS ONE) — an open-label, blocked, randomised, crossover trial in primary care clinics in 126 adults with mild-to-moderate depressive symptoms (PHQ-9 scores of 5–19); 112 provided analysable data. Six weeks of 248 mg elemental magnesium a day as magnesium chloride were compared with six weeks of no treatment. Magnesium gave a net improvement of −6.0 points on the PHQ-9 depression score (CI −7.9 to −4.2) and −4.5 points on the GAD-7 anxiety score (CI −6.6 to −2.4); effects were observed within two weeks. Average adherence was 83% by pill count, the supplements were well tolerated, and 61% of participants reported they would use magnesium in the future. The comparison was with no treatment rather than a placebo, and participants knew which period they were in.
• Schuster 2025 (Nature and Science of Sleep) — a randomised, double-blind, placebo-controlled trial in 155 adults aged 18–65 with self-reported poor sleep, giving magnesium bisglycinate (250 mg elemental magnesium daily) or placebo. The Insomnia Severity Index fell more with magnesium from baseline to week 4 (p = 0.049); the authors described the effect size as small (Cohen's d = 0.2), indicating a modest benefit, and no significant differences were seen in other psychological outcomes. The trial used questionnaires only, and the authors called for future studies with objective sleep measurements. One author directs a contract research organisation funded by nutraceutical companies.
• De Souza 2000 (Journal of Women's Health and Gender-Based Medicine) — a randomised, double-blind, placebo-controlled crossover study in 44 women, each taking 200 mg magnesium (as magnesium oxide), 50 mg vitamin B6, both, or placebo for one menstrual cycle each. There was no overall difference between the treatments, but predefined comparisons showed a small effect of the magnesium-plus-B6 combination on anxiety-related premenstrual symptoms (p = 0.040); the authors stated that further studies are needed before general recommendations can be made.
• Islam 2013 (Biological Trace Element Research) — in 50 patients with generalized anxiety disorder and 51 healthy volunteers, serum magnesium did not differ significantly between the groups, while zinc was lower and copper, manganese and iron were higher in the patients.
• Eby 2010 (Medical Hypotheses) — a review and hypothesis on magnesium for treatment-resistant depression. It cites case reports of rapid recovery with intravenous and oral magnesium and notes that only a few modern clinical trials were found; the authors hypothesise that inadequate dietary magnesium is the main cause of treatment-resistant depression. This is a hypothesis paper, not a trial.

No trial cited here tested magnesium glycinate specifically for anxiety. The 2022 WFSBP/CANMAT taskforce found that no nutrient-based product other than N-acetylcysteine, for OCD-related disorders, had sufficient evidence in any anxiety-related disorder (Sarris 2022). Decisions about treatment belong with a clinician.

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Doses Used in Trials and Reference Intakes

Doses used in the studies on this page:

The tolerable upper intake level (UL) for magnesium from supplements, set by the Institute of Medicine (now the National Academy of Medicine), is 350 mg a day for adults; it applies to supplemental magnesium, not to magnesium in food, and in Europe the corresponding figure is 250 mg a day (Blancquaert 2019). The UL is based on diarrhoea as the effect seen at higher supplemental intakes. Several of the trial doses above exceed the UL and were given under trial supervision.

Some products sold as magnesium glycinate also contain magnesium oxide, often labelled "buffered", and the oxide then appears in the ingredient list. No published analysis of how often products labelled magnesium glycinate contain oxide, or how much, was found for this page. Decisions about supplement doses belong with a clinician.

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Tests of Magnesium Status

Measuring total serum magnesium is a feasible and affordable way to monitor changes in magnesium status, although it does not necessarily reflect total body magnesium content (Jahnen-Dechent 2012). Because serum magnesium does not reflect the magnesium inside cells, which makes up more than 99% of total body magnesium, low status can go undetected by a standard blood test (DiNicolantonio 2018).

Other measures used in research and in some clinics include:

• Red blood cell (RBC) magnesium — measures magnesium inside red blood cells.
• Ionized magnesium — the free, unbound fraction in blood.
• Magnesium loading (retention) test — urine magnesium is collected after a magnesium dose given into a vein, and the share retained is measured.
• 24-hour urine magnesium — total urinary magnesium output over a day.

A 2018 review of these tests concluded that magnesium's unique mechanism of absorption and its compartmental handling in the body make status difficult to determine, and that reliance on several popular sample assays has contributed to a great deal of confusion in the literature (Workinger 2018). No trial cited here compared anxiety outcomes of supplementing with or without testing first. Other approaches studied for anxiety, such as ashwagandha or rhodiola and L-theanine, are covered on their own pages.

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Combinations With Other Supplements

Magnesium glycinate is often sold or discussed alongside other supplements marketed for calm. What the studies cited here show about each pairing:

• Magnesium glycinate + L-theanine — no trial of this combination is cited here. For L-theanine alone, a 2020 systematic review of nine randomized controlled trials of pure L-theanine supplements concluded that 200–400 mg a day may assist in reducing stress and anxiety in people exposed to stressful conditions, and that longer-term and larger studies are needed (Williams 2020); the one trial in diagnosed generalized anxiety disorder did not find an anxiety benefit over placebo (Sarris 2019).
• Magnesium glycinate + glycine — no trial of this combination is cited here; the glycine sleep trials gave glycine itself (Bannai 2012).
• Magnesium + Vitamin B6 — in one crossover study, 200 mg magnesium (as oxide) plus 50 mg vitamin B6 for one cycle had a small effect on anxiety-related premenstrual symptoms, and the authors called for further studies (De Souza 2000). No trial of magnesium glycinate with B6 is cited here.
• Magnesium glycinate + ashwagandha — no trial of this combination is cited here. The 2022 WFSBP/CANMAT taskforce rated ashwagandha as modestly supported (++) for anxiety disorders (Sarris 2022).
• Magnesium glycinate + melatonin — no trial of this combination is cited here.

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Safety and Drug Interactions

• Kidney function — the kidneys excrete excess magnesium, so people with chronic kidney disease or significantly impaired kidney function are at risk of magnesium accumulation (hypermagnesaemia). Moderately raised serum magnesium may be associated with low blood pressure, flushing, nausea and vomiting, mostly during infusion of magnesium sulphate, and very high levels can cause profound hypotension and cardiopulmonary arrest (Jahnen-Dechent 2012).
• Diarrhoea — the most common side effect of oral magnesium is diarrhoea and other gastrointestinal upset; in the 600 mg migraine trial, 18.6% reported diarrhoea (Peikert 1996). The tolerable upper intake level of 350 mg a day of supplemental magnesium was set on the basis of diarrhoea. In the isotope trial, the diglycinate chelate was better tolerated than oxide (Schuette 1994).
• Tetracycline antibiotics (such as doxycycline) — absorption is impaired by antacids containing aluminium, calcium or magnesium, according to the doxycycline label.
• Fluoroquinolone antibiotics — the ciprofloxacin label instructs that it be taken at least 2 hours before or 6 hours after magnesium/aluminium antacids and other products containing multivalent cations.
• Bisphosphonates — the alendronate label states that calcium supplements, antacids and oral medicines containing multivalent cations interfere with its absorption, and that it be taken at least 30 minutes before the first food, drink or medicine of the day.
• Levothyroxine — the label lists antacids containing aluminium and magnesium hydroxides among products that reduce its absorption, and states that it be taken at least 4 hours before or after such drugs.
• Medicines that lower magnesium — diuretics and proton pump inhibitors are among the drugs known to cause low blood magnesium (de Baaij 2015).

Interactions for a particular medicine are a question for a pharmacist or prescriber, and decisions about medicines and supplements belong with a clinician.

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Key Research Papers

1. Boyle NB, Lawton C, Dye L (2017). The effects of magnesium supplementation on subjective anxiety and stress — a systematic review. Nutrients — PubMed PMID: 28445426
2. Pickering G, Mazur A, Trousselard M et al. (2020). Magnesium status and stress: the vicious circle concept revisited. Nutrients — PubMed PMID: 33260549
3. Sartori SB, Whittle N, Hetzenauer A, Singewald N (2012). Magnesium deficiency induces anxiety and HPA axis dysregulation: modulation by therapeutic drug treatment. Neuropharmacology — PubMed PMID: 21835188
4. Eby GA, Eby KL (2010). Magnesium for treatment-resistant depression: a review and hypothesis. Medical Hypotheses — PubMed PMID: 19944540
5. De Baaij JHF, Hoenderop JG, Bindels RJM (2015). Magnesium in man: implications for health and disease. Physiological Reviews — PubMed PMID: 25540137
6. Tarleton EK, Littenberg B, MacLean CD et al. (2017). Role of magnesium supplementation in the treatment of depression: a randomized clinical trial. PLoS ONE — PubMed PMID: 28654669
7. Jacka FN, Overland S, Stewart R et al. (2009). Association between magnesium intake and depression and anxiety in community-dwelling adults. Australian and New Zealand Journal of Psychiatry — PubMed PMID: 19085527
8. Slutsky I, Abumaria N, Wu LJ et al. (2010). Enhancement of learning and memory by elevating brain magnesium. Neuron — PubMed PMID: 20152124
9. Walker AF, Marakis G, Christie S, Byng M (2003). Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study. Magnesium Research — PubMed PMID: 14596323
10. Aydin H, Deyneli O, Yavuz D et al. (2010). Short-term oral magnesium supplementation suppresses bone turnover in postmenopausal osteoporotic women. Biological Trace Element Research 133(2):136-43 — PubMed PMID: 19488681. (Editorial note: a bone-turnover study; it does not concern anxiety, and the earlier text on this page that attributed a generalized-anxiety finding to it has been removed.)
11. Cuciureanu MD, Vink R (2011). Magnesium and stress. In Vink R, Nechifor M (eds), Magnesium in the Central Nervous System. University of Adelaide Press. — PubMed PMID: 29920004
12. Schwalfenberg GK, Genuis SJ (2017). The importance of magnesium in clinical healthcare. Scientifica — PubMed PMID: 29093983
13. Poleszak E (2008). Benzodiazepine/GABA(A) receptors are involved in magnesium-induced anxiolytic-like behavior in mice. Pharmacological Reports 60(4):483-9 — PubMed PMID: 18799816
14. Abbasi B, Kimiagar M, Sadeghniiat K, Shirazi MM, Hedayati M, Rashidkhani B (2012). The effect of magnesium supplementation on primary insomnia in elderly: a double-blind placebo-controlled clinical trial. Journal of Research in Medical Sciences 17(12):1161-9 — PubMed PMID: 23853635
15. Kirkland AE, Sarlo GL, Holton KF (2018). The role of magnesium in neurological disorders. Nutrients 10(6):730 — PubMed PMID: 29882776
16. Jahnen-Dechent W, Ketteler M (2012). Magnesium basics. Clinical Kidney Journal 5(Suppl 1):i3-i14 — PubMed PMID: 26069819
17. Rosanoff A, Weaver CM, Rude RK (2012). Suboptimal magnesium status in the United States: are the health consequences underestimated? Nutrition Reviews 70(3):153-64 — PubMed PMID: 22364157
18. Zhang W, Zhao Y (2025). Global dietary magnesium deficiency: prevalence, underlying causes, health consequences, and strategic solutions. International Journal for Vitamin and Nutrition Research 95(6):46828 — PubMed PMID: 41504160
19. DiNicolantonio JJ, O'Keefe JH, Wilson W (2018). Subclinical magnesium deficiency: a principal driver of cardiovascular disease and a public health crisis. Open Heart 5(1):e000668 — PubMed PMID: 29387426
20. Blancquaert L, Vervaet C, Derave W (2019). Predicting and testing bioavailability of magnesium supplements. Nutrients 11(7):1663 — PubMed PMID: 31330811
21. Firoz M, Graber M (2001). Bioavailability of US commercial magnesium preparations. Magnesium Research 14(4):257-62 — PubMed PMID: 11794633
22. Schuette SA, Lashner BA, Janghorbani M (1994). Bioavailability of magnesium diglycinate vs magnesium oxide in patients with ileal resection. JPEN Journal of Parenteral and Enteral Nutrition 18(5):430-5 — PubMed PMID: 7815675
23. Bannai M, Kawai N (2012). New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. Journal of Pharmacological Sciences 118(2):145-8 — PubMed PMID: 22293292
24. Bannai M, Kawai N, Ono K, Nakahara K, Murakami N (2012). The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. Frontiers in Neurology 3:61 — PubMed PMID: 22529837
25. Schuster J, Cycelskij I, Lopresti A, Hahn A (2025). Magnesium bisglycinate supplementation in healthy adults reporting poor sleep: a randomized, placebo-controlled trial. Nature and Science of Sleep 17:2027-2040 — PubMed PMID: 40918053
26. De Souza MC, Walker AF, Robinson PA, Bolland K (2000). A synergistic effect of a daily supplement for 1 month of 200 mg magnesium plus 50 mg vitamin B6 for the relief of anxiety-related premenstrual symptoms: a randomized, double-blind, crossover study. Journal of Women's Health and Gender-Based Medicine 9(2):131-9 — PubMed PMID: 10746516
27. Islam MR, Ahmed MU, Mitu SA, Islam MS, Rahman GK, Qusar MM, Hasnat A (2013). Comparative analysis of serum zinc, copper, manganese, iron, calcium, and magnesium level and complexity of interelement relations in generalized anxiety disorder patients. Biological Trace Element Research 154(1):21-7 — PubMed PMID: 23754591
28. Peikert A, Wilimzig C, Köhne-Volland R (1996). Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia 16(4):257-63 — PubMed PMID: 8792038
29. Workinger JL, Doyle RP, Bortz J (2018). Challenges in the diagnosis of magnesium status. Nutrients 10(9):1202 — PubMed PMID: 30200431
30. Williams JL, Everett JM, D'Cunha NM et al. (2020). The effects of green tea amino acid L-theanine consumption on the ability to manage stress and anxiety levels: a systematic review. Plant Foods for Human Nutrition 75(1):12-23 — PubMed PMID: 31758301
31. Sarris J, Byrne GJ, Cribb L et al. (2019). L-theanine in the adjunctive treatment of generalized anxiety disorder: a double-blind, randomised, placebo-controlled trial. Journal of Psychiatric Research 110:31-37 — PubMed PMID: 30580081
32. Sarris J, Ravindran A, Yatham LN et al. (2022). Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: the World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce. World Journal of Biological Psychiatry 23(6):424-455 — PubMed PMID: 35311615

PubMed Topic Searches

1. PubMed: Magnesium and anxiety
2. PubMed: Magnesium glycinate absorption
3. PubMed: Mg NMDA receptor
4. PubMed: Mg HPA axis / cortisol
5. PubMed: Magnesium and sleep

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Connections

• All Remedies
• Natural Anxiety Relief Hub
• Natural Anxiety Relief Benefits
• L-Theanine and Green Tea
• Adaptogenic Herbs
• Breath and Cold Exposure
• Magnesium (Main Page)
• Glycine
• Taurine
• Vitamin B6
• Vitamin D3
• Zinc
• Calcium
• Migraine
• Sleep Hygiene

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