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Magnesium

Magnesium (Mg) is an element and essential mineral. It is a cofactor in over three hundred enzymatic reactions involved in protein synthesis, muscle contraction, nerve function, blood pressure, glucose regulation, hormone receptor binding, cardiac conduction, transmembrane ion flux, and calcium channel gating. (72) It is required for the production of ATP, (48) and the synthesis of RNA and DNA. (72)

Not to be confused with: Manganese

Main uses

Cardiovascular disorders
Metabolic, endocrine, and hormonal disorders
Musculoskeletal disorders
Neurological disorders
Respiratory disorders
Sleep and fatigue

Formulations

Form	Absorption rate
Magnesium aspartate	~42-45% absorption (54)(64)
Magnesium lactate (90)	~42% absorption (23)(64)
Magnesium citrate (3)(90)	~30% absorption (45)(51)(64)(85)
Magnesium glycinate (81)	~24% absorption (64)(71)(87)
Magnesium chloride (6)(25)	~20% absorption (11)(52)(64)
Magnesium gluconate	~20% absorption (52)(57)(64)
Magnesium hydroxide (13)	~15% absorption (11) (24) (64)
Magnesium sulfate (4)(9)	~4-7% (53)(64)(78)
Magnesium oxide (1)(2)	~4% absorption; ~23% in px with ileal resection (32)(64)(71)
Magnesium fumarate (64)	No absorption data
Magnesium orotate (80)	No absorption data
Magnesium pidolate (17)(29)	No absorption data
Magnesium pyrrolidone carboxylic acid (26)(27)	No absorption data

Dosing & administration

Age-related decline in physical performance
General outcomes from A-level evidence	No data currently available.
Dosing & administration	300 mg (Mg oxide) per day for 12 weeks
Outcomes	↓ short physical performance battery score & walking speed ↑ chair stand times (83)
Class of evidence	B

Asthma
General outcomes from A-level evidence	No data currently available.
Dosing & administration	1.2-2.0 g (i.v. Mg sulfate) over 15-30 minutes adjunct to standard therapy
Outcomes	↑ pulmonary function ↓ hospital admission rate in severe cases (47)(78)
Class of evidence	A
Dosing & administration	170 mg twice per day for 6.5 months
Outcomes	↓ methacholine required to decrease FEV1, peak expiratory flow (PEF) rate, QoL & control scores (46)
Class of evidence	B
Dosing & administration	200-290 mg (Mg citrate) per day for 12 weeks in children
Outcomes	↓ bronchodilator use (7)
Class of evidence	B
Dosing & administration	300 mg per day for 2 months in children
Outcomes	↑ methacholine PC20 required to test bronchial reactivity ↓ asthma exacerbations, used less salbutamol, antigen response on skin (34)
Class of evidence	C

Atrial fibrillation (AF)
General outcomes from A-level evidence	No data currently available.
Dosing & administration	Up to 14.6 g bolus post-cardiac surgery
Outcomes	↓ AF risk, ventricular arrhythmias risk (28)
Class of evidence	A
Dosing & administration	100 mg/kg (i.v. Mg sulfate) during aortic cross-clamp
Outcomes	↓ AF incidence after coronary artery bypass graft surgery, ICU stay length (4)
Class of evidence	B
Dosing & administration	4.5 g (i.v. Mg sulfate) with AV nodal blocking agents in emergency rapid AF
Outcomes	↓ ventricular rate ↑ rhythm control rate (12)
Class of evidence	B
Dosing & administration	30 mg/kg (i.v. Mg sulfate) post cardiac surgery
Outcomes	↓ arrhythmia incidence (56)
Class of evidence	B

Attention deficit hyperactivity disorder
General outcomes from A-level evidence	No data currently available.
Dosing & administration	200 mg per day for 6 months in children
Outcomes	↓ hyperactivity (79)
Class of evidence	B

Chronic alcoholism
General outcomes from A-level evidence	No data currently available.
Dosing & administration	200 mg twice per day for 8 weeks
Outcomes	↓ aspartate-aminotransferase, alanine-aminotransferase, gamma-glutamyl-transpeptidase ↑ Na, Ca, P, K, Mg (40)(61)
Class of evidence	B

Chronic kidney disease
General outcomes from A-level evidence	No data currently available.
Dosing & administration	365 mg (Mg oxide) for 3 months in obese pre-diabetic px with hypo-magnesemia
Outcomes	↓ uric acid ↑ albumin, Mg (82)
Class of evidence	B
Dosing & administration	360 mg (Mg hydroxide) twice per day for 8 weeks
Outcomes	↑ T50 propensity (delaying crystalline nanoparticle formation) (13)
Class of evidence	C

Chronic obstructive pulmonary disease
General outcomes from A-level evidence	No data currently available.
Dosing & administration	1.2 g (i.v. Mg sulfate) over 20 minutes after 2.5 mg nebulized albuterol
Outcomes	↑ peak expiratory flow (PEF) over 45 mins (76)
Class of evidence	B
Dosing & administration	2 g (i.v. Mg sulfate)
Outcomes	↓ functional respiratory capacity (FRC) ↑ inspiratory capacity, max inspiratory pressure (MIP), max expiratory pressure (MEP) (21)
Class of evidence	C
Dosing & administration	2 g (i.v. Mg sulfate) alongside cycle ergometer exercise. Test performed 100 minutes after infusion
Outcomes	↓ FRC, residual volume (RV), mean arterial pressure (MAP), cardiac double product at rest ↑ max exercise load reached (& inspiratory capacity), respiratory expiratory ratio (22)
Class of evidence	C
Dosing & administration	2 g (i.v. Mg sulfate) with bronchodilator therapy
Outcomes	↑ forced expiratory volume over 2 hours, forced vital capacity (55)
Class of evidence	C
Dosing & administration	151 mg (nebulized Mg sulfate) per dose with 500 µg ipratropium bromide
Outcomes	↓ dyspnea ↑ PEF rates (16)
Class of evidence	C

Coronary artery disease
General outcomes from A-level evidence	No data currently available.
Dosing & administration	365 mg total Mg (Mg citrate or oxide) twice per day for 6 months
Outcomes	↑ endothelium dependent brachial artery flow-mediated vasodilation (FMD), exercise tolerance & duration, VO2 max, HR response, left ventricular ejection fraction (LVEF), QoL ↓ frequency of ischemic ST-segment changes, arrhythmias, & chest pain during exercise (62)(74)(75)
Class of evidence	B
Dosing & administration	800-1200 mg (Mg oxide) per day for 3 months
Outcomes	↑ platelet dependent thrombosis (73)
Class of evidence	C

Depression
General outcomes from A-level evidence	No data currently available.
Dosing & administration	320 mg per day
Outcomes	↓ risk for depression (50)
Class of evidence	A
Dosing & administration	500 mg (Mg oxide) per day for 8 weeks
Outcomes	↑ Mg levels ↓ Beck score (63)
Class of evidence	B
Dosing & administration	50 ml (Mg chloride 5% solution = 450 mg elemental Mg) in type II diabetics with depression & hypomagnesemia
Outcomes	↓ Yasavage and Brink Scores of depression equivalently to 50mg of imipramine ↑ serum Mg (5)
Class of evidence	C

Diabetes - gestational
General outcomes from A-level evidence	No data currently available.
Dosing & administration	250 mg (Mg oxide) per day for 6 weeks in GD
Outcomes	↓ FBG, insulin, HOMA-IR, HOMA-B, hs-CRP, MDA, newborn hyperbilirubinemia & newborn hospitalization, LDL receptor expression ↑ insulin sensitivity, TGs, PPAR-γ & GLUT-1 expression (2)(44)
Class of evidence	B

Diabetes - prediabetes
General outcomes from A-level evidence	No data currently available.
Dosing & administration	30 mL (MgCl2 5% solution = 382 mg elemental Mg) per day for 4 months in prediabetes px with Mg deficiency
Outcomes	↓ fasting & post-load glucose, HOMA-IR, TGs ↑ glycemic status, HDL-C (39)
Class of evidence	C

Diabetes - type I (TID)
General outcomes from A-level evidence	No data currently available.
Dosing & administration	300 mg per day for 5 years in TID with chronic Mg depletion
Outcomes	↑ erythrocyte Mg ↓ polyneuropathy in 39% of participants, no change in 49%, or worsening in 12% (19)
Class of evidence	B

Diabetes - type II (TIID)
General outcomes from A-level evidence	No data currently available.
Dosing & administration	360 mg per day for 12 weeks in TIID
Outcomes	↓ FBG ↑ HDL-C (77)
Class of evidence	A
Dosing & administration	50 mL (MgCl2 5% solution = 450 mg) per day for 4 months in hypertensive TIID with Mg deficiency
Outcomes	↓ SBP & DBP ↑ HDL-C (38)
Class of evidence	B
Dosing & administration	374 mg (unspecified form) for 4 weeks in TIID
Outcomes	↑ insulin dependent glucose disappearance, glucose disposal & oxidation (59)
Class of evidence	B
Dosing & administration	4.5 g (Mg pidolate) per day for 1 month in TIID
Outcomes	↓ total-C, LDL-C; ↑ HDL-C (17)
Class of evidence	C

Diabetic foot ulcers (DFU)
General outcomes from A-level evidence	No data currently available.
Dosing & administration	250 mg (Mg oxide) per day for 12 weeks in px with diabetic foot ulcers
Outcomes	↓ ulcer length, width, & depth, FBG, insulin, HBA1C, & hs-CRP ↑ insulin sensitivity, total antioxidant capacity (65)
Class of evidence	B

Heart failure
General outcomes from A-level evidence	No data currently available.
Dosing & administration	8 g (i.v. Mg sulfate) over 12 hours
Outcomes	↓ ventricular ectopic beats, couplets & nonsustained ventricular tachycardia (15)
Class of evidence	B
Dosing & administration	6000 mg (Mg orotate) for 1 month and 3000 mg for 11 months
Outcomes	↑ survival rate, improvement in NYHA scale (80)
Class of evidence	B
Dosing & administration	365 mg (Mg chloride) per day for 6 weeks
Outcomes	↓ mean arterial pressure (MAP), systemic vascular resistance, epinephrine, isolated ventricular premature complexes, couplets & nonsustained ventricular tachycardia frequency (6)
Class of evidence	C
Dosing & administration	970 mg over 24 hours (i.v. Mg sulphate)
Outcomes	Stabilizes cardiac repolarization (42)
Class of evidence	C
Dosing & administration	800 mg (Mg oxide) per day for 3 months
Outcomes	↓ small arterial compliance (33)
Class of evidence	C

Hypertension
General outcomes from A-level evidence	No data currently available.
Dosing & administration	365-450 mg for 1-6 months
Outcomes	↓ SBP & DBP (20)
Class of evidence	A
Dosing & administration	300 mg per day for 1 month minimum
Outcomes	↓ SBP & DBP (91)
Class of evidence	A

Insomnia/sleep
General outcomes from A-level evidence	No data currently available.
Dosing & administration	320 mg (Mg citrate) per day for 7 weeks
Outcomes	↑ serum Mg only in Mg-deficient px ↓ plasma CRP only in px with >3.0 mg/L (an indicator of chronic inflammatory stress) (58)
Class of evidence	B
Dosing & administration	500 mg (Mg oxide) twice per day for 8 weeks
Outcomes	↑ sleep time, sleep efficiency, serum renin & serum melatonin ↓ ISI score, sleep onset latency, serum cortisol (1)
Class of evidence	C
Dosing & administration	Effervescent tablets titrated from 10 mmol to 20 mmol for 3 days each, up to 30 mmol per day for 14 days in elderly subjects
Outcomes	↑ slow-wave sleep, delta & sigma power, renin, aldosterone ↓ cortisol (41)
Class of evidence	C

Metabolic syndrome
General outcomes from A-level evidence	No data currently available.
Dosing & administration	30 ml (Mg chloride 5% solution = 382 mg elemental Mg) per day for 4 months
Outcomes	↓ SBP, DBP, HOMA-IR, fasting glucose, TGs (66)(67)
Class of evidence	B

Migraine
General outcomes from A-level evidence	No data currently available.
Dosing & administration	600 mg (Mg dicitrate) per day
Outcomes	↑ migraine prophylaxis (84)
Class of evidence	A
Dosing & administration	600 mg (tri-Mg dicitrate) per day for 12 weeks
Outcomes	↓ attack frequency, number of days with migraine (60)
Class of evidence	B
Dosing & administration	1000 mg (i.v. Mg sulphate) once
Outcomes	↓ photophobia & phonophobia intensity in px without aura ↓ pain in px with aura (10)
Class of evidence	B
Dosing & administration	600 mg (Mg citrate) per day for 3 months
Outcomes	↓ attack frequency, intensity, P1 amplitude ↑ inferolateral frontal, inferolateral temporal, insular blood flow (49)
Class of evidence	C

Muscle cramps
General outcomes from A-level evidence	No data currently available.
Dosing & administration	300 mg (Mg citrate) per day for 6 weeks
Outcomes	↓ mean number of nocturnal cramps during Mg use (68)
Class of evidence	C

Muscle cramps in pregnancy
General outcomes from A-level evidence	No data currently available.
Dosing & administration	120 mg in the morning, 240mg at night (Mg citrate or Mg lactate)
Outcomes	↓ leg cramps (90)
Class of evidence	A
Dosing & administration	300 mg (Mg bisglycinate chelate) per day for 4 weeks
Outcomes	↓ cramp frequency & intensity (81)
Class of evidence	B

Osteoporosis prevention
General outcomes from A-level evidence	No data currently available.
Dosing & administration	150 mg (Mg oxide) twice per day for 1 year in girls aged 8-14
Outcomes	↑ hip bone mineral content (14)
Class of evidence	B
Dosing & administration	1830 mg (Mg citrate) per day for 30 days in post-menopausal women
Outcomes	↓ serum iPTH, urinary deoxypyridinoline ↑ serum osteocalcin (3)
Class of evidence	C

Post-operative cardiac arrhythmias
General outcomes from A-level evidence	No data currently available.
Dosing & administration	2 g (i.v. Mg chloride) intraoperatively post cardiopulmonary bypass surgery
Outcomes	↓ ventricular dysrhythmias, supraventricular dysrhythmias, mechanical ventilatory support required ↑ postoperative cardiac indices (25)
Class of evidence	B

Pre-eclampsia and eclampsia
General outcomes from A-level evidence	No data currently available.
Dosing & administration	4-15 g (Mg sulfate i.v./i.m) + maintenance doses up to 2g/hour (i.m)
Outcomes	↓ initiation or recurrence of eclampsia at all doses (35)
Class of evidence	A
Dosing & administration	4 g (Mg sulfate i.v.) + 10 g (i.m.)
Outcomes	↓ recurrence of eclampsia to same extent as listed dose + 5.0g/4 hours (i.m) (36)
Class of evidence	A
Dosing & administration	6 g (Mg sulfate i.v.)
Outcomes	↓ pulsatility index in central retinal, posterior ciliary blood vessels & middle cerebral artery (8)(9)
Class of evidence	C

Premature ventricular and supraventricular complexes
General outcomes from A-level evidence	No data currently available.
Dosing & administration	3 g (Mg pidolate) per day for 30 days
Outcomes	↓ premature complex density and symptoms (29)
Class of evidence	B

Premenstrual syndrome
General outcomes from A-level evidence	No data currently available.
Dosing & administration	250 mg per day for 2 cycles
Outcomes	↑ depression, anxiety, water retention & somatic symptoms (30)
Class of evidence	B
Dosing & administration	360 mg (Mg pyrrolidone carboxylic acid) three times per day for 4 cycles
Outcomes	↓ menstrual Distress Questionnaire (MDQ) score, pain & negative affect score ↑ Mg in lymphocytes & polymorphonuclear cells (26)
Class of evidence	C
Dosing & administration	360 mg (Mg pyrrolidone carboxylic acid) for 4 months
Outcomes	↓ pain, number of days with headache, MDQ score ↑ Mg in lymphocytes & polymorphonuclear cells (27)
Class of evidence	C
Dosing & administration	200 mg (Mg oxide) per day for 2 cycles
Outcomes	↓ weight gain, extremity swelling, breast tenderness, bloating after 2nd month (86)
Class of evidence	C

Supraventricular tachycardia (SVT)
General outcomes from A-level evidence	No data currently available.
Dosing & administration	5 g (i.v. Mg sulfate) per day, intraoperatively and post thoracic surgery for 2 days
Outcomes	↓ SVT incidence in px undergoing pneumonectomy (69)
Class of evidence	B

Adverse effects

While Mg is generally well-tolerated, oral supplementation may cause diarrhea, nausea, or vomiting. Intravenous overdose may cause thirst, hypotension, drowsiness, muscle weakness, respiratory depression, headaches, flushing, cardiac arrhythmia, coma, and death. (37)(47) There is no evidence of adverse effects from dietary sources. (43)

Pharmacokinetics

Absorption

Occurs in the ileum (56%), jejunum (22%), duodenum (11%), and colon (11%)
At low GI concentrations, Mg is uptaken through active transport via the saturable Transient Receptor Potential Channel Melastatin members TRPM6 and TRPM7. (89)
At high GI concentrations, Mg is absorbed primarily via passive paracellular transport. (70)

Distribution

After absorption, Mg is distributed to bone (53%), muscle (27%), soft tissues (27%), and blood (0.8%). (31)

Metabolism

In bone, Mg from the blood substitutes positions with the Mg in bone promoting, chondrocyte column development, osteoblast proliferation, and osteoclast activity. (18)
In the brain, Mg inhibits post-synaptic NMDA receptor excitation by increasing chloride uptake by GABA receptor stimulation, and by antagonizing calcium, reducing pre-synaptic glutamate release. (18)
In the heart and vascular system, Mg reduces ion channel activity in the myocardium, calcium availability and binding in cardiac muscle, and inflammation in the vascular system. Mg increases vasodilation. (18)
In muscle, Mg maintains the level of muscle contractility with calcium. (18)

Excretion

If not absorbed, Mg is eliminated in the feces (20-70%). (88)
If absorbed, Mg can be eliminated in the urine (5-70%). This can occur in the proximal tubules (10-30% via passive paracellular pathways), or the thick ascending limb (40-70% via claudin proteins, 5-10% via active TRPM6 transport). (89)
The half-life of Mg is approximately 1000 hours. (72)