Magnesium

Magnesium/Drug Interactions:

  • GeneralGeneral: According to secondary sources, it is advised to separate magnesium ingestion from any other medication by two hours or more (when taken in amounts greater than recommended daily allowances or through the diet). According to a review, minerals in foods may both form complexes with drugs and change the environment of the gastrointestinal system resulting in a change in the normal absorption processes of either or both of the drugs and the minerals (183). The authors suggest that absorption, as well as depletion and retention may all be affected and that simultaneous antacid ingestion may induce drug-mineral interactions.
  • ACE inhibitorsACE inhibitors: According to secondary sources, magnesium sulfate may reduce serum ACE concentrations and test results in the short term. Deray et al. published a report on the treatment of cardiac failure with angiotensin-converting enzyme inhibitors and diuretics (184). The authors also discussed the prevention of the secondary effects of diuretics and ACE inhibitors on renal function, serum sodium, and potassium and magnesium concentrations. Further details are lacking.
  • Aldesleukin.Aldesleukin: Asymptomatic hypomagnesemia may occur with aldesleukin (interleukin-2) therapy, possibly due to an intracellular shift of magnesium (185). Urinary magnesium did not increase, and serum levels normalized a few days after the drug was discontinued.
  • AmifostineAmifostine: Amifostine reduced serum magnesium (WR-2721) levels by reducing renal tubular reabsorption of magnesium and increasing urinary losses (186; 187). This effect appeared to occur acutely after a single dose; levels may return to normal within 24 hours.
  • AminoglycosidesAminoglycosides: Concurrent use of magnesium and aminoglycosides may result in neuromuscular weakness (188). According to secondary sources, nephrotoxicity caused by aminoglycosides (e.g., streptomycin and tobramycin) may lead to increased urinary loss of various electrolytes, including magnesium. Aminoglycosides include amikacin (Amikin?), gentamicin (Garamycin?), kanamycin (Kantrex?), streptomycin, and tobramycin (Nebcin?).
  • Amphotericin-BAmphotericin-B: In human and animal research, electrolyte disturbances, including low serum magnesium levels, developed in a large proportion of patients receiving amphotericin-B (189; 190; 191). Lipid-based formulations such as Abelcet? and Anphotec? may have a lesser effect than conventional formulations (191). This disturbance has been associated with nephrotoxicity and may necessitate discontinuing the drug and administering intravenous electrolyte replacement.
  • AnalgesicsAnalgesics: In human research, magnesium had a small but beneficial effect as an analgesic (42; 42; 43; 44; 60) and resulted in a reduction in the need for morphine following surgery (42).
  • AnestheticsAnesthetics: Use of magnesium increased the duration of spinal anesthesia according to a systematic review and meta-analysis; however, there was significant heterogeneity, and significant effects on the secondary outcomes of the start of sensory and motor block, the duration of sensory and motor block, and the time to peak sensory block, were lacking (166).
  • Antiarrhythmic agentsAntiarrhythmic agents: In clinical research, intravenous magnesium has been reported to reduce the incidence of atrial fibrillation and cardiac arrhythmias (192; 25; 26; 27; 29; 28; 30; 32; 193; 194; 123; 128; 195; 124; 196; 151; 19; 20; 21; 22; 23; 31). Magnesium-containing antacids may increase urinary pH and alter excretion of the class I antiarrhythmic agent quinidine (197). Concurrent use of magnesium and quinidine may increase the risk of quinidine toxicity (198).
  • Antiasthma drugsAntiasthma drugs: In clinical research, magnesium sulfate (often in combination with pharmaceutical agents) has been shown to be effective for the treatment of acute asthma exacerbations in some studies; however, effects in children with mild to moderate symptoms were small or lacking (33; 34; 35; 36; 168; 39; 40; 199; 37; 200; 172; 201; 173; 202; 203; 169; 204; 41).
  • AntibioticsAntibiotics: In human research and according to secondary sources, magnesium was found to reduce the effectiveness of certain antibiotics, such as fluoroquinolones and cephalosporins, via chelation (117; 118). Concurrent use of magnesium and aminoglycosides may result in neuromuscular weakness (188). According to secondary sources, nephrotoxicity caused by aminoglycosides (e.g., streptomycin and tobramycin) may lead to increased urinary loss of various electrolytes, including magnesium. According to a review, gentamycin alters magnesium handling by the body (205). According to human research and clinical review, administration of oral magnesium salts with oral tetracyclines or quinolone antibiotics may form nonabsorbable complexes, resulting in decreased absorption of tetracyclines and quinolones (206; 207; 208). Therefore, it is advised that magnesium should be ingested two or more hours before or after tetracycline. However, other clinical studies have shown no effect on bioavailability by coadministration (209; 210; 211; 212; 213; 214).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In human research, magnesium has been found to inhibit platelet aggregation (99; 100; 101). In clinical research, oral magnesium treatment inhibited platelet-dependent thrombosis (PDT) in stable patients with coronary artery disease (CAD); however, there was no significant effect of magnesium treatment on platelet aggregation (102).
  • AnticonvulsantsAnticonvulsants: In clinical research, magnesium sulfate has been shown to be an effective drug for the prevention of the recurrence of seizures in eclampsia and in seizure prophylaxis in pre-eclampsia (toxemia of pregnancy) (6; 7; 8; 9; 10; 11; 12; 13; 14; 15; 16; 17; 6; 18).
  • Antidiabetic agentsAntidiabetic agents: In clinical research, oral magnesium has been reported to improve glycemic control in type 2 diabetes (45; 46; 49; 105; 106). Concurrent use of magnesium with antidiabetic agents, particularly sulfonylureas (e.g., glipizide), may increase the risk of hypoglycemia by increasing the rate of absorption (103; 104).
  • AntihypertensivesAntihypertensives: Several clinical studies have reported a small decrease in blood pressure, which is statistically significant in some, but not all, studies with magnesium (107; 108; 109; 110; 111; 112; 113; 114; 115). However, increased blood pressure has also been reported (115). A meta-analysis of epidemiological studies supported the inverse relationship between blood pressure and urinary magnesium levels (215). Concurrent use of magnesium sulfate and nifedipine has reportedly caused hypotension, hypocalcemia, and neuromuscular blockade (216; 217; 218); however, conversely, a comprehensive retrospective study found a lack of adverse effects (in particular severe hypotension) from the simultaneous administration of nifedipine and magnesium sulfate (219).
  • Antineoplastics, alkylating agentsAntineoplastics, alkylating agents: According to a review, cisplatin alters magnesium handling by the body (205). According to secondary sources, carboplatin and cisplatin may cause hypomagnesemia due to renal tubular damage, which increases urinary magnesium losses. With carboplatin, hypomagnesemia is rarely symptomatic and usually does not require magnesium supplements. Hypomagnesemia is usually more severe with cisplatin and worsens with progressive courses of treatment. Most patients who receive cumulative doses of cisplatin above 400mg/m2 will develop hypomagnesemia. Intravenous or oral magnesium supplements counteract this hypomagnesemia.
  • AntineoplasticsAntineoplastics: The combination of calcium and magnesium infusions has been studied for the prevention of oxaliplatin- or cisplatin-related neurotoxicity (220; 221; 222). Overall this combination has mixed results (benefits or lack of benefits) in terms of the incidence of acute and cumulative neurotoxicity; effects on chemotherapy efficacy were lacking. According to a systematic review, cetuximab or panitumumab use resulted in an increased risk of hypomagnesemia (223; 224). The addition of anti-EGFR monoclonal antibodies to this anti-neoplastic regimen further increased the risk of hypomagnesemia.
  • Beta-agonistsBeta-agonists: Clinically, magnesium is often used as an adjunct to treatment with beta-2 agonists (33; 34; 35; 36; 168; 39; 40; 199; 37; 200; 172; 201; 173; 202; 203; 225; 169; 204). Beta-2 agonists promote movement of magnesium from the extracellular to the intracellular space, and increase magnesium excretion in the urine. Reduced serum magnesium levels have been shown to occur after a single dose of albuterol or terbutaline orally, or by intravenous infusion, SC injection, or inhalation. The reductions are generally small (about 0.04-0.06mmol/L); it is unlikely that individuals receiving regular doses of beta-2 agonists will need magnesium supplementation unless they have other factors contributing to magnesium deficiency. According to a systematic review, there was a greater risk of adverse events with magnesium plus beta-blocker than with beta-blocker only (21).
  • BisphosphonatesBisphosphonates: According to secondary sources, oral magnesium salts may prevent absorption of oral bisphosphonates like etidronate; it is advised that magnesium salts should not be administered within two hours of oral bisphosphonates.
  • Calcium-channel blockersCalcium-channel blockers: In human research, magnesium enhanced the hypotensive effect of calcium channel blockers (226). Concurrent use of magnesium sulfate and nifedipine has reportedly caused hypotension, hypocalcemia, and neuromuscular blockade (216; 217; 218). Conversely, other studies have found a lack of adverse effects from the simultaneous administration of calcium channel blockers and magnesium sulfate (219; 6).
  • Calcium saltsCalcium salts: In animal and human research and according to secondary sources, concurrent use with magnesium caused increases in serum or magnesium concentrations, particularly in patients with renal insufficiency (227; 228; 229). According to a systematic review, use of magnesium increased hypocalcemia (54). According to a systematic review the inverse association observed in observational studies between dietary calcium intake and risk of type 2 diabetes may have been at least partially confounded by intake of magnesium (230). During blood transfusion, risk of hypomagnesemia was found to increase with hypocalcemia (231). In a review, the authors indicate that individuals taking supplementary estrogen may also be taking supplementary calcium, resulting in an increased blood ratio of calcium to magnesium, increasing the risk of thrombosis (232).
  • Cardiac glycosidesCardiac glycosides: In human research and clinical review, magnesium salts, such as magnesium sulfate, decreased digoxin levels by decreasing the absorption of digoxin (233; 234; 235). According to a review, digoxin increases magnesium excretion, increased levels of magnesium decrease the clinical effects of the cardiac glycosides, and magnesium increases the binding of cardiac glycosides to the receptor (134).
  • Cardiovascular agentsCardiovascular agents: In clinical research, magnesium has been reported to produce hypotension, reduced arterial pressure, bradycardia, tachycardia, myocardial infarction, cardiac events, and arrhythmias (123; 124; 29; 21; 44; 120; 58; 54; 53; 115; 125; 126; 43; 127). Increased blood pressure has also been reported (115).
  • CephalosporinsCephalosporins: In human research and according to secondary sources, magnesium-containing antacids form chelation complexes with cephasporins, thereby preventing their absorption, particularly in elderly patients with impaired renal function (236). However, other clinical studies have shown no effect on bioavailability by coadministration (209; 210; 211; 212; 213; 214).
  • Cetuximab (Erbitux?)Cetuximab (Erbitux?): In human research, cetuximab increased renal magnesium excretion, resulting in lowered magnesium levels in patients (237; 238; 239; 240).
  • Cholestyramine (Questran?)Cholestyramine (Questran?): Preliminary evidence suggests that cholestyramine may slightly increase urinary magnesium excretion, possibly by binding vitamin D and leading to reduced magnesium absorption (241). However, evidence of clinically significant magnesium deficiency is currently lacking, and the necessity for magnesium supplementation may be unlikely.
  • CNS depressantsCNS depressants: According to secondary sources, magnesium toxicity may be associated with central nervous system depression. According to clinical research, a high intravenous dosage (1-2g/hour) of magnesium may cause respiratory depression (9).
  • CorticosteroidsCorticosteroids: In human research, chronic use of corticosteroids increased urinary magnesium excretion (242). Magnesium-containing antacids have also been found to reduce the bioavailability of corticosteroids, such as prednisone (243).
  • Dermatologic agentsDermatologic agents: In human research, flushing, feeling of warmth, burning pain around the navel, welts, sweating, problems at the injection site, and diaphoresis have also been reported as possible adverse effects of magnesium (8; 128; 120; 129; 130; 127; 6; 116; 57; 55; 125; 127).
  • DiureticsDiuretics: According to human research and clinical review, diuretics interfere with the kidney's ability to regulate magnesium concentrations (131; 132). Long-term use of loop diuretics or thiazide diuretics may impair the magnesium-conserving ability of the kidneys and lead to hypomagnesemia (133; 134). Conversely, long-term use of potassium-sparing diuretics has been found to increase renal tubular reabsorption of magnesium, which may cause hypermagnesemia in patients also receiving magnesium supplements, especially in patients with renal insufficiency (244). Deray et al. published a report on the treatment of cardiac failure with angiotensin-converting enzyme inhibitors and diuretics (184). The authors also discussed the prevention of the secondary effects of diuretics and ACE inhibitors on renal function, serum sodium, and potassium and magnesium concentrations. Further details are lacking. Acute urinary retention has been reported as a possible adverse effect of magnesium (6).
  • Drugs used for osteoporosisDrugs used for osteoporosis: In human research, magnesium, alone or in combination with calcium, vitamin D, and zinc, reduced bone turnover (245; 246; 75). In combination with calcium, vitamin D, and other minerals, magnesium increased bone density (247). Magnesium supplementation in postmenopausal osteoporotic women resulted in decreased serum iPTH and urinary deoxypyridinoline and increased serum osteocalcin (246; 75).
  • EstrogensEstrogens: In human research and clinical review, estrogens enhance magnesium uptake by soft tissues and bones, thus lowering serum levels (248; 249). An inverse relationship between estrogen levels and magnesium serum levels has been reported. According to a review, magnesium levels were lower in women on the pill vs. women not on the pill (182). The interrelationship of magnesium and estrogen has been the topic of a review (232). The authors suggest that when estrogen levels are high and magnesium intakes are low, resulting magnesium levels may be decreased. They also indicate that individuals taking supplementary estrogen may also be taking supplementary calcium, resulting in an increased blood ratio of calcium to magnesium, increasing the risk of thrombosis. According to secondary sources, magnesium may decrease serum estrogen levels.
  • Foscarnet (Foscavir?)Foscarnet (Foscavir?): In case reports, foscarnet caused various electrolyte disturbances, including symptomatic hypomagnesemia (250; 251). This may be due to chelation of magnesium and increased elimination. Magnesium supplements may be required with foscarnet therapy.
  • Gastrointestinal agentsGastrointestinal agents: Gastrointestinal irritation, nausea, vomiting, mild abdominal pain, dry mouth, constipation, and diarrhea, soft stool, and delayed meconium (neonates) have all been suggested as possible adverse effects of magnesium (135; 136; 137; 138; 139; 120; 115; 126; 140; 141; 127; 142; 6; 6; 57; 176).
  • Hormonal agentsHormonal agents: According to secondary sources, magnesium may decrease serum estrogen levels.
  • ImmunosuppressantsImmunosuppressants: According to a review, cyclosporine alters magnesium handling by the body (205).
  • LabetalolLabetalol: According to secondary sources, concurrent use of magnesium and labetalol may result in bradycardia and reduced cardiac output.
  • LaxativesLaxatives: In human research, magnesium hydroxide lacked effect, or was less effective than a comparator, for constipation (138; 141).
  • LevomethadylLevomethadyl: According to secondary sources, magnesium may increase the risk of QT prolongation if given with levomethadyl.
  • LithiumLithium: In human research, magnesium has been shown to be of benefit in the management of manic symptoms in patients with bipolar disorder when given as supplemental therapy (159; 160).
  • Musculoskeletal agentsMusculoskeletal agents: In clinical research, magnesium has been reported to decrease skeletal muscle tone and cause limb weakness (119; 120; 53; 6), bone pain (115), hypocalcemic tetany (53), and according to secondary sources, loss of tendon reflexes.
  • Neurologic agentsNeurologic agents: According to clinical research, adverse effects have included headaches (57; 120; 143; 6), as well as slurred speech, dizziness, drowsiness, disorientation, and confusion (120; 130), and according to secondary sources, central nervous system depression. However, in human research, magnesium was beneficial in individuals with migraine headaches (163; 252; 139).
  • Neuromuscular blockersNeuromuscular blockers: In case reports, magnesium potentiated the effect of neuromuscular blockers, particularly those with renal failure (253).
  • Neuroprotective agentsNeuroprotective agents: Animal research has shown that magnesium may have neuroprotective effects (254). Systematic reviews/meta-analyses of earlier studies of antenatal magnesium sulfate therapy as a neuroprotective agent for the preterm fetus lacked a definite benefit (255; 129); however, a systematic review found a significant trend that antenatal Mg therapy may improve motor function in early childhood for infants born prematurely (255) and more recent meta-analyses of data suggests in utero use of magnesium sulfate reduces the risk of developing cerebral palsy of infants at risk for premature delivery, especially if magnesium sulfate was used for neuroprotection (55; 56; 57; 58).
  • Nonsteroidal anti-inflammatory agents (NSAIDs)Nonsteroidal anti-inflammatory agents (NSAIDs): In vitro, antacid compounds containing magnesium enhanced the solubility, dissolution, and bioavailability of nonsteroidal anti-inflammatory drugs, such as ibuprofen (256).
  • Ophthalmic agentsOphthalmic agents: Visual impairment and nystagmus have been reported in clinical trials (115; 6).
  • Oral contraceptivesOral contraceptives: According to secondary sources, magnesium may decrease serum estrogen levels.
  • Panitumumab (Vectibix?)Panitumumab (Vectibix?): According to secondary sources, panitumumab may increase renal magnesium excretion, leading to lowered magnesium levels.
  • Pentamidine (NebuPent?, Pentacarinat?, Pentam 300?)Pentamidine (NebuPent?, Pentacarinat?, Pentam 300?): In case reports, symptomatic hypomagnesemia has occurred with pentamidine, particularly if given intravenously (257; 258; 259). This is likely due to renal tubular injury, leading to increased urinary losses of magnesium. Hypomagnesemia usually requires treatment with intravenous, followed by oral, magnesium supplements.
  • PhosphatesPhosphates: Concomitant use of oral preparations in conjunction with magnesium compounds, such as antacids containing magnesium (e.g., magnesium carbonate, magnesium hydroxide), may bind phosphate in the stomach and reduce its absorption (145; 146; 147; 148; 149; 150). It is advised to separate the administration of sodium phosphate salts from magnesium-containing products by at least two hours.
  • PotassiumPotassium: According to a review, magnesium intake may affect the level of blood pressure reduction induced by potassium (260).
  • PropanololPropanolol: In one study of a systematic review, treatment with propranolol plus magnesium increased the incidence of hypotension vs. propanolol alone (29).
  • Proton pump inhibitors (PPIs)Proton pump inhibitors (PPIs): In clinical research, case studies, and reviews, use of proton pump inhibitors has been associated with decreased magnesium levels (261; 262; 263; 264; 265; 266; 267; 268; 269); severe hypomagnesemia has been reported in some cases (262; 263; 268).
  • Psychiatric agentsPsychiatric agents: In a case study, hypermagnesemia has been reported to cause delirium in a patient receiving magnesium sulfate for pre-eclampsia (144) and significant differences in occurrence of unpleasant dreams were lacking between the ketamine and magnesium groups (43).
  • Respiratory agentsRespiratory agents: In clinical research, intravenous magnesium caused respiratory depression (9; 120) and tachypnea (126).
  • QuinolonesQuinolones: In human research, magnesium reduced the effectiveness of fluoroquinolone antibiotics via chelation (117; 118).
  • Skeletal muscle relaxantsSkeletal muscle relaxants: In clinical research, oral magnesium has been reported to reduce leg cramps and muscle spasms (119; 136).
  • Tacrolimus (FK506, Prograf?)Tacrolimus (FK506, Prograf?): In human research, tacrolimus reduced renal tubular reabsorption of magnesium, resulting in increased excretion (270). This has been reported to result in hypomagnesemia in a significant proportion of people treated with tacrolimus.
  • TetracyclineTetracycline: In human research and clinical review, administration of oral magnesium salts with oral tetracyclines or quinolone antibiotics formed nonabsorbable complexes, resulting in decreased absorption of tetracyclines and quinolones (206; 207; 208). Therefore, it is advised that magnesium should be ingested two or more hours before or after tetracycline.
  • Thyroid hormonesThyroid hormones: In vitro and in animal research, changes in thyroid hormone levels had an effect on magnesium homeostasis; supplementation of thyroid hormone to hypothyroid animals restored magnesium levels and transport (271). According to secondary sources, oral magnesium salts have been reported to chelate oral levothyroxine within the gastrointestinal tract when administered simultaneously, leading to decreased thyroid hormone absorption. To minimize this interaction, it is advised to administer thyroid hormones at least four hours before or after antacids or other drugs containing magnesium.

    • Magnesium/Herb/Supplement Interactions:

  • GeneralGeneral: According to secondary sources, it is advised to separate magnesium ingestion from any other medication, including herbs or other supplements, by two hours or more (when taken in amounts greater than recommended daily allowances or through the diet). According to a review, minerals in foods may both form complexes with drugs and change the environment of the gastrointestinal system resulting in a change in the normal absorption processes of either or both of the drugs and the minerals (183). The authors suggest that absorption, as well as depletion and retention may all be affected and that simultaneous antacid ingestion may induce drug-mineral interactions.
  • AluminumAluminum: Some magnesium-containing products also contain aluminum. Theoretically, concurrent use of other aluminum-containing products may increase the risk of toxicity, particularly in patients with renal impairment.
  • AnalgesicsAnalgesics: In human research, magnesium had a small but beneficial effect as an analgesic (42; 42; 43; 44; 60) and resulted in a reduction in the need for morphine following surgery (42).
  • AntiarrhythmicsAntiarrhythmics: In clinical research, intravenous magnesium has been reported to reduce the incidence of atrial fibrillation and cardiac arrhythmias (192; 25; 26; 27; 29; 28; 30; 32; 193; 194; 123; 128; 195; 124; 196; 151; 19; 20; 21; 22; 23; 31). Magnesium-containing antacids may increase urinary pH and alter excretion of the class I antiarrhythmic agent quinidine (197). Concurrent use of magnesium and quinidine may increase the risk of quinidine toxicity (198).
  • Antiasthmatic herbs and supplementsAntiasthmatic herbs and supplements: In clinical research, magnesium sulfate (often in combination with pharmaceutical agents) has been shown to be effective for the treatment of acute asthma exacerbations in some studies; however, effects in children with mild to moderate symptoms were small or lacking (33; 34; 35; 36; 168; 39; 40; 199; 37; 200; 172; 201; 173; 202; 203; 169; 204; 41).
  • AntibacterialsAntibacterials: In human research and according to secondary sources, magnesium was found to reduce the effectiveness of certain antibiotics, such as fluoroquinolones and cephalosporins, via chelation (117; 118). Concurrent use of magnesium and aminoglycosides may result in neuromuscular weakness (188). According to secondary sources, nephrotoxicity caused by aminoglycosides (e.g., streptomycin and tobramycin) may lead to increased urinary loss of various electrolytes, including magnesium. According to a review, gentamycin alters magnesium handling by the body (205). According to human research and clinical review, administration of oral magnesium salts with oral tetracyclines or quinolone antibiotics may form nonabsorbable complexes, resulting in decreased absorption of tetracyclines and quinolones (206; 207; 208). Therefore, it is advised that magnesium should be ingested two or more hours before or after tetracycline. However, other clinical studies have shown no effect on bioavailability by coadministration (209; 210; 211; 212; 213; 214).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In human research, magnesium has been found to inhibit platelet aggregation (99; 100; 101). In clinical research, oral magnesium treatment inhibited platelet-dependent thrombosis (PDT) in stable patients with coronary artery disease (CAD); however, a significant effect of magnesium treatment on platelet aggregation was lacking (102).
  • AnticonvulsantsAnticonvulsants: In clinical research, magnesium sulfate has been shown to be an effective drug for the prevention of the recurrence of seizures in eclampsia and in seizure prophylaxis in pre-eclampsia (toxemia of pregnancy) (6; 7; 8; 9; 10; 11; 12; 13; 14; 15; 16; 17; 6; 18).
  • Anti-inflammatory herbsAnti-inflammatory herbs: In vitro, antacid compounds containing magnesium enhanced the solubility, dissolution, and bioavailability of anti-inflammatory herbs or supplements (256).
  • BoronBoron: The biochemical and physiologic consequences of boron deprivation were investigated in humans fed diets low or adequate in magnesium (details related to magnesium are lacking) (272).
  • BronchodilatorsBronchodilators: Clinically, magnesium is often used as an adjunct to treatment with beta-2 agonists (33; 34; 35; 36; 168; 39; 40; 199; 37; 200; 172; 201; 173; 202; 203; 225; 169; 204). Beta-2 agonists promote movement of magnesium from the extracellular to the intracellular space, and increase magnesium excretion in the urine. Reduced serum magnesium levels have been shown to occur after a single dose of albuterol or terbutaline orally, or by intravenous infusion, SC injection, or inhalation. The reductions are generally small (about 0.04-0.06mmol/L); it is unlikely that individuals receiving regular doses of beta-2 agonists will need magnesium supplementation unless they have other factors contributing to magnesium deficiency.
  • CalciumCalcium: In animal and human research and according to secondary sources, concurrent use with magnesium caused increases in serum or magnesium concentrations, particularly in patients with renal insufficiency (227; 228; 229). According to a systematic review, use of magnesium increased hypocalcemia (54). According to a systematic review the inverse association observed in observational studies between dietary calcium intake and risk of type 2 diabetes may have been at least partially confounded by intake of magnesium (230). During blood transfusion, risk of hypomagnesemia was found to increase with hypocalcemia (231). In a review, the authors indicate that individuals taking supplementary estrogen may also be taking supplementary calcium, resulting in an increased blood ratio of calcium to magnesium, increasing the risk of thrombosis (232).
  • Calcium-decreasing agentsCalcium-decreasing agents: In human research, magnesium enhanced the hypotensive effect of calcium channel blockers (226).
  • Cardiac glycosidesCardiac glycosides: In human research and clinical review, magnesium salts, such as magnesium sulfate, decreased digoxin levels by decreasing the absorption of digoxin (233; 234; 235). According to a review, digoxin increases magnesium excretion, increased levels of magnesium decrease the clinical effects of the cardiac glycosides, and magnesium increases the binding of cardiac glycosides to the receptor (134).
  • Cardiovascular agentsCardiovascular agents: In clinical research, magnesium has been reported to produce hypotension, reduced arterial pressure, bradycardia, tachycardia, myocardial infarction, cardiac events, and arrhythmias (123; 124; 29; 21; 44; 120; 58; 54; 53; 115; 125; 126; 43; 127). Increased blood pressure has also been reported (115).
  • Dermatologic agentsDermatologic agents: In human research, flushing, feeling of warmth, burning pain around the navel, welts, sweating, problems at the injection site, and diaphoresis have also been reported as possible adverse effects of magnesium (8; 128; 120; 129; 130; 127; 6; 116; 57; 55; 125; 127).
  • DiureticsDiuretics: According to human research and clinical review, diuretics interfere with the kidney's ability to regulate magnesium concentrations (131; 132). Long-term use of loop diuretics or thiazide diuretics may impair the magnesium-conserving ability of the kidneys and lead to hypomagnesemia (133; 134). Conversely, long-term use of potassium-sparing diuretics has been found to increase renal tubular reabsorption of magnesium, which may cause hypermagnesemia in patients also receiving magnesium supplements, especially in patients with renal insufficiency (244). Deray et al. published a report on the treatment of cardiac failure with angiotensin-converting enzyme inhibitors and diuretics (184). The authors also discussed the prevention of the secondary effects of diuretics and ACE inhibitors on renal function, serum sodium, and potassium and magnesium concentrations. Further details are lacking. Acute urinary retention has been reported as a possible adverse effect of magnesium (6).
  • ElectrolytesElectrolytes: According to a systematic review electrolyte disturbance has been reported (53).
  • Gastrointestinal agentsGastrointestinal agents: Gastrointestinal irritation, nausea, vomiting, mild abdominal pain, dry mouth, constipation, and diarrhea, soft stool, and delayed meconium (neonates) have all been suggested as possible adverse effects of magnesium (135; 136; 137; 138; 139; 120; 115; 126; 140; 141; 127; 142; 6; 6; 57; 176).
  • HypoglycemicsHypoglycemics: In clinical research, oral magnesium has been reported to improve glycemic control in type 2 diabetes (45; 46; 49; 105; 106). Concurrent use of magnesium with antidiabetic agents, particularly sulfonylureas (e.g., glipizide), may increase the risk of hypoglycemia by increasing the rate of absorption (103; 104).
  • HypotensivesHypotensives: Several clinical studies have reported a small decrease in blood pressure, which is statistically significant in some, but not all, studies with magnesium (107; 108; 109; 110; 111; 112; 113; 114; 115). However, increased blood pressure has also been reported (115). A meta-analysis of epidemiological studies supported the inverse relationship between blood pressure and urinary magnesium levels (215). Concurrent use of magnesium sulfate and nifedipine has reportedly caused hypotension, hypocalcemia, and neuromuscular blockade (216; 217; 218); however, conversely, a comprehensive retrospective study found a lack of adverse effects (in particular severe hypotension) from the simultaneous administration of nifedipine and magnesium sulfate (219).
  • ImmunosuppressantsImmunosuppressants: According to a review, cyclosporine alters magnesium handling by the body (205).
  • LaxativesLaxatives: In human research, magnesium hydroxide lacked effect, or was less effective than a comparator, for constipation (138; 141).
  • Muscle relaxantsMuscle relaxants: In clinical research, oral magnesium has been reported to reduce leg cramps and muscle spasms (119; 136).
  • Musculoskeletal agentsMusculoskeletal agents: In clinical research, magnesium has been reported to decrease skeletal muscle tone and cause limb weakness (119; 120; 53; 6), bone pain (115), hypocalcemic tetany (53), and according to secondary sources, loss of tendon reflexes.
  • Neurologic agentsNeurologic agents: According to clinical research, adverse effects have included headaches (57; 120; 143; 6), as well as slurred speech, dizziness, drowsiness, disorientation, and confusion (120; 130), and according to secondary sources, central nervous system depression. However, in human research, magnesium was beneficial in individuals with migraine headaches (163; 252; 139).
  • Neuromuscular blockersNeuromuscular blockers: In case reports, magnesium potentiated the effect of neuromuscular blockers, particularly those with renal failure (253).
  • Neuroprotective agentsNeuroprotective agents: Animal research has shown that magnesium may have neuroprotective effects (254). Systematic reviews/meta-analyses of earlier studies of antenatal magnesium sulfate therapy as a neuroprotective agent for the preterm fetus lacked a definite benefit (255; 129); however, a systematic review found a significant trend that antenatal Mg therapy may improve motor function in early childhood for infants born prematurely (255) and more recent meta-analyses of data suggests in utero use of magnesium sulfate reduces the risk of developing cerebral palsy of infants at risk for premature delivery, especially if magnesium sulfate was used for neuroprotection (55; 56; 57; 58).
  • Ocular agentsOcular agents: Visual impairment and nystagmus have been reported in clinical trials (115; 6).
  • OleanderOleander: According to a review, magnesium concentrations are not highly likely to be affected in yellow oleander poisoning (273). However, this review discussed the role of magnesium in reducing some of the symptoms of yellow oleander poisoning, such as hypomagnesemia (if it occurs) and arrhythmia (other preferred treatments exist).
  • Osteoporosis agentsOsteoporosis agents: In human research, magnesium, alone or in combination with calcium, vitamin D, and zinc, reduced bone turnover (245; 246; 75). In combination with calcium, vitamin D, and other minerals, magnesium increased bone density (247). Magnesium supplementation in postmenopausal osteoporotic women resulted in decreased serum iPTH and urinary deoxypyridinoline and increased serum osteocalcin (246; 75).
  • PhosphatesPhosphates: Concomitant use of oral preparations in conjunction with magnesium compounds such as antacids containing magnesium (e.g., magnesium carbonate, magnesium hydroxide) may bind phosphate in the stomach and reduce its absorption (145; 146; 147; 148). It is advised to separate the administration of sodium phosphate salts from magnesium-containing products by at least one hour.
  • PhytoestrogensPhytoestrogens: In human research and clinical review, estrogens enhance magnesium uptake by soft tissues and bones, thus lowering serum levels (248; 249). An inverse relationship between estrogen levels and magnesium serum levels has been reported. According to a review, magnesium levels were lower in women on the pill vs. women not on the pill (182). The interrelationship of magnesium and estrogen has been the topic of a review (232). The authors suggest that when estrogen levels are high and magnesium intakes are low, resulting magnesium levels may be decreased. They also indicate that individuals taking supplementary estrogen may also be taking supplementary calcium, resulting in an increased blood ratio of calcium to magnesium, increasing the risk of thrombosis.
  • PotassiumPotassium: According to a review, magnesium intake may affect the level of blood pressure reduction induced by potassium (260).
  • Proton pump inhibitors (PPIs)Proton pump inhibitors (PPIs): In clinical research, case studies, and reviews, use of proton pump inhibitors has been associated with decreased magnesium levels (261; 262; 263; 264; 265; 266; 267; 268; 269); severe hypomagnesemia has been reported in some cases (262; 263; 268).
  • Psychiatric agentsPsychiatric agents: In a case study, hypermagnesemia has been reported to cause delirium in a patient receiving magnesium sulfate for pre-eclampsia (144) and significant differences in occurrence of unpleasant dreams were lacking between the ketamine and magnesium groups (43).
  • Respiratory agentsRespiratory agents: In clinical research, intravenous magnesium caused respiratory depression (9; 120) and tachypnea (126).
  • SedativesSedatives: According to secondary sources, magnesium toxicity may be associated with central nervous system depression. In clinical research, a high intravenous dosage (1-2g/hour) of magnesium caused respiratory depression (9).
  • SteroidsSteroids: According to human research, chronic use of corticosteroids increases urinary magnesium excretion (242). Magnesium-containing antacids have also been found to reduce the bioavailability of corticosteroids, such as prednisone (243).
  • Thyroid agentsThyroid agents: In vitro and in animal research, changes in thyroid hormone levels had an effect on magnesium homeostasis; supplementation of thyroid hormone to hypothyroid animals restored magnesium levels and transport (271). According to secondary sources, oral magnesium salts have been reported to chelate oral levothyroxine within the gastrointestinal tract when administered simultaneously, leading to decreased thyroid hormone absorption. To minimize this interaction, it is advised to administer thyroid hormones at least four hours before or after antacids or other drugs containing magnesium.
  • Vitamin DVitamin D: According to a review, large (pharmacological) doses of vitamin D increase the absorption of vitamin D in animal models; however, vitamin D may also increase urinary excretion of magnesium (274).

    • Magnesium/Food Interactions:

  • DairyDairy: According to case reports, excessive consumption of dairy products (3L daily) with magnesium-containing antacids may cause milk-alkali syndrome (275; 276). According to a review, dairy products are a good source of magnesium (277).
  • Parenteral nutritionParenteral nutrition: In human research, cyclic parenteral nutrition infusion lacked association with magnesium losses (278).

    • Magnesium/Lab Interactions:

  • Alkaline phosphataseAlkaline phosphatase: According to secondary sources, due to an activation of enzymes used in laboratory procedures, magnesium salts may cause a false increase in serum alkaline phosphatase test results. It has been suggested that this is a short-term effect.
  • Angiotensin-converting enzyme (ACE)Angiotensin-converting enzyme (ACE): According to secondary sources, magnesium sulfate may reduce serum ACE concentrations and test results in the short term.
  • Blood glucoseBlood glucose: In clinical research, oral magnesium has been reported to improve glycemic control in type 2 diabetes (45; 46; 49; 105; 106). Concurrent use of magnesium with agents, particularly sulfonylureas (e.g., glipizide), may increase the risk of hypoglycemic by increased rate of absorption (103; 104).
  • Blood pressureBlood pressure: Several clinical studies have reported a small decrease in blood pressure, which is statistically significant in some, but not all, studies with magnesium (107; 108; 109; 110; 111; 112; 113; 114; 115). However, increased blood pressure has also been reported (115). In clinical research, intravenous magnesium has been reported to produce hypotension (123; 124).
  • Bone markersBone markers: Magnesium supplementation in postmenopausal osteoporotic women resulted in decreased serum iPTH and urinary deoxypyridinoline and increased serum osteocalcin (246; 75).
  • CalciumCalcium: According to secondary sources, magnesium salts may cause a false increase in serum calcium test results in some procedures using edetate disodium (EDTA). It has been suggested that this is a short-term effect. According to a systematic review, use of magnesium increased hypocalcemia (54).
  • Coagulation panelCoagulation panel: In human research, magnesium has been found to inhibit platelet aggregation (99; 100; 101). In clinical research, oral magnesium treatment inhibited platelet-dependent thrombosis (PDT) in stable patients with coronary artery disease (CAD); however, there was no significant effect of magnesium treatment on platelet aggregation (102).
  • CortisolCortisol: In clinical research, magnesium has been shown to decrease plasma cortisol levels (156).
  • Diagnex BlueDiagnex Blue: According to secondary sources, magnesium salts may increase urine Diagnex Blue concentrations and test results by heavy metal displacement of Diagnex Blue.
  • Electrocardiogram (ECG)Electrocardiogram (ECG): In clinical research, intravenous magnesium has been reported to reduce the incidence of atrial fibrillation and cardiac arrhythmias (24; 25; 26; 27; 29; 28; 30; 32; 193).
  • Estrogen levelsEstrogen levels: According to secondary sources, magnesium may decrease serum estrogen levels.
  • Interleukin-2Interleukin-2: Asymptomatic hypomagnesemia may occur with aldesleukin therapy, possibly due to an intracellular shift of magnesium (185). Urinary magnesium did not increase, and serum levels normalized a few days after the drug was discontinued.
  • Liver enzymesLiver enzymes: In patients with alcohol withdrawal, magnesium resulted in a decrease in gamma-glutamyl transferase (GGT) (154).
  • Parathyroid hormone (PTH)Parathyroid hormone (PTH): According to secondary sources, decreased magnesium serum levels stimulated PTH secretion. Paradoxically, a more profound decrease in serum magnesium may actually decrease PTH secretion. In severe magnesium deficiency, PTH secretion is impaired; however, serum PTH increased within minutes of intravenous magnesium administration.
  • PhosphatePhosphate: Concomitant use of oral preparations in conjunction with magnesium compounds, such as antacids containing magnesium (e.g., magnesium carbonate, magnesium hydroxide), may bind phosphate in the stomach and reduce its absorption (145; 146; 147; 148).
  • TestosteroneTestosterone: In animal and in vitro studies, intravenous magnesium sulfate reduced testosterone levels (279; 280).
  • Thyroid hormonesThyroid hormones: In vitro and in animal research, changes in thyroid hormone levels had an effect on magnesium homeostasis; supplementation of thyroid hormone to hypothyroid animals restored magnesium levels and transport (271). According to secondary sources, oral magnesium salts have been reported to chelate oral levothyroxine within the gastrointestinal tract when administered simultaneously, leading to decreased thyroid hormone absorption. To minimize this interaction, it is advised to administer thyroid hormones at least four hours before or after antacids or other drugs containing magnesium.