Magnesium

Español

Summary

• Magnesium is an essential mineral that serves as a cofactor for hundreds of enzymes. It is needed for a wide range of physiologic pathways, including energy production, nucleic acid and protein synthesis, ion transport, cell signaling, and has structural functions. (More information)

• Severe magnesium deficiency can disrupt vitamin D and calcium homeostasis. Individuals at higher risk include those with gastrointestinal or kidney disorders, those suffering from chronic alcoholism, and older adults. (More information)

• Inadequate dietary intakes and/or low serum concentrations of magnesium have been associated with increased risk of cardiovascular disease, osteoporosis, and metabolic disorders, including metabolic syndrome, hypertension, and type 2 diabetes mellitus. Magnesium supplementation may improve insulin sensitivity in individuals at risk for type 2 diabetes mellitus. Randomized controlled trials have also explored the use of intravenous magnesium to prevent complications after stroke or heart surgery. (More information)

• Intravenous magnesium sulfate is commonly used in obstetric care for the prevention of seizures in pregnant people with preeclampsia or eclampsia and to protect the brains of premature infants. (More information)

• Magnesium supplementation is currently being studied for its potential role in managing various conditions, including hypertension, cardiovascular disease, type 2 diabetes mellitus, asthma and pain. (More information)

• National surveys indicate that over one-half of US adults have inadequate dietary magnesium intake. Good dietary sources of magnesium include green leafy vegetables, unrefined grains, legumes, beans, and nuts. (More information)

• Excessive magnesium intake from supplements can lead to adverse effects, especially in individuals with impaired kidney function. The Tolerable Upper Intake Level (UL) is 350 mg/day, and this applies specifically to supplemental magnesium. (More information)

Image

[Download PDF]

Get Updates from the Institute

Vitamins

Minerals

Other Nutrients

Magnesium plays important roles in both the structure and the function of the human body. The adult human body contains about 25 grams (g) of magnesium. About 50%-60% of all the magnesium in the body is found in the skeleton and the remainder is found in soft tissue, primarily muscle. Magnesium is the second most abundant intracellular cation after potassium. Blood contains less than 1% of total body magnesium. Only the free, ionized form of magnesium (Mg²⁺) is physiologically active. Protein-bound and chelated magnesium serve to buffer the pool of free, ionized magnesium (1).

Function

Magnesium is involved in more than 300 essential metabolic reactions, some of which are discussed below (2).

Energy production

The metabolism of carbohydrates and fats to produce energy requires numerous magnesium-dependent chemical reactions. Magnesium is required for the adenosine triphosphate-synthesizing protein (ATP synthase) in mitochondria. ATP, the molecule that provides energy for almost all metabolic processes, exists primarily as a complex with magnesium (MgATP) (3).

Synthesis of essential molecules

Magnesium is required for a number of steps during synthesis of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and proteins. Several enzymes participating in the synthesis of carbohydrates and lipids require magnesium for their activity. Glutathione, an important antioxidant, requires magnesium for its synthesis (3).

Structural roles

Magnesium plays a structural role in bone, cell membranes, and chromosomes (3).

Ion transport across cell membranes

Magnesium is required for the active transport of ions like potassium and calcium across cell membranes. This function is necessary for nerve impulses conduction, muscle contraction, and normal heart rhythm (3).

Cell signaling

Cell signaling processes require MgATP for protein phosphorylation and the formation of cyclic adenosine monophosphate (cAMP), an important cell-signaling molecule. cAMP is involved in many physiological processes, including the secretion of parathyroid hormone (PTH) from the parathyroid glands (see the articles on Vitamin D and Calcium for information on the role of PTH in the body) (3).

Cell migration

Magnesium and calcium concentrations in the extracellular fluid affect the migration of various cell types. Such effects on cell migration may be important in wound healing (3).

Nutrient interactions

Zinc

High doses of supplemental zinc may interfere with magnesium absorption. One study reported that zinc supplements of 142 mg/day (well above the Tolerable Upper Intake Level (UL) of 40 mg/day for zinc) significantly decreased magnesium absorption and disrupted magnesium balance (the difference between magnesium intake and magnesium loss) in healthy adult males (4).

Fiber

Large increases in the intake of dietary fiber have been found to decrease magnesium utilization in experimental studies. However, the extent to which dietary fiber affects magnesium nutritional status in individuals with a varied diet outside the laboratory is not clear (2, 3).

Protein

Dietary protein intake may affect magnesium absorption. One study in adolescent boys found that magnesium absorption was lowest when protein intake was below 30 g/day (5).

Vitamin D and calcium

The active form of vitamin D (calcitriol) may slightly increase intestinal magnesium absorption (6). However, unlike calcium and phosphate, it is not clear whether magnesium absorption is calcitriol dependent. High calcium intake has not been found to affect magnesium balance in most studies. Inadequate blood magnesium concentrations are known to result in low blood calcium concentrations, resistance to parathyroid hormone (PTH) action, and resistance to some of the effects of vitamin D (2, 3).

Deficiency

Risk factors

Magnesium deficiency is quite rare in healthy individuals who are consuming a balanced diet, because magnesium is abundant in both plant and animal foods. In addition, the kidneys can limit urinary excretion of magnesium when intake is low. However, the following conditions increase the risk of magnesium deficiency (7):

• Gastrointestinal disorders: Prolonged diarrhea, Crohn's disease, malabsorption syndromes, celiac disease, surgical removal of parts of the small intestine, and radiation-induced intestinal inflammation can lead to magnesium depletion.
• Renal disorders (magnesium wasting): Diabetes mellitus and long-term use of certain diuretics (see Drug interactions) may result in increased urinary loss of magnesium. Several other medications may also contribute to renal magnesium wasting (3).
• Endocrine and metabolic disorders: Several conditions, such as diabetes mellitus, parathyroid gland disorders, phosphate depletion, primary aldosteronism, and even excessive lactation, can lead to magnesium depletion.
• Alcoholism: Poor dietary intake, gastrointestinal problems, and increased urinary loss of magnesium may all contribute to magnesium depletion in individuals with alcoholism.
• Older adults: Older individuals (>50 years) have relatively low dietary intakes of magnesium (8, 9). Intestinal magnesium absorption tends to decrease with age, and urinary magnesium excretion tends to increase with age; thus, suboptimal dietary magnesium intake may increase the risk of magnesium depletion in older adults (2).

Signs and symptoms

Although severe magnesium deficiency is uncommon, it has been induced experimentally. When magnesium deficiency was induced in humans, the earliest sign was a decrease in serum magnesium concentration. Hypomagnesemia is typically defined as serum magnesium concentrations less than 0.74 millimoles/liter (mmol/L), 1.40 milliequivalents/liter (mEq/L), or 1.70 milligrams/deciliter (mg/dL). Over time as magnesium deficiency progresses, serum calcium concentrations begin to decrease (hypocalcemia) despite adequate dietary calcium intake. Hypocalcemia persists despite increased secretion of parathyroid hormone (PTH), which regulates calcium homeostasis. Usually, increased PTH secretion quickly results in the mobilization of calcium from bone and normalization of blood calcium concentration. As the magnesium depletion progresses, PTH secretion diminishes (3).

In addition to hypomagnesemia, hypocalcemia, and low circulating PTH concentrations, signs of severe magnesium deficiency include low serum potassium concentrations (hypokalemia), retention of sodium, neurological and muscular symptoms (tremor, muscle spasms, tetany), loss of appetite, nausea, vomiting, and personality changes (3).

While mild magnesium deficiency may not elicit clinical symptoms, it may be associated with an increased risk of developing chronic diseases (see Disease Prevention) (1).

Assessing magnesium status

Currently, there is no reliable indicator of magnesium status. The magnesium tolerance test — used to assess magnesium retention (using a 24-hour urine collection) following intravenous administration of magnesium — is considered the gold standard for detecting hypomagnesemia in adults (1). However, this method is invasive, not practical for routine use, expensive, and lacks sensitivity to detect subtle changes in healthy individuals (10).

Another method involves measuring plasma ionized magnesium, which represents the physiologically active form of magnesium. But it is unknown whether this measurement accurately reflects total body stores of magnesium (10).

In clinical and research settings, magnesium status is commonly evaluated through dietary intake assessments, serum or plasma magnesium concentrations, and/or urinary magnesium excretion (10). Each of these indicators has limitations. Although predominantly used in epidemiological studies and the sole indicator available to clinicians, serum magnesium concentrations have been found to poorly respond to magnesium supplementation. Regarding dietary intakes of magnesium, about 30%-40% of ingested magnesium is absorbed, yet absorption varies with the amount of magnesium ingested and with the food matrix composition. Finally, a state of magnesium deficiency has not been associated with a clear cutoff concentration of magnesium in the urine. Urinary magnesium concentration fluctuates rapidly with dietary intakes, but measurements of 24-hour urinary magnesium can be used in addition to other indicators to assess population status. Presently, a combination of all three markers — dietary, serum, and urinary magnesium — may be used to obtain a valid assessment of magnesium status (reviewed in 10).

The RDA

In 1997, the Food and Nutrition Board of the National Academy of Medicine revised the Recommended Dietary Allowance (RDA) for magnesium, based on the results of tightly controlled balance studies that utilized more accurate methods of measuring magnesium (Table 1) (2). While balance studies are useful for determining the amount of a nutrient that will prevent deficiency, such studies provide little information regarding the amount of a nutrient required for chronic disease prevention or optimal health.

Disease Prevention

Metabolic syndrome

Metabolic syndrome refers to the concomitant presentation of several metabolic disorders in an individual, including dyslipidemia, hypertension, insulin resistance, and obesity (11). People with metabolic syndrome are at greater risk of developing type 2 diabetes mellitus, cardiovascular disease, and some types of cancer (12-14). Analyses of data from the US National Health and Nutrition Examination Survey (NHANES 2001-2010), involving 9,148 adults (mean age, 50 years), found a 32% lower risk of metabolic syndrome among those in the highest versus lowest quartile of magnesium intake (≥355 mg/day versus <197 mg/day) (15). Several meta-analyses of primarily cross-sectional studies have also reported an inverse association between dietary magnesium intake and risk of metabolic syndrome (16-19). Meta-analyses of four prospective cohort studies (20-23) further supported this association, finding higher dietary magnesium intake was associated with a lower risk of developing metabolic syndrome (19).

Lower serum magnesium concentrations have also been reported in individuals with metabolic syndrome compared to controls in some, but not all, observational studies (reviewed in 19). It is important to note that circulating (serum) magnesium represents only 1% of total body stores and is tightly regulated; thus, serum magnesium concentrations do not best reflect magnesium status (1).

Systemic inflammation, which contributes to the development of metabolic disorders, has been inversely correlated with magnesium intakes in a cross-sectional study of 11,686 women (≥45 years). The researchers who conducted this study reported that the lowest prevalence of metabolic syndrome was found in the group of women in the highest quintile of magnesium intakes (median intake, 422 mg/day) (24). Investigators of several randomized controlled trials also reported a reduction in circulating C-reactive protein (CRP) concentrations — a marker of inflammation — following oral magnesium supplementation (25). This anti-inflammatory effect may be one mechanism through which magnesium contributes to the prevention of metabolic disorders. Other potential mechanisms include improved glucose metabolism (see the section on Diabetes Mellitus) and reduced blood pressure (see the section on Hypertension).

Cardiovascular disease

Hypertension (high blood pressure)

Large prospective cohort studies have examined the relationship between magnesium and blood pressure. However, the fact that foods high in magnesium (fruit, vegetables, and whole grains) are frequently high in potassium and dietary fiber has made it difficult to evaluate the independent effect of magnesium on blood pressure. Findings from large cohorts, including the Health Professionals Follow-up Study (HPFS) (26), the Nurses’ Health Study (NHS) (27), the Atherosclerosis Risk in Communities (ARIC) study (28), and the Coronary Artery Risk Development in Young Adults (CARDIA) study (20), have been summarized in meta-analyses (29). Pooled analyses of seven prospective studies showed an 8% lower risk of hypertension with higher versus lower dietary magnesium intakes (29).

In one of these studies, data from 5,511 women and men followed for a median period of 7.6 years found that the highest concentrations of urinary magnesium corresponded to a 25% reduction in the risk of hypertension, whereas there was no association between plasma magnesium concentrations and the risk of hypertension (30). There was also no evidence of an association between circulating magnesium concentrations and the risk of hypertension in meta-analyses of three prospective cohort studies (29, 31).

The relationship between magnesium intake and risk of hypertension suggests that improving diet quality or using magnesium supplements might play a role in the prevention of hypertension in those with inadequate dietary intakes.

Vascular calcification

The buildup of plaque inside arterial walls — a process called atherosclerosis — is an early event in the development of cardiovascular disease. The calcification of atherosclerotic plaques that occurs with the progression of atherosclerosis has been associated with a three- to four-fold increase in the risk of cardiovascular events and mortality (32).

Individuals with chronic kidney disease (CKD)

Abnormalities in mineral and bone metabolism are not uncommon in individuals with impaired kidney function and have been associated with increased risks of cardiovascular disease and mortality (33, 34). In particular, elevated blood phosphorus concentration and increased deposition of calcium phosphate within the vasculature are thought to promote vascular calcification. Because magnesium can function as a calcium antagonist, it has been suggested that it could be utilized to slow down or reverse the calcification of vessels observed in individuals with CKD.

In a cross-sectional study in individuals with pre-dialysis CKD, higher serum magnesium concentrations were associated with lower coronary artery calcification density scores in those in the higher end of normal serum phosphorus concentrations (i.e., ≥3.4 mg/dL) (35). One small randomized, placebo-controlled trial in participants with pre-dialysis CKD examined the effect of oral, slow-release magnesium hydroxide on the calcification propensity of serum by measuring the time needed for primary calciprotein particles (containing amorphous calcium phosphate) to transform into secondary calciprotein particles (containing crystalline hydroxyapatite) (36). Increased serum calcification propensity has been associated with greater risk of mortality in individuals with impaired kidney function (37, 38). The investigators of the trial found an increase in serum magnesium concentrations and a reduction in serum calcification propensity (i.e., an increase in the time needed for 50% of the transformation to occur [T50]) with 720 mg/day of supplemental slow-release magnesium hydroxide for eight weeks compared to placebo (36). Serum calcification propensity was also reduced when magnesium concentration was increased (from 1 to 2 mEq/L for 28 days) in the dialysate of individuals with established kidney failure (39). However, in a randomized, double-blind, placebo-controlled trial in 148 individuals with pre-dialysis CKD (the MAGiCAL-CKD trial), conducted by the same investigators, oral slow-release magnesium hydroxide supplementation (720 mg/day) for 12 months increased serum magnesium but had no effect on serum calcification propensity (40). Results of an open-label study suggested a potential benefit of magnesium oxide supplementation (610 mg/day for 12 months) in slowing vascular calcification in CKD. This two-year trial was terminated early after the interim results showed less coronary artery calcification progression in the magnesium group compared to placebo (41).

While some studies suggest that magnesium supplementation might help mitigate vascular calcification in individuals with chronic kidney disease, findings to date are somewhat conflicting. Large, well-controlled trials are necessary to determine the efficacy of supplemental magnesium in this population.

Individuals with normal kidney function

Cross-sectional analyses of data from 2,695 middle-aged participants in the Framingham Heart Study showed that the odds of having coronary artery calcification as 58% lower in those in the highest versus lowest quartile of total magnesium intakes (median values, 427 mg/day versus 259 mg/day) (42). Serum magnesium concentration was also found to be inversely associated with vascular calcification in population-based cross-sectional studies (43-45). However, in cross-sectional analyses of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), which included 4,306 participants, no association between dietary magnesium intake and the presence of coronary artery calcification was found (46). No research has yet examined whether improving magnesium status of generally healthy people could play a role in prevention of atherosclerosis.

Risk of cardiovascular disease

Dietary magnesium intakes

Several large prospective cohort studies, including the Health Professionals Follow-up Study (HPFS) and the Nurses’ Health Study (NHS), have examined magnesium intakes in relation to cardiovascular outcomes. In the most recent analyses of the NHS, which followed nearly 90,000 female nurses for 28 years, those in the highest quintile of magnesium intake had a 39% lower risk of fatal myocardial infarction (but not nonfatal coronary heart disease [CHD]) compared to those in the lowest quintile (>342 mg/day versus <246 mg/day) (47). Meta-analyses of nine prospective cohort studies, mostly conducted in participants without cardiovascular disease at baseline, reported a 22% lower risk of CHD per 200 mg/day incremental intake in dietary magnesium (48). A more recent meta-analyses by Fang et al. (49) included six studies; the authors reported a 10% lower risk of CHD with higher versus lower dietary magnesium intakes.

Higher magnesium intakes were associated with an 8 to 11% reduction in stroke risk in two meta-analyses of prospective studies, each including over 240,000 participants (50, 51). A more recent pooled analyses of 18 cohorts, including 20,138 stroke cases among 692,998 participants, found a 11% lower risk of total stroke and a 12% lower risk of ischemic stroke with higher versus lower magnesium intakes (52).

Only two prospective studies have examined the risk of heart failure in relation to magnesium intakes. The pooled analyses suggested a 31% lower risk of heart failure with higher dietary magnesium intakes (49).

Finally, meta-analyses of 13 prospective studies in over 475,000 participants reported that the risk of total cardiovascular events, including stroke, nonfatal myocardial infarction, and CHD, was 15% lower in individuals with higher intakes of magnesium (53). However, in meta-analyses of eight studies by Fang et al. (49), there was no association between dietary magnesium intake and risk of total cardiovascular disease.

It is important to note that while these prospective cohort studies assessed the association between dietary magnesium and cardiovascular disease, they did not account for the use of supplemental magnesium by a significant fraction of participants.

Serum magnesium concentrations

One large prospective study (almost 14,000 women and men followed for 4 to 7 years), the Atherosclerosis Risk in Communities (ARIC) Study, associated higher serum magnesium concentrations with a lower risk of CHD in women but not in men (54). These sex-specific findings persisted in a subsequent follow-up of the same cohort after 27 years: women in the lowest quintile of serum magnesium concentration (median=1.45 mEq/L) had a 53% higher risk of CHD compared to women in the highest quintile (median=1.80 mEq/L), while no association was found in men (55). This study was included in meta-analyses of five observational studies, which found a 18% increased risk of CHD with the lowest versus highest serum magnesium concentration (55).

In another meta-analyses, which pooled the results of eight prospective cohort studies, each 0.2 mmol/L increment in serum magnesium concentration was associated with a 30% lower risk of total cardiovascular disease (48). In the British Regional Heart Study that followed 3,523 men for a mean 15 years, no association between serum magnesium concentration and incidental CHD events was found, yet serum magnesium concentration was inversely associated with the risk of heart failure (56).

Cardiovascular mortality

Lower cardiovascular-related mortality has been observed in populations who routinely consume "hard" water. Hard (alkaline) water is generally high in magnesium but may also contain more calcium and fluoride than "soft" water, making the cardioprotective effects of hard water difficult to attribute to magnesium alone (57). No consistent associations between magnesium intake and mortality from cardiovascular disease have been reported by investigators conducting meta-analyses of prospective cohort studies (58, 59). In prospective analyses of NHANES data from 14,353 participants, followed for a median period of 28.6 years, the risk of stroke-related mortality was significantly increased in those with low rather than normal serum concentrations of magnesium (<0.7 mmol/L versus 0.8-0.89 mmol/L) (60). In contrast, hypermagnesemia (serum magnesium concentration >0.89 mmol/L) — rather than hypomagnesemia — in people with heart failure was associated with an increased risk of cardiovascular-related mortality (61).

Aneurysmal subarachnoid hemorrhage

Occurrence of hypomagnesemia has been reported in individuals who suffered from a subarachnoid hemorrhage (a type of stroke) caused by the rupture of a cerebral aneurysm (62). Poor neurologic outcomes following an aneurysmal subarachnoid hemorrhage (aSAH) have been linked to inappropriate calcium-dependent contraction of arteries (known as cerebral arterial vasospasm), leading to delayed cerebral ischemia (63). Because magnesium is a calcium antagonist and potent vasodilator, several randomized controlled trials have examined whether intravenous magnesium sulfate infusions could reduce the incidence of vasospasm after aSAH. Meta-analysis of nine randomized controlled trials found that magnesium therapy after aSAH significantly reduced vasospasm but failed to prevent neurologic deterioration or decrease the risk of death (64). Another meta-analyses of 13 trials in 2,413 aSAH sufferers concluded that the infusion of magnesium sulfate had no benefit regarding neurologic outcome and mortality, despite a reduction in the incidence of delayed cerebral ischemia (65). A recent network meta-analysis of 53 randomized trials, including 11 evaluating intravenous magnesium sulfate, confirmed that magnesium sulfate reduces the risk of delayed cerebral ischemia and vasospasm but does not reduce mortality. Notably, 10 of the 11 trials co-administered the calcium-channel blocker nimodipine, making it impossible to isolate the independent effects of magnesium (66).

Post-hoc analyses of a small randomized controlled trial suggested that maintaining magnesium sulfate infusion for 10 days post-aSAH or until signs of vasospasm disappear might protect against secondary cerebral infarction when markers of vasoconstriction and reduced brain perfusion are present (67, 68). Current evidence does not support the use of magnesium supplementation in clinical practice for individuals with aSAH beyond magnesium status normalization.

Complications of heart surgery

Atrial arrhythmia (also called atrial fibrillation) is a condition defined as the occurrence of persistent heart rate abnormalities; such arrhythmias often complicate the recovery of individuals after cardiac surgery. Magnesium has been investigated as a prophylactic agent for postoperative atrial arrhythmia after coronary artery bypass grafting, either alone or as an adjunctive agent to standard antiarrhythmic therapies (i.e., β-blockers and amiodarone) in several prospective, randomized controlled trials.

Meta-analysis of 21 intervention studies showed that intravenous magnesium infusions could significantly reduce postoperative atrial arrhythmia in those treated compared to those not treated (69). The results of more recent meta-analyses of 22 placebo-controlled trials suggested that magnesium may effectively reduce atrial arrhythmia when administered post-operatively, as a bolus, and for more than 24 hours (70). However, another meta-analyses of four trials found that magnesium was no more effective than other antiarrhythmic agents (70). Moreover, meta-analyses of five randomized controlled trials also suggested that intravenous magnesium added to β-blocker treatment did not decrease the risk of atrial arrhythmia compared to β-blocker alone and was associated with more adverse effects (bradycardia and hypotension) (71).

Presently, high-quality evidence is still lacking to support the use of magnesium in the prophylaxis of post-operative atrial fibrillation and other arrhythmias in individuals with contraindications to first-line antiarrhythmic agents (70). A large, ongoing phase II randomized controlled trial (the POMPAE trial) is currently evaluating whether continuous intravenous magnesium sulfate infusing might reduce the incidence of postoperative atrial fibrillation in individuals undergoing cardiac surgery (72).

Diabetes mellitus

Public health concerns regarding the epidemics of obesity and type 2 diabetes mellitus and the prominent role of magnesium in glucose metabolism have led scientists to investigate the relationship between magnesium intake and type 2 diabetes mellitus. A prospective cohort study that followed more than 25,000 individuals, 35 to 65 years of age, for seven years found no difference in incidence of type 2 diabetes mellitus when comparing the highest (377 mg/day) quintile of magnesium intake to the lowest quintile (268 mg/day) (73). However, inclusion of this study in meta-analyses of eight cohort studies showed that the risk of type 2 diabetes mellitus was inversely correlated with magnesium intake (73).

A 2016 meta-analyses of 25 prospective cohort studies, including 637,922 individuals and 26,828 new cases of type 2 diabetes mellitus, found that higher magnesium intakes were associated with a 17% lower risk of type 2 diabetes mellitus (74). Several meta-analyses have reported an 8%-15% decrease in the risk of developing type 2 diabetes mellitus with each 100 mg-increment in dietary magnesium intake (74-77). More recently, meta-analyses that pooled results of 26 prospective cohort studies found that adults with the highest dietary magnesium intakes had a 22% lower risk of developing type 2 diabetes mellitus compared to these with the lowest intakes (52). This meta-analyses reported a 6% reduction in disease risk for each 100 mg/day incremental increase in dietary magnesium intake (52). In addition, an umbrella review of systematic reviews and meta-analyses, including analyses of 32 observational studies (1,084,602 participants), concluded that higher dietary intakes of magnesium were associated with a lower risk of type 2 diabetes mellitus in the general population (78). The highest versus lowest quartile of dietary magnesium intake was associated with a 28% lower risk (78).

Insulin resistance, characterized by alterations in both insulin secretion by the pancreas and insulin action on target tissues, has been linked to inadequate magnesium status. A cross-sectional analyses of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, which included 15 cohorts with a total of 52,684 participants without diagnosed diabetes mellitus, showed that magnesium intakes were inversely associated with fasting insulin concentrations after multiple adjustments, including various lifestyle factors, body mass index (BMI), caffeine intake, and fiber intake (76). It is thought that pancreatic β-cells, which secrete insulin, could become less responsive to changes in insulin sensitivity in individuals with magnesium-deficiency (79). A randomized, double-blind, placebo-controlled trial that enrolled 97 healthy adults with significant hypomagnesemia (serum magnesium concentration ≤0.70 mmol/L) showed that daily consumption of 638 mg of magnesium (from a solution of magnesium chloride) for three months improved the function of pancreatic β-cells, resulting in lower fasting glucose and insulin concentrations (80). In a follow-up randomized controlled trial, the administration of 382 mg/day of magnesium for four months to participants (mean age, 42 years) with both hypomagnesemia (serum magnesium concentration <0.74 mmol/L) and impaired fasting glucose improved serum magnesium concentrations, as well as fasting and post-load glucose concentrations (81). Other metabolic markers, including measures of serum triglycerides and HDL-cholesterol concentrations, and a measure of insulin resistance, also improved in magnesium- versus placebo-treated individuals (81). Additionally, similar metabolic improvements have been reported following the supplementation with magnesium chloride solution (equivalent to 382 mg/day of magnesium for four months) to participants who had hypomagnesemia and were lean, yet metabolically obese (i.e., with metabolic disorders usually associated with obesity) (82). In another study, supplementation with 365 mg/day of magnesium (from magnesium aspartate hydrochloride) for six months reduced insulin resistance in 27 overweight individuals with normal values of serum and intracellular magnesium (83). This latter study suggests that magnesium might have additional effects on glucose tolerance and insulin sensitivity that go beyond the normalization of serum magnesium concentrations in individuals who had hypomagnesemia. Meta-analyses of randomized, double-blind placebo-controlled trials found that magnesium supplementation significantly improved fasting glucose concentration (11 trials), glucose tolerance (3 trials), and insulin resistance (9 trials) in individuals at high risk of developing type 2 diabetes mellitus, including those who were overweight or had prediabetes, metabolic syndrome, or polycystic metabolic syndrome (84).

Osteoporosis

Although decreased bone mineral density (BMD) is the primary feature of osteoporosis, other osteoporotic changes in the collagenous matrix and mineral composition of bone may result in bones that are brittle and more susceptible to fracture (85). Around 60% of total body magnesium is stored in the skeleton and is known to influence both bone matrix and bone mineral metabolism. Magnesium at the surface of bones is also available for dynamic exchange with blood (86). As the magnesium content of bone mineral decreases, hydroxyapatite crystals of bone may become larger and more brittle. Some studies have found lower magnesium content and larger hydroxyapatite crystals in bones of women with osteoporosis compared to disease-free women (87). Inadequate serum magnesium concentrations are known to result in low serum calcium concentrations, resistance to parathyroid hormone (PTH) action, and resistance to some of the effects of vitamin D (calcitriol), all of which can lead to increased bone loss (see the articles on Vitamin D and Calcium). Lower serum magnesium concentrations may not be unusual in postmenopausal women with osteoporosis (88, 89), and hypomagnesemia has been reported as an adverse effect of using the prescription drug teriparatide (Forteo) in the treatment of osteoporosis (90).

Higher dietary magnesium intakes have been associated with increased site-specific (91) and total-body BMD (92) in observational studies, including studies of older adults. In a large cohort study conducted in almost two-thirds of the Norwegian population, the concentration of magnesium in drinking water was inversely associated with the risk of hip fracture (93). In the Women’s Health Initiative study, data analyses from 4,778 participants (mean age, 63 years), followed for about seven years, showed that higher magnesium intakes were associated with higher hip and whole-body BMD but not with reduced hip or total fractures (94). Moreover, the highest versus lowest quintile of total magnesium intakes was associated with a 23% increased risk of lower arm and wrist fractures (94). Large prospective, observational studies of Chinese adults have associated very high dietary intakes of magnesium (>400 mg/day) with an increased risk of osteoporotic fracture in a men (95) but not in women (96). Yet, in a case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study, which included 5,319 individuals, total magnesium and potassium intakes were found to be inversely associated with heel bone (calcaneus) broadband ultrasound attenuation (BUA) measurements — which are predictive of the risk of incidental fracture — and with the risk of hip fractures (97).

Few studies have addressed the effect of magnesium supplementation on BMD or osteoporosis in humans. In a small group of postmenopausal women with osteoporosis, magnesium supplementation of 750 mg/day for six months followed by 250 mg/day for 18 more months resulted in increased BMD at the wrist after one year, with no further increase after two years of supplementation (98). A study in postmenopausal women who were taking estrogen replacement therapy and a multivitamin supplement found that supplementation with an additional 400 mg/day of magnesium and 600 mg/day of calcium resulted in increased BMD at the heel compared to postmenopausal women receiving estrogen replacement therapy only (99). In a randomized controlled study conducted in 20 postmenopausal women with osteoporosis, high-dose supplementation with magnesium citrate (1,830 mg/day) for one month reduced the rapid rate of bone loss that characterizes osteoporosis (100). Evidence is not yet sufficient to suggest that supplemental magnesium in excess of the RDA could be effective in the prevention of osteoporosis unless normalization of serum magnesium concentration is required (101, 102).

Sarcopenia

Sarcopenia is a condition characterized by a loss of skeletal muscle mass that increases frailty and risk of falls in older adults (103). Several cross-sectional studies have reported a positive association between dietary magnesium intakes and proxy measures of skeletal muscle mass in middle-age and older adults (104-107) or with a lower risk of sarcopenia (104, 108, 109). A 2014 randomized controlled study in 139 physically active and healthy older women (mean age, 71.5 years) found little-to-no impact of magnesium supplementation (900 mg/day of magnesium oxide) for 12 weeks on body composition and muscle strength, yet the Short Physical Performance Battery [SPPB] test score — a composite indicator of physical function — improved (110). More research is needed to examine further the effect of magnesium supplementation on body composition, muscle strength, and physical performance in older adults, whether physically active or sedentary, and with normal or inadequate magnesium status.

Disease Treatment

The use of pharmacologic doses of magnesium to treat specific disorders is discussed below. Although many of the cited studies utilized supplemental magnesium at doses considerably higher than the Tolerable Upper Intake Level (UL) established by the Food and Nutrition Board, which is 350 mg/day from supplements (see Safety), it is important to note that these studies were all conducted under medical supervision. Because of the potential side effects of high supplemental doses of magnesium, especially in the presence of impaired kidney function, any disease treatment trial using oral magnesium doses higher than the UL should be conducted under medical supervision. Moreover, intravenous magnesium has been used in the management of several conditions.

Pregnancy complications

Preeclampsia and eclampsia

Preeclampsia and eclampsia are hypertensive disorders of pregnancy that may occur at any time after 20 weeks’ gestation and persist up to six weeks following birth. Preeclampsia (sometimes called toxemia of pregnancy) affects approximately 4% of pregnant women in the US (111). Preeclampsia is defined as the presence of elevated blood pressure (hypertension), protein in the urine, and severe swelling (edema) during pregnancy (112). Eclampsia occurs with the addition of seizures to the triad of preeclamptic symptoms and is a significant cause of perinatal and maternal mortality (112, 113). Although cases of preeclampsia are at high risk of developing eclampsia, one-quarter of eclamptic women do not initially exhibit preeclamptic symptoms (114).

Although lower magnesium concentrations have been reported in the blood and brain of women with preeclampsia than in healthy pregnant women, there is little evidence that magnesium imbalance may cause adverse pregnancy events. A Cochrane meta-analyses of randomized controlled trials found no effect of oral magnesium salt administration during normal and at-risk pregnancies on the risk of preeclampsia (3 trials) (115). However, a more recent meta-analyses of seven randomized controlled trials, including 2,653 pregnant women, found that oral magnesium supplementation reduced the risk of preeclampsia (RR, 0.76; 95% CI, 0.59-0.98) (116).

For many years, high-dose intravenous magnesium sulfate has been the treatment of choice for preventing eclamptic seizures that may occur in association with severe preeclampsia in pregnancy or during labor (117, 118). A systematic review of seven randomized trials in 1,396 women with eclampsia compared the effect of magnesium sulfate administration with diazepam (a known anticonvulsant) treatment on perinatal outcomes. Risks of recurrent seizures and maternal death were significantly reduced by the magnesium regimen compared to diazepam. Moreover, the use of magnesium for the care of eclamptic women resulted in newborns with higher Apgar scores; there was no significant difference in the risk of preterm birth and perinatal mortality (114). Additional research has confirmed that infusion of magnesium sulfate should always be considered in the management of severe preeclampsia and eclampsia to prevent initial and recurrent seizures (119). Moreover, the World Health Organization (WHO) recommends the use of magnesium sulfate — administered either intramuscularly or intravenously — as first-line treatment for the prevention of eclampsia in women with severe preeclampsia, in preference to other anticonvulsants (120). Further research is needed to evaluate the efficacy of magnesium salt infusion in eclampsia prophylaxis in women with mild preeclampsia (121). In addition, it is unclear whether prolonging magnesium use post-partum in women who presented with severe preeclampsia during pregnancy is necessary to lower the risk of eclampsia after delivery (122). Different regimens (i.e., doses, length of treatment [12-hour vs. 24-hour infusion]) of intravenous magnesium sulfate administration have been evaluated, but evidence is presently lacking for a superior treatment protocol (123, 124).

Perinatal neuroprotection

The relationship between magnesium sulfate and risk of cerebral damage in premature infants has been assessed in observational studies. A meta-analysis of six case-control and five prospective cohort studies showed that the use of magnesium significantly reduced the risk of cerebral palsy, as well as mortality (107). However, the high degree of heterogeneity among the cohort studies and the fact that corticosteroid exposure (which is known to decrease antenatal mortality) was higher in the cases of children exposed to magnesium compared to controls imply a cautious interpretation of the results. Nonetheless, a meta-analysis of five randomized controlled trials, which included 5,493 women at risk of preterm birth and 6,135 babies, found that magnesium therapy given to mothers delivering before term decreased the risk of cerebral palsy by 32% without causing severe adverse maternal events, but this treatment did not reduce the risk of other neurologic impairments or mortality in early childhood (108). Another meta-analysis conducted on five randomized controlled trials found that intravenous magnesium administration to newborns who suffered from perinatal asphyxia could be beneficial in terms of short-term neurologic outcomes, although there was no effect on mortality (109). Additional trials are needed to evaluate the long-term benefits of magnesium in pediatric care.

While intravenous magnesium sulfate is included in the medical care of preeclampsia and eclampsia, the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine support its use in two additional situations: specific conditions of short-term prolongation of pregnancy and neuroprotection of the fetus in anticipated premature delivery (125).

Preterm birth, which is defined by the premature delivery of an infant between the 20^th and 37^th weeks of estimated gestation, is associated with an increased risk of perinatal mortality and both short- and long-term morbidity. The ACOG approves the use of different classes of drugs — known as tocolytics — that are meant to delay delivery for long enough so that antenatal corticoids can be used to accelerate lung maturation in the fetus of women at imminent risk of preterm labor (126). A 2014 meta-analyses of 37 trials found that intravenous infusion of magnesium sulfate was no more efficacious than commonly used tocolytics (e.g., β-adrenergic receptor agonists, calcium channel blockers, prostaglandin inhibitors) in delaying delivery or preventing serious infant outcomes (127). Very limited evidence also suggested that high- versus low-dose magnesium infusion may reduce the length of hospital stays in neonates admitted to intensive care units (128).

The relationship between magnesium sulfate and cerebral damage in premature infants has also been studied. In a recent multicenter, randomized, placebo-controlled trial of 1,433 pregnant individuals (the MAGENTA trial), intravenous magnesium sulfate administered between 30 and 34 weeks’ gestation did not reduce the incidence of cerebral palsy or risk of death in children at two years of age compared to placebo (129). However, a 2024 meta-analyses that included the MAGENTA trial and six other randomized controlled trials found intravenous magnesium sulfate significantly reduced the risk of fetal neurological impairment, which included cerebral palsy, compared to placebo (RR=0.70; 95% CI, 0.56-0.87) (130). Yet no benefit was observed with respect to neonatal mortality (RR = 1.03; 95% CI, 0.88-1.21) (130).

Another meta-analyses conducted on five randomized controlled trials indicated that intravenous magnesium sulfate administered to newborns with perinatal asphyxia and hypoxic-ischemic encephalopathy (HIE) may improve short-term neurological outcomes but not mortality (131). Some small clinical trials have investigated intravenous magnesium sulfate as an adjunct to therapeutic hypothermia (132-134), which is standard treatment for moderate-to-severe HIE (135). However, large, well-controlled trials are needed to inform whether intravenous magnesium sulfate has utility as an adjunctive treatment in this pediatric population.

Cardiovascular disease

Hypertension

Recent clinical evidence suggests a modest therapeutic benefit of oral magnesium supplementation in the treatment of hypertension (136-138). A 2021 systematic review and meta-analyses of 49 randomized controlled trials found that magnesium supplementation reduced both systolic and diastolic blood pressure, particularly in individuals whose blood pressure remained uncontrolled despite medication (136). These analyses indicated that doses of ≥240 mg/day of supplemental magnesium may serve as an effective adjunct therapy in this population (136).

Oral magnesium supplementation may be especially beneficial in hypertensive individuals who are depleted of magnesium due to chronic diuretic use and/or inadequate dietary intake (7). However, several dietary factors play a role in hypertension. For example, adherence to the DASH diet — a diet rich in fruit, vegetables, and low-fat dairy and low in saturated and total fats — has been linked to significant reductions in systolic and diastolic blood pressures (139). See the topic page: High Blood Pressure.

Atherosclerosis

Vascular endothelial cells line arterial walls where they are in contact with the blood that flows through the circulatory system. Normally functioning vascular endothelium promotes vasodilation when needed, for example, during exercise, and inhibits the formation of blood clots. Conversely, endothelial dysfunction results in widespread vasoconstriction and coagulation abnormalities. In cardiovascular disease, chronic inflammation is associated with the formation of atherosclerotic plaques in arteries. Atherosclerosis impairs normal endothelial function, increasing the risk of vasoconstriction and clot formation, which may lead to heart attack or stroke (reviewed in 140). A systematic review identified six randomized controlled trials that examined the effect of pharmacologic doses of oral magnesium on vascular endothelial function (141). Three out of six trials, which included individuals with coronary artery disease (142), diabetes mellitus (143), or hypertension (144), reported an improvement in flow-mediated dilation (FMD) with supplemental magnesium compared to control. In other words, the normal dilation response of the brachial (arm) artery to increased blood flow was improved. In contrast, there was no evidence of an effect of magnesium supplementation on FMD in three trials conducted in individuals undergoing hemodialysis (145) or healthy participants with normal (146) or high body mass index (BMI) (147). A pooled analyses of the six trials in 262 participants found that supplementation with 107 to 730 mg/day of magnesium for one to six months resulted in an overall improvement of FMD, regardless of the health status or baseline magnesium concentrations of participants (141).

The measurement of the thickness of the inner layers of the carotid arteries is sometimes used as a surrogate marker of atherosclerosis (148). Higher serum magnesium concentrations have been associated with reduced carotid intima-media thickness (CIMT) in all women and in Caucasian men participating in the Atherosclerosis Risk in Communities (ARIC) study (149). A meta-analyses of four small (145 participants in total) and heterogeneous intervention studies found no effect of magnesium supplementation (98.6 to 368 mg/day for 2 to 6 months) on CIMT (141).

Survival after myocardial infarction

Results from several randomized, placebo-controlled trials have suggested that an intravenous magnesium administered early after a suspected myocardial infarction could decrease the risk of death. The most influential study was a randomized, placebo-controlled trial conducted in 2,316 individuals. The researchers reported a significant reduction in mortality in the group of individuals given intravenous magnesium sulfate within 24 hours of suspected myocardial infarction (7.8% all-cause mortality in the experimental group vs. 10.3% all-cause mortality in the placebo group) (150). Follow-up from one to five years after treatment revealed that the mortality from cardiovascular disease was 21% lower in the magnesium-treated group (151). However, a larger placebo-controlled trial in more than 58,000 individuals found no significant reduction in five-week mortality in individuals treated with intravenous magnesium sulfate within 24 hours of suspected myocardial infarction, resulting in controversy regarding the efficacy of this treatment (152). A United States (US) survey of the treatment of more than 173,000 individuals with acute myocardial infarction found that only 5% were given intravenous magnesium in the first 24 hours post-infarction and that mortality was higher in this group compared to the group of individuals not treated with magnesium (153). A 2007 systematic review of 26 clinical trials, including 73,363 participants, concluded that intravenous magnesium administration does not appear to reduce post-myocardial infarction mortality and should not be utilized as a treatment (154). Thus, the use of intravenous magnesium sulfate in the therapy of acute myocardial infarction remains controversial.

Diabetes mellitus

Magnesium depletion has been associated with type 1 (insulin-dependent) and type 2 diabetes mellitus, as well as with gestational diabetes. Low serum concentrations of magnesium (hypomagnesemia) have been reported in 32% of individuals with type 2 diabetes mellitus (155). One cause of the depletion may be an increased urinary loss of magnesium caused by an increased urinary excretion of glucose that accompanies poorly controlled diabetes. Magnesium depletion has been shown to increase insulin resistance in a few studies and may adversely affect blood glucose control in diabetes mellitus (see also Diabetes Mellitus under Disease Prevention) (156).

A small study in nine individuals with type 2 diabetes mellitus reported that supplemental magnesium (300 mg/day for 30 days), in the form of a liquid, magnesium-containing salt solution, improved fasting insulin but not fasting glucose concentrations (157). One randomized, double-blind, placebo-controlled study in 63 individuals with type 2 diabetes mellitus and hypomagnesemia found that those taking an oral magnesium chloride solution (638 mg/day of elemental magnesium) for 16 weeks had improved measures of insulin sensitivity and glycemic control compared to those taking a placebo (158). Meta-analyses of randomized, double-blind, controlled trials concluded that oral supplemental magnesium lowered fasting plasma glucose concentrations in individuals with diabetes (84, 159). However, magnesium supplementation did not improve other markers of glucose homeostasis, such as glycated hemoglobin (HbA1c) concentration, fasting and post-glucose load insulin concentrations, and measures of insulin resistance (84, 159). Another meta-analyses of trials that included participants either at risk of diabetes mellitus or with diabetes mellitus suggested that evidence to support a benefit of magnesium supplementation on measures of insulin resistance was stronger in individuals who were magnesium deficient than in those with normal serum concentrations of magnesium (160). Correcting existing magnesium deficiencies may improve glucose metabolism and insulin sensitivity in individuals with diabetes mellitus, but it remains uncertain whether magnesium supplementation can have any therapeutic benefit in individuals with adequate magnesium status.

Asthma

The occurrence of hypomagnesemia may be greater in individuals with asthma than in individuals without asthma (161). Several clinical trials have examined the effect of intravenous magnesium infusions on acute asthmatic attacks in children or adults who did not respond to initial treatment in the emergency room. Indeed, magnesium can promote bronchodilation in individuals with asthma by interfering with mechanisms like the activation of N-methyl D-aspartate (NMDA) receptors that trigger bronchoconstriction through facilitating calcium influx in airway smooth muscle cells (162). In a meta-analyses of six (quasi) randomized controlled trials in 325 children with acute asthma treated with a short-acting β₂-adrenergic receptor agonist (e.g., salbutamol) and systemic steroids, intravenous magnesium sulfate treatment improved measurements of the respiratory function and reduced the risk of hospital admission by 30% compared to control (163). Moreover, a Cochrane review (i.e., pooled analyses of studies with stricter inclusion criteria) of three randomized controlled trials in children with moderate-to-severe asthma (115 children in total) found treatment with intravenous magnesium sulfate on top of standard therapy reduced hospital admission in children with acute asthma by 68% (95% CI, 0.14-0.74) (164). Another meta-analyses of randomized controlled trials primarily conducted in adults with asthma exacerbations indicated that single infusions of 1.2 to 2 g of magnesium sulfate over 15 to 30 minutes could reduce the risk of hospital admission and improve lung function after initial treatments failed (i.e., oxygen, short-acting β₂ agonist, and steroids) (165).

The use of nebulized, inhaled magnesium for treating asthma has also been investigated. A systematic review of 25 randomized controlled trials, including adults, children, or both, found little evidence that inhaled magnesium sulfate alone or along with a β₂-adrenergic receptor agonist and/or a muscarinic anticholinergic (e.g., ipratropium) could improve pulmonary function in individuals with acute asthma (166). In addition, oral magnesium supplementation is of no known value in the management of chronic asthma (167-169).

Pain management

The potential analgesic effect of magnesium is attributed in particular to its capacity to block NMDA receptors, which are located in the brain and spinal cord and are involved in pain transduction (170).

Post-operative pain

Several intervention studies have examined the role of magnesium on pain control and analgesic requirement in individuals during the immediate post-surgery period.

After cesarean section

Pain management strategies after cesarean section usually involve the injection of an analgesic into either the epidural space (for epidural analgesia) or the subarachnoid space (for spinal [intrathecal] analgesia). A meta-analyses of nine randomized controlled trials summarized the evidence regarding the potential use of magnesium sulfate to control or relieve postoperative pain in 827 women who underwent cesarean section (171). All the trials evaluated the effect of a first-line analgesic regimen (i.e., bupivacaine or lidocaine, with or without opioids) with and without the addition of magnesium sulfate. The results suggested that the anesthesia (8 studies) and sensory blockade (6 studies) lasted longer in women who received the additional magnesium sulfate. The use of magnesium sulfate also resulted in lower pain score (3 studies) and in lower postoperative consumption of analgesics (4 studies). Additionally, there was no difference in occurrence of side effects between regimens (171). A randomized controlled trial in 60 healthy women undergoing elective cesarean section confirmed that the addition of magnesium sulfate to a bupivacaine/opioid regimen increased the duration of spinal anesthesia and lowered the pain level yet did not improve the potency of bupivacaine (172). In another study in women with mild preeclampsia who received an epidural injection of ropivacaine after cesarean section, spinal infusion of magnesium sulfate increased the duration of sensory and motor blockade, as well as the time before individuals requested an analgesic, compared to midazolam (173). A more recent meta-analyses of 14 randomized controlled trials (880 women in total), including these more recent trials, confirmed that magnesium sulfate may be an efficacious adjunct in reducing postoperative pain in women undergoing cesarean section (174). However, it is important to note that the included trials were highly heterogeneous.

After a variety of other surgeries

The efficacy of intravenous magnesium has also been examined for local, regional, or systemic pain control following a range of different surgeries. A review of four small randomized controlled studies suggested that, when added to local analgesics, magnesium infusion to individuals undergoing tonsillectomy might decrease pain and incidence of laryngospasm, extend the time to first post-operative analgesic requirement, and reduce the number of post-operative analgesic requests (175). Similar observations were reported in two additional meta-analyses, yet there was discrepancy regarding the ability of magnesium to alleviate pain following tonsillectomy (176, 177). Indeed, the review of eight trials in children undergoing tonsillectomy (177), of which only two trials scored pain using the same scale, showed no pain reduction with magnesium compared to control. Both meta-analyses reported no reduction in risk of post-operative nausea and vomiting with intravenous magnesium administration (175, 177).

Moreover, a 2018 meta-analyses of four randomized controlled trials in 263 individuals suggested that magnesium sulfate infusion may help reduce pain scores at 2 and 8 hours (but not 24 hours) after laparoscopic cholecystectomy (178). Meta-analyses of randomized controlled trials have found magnesium sulfate infusion may reduce pain and opioid use following spinal surgery (179, 180). Further, studies have examined the use of magnesium sulfate for pain control after other surgeries, including hysterectomy (181, 182) and during endoscopic sinus (183) or cochlear implantation (184) surgery. Despite conflicting results or reports of limited benefits of magnesium, further research is needed before any conclusions can be drawn.

Neuropathic pain

The effect of magnesium on neuropathic pain has been examined in some clinical studies. The intravenous administration of magnesium sulfate was found to partially or completely alleviate pain in individuals with postherpetic neuralgia, a type of neuropathic pain caused by herpes zoster infection (shingles) (185, 186). In a randomized controlled trial in 45 individuals with either postherpetic neuralgia or neuropathic pain of traumatic or surgical origin, oral supplementation with magnesium failed to improve measures of pain and quality of life compared to a placebo (187). Moreover, a randomized, double-blind, cross-over trial in 20 individuals with refractory neuropathic pain found intravenous magnesium sulfate combined with ketamine did not affect daily pain intensity over the 35-day study compared to ketamine alone (188).

Migraine headaches

Lower intracellular magnesium concentrations (in both red blood cells and white blood cells) have been reported in individuals who suffer from recurrent migraine headaches compared to migraine-free individuals (189). Additionally, the incidence of hypomagnesemia appears to be greater in women who experience menstrual migraines compared to those without (190).

Several intervention studies have examined whether increasing intracellular magnesium concentration through oral magnesium supplementation could help decrease the frequency and severity of migraine headaches in affected individuals. Two early placebo-controlled trials demonstrated modest decreases in the frequency of migraine headaches with 600 mg/day of magnesium (189, 191). Another placebo-controlled trial in 86 children with frequent migraine headaches found that oral magnesium oxide (9 mg/kg body weight/day) reduced headache frequency over the 16-week intervention (192). However, a separate placebo-controlled study in 69 adults found no benefit of 485 mg/day of magnesium (193). The efficiency of magnesium absorption varies with the type of oral magnesium complex, and this might explain the conflicting results. Although no serious adverse effects were noted during these trials, 19 to 40% of individuals taking the magnesium supplements have reported diarrhea and gastric irritation. More recently, a randomized, double-blind, 24-week cross-over trial in 63 adults suffering from migraines found that 500 mg/day of magnesium oxide was equally effective as sodium valproate for reducing the migraine frequency and duration over the eight-week treatment period (194). Another trial suggested that co-treatment with magnesium oxide (500 mg/day) with sodium valproate may be more efficacious than either treatment alone (195).

The efficacy of intravenous magnesium sulfate for acute migraine treatment has also been investigated, with studies reporting mixed results. In a randomized, single-blind, placebo-controlled, cross-over trial of 30 individuals with migraine headaches, the administration of 1 gram of intravenous magnesium sulfate ended the attacks, abolished associated symptoms, and prevented recurrence within 24 hours in nearly 90% of the participants (196). While this promising result was confirmed in another trial (197), two additional randomized, placebo-controlled studies found that magnesium sulfate was less effective than other molecules (e.g., metoclopramide) in treating migraines (198, 199). A 2014 meta-analyses of five randomized, double-blind, controlled trials reported no beneficial effect of magnesium infusion for migraine in adults (200). More recent intervention studies suggested that magnesium sulfate infusion could be more effective and faster than dexamethasone/metoclopramide (201) or caffeine citrate (202) to relieve pain in individuals with acute migraine.

The efficacy of magnesium — whether administered orally or intravenously — should be further examined in larger, well-controlled studies that consider the magnesium status of migraine sufferers (203).

Critical injury or illness

Hypomagnesemia is not uncommon in individuals admitted to intensive care units (ICU). Two meta-analyses of prospective and retrospective cohort studies reported serum magnesium concentrations ≤0.75 mmol/L in individuals admitted into the ICU at admission or within 24 hours following admission to be associated with a greater need for mechanical ventilation, longer ICU stay, and higher risk of hospital mortality (204, 205). Pooled analyses of three studies also suggested a higher risk of sepsis in individuals in the ICU with hypomagnesemia (204). A prospective study conducted in individuals admitted with severe head injury found better neurological outcomes after six months in those who presented with normal serum magnesium concentrations at admission compared to those with hypomagnesemia (serum magnesium concentrations <0.65 mmol/L) (206).

In an open-label, placebo-controlled trial in 58 individuals who were critically ill with severe sepsis, intravenous magnesium improved lactate clearance and shortened length of ICU stay compared to placebo but did not improve mortality (207). While evidence that magnesium administration improves outcomes in individuals who are critically ill or severely injured is largely lacking (208), correcting imbalances in magnesium and other electrolytes is standard clinical practice in the critically ill, since electrolyte imbalances are common in this population and associated with increased morbidity and mortality (209).

Sources

Food sources

Data from a US national survey, National Health and Nutrition Examination Survey (NHANES) 2017-March 2020, show an average dietary magnesium intake of 339 mg/day for men (ages ≥19 years) and 269 mg/day for women. Concerningly, 57% of men and 52% of women had inadequate dietary intakes (i.e., less than the EAR) of magnesium (210). Yet, the long-term consequences of inadequate dietary intakes remain unclear (1).

Since magnesium is part of chlorophyll, the green pigment in plants, green leafy vegetables are good sources of magnesium. Unrefined grains (whole grains) and nuts also have high magnesium content. Meats and milk have an intermediate content of magnesium, while refined foods generally have the lowest. Water is a variable source of intake; harder water usually has a higher concentration of magnesium salts (2). Some foods that are relatively rich in magnesium are listed in Table 2, along with their magnesium content in milligrams (mg). For more information on the nutrient content of foods, search USDA's FoodData Central.

Supplements

Magnesium supplements are available as magnesium oxide, magnesium hydroxide, magnesium gluconate, magnesium chloride, and magnesium citrate salts, as well as a number of amino acid chelates like magnesium aspartate. Magnesium hydroxide, oxide, or trisilicate salts are used as antacids to mitigate gastric hyperacidity and symptoms of gastroesophageal reflux disease (211).

Safety

Toxicity

Adverse effects have not been identified from magnesium occurring naturally in food. However, adverse effects from excessive magnesium have been observed with intakes of various magnesium salts (i.e., supplemental magnesium) (6). The initial symptom of excess magnesium supplementation is diarrhea — a well-known side effect of magnesium that is used therapeutically as a laxative. Individuals with impaired kidney function are at higher risk for adverse effects of magnesium supplementation, and symptoms of magnesium toxicity have occurred in people with impaired kidney function taking moderate doses of magnesium-containing laxatives or antacids. Elevated serum concentrations of magnesium (hypermagnesemia) may result in a fall in blood pressure (hypotension). Some of the later effects of magnesium toxicity, such as lethargy, confusion, disturbances in normal cardiac rhythm, and deterioration of kidney function, are related to severe hypotension. As hypermagnesemia progresses, muscle weakness and difficulty breathing may occur. Severe hypermagnesemia may result in cardiac arrest (2, 3).

The Food and Nutrition Board (FNB) of the US National Academy of Medicine set the Tolerable Upper Intake Level (UL) for magnesium at 350 mg/day (Table 3); this UL represents the highest level of daily supplemental magnesium intake likely to pose no risk of diarrhea or gastrointestinal disturbance in almost all individuals. The FNB cautions that individuals with renal impairment are at higher risk for adverse effects from excess supplemental magnesium intake. However, the FNB also notes that there are some conditions that may warrant higher doses of magnesium under medical supervision (2).

Drug interactions

Magnesium interferes with the absorption of digoxin (a heart medication), nitrofurantoin (an antibiotic), and certain anti-malarial drugs, which could potentially reduce drug efficacy. Bisphosphonates (e.g., alendronate, etidronate), which are drugs used to treat osteoporosis, and magnesium should be taken two hours apart so that the absorption of the bisphosphonates is not inhibited (212, 213). Magnesium has also been found to reduce the efficacy of chlorpromazine (a tranquilizer), penicillamine, oral anticoagulants, and the quinolone and tetracycline classes of antibiotics (212, 213). Intravenous magnesium might inhibit calcium entry into smooth muscle cells and lead to hypotension and muscular weakness if administered with calcium channel blockers (e.g., nifedipin, nicardipin) (213). Because intravenous magnesium has increased the effects of certain muscle-relaxing medications used during anesthesia, it is advisable to let medical staff know if you are taking oral magnesium supplements, laxatives, or antacids prior to surgical procedures. Moreover, long-term use (three months or longer) of proton-pump inhibitors (drugs used to reduce the amount of stomach acid) may increase the risk of hypomagnesemia (214, 215). High doses of furosemide (Lasix) and some thiazide diuretics (e.g., hydrochlorothiazide), if taken for extended periods, may interfere with magnesium reabsorption in the kidneys and result in magnesium depletion (213). Many other medications may also result in renal magnesium loss (3).

LPI Recommendation

The Linus Pauling Institute supports the latest RDA for magnesium intake (400 to 420 mg/day for men and 310 to 320 mg/day for women). Despite magnesium being plentiful in foods, it is considered a shortfall nutrient (see the article on Micronutrient Inadequacies in the US Population). Following the Linus Pauling Institute recommendation to take a daily multivitamin/mineral supplement might ensure an intake of at least 100 mg/day of magnesium. Few multivitamin/mineral supplements contain more than 100 mg of magnesium due to its bulk. Eating a varied diet that provides green vegetables, whole grains, and nuts daily should provide the rest of an individual's magnesium requirement.

Older adults (>50 years)

Adults older than 50 years of age are less likely than younger adults to consume enough magnesium to meet their needs and should therefore consume magnesium-rich foods in addition to taking a multivitamin/mineral supplement daily (see the article on Micronutrient Inadequacies: Subpopulations at Risk). Because older adults are also more likely to have impaired kidney function, they should avoid taking more than 350 mg/day of supplemental magnesium without medical consultation (see Safety).

---

Authors and Reviewers

Originally written in 2001 by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University

Updated in April 2003 by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University

Updated in August 2007 by:
Victoria J. Drake, Ph.D.
Linus Pauling Institute
Oregon State University

Updated in October 2013 by:
Barbara Delage, Ph.D.
Linus Pauling Institute
Oregon State University

Updated in November 2018 by:
Barbara Delage, Ph.D.
Linus Pauling Institute
Oregon State University

Updated in July 2025 by:
Victoria J. Drake, Ph.D.
Linus Pauling Institute
Oregon State University

Reviewed in October 2025 by:
Stella Lucia Volpe, Ph.D., RDN, ACSM-CEP, FACSM
Professor and Head
Department of Human Nutrition, Foods, and Exercise
Virginia Polytechnic Institute and State University (Virginia Tech)

Copyright 2001-2025 Linus Pauling Institute

---

References

1. Volpe SL. Magnesium. In: Erdman Jr. JW, Macdonald IA, Ziegler EE, eds. Present Knowledge in Nutrition. 10^th ed: ILSI Press; 2012:459-474.
2. Food and Nutrition Board, Institute of Medicine. Magnesium. Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington D.C.: National Academy Press; 1997:190-249. (National Academy Press)
3. Rude RK, Shils ME. Magnesium. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, eds. Modern Nutrition in Health and Disease. 10^th ed. Baltimore: Lippincott Williams & Wilkins; 2006:223-247.
4. Spencer H, Norris C, Williams D. Inhibitory effects of zinc on magnesium balance and magnesium absorption in man. J Am Coll Nutr. 1994;13(5):479-484. (PubMed)
5. Schwartz R, Walker G, Linz MD, MacKellar I. Metabolic responses of adolescent boys to two levels of dietary magnesium and protein. I. Magnesium and nitrogen retention. Am J Clin Nutr. 1973;26(5):510-518. (PubMed)
6. Navarro-Gonzalez JF, Mora-Fernandez C, Garcia-Perez J. Clinical implications of disordered magnesium homeostasis in chronic renal failure and dialysis. Semin Dial. 2009;22(1):37-44. (PubMed)
7. Rude RK. Magnesium. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Modern Nutrition in Health and Disease. 11^th ed. China: Williams & Wilkins; 2014:159-175.
8. Moshfegh A, Goldman J, Ahuja J, Rhodes D, LaComb R. What We Eat in America, NHANES 2005-2006: Usual Nutrient Intakes from Food and Water Compared to 1997 Dietary Reference Intakes for Vitamin D, Calcium, Phosphorus, and Magnesium. 2009.
9. US Department of Agriculture, Agricultural Research Service. 2024. Nutrient Intakes from Food and Beverages: Mean Amounts Consumed per Individual, by Male/Female and Age. What We Eat in America, NHANES August 2021-August 2023.
10. Costello RB, Nielsen F. Interpreting magnesium status to enhance clinical care: key indicators. Curr Opin Clin Nutr Metab Care. 2017;20(6):504-511. (PubMed)
11. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112(17):2735-2752. (PubMed)
12. Esposito K, Chiodini P, Colao A, Lenzi A, Giugliano D. Metabolic syndrome and risk of cancer: a systematic review and meta-analysis. Diabetes Care. 2012;35(11):2402-2411. (PubMed)
13. Ninomiya JK, L'Italien G, Criqui MH, Whyte JL, Gamst A, Chen RS. Association of the metabolic syndrome with history of myocardial infarction and stroke in the Third National Health and Nutrition Examination Survey. Circulation. 2004;109(1):42-46. (PubMed)
14. Sung KC, Lee MY, Kim YH, et al. Obesity and incidence of diabetes: Effect of absence of metabolic syndrome, insulin resistance, inflammation and fatty liver. Atherosclerosis. 2018;275:50-57. (PubMed)
15. Moore-Schiltz L, Albert JM, Singer ME, Swain J, Nock NL. Dietary intake of calcium and magnesium and the metabolic syndrome in the National Health and Nutrition Examination (NHANES) 2001-2010 data. Br J Nutr. 2015;114(6):924-935. (PubMed)
16. Dibaba DT, Xun P, Fly AD, Yokota K, He K. Dietary magnesium intake and risk of metabolic syndrome: a meta-analysis. Diabet Med. 2014;31(11):1301-1309. (PubMed)
17. Ju SY, Choi WS, Ock SM, Kim CM, Kim DH. Dietary magnesium intake and metabolic syndrome in the adult population: dose-response meta-analysis and meta-regression. Nutrients. 2014;6(12):6005-6019. (PubMed)
18. Sarrafzadegan N, Khosravi-Boroujeni H, Lotfizadeh M, Pourmogaddas A, Salehi-Abargouei A. Magnesium status and the metabolic syndrome: A systematic review and meta-analysis. Nutrition. 2016;32(4):409-417. (PubMed)
19. Kim Y, Je Y. Intake or blood levels of magnesium and risk of metabolic syndrome: a meta-analysis of observational studies. Nutrients. 2025;17(10):1667. (PubMed)
20. He K, Liu K, Daviglus ML, et al. Magnesium intake and incidence of metabolic syndrome among young adults. Circulation. 2006;113(13):1675-1682. (PubMed)
21. Dibaba DT, Chen C, Lu L, et al. Magnesium intake is inversely associated with the risk of metabolic syndrome in the reasons for geographic and racial differences in stroke (REGARDS) cohort study. Clin Nutr. 2021;40(4):2337-2342. (PubMed)
22. Jin S, Liu J, Jia Y, et al. The association of dietary flavonoids, magnesium and their interactions with the metabolic syndrome in Chinese adults: a prospective cohort study. Br J Nutr. 2021;126(6):892-902. (PubMed)
23. Jiao Y, Li W, Wang L, et al. Relationship between dietary magnesium intake and metabolic syndrome. Nutrients. 2022;14(10):2013. (PubMed)
24. Song Y, Ridker PM, Manson JE, Cook NR, Buring JE, Liu S. Magnesium intake, C-reactive protein, and the prevalence of metabolic syndrome in middle-aged and older U.S. women. Diabetes Care. 2005;28(6):1438-1444.(PubMed)
25. Dibaba DT, Xun P, He K. Dietary magnesium intake is inversely associated with serum C-reactive protein levels: meta-analysis and systematic review. Eur J Clin Nutr. 2014;68(4):510-516. (PubMed)
26. Ascherio A, Rimm EB, Giovannucci EL, et al. A prospective study of nutritional factors and hypertension among US men. Circulation. 1992;86(5):1475-1484. (PubMed)
27. Ascherio A, Hennekens C, Willett WC, et al. Prospective study of nutritional factors, blood pressure, and hypertension among US women. Hypertension. 1996;27(5):1065-1072. (PubMed)
28. Peacock JM, Folsom AR, Arnett DK, Eckfeldt JH, Szklo M. Relationship of serum and dietary magnesium to incident hypertension: the Atherosclerosis Risk in Communities (ARIC) Study. Ann Epidemiol. 1999;9(3):159-165. (PubMed)
29. Han H, Fang X, Wei X, et al. Dose-response relationship between dietary magnesium intake, serum magnesium concentration and risk of hypertension: a systematic review and meta-analysis of prospective cohort studies. Nutr J. 2017;16(1):26. (PubMed)
30. Joosten MM, Gansevoort RT, Mukamal KJ, et al. Urinary magnesium excretion and risk of hypertension: the prevention of renal and vascular end-stage disease study. Hypertension. 2013;61(6):1161-1167. (PubMed)
31. Tirani SA, Rouhani P, Saneei P. Hypertension in relation to circulating magnesium levels: a systematic review and meta-analysis of observational studies. Nutr Rev. 2025;83(7):1277-1289. (PubMed)
32. Rennenberg RJ, Kessels AG, Schurgers LJ, van Engelshoven JM, de Leeuw PW, Kroon AA. Vascular calcifications as a marker of increased cardiovascular risk: a meta-analysis. Vasc Health Risk Manag. 2009;5(1):185-197. (PubMed)
33. Major RW, Cheng MRI, Grant RA, et al. Cardiovascular disease risk factors in chronic kidney disease: A systematic review and meta-analysis. PLoS One. 2018;13(3):e0192895. (PubMed)
34. Palmer SC, Hayen A, Macaskill P, et al. Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease: a systematic review and meta-analysis. JAMA. 2011;305(11):1119-1127. (PubMed)
35. Sakaguchi Y, Hamano T, Nakano C, et al. Association between density of coronary artery calcification and serum magnesium levels among patients with chronic kidney disease. PLoS One. 2016;11(9):e0163673. (PubMed)
36. Bressendorff I, Hansen D, Schou M, et al. Oral magnesium supplementation in chronic kidney disease stages 3 and 4: efficacy, safety, and effect on serum calcification propensity-a prospective randomized double-blinded placebo-controlled clinical trial. Kidney Int Rep. 2017;2(3):380-389. (PubMed)
37. Pasch A, Block GA, Bachtler M, et al. Blood calcification propensity, cardiovascular events, and survival in patients receiving hemodialysis in the EVOLVE trial. Clin J Am Soc Nephrol. 2017;12(2):315-322. (PubMed)
38. Smith ER, Ford ML, Tomlinson LA, et al. Serum calcification propensity predicts all-cause mortality in predialysis CKD. J Am Soc Nephrol. 2014;25(2):339-348. (PubMed)
39. Bressendorff I, Hansen D, Schou M, Pasch A, Brandi L. The effect of increasing dialysate magnesium on serum calcification propensity in subjects with end stage kidney disease: a randomized, controlled clinical trial. Clin J Am Soc Nephrol. 2018;13(9):1373-1380. (PubMed)
40. Bressendorff I, Hansen D, Schou M, et al. The effect of magnesium supplementation on vascular calcification in CKD: a randomized clinical trial (MAGiCAL-CKD). J Am Soc Nephrol. 2023;34(5):886-894. (PubMed)
41. Sakaguchi Y, Hamano T, Obi Y, et al. A randomized trial of magnesium oxide and oral carbon adsorbent for coronary artery calcification in predialysis CKD. J Am Soc Nephrol. 2019;30(6):1073-1085. (PubMed)
42. Hruby A, O'Donnell CJ, Jacques PF, Meigs JB, Hoffmann U, McKeown NM. Magnesium intake is inversely associated with coronary artery calcification: the Framingham Heart Study. JACC Cardiovasc Imaging. 2014;7(1):59-69. (PubMed)
43. Hisamatsu T, Miura K, Fujiyoshi A, et al. Serum magnesium, phosphorus, and calcium levels and subclinical calcific aortic valve disease: A population-based study. Atherosclerosis. 2018;273:145-152. (PubMed)
44. Lee SY, Hyun YY, Lee KB, Kim H. Low serum magnesium is associated with coronary artery calcification in a Korean population at low risk for cardiovascular disease. Nutr Metab Cardiovasc Dis. 2015;25(11):1056-1061. (PubMed)
45. Posadas-Sanchez R, Posadas-Romero C, Cardoso-Saldana G, et al. Serum magnesium is inversely associated with coronary artery calcification in the Genetics of Atherosclerotic Disease (GEA) study. Nutr J. 2016;15:22. (PubMed)
46. Levy J, Miranda AAM, De Carli E, et al. Ingestion of magnesium was not associated with coronary calcium score in a cross-sectional study. Int J Vitam Nutr Res. 2021;91(3-4):217-223. (PubMed)
47. Chiuve SE, Sun Q, Curhan GC, et al. Dietary and plasma magnesium and risk of coronary heart disease among women. J Am Heart Assoc. 2013;2(2):e000114. (PubMed)
48. Del Gobbo LC, Imamura F, Wu JH, de Oliveira Otto MC, Chiuve SE, Mozaffarian D. Circulating and dietary magnesium and risk of cardiovascular disease: a systematic review and meta-analysis of prospective studies. Am J Clin Nutr. 2013;98(1):160-173. (PubMed)
49. Fang X, Wang K, Han D, et al. Dietary magnesium intake and the risk of cardiovascular disease, type 2 diabetes, and all-cause mortality: a dose-response meta-analysis of prospective cohort studies. BMC Med. 2016;14(1):210. (PubMed)
50. Larsson SC, Orsini N, Wolk A. Dietary magnesium intake and risk of stroke: a meta-analysis of prospective studies. Am J Clin Nutr. 2012;95(2):362-366. (PubMed)
51. Nie ZL, Wang ZM, Zhou B, Tang ZP, Wang SK. Magnesium intake and incidence of stroke: meta-analysis of cohort studies. Nutr Metab Cardiovasc Dis. 2013;23(3):169-176. (PubMed)
52. Zhao B, Zeng L, Zhao J, et al. Association of magnesium intake with type 2 diabetes and total stroke: an updated systematic review and meta-analysis. BMJ Open. 2020;10(3):e032240. (PubMed)
53. Qu X, Jin F, Hao Y, et al. Magnesium and the risk of cardiovascular events: a meta-analysis of prospective cohort studies. PLoS One. 2013;8(3):e57720. (PubMed)
54. Liao F, Folsom AR, Brancati FL. Is low magnesium concentration a risk factor for coronary heart disease? The Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J. 1998;136(3):480-490. (PubMed)
55. Rooney MR, Alonso A, Folsom AR, et al. Serum magnesium and the incidence of coronary artery disease over a median 27 years of follow-up in the Atherosclerosis Risk in Communities (ARIC) Study and a meta-analysis. Am J Clin Nutr. 2020;111(1):52-60. (PubMed)
56. Wannamethee SG, Papacosta O, Lennon L, Whincup PH. Serum magnesium and risk of incident heart failure in older men: The British Regional Heart Study. Eur J Epidemiol. 2018;33(9):873-882. (PubMed)
57. Catling LA, Abubakar I, Lake IR, Swift L, Hunter PR. A systematic review of analytical observational studies investigating the association between cardiovascular disease and drinking water hardness. J Water Health. 2008;6(4):433-442. (PubMed)
58. Xu T, Sun Y, Xu T, Zhang Y. Magnesium intake and cardiovascular disease mortality: A meta-analysis of prospective cohort studies. Int J Cardiol. 2013;167(6):3044-3047. (PubMed)
59. Bagheri A, Naghshi S, Sadeghi O, Larijani B, Esmaillzadeh A. Total, dietary, and supplemental magnesium intakes and risk of all-cause, cardiovascular, and cancer mortality: a systematic review and dose-response meta-analysis of prospective cohort studies. Adv Nutr. 2021;12(4):1196-1210. (PubMed)
60. Zhang X, Xia J, Del Gobbo LC, Hruby A, Dai Q, Song Y. Serum magnesium concentrations and all-cause, cardiovascular, and cancer mortality among U.S. adults: Results from the NHANES I Epidemiologic Follow-up Study. Clin Nutr. 2018;37(5):1541-1549. (PubMed)
61. Angkananard T, Anothaisintawee T, Eursiriwan S, et al. The association of serum magnesium and mortality outcomes in heart failure patients: A systematic review and meta-analysis. Medicine (Baltimore). 2016;95(50):e5406. (PubMed)
62. van den Bergh WM, Algra A, van der Sprenkel JW, Tulleken CA, Rinkel GJ. Hypomagnesemia after aneurysmal subarachnoid hemorrhage. Neurosurgery. 2003;52(2):276-281; discussion 281-272. (PubMed)
63. Chen T, Carter BS. Role of magnesium sulfate in aneurysmal subarachnoid hemorrhage management: A meta-analysis of controlled clinical trials. Asian J Neurosurg. 2011;6(1):26-31. (PubMed)
64. Yarad EA, Hammond NE. Intravenous magnesium therapy in adult patients with an aneurysmal subarachnoid haemorrhage: A systematic review and meta-analysis. Aust Crit Care. 2013;26(3):105-117. (PubMed)
65. Golan E, Vasquez DN, Ferguson ND, Adhikari NK, Scales DC. Prophylactic magnesium for improving neurologic outcome after aneurysmal subarachnoid hemorrhage: systematic review and meta-analysis. J Crit Care. 2013;28(2):173-181. (PubMed)
66. Dayyani M, Sadeghirad B, Grotta JC, et al. Prophylactic therapies for morbidity and mortality after aneurysmal subarachnoid hemorrhage: a systematic review and network meta-analysis of randomized trials. Stroke. 2022;53(6):1993-2005. (PubMed)
67. Kunze E, Lilla N, Stetter C, Ernestus RI, Westermaier T. Magnesium protects in episodes of critical perfusion after aneurysmal SAH. Transl Neurosci. 2018;9:99-105. (PubMed)
68. Westermaier T, Stetter C, Vince GH, et al. Prophylactic intravenous magnesium sulfate for treatment of aneurysmal subarachnoid hemorrhage: a randomized, placebo-controlled, clinical study. Crit Care Med. 2010;38(5):1284-1290. (PubMed)
69. Arsenault KA, Yusuf AM, Crystal E, et al. Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery. Cochrane Database Syst Rev. 2013;1:CD003611. (PubMed)
70. Fairley JL, Zhang L, Glassford NJ, Bellomo R. Magnesium status and magnesium therapy in cardiac surgery: A systematic review and meta-analysis focusing on arrhythmia prevention. J Crit Care. 2017;42:69-77. (PubMed)
71. Wu X, Wang C, Zhu J, Zhang C, Zhang Y, Gao Y. Meta-analysis of randomized controlled trials on magnesium in addition to beta-blocker for prevention of postoperative atrial arrhythmias after coronary artery bypass grafting. BMC Cardiovasc Disord. 2013;13:5. (PubMed)
72. Meerman M, Buijser M, van den Berg L, et al. Magnesium sulphate to prevent perioperative atrial fibrillation in cardiac surgery: a randomized clinical trial : A protocol description of the PeriOperative Magnesium Infusion to Prevent Atrial fibrillation Evaluated (POMPAE) trial. Trials. 2024;25(1):540. (PubMed)
73. Schulze MB, Schulz M, Heidemann C, Schienkiewitz A, Hoffmann K, Boeing H. Fiber and magnesium intake and incidence of type 2 diabetes: a prospective study and meta-analysis. Arch Intern Med. 2007;167(9):956-965. (PubMed)
74. Fang X, Han H, Li M, et al. Dose-response relationship between dietary magnesium intake and risk of type 2 diabetes mellitus: a systematic review and meta-regression analysis of prospective cohort studies. Nutrients. 2016;8(11). (PubMed)
75. Dong JY, Xun P, He K, Qin LQ. Magnesium intake and risk of type 2 diabetes: meta-analysis of prospective cohort studies. Diabetes Care. 2011;34(9):2116-2122. (PubMed)
76. Hruby A, Ngwa JS, Renstrom F, et al. Higher magnesium intake is associated with lower fasting glucose and insulin, with no evidence of interaction with select genetic loci, in a meta-analysis of 15 CHARGE Consortium Studies. J Nutr. 2013;143(3):345-353. (PubMed)
77. Larsson SC, Wolk A. Magnesium intake and risk of type 2 diabetes: a meta-analysis. J Intern Med. 2007;262(2):208-214. (PubMed)
78. Veronese N, Demurtas J, Pesolillo G, et al. Magnesium and health outcomes: an umbrella review of systematic reviews and meta-analyses of observational and intervention studies. Eur J Nutr. 2020;59(1):263-272. (PubMed)
79. Simental-Mendia LE, Rodriguez-Moran M, Guerrero-Romero F. Failure of beta-cell function for compensate variation in insulin sensitivity in hypomagnesemic subjects. Magnes Res. 2009;22(3):151-156. (PubMed)
80. Guerrero-Romero F, Rodriguez-Moran M. Magnesium improves the beta-cell function to compensate variation of insulin sensitivity: double-blind, randomized clinical trial. Eur J Clin Invest. 2011;41(4):405-410. (PubMed)
81. Guerrero-Romero F, Simental-Mendia LE, Hernandez-Ronquillo G, Rodriguez-Moran M. Oral magnesium supplementation improves glycaemic status in subjects with prediabetes and hypomagnesaemia: A double-blind placebo-controlled randomized trial. Diabetes Metab. 2015;41(3):202-207. (PubMed)
82. Rodriguez-Moran M, Guerrero-Romero F. Oral magnesium supplementation improves the metabolic profile of metabolically obese, normal-weight individuals: a randomized double-blind placebo-controlled trial. Arch Med Res. 2014;45(5):388-393. (PubMed)
83. Mooren FC, Kruger K, Volker K, Golf SW, Wadepuhl M, Kraus A. Oral magnesium supplementation reduces insulin resistance in non-diabetic subjects - a double-blind, placebo-controlled, randomized trial. Diabetes Obes Metab. 2011;13(3):281-284. (PubMed)
84. Veronese N, Dominguez LJ, Pizzol D, Demurtas J, Smith L, Barbagallo M. Oral magnesium supplementation for treating glucose metabolism parameters in people with or at risk of diabetes: a systematic review and meta-analysis of double-blind randomized controlled trials. Nutrients. 2021;13(11):4074. (PubMed)
85. Castiglioni S, Cazzaniga A, Albisetti W, Maier JA. Magnesium and osteoporosis: current state of knowledge and future research directions. Nutrients. 2013;5(8):3022-3033. (PubMed)
86. Vormann J. Magnesium: Nutrition and Homeostasis. AIMS Public Health. 2016;3(2):329-340. (PubMed)
87. Sojka JE, Weaver CM. Magnesium supplementation and osteoporosis. Nutr Rev. 1995;53(3):71-74. (PubMed)
88. Zheng J, Mao X, Ling J, He Q, Quan J, Jiang H. Association between serum level of magnesium and postmenopausal osteoporosis: a meta-analysis. Biol Trace Elem Res. 2014;159(1-3):8-14. (PubMed)
89. Chang J, Yu D, Ji J, Wang N, Yu S, Yu B. The association between the concentration of serum magnesium and postmenopausal osteoporosis. Front Med (Lausanne). 2020;7:381. (PubMed)
90. Begin MJ, Ste-Marie LG, Coupal L, Ethier J, Rakel A. Hypomagnesemia during teriparatide treatment in osteoporosis: incidence and determinants. J Bone Miner Res. 2018;33(8):1444-1449. (PubMed)
91. Tucker KL, Hannan MT, Chen H, Cupples LA, Wilson PW, Kiel DP. Potassium, magnesium, and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women. Am J Clin Nutr. 1999;69(4):727-736. (PubMed)
92. Ryder KM, Shorr RI, Bush AJ, et al. Magnesium intake from food and supplements is associated with bone mineral density in healthy older white subjects. J Am Geriatr Soc. 2005;53(11):1875-1880. (PubMed)
93. Dahl C, Sogaard AJ, Tell GS, et al. Nationwide data on municipal drinking water and hip fracture: Could calcium and magnesium be protective? A NOREPOS study. Bone. 2013;57(1):84-91. (PubMed)
94. Orchard TS, Larson JC, Alghothani N, et al. Magnesium intake, bone mineral density, and fractures: results from the Women's Health Initiative Observational Study. Am J Clin Nutr. 2014;99(4):926-933. (PubMed)
95. Cui Y, Cai H, Zheng W, Shu XO. Associations of dietary intakes of calcium, magnesium, and soy isoflavones with bone fracture risk in men: a prospective study. JBMR Plus. 2022;6(2):e10563. (PubMed)
96. Cui Y, Cai H, Gao Y, et al. Associations of dietary intakes of calcium, magnesium and soy isoflavones with osteoporotic fracture risk in postmenopausal women: a prospective study. J Nutr Sci. 2022;11:e62. (PubMed)
97. Hayhoe RP, Lentjes MA, Luben RN, Khaw KT, Welch AA. Dietary magnesium and potassium intakes and circulating magnesium are associated with heel bone ultrasound attenuation and osteoporotic fracture risk in the EPIC-Norfolk cohort study. Am J Clin Nutr. 2015;102(2):376-384. (PubMed)
98. Stendig-Lindberg G, Tepper R, Leichter I. Trabecular bone density in a two year controlled trial of peroral magnesium in osteoporosis. Magnes Res. 1993;6(2):155-163. (PubMed)
99. Abraham GE, Grewal H. A total dietary program emphasizing magnesium instead of calcium. Effect on the mineral density of calcaneous bone in postmenopausal women on hormonal therapy. J Reprod Med. 1990;35(5):503-507. (PubMed)
100. Aydin H, Deyneli O, Yavuz D, et al. Short-term oral magnesium supplementation suppresses bone turnover in postmenopausal osteoporotic women. Biol Trace Elem Res. 2010;133(2):136-143. (PubMed)
101. Nieves JW. Bone. Maximizing bone health--magnesium, BMD and fractures. Nat Rev Endocrinol. 2014;10(5):255-256. (PubMed)
102. Capozzi A, Scambia G, Lello S. Calcium, vitamin D, vitamin K2, and magnesium supplementation and skeletal health. Maturitas. 2020;140:55-63. (PubMed)
103. Landi F, Liperoti R, Russo A, et al. Sarcopenia as a risk factor for falls in elderly individuals: results from the ilSIRENTE study. Clin Nutr. 2012;31(5):652-658. (PubMed)
104. Hayhoe RPG, Lentjes MAH, Mulligan AA, Luben RN, Khaw KT, Welch AA. Cross-sectional associations of dietary and circulating magnesium with skeletal muscle mass in the EPIC-Norfolk cohort. Clin Nutr. 2019;38(1):317-323. (PubMed)
105. Scott D, Blizzard L, Fell J, Giles G, Jones G. Associations between dietary nutrient intake and muscle mass and strength in community-dwelling older adults: the Tasmanian Older Adult Cohort Study. J Am Geriatr Soc. 2010;58(11):2129-2134. (PubMed)
106. Welch AA, Kelaiditi E, Jennings A, Steves CJ, Spector TD, MacGregor A. Dietary magnesium is positively associated with skeletal muscle power and indices of muscle mass and may attenuate the association between circulating C-reactive protein and muscle mass in women. J Bone Miner Res. 2016;31(2):317-325. (PubMed)
107. Welch AA, Skinner J, Hickson M. Dietary magnesium may be protective for aging of bone and skeletal muscle in middle and younger older age men and women: cross-sectional findings from the UK Biobank cohort. Nutrients. 2017;9(11). (PubMed)
108. Petermann-Rocha F, Chen M, Gray SR, Ho FK, Pell JP, Celis-Morales C. Factors associated with sarcopenia: A cross-sectional analysis using UK Biobank. Maturitas. 2020;133:60-67. (PubMed)
109. Beaudart C, Locquet M, Touvier M, Reginster JY, Bruyere O. Association between dietary nutrient intake and sarcopenia in the SarcoPhAge study. Aging Clin Exp Res. 2019;31(6):815-824. (PubMed)
110. Veronese N, Berton L, Carraro S, et al. Effect of oral magnesium supplementation on physical performance in healthy elderly women involved in a weekly exercise program: a randomized controlled trial. Am J Clin Nutr. 2014;100(3):974-981. (PubMed)
111. Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Screening for preeclampsia: US Preventive Services Task Force Recommendation Statement. JAMA. 2017;317(16):1661-1667. (PubMed)
112. Jeyabalan A. Epidemiology of preeclampsia: impact of obesity. Nutr Rev. 2013;71 Suppl 1:S18-25. (PubMed)
113. Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009;33(3):130-137. (PubMed)
114. Duley L, Henderson-Smart DJ, Chou D. Magnesium sulphate versus phenytoin for eclampsia. Cochrane Database Syst Rev. 2010(10):CD000128. (PubMed)
115. Makrides M, Crosby DD, Bain E, Crowther CA. Magnesium supplementation in pregnancy. Cochrane Database Syst Rev. 2014(4):Cd000937. (PubMed)
116. Yuan J, Yu Y, Zhu T, Lin X, Jing X, Zhang J. Oral magnesium supplementation for the prevention of preeclampsia: a meta-analysis or randomized controlled trials. Biol Trace Elem Res. 2022;200(8):3572-3581. (PubMed)
117. Sibai BM. Diagnosis, prevention, and management of eclampsia. Obstet Gynecol. 2005;105(2):402-410. (PubMed)
118. Altman D, Carroli G, Duley L, et al. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet. 2002;359(9321):1877-1890. (PubMed)
119. McDonald SD, Lutsiv O, Dzaja N, Duley L. A systematic review of maternal and infant outcomes following magnesium sulfate for pre-eclampsia/eclampsia in real-world use. Int J Gynaecol Obstet. 2012;118(2):90-96. (PubMed)
120. World Health Organization. WHO recommendations for prevention and treatment of pre-eclampsia and eclampsia. Implications and actions. Available at: http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/program-action-eclampsia/en/. Accessed 10/9/18.
121. Berhan Y, Berhan A. Should magnesium sulfate be administered to women with mild pre-eclampsia? A systematic review of published reports on eclampsia. J Obstet Gynaecol Res. 2015;41(6):831-842. (PubMed)
122. Vigil-DeGracia P, Ludmir J, Ng J, et al. Is there benefit to continue magnesium sulphate postpartum in women receiving magnesium sulphate before delivery? A randomised controlled study. BJOG. 2018;125(10):1304-1311. (PubMed)
123. Diaz V, Long Q, Oladapo OT. Alternative magnesium sulphate regimens for women with pre-eclampsia and eclampsia. Cochrane Database Syst Rev. 2023;10(10):CD007388. (PubMed)
124. Shaheen RS, Ismail RA, Salama EY, Korini SM, Elsaeidy AS. Efficacy and safety of 12-hour versus 24-hour magnesium sulfate in management of patients with pre-eclampsia and eclampsia: a systematic review and meta-analysis. BMC Womens Health. 2024;24(1):421. (PubMed)
125. American College of Obstetricians and Gynecologists Committee. Committee opinion no. 573: magnesium sulfate use in obstetrics. Obstet Gynecol. 2013;122(3):727-728. (PubMed)
126. Roberts D, Brown J, Medley N, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2017;3:Cd004454. (PubMed)
127. Crowther CA, Brown J, McKinlay CJ, Middleton P. Magnesium sulphate for preventing preterm birth in threatened preterm labour. Cochrane Database Syst Rev. 2014(8):Cd001060. (PubMed)
128. McNamara HC, Crowther CA, Brown J. Different treatment regimens of magnesium sulphate for tocolysis in women in preterm labour. Cochrane Database Syst Rev. 2015(12):Cd011200. (PubMed)
129. Crowther CA, Ashwood P, Middleton PF, et al. Prenatal intravenous magnesium at 30-34 weeks' gestation and neurodevelopmental outcomes in offspring: the MAGENTA randomized clinical trial. JAMA. 2023;330(7):603-614. (PubMed)
130. Jafarabady K, Shafiee A, Eshraghi N, et al. Magnesium sulfate for fetal neuroprotection in preterm pregnancy: a meta-analysis of randomized controlled trials. BMC Pregnancy Childbirth. 2024;24(1):519. (PubMed)
131. Tagin M, Shah PS, Lee KS. Magnesium for newborns with hypoxic-ischemic encephalopathy: a systematic review and meta-analysis. J Perinatol. 2013;33(9):663-669. (PubMed)
132. Kumar C, Adhisivam B, Bobby Z, Bhat BV. Magnesium sulfate as an adjunct to therapeutic hypothermia in the management of term infants with hypoxic-ischemic encephalopathy: a randomized, parallel-group, controlled trial. Indian J Pediatr. 2023;90(9):886-892. (PubMed)
133. Siddiqui MA, Butt TK. Role of intravenous magnesium sulphate in term neonates with hypoxic ischemic encephalopathy (HIE) in a low-income country: a randomised clinical trial. J Coll Physicians Surg Pak. 2021;31(7):817-820. (PubMed)
134. Ichiba H, Tamai H, Negishi H, et al. Randomized controlled trial of magnesium sulfate infusion for severe birth asphyxia. Pediatr Int. 2002;44(5):505-509. (PubMed)
135. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2013;2013(1):CD003311. (PubMed)
136. Rosanoff A, Costello RB, Johnson GH. Effectively prescribing oral magnesium therapy for hypertension: a categorized systematic review of 49 clinical trials. Nutrients. 2021;13(1):195. (PubMed)
137. Xu L, Li X, Wang X, Xu M. Effects of magnesium supplementation on improving hyperglycemia, hypercholesterolemia, and hypertension in type 2 diabetes: A pooled analysis of 24 randomized controlled trials. Front Nutr. 2022;9:1020327. (PubMed)
138. Parsanathan R. Trace element magnesium: a key player in hypertension management. Hypertens Res. 2023;46(10):2442-2444. (PubMed)
139. Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N Engl J Med. 1997;336(16):1117-1124. (PubMed)
140. Maier JA. Endothelial cells and magnesium: implications in atherosclerosis. Clin Sci (Lond). 2012;122(9):397-407. (PubMed)
141. Darooghegi Mofrad M, Djafarian K, Mozaffari H, Shab-Bidar S. Effect of magnesium supplementation on endothelial function: A systematic review and meta-analysis of randomized controlled trials. Atherosclerosis. 2018;273:98-105. (PubMed)
142. Shechter M, Sharir M, Labrador MJ, Forrester J, Silver B, Bairey Merz CN. Oral magnesium therapy improves endothelial function in patients with coronary artery disease. Circulation. 2000;102(19):2353-2358. (PubMed)
143. Barbagallo M, Dominguez LJ, Galioto A, Pineo A, Belvedere M. Oral magnesium supplementation improves vascular function in elderly diabetic patients. Magnes Res. 2010;23(3):131-137. (PubMed)
144. Cunha AR, D'El-Rei J, Medeiros F, et al. Oral magnesium supplementation improves endothelial function and attenuates subclinical atherosclerosis in thiazide-treated hypertensive women. J Hypertens. 2017;35(1):89-97. (PubMed)
145. Mortazavi M, Moeinzadeh F, Saadatnia M, Shahidi S, McGee JC, Minagar A. Effect of magnesium supplementation on carotid intima-media thickness and flow-mediated dilatation among hemodialysis patients: a double-blind, randomized, placebo-controlled trial. Eur Neurol. 2013;69(5):309-316. (PubMed)
146. Cosaro E, Bonafini S, Montagnana M, et al. Effects of magnesium supplements on blood pressure, endothelial function and metabolic parameters in healthy young men with a family history of metabolic syndrome. Nutr Metab Cardiovasc Dis. 2014;24(11):1213-1220. (PubMed)
147. Joris PJ, Plat J, Bakker SJ, Mensink RP. Effects of long-term magnesium supplementation on endothelial function and cardiometabolic risk markers: A randomized controlled trial in overweight/obese adults. Sci Rep. 2017;7(1):106. (PubMed)
148. Mookadam F, Moustafa SE, Lester SJ, Warsame T. Subclinical atherosclerosis: evolving role of carotid intima-media thickness. Prev Cardiol. 2010;13(4):186-197. (PubMed)
149. Ma J, Folsom AR, Melnick SL, et al. Associations of serum and dietary magnesium with cardiovascular disease, hypertension, diabetes, insulin, and carotid arterial wall thickness: the ARIC study. Atherosclerosis Risk in Communities Study. J Clin Epidemiol. 1995;48(7):927-940. (PubMed)
150. Woods KL, Fletcher S, Roffe C, Haider Y. Intravenous magnesium sulphate in suspected acute myocardial infarction: results of the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2). Lancet. 1992;339(8809):1553-1558. (PubMed)
151. Woods KL, Fletcher S. Long-term outcome after intravenous magnesium sulphate in suspected acute myocardial infarction: the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2). Lancet. 1994;343(8901):816-819. (PubMed)
152. Fourth International Study of Infarct Survival (ISIS-4) Collaborative Group. A randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. Lancet. 1995;345(8951):669-685. (PubMed)
153. Ziegelstein RC, Hilbe JM, French WJ, Antman EM, Chandra-Strobos N. Magnesium use in the treatment of acute myocardial infarction in the United States (observations from the Second National Registry of Myocardial Infarction). Am J Cardiol. 2001;87(1):7-10. (PubMed)
154. Li J, Zhang Q, Zhang M, Egger M. Intravenous magnesium for acute myocardial infarction. Cochrane Database Syst Rev. 2007(2):CD002755. (PubMed)
155. Pitliya A, Vasudevan SS, Batra V, et al. Global prevalence of hypomagnesemia in type 2 diabetes mellitus - a comprehensive systematic review and meta-analysis of observational studies. Endocrine. 2024;84(3):842-851. (PubMed)
156. Takaya J, Higashino H, Kobayashi Y. Intracellular magnesium and insulin resistance. Magnes Res. 2004;17(2):126-136. (PubMed)
157. Yokota K, Kato M, Lister F, et al. Clinical efficacy of magnesium supplementation in patients with type 2 diabetes. J Am Coll Nutr. 2004;23(5):506S-509S. (PubMed)
158. Rodriguez-Moran M, Guerrero-Romero F. Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subjects: a randomized double-blind controlled trial. Diabetes Care. 2003;26(4):1147-1152. (PubMed)
159. Veronese N, Watutantrige-Fernando S, Luchini C, et al. Effect of magnesium supplementation on glucose metabolism in people with or at risk of diabetes: a systematic review and meta-analysis of double-blind randomized controlled trials. Eur J Clin Nutr. 2016;70(12):1354-1359. (PubMed)
160. Simental-Mendia LE, Sahebkar A, Rodriguez-Moran M, Guerrero-Romero F. A systematic review and meta-analysis of randomized controlled trials on the effects of magnesium supplementation on insulin sensitivity and glucose control. Pharmacol Res. 2016;111:272-282. (PubMed)
161. Hashimoto Y, Nishimura Y, Maeda H, Yokoyama M. Assessment of magnesium status in patients with bronchial asthma. J Asthma. 2000;37(6):489-496. (PubMed)
162. Irazuzta JE, Chiriboga N. Magnesium sulfate infusion for acute asthma in the emergency department. J Pediatr (Rio J). 2017;93 Suppl 1:19-25. (PubMed)
163. Su Z, Li R, Gai Z. Intravenous and nebulized magnesium sulfate for treating acute asthma in children: a systematic review and meta-analysis. Pediatr Emerg Care. 2018;34(6):390-395. (PubMed)
164. Griffiths B, Kew KM. Intravenous magnesium sulfate for treating children with acute asthma in the emergency department. Cochrane Database Syst Rev. 2016;4(4):CD011050. (PubMed)
165. Kew KM, Kirtchuk L, Michell CI. Intravenous magnesium sulfate for treating adults with acute asthma in the emergency department. Cochrane Database Syst Rev. 2014(5):Cd010909. (PubMed)
166. Knightly R, Milan SJ, Hughes R, et al. Inhaled magnesium sulfate in the treatment of acute asthma. Cochrane Database Syst Rev. 2017;11:Cd003898. (PubMed)
167. Monteleone CA, Sherman AR. Nutrition and asthma. Arch Intern Med. 1997;157(1):23-34. (PubMed)
168. Beasley R, Aldington S. Magnesium in the treatment of asthma. Curr Opin Allergy Clin Immunol. 2007;7(1):107-110. (PubMed)
169. Fogarty A, Lewis SA, Scrivener SL, et al. Oral magnesium and vitamin C supplements in asthma: a parallel group randomized placebo-controlled trial. Clin Exp Allergy. 2003;33(10):1355-1359. (PubMed)
170. Na HS, Ryu JH, Do SH. The role of magnesium in pain. In: Vink R, Nechifor M, eds. Magnesium in the Central Nervous System. Adelaide (AU): University of Adelaide Press (c) 2011.
171. Wang SC, Pan PT, Chiu HY, Huang CJ. Neuraxial magnesium sulfate improves postoperative analgesia in Cesarean section delivery women: A meta-analysis of randomized controlled trials. Asian J Anesthesiol. 2017;55(3):56-67. (PubMed)
172. Xiao F, Xu W, Feng Y, et al. Intrathecal magnesium sulfate does not reduce the ED50 of intrathecal hyperbaric bupivacaine for cesarean delivery in healthy parturients: a prospective, double blinded, randomized dose-response trial using the sequential allocation method. BMC Anesthesiol. 2017;17(1):8. (PubMed)
173. Paleti S, Prasad PK, Lakshmi BS. A randomized clinical trial of intrathecal magnesium sulfate versus midazolam with epidural administration of 0.75% ropivacaine for patients with preeclampsia scheduled for elective cesarean section. J Anaesthesiol Clin Pharmacol. 2018;34(1):23-28. (PubMed)
174. Ma S, Zhang Y, Li Q. Magnesium sulfate reduces postoperative pain in women with cesarean section: A meta-analysis of randomized controlled trials. Pain Pract. 2022;22(1):8-18. (PubMed)
175. Vlok R, Melhuish TM, Chong C, Ryan T, White LD. Adjuncts to local anaesthetics in tonsillectomy: a systematic review and meta-analysis. J Anesth. 2017;31(4):608-616. (PubMed)
176. Cho HK, Park IJ, Yoon HY, Hwang SH. Efficacy of adjuvant magnesium for posttonsillectomy morbidity in children: a meta-analysis. Otolaryngol Head Neck Surg. 2018;158(1):27-35. (PubMed)
177. Xie M, Li XK, Peng Y. Magnesium sulfate for postoperative complications in children undergoing tonsillectomies: a systematic review and meta-analysis. J Evid Based Med. 2017;10(1):16-25. (PubMed)
178. Chen C, Tao R. The impact of magnesium sulfate on pain control after laparoscopic cholecystectomy: a meta-analysis of randomized controlled studies. Surg Laparosc Endosc Percutan Tech. 2018;28(6):349-353. (PubMed)
179. Campos J, Bas JL, Campos C, Mariscal G, Bas T, Bas P. Efficacy and safety of intravenous magnesium sulfate in spinal surgery: a systematic review and meta-analysis. J Clin Med. 2024;13(11):3122. (PubMed)
180. Jin Z, Zhao J. Effectiveness and impact of intravenous magnesium sulfate in spinal surgery systematic review and meta-analysis. Front Pharmacol. 2025;16:1624119. (PubMed)
181. Abd-Elsalam KA, Fares KM, Mohamed MA, Mohamed MF, El-Rahman AMA, Tohamy MM. Efficacy of magnesium sulfate added to local anesthetic in a transversus abdominis plane bock for analgesia following total abdominal hysterectomy: a randomized trial. Pain Physician. 2017;20(7):641-647. (PubMed)
182. Imani F, Rahimzadeh P, Faiz HR, Abdullahzadeh-Baghaei A. An evaluation of the adding magnesium sulfate to ropivacaine on ultrasound-guided transverse abdominis plane block after abdominal hysterectomy. Anesth Pain Med. 2018;8(4):e74124. (PubMed)
183. Hamed MA. Comparative study between magnesium sulfate and lidocaine for controlled hypotension during functional endoscopic sinus surgery: a randomized controlled study. Anesth Essays Res. 2018;12(3):715-718. (PubMed)
184. Hassan PF, Saleh AH. Dexmedetomidine versus magnesium sulfate in anesthesia for cochlear implantation surgery in pediatric patients. Anesth Essays Res. 2017;11(4):1064-1069. (PubMed)
185. Brill S, Sedgwick PM, Hamann W, Di Vadi PP. Efficacy of intravenous magnesium in neuropathic pain. Br J Anaesth. 2002;89(5):711-714. (PubMed)
186. Tanaka M, Shimizu S, Nishimura W, et al. Relief of neuropathic pain with intravenous magnesium [Article in Japanese]. Masui. 1998;47(9):1109-1113. (PubMed)
187. Pickering G, Morel V, Simen E, et al. Oral magnesium treatment in patients with neuropathic pain: a randomized clinical trial. Magnes Res. 2011;24(2):28-35. (PubMed)
188. Pickering G, Pereira B, Morel V, et al. Ketamine and magnesium for refractory neuropathic pain: a randomized, double-blind, crossover trial. Anesthesiology. 2020;133(1):154-164. (PubMed)
189. Mauskop A, Altura BM. Role of magnesium in the pathogenesis and treatment of migraines. Clin Neurosci. 1998;5(1):24-27. (PubMed)
190. Mauskop A, Altura BT, Altura BM. Serum ionized magnesium levels and serum ionized calcium/ionized magnesium ratios in women with menstrual migraine. Headache. 2002;42(4):242-248. (PubMed)
191. Peikert A, Wilimzig C, Kohne-Volland R. Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia. 1996;16(4):257-263. (PubMed)
192. Wang F, Van Den Eeden SK, Ackerson LM, Salk SE, Reince RH, Elin RJ. Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a randomized, double-blind, placebo-controlled trial. Headache. 2003;43(6):601-610. (PubMed)
193. Pfaffenrath V, Wessely P, Meyer C, et al. Magnesium in the prophylaxis of migraine--a double-blind placebo-controlled study. Cephalalgia. 1996;16(6):436-440. (PubMed)
194. Karimi N, Razian A, Heidari M. The efficacy of magnesium oxide and sodium valproate in prevention of migraine headache: a randomized, controlled, double-blind, crossover study. Acta Neurol Belg. 2021;121(1):167-173. (PubMed)
195. Khani S, Hejazi SA, Yaghoubi M, Sharifipour E. Comparative study of magnesium, sodium valproate, and concurrent magnesium-sodium valproate therapy in the prevention of migraine headaches: a randomized controlled double-blind trial. J Headache Pain. 2021;22(1):21. (PubMed)
196. Demirkaya S, Vural O, Dora B, Topcuoglu MA. Efficacy of intravenous magnesium sulfate in the treatment of acute migraine attacks. Headache. 2001;41(2):171-177. (PubMed)
197. Bigal ME, Bordini CA, Tepper SJ, Speciali JG. Intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura. A randomized, double-blind, placebo-controlled study. Cephalalgia. 2002;22(5):345-353. (PubMed)
198. Corbo J, Esses D, Bijur PE, Iannaccone R, Gallagher EJ. Randomized clinical trial of intravenous magnesium sulfate as an adjunctive medication for emergency department treatment of migraine headache. Ann Emerg Med. 2001;38(6):621-627. (PubMed)
199. Cete Y, Dora B, Ertan C, Ozdemir C, Oktay C. A randomized prospective placebo-controlled study of intravenous magnesium sulphate vs. metoclopramide in the management of acute migraine attacks in the Emergency Department. Cephalalgia. 2005;25(3):199-204. (PubMed)
200. Choi H, Parmar N. The use of intravenous magnesium sulphate for acute migraine: meta-analysis of randomized controlled trials. Eur J Emerg Med. 2014;21(1):2-9. (PubMed)
201. Shahrami A, Assarzadegan F, Hatamabadi HR, Asgarzadeh M, Sarehbandi B, Asgarzadeh S. Comparison of therapeutic effects of magnesium sulfate vs. dexamethasone/metoclopramide on alleviating acute migraine headache. J Emerg Med. 2015;48(1):69-76. (PubMed)
202. Baratloo A, Mirbaha S, Delavar Kasmaei H, Payandemehr P, Elmaraezy A, Negida A. Intravenous caffeine citrate vs. magnesium sulfate for reducing pain in patients with acute migraine headache; a prospective quasi-experimental study. Korean J Pain. 2017;30(3):176-182. (PubMed)
203. Mauskop A, Varughese J. Why all migraine patients should be treated with magnesium. J Neural Transm. 2012;119(5):575-579. (PubMed)
204. Jiang P, Lv Q, Lai T, Xu F. Does hypomagnesemia impact on the outcome of patients admitted to the intensive care unit? A systematic review and meta-analysis. Shock. 2017;47(3):288-295. (PubMed)
205. Upala S, Jaruvongvanich V, Wijarnpreecha K, Sanguankeo A. Hypomagnesemia and mortality in patients admitted to intensive care unit: a systematic review and meta-analysis. QJM. 2016;109(7):453-459. (PubMed)
206. Nayak R, Attry S, Ghosh SN. Serum magnesium as a marker of neurological outcome in severe traumatic brain injury patients. Asian J Neurosurg. 2018;13(3):685-688. (PubMed)
207. Noormandi A, Khalili H, Mohammadi M, Abdollahi A. Effect of magnesium supplementation on lactate clearance in critically ill patients with severe sepsis: a randomized clinical trial. Eur J Clin Pharmacol. 2020;76(2):175-184. (PubMed)
208. Ardehali SH, Dehghan S, Baghestani AR, Velayati A, Vahdat Shariatpanahi Z. Association of admission serum levels of vitamin D, calcium, Phosphate, magnesium and parathormone with clinical outcomes in neurosurgical ICU patients. Sci Rep. 2018;8(1):2965. (PubMed)
209. Bulloch MN, Cardinale-King M, Cogle S, et al. Correction of electrolyte abnormalities in critically ill patients. Intensive Care Research. 2024;4:19-37.
210. USDA, Agricultural Research Service, 2023. Usual Nutrient Intake from Food and Beverages, by Male/Female and Age, What We Eat in America, NHANES 2017-March 2020 Prepandemic. Available at http://www.ars.usda.gov/nea/bhnrc/fsrg. Accessed 7/8/25.
211. Natural Medicines. Magnesium. Professional handout/Effectiveness. Available at: https://naturalmedicines-therapeuticresearch-com. Accessed 10/29/18.
212. Hendler SS, Rorvik DM. PDR for Nutritional Supplements. Montvale: Thomson Reuters; 2008.
213. Natural Medicines. Magnesium. Professional handout/Drug Interactions. Available at: https://naturalmedicines-therapeuticresearch-com. Accessed 10/19/18.
214. Wilhelm SM, Rjater RG, Kale-Pradhan PB. Perils and pitfalls of long-term effects of proton pump inhibitors. Expert Rev Clin Pharmacol. 2013;6(4):443-451. (PubMed)
215. US Food and Drug Administration. Proton Pump Inhibitor drugs (PPIs): Drug Safety Communication - Low Magnesium Levels Can Be Associated With Long-Term Use. 08/04/2017 Available at: https://www.fda.gov/Drugs/DrugSafety/ucm245011.htm. Accessed 10/22/18.

Disclaimer

The Linus Pauling Institute's Micronutrient Information Center provides scientific information on the health aspects of dietary factors and supplements, food, and beverages for the general public. The information is made available with the understanding that the author and publisher are not providing medical, psychological, or nutritional counseling services on this site. The information should not be used in place of a consultation with a competent health care or nutrition professional.

The information on dietary factors and supplements, food, and beverages contained on this website does not cover all possible uses, actions, precautions, side effects, and interactions. It is not intended as nutritional or medical advice for individual problems. Liability for individual actions or omissions based upon the contents of this site is expressly disclaimed.

You may not copy, modify, distribute, display, transmit, perform, publish or sell any of the copyrightable material on this website. You may hyperlink to this website but must include the following statement:

"This link leads to a website provided by the Linus Pauling Institute at Oregon State University. [Your name] is not affiliated or endorsed by the Linus Pauling Institute or Oregon State University."