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Abstract

Magnesium is an essential mineral necessary for optimal cellular health and well-being. Many adults in the United States fail to get recommended amounts of magnesium from their diets. Even so, symptoms of magnesium deficiency are rarely seen; however, maintaining normal body stores could be preventative against common diseases.

Keywords

magnesium supplementation benefits

Magnesium is the fourth most abundant body mineral and is predominately an intracellular cation found in bones, tissues, and organs with only very small amounts (1%) found in blood. More than 300 biochemical reactions in the body require magnesium, which supports maintenance of normal nerve and muscle function, strong bones, a steady heart rhythm, and a healthy immune system.¹

Serum magnesium levels² usually range between 1.5 and 2.3 mg/dL or 0.62 to 0.95 mmol/L with more than half of magnesium being ionized (usable) and the rest being bound to plasma proteins.^3,4 Studies have suggested that as many as 23% of adults in the United States had hypomagnesemia and failed to meet the recommended dietary intake of magnesium (see Table 1).^1,5 Many people with common diseases such as diabetes were also found to have an even greater risk for hypomagnesemia as were older adults.^1,6 Jaffe⁷ reported that as many as 75% of adults were magnesium deficient. Malnutrition or poor absorption of magnesium along with excessive renal loss via diuretics or other medications, diabetes, or alcohol abuse add to the high incidence of magnesium deficiency.^1,4

Table 1.

Recommended Allowances for Dietary Magnesium in Adults and Children by Age in Years^a

Age (Years)	Female (mg/d)	Male (mg/d)	In Pregnancy (mg/d)	In Lactating Women (mg/d)
1-3	80	80	—	—
4-8	130	130	—	—
9-13	240	240	—	—
14-18	360	410	400	360
19-30	310	400	350	310
≥31	320	420	360	320

^a Adapted from the Office of Dietary Supplements magnesium fact sheet.^1,5

Researchers analyzed the 24-hour dietary recall data from the National Health and Nutrition Examination Survey (NHANES) finding that magnesium intake decreases with increasing age and more significantly in some ethnic groups than others (P = .035 for Caucasians versus P < .001 for both African-Americans and Mexican-Americans). Furthermore, women were typically found to have a lower dietary intake of magnesium than were men (P < .001).^1,6

Although diet surveys suggest Americans do not get recommended amounts of magnesium in their diets, severe symptoms of magnesium deficiencies are rarely seen in the United States. However, there is concern that many people might have low body storage of magnesium because of consistently low dietary intake. Adequate magnesium body storage has been suggested to be protective against many common disorders such as cardiovascular disease and dysfunction of the immune system. Early signs of magnesium deficiency can include nausea, vomiting, weakness, fatigue, and loss of appetite.¹

Hypermagnesemia is very rare. Hypermagnesemia is most commonly caused by renal failure and can result in muscle weakness, hypotension, respiratory distress, bradycardia, and nausea and vomiting.⁴

Foods with high levels of magnesium are green vegetables, beans and peas, nuts, and whole unrefined grains (see Table 2).⁵ Tap water (hard water being best) can also be a source of magnesium, but the magnesium levels in water vary greatly depending on the mineral content of the water supply.¹

Table 2.

Top 20 Food Sources of Magnesium

Food	Milligrams	%DV^a
1. Cooked halibut (3 oz)	90	20
2. Dry roasted almonds (1 oz)	80	20
3. Dry roasted cashews (1 oz)	75	20
4. Cooked soybeans (1/2 cup)	75	20
5. Cooked spinach (1/2 cup)	75	20
6. Dry, roasted mixed nuts (1 oz)	65	15
7. Shredded wheat cereal (2 biscuits)	55	15
8. Instant oatmeal, fortified (1 cup)	55	15
9. Potato, with skin-baked (1 medium)	50	15
10. Dry roasted peanuts (1 oz)	50	15
11. Peanut butter, smooth (2 tablespoons)	50	15
12. Wheat bran (2 tablespoons)	45	10
13. Cooked black-eyed peas (1/2 cup)	45	10
14. Yogurt, plain (8 fluid oz.)	45	10
15. Bran flakes (1/2 cup)	40	10
16. Baked beans, vegetarian (1/2 cup)	40	10
17. Long-grained brown rice (1/2 cup)	40	10
18. Lentils cooked (1/2 cup)	35	8
19. Avocado (1/2 cup pureed)	35	8
20. Kidney beans, canned (1/2 cup)	35	8

^a %DV = percentage daily value (DV) is the percentage reported by the Food and Drug Administration showing how much of the total daily value is provided by one serving. The estimated total daily value for magnesium is 400 mg. Adapted from the Office of Dietary Supplements magnesium fact sheet.¹

Magnesium is so integral to optimal cellular function that a deficiency of magnesium is believed to result in numerous medical conditions including asthma, migraines, hypertension, diabetes mellitus, arrhythmias, osteoporosis and osteopenia, insomnia, pre-eclampsia, fibromyalgia, premature ejaculation, premenstrual syndrome, ischemic heart disease, leg cramps, attention-deficit hyperactivity disorder (ADHD), anxiety and psychiatric disorders, chronic pain, hearing loss, metabolic syndrome, autism, and stroke.^8,9 Low plasma concentrations of magnesium reportedly also promote inflammation and have been associated with increased endothelial injury.^3,10 This article examines evidence regarding the benefits and risks (when reported) of magnesium supplementation in many common medical conditions.

Methods

An electronic search was conducted to identify studies from 2005 to 2010 in the following databases: CINAHL, Medline, Health Source: Nursing/Academic Edition and Consumer Edition, ERIC, Alt HealthWatch, PsycINFO, and Cochrane library. The search terms included magnesium, treatment, therapeutic, oral, supplement, prevent, prophylaxis, asthma, hypertension, diabetes mellitus, heart disease, migraine, and headache. Initial results showed 142 articles. Publication type was then limited to clinical trials; clinical trial phases I, II, III, and IV; controlled clinical trial; meta-analysis; and randomized controlled trials bringing the total number to 89 articles. Studies were excluded if only specific populations were used, if multiple treatments were used, if animals were used as subjects, or if mineral water was used for the magnesium supplementation. References from articles were reviewed for relevant additional studies with multiple studies being identified.

Results

Magnesium and Asthma

The World Health Organization (WHO) estimated in 2004 that 300 million people worldwide had asthma.¹¹ In 2007, 34 million people, or 1 in 9 Americans (11.5%), had been diagnosed with asthma during their lifetimes.¹¹ Asthma costs more than $30 billion each year with an estimated annual 1.1 million hospital outpatient visits and 1.6 million emergency department visits.¹¹ Magnesium, as a bronchial smooth muscle relaxant, has been suggested to improve asthma symptoms.

In 1912, Trendelenburg¹² was the first to observe bronchial smooth muscle relaxation in cows after magnesium administration. In 1936, Rosello and Pla¹³ demonstrated the same bronchodilator effect in asthmatic patients. Magnesium causes smooth muscle cell relaxation by decreasing intracellular calcium, thus limiting cellular contraction. Magnesium inhibits the inflammatory response through stabilization of T-cells and suppression of mast cell degranulation. Magnesium also depresses muscle fiber excitability by inhibiting acetylcholine release and inhibiting nitric oxide and prostacyclin synthesis. These functions of magnesium all have a beneficial effect on asthma and could contribute to reducing the severity of symptoms in asthmatic patients.^14,15

Oral supplemental or dietary magnesium in asthma

Reports have been published about the benefits of a high oral magnesium intake to relieve asthma symptoms.^15–23 Nine research articles were found pertaining to dietary or oral magnesium supplementation and its effect on asthma. Of the 9 articles, 7 were randomized controlled trials with an intervention of magnesium supplements,^{15–17,19,20,22,23} and 2 were descriptive correlational design in which dietary magnesium intake was measured.^18,21 Four of the studies used only children; boys and girls ages 19 years and younger.^15–17,21 Five studies evaluated men and women of ages 18 years and older.^{18–20,22,23}

Seven of 9 research articles reported a statistically significant correlation between high magnesium intake and a decrease in severity of asthma symptoms.^{15–18,21–23} Two studies found no significant correlation between an increase in magnesium intake and a decrease in the severity of asthma symptoms.^19,20 Of the 7 studies that found positive correlations, 5 were randomized controlled trials that had a magnesium supplementation intervention of 340 to 400 mg a day for adults and 200 to 300 mg a day for children.^{15–17,22,23} Outcomes measured in these studies were markers of asthma control such as the methacholine challenge test, pulmonary function tests (forced expiratory volume in 1 second and forced vital capacity), antioxidant activity, skin response to recognized antigens, bronchodilator use, and symptom scores. All found a significant result (P < .05) in one or more outcome measures in the magnesium supplementation group and provide support for the hypothesis that oral magnesium supplementation does decrease the severity of asthma symptoms.^{15–17,22,23}

Two other studies reporting a statistically significant correlation between high magnesium intake and a decrease in the severity of asthma symptoms were descriptive studies that looked at the amount of magnesium in subjects' diets compared with lung function, airway reactivity, and wheezing.^18,21 Both studies used food frequency questionnaires and then adjusted analyses for variables such as age, sex, social and medical details, and smoking history. These studies found that dietary magnesium intake positively impacted lung function, airway hyperactivity, and wheezing with the conclusion that a high dietary magnesium intake could benefit people with asthma.^18,21

Two studies did not show a significant relationship between magnesium supplementation and decreased asthma symptom severity.^19,20 The studies were randomized controlled trials with an intervention of magnesium supplementation (450 mg magnesium per day) in adults whose asthma was controlled with at least one dose of a daily inhaled corticosteroid. Examples of measured asthma control outcomes were the methacholine challenge test, pulmonary function tests (such as forced expiratory volume in 1 second and forced vital capacity), bronchodilator use, corticosteroid dose, and symptom scores. No significant difference was found between the magnesium supplemented group and the control group in terms of asthma improvement.^19,20 Nonsignificant findings could be because of subjects already having good asthma control as demonstrated by their low baseline levels of asthma symptoms; therefore, magnesium supplementation would not have provided any significant improvement.¹⁹

Intravenous or inhaled magnesium

The use of both intravenous and inhaled magnesium to treat acute asthma attacks in adults has been reported. In a review updated in 2009, research did not support the use of intravenous magnesium treatment for all acute asthma attacks but did note that intravenous magnesium was effective in improving peak expiratory flow rate and forced expiratory volume in 1 second. This review concluded that intravenous magnesium sulfate in addition to bronchodilators seemed to be safe and beneficial for people with severe asthma attacks or for those in whom bronchodilators do not work. Another study supported use of inhaled magnesium sulfate in addition to a β₂-agonist in the treatment of an acute asthma exacerbation and reported an outcome of these treatments was a decrease in hospital admissions.²⁴ In 2 literature reviews regarding the treatment of acute asthma in children, the use of intravenous or inhaled magnesium was shown to be effective. The reviews also showed that when magnesium was used as an adjuvant therapy it was also safe.^14,25

In synthesizing the research studies for magnesium and asthma, the overall conclusion is that oral magnesium supplementation or an increased dietary magnesium intake can improve the severity of asthma symptoms. The studies reviewed reported no serious adverse outcomes suggesting safety and efficacy of magnesium supplementation.^{15–17,19,20,22,23} Although not every patient with asthma should receive routine intravenous magnesium, such treatment does seem to improve forced expiratory volume in 1 second and peak expiratory flow rate.²⁶

Magnesium and Migraine Headaches

Migraines are relatively severe headaches with attacks lasting between 4 hours and 3 days. It is a common neurological problem that can be as disabling as active psychosis or dementia with features such as nausea or vomiting and severe intolerance to light, sound, odors, and body movement.²⁷ The 2009 United States National Health Interview Survey showed that 16% of adults suffered from migraines, with the prevalence higher in women.²⁸ The economic consequences are substantial, incurring an average cost of $777 per patient per year in some Western European countries. This includes time off from work and reduced efficiency at work due to migraine headaches.²⁷ Studies have shown a magnesium deficiency in people with migraines.^29,30

The role of magnesium in migraines is not completely understood, but it is known that magnesium inhibits the synthesis of nitric oxide, a vasoactive substance and neurotransmitter that is activated early in the cascade of events leading to a migraine attack.^15,29 Low levels of magnesium increase the release of substance P, which potentiates constriction of cerebral vessels during the migraine attack. Low levels of ionized magnesium can also increase the affinity for cerebral vascular muscle serotonin receptor sites leading to an increase of serotonin which potentiates migraine headaches.²⁹ An in vitro study reported that magnesium had a relaxant effect on vascular tone indicating the potential effect of decreasing migraine headaches.³¹

Intravenous magnesium

Several research studies have been completed on the effectiveness of intravenous magnesium in the treatment of acute migraines, but the results have been mixed. Multiple studies have found that intravenous magnesium was successful in the treatment of migraines.^32–36 In contrast, 2 studies done in emergency departments found that intravenous magnesium was not effective in the treatment of acute migraines.^37,38 Differences in the study results might be because of the causes of headaches patients were experiencing and whether magnesium levels of participants was known before intravenous magnesium was given. In the studies that found magnesium effective, participants with acute migraines were known to be deficient in magnesium as evidenced by low serum blood levels drawn before supplemental magnesium treatment was given.^32,33

Prevention of migraines with magnesium

Although treatment of migraine headaches is important, preventing them is likely even more important. There are few safe, well-tolerated, and cost-effective medications that prevent migraine headaches. Ten research articles were found reporting the use of oral magnesium supplementation as a prophylaxis for migraine headaches. Of the 10 studies, 2 were excluded because one study had 2 different interventions used concomitantly (magnesium supplementation and correction of mandibular muscular irritation)³⁹ and in the other study the participants were suffering from hemodialysis headaches.⁴⁰

Seven of the final 8 articles had similar results, finding a statistically significant correlation between oral magnesium supplementation and a decrease in the frequency or severity of migraines.^41–48 Five were randomized control trials^44–48 that used a magnesium supplementation ranging between 360 and 600 mg per day for adults, and 9 mg/kg/day for children. Duration of all studies was either 12 or 16 weeks and had between 35 and 86 participants. Each study measured migraine headache frequency and severity as primary outcomes.^44–47 Koseoglu et al⁴⁶ also measured electrophysiological assessments such as cerebral cortical blood flow before and after the study with visual evoked potentials (VEPs) and brain single photon emission computed tomography (SPECT). Included in the primary outcomes of the study by Peikert et al⁴⁷ was the use of medications for symptomatic treatment.

Five studies found a significant decrease in migraine headache frequency as well as severity in the magnesium treated group compared with the placebo group (P < .05).^44–47 Peikert et al⁴⁷ found a decrease in the medication use for symptomatic treatment compared with placebo, but this decrease failed to be statistically significant. Koseoglu et al⁴⁶ found a significant increase in cerebral cortical blood flow in the 3 different regions of the brain that were tested compared with the pretreatment measures (P < .01). The placebo group did not have a significant change.⁴⁶ Adverse events included diarrhea (4% to 18% of subjects) or gastric irritation (≤5% of subjects), which were reported in each of the studies. A very small number (≤1%) of participants dropped out because of adverse events. These 4 studies showed strong evidence that oral magnesium supplementation was safe and effective in the treatment and prevention of migraine headaches.^44–47

Three studies that found significant results for oral magnesium in the prophylaxis of migraine headaches were performed without a control group. Castelli et al⁴¹ and Grazzi et al^42,43 studied children and used between 122 and 450 mg per day of an oral magnesium supplement over an 8- to 12-week period. The results were a decrease in frequency of headache, a reduction of symptoms, and a decrease in the consumption of analgesics for acute treatment of migraine headaches. The only adverse event reported was the unpleasant taste of the supplement.

A single randomized controlled trial found negative results in that there was no benefit of the supplemental magnesium in regards to the number of migraine days or migraine attacks.⁴⁸ An important note in this study was that the response rate at the end of the 12-week study was only 28.6% for the magnesium group and 29.4% for the placebo group. These low response rates were likely because of the high percentage of diarrhea experienced by the groups (45.7% and 23.5% in the magnesium and placebo groups, respectively).⁴⁸ The high percentage of diarrhea suggests that a poorly absorbed magnesium preparation was used, which could have affected the findings.⁴⁹

Evaluating the risks and benefits of using magnesium supplementation for the prophylaxis of migraine headaches, there is significant evidence suggesting that magnesium decreases the frequency and duration of migraines while having minimal side effects.⁵⁰ The recommended dose of oral magnesium supplementation for the prophylaxis of migraine headaches is 600 mg a day of a chelated magnesium diglycinate prepartation.²⁹

Magnesium and Hypertension

High blood pressure (hypertension) is defined as a systolic blood pressure ≥140 mm Hg and a diastolic blood pressure of ≥90 mm Hg. Over time, high blood pressure causes vascular wall damage, increased risk of blood clots, and plaque buildup leading to a stroke or heart attack. Hypertension can also lead to tissue and organ damage from narrowed and blocked arteries and heart failure from an increased workload.⁵¹ It is estimated that 74.5 million Americans, or 1 out of every 3 adults, have high blood pressure. In 2006 in the United States, 56 561 people died from hypertension. There is increased interest in the role of magnesium in preventing and managing hypertension.⁵²

Studies suggest that magnesium has a role in the regulation of blood pressure. Magnesium competes with calcium for binding sites in vascular smooth muscle cells, thus preventing calcium induced vasoconstriction.⁵³ Magnesium influences the sodium–potassium transport through the cellular membrane, thereby interfering with vascular reactivity, blood pressure, and vascular tone.⁵⁴ Hypotheses suggest that magnesium causes peripheral vasodilatation via inhibition of sympathetic nervous activity and vasorelaxation by endothelium- and cyclooxygenase-dependent mechanisms.⁵⁵ Magnesium deficiency can lead to an increase in thromboxane A2, angiotensin II, and aldosterone concentration, which can increase blood pressure.⁵⁵

In 2010, Rosanoff⁵⁶ completed a large analytical review of the use of oral magnesium supplementation for the treatment of stage 1 hypertension. A total of 44 studies with a wide variety of designs, completed between 1983 and 2009, were reviewed. Oral magnesium supplementation was given to a total of 1556 participants with study sizes of the individual trials ranging from 7 to 227 participants. Studies were sorted into 3 categories: participants with hypertension on antihypertensive medications, participants with hypertension not being treated with medications, and normotensive participants.⁵⁶ After categorizing the studies, the investigator listed them by ascending magnesium daily dose. Blood pressure results from each study were then recorded.⁵⁶

In the 8 studies with subjects (n = 299) who were hypertensive and on antihypertensive medications, the range of oral magnesium supplementation was between 240 and 480 mg per day.⁵⁶ All 8 studies found a decrease in the participants' blood pressure showing that oral magnesium supplementation, even in a dose as small as 240 mg per day, could be effective in lowering the blood pressure of hypertensive participants on antihypertensive medications.⁵⁶

In the 23 studies with hypertensive patients (n = 487) who were not being treated with antihypertensive medications, subjects received between 120 and 960 mg per day of oral magnesium supplementation.⁵⁶ When the dose used in the study was <480 mg per day of magnesium supplementation, there was either no change in blood pressure or only a decrease in either systolic or diastolic pressure. For studies that supplemented with ≥480 mg per day, 7 of 10 found a significant decrease in blood pressure. The 3 studies that found no change in blood pressure represented only 16.2% (33 out of 204) of the subjects in this category.⁵⁶ Results show that smaller doses (<480 mg per day) of oral magnesium supplementation are ineffective at lowering blood pressure in this category. In large enough doses (≥480 mg per day), oral magnesium supplementation can be effective at lowering the blood pressure of hypertensive patients who are not taking antihypertensive medications.⁵⁶

In the 12 studies of participants who were either normotensive or prehypertensive (n = 770), these subjects received magnesium supplementation between 97.2 and 600 mg per day. Results showed no changes in blood pressure after supplementation. Conclusions were that oral magnesium supplementation does not lower blood pressure on normotensive participants, even at high doses.⁵⁶

One additional article published after the analytical review by Rosanoff⁵⁶ confirmed that there were significant reductions in ambulatory blood pressure after 12 weeks of 600 mg per day of magnesium supplementation in stage 1 hypertensive participants (P ≤ .002).⁵⁷

From a review of the literature, it can be concluded that magnesium supplementation can decrease the blood pressure of hypertensive subjects taking antihypertensive medications in small doses. Oral magnesium supplementation can also decrease blood pressure in untreated stage 1 hypertensive subjects in doses ≥480 mg per day. Oral magnesium supplementation is not effective in lowering blood pressure in normotensive subjects.⁵⁶

Magnesium and the Treatment of Pre-eclampsia

Pre-eclampsia in pregnancy is a multisystem disorder of hypertension that significantly contributes to fetal and maternal morbidity⁵⁸ by increasing the risk of maternal cardiac failure, renal failure, and cerebral vascular events.⁵⁹ Uncontrolled hypertension associated with pre-eclampsia also increases fetal incidences of preterm births, growth restrictions, and stillbirths.⁵⁹

The etiology of pre-eclampsia is unknown and delivery remains the only definitive cure.⁵⁸ Pre-eclampsia is diagnosed when a pregnant women presents with new-onset hypertension (blood pressure >140/90) and proteinuria (>300 mg per day) after 20 weeks of gestation.⁵⁹ The incidence rate for pre-eclampsia in 2011 was reported to be approximately 1 in 1858 or about 0.05% in the United States.⁶⁰ Pre-eclampsia has been reported to be responsible for nearly 20% of maternal deaths in the United States.⁵⁹

Historically, early treatments of pre-eclampsia focused on ways to suppress and eliminate convulsions. In 1906, Horn introduced magnesium sulfate as a management for pre-eclampsia–eclampsia.⁵⁸ By 1929, the practice of administering intramuscular magnesium sulfate reduced maternal mortality at one hospital from 36% to 7%.⁶¹ Today, magnesium sulfate is the drug of choice for the prevention and control of seizures in patients with severe pre-eclampsia and eclampsia.⁵⁹

Although the mechanism of action for the treatment of seizures is not well understood, magnesium is known to cause cerebral vasodilation, which then reverses the cerebral vasospasm-induced ischemia caused during eclamptic episodes thus decreasing maternal mortality.⁵⁹ In a large international study known as the Magpie Trial, patients with pre-eclampsia were randomized for magnesium sulfate or placebo.⁶² The women who received magnesium sulfate supplementation had a 58% lower risk of eclampsia (95% confidence interval [CI] = 40% to 71%) than those receiving placebo and also had lower mortality rates (relative risk [RR] = 0.55, 99% CI = 0.26-1.14).^59,62 Initial and follow-up data from this trial also confirmed that there were no substantive harmful effects on either the mother or baby at the time of delivery,⁵⁹ no difference in the risk of death or disability for children at 18 months postdelivery,⁶³ nor for the women at 2 years after treatment.⁶²

Though magnesium was not initially appreciated as the drug of choice for eclampsia, there is now international consensus regarding magnesium as the treatment of choice for pre-eclampsia and eclampsia.⁶¹ Intravenous magnesium sulfate is now considered a mainstay for the treatment of seizures associated with pre-eclampsia.⁵⁸

Magnesium and Coronary Heart Disease

Most conventional medicine focuses on treatment of myocardial infarction through a variety of interventions that repair impaired blood flow to the myocardium. Evidence exists that there could be other factors besides ischemia that are partly to blame for sudden coronary death in myocardial infarction.^64,65 The importance of nonischemic factors in the treatment of myocardial infarction, such as nutritional deficiencies leading to increased myocardial vulnerability, should also be considered. Magnesium is known to play a role in myocardial energy production, in the prevention of dysrhythmias, and in promoting vasodilation, which then helps prevent vasospasm.⁶⁴

Singh⁶⁶ randomized 400 high-risk subjects into 2 different dietary groups. Group A ate a magnesium-rich diet whereas group B ate their usual diet. Subjects were studied over a 10-year period. Those eating magnesium-rich diets had significantly higher serum magnesium levels (P > .01), fewer complications such as ischemic heart disease, arrhythmias, or angina (P < .001), lower mortality (P < .01), and experienced fewer sudden deaths than group B. This study suggested that protection against cardiovascular death could be achieved through the intake of dietary magnesium.⁶⁶

Although there was no significant relationship between magnesium supplementation and the development of cardiovascular disease in the one prospective cohort study of women,⁶⁷ elsewhere in the research, coronary heart disease risks have been shown to be inversely correlated to dietary magnesium supplementation.^3,68–72 Mathers and Beckstrand⁶⁷ reviewed 6 research studies examining the relationship between magnesium supplementation and coronary heart disease or coronary heart disease risk.^{68–71,73,74} Reported results from magnesium supplementation included better small artery elasticity or compliance as a measure of endothelial function, favorable effects on exercise tolerance and left ventricular function in coronary artery disease patients, significantly fewer supraventricular beats (P < .02), and reduced risk of coronary heart disease.

Magnesium could be important in the pathogenesis of sudden death and coronary heart disease.⁶⁶ Magnesium supplementation can improve endothelial function in heart failure patients, help reduce the risk of coronary heart disease, and provide positive effects on exercise tolerance; however, there are inconclusive data regarding magnesium supplementation and the reduction of heart disease in women.⁶⁷ Nevertheless, dietary magnesium should be considered as a preventive element for ischemic heart disease and atherosclerosis.⁷⁵

Magnesium and Diabetes Mellitus

Diabetes mellitus is a disease where either the production or utilization of insulin is impaired. Magnesium plays an important role in glucose metabolism and could influence the release and activity of insulin.^1,76 Insulin also has an effect on magnesium and, in insulin-sensitive tissues, insulin stimulates magnesium uptake.⁷⁷ Hypomagnesemia is frequently noted in patients with either type 1 or type 2 diabetes and could worsen insulin resistance or be a consequence of insulin resistance.^1,78

Magnesium and insulin sensitivity or insulin resistance

Many research studies have been completed investigating the connection between magnesium and type 2 diabetes. In 1998, de Valk et al⁷⁹ found that magnesium supplementation over a 3-month period had no significant effect on glycemic control in moderately controlled, type 2 diabetic patients. Another study using 24 obese nondiabetic children who were matched with 24 lean control subjects noted that the dietary magnesium intake was significantly lower in obese children (P = .0003) and was inversely associated with fasting insulin levels (P = .0002).⁸⁰ Huerta et al⁸⁰ concluded that the association between insulin resistance and magnesium deficiency was present in childhood and that increasing magnesium levels, through supplementation or diet, could be important in the prevention of type 2 diabetes in children who are obese. Larsson and Wolk⁸¹ reviewed 7 studies and found that magnesium intake was inversely associated with the incidence of type 2 diabetes. They concluded that increasing the amount of foods high in magnesium in the diet could reduce the risk of developing type 2 diabetes.⁸¹ Finally, Hadjistavri et al⁸² investigated the effects of oral magnesium supplementation on insulin sensitivity. They reported that magnesium supplementation improved insulin sensitivity and could be helpful with cardiovascular risk reduction in patients with mild uncomplicated hypertension.⁸²

Magnesium and diabetes-associated polyneuropathy

De Leeuw et al⁷⁸ studied 97 type 1 diabetic patients, half of whom received 300 mg per day magnesium supplementation for more than 5 years to determine whether long-term supplementation influenced the natural evolution of polyneuropathy. Findings showed that long-term magnesium supplementation was able to restore normal magnesium levels and positively influence polyneuropathy as compared with the nonsupplemented control subjects.⁷⁸

Magnesium and Constipation

Common treatments

Constipation is a common disorder of gastrointestinal motility that is often chronic and associated with high health care costs.⁸³ In 2003, there were more than 2.5 million visits to physicians for treatment of constipation with several hundred millions of dollars spent on laxatives.⁸⁴

A wide range of nonpharmacologic treatment modalities exist for constipation including first-line approaches such as exercise or increased fluid intake; however, data on the effectiveness of these treatments are limited.^83,84 Increasing fluid intake and physical activity does not seem to improve chronic constipation except in instances where the patient is dehydrated.⁸⁴

Increasing dietary fiber to 20 to 25 g per day is considered the next line of treatment for constipation yet many patients have difficulty with compliance because of the side effects of flatulence, distention, and bloating.⁸⁴ Patients who do not respond to increased dietary fiber are usually instructed to try an osmotic laxative such as sorbitol, lactulose, polyethylene glycol, or milk of magnesia. Milk of magnesia (magnesium hydroxide) is most commonly in liquid form and can work as both an antacid and an osmotic laxative. As a laxative, milk of magnesia pulls salt from the blood into the intestines with water following, which results in an increased intestinal water content resulting in a laxative action.⁸⁵

Osmotic laxatives take several days to work and should be used cautiously in patients with renal or cardiac failure as they can result in electrolyte and volume overload from excessive absorption of sodium, phosphorus, or magnesium. Dehydration is also a risk of osmotic laxative overuse.⁸⁴

Magnesium supplementation

There is anecdotal support for magnesium supplementation in constipation. Magnesium is known to cause relaxation of the muscles lining the colon walls, which allows for smoother wall contractions. These smoother wall contractions allow for effective pushing of stool. Magnesium also attracts water into the colon making stool softer and easier to pass.⁸⁶ In a cross-sectional study of 3835 female Japanese students aged 18 to 20 years, constipation was not associated with low fiber or low water intake from foods but was associated with a low intake of magnesium.^87,88

Discussion

The recognition of magnesium sulfate as an essential part of Epsom salts was discovered by Grew in 1695. Over the next 200 years, there was an increase in chemical and pharmacologic knowledge of magnesium. In recent history, physiological, analytical, and epidemiological data have provided a solid background for the first clinical studies with magnesium. Today, research regarding the effects of magnesium on both health and disease has increased exponentially.⁸⁹

Though research reports for only a few common diseases were presented in this article, magnesium is known to be an essential nutrient that is involved in hundreds of biochemical processes that can impact the development of disease states. Current data note very few adverse effects from supplementation of magnesium through oral or dietary means as long as renal function is normal, since magnesium is excreted through the kidneys. Supplementation of magnesium through the intravenous route does have inherently higher risks and should be instituted only under proper medical supervision.

Conclusion

Studies suggest that magnesium supplementation is inexpensive, generally safe, and well tolerated at recommended dosages. Magnesium supplementation has been suggested to decrease airway resistance in asthma, decrease the frequency and duration of migraine headaches, decrease blood pressure in mild hypertension, decrease maternal mortality rates as a result of pre-eclampsia, decrease insulin resistance, and delay the onset of type 2 diabetes. Magnesium has also been noted to favorably influence the natural progression of diabetic associated neuropathy and to help treat constipation.

Taken together, findings indicate that supplemental magnesium could play an important role in the prevention and management of many common diseases. Nevertheless, stronger evidence and more long-term research studies investigating the potential benefits of supplemental magnesium in different disease states are needed.

Footnotes

Renea L. Beckstrand was the primary author with, graduate nurse practitioner student, Jann Pickens being second author. Both authors contributed to the research, writing, editing, and formatting of this article.

The authors declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

The authors received no financial support for the research and/or authorship of this article.

As a review article, there was no need for human subject approval.

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Beneficial Effects of Magnesium Supplementation

Abstract

Keywords

Methods

Results

Magnesium and Asthma

Oral supplemental or dietary magnesium in asthma

Intravenous or inhaled magnesium

Magnesium and Migraine Headaches

Intravenous magnesium

Prevention of migraines with magnesium

Magnesium and Hypertension

Magnesium and the Treatment of Pre-eclampsia

Magnesium and Coronary Heart Disease

Magnesium and Diabetes Mellitus

Magnesium and insulin sensitivity or insulin resistance

Magnesium and diabetes-associated polyneuropathy

Magnesium and Constipation

Common treatments

Magnesium supplementation

Discussion

Conclusion

Footnotes

References