Magnesium

• How It Works

  There are many benefits to adequate intake of dietary magnesium. However, supplementation may increase the risk of interactions with many drugs.

  Magnesium plays many essential roles in the human body. Adequate intake can help prevent chronic ailments such as heart disease and diabetes, but its potential role in cancer prevention is unclear. Many adults may not get enough through diet, but a true deficiency most often occurs with serious illnesses. Certain medications can also cause deficiency. Magnesium products are also used as drugs for a variety of medical conditions, and treatment is carefully monitored to prevent serious side effects. There are case reports of excess levels due to supplements. Because supplements may interact with many drugs, and magnesium itself is a component of certain over-the-counter drugs, supplements should be avoided in patients with heart, kidney, or gastrointestinal disorders. You should also inform your doctor of any over-the-counter products that you are taking which could contain magnesium.

• Purported Uses
  • To prevent asthma
    Low levels of magnesium from the diet have been associated with the occurrence of asthma and a few small studies show that supplements may benefit lung function.

  • To prevent heart disease
    Magnesium supplements may be beneficial for certain types of heart disease, but there are no studies to show that supplements prevent heart disease.

  • To lower high blood pressure
    Studies conflict on whether magnesium supplements provide benefit. Larger and longer-term studies are needed.

  • To prevent diabetes
    Magnesium supplements have been shown to improve insulin levels in overweight non-diabetic individuals, suggesting that adequate levels may help prevent the onset of diabetes. Larger studies are needed.

  • To help bone development or prevent weak bones
    Small studies show that magnesium supplements have positive effects on bone development in adolescents and can prevent bone loss in postmenopausal women.

  • To prevent fatigue
    There are no studies of oral magnesium supplements for chronic fatigue. A small study has shown that they reduced fatigue symptoms in breast cancer patients with menopausal hot flashes.

  • To reduce hot flashes
    A small study has shown that magnesium can reduce hot flashes with few side effects in breast cancer patients.

  • To improve premenstrual syndrome (PMS) symptoms
    It is unclear whether magnesium can help premenstrual syndrome.

  • To prevent migraines
    There is some evidence that magnesium can help prevent migraines, and several medical guidelines include it as a potential therapy.

  • To relieve leg cramps
    Some studies of moderate quality support the use of magnesium for leg cramps during pregnancy.

  • To relieve acid indigestion, heartburn, sour stomach, and constipation
    (Common Use)
    Magnesium is an active ingredient in many over-the-counter preparations including laxatives and antacids. Many individuals may not realize that they are possibly getting magnesium from these common sources.
• Patient Warnings

  Supplements, antacids or laxatives containing magnesium can interact with many drugs, including antibiotics and medications for chronic diseases such as diabetes and heart disease. Magnesium levels in the body can also be affected by numerous prescription drugs, including the long-term use of drugs commonly used to treat digestive disorders. If you are under treatment for a medical condition, have a complicated medical history, or are in frail condition, you should discuss supplements or antacids that you are taking with your doctor.

• Do Not Take If
  • You have kidney problems such as renal insufficiency or end-stage renal disease.
  • You have gastrointestinal problems such as a bowel obstruction or other bowel disorders.
  • You are taking antibiotics: Supplements, antacids and laxatives containing magnesium may reduce their effectiveness.
  • You are a patient with heart block, a conduction disturbance in the heart.
  • You are taking cardiovascular drugs for heart disease: Magnesium and other electrolyte levels should be monitored by your doctor.
  • You are taking drugs for high blood pressure including calcium channel blockers: Magnesium-containing products could have an additive effect.
  • You are taking sulphonylurea drugs for diabetes: Magnesium supplements or antacids may cause low blood sugar levels.
• Side Effects
  • Diarrhea, nausea, and mild abdominal or bone pain with high doses of magnesium.
  • Although magnesium overdose is relatively rare, there have been some cases in patients with a poor health status using laxatives and with gastrointestinal or kidney problems.
  • Getting magnesium through a diet rich in leafy vegetables, nuts, legumes, whole grains, fruits, and fish is not associated with any side effects.
• Brand Name

  Slow-mag®, MAG 2®, Mag-Ox®

• Clinical Summary

  Magnesium is an essential mineral involved in numerous biochemical processes, including adenosine triphosphate (ATP) production, cellular signal transduction, DNA, RNA and protein synthesis, and bone formation ^(1) (2). It also helps regulate blood pressure and enzymes such as those that control intracellular calcium and potassium, and is essential for normal heart functioning ^(1) (3). The dietary form can be found in many foods, and especially in dark green leafy vegetables, nuts, legumes, whole grains, fruits, and fish ⁽⁴⁾.

  In dietary supplements, other over-the-counter products, and pharmaceutical preparations, magnesium is combined with another substance such as a salt or acid, and has specific therapeutic uses. The carbonate, hydroxide, and oxide forms are found in antacid and laxative products whereas citrate is used as a laxative before diagnostic procedures or surgery of the colon. The chloride, gluconate, lactate, and sulfate forms are clinically used to treat magnesium deficiency.

  Both dietary and supplemental forms have been studied widely for their potential role in chronic ailments such as heart disease and diabetes. Dietary intake is associated with reduced mortality from cardiovascular disease, especially for women ⁽⁵⁾. It is also associated with reduced risk of sudden cardiac death (SCD), although studies have been mixed and more affirmative for the effect of serum magnesium on SCD ^(6) (7). It may help reduce the risk of ischemic stroke ⁽⁸⁾, metabolic syndrome ^(9) (10), type 2 diabetes ⁽¹¹⁾ and insulin resistance ⁽¹²⁾, asthma ⁽¹³⁾, and osteoporosis ⁽¹⁾, but findings from studies on depression are conflicting ^(14) (15). Other studies also have not linked dietary consumption with cancer incidence and mortality ⁽¹⁶⁾, or pancreatic cancer risk ⁽¹⁷⁾, but have associated higher intake with a lower risk for colorectal tumors ⁽¹⁸⁾ and lung cancer ⁽¹⁹⁾. Additional studies are needed to confirm these effects.

  Magnesium supplementation has been evaluated for a variety of health conditions. Oral intake may increase survival in patients with heart failure ^(20) (21), and improve insulin sensitivity in healthy adults ^(22) (77), and in those with diabetes ⁽⁷⁷⁾. In a study of overweight individuals, supplementation resulted in changes in gene expression and other positive effects on metabolic pathways ⁽²³⁾. Some studies have shown a reduction in blood pressure following supplementation ^(24) (25), but an earlier systematic review suggests the positive findings are due to poor trial design and short duration ⁽²⁶⁾. Also in contrast, data from a large, community-based cohort did not show low serum levels to be a risk factor for developing hypertension or cardiovascular disease ⁽²⁷⁾.

  Other studies of oral supplements have demonstrated positive effects on bone mass accrual in healthy adolescents with inadequate intake ⁽²⁸⁾, and suppressed bone turnover in postmenopausal osteoporotic women ⁽²⁹⁾. In adults with asthma, supplementation improved objective measures of airway resistance and subjective measures of asthma control and quality of life ⁽¹³⁾; in pediatric patients with cystic fibrosis, it has improved respiratory muscle strength ⁽³⁰⁾. There is also moderate evidence for its use in migraine headache and prophylaxis ⁽³¹⁾. Although preliminary data have shown mixed results with oral supplementation for premenstrual syndrome ⁽³²⁾, a pilot study indicates that it reduces menopausal hot flashes in breast cancer patients ⁽³³⁾, and a systematic review supports its use for leg cramps during pregnancy ⁽³⁴⁾. Larger studies are needed to elucidate conflicting results and clarify the roles for supplementation across various health conditions.

  Many adults, particularly African-Americans ⁽³⁵⁾ and the elderly ⁽⁹⁾, may not have adequate dietary intakes of magnesium. However, true deficiency most often occurs with critical illness including cardiac conditions and preeclampsia, as well as gastrointestinal and renal conditions, poorly-controlled diabetes, and alcoholism ⁽³⁾. In addition, certain medications including calcineurin inhibitors ⁽³⁶⁾, high-dose antivirals ⁽³⁷⁾, and the long-term use of proton pump inhibitors ⁽³⁸⁾, as well as some cancer therapy regimens ^(39) (40) and surgical procedures ^(41) (42), may also cause hypomagnesemia. If deficiency is suspected, patients should be evaluated by their treating physician to determine the extent of inadequate intake and its effective management, as well as to avoid potential drug interactions or magnesium toxicity.

  Hypermagnesemia is rare and results from failure to excrete magnesium or because of excessive intake. It may especially occur in patients with gastrointestinal or renal dysfunction, and have serious effects such as hypotension, bradycardia, depression of tendon reflexes, and other cardiovascular and neuromuscular manifestations ^(43) (44).

• Food Sources

  Leafy vegetables, nuts, legumes, whole grains, fruits and fish ⁽⁴⁾

• Purported Uses
  • Asthma
  • Cardiovascular disease
  • Diabetes
  • Fatigue
  • Hot flashes
  • Hypertension
  • Leg cramps
  • Migraines
  • Osteoporosis
  • Premenstrual syndrome
• Mechanism of Action

  Magnesium plays a significant role in vascular and metabolic biology as well as numerous biochemical reactions. It negatively regulates vascular calcification and osteogenic differentiation through an increase or restoration of transient receptor potential melastatin 7 (TRPM7) activity and increased expression of anticalcification proteins, in vitro ⁽⁴⁵⁾. It also influences blood pressure levels through interactions with the renin-angiotensin system, by acting as a calcium channel blocker to reduce vascular resistance, and by modulating vascular tone and reactivity ^(46) (47). Further, it contributes to the homeostasis of electrolytes in cells via sodium-potassium pump activation ⁽⁴⁷⁾ and can revert impaired intracellular ion homeostasis ⁽²⁵⁾.

  As a cofactor of all reactions involving ATP transfer, magnesium is a major determinant of insulin and glucose metabolism, critical to carbohydrate metabolism, and regulates the activity of all enzymes involved in phosphorylation reactions ⁽⁴⁸⁾. These vascular and metabolic mechanisms are echoed by observed relationships between deficiency and oxidative stress, proinflammatory states, endothelial dysfunction, platelet aggregation, insulin resistance, and hyperglycemia ^(48) (49). A possible mechanism of cardiovascular benefits may be via a reduction in arterial stiffness ⁽⁷⁶⁾.

  Magnesium can also serve an immunomodulatory function by regulating NF-kB activation and cytokine production, and limiting systemic inflammation ⁽⁵⁰⁾. It also reduces markers for systemic inflammation and endothelial dysfunction including C-reactive protein ^(4) (51). Its salts are poorly absorbed, and act as an osmotic laxative by retaining water in the intestine. The mechanism by which it may affect the bioavailability of concomitantly administered drugs is through the formation of insoluble chelate complexes with those drugs, substantially reducing their bioavailability ⁽⁵²⁾.

  Experimental and epidemiological evidence for the role of magnesium in cancer is conflicting. Its part in cellular metabolism and maintaining genetic stability, regulation of cell proliferation, and protection against insulin resistance, oxidative stress, and systemic inflammation are also cancer-preventive attributes ^(18) (19). At the same time, hypomagnesemia as a side effect of some cancer treatments may produce an inhibitory effect on tumor growth and neo-angiogenesis, but magnesium levels are also increased in tumors both in vivo and in vitro, suggesting its multiple and possibly dichotomous roles in cancer ^(53) (54).

• Contraindications

  Individuals with other heart, kidney, or gastrointestinal disorders ⁽⁴⁴⁾, should not take magnesium supplements without a doctor’s supervision.

• Adverse Reactions

  Gastrointestinal symptoms including diarrhea, nausea; nonspecific mild abdominal or bone pain ^{(24) (26) (33)}.

  Case reports

  • Hypermagnesemia due to ingestion of magnesium oxide by a 72-year-old woman with constipation and prolonged colonic retention caused prolonged hypotension and decreased perfusion, which led to hypoxic encephalopathy ⁽⁴⁴⁾.
  • Laxatives-induced severe hypermagnesemia complicated with cardiopulmonary arrest in a 55-year-old woman with nephritic syndrome and anorexia nervosa ⁽⁵⁸⁾.
  • Hypermagnesemia in the absence of pre-existing renal dysfunction in a 76-year-old woman with ileus ⁽⁵⁹⁾.
• Herb-Drug Interactions

  Aminoglycosides: Can cause renal magnesium wasting and subsequent deficiency ⁽⁶⁰⁾.
  Antibiotics: Magnesium or antacids may reduce the absorption of fluoroquinolones, tetracyclines, and nitrofurantoin. Magnesium-containing products, if needed, should be taken in accordance with the prescribing information of these antibacterials ^{(52) (61) (62)}.
  Anticoagulants: Magnesium or antacids can increase rate and extent of absorption ⁽⁶³⁾.
  Antidiabetics: Magnesium or antacids can increase rate and extent of absorption of sulphonylurea drugs ⁽⁶³⁾.
  Antifungals: Magnesium or antacids may reduce the rate and extent of itraconazole absorption ⁽⁶⁴⁾.
  Antimicrobials (pentamidine): Can cause renal magnesium wasting and subsequent deficiency ⁽⁶⁰⁾.
  Antivirals (ribavirin): High-dose antivirals may cause hypomagnesemia ⁽³⁷⁾.
  Bisphosphonates: Calcium/magnesium levels may be affected in patients receiving bisphosphonate therapy ⁽⁶⁵⁾. In addition, antacids may interfere with absorption of bisphosphonates ⁽⁵²⁾.
  Calcineurin inhibitors: May cause hypomagnesemia ⁽³⁶⁾.
  Calcium channel blockers: Magnesium may potentiate blood pressure-lowering effects ⁽⁶⁶⁾.
  Cisplatin-based chemotherapy: May cause hypomagnesemia ⁽³⁹⁾.
  Dasatinib: May increase blood levels of magnesium ⁽⁶⁷⁾.
  Digoxin: Digoxin reduces tubular magnesium reabsorption. In patients with congestive heart failure effects may be cumulative with diuretics, diet, and poor intestinal absorption. Hypomagnesemia may increase adverse effects such as palpitations and nausea with digoxin. Magnesium and other electrolyte levels should be monitored in patients treated with cardiovascular drugs ^(68) (69).
  Diuretics: Loop and thiazide diuretics are electrolyte-depleting, and can cause renal magnesium wasting and subsequent deficiency ⁽⁶⁰⁾. Cumulative effects with other cardiovascular drugs may occur (see Digoxin entry).
  Monoclonal antibodies (cetuximab, panitumumab): These cancer drugs target the epidermal-growth-factor receptor and hypomagnesemia is a frequent side effect ⁽⁴⁰⁾. Electrolytes are monitored during and following treatment, and appropriate treatment instituted ^(70) (71).
  Neuromuscular blockers: Magnesium supplements may potentiate the effects of neuromuscular blockers used in clinical settings ^(72) (73).
  Nonsteroidal anti-inflammatory drugs: Antacids can increase rate and extent of absorption ⁽⁶³⁾.
  Proton pump inhibitors: Long-term use may cause hypomagnesemia ⁽³⁸⁾.
  Synthetic thyroid hormone: Two case reports of magnesium-containing antacids/laxatives reduced the effectiveness of levothyroxine ⁽⁷⁴⁾.

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