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, especially dark green leafy vegetables, nuts, legumes, whole grains, fruits, and fish ⁽⁴⁾.

In dietary supplements, 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 to reduce risk of chronic ailments including cancer, heart disease, and diabetes. Among colorectal cancer patients, adequate magnesium intake through diet and/or supplements along with vitamin D status was associated with lower mortality risk ⁽⁸³⁾. Other studies have not linked dietary/supplement consumption with cancer incidence and mortality ^(16) (86), or pancreatic cancer risk ⁽¹⁷⁾, but have associated higher intake with a lower risk for colorectal tumors ⁽¹⁸⁾ and lung cancer ⁽¹⁹⁾. Additionally, both low and high plasma levels were associated with an increased incident risk of cancer in hypertensive adults ⁽⁸⁷⁾.

Dietary intake is also associated with reduced mortality from cardiovascular disease ⁽⁵⁾ and sudden cardiac death (SCD), although studies may be more affirmative for serum magnesium on SCD ^(6) (7). Other studies on magnesium intake suggest increased survival in patients with heart failure ^(20) (21), reduced stroke risk ⁽⁸⁾, and benefits with supplementation on endothelial function ⁽⁸⁴⁾. Some studies have shown a reduction in blood pressure following supplementation ^{(24) (25) (80)}, and a meta-analysis also suggests antihypertensive effects ⁽²⁶⁾. However, 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 small studies suggest it may help patients with asthma ⁽¹³⁾ or cystic fibrosis ⁽³⁰⁾.

Magnesium intake has demonstrated benefits against metabolic disorders including diabetes ^{(9) (10) (11) (12) (22) (23) (77) (88)}, and a meta-analysis also suggests supplementation may benefit those with or at risk of diabetes ⁽⁸⁵⁾. In other studies, positive effects were observed on bone mass accrual in healthy adolescents ⁽²⁸⁾ and bone turnover in postmenopausal osteoporotic women ⁽²⁹⁾, while deficiencies have been linked to osteoporosis ⁽¹⁾.

There is moderate evidence for use of magnesium in migraine headaches and as prophylaxis ⁽³¹⁾, but studies of dietary or supplemental magnesium on depression are conflicting ^{(14) (15) (78) (79)}. Although preliminary data show mixed results with oral supplementation for premenstrual syndrome ⁽³²⁾, a pilot study indicates that it reduces menopausal hot flashes in breast cancer patients ⁽³³⁾. Supplementation does not appear to reduce leg cramps in older adults ⁽⁸¹⁾, but a systematic review found it may help 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).

Other recent findings suggest that magnesium status and supplementation differentially affects vitamin D metabolism and may therefore affect 25(OH)D status ⁽⁸²⁾.