Magnesium – an important mineral with many health benefits

Magnesium is the fourth most abundant mineral in the human body and an essential nutrient for optimal health.^1,2 It is involved in multiple biochemical processes including energy metabolism, muscle contraction, protein synthesis and neurotransmission. Magnesium (Mg) is a cofactor for at least 300 enzymatic reactions and facilitates the conversion of adenosine triphosphate (ATP) to adenosine diphosphate (ADP), for energy production. Most magnesium is found within bones, muscles and soft tissues, and less than 1 per cent of total magnesium is found within the blood.

Many different foods contain magnesium, particularly green leafy vegetables, whole grains, nuts, seeds and legumes. However, while magnesium balance is strictly controlled by the kidneys, hypomagnesaemia can occur, particularly in those with a poor diet or people with various health conditions. An estimated 15 per cent of the US population are thought to have hypomagnesaemia, and increasing evidence points to a role for mild-to-moderate chronic hypomagnesaemia in the pathogenesis of several chronic diseases.²

Common causes include alcoholism, type 2 diabetes, chronic kidney disease and the use of drugs such as proton-pump inhibitors, calcineurin inhibitors and thiazide diuretics.^3–5 Many women have intakes of magnesium below recommended levels during pregnancy,⁶ and diminished magnesium intake and impaired intestinal absorption also occur with ageing.⁷ Magnesium status can also relate to that of other nutrients such as vitamin D, with shortfalls or surpluses in one impacting on others.⁸

While much less common than magnesium insufficiency, levels may be increased in Addison disease, adrenocortical insufficiency, multiple myeloma, antacid overuse, fluid depletion and hypothyroidism. Severe hypermagnesaemia is almost exclusively seen in patients with end-stage renal disease or in women with preeclampsia after magnesium therapy. However, it can also occur through high magnesium intake via excessive use of supplements or magnesium-containing laxatives or antacids.^2,9

Cardiovascular disease: Magnesium contributes to the regulation of cardiac excitation-contraction coupling, endothelial functioning and coagulation.¹⁰ Its deficiency has been linked to cardiovascular disease and vascular calcification.^9,10 Epidemiological evidence suggests that higher magnesium intake may be associated with a reduced risk of hypertension and cardiovascular diseases.^3,11,12 A possible role for magnesium supplementation in the treatment of cerebral ischaemia and in the management of ischaemic stroke, has recently been suggested.^13,14

Diabetes: Magnesium has also been significantly implicated in the pathophysiology of type 2 diabetes, with its deficiency contributing to insulin resistance and impaired glucose metabolism. Supplementation was associated with improvements in glucose tolerance and insulin sensitivity markers in those with a high risk of diabetes or with diabetes, in a 2021 review.¹⁵ A recent meta-analysis of five randomised clinical trials also reported improvements in fasting blood glucose levels and insulin resistance in 266 patients with gestational diabetes following magnesium supplementation.¹⁶

Inflammatory bowel disease: A recent systematic review reported a significant association between low serum magnesium levels and elevated C-reactive protein levels as an indicator of severity of Crohn disease, particularly in men. This review also correlated low magnesium levels with increased sleep latency and decreased sleep duration.¹⁷

Magnesium seems to play a key role in the regulation of sleep, and the use of magnesium-containing supplements for sleeping disorders has become more common in recent years.

Several possible mechanisms may account for magnesium’s influence on sleep. They include acting as an ion channel blocker and facilitating antagonistic effects on N-methyl-D-aspartic acid (NMDA) receptors,¹⁸ agonist-like influences on GABA-A receptors, and ameliorating membrane excitability.^19,20 Anxiolytic-like activity has also been reported following administration of large doses of magnesium to rats and mice.^21–22 Amelioration of oxidative stress and elevated brain nitric oxide levels were associated with these effects.²²

A clinical trial involving 46 older people reported improved subjective measures of insomnia, increased serum melatonin levels and reduced serum cortisol levels, following an eight-week course of magnesium.²³ Another study reported improved sleep quality in a group of 60 patients given magnesium at a dose of 500mg daily for five days following heart surgery.²⁴ However, no placebo was used in this study. Most recently, magnesium-L-threonate was shown to improve sleep quality in a 21-day clinical trial involving 80 adults aged 35 to 55 years with self-assessed sleep problems.²⁵ Magnesium supplementation was associated with improved deep/REM sleep stages, mood, energy, alertness and daily activity and productivity.

A recent systematic review of population observational and interventional studies, involving 7582 subjects across nine published cross-sectional, cohort, and randomised clinical trials systematically reviewed the possible links between magnesium and sleep quality in an adult population. This review found that while observational studies suggested an association between magnesium status and sleep quality, findings were less clear from clinical trials.²⁶ The authors concluded the need for additional well-designed randomised clinical trials with a larger sample size and longer follow-up time to further clarify the relationship.

Magnesium plays an essential role in nerve transmission and neuroprotection

Magnesium plays an essential role in nerve transmission and neuroprotection.^27,28 Magnesium sulphate has an established role for the treatment of eclampsia and neonatal encephalopathy and is sometimes used during pregnancy to reduce the risk of cerebral palsy and death in preterm infants.^29,30

Magnesium deficiency may also be a factor in some forms of migraine and contribute to the induction of cortical depression or abnormal glutamatergic neurotransmission. Supplementation has been trialled as a prophylactic or parenteral treatment for migraine attacks, especially in patients with contraindications to standard medications.³¹

Some data suggests a potential role for magnesium supplementation in stressed patients or those with depression. A small number of clinical trials have reported improvements in mood and alertness with magnesium supplements,^24,25 although findings from clinical studies overall have been mixed.^26,28,32,33 Magnesium has also been combined with ketamine to treat depression, and it appears to produce some kind of synergistic effect.³⁴

Maintaining optimal magnesium levels appears important for cognitive function and behavioural regulation,³⁵ and research is under way into magnesium supplementation as an intervention for neuropsychiatric and neurodegenerative conditions such as schizophrenia and Parkinson disease.^36–38

Individuals engaged in intense exercise have a magnesium requirement 10–20 per cent higher than sedentary people

Magnesium has an important role in regulating skeletal muscle function, and is essential for the proper functioning of calcium and other ion channels influencing nerve transmission and muscle relaxation. It also plays a vital role in bone health, and adequate intake is needed to maintain optimal vitamin D metabolism and bone density and reduce the risk of osteoporosis. Clinical studies have found magnesium supplementation can alleviate osteoporosis symptoms in some patients.³⁹

Magnesium supplements are marketed for the prophylaxis of skeletal muscle cramps. However, a 2020 Cochrane review concluded it is unlikely that magnesium supplementation provides clinically meaningful cramp prophylaxis to older adults, although some evidence of benefit existed for those experiencing pregnancy-associated rest cramps.⁴⁰

The body’s requirement for magnesium also appears to increase during intense exercise, and individuals engaged in intense exercise have a magnesium requirement 10–20 per cent higher than sedentary people.⁴¹ Hypomagnesaemia can lead to glucose depletion, increased lactate accumulation and increased muscle soreness after exercise. Therefore, physically active individuals should consider their magnesium status and perhaps have a trial of supplementation when these symptoms occur.

A large number of dietary supplements and natural health products based on magnesium are available in the Aotearoa New Zealand marketplace. However, most products contain other active or nutritional medicaments in addition to magnesium, which makes evaluation challenging.

Several different salt forms of magnesium are used in these formulations, such as magnesium aspartate, magnesium citrate, magnesium glycinate, magnesium orotate, magnesium sulphate, and many more. Some evidence suggests that water soluble and liquid forms of magnesium result in higher absorption, and certain forms, such as magnesium citrate, seem to be better absorbed than others such as magnesium oxide.^42–44

As with other dietary supplements, the incorporation of liposomal, chelation and other formulation technologies can influence oral bioavailability. However, while our understanding of the pharmacokinetics of some products is increasing, limited data exists on the bioavailability of most magnesium preparations, and how different product formats affect long-term magnesium status and health.⁴⁵

Data from numerous reviews, animal experiments, human observational data and, increasingly, clinical trials, suggests that magnesium deficiency can contribute to many disease states. These include diabetes, cardiovascular disease, immunological conditions, inflammation, neurological and cognitive dysfunction, depression and stress-related conditions. Chronic subclinical magnesium deficiency also appears to be an increasingly prevalent condition in the general population.

Compelling evidence now suggests that magnesium supplementation can have benefits across a wide range of chronic health conditions.⁴⁶ People engaged in intense or prolonged exercise may also have increased magnesium requirements. However, with numerous different magnesium supplement products now available, more research to better define specific supplementation protocols is needed to improve our understanding of how to incorporate supplementation into the diet or treatment of particular conditions.

What seems certain is, as with other minerals such as calcium, zinc and selenium, we are likely to hear much more about the importance of magnesium in human health in the next few years.