Background and Relevant Pharmacokinetics
Magnesium (Mg) is the fourth most abundant cation in the body, with 50-60% sequestered in the bone and the remaining being distributed equally between muscle and non-muscular soft tissue. Only about 1% of total body Mg is found in the extracellular fluid.
Dietary intake, renal and intestinal function finely balance and maintain plasma magnesium concentrations.
Absorption of dietary Mg starts within 1 hour of ingestion, with salts of high solubility having the most complete absorption (e.g. magnesium citrate). Magnesium absorption also requires selenium, parathyroid hormone and vitamins B6 and D and is hindered by phytate, fibre, alcohol, excess saturated fat, phosphorus or calcium intake. Healthy people absorb 30-40% of ingested Mg; this can increase to 70% in cases of low intake or deficiency. Once absorbed, it is transported to the liver, enters the systemic circulation and is transported around the body and ultimately excreted via the kidneys.
Clinical note — Magnesium citrate: the superior supplement
Several forms of Mg are available in OTC supplements; however, not all exhibit the same bioavailability. According to a randomised, double-blind, placebo-controlled study, magnesium amino chelate and magnesium citrate are better absorbed than magnesium oxide in healthy individuals. Of the three, magnesium citrate led to the greatest increase in mean serum Mg concentration, a result evident after acute dosing (24 hours) and chronic dosing (60 days). Furthermore, although mean erythrocyte Mg concentration showed no differences among groups, chronic magnesium citrate supplementation resulted in the greatest mean salivary Mg concentration compared with all other treatments.
Good dietary sources of Mg include legumes, wholegrain cereals, nuts, dark green leafy vegetables, cocoa, soy flour, seeds, nuts, mineral water and hard water.
The word magnesium comes from the name of the Greek city Magnesia, where large deposits of magnesium were found. Magnesium, in the form of Epsom salts, has long been used therapeutically as a laxative although it is also used in many other ways, such as a foot soak to soften rough spots and absorb foot odour and as a bath additive to ease muscle aches and pains.
Magnesium: Deficiency Signs and Symptoms
When reduced intakes or increased losses of magnesium, potassium or phosphorus occur (the three major intracellular elements), losses of the others generally follow. As such, many deficiency symptoms are also due to alterations in potassium and/or phosphorus status and manifest as neurological or neuromuscular symptoms.
Symptoms of deficiency include:
• muscle spasms
• muscular weakness and spasms
• mental confusion and decreased attention span
• personality changes
• hyper-irritability and excitability
• cardiac arrhythmia, tetany and ultimately convulsions can develop if deficiency is prolonged.
Although Mg deficiency is a common clinical problem, serum levels are often overlooked or not measured in patients at risk for the disorder. About 10% of patients admitted to hospitals and up to 65% of patients in intensive care units may be Mg deficient.
Low Mg states are associated with several serious diseases such as congestive heart failure, ischaemic heart disease, cardiac arrhythmias, hypertension, mitral valve prolapse, metabolic syndrome, diabetes mellitus, hyperlipidaemia, pre-eclampsia and eclampsia. Epidemiological evidence suggests that a low dietary intake of Mg is also associated with impaired lung function, bronchial hyperreactivity and wheezing, and risk of stroke. Magnesium deficiency may also play a role in the pathophysiology of Tourette’s syndrome.
A primary deficiency is rare in healthy people as the kidneys are extremely efficient at maintaining Mg homeostasis. However, deficiency is possible in protein-calorie malnutrition (e.g. kwashiorkor). Experiments have shown that people fed low Mg diets develop deficiency symptoms such as anorexia, nausea and vomiting, weakness and lethargy within weeks.
Marginal deficiencies are far more common and very often undiagnosed. There is evidence that daily Mg intake has declined substantially since the beginning of last century, with dietary surveys showing the average intake in Western countries is often below the RDI.
Most Mg deficiencies occur due to a combination of insufficient dietary intake and/or intestinal malabsorption and increased Mg depletion. There are many factors that predispose to deficiency and these are listed in the table below.
Medicines increasing risk of deficiency
Risk Factors for Magnesium Depletion
|Dietary||Excessive intake of ethanol, salt, phosphoric acid (soft drinks), caffeine
Hyperparathyroidism with hypercalcaemia
Diabetes mellitus and glycosuria
Intense, prolonged stress
|Gastrointestinal disorders||Coeliac disease
Inflammatory bowel diseases
Partial bowel obstruction
|Pharmaceutical drugs||Aminoglycoside antibiotics
Nephrotoxic drugs (e.g. cisplatin, cyclosporin)
Hypercatabolic states such as burns
Long-term parenteral nutrition combined with loss of body fluids (e.g. diarrhea)
Parasitic infection (e.g. pinworms)