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EBMG

Magnesium Deficiency

Essentials

  • Magnesium is a participant in many metabolic processes. Its concentration in the body is regulated by the kidneys. Normal diet contains sufficient amounts of magnesium, and significant magnesium deficiency in healthy individuals with normal nutritional status is rare.
  • Magnesium deficiency should be suspected if the patient has compatible symptoms or clinical findings or an underlying factor predisposing to such deficiency.
  • The most common symptoms and findings in hypomagnesaemia are neurological or psychiatric.
  • Only 1% of total body magnesium is in the plasma, which impedes the evaluation of magnesium deficiency. Normal plasma magnesium concentration does not rule out deficiency, but low plasma magnesium concentration almost always signifies true deficiency.

Magnesium balance

  • 1 mmol = 24 mg elemental magnesium (Mg2+ )
  • The body of an adult contains about 1 000 mmol of magnesium, of which
    • 1 % is in the extracellular fluid space
    • 50-60 % bound in the skeleton
    • the rest is inside cells.
  • For adults, the recommended daily intake of magnesium is 13-18 mmol (310-420 mg), depending on age and sex. The weight-dependent recommended enteral dose is 0.2 mmol (4.8 mg)/kg/day.
  • Diet contains on average about 10-15 mmol (240-360 mg) magnesium, of which 30-40 % is absorbed.
    • During low-magnesium diet, the absorption from the gastrointestinal channel is increased to two-fold.
    • Good sources of magnesium include wholegrains, seeds, nuts, green vegetables, as well as internal organs and meat.
  • In addition to the intestinal track, also bone tissue and kidneys participate in the regulation of magnesium balance. Normally the kidneys efficiently spare magnesium for use by the organ system.
  • Excretion by kidneys is the most important factor regulating magnesium balance.
    • When plasma concentration rises, excretion to urine is increased.
    • This so-called renal threshold is close to normal plasma concentration.
  • The main causes of hypomagnesaemia are inadequate absorption from the intestinal track, loss through kidneys and transfer into cells or the skeleton.

Causes of magnesium deficiency

  • Insufficient absorption in the intestine
    • Malabsorption conditions
    • Alcoholism (often also associated with sparse intake and impaired absorption)
    • Prolonged fluid therapy
  • Intestinal wasting
    • Vomiting, diarrhoea
    • Nasogastric suction
    • Intestinal fistula
  • Renal wasting
    • Excessive alcohol consumption increases the excretion of magnesium into the urine.
    • Diabetes with poor control
    • Acquired renal diseases (interstitial nephritis, acute tubular necrosis, sequela of renal transplantation)
    • Hyperthyroidism
    • Hyperaldosteronism
    • Congenital conditions and syndromes
  • Other losses
    • Blood transfusion, excessive sweating, burn injuries, pancreatitis, pregnancy and breastfeeding
  • Drugs
  • Transport to the intracellular space or to bones
    • E.g. after surgery for hyperparathyroidism or during recovery from diabetic ketoacidosis or respiratory acidosis

Main symptoms

  • Neurological/psychiatric symptoms
    • Muscle weakness
    • Tremor
    • Muscle cramps
    • Tetany
    • Increased reflexes
    • Seizures
    • Depression
    • Memory difficulties
    • Irritability
    • Delirium or psychosis
  • Cardiac symptoms
    • Therapy-resistant arrhythmias (including atrial fibrillation)
    • Disorders of conduction
    • Hypomagnesaemia increases the cardiac toxicity of digoxin.
  • Symptoms caused by other electrolyte disturbances associated with the deficiency
    • Persistent hypokalaemia that is not corrected without the administration of magnesium (magnesium deficiency prevents the function of the sodium-potassium pump; potassium cannot enter the intracellular space but is wasted into the urine)
    • Hyponatraemia
    • Hypocalcaemia (decreased secretion and end-organ effects of PTH)
  • Symptoms usually develop only when the plasma magnesium concentration falls below 0.5 mmol/l.

Diagnosis

  • Suspicion may be raised by the presence of risk factors (longstanding diarrhoea, alcoholism, use of PPI drugs or diuretics) or symptoms (unexplained hypocalcaemia, difficult-to-manage hypokalaemia, neuromuscular symptoms, ventricular arrhythmias).
  • Determine plasma magnesium; normal range in adults is 0.71-0.94 mmol/l.
  • Low plasma magnesium level is a sign of magnesium deficiency (except in acute stress reaction, when magnesium moves from the extracellular space into cells), but a normal level does not exclude deficiency.
  • Magnesium deficiency may also be assessed through daily (24 hour) excretion in urine (about 5.0 mmol/24 h in normomagnesaemia and about 0.5 mmol/24 h in magnesium deficiency).
  • The cause of established hypomagnesaemia is often revealed through patient history.
  • If the aetiology of magnesium deficiency is not kidney-related, the magnesium amount in a 24-hour urine sample decreases from 3-5 mmol to less than 1 mmol.

TreatmentInterventions for Leg Cramps in Pregnancy, Magnesium for Skeletal Muscle Cramps

  • Magnesium tablets are frequently used without plasma magnesium assay for symptomatic treatment of cardiac arrhythmias and leg cramps. The evidence on the effectiveness of the therapy is, however, deficient . A small, even if unnecessary magnesium supplement in the diet is not harmful if the renal function is normal.
  • A diagnosed deficiency is treated.
    • Treat the underlying cause if such can be identified. If magnesium deficiency has been caused by diuretic therapy that cannot be discontinued, adding a potassium sparing diuretic in the treatment may help.
    • Patients on intravenous nutrition need, as maintenance dose, substitution with 4-8 mmol/day (0.1 mmol/kg/day).
    • Correcting the deficiency requires higher dose, in adults usually 20-40 mmol/day.
    • Due to the low renal threshold of magnesium (in relation to plasma concentration), it is most efficient to correct the deficiency gradually, over several days.
  • Mild deficiency is treated orally. Magnesium (Mg2+ ) administered at a dose of 10-40 mmol/day (approximately 240-1 000 mg/day) is usually an appropriate dose to correct the deficiency in a patient with normal renal function. Several different magnesium salts are available, the Mg2+ concentrations of which vary.
  • Severe deficiency (plasma magnesium < 0.5 mmol/l) is treated with intravenous infusion.
    • Rapid correction on a high dependency unit: 20 mmol of magnesium sulphate is mixed in 100 ml of 0.9% sodium chloride solution and infused over 2 hours.
      • When using different products, the following conversions may be used: 1 mmol = 2 meq = 24 mg of elementar magnesium (Mg2+ ) = 246 mg of magnesium sulphate.
    • As an alternative, 25-50 mmol of magnesium sulphate is mixed in 1 000 ml of 5% glucose solution and infused over 24 hours, followed by slow infusion of 25 mmol/24 h for 3-5 days.
  • In renal failure, magnesium should be administered carefully and plasma magnesium concentration should be closely monitored in order to avoid severe hypermagnesaemia.
    • If GFR < 30 ml/min/1.73 m2 , dose reduction by at least 50%.

Evidence Summaries ⬆