Magnesium is a major intracellular cation, second only to potassium in abundance. In cells, magnesium is involved as a catalyst or activator in many enzymatic reactions; it is needed for all reactions that utilize ATP, since a Mg-ATP complex is the immediate substrate in these reactions. The majority of the body’s magnesium is present in bone (50%) and skeletal muscle and soft tissue, while only roughly 1% is present in the blood; thus, the level measured in serum or plasma is a poor indicator of total body stores.


Of the magnesium in blood, about 20-30% circulates bound to serum proteins (mainly albumin, which binds around 75% of magnesium), while the remainder is either free (60%, called ionized magnesium or Mg2+) or bound to phosphates, citrates, and other compounds. Magnesium homeostasis is determined largely by the balance between intestinal absorption and renal excretion. Magnesium is also secreted in saliva (ruminants especially), sweat (horses) and mammary secretions.

Overall, very little is known about the factors that control magnesium homestasis; indeed magnesium is referred to as the “forgotten” element. The ileum is the site of magnesium absorption in the gastrointestinal tract. Within the intestinal tract, magnesium is resorbed actively via the transient receptor potential melastatin (TRPM) channels and passively via the paracellular pathway. Intestinal absorption is influenced by magnesium concentration in the diet and proton pump inhibitors, which downregulate TRPM channels (Blaine et al 2015). The kidneys play a pivotal role in controlling serum magnesium levels by modulating tubular reabsorption; 70-80% of magnesium is filtered through the glomerulus. Of this, 10-30% is absorbed in the proximal convoluted tubules with sodium and 40-70% is absorbed in the thick ascending limb of the loop of Henle via a paracellular pathway modulated by tight junction proteins called claudins and absorption of sodium chloride and potassium via the NaK2Cl transporter (with back-leak of potassium into the lumen), which creates a lumen-positive potential differences, favoring passive magnesium (and calcium) absorption (Blaine et al 2015). The remaining 5-10% is absorbed in the distal tubules via an active pathway involving the cation channels, TRPM, with basolateral excretion into blood being mediated through a sodium/magnesium exchanger. Other proteins may also be involved in magnesium absorption (e.g. cyclin M2, since genetic defects in the latter protein are associated with hypomagnesemia and increased urinary excretion of magnesium [Blaine et al 2015]). The control of reabsorption is complex; factors involved include dietary content, several hormones (parathyroid hormone, PTH-related protein, calcitonin, antidiuretic hormone, aldosterone, thyroxine and others), and serum levels of magnesium and calcium.

  • Parathyroid hormone stimulates intestinal absorption and renal resorption of magnesium and release of magnesium from bone (will increase values).
  • Aldosterone promotes magnesium excretion into feces and urine (will decrease values).
  • Thyroxine promotes fecal and urinary losses (will decrease values).

Method of measurement

The colorimetric method used on the chemistry analyzer at Cornell University measures total magnesium. With ion-specific electrodes, selective measurement of ionized Mg2+ is possible.

Reaction type

Colorimetric end-point


In an alkaline medium (Tris/6-aminocarpoic acid, pH 11.25 with 129 umol/L EGTA), magnesium reacts with the diazonium salt xylidyl blue resulting in the formation of a purple complex. The generation of this purple complex causes a decrease in the absorbance of xylidyl blue that is directly proportional to the magnesium concentration (reported in mEq/L).

The reaction is shown below:

Magnesium + diazonium salt xylidyl blue alkaline solutionPurple complex

Units of measurement

The concentration of magnesium is reported in mEq/L (conventional units – our results), mg/dL (conventional units) or mmol/L (SI units). The conversion formulas are below:

mEq/L x 1.22 = mg/dL

mEq/L x 0.5 = mmol/L

mg/dL x 0.411 = mmol/L 

Sample considerations

Sample type

Serum, plasma, aqueous or vitreous humor, body cavity fluids (e.g. cerebrospinal fluid) and urine. Magnesium can be measured in ocular fluids post-mortem in ruminants with sudden death to rule out hypomagnesemic syndromes, such as grass tetany (McCoy 2004).


Lithium heparin is the preferred anticoagulant use in plasma samples for magnesium measurements. Anticoagulants with chelating agents such as EDTA, oxalate, and fluoride should not be used. Internal studies in the Clinical Pathology Laboratory at Cornell University in bovine blood show that values in heparinized plasma are similar to serum (Naeves and Stokol, unpublished data).


With prolonged storage, magnesium is expected to leak out of cells (which develop permeable membranes due to reduced ATP) and increase in serum and plasma if not separated from cells. This may occur with or without overt hemolysis (red blood cells are the most abundant cell in blood and magnesium occurs in higher concentrations intracellularly than in plasma or serum).

  • Human: Per reagent manufacturer product information sheet
    • Serum and plasma: 7 days at room temperature, 7 days refrigerated, and 1 year frozen (-20°C).
    • Urine: 6 months refrigerated when acidified, and 3 weeks frozen (-20°C).
  • Bovine:
    • Serum/plasma: Internal studies in the Clinical Pathology Laboratory at Cornell University show that there are minimal differences in magnesium results (i.e. change of 0.1 mg/dL) in whole blood stored in a red top or green top (heparin) tube (before separation) for up to 6 hours at 4 or 22°C (Naeves and Stokol, unpublished data).
    • Ocular fluid: Magnesium is more stable in vitreous (24 hours in sheep and 48 hours in cattle) than aqueous humor (McCoy et al 2004).


  • Turbidity: No interference with severe turbidity (up to 2000 turbidity index). The turbidity index correlates weakly with triglyceride concentrations.
  • Hemolysis: May increase magnesium with severe hemolysis (>800 hemolysis index), due to release of intra-erythrocyte magnesium. This does not always occur and one study, using the same method, showed little change in magnesium when hemolysis was induced in equine or bovine samples and samples were analyzed immediately (not stored) (Jacobs et al 1992). 
  • Icterus: No interference up to an icteric index of 60 with unconjugated or conjugated bilirubin (per product information sheet)

Test interpretation

Increased concentration (hypermagnesemia)

  • Artifact: Spurious elevations in magnesium can be seen in severely hemolyzed samples due to release of Mg2+ from erythrocytes (see above). This does not appear to occur in cattle or horses when freshly spiked with red blood cell lysate (Jacobs et al., 1992). Serum collected from animals after death will have high magnesium concentrations due to release from intracellular stores (magnesium is higher in cells than in serum or plasma). We do not typically see a high magnesium in serum or plasma samples in which separation from cells was delayed for 24-48 hours (i.e. from leakage of red blood cells without severe hemolysis), but longer storage may result in increases (with or without hemolysis – hemoglobin is a much larger molecule than magnesium and the latter will leak out quicker with altered membrane permeability).
  • Physiologic: There is a transient post-partum increase in total and free magnesium in cattle (Riond et al., 1995).
  • Iatrogenic: Excessive supplementation (fluids, diet, oral supplements such as antacids) may lead to increased absorption of magnesium.
  • Pathophysiologic
    • Increased absorption: Iatrogenic administration of magnesium would be the most common cause of hypermagnesemia due to increased absorption. In theory, high PTH (e.g. primary hyperparathyroidism) or lack of aldosterone (Addison’s disease) may increase magnesium levels through this mechanism, however hypermagnesemia is not a clinical feature of hyperparathyroidism in dogs.
    • Decreased excretion: Reduced glomerular filtration in renal azotemia or post-renal azotemia (e.g. urinary tract obstruction), hypocalcemia (? renal antagonism with magnesium), high PTH (possible), and Addison’s disease (aldosterone promotes renal excretion of magnesium) are all potential causes of high magnesium, although in our experience, renal azotemia is the most common cause. Oliguric or anuric renal failure in dogs and cats consistently increases magnesium levels.
    • Release from cells: Since magnesium is stored in skeletal muscle and soft tissue, massive tissue necrosis (particularly of skeletal muscle, which constitutes a large mass overall) could release magnesium (would expect a very high CK if this was occurring).

Decreased concentration (hypomagnesemia)

Magnesium levels should be measured under the following situations: Unexplained hypocalcemia (magnesium inhibits PTH or stimulates uptake of calcium into bone), resistant hypokalemia (if magnesium is not administered, the hypokalemia is refractory to potassium supplementation), myopathy, neuromyopathy, critically ill animals and potentially unexplained sudden death in ruminants. Magnesium is often decreased in critical patients and is associated with outcome. Whether the hypomagnesemia is a cause of increased morbidity or a result of the illness is not yet known and the hypomagnesemia is, as yet, unexplained. Very low levels of magnesium result in cardiac arrest, weakness, tetany, and convulsions.

  • PhysiologicMagnesium decreases by 6 weeks of age due to decreased absorption with age.
  • Iatrogenic:  Administration of magnesium-poor fluids or total parenteral nutrition in small animals.
  • Pathophysiologic: 

    • Decreased albumin: Syndromes resulting in hypoalbuminemia may result in decreased magnesium because approximately 33% of magnesium is bound to protein, particularly albumin. However, in internal studies at Cornell University, there is little correlation between albumin and magnesium levels in animals.
    • Decreased intake: Decreased intake due to prolonged anorexia (particularly in lactating dairy cattle) or insufficiency of magnesium in the diet can lead to hypomagnesemia. This seems to be more of a problem in ruminants than other species. In one study, magnesium concentrations in ocular fluids freshly collected post-mortem <0.8 mg/dL  or <0.7 mEq/L (<0.33 mmol/L) in adult sheep and <0.6 mg/dL or <0.5 mEq/L (<0.25 mmol/L) in adult cattle were compatible with a diagnosis of clinical hypomagnesemia (McCoy, 2004).
      • Grass tetany in ruminants: Cattle fed on rich spring grass pastures or dry feed that is low in magnesium develop grass or hypomagnesemic tetany. Furthermore, fertilization of pastures with calcium, nitrates, ammonia, sulphates and potassium result in decreased magnesium uptake into the grass and other plants in pastures. This syndrome occurs rapidly in dairy cattle, especially if pregnant or lactating as they have increased magnesium demands. Grass tetany is characterized by severe hypomagnesemia, hypocalcemia (due to PTH resistance and inhibition of PTH secretion) and low or normal phosphate. Clinical signs are often precipitated by stress (e.g. reduced food intake, cold weather, transport etc) or a sudden decrease in dietary magnesium.
      • Transport tetany and winter tetany (associated with poor quality feed with decreased feed intake) are similar syndromes.
      • Milk tetany occurs in calves fed whole milk, especially veal calves.
    • Translocation into cells: Magnesium can move intracellularly in response to insulin, hypothermia or endotoxemia in horses. This is a postulated reason for hypomagnesemia in endotoxemic horses (and may be secondary to insulin release).
    • Excess loss:
      • Gastrointestinal tract: Decreased absorption or loss can occur with gastrointestinal conditions resulting in malabsorption or diarrhea, e.g intestinal resection. Saliva is also high in magnesium in ruminants, therefore loss of saliva in this species may result in hypomagnesemia (e.g. rabies, choke). Hyperaldosteronism (a rare condition) may cause hypomagnesemia due to increased fecal loss.
      • Renal: Diuresis of any cause (administration of intravenous fluids, chemical or osmotic diuresis, e.g. diabetes mellitus) can result in increased urinary losses of magnesium. Other potential causes of renal loss are hyperthyroidism (thyroid hormone decreases magnesium by promoting fecal and urinary losses), primary hypoparathyroidism (PTH stimulates renal resorption of magnesium and magnesium release from bone), and acidosis.
      • Cutaneous: Sweating in endurance or competitive horses. Sweat contains high concentrations of potassium chloride, magnesium and calcium. Endurance horses that sweat excessively are predisposed to hypokalemia, metabolic alkalosis, hypomagnesemia and hypocalcemia.
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