Human biomarkers of population magnesium intakes
Since almost all body magnesium is split between bone and soft tissue, magnesium status is physiologically difficult to measure. Possible methods for magnesium analysis have been described in several reviews:
Arnaud MJ 2008 Update on the assessment of magnesium status. Br J Nutr 99 Suppl 3:S24-36.
Elin RJ 2010 Assessment of magnesium status for diagnosis and therapy. Magnes Res 23:S194-198.
Witkowski M, Hubert J, Mazur A 2011 Methods of assessment of magnesium status in humans: a systematic review. Magnes Res 24:163-180.
Serum magnesium is the most available and most commonly-used assay in clinical practice for the determination of magnesium status in normal subjects or those with pathologies that could lead to increased magnesium excretion (2, 5, 12). Serum magnesium can also be used to investigate hypermagnesaemia, however must be creatinine-corrected, thereby needing measurement of serum creatinine.
Reference values for serum magnesium concentration have been determined for the US population using NHANES I data (5), however confounding factors may indicate that these reference values do not apply to other populations. For more information on confounding factors, Page 4.
Serum magnesium concentration is not considered as representative of true magnesium status (2, 3, 5, 6) due uncertainty over equilibration and homeostatic mechanisms regulating magnesium between body pools, thus serum magnesium may not reflect total body stores. Serum magnesium concentrations have been measured in previous national surveys, e.g. the US NHANES (NHANES I only) and UK NDNS publications.
The reference method for magnesium assessment is Atomic Absorption Spectrometry (AAS).
Urine / Serum / Plasma are routinely measured photometrically in the clinical setting using automated clinical chemistry analysers. Reagents contain a mettalochromatic indicator such as; calmagite, xylidil blue or magon, chlorophosphonazo III and arsenazol.
Inductively-coupled plasma mass spectrometry (ICP-MS) and inductively-coupled plasma optical emission spectroscopy (ICP-OES) methods have also been developed (18, 19), including measurement from dried blood spots (18).
Considerations for serum/plasma magnesium assessment from the UK Association for Clinical Biochemistry.
Blood samples should be collected in metal-free blood collection tubes. Serum is preferred over zinc-free heparinised plasma but all other anti-coagulants should be avoided. High concentrations of magnesium are found in RBCs therefore blood samples should be centrifuged within an hour to avoid artificially increasing magnesium concentration via cellular leakage. Haemolysed samples may give rise to falsely elevated readings for the same reason.
Magnesium in serum is stable for several days if refrigerated (23).
The concentration of magnesium in erthyocytes is approximately three-fold that of serum. The measurement of erythrocyte magnesium may better reflect longer term magnesium status due to the lifespan of erthrocytes in the circulation.
This assay measures magnesium wasting via the kidney. This assay is not strictly an assessment of magnesium intake or status (2), rather, it is used to assess the effects of medication, physiological status or disease on magnesium status (6)(see confounding factors, Page 4). A 24 h sample is critical for this assay due to the circadian rhythm of magnesium excretion (maximal excretion occurs at night) (6). A high concentration of excreted magnesium indicates that a patient is losing magnesium via the kidney, whereas a low excretion suggests an inadequate intake or absorption.
It is recommended that urine samples are acidified to prevent precipitation of magnesium complexes.
Hair and nail magnesium has been measured in some studies (e.g. (20-22), though this method and guidelines on interpretation of results require further validation (12).
ICP-AES has also been used to measure metals, including magnesium, in nail samples in workers with routine exposure to metals.
Magnesium retention test or loading test, is considered by some as the best assessment of individual magnesium status (12). It involves the oral or intravenous administration of magnesium and the measurement of magnesium excretion in the urine. If bone magnesium stores are normal, the individual being tested will not retain a significant amount of the administered magnesium. On the other hand, if the individual is magnesium-deficient, and bone stores are inadequate, part of the administered magnesium will be retained and not excreted. This technique is restricted to a clinical or research setting, and requires trained staff and controlled conditions (12). The test also assumes normal kidney function and is not suitable for use in children.
Ionized serum magnesiumis the active fraction of circulating magnesium, and can be assessed by ion-selective electrode. However, the clinical value of this assay is not established (1), and is reserved for a research setting.
Though malnutrition is a primary cause of hypomagnesaemia, certain pathologies or lifestyles can influence population survey results. By affecting the absorption of magnesium from the gastrointestinal tract, such conditions increase the probability for magnesium wasting via the kidney (excretion in urine). In turn, this promotes a loss of magnesium from bone to maintain the serum magnesium concentration. Under these conditions, the serum magnesium concentration may give a false indication of magnesium status. Such conditions include chronic diarrhoea and other malabsorption disorders e.g. Crohn’s disease (12), diabetes mellitus, chronic alcoholism, renal tube disorders, hypercalcaemia, hyperthyroidism (6, 10)or genetic disorders (4). Severe illness may also cause altered magnesium compartmentalisation between body pools, thereby influencing magnesium excretion (6, 10)and older subjects are at a higher risk of inadequate magnesium intakes (12), due to a lower intake than the general population, and a decreased absorption seen with age (5), which may influence population data. Persons with extreme levels of activity, such as athletes, may show abnormal values of magnesium, depending on the assay used (5).
Further, certain drugs that can influence magnesium excretion, including aminoglycosides (e.g. streptomycin, gentamycin), cisplatin, digoxin, loop diuretics (e.g. furosemide), omeprazole, amphotericin B and cyclosporine (6). In population studies, individuals under therapy with such agents should not be sampled.
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