Magnesium Abstracts 2 - Measurement

© 2012

Update on the assessment of magnesium status

         (Arnaud 2008) Download

Magnesium (Mg) is the fourth most abundant mineral in the body and the most abundant intracellular divalent cation, with essential roles in many physiological functions. Consequently, the assessment of Mg status is important for the study of diseases associated with chronic deficiency. In spite of intense research activities there is still no simple, rapid, and accurate laboratory test to determine total body Mg status in humans. However, serum Mg < 0.75 mmol/l is a useful measurement for severe deficiency, and for values between 0.75 and 0.85 mmol/l a loading test can identify deficient subjects. The loading test seems to be the gold standard for Mg status, but is unsuitable in patients with disturbed kidney and intestinal functions when administered orally. There is also a need to reach a consensus on a standardized protocol in order to compare results obtained in different clinical units. Other cellular Mg measurements, such as total or ionized Mg, frequently disagree and more research and systematic evaluations are needed. Muscle Mg appears to be a good marker, but biopsies limit its usefulness, as is the case with bone Mg, the most important but heterogeneous Mg compartment. The development of new and non invasive techniques such as nuclear magnetic resonance (NMR) may provide valuable tools for routinely analysing ionized Mg in tissues. With the development of molecular genetics techniques, the recent discovery of Transient Receptor Potential Melastatin channels offers new possibilities for the sensitive and rapid evaluation of Mg status in humans.

How should hypomagnesaemia be investigated and treated?

            (Ayuk and Gittoes 2011) Download

Hypomagnesaemia is relatively common, with an estimated prevalence in the general population ranging from 2.5% to 15%. It may result from inadequate magnesium intake, increased gastrointestinal or renal loss or redistribution from extracellular to intracellular space. Drug-induced hypomagnesaemia, particularly related to proton pump inhibitor (PPI) therapy, is being increasingly recognized. Most patients with hypomagnesaemia are asymptomatic; symptomatic magnesium depletion is often associated with multiple other biochemical abnormalities, including hypokalaemia, hypocalcaemia and metabolic acidosis. Manifestations of symptomatic hypomagnesaemia most often involve neuromuscular, cardiovascular and metabolic features. Patients with symptomatic hypomagnesaemia should be treated with intravenous magnesium, reserving oral replacement for asymptomatic patients.

Physiologic assessment of magnesium status in humans: a combination of load retention and renal excretion

            (Cohen 2000) Download

Assessment of magnesium status for diagnosis and therapy

         (Elin 2010) Download

Magnesium is an essential element needed for health. Even though only 1% of the total body magnesium is present in blood, the serum magnesium concentration (SMC) is the predominant test used by medicine to assess magnesium status in patients. The traditional method to establish a reference interval for the SMC is flawed by the large number of "normal" individuals who have a subtle chronic negative magnesium balance due to a significant decrease in magnesium intake over the past century. Evidence-based medicine should be used to establish the appropriate lower limit of the reference interval for health and I recommend 0.85 mmol/L based on current literature. The decrease in magnesium in the diet has led to chronic latent magnesium deficiency in a large number of people since their SMC is still within the reference interval due to primarily the bone magnesium supplementing the SMC. These individuals need adjustment of their diet or magnesium supplementation to achieve a normal magnesium status for health.

A functional biological marker is needed for diagnosing magnesium deficiency

            (Franz 2004) Download

Functional biological markers or biomarkers are now available for many nutrients which are used as nutritional status markers. Most sources of these biomarkers are products or precursors of enzymatic processes that can be measured in serum and plasma. At this time measurements of total or ionized magnesium (Mg) in serum, plasma, cellular components, urine or Mg retention from a load test are performed, but they may not always reflect Mg nutritional status. Biomarkers for Mg are needed which would reflect changes in biochemical processes where Mg is involved. Biomarkers for Mg need to be identified and evaluated in both animals and humans, with a determination of possible factors that may affect the reaction and biomarker concentrations. Some possible biomarkers for Mg include the following: Na/K ATPase, thromboxane B2, C-reactive protein, and endothelin-1. Other possible biomarkers for Mg need to be identified.

Noninvasive Measurement of Tissue Magnesium and Correlation With Cardiac Levels

         (Haigney, Silver et al. 1995) Download

BACKGROUND: Intracellular magnesium ([Mg]i) plays an important role in the regulation of myocardial metabolism, contractility, and the maintenance of transsarcolemmal and intracellular ionic gradients. An understanding of the role of magnesium in the clinical setting, however, is hampered by the lack of an assay of intracellular tissue magnesium levels. METHODS AND RESULTS: We used energy-dispersive x-ray analysis to measure [Mg]i in sublingual epithelial cells and to correlate the level with those in atrial biopsy specimens from the same patients during cardiopulmonary bypass. Levels were also measured in acute myocardial infarction (AMI) patients before and after intravenous magnesium sulfate administration and compared with those from intensive care unit (ICU) patients and healthy individuals. A strong correlation between sublingual epithelial cell (mean, 32.1 +/- 0.3 mEq/L) and atrial tissue (mean, 32.1 +/- 0.3 mEq/L) [Mg]i was present in 18 cardiac surgery patients (r = .68, P < .002). Epithelial and atrial [Mg]i levels were lower than in healthy individuals (33.7 +/- 0.5 mEq/L, P < .01) studied at that time and correlated poorly with serum magnesium. Mean [Mg]i in 22 AMI patients was 30.7 +/- 0.4 mEq/L, which was significantly lower than in 21 ICU patients and 15 healthy individuals (35.0 +/- 0.5 mEq/L and 34.5 +/- 0.7 mEq/L, respectively, P < .001). Intravenous magnesium sulfate was administered to most of the AMI patients (mean dose, 36 +/- 6 mmol). [Mg]i rose significantly in the AMI patients over the first 24 hours, and the magnitude of the increase was greater in those who received higher doses of intravenous magnesium sulfate. CONCLUSIONS: Sublingual epithelial cell [Mg]i correlates well with atrial [Mg]i but not with serum magnesium. [Mg]i levels are low in patients undergoing cardiac surgery and those with AMI. Intravenous magnesium sulfate corrects low [Mg]i levels in AMI patients. Energy-dispersive x-ray analysis determination of sublingual cell [Mg]i may expedite the investigation of the role of magnesium deficiency in heart disease.

Magnesium levels in critically ill patients. What should we measure?

            (Huijgen, Soesan et al. 2000) Download

We studied the relation between ionized magnesium, total magnesium, and albumin levels in serum of 115 critically ill patients and the role of extracellular and intracellular magnesium in outcome prediction. Levels of serum total and ionized magnesium, serum albumin, and magnesium in mononuclear blood cells and erythrocytes were measured and the APACHE II score and 1-month mortality recorded. Of all patients, 51.3% had a serum total magnesium concentration below the reference range. In 71% of these hypomagnesemic patients, a normal serum ionized magnesium concentration was measured. None of the patients had an intracellular magnesium concentration below the reference limit. Except for serum total and ionized magnesium, none of the magnesium parameters correlated significantly with each other. A significantly negative correlation was found between serum albumin and the fraction ionized magnesium. There was no association between low extracellular or intracellular magnesium and clinical outcome. The observation of hypomagnesemia in critically ill patients depends on which magnesium fraction is measured. The lack of correlation with clinical outcome suggests hypomagnesemia to be merely an epiphenomenon. Reliable concentrations of serum ionized magnesium can be obtained only by direct measurement and not by calculation from serum total magnesium and albumin.

The underestimated problem of using serum magnesium measurements to exclude magnesium deficiency in adults; a health warning is needed for "normal" results

            (Ismail and Ismail 2010) Download

BACKGROUND: A major use of serum magnesium measurements in clinical practice is to identify patients with deficiency. However, numerous studies have shown that magnesium deficiency is common and may be present in over 10% of hospitalized patients, as well as in the general population. An important cause for under diagnosis of deficiency is that serum magnesium, the most commonly used test, can be normal despite negative body stores. This article focuses on the limitations of "normal" magnesium results and highlights the importance of lifestyle or "modus vivendi" as a pragmatic means of identifying those individuals potentially at risk for negative body magnesium stores. METHODS: Researched peer reviewed articles on magnesium published between 1990 and 2008 in MEDLINE and EMBASE, using database keywords "magnesium, deficiency, diagnosis, treatment and hypomagnesaemia". Bibliographies of retrieved articles have been searched and followed. We have also performed a manual search of each individual issue in which most of these reports have appeared. RESULTS: In 183 peer reviewed studies published from 1990 to 2008, magnesium deficiency was associated with increased prevalence and risk in 11 major conditions. Similarly, in 68 studies performed over the same period, magnesium deficiency was found to predict adverse events and a decreased risk of pathology was noted when supplementation or treatment was instituted. CONCLUSIONS: The perception that "normal" serum magnesium excludes deficiency is common among clinicians. This perception is probably enforced by the common laboratory practice of highlighting only abnormal results. A health warning is therefore warranted regarding potential misuse of "normal" serum magnesium because restoration of magnesium stores in deficient patients is simple, tolerable, inexpensive and can be clinically beneficial.


About the misdiagnosis of magnesium deficiency

            (Liebscher and Liebscher 2004) Download

The experience of our self-help organisation shows that the reason patients with symptoms of magnesium (Mg) deficiency do not get Mg therapy is acceptance of an inappropriate lower limit of the reference values for serum Mg concentration. The commonly designated low limit of the normal range seems to have been selected from values obtained for symptomatic patients. It is below levels that exist in patients with marginal deficiencies that can predispose to development of pathologic findings, so that the prevalence and importance of this disease is insufficiently considered. The lower reference limit of the normal population is erroneously regarded as a diagnostic criterion that excludes Mg deficiency when the serum level is even slightly above the reference limit that only excludes normality at lower levels. It is a statistical error to use the confidence limits of the normal population as the exclusion limit for those with abnormal Mg status.

Values for tissue magnesium as a guide in detecting magnesium deficiency

            (Lim, Jacob et al. 1969) Download

A large-scale survey of the normal magnesium content of various human tissues was carried out to facilitate clinical detection of magnesium deficiency, especially occult deficiency.A review of the literature favours the magnesium content of skeletal muscle as the most reliable index of the body's store of magnesium. There is a significant difference (P < 0.001) in both the serum and erythrocyte magnesium levels between normal pregnant women in the third trimester and the average normal population. The reason for this difference is discussed.

Possible magnesium deficiency should be investigated

         (Ratzmann 2012) Download

Abnormal magnesium status in patients with cardiovascular diseases

         (Sasaki, Oshima et al. 2000) Download

To investigate magnesium status in patients with cardiovascular diseases and in those presenting high factors for these diseases, we measured the concentrations of serum total Mg, serum ionized Mg and intra-erythrocyte Mg. Mg is an important cofactor for many enzymes, especially those involved in phosphate transfer reactions. Mg deficiency has been shown to be associated with fatal cardiovascular diseases, as well as with risk factors for these diseases. Only measurement of the serum concentration of total Mg is routinely available, but ionized Mg is the physiologically active component. Furthermore, most of the body's Mg is present in the intracellular space. Subjects included patients with ischaemic heart disease (n=80), cardiac arrhythmia (n=60), diabetes mellitus (n=36), essential hypertension (n=194) and hypercholesterolaemia (n=60). The same measurements were made in healthy controls (30 men and 26 women; mean age 58+/-11 years). The serum ionized Mg concentration was measured with a selective ion electrode. The intra-erythrocyte Mg concentration was measured by atomic absorption. No gender difference was found for any Mg parameter, nor was age related to any Mg parameter. The serum albumin concentration was positively correlated only with the serum total Mg concentration. Although the serum total Mg concentration was similar in all groups, patients with diabetes mellitus and arrhythmia had lower serum levels of ionized Mg. Patients with essential hypertension exhibited higher intra-erythrocyte Mg concentrations than the healthy controls. Thus the measurement of serum total Mg concentration may obscure the presence of extracellular Mg deficiency in patients with arrhythmia and diabetes mellitus. Furthermore, the intracellular accumulation of Mg does not support the hypothesis of Mg deficiency in patients with essential hypertension.

How best to determine magnesium status: a new laboratory test worth trying

            (Seelig and Altura 1997) Download

Development of cellular magnesium nano-analysis in treatment of clinical magnesium deficiency

            (Silver 2004) Download

A novel technique, using energy dispersive X-ray microanalysis (EXAtm), for noninvasive intracellular (i.c.) measurement of magnesium [Mg2+]i has now been accomplished and proven to be a valuable tool in multiple aspects of normal as well as pathological magnesium metabolism. Since only 1% of total body Mg2+ is found in the intravascular space, serum levels of Mg2+ give little information about a patient's overall Mg2+ status with respect to this essential mineral. Using the EXAtm analysis it has shown been determined that Mg2+ levels are significantly reduced in many physiological states which may lead to serious pathological conditions [15]. Description of the methodology and examples of data as well as potential applications will focus on intracellular (i.c.) [Mg2+]i determinations obtained in cells from subjects with cardiovascular disease (CVD) syndromes related to Mg2+ deficiency. Examples of the application of EXAtm evaluation include examination of intracellular magnesium and other minerals in a wide spectrum of conditions which include cardiovascular conditions, arrhythmias, heart failure, myocardial infarction, and bypass surgery. Standardization of control values were performed at NASA.


Urinary excretion of an intravenous 26Mg dose as an indicator of marginal magnesium deficiency in adults

            (Walti, Walczyk et al. 2006) Download

BACKGROUND: Measurement of magnesium (Mg) status is problematic because tissue Mg deficiency can be present without low serum Mg concentrations. OBJECTIVE: To evaluate a modified version of the Mg retention test using stable isotopes for the assessment of Mg status in general, and the detection of marginal Mg deficiency in particular. DESIGN: A modified version of the Mg retention test using a small dose of (26)Mg was evaluated for assessment of Mg status in 22 healthy subjects. Muscle Mg concentration was used as reference for Mg status. A muscle biopsy was taken from the lateral portion of the quadriceps muscle from each subject. After 2 to 4 weeks, 11 mg of (26)Mg (as MgCl(2) in 14 ml water) were injected i.v. over a period of 10 min and all urine was collected for the following 24 h. Excretion of the isotopic label was expressed as percentage of the administered dose excreted in urine within 24 h. RESULTS: Mean +/- s.d. Mg concentration in muscle was 3.85 +/- 0.17 mmol/100 g fat-free dried solids. Mean +/- s.d. excretion of the injected dose within 24 h was 7.9 +/- 2.1%. No correlation was found between muscle Mg concentration and excretion of the isotopic label (r (2 ) = 0.061, P = 0.27). CONCLUSIONS: In this study, urinary excretion of an intravenous Mg tracer was not influenced by muscle Mg concentration and its usefulness for the detection of marginal Mg deficiency could therefore not be demonstrated. SPONSORSHIP: Swiss Foundation for Nutrition Research and Swiss Federal Institute of Technology, Zurich, Switzerland.

Intravenous magnesium sulfate with and without EDTA as a magnesium load test-is magnesium deficiency widespread?

            (Waters, Fernholz et al. 2008) Download

Serum/plasma measurements do not reflect magnesium deficits in clinical situations, and magnesium load tests are used as a more accurate method to identify magnesium deficiency in a variety of disease states as well as in subclinical conditions. The objective of this study was to determine if people are indeed magnesium deficient or if the apparent magnesium deficiency is due to the composition of the infusate used in the load test. Magnesium load tests were performed on seven patients using three different Mg solution infusions-a Mg-EDTA (ethylene diamine tetraacetic acid)-nutrient cocktail used in EDTA chelation therapy containing several components including vitamins and minerals, and the same cocktail without EDTA and an infusion of an identical amount of magnesium in normal saline solution. There was no significant difference in the amount of magnesium retained in the 24 h after infusion among the three infusates. All infusates resulted in very high magnesium retention compared to previous published magnesium load studies. Magnesium deficiency may be widespread, and the relationship of Mg deficiency to related diseases requires further study.

Interpretation of the serum magnesium level

            (Zaloga 1989) Download


References

Arnaud, M. J. (2008). "Update on the assessment of magnesium status." Br J Nutr 99 Suppl 3: S24-36.

Ayuk, J. and N. J. Gittoes (2011). "How should hypomagnesaemia be investigated and treated?" Clin Endocrinol (Oxf) 75(6): 743-6.

Cohen, L. (2000). "Physiologic assessment of magnesium status in humans: a combination of load retention and renal excretion." Isr Med Assoc J 2(12): 938-9.

Elin, R. J. (2010). "Assessment of magnesium status for diagnosis and therapy." Magnes Res 23(4): S194-8.

Franz, K. B. (2004). "A functional biological marker is needed for diagnosing magnesium deficiency." J Am Coll Nutr 23(6): 738S-41S.

Haigney, M. C., B. Silver, et al. (1995). "Noninvasive measurement of tissue magnesium and correlation with cardiac levels." Circulation 92(8): 2190-7.

Huijgen, H. J., M. Soesan, et al. (2000). "Magnesium levels in critically ill patients. What should we measure?" Am J Clin Pathol 114(5): 688-95.

Ismail, Y. and A. A. Ismail (2010). "The underestimated problem of using serum magnesium measurements to exclude magnesium deficiency in adults; a health warning is needed for "normal" results." Clin Chem Lab Med 48(3): 323-7.

Liebscher, D. H. and D. E. Liebscher (2004). "About the misdiagnosis of magnesium deficiency." J Am Coll Nutr 23(6): 730S-1S.

Lim, P., E. Jacob, et al. (1969). "Values for tissue magnesium as a guide in detecting magnesium deficiency." J Clin Pathol 22(4): 417-21.

Ratzmann, G. W. (2012). "Possible magnesium deficiency should be investigated." Dtsch Arztebl Int 109(6): 109-10.

Sasaki, S., T. Oshima, et al. (2000). "Abnormal magnesium status in patients with cardiovascular diseases." Clin Sci (Lond) 98(2): 175-81.

Seelig, M. S. and B. M. Altura (1997). "How best to determine magnesium status: a new laboratory test worth trying." Nutrition 13(4): 376-7.

Silver, B. B. (2004). "Development of cellular magnesium nano-analysis in treatment of clinical magnesium deficiency." J Am Coll Nutr 23(6): 732S-7S.

Walti, M. K., T. Walczyk, et al. (2006). "Urinary excretion of an intravenous 26Mg dose as an indicator of marginal magnesium deficiency in adults." Eur J Clin Nutr 60(2): 147-54.

Waters, R. S., K. Fernholz, et al. (2008). "Intravenous magnesium sulfate with and without EDTA as a magnesium load test-is magnesium deficiency widespread?" Biol Trace Elem Res 124(3): 243-50.

Zaloga, G. P. (1989). "Interpretation of the serum magnesium level." Chest 95(2): 257-8.