Magnesium Isotopes in Nutritional Research

By: Dr. Matthew Yong
Date: 2 May 2017

Executive Summary

In humans, Magnesium (Mg) is the second most abundant intracellular cation and a cofactor in more than 300 enzymatic reactions involving energy metabolism, protein and nucleic acid synthesis. About half the magnesium found in the human body is present in soft tissue; the other half is present in the bones. Less than 1% of total body Mg is found in the blood [1]. The involvement of Mg as a critical element in the proper function of the human body means that magnesium isotopes are a useful and exciting tool in nutrition and clinical studies as well as fundamental research.

Although magnesium deficiency in humans is rare, it may result from chronic alcoholism, certain health conditions (the elderly, people with diabetes and gastrointestinal disorders) and as a consequence of some medications.[2]

Of the 22 isotopes of magnesium, 3 are stable (24Mg, 25Mg and 26Mg) [3]. The stable isotopes are naturally present in proportions of 78.9%:10.0%:11.1% respectively. For research into human absorption and utilization of magnesium, the stable isotopes may be introduced orally as part of a diet, or intravenously [4]. The stable isotopes are entirely safe to use for absorption and retention studies not only in adult humans, but also pregnant women and newborn infants [5]. This paper will present an overview of the use of stable magnesium isotopes in research involving human health and well-being.

Contents

Dietary sources of magnesium

There is experimental and clinical evidence that indicates that magnesium intake in the typical Western diet is often insufficient to meet individual needs [6], or that not all children get their recommended magnesium intake [7]. Dietary sources of magnesium include some types of dark leafy greens, nuts and seeds, legumes, beans and whole grains. The rule of thumb is that foods containing dietary fibre tend to contain magnesium. Of the magnesium ingested from dietary sources, about 30 – 40% is absorbed by the body. [2] Magnesium may also be absorbed through our drinking water. Research work involving 4.5mmol/L of 25Mg in 500ml of water, consumed twice a day over two days resulted in absorption values of 45.7±4.6% [8].

Introducing stable isotopes into dietary sources is an established method of measuring the uptake and utilization of magnesium by the human body. In addition to the quantity of magnesium ingested, it is also important that the magnesium be in bioavailable form. For research purposes, the bioavailable form must typically mimic forms typically accessible in the human diet. Tests have shown that extrinsic labelling with 28Mg of leafy vegetables results in similar absorption values to intrinsic labelling with 25Mg [5]. Homeostasis of magnesium is affected by factors such as intestinal absorption, cellular and extra-cellular distribution, and urine excretion [6].

Of the dietary sources above, it is reported that soybean and green beans are the best plant species to obtain large quantities of edible parts quickly, with minimal loss of the valuable magnesium isotopes [5]. The daily magnesium balance is shown in Figure 1 below:


Figure 1: Magnesium balance, from [9]

Utilization of magnesium in the human body

Unlike calcium, which is almost entirely concentrated in the bone, about 40% of magnesium is found in soft tissue. In a 1998 study, no significant gender differences exist in magnesium uptake and utilization [10], although a more recent 2014 study showed a small but significant difference in magnesium absorption in males vs. females (67% ± 12% vs. 60% ± 8%) [7]. Of the magnesium found in soft tissue, a study with rats and radioactive 28Mg showed that about 20% of magnesium in skeletal muscle can exchange readily with extracellular fluid, with the remainder being relatively inexchangeable [11]. Of the magnesium in bone, about 50-60% of it is present as surface substituents of the hydroxyapatite mineral component of bone. Deposits of magnesium in bone decreases with age, with the bone providing a reservoir to buffer changes in extracellular magnesium levels.

Research involving stable magnesium isotopes

Overview

One of the main difficultie in using stable magnesium isotopes for research is the lack of a suitable tracer [12]. None of the stable isotopes of magnesium are of low abundance (>5%) and the 28Mg radioisotope has a short half-life of 21 hours. Therefore, to achieve measurable enrichment of an isotope in the urine or serum samples, relatively large doses need to be given. This raises the cost of research involving stable magnesium isotopes. In the past, measurement of the stable isotope ratios was done using expensive and time consuming neutron activation or thermal ionisation mass spectrometry techniques[4]. However, recent advances in analytical precision through techniques such as inductively coupled plasma mass spectrometry (ICP-MS) has improved measurement sensitivity and thus reduced the doses of stable magnesium isotopes required, thereby offsetting this disadvantage to some extent. [6], [13] ICP-MS offers high sensitivity, rapid throughput and simple sample preparation[4].

Human studies: magnesium deficiency and its effects

For studies into magnesium absorption, typical quantities of magnesium isotopes needed is 20mg over 7 days, resulting in faecal isotopic enrichments of 10%. For higher enrichments, 80mg of 26Mg (orally) and 40mg of 25Mg (intravenously) would result in 10% urine and plasma enrichment 48 hours after administration [6].

Human studies: Magnesium in human health and disease

Inadequate intake or absorption of magnesium has been linked to various pathologies in humans, including hypertension, migraine, artherosclerotic vascular disease and possibly osteoporosis [2], [5]. Poor magnesium intake also has links to metabolic disorders [6].

Safety Aspects

Occasionally, the 28Mg radioisotope is used in human studies, but its use is restricted by its short half-life (21.3hrs), the subject’s accessibility to radioactivity measuring devices and safety considerations that preclude infants, adolescents and pregnant women from the studies [6]. The stable magnesium isotopes themselves are considered to be safe and established for human studies including of more vulnerable groups such as children, adolescents and the pregnant [10], [7].

Conclusions

The use of stable magnesium isotopes presents an exciting opportunity to study the absorption and utilization of magnesium in our diet. Their safety in comparison to radioactive isotopes means that these studies may be conducted in subject categories such as the young and pregnant. The fact that all stable isotopes of magnesium are fairly abundant means that larger quantities of stable isotopes are needed, in conjunction with more sensitive measurement techniques (ICP-MS) to reduce the cost of the research.

Suppliers of stable magnesium isotopes

Bibliography

[1] R. J. Elin, “Magnesium: the fifth but forgotten electrolyte,” Am. J. Clin. Pathol., vol. 102, no. 5, pp. 616–622, 1994.

[2] “Magnesium: Fact Sheet for Health Professionals,” Magnesium Fact Sheet for Health Professionals, 11-Feb-2016. [Online]. Available: https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/.

[3] “Isotopes of Magnesium,” Wikipedia - Isotopes of Magnesium, 15-Apr-2017. [Online]. Available: https://en.wikipedia.org/wiki/Isotopes_of_magnesium.

[4] C. Coudray, D. Pepin, J. C. Tressol, J. Bellanger, and Y. Rayssiguier, “Study of magnesium bioavailability using stable isotopes and the inductively-coupled plasma mass spectrometry technique in the rat: single and double labelling approaches,” Br. J. Nutr., vol. 77, no. 06, p. 957, Jun. 1997.

[5] D. Courtois, P. Kastenmayer, J. Clough, M. Vigo, M. Sabatier, and M. J. Arnaud, “Magnesium enrichment and distribution in plants,” Isotopes Environ. Health Stud., vol. 39, no. 4, pp. 273–279, Dec. 2003.

[6] C. Coudray, C. Feillet-Coudray, M. Rambeau, A. Mazur, and Y. Rayssiguier, “Stable isotopes in studies of intestinal absorption, exchangeable pools and mineral status: The example of magnesium,” J. Trace Elem. Med. Biol., vol. 19, no. 1, pp. 97–103, Sep. 2005.

[7] S. A. Abrams, Z. Chen, and K. M. Hawthorne, “Magnesium Metabolism in 4-Year-Old to 8-Year-Old Children: MAGNESIUM METABOLISM IN CHILDREN 4 TO 8 YEARS OLD,” J. Bone Miner. Res., vol. 29, no. 1, pp. 118–122, Jan. 2014.

[8] M. Sabatier, M. J. Arnaud, and J. R. Turnlund, “Magnesium absorption from mineral water,” Eur. J. Clin. Nutr., vol. 57, no. 6, pp. 801–802, Jun. 2003.

[9] W. Jahnen-Dechent and M. Ketteler, “Magnesium basics,” Clin. Kidney J., vol. 5, no. Suppl 1, pp. i3–i14, Feb. 2012.

[10] S. A. Abrams, “The Relationship Between Magnesium and Calcium Kinetics in 9-to 14-Year-Old Children,” J. Bone Miner. Res., vol. 13, no. 1, pp. 149–153, 1998.

[11] T. A. Rogers and P. E. Mahan, “Exchange of Radioactive Magnesium in the Rat,” Proc. Soc. Exp. Biol. Med., vol. 100, no. 2, pp. 235–239, 1959.

[12] J. Sojka et al., “Magnesium kinetics in adolescent girls determined using stable isotopes: effects of high and low calcium intake,” Am. J. Physiol.-Regul. Integr. Comp. Physiol., vol. 273, no. 2, pp. R710–R715, 1997.

[13] S. A. Abrams, “Using stable isotopes to assess mineral absorption and utilization by children,” Am. J. Clin. Nutr., vol. 70, no. 6, pp. 955–964, 1999.