Challenges in the Diagnosis of Magnesium Status

Abstract

Magnesium is a critical mineral in the human body and is involved in ~80% of known metabolic functions. It is currently estimated that 60% of adults do not achieve the average dietary intake (ADI) and 45% of Americans are magnesium deficient, a condition associated with disease states like hypertension, diabetes, and neurological disorders, to name a few. Magnesium deficiency can be attributed to common dietary practices, medications, and farming techniques, along with estimates that the mineral content of vegetables has declined by as much as 80⁻90% in the last 100 years. However, despite this mineral's importance, it is poorly understood from several standpoints, not the least of which is its unique mechanism of absorption and sensitive compartmental handling in the body, making the determination of magnesium status difficult. The reliance on several popular sample assays has contributed to a great deal of confusion in the literature. This review will discuss causes of magnesium deficiency, absorption, handling, and compartmentalization in the body, highlighting the challenges this creates in determining magnesium status in both clinical and research settings.

Keywords: magnesium; magnesium absorption; magnesium assays; magnesium deficiency; magnesium sampling; magnesium status.

Figure 1

Number of basic and clinical research papers published (Y-axis) as screened using Web of Science [v.5.28.1] under the search terms “magnesium deficiency” (yellow), “calcium deficiency” (green) or “iron deficiency” (blue) (performed 4 May 2018) over the past 25 years (X-axis; 2017–1992). (Inset) Trend lines show the relatively flat research output on magnesium deficiency relative to calcium and iron.

Figure 2

The average mineral content of calcium, magnesium, and iron in cabbage, lettuce, tomatoes, and spinach has dropped 80–90% between 1914 and 2018 [30,34,35,36,37]. Asterisks indicate numbers could not be independently verified.

Figure 3

Percentage of magnesium absorption in the GI tract. The majority of magnesium is absorbed in the distal portion of the small intestine. The ileum absorbs 56%, the jejunum 22%, the duodenum 11%, and colon 11% [3,58].

Figure 4

Magnesium absorption in the intestine. Magnesium is absorbed through either a saturable transcellular pathway (left) in which TRPM6 and TRPM7 actively transport magnesium into the GI epithelial cells, which is effluxed through a Na⁺/Mg²⁺ exchanger and/or a paracellular pathway (right) where magnesium transverses the tight junctions of the intestinal epithelium, assisted by magnesium associated claudin proteins.

Figure 5

Hydration shells of both magnesium and calcium. The hydrated radius of magnesium is >400 times larger than its dehydrated radius, which is much more prominent than calcium (~25-fold difference) [83,84]. This increase in radius, unlike calcium, prevents magnesium from passing through narrow ion channels.

Figure 6

Magnesium homeostasis. Dietary magnesium can be absorbed along the entire length of the GI tract and into the blood but can also be excreted in feces (between 20% and 70% of the ingested amount) [69]. Once in the blood, magnesium is quickly taken up into tissues with muscle containing 27%, bone 53%, and other tissues holding 19% [3,58,93]. Blood and tissue magnesium are in a constant state of exchange and the kidney, which can filter up to 2400 mg of magnesium per day [94] (or 10% of average magnesium content in an adult [95]) can excrete between 5% and 70% of that magnesium depending on multiple variables.