General Introduction 11 1 magnesium ingested is 156 mg, which is about 52% of the total daily requirement for women and 45% for men, respectively. Given the presumed health effects and the observed low intake of magnesium with a normal contemporary diet, an increasing interest in dietary magnesium supplements has emerged over the past decades. Results from a recent study showed that magnesium was the most popular topic when it comes to dietary supplements among global Google users and was even more popular than vitamin D and iron 18. Numerous magnesium supplements are commercially available, of which the organic formulation magnesium citrate is most commonly preferred because of its suggested high bioavailability. Inorganic formulations, such as magnesium oxide and magnesium sulfate, are often considered less desirable because of their poorer solubility in water 19. To date, several studies investigated the bioavailability of different magnesium formulations, in which in vitro solubility and/or in vivo gastro-intestinal absorbability were tested. Three studies have suggested a higher bioavailability of the magnesium citrate formulation based on a higher renal excretion of magnesium 20,21 or higher serum magnesium levels 22 when compared to other inorganic compounds. The opposite has, however, been suggested by a recent meta-analysis, which found that inorganic magnesium, particularly magnesium oxide, exhibited a greater increase in serum magnesium compared to organic magnesium formulations 15. As a consequence, no consensus has been reached with respect to the best magnesium formulation to be used. Magnesium homeostasis and status Magnesium homeostasis mainly depends on the interplay between intestinal absorption and renal excretion. The predominant sites of intestinal absorption are the distal jejunum and the ileum, via a paracellular pathway, whereas a small part is absorbed in the colon,which mainly involves a transcellular pathway 23. Under normal circumstances, approximately 30-50% of the magnesium is absorbed in the intestine. However, during a period of low magnesium intake, fractional absorption can reach values of as high as 80-90%, whereas it decreases significantly to values as low as 10-20% when intake is high. In the kidney, the vast majority of magnesium is reabsorbed in the loop of Henle, mainly in the thick ascending limb. Renal magnesium handling is regulated by several magnesium transporters, including the transient receptor potential channel melastatin member 6 (TRPM6) 24. The body is able to maintain normal plasma levels by increasing the intestinal absorption and decreasing renal excretion when low intakes occur. It is worth noting that the plasma level of magnesium is not representative of the total body magnesium, as magnesium is mainly located in cells and bones and the plasma
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