*NRV: nutritional reference values
**In France, magnesium formulas are limited to 81% of NRVs (300mg/day)

Ingredients: Magshape® microcapsules* (corn starch, magnesium oxide, sunflower lecithin), magnesium malate, coating agent: hydroxypropylmethylcellulose, spirulina and apple concentrate, GivoMag® (magnesium glycerophosphate), Vitamin B6 (pyridoxal-5-phosphate).*Magshape is a brand from Lypotec S.A.

What is magnesium?

Magnesium is the 4th most abundant mineral in our body. It is involved in more than 300 enzymatic reactions in humans (lipid, protein and DNA metabolism), which explains its importance. Dietary magnesium is mainly found in cereal bran (whole grains), dried herbs, seeds and oilseeds (the nutritional composition of food can be consulted on the site of ANSES - National Agency for Food, Environmental and Occupational Safety :https://www.anses.fr/fr/content/la-table-de-composition-nutritionnelle-du-ciqual).

About 99% of the body's magnesium is stored in our tissues, and 1% circulates in serum and red blood cells (erythrocytes). Bone tissue contains most of the body's magnesium (50-60%). The rest is stored in skeletal muscle and soft tissue. Since 0.3% of body magnesium is found in serum, serum assays do not reflect magnesium status. Storage (retention), absorption, reabsorption and excretion are the result of exchanges between different body compartments (small intestine, colon, kidney, muscle and bone) from dietary intake of magnesium [1] (see diagram magnesium storage and exchange). For this reason, there is no simple and accurate method of measurement to determine the magnesium status. Nevertheless, the most common measurement is still the measurement of serum concentration, even though it is not very revealing of the status [2]. The erythrocyte assay is more accurate but also more complex and is rather practiced by elite athletes.

(Figure tirée de [3])

For who, for what and why?

The nutritional reference values (NRVs, new name for RDAs: "Recommended Daily Intakes") defined by the EFSA (different from the regulatory values for labelling) depend on the type of population under consideration (NRV table). If there does not seem to be specific NRVs for the elderly, pregnant or breastfeeding women or specific populations such as sportsmen and women, the needs could be increased.[4,5].

Optimal magnesium intakes are determined by body requirements, absorption, excretion and retention. For this reason, magnesium deficiencies can be multifactorial [1,6,7] and affect a large part of the population:

• Reduction in food choices for "raw" products and more for industrial products (refined products),
• Reduction in absorption due to intestinal disorders, vitamin D deficiency, proton pump inhibiting drugs,
• Gastrointestinal losses resulting from diarrhoea, vomiting, malabsorption, fistulas, Use of laxatives,
• Kidney losses due to alcohol intake, diabetic treatments, hypercalcemia,
• Losses by sweating,
• Genetic manifestations (CCHF type 1 or type 2, Bartter syndrome, Gitelman syndrome...) [8],
• Not covering needs in particular physiological situations (intense stress for example).

Several levels of clinical signs are observable depending on the level of magnetic deficiency. The first signs are characterized by vomiting, facial redness, urinary retention, gastrointestinal disorders, hypotension and muscle pain. Drowsiness, migraines, absence of tendon reflexes, respiratory and especially cardiac disorders (cardiac arrhythmias) may subsequently occur [8]. Beyond the clinical signs, several studies have shown a positive relationship between magnesium and a reduction in moderate to moderate anxiety by acting directly on the stress pathways in our central nervous system. [9].

Mg supplementation makes sense since:

• On the one hand, the intake of magnesium would make it possible to make up the deficits and to ensure the needs to avoid magnesium deficiency, i.e. the moment when the direct manifestations linked to the lack of magnesium become too serious.

This is why magnesium supplementation would be a real preventive asset for intakes increased from 150mg to 400mg.[12].

How?

Magnesium is an ion that needs to be grafted to a carrier to be stabilized and absorbed, i.e., to pass through the intestinal barrier to reach the bloodstream.

And it is within this area that we are touching on the main problem with magnesium supplementation. If magnesium is a major element of choice for the physiological balance of our organism, the selection of the forms in which it must be consumed (when dissociated from food), is essential. In other words, which form of magnesium is to be preferred ?

• The first magnesium salts were in the form of magnesium oxide or marine magnesium (inorganic salts). Although their magnesium content is high (60%), neither absorption nor digestive comfort is optimised [13]. Indeed, these salts often have laxative effects.
• Then come the magnesium salts in which magnesium is chelated (organic salts): bisglycinate, malate, taurinate or citrate, which show a lower magnesium content (on average 12%) compensated by increased absorption and better digestive comfort [14]. In particular, preclinical studies have shown a higher efficacy of magnesium acetyl taurinate in specifically and rapidly reaching cerebral and cognitive nerve tissue [15,16] as well as serum levels of magnesium malate that persisted higher over time [16].

These observations suggest that the combination of the most effective soluble salts (taurinate and malate) and liposomal magnesium (high content and high absorption) seems to be one of the best nutraceutical strategies in the field of magnesium. Moreover, it is important to note that the intake of magnesium is the fractionation dimension of the consumed dose. Indeed, it has been reported that low doses of magnesium are more efficiently absorbed compared to high doses. This is why the European authorities recommend a dose divided by 2 or 3 "portions" ranging from 80 to 100mg per dose [18].

Additional magnesium ?

As a reminder, magnesium is involved in more than 300 enzymatic reactions in the human body. Indeed, several major roles characterize magnesium: role of co-factor, role in active transport, structural role, role in immunological functions [3,8]. Due to its affinity with phosphate, magnesium (in its ionized form) plays a role in the phosphorylation of ATP and thus in energy metabolism. At the muscular level, magnesium is a co-factor of phosphocreatine, essential for the resynthesis of ATP (an intermediate energy molecule). This role as a co-factor in the muscle gives magnesium a primordial action in muscle contraction because this phenomenon is known as "ATP-dependent". But more broadly, magnesium as a co-factor is essential to the process of protein synthesis, muscle nerve transmission, neuromuscular conduction and carbohydrate homeostasis. Magnesium as a transporter facilitates the transport of calcium and potassium across cell membranes, which is especially important for nerve conduction, muscle contraction and regulation of cardiac function. Magnesium is also involved in the structure of many physiological components of our body: bones, proteins, a large number of enzymes, mitochondria, DNA and RNA. Finally, it is important in immunological functions, including macrophage activation, cell adhesion, bactericidal activity, lymphocyte proliferation and the binding of endotoxins to monocytes. In conclusion, magnesium is everywhere. It is therefore through all its major physiological implications that magnesium is also associated with a reduced risk of certain cardio-metabolic pathologies. Low serum magnesium levels are linked to a greater prevalence of metabolic syndrome, type II diabetes, hypertension and atherosclerosis [19,20].

Publications

1. Ahmed, F.; Mohammed, A. Magnesium: The Forgotten Electrolyte—A Review on Hypomagnesemia. Med. Sci. 2019, 7, 56.
2. Jahnen-Dechent, W.; Ketteler, M. Magnesium basics. Clin. Kidney J. 2012, 5, i3–i14.
3. de Baaij, J.H.F.; Hoenderop, J.G.J.; Bindels, R.J.M. Magnesium in Man: Implications for Health and Disease. Physiol. Rev. 2015, 95, 1–46.
4. Swaminathan, R. Magnesium Metabolism and its Disorders. Clin Biochem Rev 2003, 24, 20.
5. Laires, M.J. Role of cellular magnesium in health and human disease. Front. Biosci. 2004, 9, 262.
6. Elin, R.J. Assessment of magnesium status for diagnosis and therapy. 2016, 5.
7. Schwalfenberg, G.K.; Genuis, S.J. The Importance of Magnesium in Clinical Healthcare. Scientifica 2017, 2017, 1–14.
8. Al Alawi, A.M.; Majoni, S.W.; Falhammar, H. Magnesium and Human Health: Perspectives and Research Directions. Int. J. Endocrinol. 2018, 2018, 1–17.
9. Neil Boyle; Clare Lawton; Louise Dye The Effects of Magnesium Supplementation on Subjective Anxiety and Stress—A Systematic Review. Nutrients 2017, 9, 429.
10. Vormann, J. Magnesium: nutrition and metabolism. Mol. Aspects Med. 2003, 24, 27–37.
11. DiNicolantonio, J.J.; O’Keefe, J.H.; Wilson, W. Subclinical magnesium deficiency: a principal driver of cardiovascular disease and a public health crisis. Open Heart 2018, 5, e000668.
12. Razzaque, M. Magnesium: Are We Consuming Enough? Nutrients 2018, 10, 1863.
13. Blancquaert, L.; Vervaet, C.; Derave, W. Predicting and Testing Bioavailability of Magnesium Supplements. Nutrients 2019, 11, 1663.
14. Kappeler, D.; Heimbeck, I.; Herpich, C.; Naue, N.; Höfler, J.; Timmer, W.; Michalke, B. Higher bioavailability of magnesium citrate as compared to magnesium oxide shown by evaluation of urinary excretion and serum levels after single-dose administration in a randomized cross-over study. BMC Nutr. 2017, 3, 7.
15. Lambuk, L.; Jafri, A.J.A.; Arfuzir, N.N.N.; Iezhitsa, I.; Agarwal, R.; Rozali, K.N.B.; Agarwal, P.; Bakar, N.S.; Kutty, M.K.; Yusof, A.P.Md.; et al. Neuroprotective Effect of Magnesium Acetyltaurate Against NMDA-Induced Excitotoxicity in Rat Retina. Neurotox. Res. 2017, 31, 31–45.
16. Uysal, N.; Kizildag, S.; Yuce, Z.; Guvendi, G.; Kandis, S.; Koc, B.; Karakilic, A.; Camsari, U.M.; Ates, M. Timeline (Bioavailability) of Magnesium Compounds in Hours: Which Magnesium Compound Works Best? Biol. Trace Elem. Res. 2019, 187, 128–136.
17. Brilli, E.; Khadge, S.; Fabiano, A.; Zambito, Y.; Williams, T.; Tarantino, G. Biovailability of Sucrosomial® magnesium vs. standard formulations. Eur Rev Med Pharmacol Sci 2018, 22, 1843–1851.
18. Siebrecht, S. Magnesium Bisglycinate as safe form for mineral supplementation in human nutrition. Sonderdruck 2013, 144, 16.
19. Chacko, S.A.; Sul, J.; Song, Y.; Li, X.; LeBlanc, J.; You, Y.; Butch, A.; Liu, S. Magnesium supplementation, metabolic and inflammatory markers, and global genomic and proteomic profiling: a randomized, double-blind, controlled, crossover trial in overweight individuals. Am. J. Clin. Nutr. 2011, 93, 463–473.
20. Geiger, H.; Wanner, C. Magnesium in disease. Clin. Kidney J. 2012, 5, i25–i38.