Submitted Successfully!
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Ver. Summary Created by Modification Content Size Created at Operation
1 + 954 word(s) 954 2021-01-22 07:42:46 |
2 format correct Meta information modification 954 2021-02-02 08:47:11 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Jonckheere, N. Mg2+ Transporters in Digestive Cancers. Encyclopedia. Available online: (accessed on 11 December 2023).
Jonckheere N. Mg2+ Transporters in Digestive Cancers. Encyclopedia. Available at: Accessed December 11, 2023.
Jonckheere, Nicolas. "Mg2+ Transporters in Digestive Cancers" Encyclopedia, (accessed December 11, 2023).
Jonckheere, N.(2021, January 28). Mg2+ Transporters in Digestive Cancers. In Encyclopedia.
Jonckheere, Nicolas. "Mg2+ Transporters in Digestive Cancers." Encyclopedia. Web. 28 January, 2021.
Mg2+ Transporters in Digestive Cancers

Magnesium (Mg2+) is one of the most important ions in health and is the second most abundant cation in the cell with a concentration estimated between 10 and 30 mM. Due to its importance, Mg2+, requires a specific transport system. In Mammals, several transporters have been identified (TRPM6/7, CNNM1/2/3/4, MAGT1, SLC41A1, MRS2). There is numerous evidence suggesting an association between Mg2+ intake and digestive cancer risk and/or development.

magnesium transporters digestive cancers

1. Magnesium

Magnesium (Mg2+) is one of the most important ions in health and is the second most abundant cation in the cell with a concentration estimated between 10 and 30 mM. Due to the binding to different partners like ATP, ribosomes, or nucleotides, the free intracellular Mg2+ levels lower to 0.5 to 1.2 mM [1]. Mg2+ is essential in almost all cellular processes, acting as a cofactor and activator for various enzymes [1]. For example, Mg2+ is essential in DNA stabilization, DNA repair mechanisms, or even protein synthesis [2][3][4][5]. New interactions are still being discovered, expanding the importance of this cation [6].

Normal Mg2+ in blood serum levels for healthy people is about 0.7–1 mM, corresponding to an average daily intake (ADI) of 320–420 mg/day [7][8]. This Mg2+ intake is absorbed mostly in the small intestine by two mechanisms: paracellular transport and via the expression of membrane transporters (Figure 1). Paracellular transport is predominant, mainly because of low expression of claudins in the small intestine [9][10]. Numerous Mg2+ transporters are also present in the plasma membrane of intestine cells for Mg2+ absorption. An average of 100 mg is absorbed in the intestine, depending on the daily Mg2+ intake [1]. Kidneys filters around 2400 mg of Mg2+ per day in the glomeruli, where most of the Mg2+ (2300 mg) is reabsorbed in the thick ascending limb of Henle’s loop. Mg2+ is mainly stored in bones but also in muscles and soft tissues. [1][11]. This organization allows the Mg2+ homeostasis balance, maintaining a constant 0.7–1 mM Mg2+ serum level in normal conditions.

Figure 1. Summary of Mg2+ homeostasis.

Unfortunately, our alimentation contains nowadays less Mg2+ because of the development of the food industry and changes in soils due to intensive farming [12][13]. Along with the modifications of our eating habits and the prevalence of processed foods, it is shown that a large number of adults do not reach the recommended Mg2+ average daily intake [14]. Hypomagnesemia is characterized by Mg2+ serum levels <0.7 mM, but it is often underestimated because the serum levels are not representative of the whole Mg2+ availability [15]. Hypomagnesemia is associated with several health issues such as epilepsy, cystic fibrosis, atherosclerosis, and type 2 diabetes [16][17][18][19].

Several studies suggest that calcium (Ca2+) and Mg2+ can compete during intestinal absorption, leading to the consideration also of the Ca2+/Mg2+ ratio for assessing Ca2+ and Mg2+ intakes [20].

Due to its importance, Mg2+, requires a specific transport system. The first magnesium transporters were identified in prokaryotes, with the identification of the proteins magnesium/cobalt transporter (CorA), magnesium-transporting ATPase (MgtA/B/E) [21]. Subsequently, Mg2+ transporters were identified and cloned in other models (Figure 2). In Mammals, several transporters have been identified and will be described in this manuscript.

Figure 2. General distribution and localization of Mg2+ transporters in cells. Mg2+, magnesium; Na+, sodium; CNNM2/3/4, Cyclin and CBS Domain Divalent Metal Cation Transport Mediator2/3/4; MAGT1, Magnesium Transporter 1; SLC41A1, Solute Carrier Family 41, Member 1; TRPM7, Transient Receptor Potential Cation Channel Subfamily M Member 7; TRPM6, Transient Receptor Potential Cation Channel Subfamily M Member 6; CNNM1, Cyclin and CBS Domain Divalent Metal Cation Transport Mediator1; MRS2, Mitochondrial RNA Splicing Protein 2.

2. Mg2+ Intake and Digestive Cancers

There is much evidence suggesting an association between Mg2+ intake and digestive cancer risk and/or development. For example, high Mg2+ intake and particularly low Ca2+/Mg2+ ratio protects against reflux esophagitis and Barret’s esophagus, two precursors of ESAC. However, no significant associations were observed between Mg2+ intake and ESAC incidence . However, the association is less evident for GC because there is only a suggestive trend for a preventive effect of high Mg2+ intake in non-cardia GC depending of gender and dietary source of Mg2+ .

In PDAC, a first study from 2012 in a large cohort (142,203 men and 334,999 women) recruited between 1992 and 2000 shows no association between Mg2+ intake and cancer risk [22]. Another study has investigated the association between nutrients intake from fruit and vegetable and PDAC risk [23]. The results show an inverse association between PDAC risk and nutrient intake, including Mg2+, in a dose-dependent manner. Importantly, Dibaba et al. have shown in a large cohort, followed from 2000 to 2008, that every 100 mg per day decrement in Mg2+ intake was associated with a 24% increase in PDAC incidence [24]. Moreover, analysis of metallomics in PDAC reveals a lower concentration of Mg2+ in urine of patients with PDAC [25].

Mg2+ intake was associated with a lower risk for CRC, particularly in people with low Ca2+/Mg2+ intake ratio [26]. Importantly, Dai et al. also show that the Thr1482Ile polymorphism in the TRPM7 gene increases the risk for adenomatous and hyperplastic polyps [27]. It was also shown that Mg2+ intake around 400 mg per day has a protective effect for CRC incidence in postmenopausal women [28]. A meta-analysis from 29 studies published on PubMed, Web of Science and the Chinese National Knowledge Infrastructure confirms that the high intake of Mg2+ is inversely associated with the risk of CRC [29]. Assessment of Mg2+ concentration in serum showed an inverse association with CRC risk in female but not in male. Moreover, no significant association was detected between dietary Mg2+ and CRC risk in this study [30]. Finally, Wesselink et al. suggested that an interaction between normal 25-hydroxyvitamin D3 concentration and high Mg2+ intake is essential for reducing the risk of mortality by CRC [31].

To summarize, these epidemiologic studies suggested that high Mg2+ intake by diet and/or supplemental compounds is inversely associated with CRC, PDAC and possibly ESAC risk, but not with GC risk.


  1. De Baaij, J.H.; Hoenderop, J.G.; Bindels, R.J. Magnesium in man: Implications for health and disease. Physiol. Rev. 2015, 95, 1–46, doi:10.1152/physrev.00012.2014
  2. Rubin, H. Central role for magnesium in coordinate control of metabolism and growth in animal cells. Proc. Natl. Acad. Sci. USA 1975, 72, 3551–3555, doi:10.1073/pnas.72.9.3551.
  3. Chiu, T.K.; Dickerson, R.E. 1 A crystal structures of B-DNA reveal sequence-specific binding and groove-specific bending of DNA by magnesium and calcium. J. Mol. Biol. 2000, 301, 915–945, doi:10.1006/jmbi.2000.4012.
  4. Ban, C.; Junop, M.; Yang, W. Transformation of MutL by ATP binding and hydrolysis: A switch in DNA mismatch repair. Cell 1999, 97, 85–97, doi:10.1016/s0092-8674(00)80717-5.
  5. Calsou, P.; Salles, B. Properties of damage-dependent DNA incision by nucleotide excision repair in human cell-free extracts. Nucleic Acids Res. 1994, 22, 4937–4942, doi:10.1093/nar/22.23.4937.
  6. Caspi, R.; Billington, R.; Keseler, I.M.; Kothari, A.; Krummenacker, M.; Midford, P.E.; Ong, W.K.; Paley, S.; Subhraveti, P.; Karp, P.D. The MetaCyc database of metabolic pathways and enzymes—A 2019 update. Nucleic Acids Res. 2020, 48, D445–D453, doi:10.1093/nar/gkz862.
  7. Lowenstein, F.W.; Stanton, M.F. Serum magnesium levels in the United States, 1971–1974. J. Am. Coll. Nutr. 1986, 5, 399–414, doi:10.1080/07315724.1986.10720143.
  8. IMSC. Dietary reference intakes for calcium, phosphorus, magnesium, vitamin d, and fluoride. In Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride; National Academies Press: Washington, DC, USA, 1997; doi:10.17226/5776.
  9. Lameris, A.L.; Huybers, S.; Kaukinen, K.; Makela, T.H.; Bindels, R.J.; Hoenderop, J.G.; Nevalainen, P.I. Expression profiling of claudins in the human gastrointestinal tract in health and during inflammatory bowel disease. Scand. J. Gastroenterol. 2013, 48, 58–69, doi:10.3109/00365521.2012.741616.
  10. Amasheh, S.; Fromm, M.; Gunzel, D. Claudins of intestine and nephron—A correlation of molecular tight junction structure and barrier function. Acta Physiol. 2011, 201, 133–140, doi:10.1111/j.1748-1716.2010.02148.x.
  11. Elin, R.J. Magnesium: The fifth but forgotten electrolyte. Am. J. Clin. Pathol. 1994, 102, 616–622, doi:10.1093/ajcp/102.5.616.
  12. Worthington, V. Nutritional quality of organic versus conventional fruits, vegetables, and grains. J. Altern. Complement. Med. 2001, 7, 161–173, doi:10.1089/107555301750164244.
  13. Rosanoff, A. Changing crop magnesium concentrations: Impact on human health. Plant Soil 2012, 368, 139–153, doi:10.1007/s11104-012-1471-5.
  14. Fulgoni, V.L., 3rd; Keast, D.R.; Bailey, R.L.; Dwyer, J. Foods, fortificants, and supplements: Where do Americans get their nutrients? J. Nutr. 2011, 141, 1847–1854, doi:10.3945/jn.111.142257.
  15. Workinger, J.L.; Doyle, R.P.; Bortz, J. Challenges in the diagnosis of magnesium status. Nutrients 2018, 10, doi:10.3390/nu10091202.
  16. Sinert, R.; Zehtabchi, S.; Desai, S.; Peacock, P.; Altura, B.T.; Altura, B.M. Serum ionized magnesium and calcium levels in adult patients with seizures. Scand. J. Clin. Lab Invest. 2007, 67, 317–326, doi:10.1080/00365510601051441.
  17. Gupta, A.; Eastham, K.M.; Wrightson, N.; Spencer, D.A. Hypomagnesaemia in cystic fibrosis patients referred for lung
  18. transplant assessment. J. Cyst. Fibros. 2007, 6, 360–362, doi:10.1016/j.jcf.2007.01.004.
  19. Liao, F.; Folsom, A.R.; Brancati, F.L. Is low magnesium concentration a risk factor for coronary heart disease? The
  20. Atherosclerosis Risk in Communities (ARIC) Study. Am. Heart J. 1998, 136, 480–490, doi:10.1016/s0002-8703(98)70224-8.
  21. Barbagallo, M.; Dominguez, L.J. Magnesium metabolism in type 2 diabetes mellitus, metabolic syndrome and insulin
  22. magnesium intake and the risk of incident gastric cancer: A prospective cohort analysis of the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study. Int. J. Cancer 2019, doi:10.1002/ijc.32659.
  23. Molina-Montes, E.; Wark, P.A.; Sánchez, M.-J.; Norat, T.; Jakszyn, P.; Luján-Barroso, L.; Michaud, D.S.; Crowe, F.; Allen, N.; Khaw, K.-T.; et al. Dietary intake of iron, heme-iron and magnesium and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort. Int. J. Cancer 2012, 131, E1134–E1147, doi:10.1002/ijc.27547.
  24. Jansen, R.J.; Robinson, D.P.; Stolzenberg-Solomon, R.Z.; Bamlet, W.R.; de Andrade, M.; Oberg, A.L.; Rabe, K.G.; Anderson, K.E.; Olson, J.E.; Sinha, R.; et al. Nutrients from fruit and vegetable consumption reduce the risk of pancreatic cancer. 2013, 44, 152–161, doi:10.1007/s12029-012-9441-y.
  25. Dibaba, D.; Xun, P.; Yokota, K.; White, E.; He, K. Magnesium intake and incidence of pancreatic cancer: The VITamins and Lifestyle study. Br. J. Cancer 2015, 113, 1615–1621, doi:10.1038/bjc.2015.382.
  26. Schilling, K.; Larner, F.; Saad, A.; Roberts, R.; Kocher, H.M.; Blyuss, O.; Halliday, A.N.; Crnogorac-Jurcevic, T. Urine
  27. metallomics signature as an indicator of pancreatic cancer. Metallomics 2020, doi:10.1039/d0mt00061b.
  28. Dai, Q.; Shrubsole, M.J.; Ness, R.M.; Schlundt, D.; Cai, Q.; Smalley, W.E.; Li, M.; Shyr, Y.; Zheng, W. The relation of magne-sium and calcium intakes and a genetic polymorphism in the magnesium transporter to colorectal neoplasia risk. Am. J. Clin. Nutr. 2007, 86, 743–751, doi:10.1093/ajcn/86.3.743.
  29. Gorczyca, A.M.; He, K.; Xun, P.; Margolis, K.L.; Wallace, J.P.; Lane, D.; Thomson, C.; Ho, G.Y.; Shikany, J.M.; Luo, J.
  30. Association between magnesium intake and risk of colorectal cancer among postmenopausal women. Cancer Causes Control 2015, 26, 1761–1769, doi:10.1007/s10552-015-0669-2.
  31. Meng, Y.; Sun, J.; Yu, J.; Wang, C.; Su, J. Dietary intakes of calcium, iron, magnesium, and potassium elements and the risk of colorectal cancer: A meta-analysis. Biol. Trace Elem. Res. 2019, 189, 325–335, doi:10.1007/s12011-018-1474-z.
  32. Polter, E.; Onyeaghala, G.C.; Lutsey, P.L.; Folsom, A.R.; Joshu, C.E.; Platz, E.A.; Prizment, A.E. Prospective association of serum and dietary magnesium with colorectal cancer incidence. Cancer Epidemiol. Biomark. Prev. 2019, doi:10.1158/1055-9965.epi-18-1300.
  33. Wesselink, E.; Kok, D.E.; Bours, M.J.L.; de Wilt, J.H.; van Baar, H.; van Zutphen, M.; Geijsen, A.M.J.R.; Keulen, E.T.P.; Hans-son, B.M.E.; van den Ouweland, J.; et al. Vitamin D, magnesium, calcium, and their interaction in relation to colorectal can-cer
  34. recurrence and all-cause mortality. Am. J. Clin. Nutr. 2020, doi:10.1093/ajcn/nqaa049.
  35. Wesselink, E.; Kok, D.E.; Bours, M.J.L.; de Wilt, J.H.; van Baar, H.; van Zutphen, M.; Geijsen, A.M.J.R.; Keulen, E.T.P.; Hans-son, B.M.E.; van den Ouweland, J.; et al. Vitamin D, magnesium, calcium, and their interaction in relation to colorectal can-cerrecurrence and all-cause mortality. Am. J. Clin. Nutr. 2020, doi:10.1093/ajcn/nqaa049.
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to :
View Times: 488
Revisions: 2 times (View History)
Update Date: 02 Feb 2021