Effect of drinking water calcium, magnesium, and hardness on colorectal cancer mortality: A systematic review

Mattia Acito; Edoardo Franceschini; Tommaso Rondini; Francesca Serio; Cristina Fatigoni; Milena Villarini; Massimo Moretti

doi:10.23750/abm.2026.17178

Effect of drinking water calcium, magnesium, and hardness on colorectal cancer mortality: A systematic review

Authors

Mattia Acito School of Pharmacy, University of Camerino, Camerino, Italy https://orcid.org/0000-0003-1808-1999
Edoardo Franceschini Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy https://orcid.org/0009-0008-3769-6706
Tommaso Rondini Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy https://orcid.org/0009-0007-2687-3255
Francesca Serio Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy. https://orcid.org/0000-0002-2782-2798
Cristina Fatigoni Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy https://orcid.org/0000-0002-7495-8671
Milena Villarini Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy https://orcid.org/0000-0002-8769-883X
Massimo Moretti Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy https://orcid.org/0000-0002-5038-8619

Keywords:

calcium, magnesium, hardness, drinking water, colorectal cancer

Abstract

Background and aim: This systematic review aimed to summarise findings from studies investigating the association between calcium, magnesium, and drinking water hardness and colorectal cancer mortality.

Methods: A systematic literature search was conducted on PubMed, Scopus, and Web of Science databases. The work was carried out according to the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The protocol was registered in Open Science Framework (OSF) Registries (https://doi.org/10.17605/OSF.IO/5HEVS).

Results: One hundred thirty-three records were identified, and at the end of the selection process, nine studies met the inclusion criteria. All the studies were conducted before 2011 in the same geographical area (Taiwan, China). All the studies suggested a protective effect of higher calcium concentration in drinking water towards colon cancer mortality, whereas the effects on rectal cancer mortality were mixed. High water hardness seems to be protective towards mortality from both cancer types.

Conclusions: This systematic review found interesting results on the potential role of calcium-rich water in the management of colon cancer. These results, however, should be confirmed in novel, large and preferably longitudinal studies conducted in other parts of the world before drawing definitive conclusions.

References

1. Sharma R, Abbasi-Kangevari M, Abd-Rabu R, et al. Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the global burden of disease study 2019. Lancet Gastroenterol Hepatol. 2022;7:627–47. doi: 10.1016/S2468-1253(22)00044-9.

2. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834.

3. International Agency for Research on Cancer. Global Cancer Observatory: Cancer Today 2024. Available from: https://gco.iarc.who.int/today.

4. Vos T, Lim SS, Abbafati C, et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the global burden of disease study 2019. Lancet. 2020;396:1204–22. doi: 10.1016/S0140-6736(20)30925-9.

5. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66:683–91. doi: 10.1136/gutjnl-2015-310912.

6. Smith RA, Fedewa S, Siegel R. Early colorectal cancer detection—current and evolving challenges in evidence, guidelines, policy, and practices. In: Berger FG, Boland CR, eds. Adv. Cancer Res. Academic Press; 2021. p. 69–107. doi: 10.1016/bs.acr.2021.03.005.

7. Centers for Disease Control and Prevention. What are the risk factors for colorectal cancer? 2023. Available from: https://www.cdc.gov/cancer/colorectal/basic_info/risk_factors.htm

8. World Cancer Research Fund. Colorectal cancer – what causes colorectal cancer? 2018. Available from: https://www.wcrf.org/diet-activity-and-cancer/cancer-types/colorectal-cancer/

9. National Institutes of Health. Calcium – fact sheet for consumers. 2022. Available from: https://ods.od.nih.gov/factsheets/Calcium-Consumer/

10. Jin S, Kim Y, Je Y. Dairy consumption and risks of colorectal cancer incidence and mortality: a meta-analysis of prospective cohort studies. Cancer Epidemiol Biomark Prev. 2020;29:2309–22. doi: 10.1158/1055-9965.EPI-20-0127.

11. Zhao Z, Wu D, Gao S, et al. The association between dairy products consumption and prostate cancer risk: a systematic review and meta-analysis. Br J Nutr. 2023;129:1714–31. doi: 10.1017/S0007114522002380.

12. Rosborg I, Nihlgård B. Health consequences of acid rain in south west Sweden. J Geosci Environ Prot. 2018;6:126–42. doi: 10.4236/gep.2018.62009.

13. Lipkin M, Newmark H. Calcium and the prevention of colon cancer. J Cell Biochem Suppl. 1995;22:65–73. doi: 10.1002/jcb.240590810.

14. Pence BC. Role of calcium in colon cancer prevention: experimental and clinical studies. Mutat Res. 1993;290:87–95. doi: 10.1016/0027-5107(93)90036-f.

15. World Cancer Research Fund. Vitamins, minerals and other nutrients and cancer risk. 2018. Available from: https://www.wcrf.org/diet-activity-and-cancer/risk-factors/vitamins-minerals-and-other-nutrients-and-cancer-risk/

16. Jahnen-Dechent W, Ketteler M. Magnesium basics. Clin Kidney J. 2012;5:i3–14. doi: 10.1093/ndtplus/sfr163.

17. 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;189:325–35. doi: 10.1007/s12011-018-1474-z.

18. Qu X, Jin F, Hao Y, et al. Nonlinear association between magnesium intake and the risk of colorectal cancer. Eur J Gastroenterol Hepatol. 2013;25:309–18. doi: 10.1097/MEG.0b013e32835c073c.

19. Bagheri A, Naghshi S, Sadeghi O, Larijani B, Esmaillzadeh A. Total, dietary, and supplemental magnesium intakes and risk of all-cause, cardiovascular, and cancer mortality: a systematic review and dose-response meta-analysis of prospective cohort studies. Adv Nutr. 2021;12:1196–210. doi: 10.1093/advances/nmab001.

20. Kozisek F. Regulations for calcium, magnesium or hardness in drinking water in the European Union member states. Regul Toxicol Pharmacol. 2020;112:104589. doi: 10.1016/j.yrtph.2020.104589.

21. World Health Organization. Hardness in drinking-water. Background document for development of WHO Guidelines for Drinking-water Quality. 2011. Available from: https://cdn.who.int/media/docs/default-source/wash-documents/wash-chemicals/hardness-bd.pdf?sfvrsn=a13853a9_4.

22. Suzuki M, Wu S, Ootawa T, et al. Relationship between regional distribution of centenarians and drinking water hardness in the Amami Islands, Kagoshima Prefecture, Japan. Nutrients. 2023;15:1569. doi: 10.3390/nu15071569.

23. Yang CY, Tsai SS, Lai TC, Hung CF, Chiu HF. Rectal cancer mortality and total hardness levels in Taiwan’s drinking water. Environ Res. 1999;80:311–6. doi: 10.1006/enrs.1998.3921.

24. Yang CY, Hung CF. Colon cancer mortality and total hardness levels in Taiwan’s drinking water. Arch Environ Contam Toxicol. 1998;35:148–51. doi: 10.1007/s002449900362.

25. Chang CC, Chen CC, Wu DC, Yang CY. Nitrates in drinking water and the risk of death from rectal cancer: does hardness in drinking water matter? J Toxicol Environ Health A. 2010;73:1337–47. doi: 10.1080/15287394.2010.490178.

26. Kuo HW, Peng CY, Feng A, Wu TN, Yang CY. Magnesium in drinking water modifies the association between trihalomethanes and the risk of death from colon cancer. J Toxicol Environ Health A. 2011;74:392–403. doi: 10.1080/15287394.2011.538836.

27. Higgins JPT, Altman DG, Gøtzsche PC, et al. The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. doi: 10.1136/bmj.d5928.

28. Higgins JPT, Thomas J. Cochrane handbook for systematic reviews of interventions. 2023. Available from: https://training.cochrane.org/handbook/current

29. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700. doi: 10.1136/bmj.b2700.

30. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097. doi: 10.1371/journal.pmed.1000097.

31. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71.

32. Brown P, Brunnhuber K, Chalkidou K, et al. How to formulate research recommendations. BMJ. 2006;333:804–6. doi: 10.1136/bmj.38987.492014.94.

33. Yang CY, Chiu HF, Chiu JF, Tsai SS, Cheng MF. Calcium and magnesium in drinking water and risk of death from colon cancer. Jpn J Cancer Res Gann. 1997;88:928–33. doi: 10.1111/j.1349-7006.1997.tb00310.x.

34. Chiu HF, Tsai SS, Chen PS, Wu TN, Yang CY. Does calcium in drinking water modify the association between nitrate in drinking water and risk of death from colon cancer? J Water Health. 2011;9:498–506. doi: 10.2166/wh.2011.006.

35. Yang CY, Chiu HF. Calcium and magnesium in drinking water and risk of death from rectal cancer. Int J Cancer. 1998;77:528–32. doi: 10.1002/(sici)1097-0215(19980812)77:4<528::aid-ijc9>3.0.co;2-w.

36. Kuo HW, Chen PS, Ho SC, Wang LY, Yang CY. Trihalomethanes in drinking water and the risk of death from rectal cancer: does hardness in drinking water matter? J Toxicol Environ Health A. 2010;73:807–18. doi: 10.1080/15287391003689267.

37. Kuo HW, Tiao MM, Tsai SS, Wu TN, Yang CY. Does calcium in drinking water modify the association between trihalomethanes and the risk of death from colon cancer? J Toxicol Environ Health A. 2010;73:657–68. doi: 10.1080/15287390903578513.

38. Beggs MR, Bhullar H, Dimke H, Alexander RT. The contribution of regulated colonic calcium absorption to the maintenance of calcium homeostasis. J Steroid Biochem Mol Biol. 2022;220:106098. doi: 10.1016/j.jsbmb.2022.106098.

39. Diaz de Barboza G, Guizzardi S, Tolosa de Talamoni N. Molecular aspects of intestinal calcium absorption. World J Gastroenterol. 2015;21:7142–54. doi: 10.3748/wjg.v21.i23.7142.

40. Bronner F, Pansu D. Nutritional aspects of calcium absorption. J Nutr. 1999;129:9–12. doi: 10.1093/jn/129.1.9.

41. Ohta A, Ohtsuki M, Baba S, Adachi T, Sakata T, Sakaguchi E. Calcium and magnesium absorption from the colon and rectum are increased in rats fed fructooligosaccharides. J Nutr. 1995;125:2417–24. doi: 10.1093/jn/125.9.2417.

42. Trinidad TP, Wolever TM, Thompson LU. Effect of acetate and propionate on calcium absorption from the rectum and distal colon of humans. Am J Clin Nutr. 1996;63:574–8. doi: 10.1093/ajcn/63.4.574.

43. World Cancer Research Fund. Prostate cancer – what causes prostate cancer? 2018. Available from: https://www.wcrf.org/diet-activity-and-cancer/cancer-types/prostate-cancer/

44. de Baaij JHF, Hoenderop JGJ, Bindels RJM. Magnesium in man: implications for health and disease. Physiol Rev. 2015;95:1–46. doi: 10.1152/physrev.00012.2014.

45. EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA). Scientific opinion on dietary reference values for water. EFSA J. 2010;8:1459. doi: 10.2903/j.efsa.2010.1459.

46. Institute of Medicine of the National Academies. Dietary reference intakes for water, potassium, sodium, chloride, and sulfate. 2004. doi: 10.17226/10925.

47. National Health Service. Water, drinks and hydration. 2023. Available from: https://www.nhs.uk/live-well/eat-well/food-guidelines-and-food-labels/water-drinks-nutrition/

48. Feretti D, Acito M, Dettori M, et al. Genotoxicity of source, treated and distributed water from four drinking water treatment plants supplied by surface water in Sardinia, Italy. Environ Res. 2020;185:109385. doi: 10.1016/j.envres.2020.109385.

49. Yang CY, Chiu HF, Cheng MF, Hsu TY, Cheng MF, Wu TN. Calcium and magnesium in drinking water and the risk of death from breast cancer. J Toxicol Environ Health A. 2000;60:231–41.

50. Tsilidis K. Vitamins, minerals, and their link to breast cancer. 2020. Available from: https://www.wcrf.org/vitamins-minerals-and-their-link-to-breast-cancer/

51. World Cancer Research Fund. Breast cancer – what causes breast cancer? 2018. Available from: https://www.wcrf.org/diet-activity-and-cancer/cancer-types/breast-cancer/

52. Acito M, Natalucci V, Rondini T, et al. The DianaWeb cohort during the first COVID-19 lockdown: changes in eating behaviour in women with breast cancer. Acta Bio-Medica Atenei Parm. 2023;94:e2023135. doi: 10.23750/abm.v94iS3.14285.

53. Acito M, Rondini T, Gargano G, Moretti M, Villarini M, Villarini A. How the COVID-19 pandemic has affected eating habits and physical activity in breast cancer survivors: the DianaWeb study. J Cancer Surviv Res Pract. 2022. doi: 10.1007/s11764-022-01294-w.

54. Gianfredi V, Nucci D, Balzarini M, et al. E-coaching: the DianaWeb study to prevent breast cancer recurrences. Clin Ter. 2020;170:e59–65. doi: 10.7417/CT.2020.2190.

55. Brown EM, MacLeod RJ. Extracellular calcium sensing and extracellular calcium signaling. Physiol Rev. 2001;81(1):239–97. doi: 10.1152/physrev.2001.81.1.239.

56. Hardwick LL, Jones MR, Brautbar N, Lee DB. Magnesium absorption: mechanisms and the influence of vitamin D, calcium and phosphate. J Nutr. 1991;121(1):13–23. doi: 10.1093/jn/121.1.13.

57. Norman DA, Fordtran JS, Brinkley LJ, et al. Jejunal and ileal adaptation to alterations in dietary calcium: changes in calcium and magnesium absorption and pathogenetic role of parathyroid hormone and 1,25-dihydroxyvitamin D. J Clin Invest. 1981;67(6):1599–603. doi: 10.1172/jci110194.

58. Nielsen FH, Milne DB, Gallagher S, Johnson L, Hoverson B. Moderate magnesium deprivation results in calcium retention and altered potassium and phosphorus excretion by postmenopausal women. Magnes Res. 2007;20(1):19–31. doi: 10.1684/mrh.2007.0089.

59. Bussière FI, Gueux E, Rock E, Mazur A, Rayssiguier Y. Protective effect of calcium deficiency on the inflammatory response in magnesium-deficient rats. Eur J Nutr. 2002;41(5):197–202. doi: 10.1007/s00394-002-0376-0.

60. Swaminath S, Um CY, Prizment AE, Lazovich D, Bostick RM. Combined mineral intakes and risk of colorectal cancer in postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2019;28(2):392–9. doi: 10.1158/1055-9965.EPI-18-0412.

61. Dai Q, Shrubsole MJ, Ness RM, et al. The relation of magnesium and calcium intakes and a genetic polymorphism in the magnesium transporter to colorectal neoplasia risk. Am J Clin Nutr. 2007;86(3):743–51. doi: 10.1093/ajcn/86.3.743.

62. Zhu X, Shrubsole MJ, Ness RM, et al. Calcium/magnesium intake ratio, but not magnesium intake, interacts with genetic polymorphism in relation to colorectal neoplasia in a two-phase study. Mol Carcinog. 2016;55(10):1449–57. doi: 10.1002/mc.22387.

63. Dai Q, Sandler R, Barry E, Summers R, Grau M, Baron J. Calcium, magnesium, and colorectal cancer. Epidemiology. 2012;23(3):504–5. doi: 10.1097/EDE.0b013e31824deb09.

64. Zhao J, Giri A, Zhu X, et al. Calcium: magnesium intake ratio and colorectal carcinogenesis, results from the prostate, lung, colorectal, and ovarian cancer screening trial. Br J Cancer. 2019;121(9):796–804. doi: 10.1038/s41416-019-0579-2.

65. Dai Q, Shu XO, Deng X, et al. Modifying effect of calcium/magnesium intake ratio and mortality: a population-based cohort study. BMJ Open. 2013;3(2):e002111. doi: 10.1136/bmjopen-2012-002111.

66. Higgins JPT, Morgan RL, Rooney AA, et al. A tool to assess risk of bias in non-randomized follow-up studies of exposure effects (ROBINS-E). Environ Int. 2024;186:108602. doi: 10.1016/j.envint.2024.108602.