Modifying effect of calcium/magnesium intake ratio and mortality: a population-based cohort study

Objectives Magnesium (Mg) and calcium (Ca) antagonise each other in (re)absorption, inflammation and many other physiological activities. Based on mathematical estimation, the absorbed number of Ca or Mg depends on the dietary ratio of Ca to Mg intake. We hypothesise that the dietary Ca/Mg ratio modifies the effects of Ca and Mg on mortality due to gastrointestinal tract cancer and, perhaps, mortality due to diseases occurring in other organs or systems. Design Prospective studies. Setting Population-based cohort studies (The Shanghai Women's Health Study and the Shanghai Men's Health Study) conducted in Shanghai, China. Participants 74 942 Chinese women aged 40–70 years and 61 500 Chinese men aged 40–74 years participated in the study. Primary outcome measures All-cause mortality and disease-specific mortality. Results In this Chinese population with a low Ca/Mg intake ratio (a median of 1.7 vs around 3.0 in US populations), intakes of Mg greater than US Recommended Daily Allowance (RDA) levels (320 mg/day among women and 420 mg/day among men) were related to increased risks of total mortality for both women and men. Consistent with our hypothesis, the Ca/Mg intake ratio significantly modified the associations of intakes of Ca and Mg with mortality risk, whereas no significant interactions between Ca and Mg in relation to outcome were found. The associations differed by gender. Among men with a Ca/Mg ratio >1.7, increased intakes of Ca and Mg were associated with reduced risks of total mortality, and mortality due to coronary heart diseases. In the same group, intake of Ca was associated with a reduced risk of mortality due to cancer. Among women with a Ca/Mg ratio ≤1.7, intake of Mg was associated with increased risks of total mortality, and mortality due to cardiovascular diseases and colorectal cancer. Conclusions These results, if confirmed, may help to understand the optimal balance between Ca and Mg in the aetiology and prevention of these common diseases and reduction in mortality.

[1]  R. Lau,et al.  Magnesium intake and colorectal tumor risk: a case-control study and meta-analysis. , 2012, The American journal of clinical nutrition.

[2]  J. Baron,et al.  Calcium, magnesium, and colorectal cancer. , 2012, Epidemiology.

[3]  A. Tamakoshi,et al.  Associations of dietary magnesium intake with mortality from cardiovascular disease: the JACC study. , 2012, Atherosclerosis.

[4]  W. Willett,et al.  Magnesium intake, plasma C-peptide, and colorectal cancer incidence in US women: a 28-year follow-up study , 2012, British Journal of Cancer.

[5]  S. Larsson,et al.  Dietary magnesium intake and risk of stroke: a meta-analysis of prospective studies. , 2012, The American journal of clinical nutrition.

[6]  K. He,et al.  Magnesium Intake and Risk of Type 2 Diabetes , 2011, Diabetes Care.

[7]  R. Kaaks,et al.  Dietary calcium and magnesium intake in relation to cancer incidence and mortality in a German prospective cohort (EPIC-Heidelberg) , 2011, Cancer Causes & Control.

[8]  X. Shu,et al.  Cruciferous vegetable consumption is associated with a reduced risk of total and cardiovascular disease mortality. , 2011, The American journal of clinical nutrition.

[9]  D. Barocas,et al.  Blood Magnesium, and the Interaction with Calcium, on the Risk of High-Grade Prostate Cancer , 2011, PloS one.

[10]  A. Avenell,et al.  Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis , 2011, BMJ : British Medical Journal.

[11]  B. Clarke,et al.  Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis , 2011 .

[12]  A. Rosanoff Rising Ca:Mg intake ratio from food in USA Adults: a concern? , 2010, Magnesium research.

[13]  A. Avenell,et al.  Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis , 2010, BMJ : British Medical Journal.

[14]  A. Wolk,et al.  Dietary calcium and magnesium intake and mortality: a prospective study of men. , 2010, American journal of epidemiology.

[15]  X. Shu,et al.  Is green tea drinking associated with a later onset of breast cancer? , 2010, Annals of epidemiology.

[16]  David W. Hosmer,et al.  Applied Survival Analysis: Regression Modeling of Time-to-Event Data , 2008 .

[17]  W. Zheng,et al.  The relation of magnesium and calcium intakes and a genetic polymorphism in the magnesium transporter to colorectal neoplasia risk. , 2007, The American journal of clinical nutrition.

[18]  Alan D. Lopez,et al.  Validation of cause-of-death statistics in urban China. , 2007, International journal of epidemiology.

[19]  X. Shu,et al.  A Prospective Study of Dietary Patterns and Mortality in Chinese Women , 2007, Epidemiology.

[20]  X. Shu,et al.  Validity and reproducibility of the food-frequency questionnaire used in the Shanghai men's health study. , 2007, The British journal of nutrition.

[21]  F. Nielsen,et al.  Moderate magnesium deprivation results in calcium retention and altered potassium and phosphorus excretion by postmenopausal women. , 2007, Magnesium research.

[22]  R. Goldbohm,et al.  Magnesium intake and colorectal cancer risk in the Netherlands Cohort Study , 2007, British Journal of Cancer.

[23]  F. Wolf,et al.  Magnesium and neoplasia: from carcinogenesis to tumor growth and progression or treatment. , 2007, Archives of biochemistry and biophysics.

[24]  J. Manson,et al.  Effects of oral magnesium supplementation on glycaemic control in Type 2 diabetes: a meta‐analysis of randomized double‐blind controlled trials , 2006, Diabetic medicine : a journal of the British Diabetic Association.

[25]  D. Hosking,et al.  Vitamin D insufficiency and the blunted PTH response in established osteoporosis: the role of magnesium deficiency , 2006, Osteoporosis International.

[26]  P. Savage,et al.  Magnesium Intake and Incidence of Metabolic Syndrome Among Young Adults , 2006, Circulation.

[27]  A. Folsom,et al.  Magnesium intake and reduced risk of colon cancer in a prospective study of women. , 2006, American journal of epidemiology.

[28]  N. Rothman,et al.  The Shanghai Women's Health Study: rationale, study design, and baseline characteristics. , 2005, American journal of epidemiology.

[29]  X. Shu,et al.  Sources of variation in nutrient intakes among men in Shanghai, China , 2005, Public Health Nutrition.

[30]  G. Sigurdsson,et al.  Relationship between serum parathyroid hormone levels, vitamin D sufficiency, and calcium intake. , 2005, JAMA.

[31]  J. Manson,et al.  Dietary magnesium intake and risk of cardiovascular disease among women. , 2005, The American journal of cardiology.

[32]  F. Lang,et al.  Thymocyte K+, Na+ and Water Balance During Dexamethasone- and Etoposide-Induced Apoptosis , 2005, Cellular Physiology and Biochemistry.

[33]  D. Ziegler Type 2 diabetes as an inflammatory cardiovascular disorder. , 2005, Current molecular medicine.

[34]  S. Larsson,et al.  Magnesium intake in relation to risk of colorectal cancer in women. , 2005, JAMA.

[35]  J. Hoenderop,et al.  Epithelial Ca2+ and Mg2+ channels in health and disease. , 2004, Journal of the American Society of Nephrology : JASN.

[36]  M. Bindels Epithelial Ca 2 and Mg 2 Channels in Health and Disease , 2005 .

[37]  H. Cai,et al.  Variation in nutrient intakes among women in Shanghai, China , 2004, European Journal of Clinical Nutrition.

[38]  B. Altura,et al.  Benefits and Risks of Sex Hormone Replacement in Postmenopausal Women , 2004, Journal of the American College of Nutrition.

[39]  M. Karagas,et al.  Effect of calcium supplementation on the risk of large bowel polyps. , 2004, Journal of the National Cancer Institute.

[40]  Jacqueline D Wright,et al.  Dietary intake of selected minerals for the United States population: 1999-2000. , 2004, Advance data.

[41]  E. Rimm,et al.  Magnesium Intake and Risk of Coronary Heart Disease among Men , 2004, Journal of the American College of Nutrition.

[42]  J. Hoenderop,et al.  Epithelial Ca 2 (cid:1) and Mg 2 (cid:1) Channels in Health and Disease , 2004 .

[43]  X. Shu,et al.  Validity and reproducibility of the food frequency questionnaire used in the Shanghai Women's Health Study , 2004, European Journal of Clinical Nutrition.

[44]  J. Manson,et al.  Dietary magnesium intake in relation to plasma insulin levels and risk of type 2 diabetes in women. , 2004, Diabetes care.

[45]  J. Manson,et al.  Magnesium intake and risk of type 2 diabetes in men and women. , 2004, Diabetes care.

[46]  D. D. Bansal,et al.  Effect of magnesium supplementation on oxidative stress in alloxanic diabetic rats. , 2003, Magnesium research.

[47]  E. Giovannucci Diet, body weight, and colorectal cancer: a summary of the epidemiologic evidence. , 2003, Journal of women's health.

[48]  M. Konrad,et al.  Genetics of hereditary disorders of magnesium homeostasis , 2003, Pediatric Nephrology.

[49]  E. Rock,et al.  Protective effect of calcium deficiency on the inflammatory response in magnesium-deficient rats , 2002, European journal of nutrition.

[50]  Jing Liu,et al.  Sino-MONICA Project: A Collaborative Study on Trends and Determinants in Cardiovascular Diseases in China, Part I: Morbidity and Mortality Monitoring , 2001, Circulation.

[51]  E. Brown,et al.  Extracellular calcium sensing and extracellular calcium signaling. , 2001, Physiological reviews.

[52]  Peter Lipp,et al.  Calcium - a life and death signal , 1998, Nature.

[53]  A. Folsom,et al.  Is low magnesium concentration a risk factor for coronary heart disease? The Atherosclerosis Risk in Communities (ARIC) Study. , 1998, American heart journal.

[54]  E L Korn,et al.  Time-to-event analysis of longitudinal follow-up of a survey: choice of the time-scale. , 1997, American journal of epidemiology.

[55]  Martin D. Bootman,et al.  The elemental principles of calcium signaling , 1995, Cell.

[56]  H. Spencer,et al.  Effect of magnesium on the intestinal absorption of calcium in man. , 1994, Journal of the American College of Nutrition.

[57]  G. Paolisso,et al.  Daily magnesium supplements improve glucose handling in elderly subjects. , 1992, The American journal of clinical nutrition.

[58]  J. Manson,et al.  Diet and risk of clinical diabetes in women. , 1992, The American journal of clinical nutrition.

[59]  N. Brautbar,et al.  Magnesium absorption: mechanisms and the influence of vitamin D, calcium and phosphate. , 1991, The Journal of nutrition.

[60]  P. Savage,et al.  Correlates of fasting insulin levels in young adults: the CARDIA study. , 1991, Journal of clinical epidemiology.

[61]  P. Flatman Mechanisms of magnesium transport. , 1991, Annual review of physiology.

[62]  Seelig Ms Increased need for magnesium with the use of combined oestrogen and calcium for osteoporosis treatment. , 1990 .

[63]  Singh Rb Effect of dietary magnesium supplementation in the prevention of coronary heart disease and sudden cardiac death. , 1990, Magnesium and trace elements.

[64]  R. Singh Effect of dietary magnesium supplementation in the prevention of coronary heart disease and sudden cardiac death. , 1990, Magnesium and trace elements.

[65]  M. Seelig Increased need for magnesium with the use of combined oestrogen and calcium for osteoporosis treatment. , 1990, Magnesium research.

[66]  J. French,et al.  Magnesium: nature's physiologic calcium blocker. , 1984, American heart journal.

[67]  S. Strowig,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. , 1981, The Journal of clinical investigation.

[68]  J. Ferlay,et al.  Cancer Incidence in Five Continents , 1970, Union Internationale Contre Le Cancer / International Union against Cancer.

[69]  M. Seelig THE REQUIREMENT OF MAGNESIUM BY THE NORMAL ADULT. SUMMARY AND ANALYSIS OF PUBLISHED DATA. , 1964, The American journal of clinical nutrition.