Magnesium intake and cardiovascular disease mortality: A meta-analysis of prospective cohort studies

Over the last two decades, cardiovascular disease (CVD) mortality has declined in many high-income countries but increased at an astonishingly fast rate in low- and middle-income countries. An estimated 17.3 million people died from CVDs in 2008, representing 30% of all global deaths [ [1] WHO The top 10 causes of death. World Health Organization, Geneva, Switzerland2008 Google Scholar ]. CVDs remain the number one cause of death globally. Since 1950s, more and more epidemiological studies focused on magnesium intake and CVD incidence and mortality [ 2 Chiuve S.E. Korngold E.C. Januzzi Jr., J.L. Gantzer M.L. Albert C.M. Plasma and dietary magnesium and risk of sudden cardiac death in women. Am J Clin Nutr. 2011; 93: 253-260 Crossref PubMed Scopus (94) Google Scholar , 3 Iso H. Stampfer M.J. Manson J.E. et al. Prospective study of calcium, potassium, and magnesium intake and risk of stroke in women. Stroke. 1999; 30: 1772-1779 Crossref PubMed Scopus (254) Google Scholar , 4 Kaluza J. Orsini N. Levitan E.B. Brzozowska A. Roszkowski W. Wolk A. Dietary calcium and magnesium intake and mortality: a prospective study of men. Am J Epidemiol. 2010; 171: 801-807 Crossref PubMed Scopus (62) Google Scholar , 5 Larsson S.C. Virtanen M.J. Mars M. et al. Magnesium, calcium, potassium, and sodium intakes and risk of stroke in male smokers. Arch Intern Med. 2008; 168: 459-465 Crossref PubMed Scopus (118) Google Scholar , 6 Leurs L.J. Schouten L.J. Mons M.N. Goldbohm R.A. van den Brandt P.A. Relationship between tap water hardness, magnesium, and calcium concentration and mortality due to ischemic heart disease or stroke in The Netherlands. Environ Health Perspect. 2010; 118: 414-420 Crossref PubMed Scopus (48) Google Scholar , 7 Morris R.W. Walker M. Lennon L.T. Shaper A.G. Whincup P.H. Hard drinking water does not protect against cardiovascular disease: new evidence from the British Regional Heart Study. Eur J Cardiovasc Prev Rehabil. 2008; 15: 185-189 Crossref PubMed Scopus (30) Google Scholar , 8 Song Y. Manson J.E. Cook N.R. Albert C.M. Buring J.E. Liu S. Dietary magnesium intake and risk of cardiovascular disease among women. Am J Cardiol. 2005; 96: 1135-1141 Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar , 9 Zhang W. Iso H. Ohira T. Date C. Tamakoshi A. Associations of dietary magnesium intake with mortality from cardiovascular disease: the JACC study. Atherosclerosis. 2012; 221: 587-595 Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar ]. Controversy still remains between magnesium intake and CVD mortality risk. We conducted a meta-analysis of prospective cohort studies to evaluate the association between magnesium intake and CVD mortality (Table 1). Table 1Characteristics of prospective cohort studies of magnesium intake and cardiovascular disease mortality risk. Study, year, country Cohort size, sex and age Follow-up years Intake comparison Intake assessment Outcome Outcome assessment Adjusted variables Hazard ratios or relative risk (95% CIs) Song et al. [8] Song Y. Manson J.E. Cook N.R. Albert C.M. Buring J.E. Liu S. Dietary magnesium intake and risk of cardiovascular disease among women. Am J Cardiol. 2005; 96: 1135-1141 Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar 2005USA 35,601 women aged 39–89 10 years (median) Median: 433 mg/day vs 255 mg/day FFQ CVD mortality Medical records, autopsy reports, and death certificates Age, randomized treatment assignment, BMI, energy intake, smoking, exercise, alcohol, postmenopausal hormone use, multivitamin use, history of diabetes, hypertension, hypercholesterolemia and parental history of MI at <60 years 1.32 (0.71, 2.47) Kaluza et al. [4] Kaluza J. Orsini N. Levitan E.B. Brzozowska A. Roszkowski W. Wolk A. Dietary calcium and magnesium intake and mortality: a prospective study of men. Am J Epidemiol. 2010; 171: 801-807 Crossref PubMed Scopus (62) Google Scholar 2010Sweden 23,366 men, aged 45–79 10 years ≥481 mg/day vs <426 mg/day FFQ CVD mortality ICD 10 ICD 10 Age, marital status, education, self-reported health status, smoking status, physical activity, waist-to-hip ratio, alcohol consumption, energy-adjusted dietary fiber, saturated fatty acid, vitamin D, calcium and phosphorus intake 1.25 (0.96, 1.61) Zhang et al. [9] Zhang W. Iso H. Ohira T. Date C. Tamakoshi A. Associations of dietary magnesium intake with mortality from cardiovascular disease: the JACC study. Atherosclerosis. 2012; 221: 587-595 Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar 2012Japan 58,615 men and women aged 40–79 14.7 years (median) Median: 294 mg/day vs 173 mg/day for menMedian: 274 mg/day vs 175 mg/day for women FFQ CVD mortalityStroke mortalityCHD mortalityHF mortality ICD 9 and ICD 10 BMI, smoking status, ethanol intake, history of hypertension, history of diabetes mellitus, sports time, walking time, dietary sodium intake, educational status and perceived mental stress, and for women, menopausal status and hormone replacement therapy Men: 1.02 (0.85, 1.22) 1.03 (0.79, 1.35) 0.81 (0.56, 1.18) 0.88 (0.53, 1.46)Women: 0.64 (0.51, 0.80) 0.68 (0.48, 0.96) 0.50 (0.30, 0.84) 0.50 (0.28, 0.87) Chiuve et al. [2] Chiuve S.E. Korngold E.C. Januzzi Jr., J.L. Gantzer M.L. Albert C.M. Plasma and dietary magnesium and risk of sudden cardiac death in women. Am J Clin Nutr. 2011; 93: 253-260 Crossref PubMed Scopus (94) Google Scholar 2011USA 88,375 women aged 30–55 26 years 383 mg/day vs 235 mg/day FFQ CHD mortality Medical records or kin reports History of cardiovascular disease; total calories; smoking; BMI; parental history of myocardial infarction before age 60 years; alcohol intake; physical activity; use of postmenopausal hormones, thiazide diuretics, and aspirin. 22 days/month; and intakes of long-chain omega-3 fatty acid (% of energy), calcium (mg/day), potassium (mg/day), and vitamin D (IU/day); hypertension, hypercholesterolemia, and diabetes 0.66 (0.46, 0.95) Morris et al. [7] Morris R.W. Walker M. Lennon L.T. Shaper A.G. Whincup P.H. Hard drinking water does not protect against cardiovascular disease: new evidence from the British Regional Heart Study. Eur J Cardiovasc Prev Rehabil. 2008; 15: 185-189 Crossref PubMed Scopus (30) Google Scholar 2008England 705 men aged 40–59 years 25 years Per two-fold increase of Mg intake of water Water magnesium concentration analysis and water consumption questionnaire CHD mortality ICD 9 Age, total blood cholesterol, BMI, smoking status, physical activity, alcohol consumption, social class and height 1.09 (0.91, 1.31) Leurs et al. [6] Leurs L.J. Schouten L.J. Mons M.N. Goldbohm R.A. van den Brandt P.A. Relationship between tap water hardness, magnesium, and calcium concentration and mortality due to ischemic heart disease or stroke in The Netherlands. Environ Health Perspect. 2010; 118: 414-420 Crossref PubMed Scopus (48) Google Scholar 2010 Netherlands 4114 men and women aged 55–69 10 years 8.5–26.2 mg/L vs 1.7–3.8 mg/L of Mg concentration of tap water Tap water hardness data in 1986; mailed self-administered questionnaire Stroke mortality, IHD mortality ICD 9 and ICD 10 Age, current smoking, number of cigarettes smoked, years of active smoking, diabetes, hypertension, BMI, dietary calcium, dietary magnesium, saturated fat, mono-unsaturated fat, polyunsaturated fat, fruit and vegetable consumption, alcohol consumption, total energy intake (kilocalories), physical activity, educational level, volume of water consumption, magnesium or calcium concentration in tap water (depending on the exposure variable), use of diuretics, and use of multivitamins with minerals or calcium supplementation. Men: 0.69 (0.37, 1.31) 1.23 (0.82, 1.86) Women: 0.77 (0.38, 1.57) 0.89 (0.50, 1.59) CVD: cardiovascular disease; IHD: ischemic heart disease; HF: heart failure; BMI: body mass index; FFQ: food-frequency questionnaire. ICD: International classification of disease. Open table in a new tab CVD: cardiovascular disease; IHD: ischemic heart disease; HF: heart failure; BMI: body mass index; FFQ: food-frequency questionnaire. ICD: International classification of disease.