Some recent reports suggest that calcium supplement use may increase risk of cardiovascular disease. In a prospective cohort study of 74,245 women in the Nurses' Health Study with 24 years of follow-up, we found no independent associations between supplemental calcium intake and risk of incident coronary heart disease (CHD) and stroke.
Some recent reports suggest that calcium supplements may increase cardiovascular disease (CVD) risk. The objective was to examine the independent associations between calcium supplement use and risk of CVD.
We conducted a prospective cohort study of supplemental calcium use and incident CVD in 74,245 women in the Nurses' Health Study (1984–2008) free of CVD and cancer at baseline. Calcium supplement intake was assessed every 4 years. Outcomes were incident CHD (nonfatal or fatal MI) and stroke (ischemic or hemorrhagic), confirmed by medical record review.
During 24 years of follow-up, 4,565 cardiovascular events occurred (2,709 CHD and 1,856 strokes). At baseline, women who took calcium supplements had higher levels of physical activity, smoked less, and had lower trans fat intake compared with those who did not take calcium supplements. After multivariable adjustment for age, body mass index, dietary calcium, vitamin D intake, and other CVD risk factors, the relative risk of CVD for women taking >1,000 mg/day of calcium supplements compared with none was 0.82 (95 % confidence interval [CI] 0.74 to 0.92; p for trend <0.001). For women taking >1,000 mg/day of calcium supplements compared with none, the multivariable-adjusted relative risk for CHD was 0.71 (0.61 to 0.83; p for trend < 0.001) and for stroke was 1.03 (0.87 to 1.21; p for trend = 0.61). The relative risks were similar in analyses limited to non-smokers, women without hypertension, and women who had regular physical exams.
Our findings do not support the hypothesis that calcium supplement intake increases CVD risk in women.
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Gahche J, Bailey R, Burt V, Hughes J, Yetley E, Dwyer J, Picciano M, McDowell M, Sempos C (2011) Dietary supplement use among U.S. adults has increased since NHANES III (1988–1994). NCHS Data Brief 61:1–8
Reid I, Mason B, Horne A, Ames R, Clearwater J, Bava U, Orr-Walker B, Wu F, Evans M, Gamble G (2002) Effects of calcium supplementation on serum lipid concentrations in normal older women: a randomized controlled trial. Am J Med 112:343–347
Griffith L, Guyatt G, Cook R, Bucher H, Cook D (1999) The influence of dietary and nondietary calcium supplementation on blood pressure: an updated metaanalysis of randomized controlled trials. Am J Hypertens 12(1 Pt 1):84–92
Heller HJ, Greer LG, Haynes SD, Poindexter JR, Pak CY (2000) Pharmacokinetic and pharmacodynamic comparison of two calcium supplements in postmenopausal women. J Clin Pharmacol 40:1237–1244
Rubin M, Rundek T, McMahon D, Lee H, Sacco R, Silverberg S (2007) Carotid artery plaque thickness is associated with increased serum calcium levels: the Northern Manhattan study. Atherosclerosis 194:426–432
Foley RN, Collins AJ, Ishani A, Kalra PA (2008) Calcium-phosphate levels and cardiovascular disease in community-dwelling adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J 156:556–563
Wang L, Manson JE, Sesso HD (2012) Calcium intake and risk of cardiovascular disease: a review of prospective studies and randomized clinical trials. Am J Cardiovasc Drugs 12:105–116
Reid IR, Bolland MJ, Avenell A, Grey A (2011) Cardiovascular effects of calcium supplementation. Osteoporos Int 22:1649–1658
Wang L, Manson J, Song Y, Sesso H (2010) Systematic review: Vitamin D and calcium supplementation in prevention of cardiovascular events. Ann Intern Med 152:315–323
Abrahamsen B, Sahota O (2011) Do calcium plus vitamin D supplements increase cardiovascular risk? BMJ 342:d2080
Reid IR, Bolland MJ, Grey A (2010) Does calcium supplementation increase cardiovascular risk? Clin Endocrinol 73:689–695
Michaelsson K, Melhus H, Warensjo Lemming E, Wolk A, Byberg L (2013) Long term calcium intake and rates of all cause and cardiovascular mortality: community based prospective longitudinal cohort study. BMJ 346:f228
Xiao Q, Murphy RA, Houston DK, Harris TB, Chow WH, Park Y (2013) Dietary and supplemental calcium intake and cardiovascular disease mortality: the National Institutes of Health-AARP Diet and Health Study. JAMA Intern Med 1–8
Bolland M, Barber P, Doughty R, Mason B, Horne A, Ames R, Gamble G, Grey A, Reid I (2008) Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ 336:262–266
Reid IR, Ames RW, Evans MC, Gamble GD, Sharpe SJ (1995) Long-term effects of calcium supplementation on bone loss and fractures in postmenopausal women: a randomized controlled trial. Am J Med 98:331–335
Reid IR, Mason B, Horne A, Ames R, Reid HE, Bava U, Bolland MJ, Gamble GD (2006) Randomized controlled trial of calcium in healthy older women. Am J Med 119:777–785
Reid IR, Ames RW, Evans MC, Gamble GD, Sharpe SJ (1993) Effect of calcium supplementation on bone loss in postmenopausal women. N Engl J Med 328:460–464
Baron JA, Beach M, Mandel JS et al (1999) Calcium supplements for the prevention of colorectal adenomas. Calcium Polyp Prevention Study Group. N Engl J Med 340:101–107
Prince RL, Devine A, Dhaliwal SS, Dick IM (2006) Effects of calcium supplementation on clinical fracture and bone structure: results of a 5-year, double-blind, placebo-controlled trial in elderly women. Arch Intern Med 166:869–875
Riggs BL, O'Fallon WM, Muhs J, O'Connor MK, Kumar R, Melton LJ 3rd (1998) Long-term effects of calcium supplementation on serum parathyroid hormone level, bone turnover, and bone loss in elderly women. J Bone Miner Res 13:168–174
Bonnick S, Broy S, Kaiser F, Teutsch C, Rosenberg E, DeLucca P, Melton M (2007) Treatment with alendronate plus calcium, alendronate alone, or calcium alone for postmenopausal low bone mineral density. Curr Med Res Opin 23:1341–1349
Grant AM, Avenell A, Campbell MK et al (2005) Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Lancet 365:1621–1628
Bonithon-Kopp C, Kronborg O, Giacosa A, Rath U, Faivre J (2000) Calcium and fibre supplementation in prevention of colorectal adenoma recurrence: a randomised intervention trial. European Cancer Prevention Organisation Study Group. Lancet 356:1300–1306
Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP (2007) Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr 85:1586–1591
Bolland M, Avenell A, Baron J, Grey A, MacLennan G, Gamble G, Reid I (2010) Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 341:c3691
Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR (2011) 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. BMJ 342:d2040
Lewis JR, Calver J, Zhu K, Flicker L, Prince RL (2011) Calcium supplementation and the risks of atherosclerotic vascular disease in older women: results of a 5-year RCT and a 4.5-year follow-up. J Bone Miner Res 26:35–41
Brazier M, Grados F, Kamel S, Mathieu M, Morel A, Maamer M, Sebert JL, Fardellone P (2005) Clinical and laboratory safety of one year's use of a combination calcium + vitamin D tablet in ambulatory elderly women with vitamin D insufficiency: results of a multicenter, randomized, double-blind, placebo-controlled study. Clin Ther 27:1885–1893
Hsia J, Heiss G, Ren H et al (2007) Calcium/vitamin D supplementation and cardiovascular events. Circulation 115:846–854
Lappe JM, Heaney RP (2008) Calcium supplementation: Results may not be generalisable. BMJ 336:403; author reply 404
Pentti K, Tuppurainen M, Honkanen R, Sandini L, Kröger H, Alhava E, Saarikoski S (2009) Use of calcium supplements and the risk of coronary heart disease in 52–62-year-old women: the Kuopio Osteoporosis Risk Factor and Prevention Study. Maturitas 63:73–78
Li K, Kaaks R, Linseisen J, Rohrmann S (2012) Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition study (EPIC-Heidelberg). Heart 98:920–925
Prentice RL, Pettinger MB, Jackson RD et al (2013) Health risks and benefits from calcium and vitamin D supplementation: Women's Health Initiative clinical trial and cohort study. Osteoporos Int 24:567–580
Bostick R, Kushi L, Wu Y, Meyer K, Sellers T, Folsom A (1999) Relation of calcium, vitamin D, and dairy food intake to ischemic heart disease mortality among postmenopausal women. Am J Epidemiol 149:151–161
Willett W, Sampson L, Stampfer M, Rosner B, Bain C, Witschi J, Hennekens C, Speizer F (1985) Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol 122:51–65
Salvini S, Hunter D, Sampson L, Stampfer M, Colditz G, Rosner B, Willett W (1989) Food-based validation of a dietary questionnaire: the effects of week-to-week variation in food consumption. Int J Epidemiol 18:858–867
Fung TT, Chiuve SE, McCullough ML, Rexrode KM, Logroscino G, Hu FB (2008) Adherence to a DASH-style diet and risk of coronary heart disease and stroke in women. Arch Intern Med 168:713–720
Rimm E, Stampfer M, Colditz GA, Chute C, Litin L, Willett W (1990) Validity of self-reported waist and hip circumference in men and women. Epidemiology 1:466–473
Wolf A, Hunter D, Colditz G, Manson J, Stampfer M, Corsano K, Rosner B, Kriska A, Willett W (1994) Reproducibility and validity of a self-administered physical activity questionnaire. Int J Epidemiol 23:991–999
Walker AE, Robins M, Weinfeld FD (1981) The National Survey of Stroke. Clinical findings. Stroke 12:I13–I44
Schwarzpaul S, Strassburg A, Luhrmann PM, Neuhauser-Berthold M (2006) Intake of vitamin and mineral supplements in an elderly german population. Ann Nutr Metab 50:155–162
Michaelsson K, Holmberg L, Mallmin H, Sorensen S, Wolk A, Bergstrom R, Ljunghall S (1995) Diet and hip fracture risk: a case-control study. Study Group of the Multiple Risk Survey on Swedish Women for Eating Assessment. Int J Epidemiol 24:771–782
Michaelsson K, Melhus H, Bellocco R, Wolk A (2003) Dietary calcium and vitamin D intake in relation to osteoporotic fracture risk. Bone 32:694–703
Nordin BE, Lewis JR, Daly RM, Horowitz J, Metcalfe A, Lange K, Prince RL (2011) The calcium scare—what would Austin Bradford Hill have thought? Osteoporos Int 22:3073–3077
Lewis JR, Zhu K, Prince RL (2012) Adverse events from calcium supplementation: relationship to errors in myocardial infarction self-reporting in randomized controlled trials of calcium supplementation. J Bone Miner Res 27:719–722
We are indebted to the participants in the Nurses’ Health Study for their continuing cooperation. Funding. This research was supported by the National Institutes of Health grants HL092947, HL34594, HL088521, DK091417, CA087969 and DK100447.
Conflicts of interest
Julie M. Paik, Gary C. Curhan, Qi Sun, Kathryn M. Rexrode, JoAnn E. Manson, Eric B. Rimm, and Eric N. Taylor declare that they have no conflicts of interest. The authors declare no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.
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Paik, J.M., Curhan, G.C., Sun, Q. et al. Calcium supplement intake and risk of cardiovascular disease in women. Osteoporos Int 25, 2047–2056 (2014). https://doi.org/10.1007/s00198-014-2732-3
- Calcium supplements
- Cardiovascular disease
- Coronary heart disease
- Prospective study