Skip to main content
Log in

Calcium supplement intake and risk of cardiovascular disease in women

Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

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.

Introduction

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.

Methods

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.

Results

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.

Conclusions

Our findings do not support the hypothesis that calcium supplement intake increases CVD risk in women.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. 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

    PubMed  Google Scholar 

  2. 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

    Article  CAS  PubMed  Google Scholar 

  3. 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

    Article  CAS  PubMed  Google Scholar 

  4. 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

    CAS  PubMed  Google Scholar 

  5. 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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. 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

    Article  CAS  PubMed  Google Scholar 

  7. 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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Reid IR, Bolland MJ, Avenell A, Grey A (2011) Cardiovascular effects of calcium supplementation. Osteoporos Int 22:1649–1658

    Article  CAS  PubMed  Google Scholar 

  9. 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

    Article  PubMed  Google Scholar 

  10. Abrahamsen B, Sahota O (2011) Do calcium plus vitamin D supplements increase cardiovascular risk? BMJ 342:d2080

    Article  PubMed  Google Scholar 

  11. Reid IR, Bolland MJ, Grey A (2010) Does calcium supplementation increase cardiovascular risk? Clin Endocrinol 73:689–695

    Article  CAS  Google Scholar 

  12. 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

    Article  PubMed Central  PubMed  Google Scholar 

  13. 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

  14. 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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. 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

    Article  CAS  PubMed  Google Scholar 

  16. 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

    Article  CAS  PubMed  Google Scholar 

  17. 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

    Article  CAS  PubMed  Google Scholar 

  18. 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

    Article  CAS  PubMed  Google Scholar 

  19. 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

    Article  CAS  PubMed  Google Scholar 

  20. 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

    Article  CAS  PubMed  Google Scholar 

  21. 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

    Article  CAS  PubMed  Google Scholar 

  22. 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

    Article  CAS  PubMed  Google Scholar 

  23. 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

    Article  CAS  PubMed  Google Scholar 

  24. 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

    CAS  PubMed  Google Scholar 

  25. 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

    Article  PubMed Central  PubMed  Google Scholar 

  26. 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

    Article  PubMed Central  PubMed  Google Scholar 

  27. 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

    Article  CAS  PubMed  Google Scholar 

  28. 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

    Article  CAS  PubMed  Google Scholar 

  29. Hsia J, Heiss G, Ren H et al (2007) Calcium/vitamin D supplementation and cardiovascular events. Circulation 115:846–854

    Article  CAS  PubMed  Google Scholar 

  30. Lappe JM, Heaney RP (2008) Calcium supplementation: Results may not be generalisable. BMJ 336:403; author reply 404

  31. 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

    Article  CAS  PubMed  Google Scholar 

  32. 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

    Article  CAS  PubMed  Google Scholar 

  33. 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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. 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

    Article  CAS  PubMed  Google Scholar 

  35. 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

    CAS  PubMed  Google Scholar 

  36. 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

    Article  CAS  PubMed  Google Scholar 

  37. 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

    Article  PubMed  Google Scholar 

  38. 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

    Article  CAS  PubMed  Google Scholar 

  39. 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

    Article  CAS  PubMed  Google Scholar 

  40. Walker AE, Robins M, Weinfeld FD (1981) The National Survey of Stroke. Clinical findings. Stroke 12:I13–I44

    CAS  PubMed  Google Scholar 

  41. 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

    Article  CAS  PubMed  Google Scholar 

  42. 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

    Article  CAS  PubMed  Google Scholar 

  43. 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

    Article  CAS  PubMed  Google Scholar 

  44. 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

    Article  CAS  PubMed  Google Scholar 

  45. 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

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. M. Paik.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOCX 22.4 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-014-2732-3

Keywords

Navigation