Vitamin D, Calcium, and Atherosclerotic Risk: Evidence from Serum Levels and Supplementation Studies

Nonstatin Drugs (WB Borden, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Nonstatin Drugs

Abstract

Vitamin D and calcium have traditionally been viewed in relation to bone health. However, recent research has suggested relations between these nutrients and cardiovascular disease (CVD). Specifically, evidence from both observational studies and clinical trials suggests that vitamin D may be related to lower risk of CVD. The picture for calcium is more complex. Dietary intake of calcium may be associated with lower CVD risk, while calcium supplementation may elevate CVD risk. In this review, we summarize evidence of these relations, and comment on the recent Institute of Medicine (IOM) recommendations regarding use of vitamin D and calcium supplements.

Keywords

Calcium Vitamin D Supplements Cardiovascular disease Review 

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    Lips P. Worldwide status of vitamin D nutrition. The Journal of Steroid Biochemistry and Molecular Biology. 2010;121:297–300.PubMedCrossRefGoogle Scholar
  2. 2.
    Wardlaw GM. Perspectives in nutrition. Boston: McGraw Hill; 2002.Google Scholar
  3. 3.
    Reid I, Bolland M, Avenell A, Grey A. Cardiovascular effects of calcium supplementation. Osteoporos Int. 2011;22:1649–58.PubMedCrossRefGoogle Scholar
  4. 4.
    Reid IR, Bolland MJ. Calcium supplements: bad for the heart? Heart. 2012;98:895–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Holick MF. Vitamin D, deficiency. N Engl J Med. 2007;357:266–81.PubMedCrossRefGoogle Scholar
  6. 6.
    Office of Dietary Supplements. Dietary supplement fact sheet: vitamin D. 2008.Google Scholar
  7. 7.
    Willett WC. Nutritional epidemiology. New York: Oxford University Press; 1998.CrossRefGoogle Scholar
  8. 8.
    Li YC. Vitamin D, regulation of the renin-angiotensin system. J Cell Biochem. 2003;88:327–31.PubMedCrossRefGoogle Scholar
  9. 9.
    Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP. 1,25-dihydroxyvitamin d(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest. 2002;110:229–38.PubMedGoogle Scholar
  10. 10.
    Xiang W, Kong J, Chen S, Cao LP, Qiao G, Zheng W, et al. Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems. Am J Physiol Endocrinol Metab. 2005;288:E125–132.PubMedCrossRefGoogle Scholar
  11. 11.
    Forman JP, Giovannucci E, Holmes MD, Bischoff-Ferrari HA, Tworoger SS, Willett WC, et al. Plasma 25-hydroxyvitamin D levels and risk of incident hypertension. Hypertension. 2007;49:1063–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Forman JP, Curhan GC, Taylor EN. Plasma 25-hydroxyvitamin D levels and risk of incident hypertension among young women. Hypertension. 2008;52:828–32.PubMedCrossRefGoogle Scholar
  13. 13.
    Jorde R, Figenschau Y, Emaus N, Hutchinson M, Grimnes G. Serum 25-hydroxyvitamin D levels are strongly related to systolic blood pressure but do not predict future hypertension. Hypertension. 2010;55:792–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Krause R, Bühring M, Hopfenmüller W, Holick MF, Sharma AM. Ultraviolet b and blood pressure. Lancet. 1998;352:709–10.PubMedCrossRefGoogle Scholar
  15. 15.
    Pfeifer M, Begerow B, Minne HW, Nachtigall D, Hansen C. Effects of a short-term vitamin d3 and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. J Clin Endocrinol Metab. 2001;86:1633–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Witham M, Dove F, Dryburgh M, Sugden J, Morris A, Struthers A. The effect of different doses of vitamin D < sub > 3</sub > on markers of vascular health in patients with type 2 diabetes: a randomised controlled trial. Diabetologia. 2010;53:2112–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Sugden JA, Davies JI, Witham MD, Morris AD, Struthers AD. Vitamin D improves endothelial function in patients with type 2 diabetes mellitus and low vitamin D levels. Diabet Med. 2008;25:320–5.PubMedCrossRefGoogle Scholar
  18. 18.
    Judd SE, Raiser SN, Kumari M, Tangpricha V. 1,25-dihydroxyvitamin d3 reduces systolic blood pressure in hypertensive adults: a pilot feasibility study. The Journal of Steroid Biochemistry and Molecular Biology. 2010;121:445–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Thadhani R, Appelbaum E, Pritchett Y, et al. Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the primo randomized controlled trial. JAMA: The Journal of the American Medical Association. 2012;307:674–84.CrossRefGoogle Scholar
  20. 20.
    Boucher BJ. Inadequate vitamin D status: does it contribute to the disorders comprising syndrome x? Br J Nut. 1998;79:315–27.CrossRefGoogle Scholar
  21. 21.
    Palomer X, González-Clemente J, Blanco-Vaca F, Mauricio D. Role of vitamin D in the pathogenesis of type 2 diabetes mellitus. Diabetes Obes Metab. 2008;10:185–97.PubMedCrossRefGoogle Scholar
  22. 22.
    Borissova AM, Tankova T, Kirilov G, Dakovska L, Kovacheva R. The effect of vitamin d3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients. Int J Clin Pract. 2003;57:258–61.PubMedGoogle Scholar
  23. 23.
    Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007;92:2017–29.PubMedCrossRefGoogle Scholar
  24. 24.
    Knekt P, Laaksonen M, Mattila C, Harkanen T, Marniemi J, Heliovaara M, et al. Serum vitamin D and subsequent occurrence of type 2 diabetes. Epidemiology. 2008;19:666–71. 610.1097/EDE.1090b1013e318176b318178ad.PubMedCrossRefGoogle Scholar
  25. 25.
    Mattila C, Knekt P, Männistö S, Rissanen H, Laaksonen MA, Montonen J, et al. Serum 25-hydroxyvitamin D concentration and subsequent risk of type 2 diabetes. Diabetes Care. 2007;30:2569–70.PubMedCrossRefGoogle Scholar
  26. 26.
    Grimnes G, Emaus N, Joakimsen RM, Figenschau Y, Jenssen T, Njølstad I, et al. Baseline serum 25-hydroxyvitamin D concentrations in the tromsø study 1994–95 and risk of developing type 2 diabetes mellitus during 11 years of follow-up. Diabet Med. 2010;27:1107–15.PubMedCrossRefGoogle Scholar
  27. 27.
    Gagnon C, Lu ZX, Magliano DJ, Dunstan DW, Shaw JE, Zimmet PZ, et al. Serum 25-hydroxyvitamin d, calcium intake, and risk of type 2 diabetes after 5 years: results from a national, population-based prospective study (the australian diabetes, obesity and lifestyle study). Diabetes Care. 2011;34:1133–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Pittas AG, Sun Q, Manson JE, Dawson-Hughes B, Hu FB. Plasma 25-hydroxyvitamin D concentration and risk of incident type 2 diabetes in women. Diabetes Care. 2010;33:2021–3.PubMedCrossRefGoogle Scholar
  29. 29.
    Robinson JG, Manson JE, Larson J, Liu S, Song Y, Howard BV, et al. Lack of association between 25(oh)d levels and incident type 2 diabetes in older women. Diabetes Care. 2011;34:628–34.PubMedCrossRefGoogle Scholar
  30. 30.
    Jorde R, Sneve M, Torjesen P, Figenschau Y. No improvement in cardiovascular risk factors in overweight and obese subjects after supplementation with vitamin d3 for 1 year. Journal of Internal Medicine. 2010;267:462–72.PubMedCrossRefGoogle Scholar
  31. 31.
    von Hurst PR, Stonehouse W, Coad J. Vitamin D supplementation reduces insulin resistance in south Asian women living in New Zealand who are insulin resistant and vitamin D deficient? A randomised, placebo-controlled trial. Br J Nutr. 2010;103:549–55.CrossRefGoogle Scholar
  32. 32.
    Mitri J, Dawson-Hughes B, Hu FB, Pittas AG. Effects of vitamin D and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the calcium and vitamin D for diabetes mellitus (caddm) randomized controlled trial. Am J Clin Nutr. 2011;94:486–94.PubMedCrossRefGoogle Scholar
  33. 33.
    Zittermann A. Vitamin D, and disease prevention with special reference to cardiovascular disease. Prog Biophys Mol Biol. 2006;92:39–48.PubMedCrossRefGoogle Scholar
  34. 34.
    Martin-Ventura JL, Ortego M, Esbrit P, Hernandez-Presa MA, Ortega L, Egido J. Possible role of parathyroid hormone-related protein as a proinflammatory cytokine in atherosclerosis. Stroke. 2003;34:1783–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Somjen D, Weisman Y, Kohen F, Gayer B, Limor R, Sharon O, et al. 25-hydroxyvitamin d3-1alpha-hydroxylase is expressed in human vascular smooth muscle cells and is upregulated by parathyroid hormone and estrogenic compounds. Circulation. 2005;111:1666–71.PubMedCrossRefGoogle Scholar
  36. 36.
    Rigby WF, Denome S, Fanger MW. Regulation of lymphokine production and human t lymphocyte activation by 1,25-dihydroxyvitamin d3. Specific inhibition at the level of messenger rna. J Clin Invest. 1987;79:1659–64.PubMedCrossRefGoogle Scholar
  37. 37.
    Michos ED, Blumenthal RS. Vitamin D supplementation and cardiovascular disease risk. Circulation. 2007;115:827–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle P, Koerfer R. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2006;83:754–9.PubMedGoogle Scholar
  39. 39.
    Martins D, Wolf M, Pan D, Zadshir A, Tareen N, Thadhani R, et al. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the third national health and nutrition examination survey. Arch Intern Med. 2007;167:1159–65.PubMedCrossRefGoogle Scholar
  40. 40.
    Ford ES, Ajani UA, McGuire LC, Liu S. Concentrations of serum vitamin D and the metabolic syndrome among U.S. adults. Diabetes Care. 2005;28:1228–30.PubMedCrossRefGoogle Scholar
  41. 41.
    Zittermann A, Frisch S, Berthold HK, Götting C, Kuhn J, Kleesiek K, et al. Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers. Am J Clin Nutr. 2009;89:1321–7.PubMedCrossRefGoogle Scholar
  42. 42.
    Oh J, Weng S, Felton SK, Bhandare S, Riek A, Butler B, et al. 1,25(oh)2 vitamin D inhibits foam cell formation and suppresses macrophage cholesterol uptake in patients with type 2 diabetes mellitus. Circulation. 2009;120:687–98.PubMedCrossRefGoogle Scholar
  43. 43.
    Rostand SG, Drueke TB. Parathyroid hormone, vitamin d, and cardiovascular disease in chronic renal failure. Kidney Int. 1999;56:383–92.PubMedCrossRefGoogle Scholar
  44. 44.
    Perkovic V, Hewitson TD, Kelynack KJ, Martic M, Tait MG, Becker GJ. Parathyroid hormone has a prosclerotic effect on vascular smooth muscle cells. Kidney Blood Press Res. 2003;26:27–33.PubMedCrossRefGoogle Scholar
  45. 45.
    Amann K, Tornig J, Flechtenmacher C, Nabokov A, Mall G, Ritz E. Blood-pressure-independent wall thickening of intramyocardial arterioles in experimental uraemia: evidence for a permissive action of pth. Nephrol Dial Transplant. 1995;10:2043–8.PubMedGoogle Scholar
  46. 46.
    Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008;117:503–11.PubMedCrossRefGoogle Scholar
  47. 47.
    Anderson JL, May HT, Horne BD, Bair TL, Hall NL, Carlquist JF, et al. Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol. 2010;106:963–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Kilkkinen A, Knekt P, Aro A, Rissanen H, Marniemi J, Heliovaara M, et al. Vitamin D status and the risk of cardiovascular disease death. Am J Epidemiol. 2009;170:1032–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Virtanen JK, Nurmi T, Voutilainen S, Mursu J, Tuomainen TP. Association of serum 25-hydroxyvitamin D with the risk of death in a general older population in finland. European Journal of Nutrition. 2011;50:305–12.Google Scholar
  50. 50.
    Pilz S, Dobnig H, Nijpels G, Heine RJ, Stehouwer CD, Snijder MB, et al. Vitamin D and mortality in older men and women. Clin Endocrinol. 2009;71:666–72.CrossRefGoogle Scholar
  51. 51.
    Semba RD, Houston DK, Bandinelli S, Sun K, Cherubini A, Cappola AR, et al. Relationship of 25-hydroxyvitamin D with all-cause and cardiovascular disease mortality in older community-dwelling adults. Eur J Clin Nutr. 2010;64:203–209Google Scholar
  52. 52.
    Fiscella K, Franks P. Vitamin d, race, and cardiovascular mortality: Findings from a national us sample. Ann Fam Med. 2010;8:11–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Ginde AA, Scragg R, Schwartz RS, Camargo Jr CA. Prospective study of serum 25-hydroxyvitamin D level, cardiovascular disease mortality, and all-cause mortality in older U.S. adults. J Am Geriatr Soc. 2009;57:1595–603.PubMedCrossRefGoogle Scholar
  54. 54.
    Wang AY, Lam CW, Sanderson JE, Wang M, Chan IH, Lui SF, et al. Serum 25-hydroxyvitamin D status and cardiovascular outcomes in chronic peritoneal dialysis patients: a 3-y prospective cohort study. Am J Clin Nutr. 2008;87:1631–8.PubMedGoogle Scholar
  55. 55.
    Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, et al. Independent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Arch Intern Med. 2008;168:1340–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med. 2008;168:1174–80.PubMedCrossRefGoogle Scholar
  57. 57.
    Kestenbaum B, Katz R, de Boer I, Hoofnagle A, Sarnak MJ, Shlipak MG, et al. Vitamin d, parathyroid hormone, and cardiovascular events among older adults. J Am Coll Cardiol. 2011;58:1433–41.PubMedCrossRefGoogle Scholar
  58. 58.
    Lund B, Badskjaer J, Lund B, Soerensen OH. Vitamin D and ischaemic heart disease. Horm Metab Res. 1978;10:553–6.Google Scholar
  59. 59.
    Scragg R, Jackson R, Holdaway IM, Lim T, Beaglehole R. Myocardial infarction is inversely associated with plasma 25-hydroxyvitamin d3 levels: a community-based study. International Journal of Epidemiology. 1990;19:559–63.PubMedCrossRefGoogle Scholar
  60. 60.
    Vik B, Try K, Thelle DS, Forde OH. Tromso heart study: vitamin D metabolism and myocardial infarction. British Medical Journal. 1979;2:176.PubMedCrossRefGoogle Scholar
  61. 61.
    Kim DH, Sabour S, Sagar UN, Adams S, Whellan DJ. Prevalence of hypovitaminosis D in cardiovascular diseases (from the national health and nutrition examination survey 2001 to 2004). Am J Cardiol. 2008;102:1540–4.PubMedCrossRefGoogle Scholar
  62. 62.
    Deo R, Katz R, Shlipak MG, Sotoodehnia N, Psaty BM, Sarnak MJ, et al. Vitamin d, parathyroid hormone, and sudden cardiac death. Hypertension. 2011;58:1021–8.PubMedCrossRefGoogle Scholar
  63. 63.
    •• de Boer IH, Levin G, Robinson-Cohen C, Biggs ML, Hoofnagle AN, Siscovick DS, et al. Serum 25-hydroxyvitamin D concentration and risk for major clinical disease events in a community-based population of older adultsa cohort study. Annals of Internal Medicine. 2012;156:627–34. This recent observational study adds to the epidemiology literature by suggesting (1) season specific levels may be most appropriate for targeting 25(OH)D concentrations and (2) the season-specific threshold of increased risk centers close to levels below 20 ng/ml (rather than 30 ng/ml), reaffirming the optimal serum level of 25(OH)D ≥ 20 ng/ml set by the IOM guidelines.Google Scholar
  64. 64.
    Michos ED, Reis JP, Post WS, Lutsey PL, Gottesman RF, Mosley TH, et al. 25-hydroxyvitamin D deficiency is associated with fatal stroke among whites but not blacks: The NHANES-III linked mortality files. Nutrition. 2012;28(4):367–71.PubMedCrossRefGoogle Scholar
  65. 65.
    Pilz S, Dobnig H, Fischer JE, Wellnitz B, Seelhorst U, Boehm BO, et al. Low vitamin D levels predict stroke in patients referred to coronary angiography. Stroke. 2008;39:2611–3.PubMedCrossRefGoogle Scholar
  66. 66.
    Marniemi J, Alanen E, Impivaara O, Seppanen R, Hakala P, Rajala T, et al. Dietary and serum vitamins and minerals as predictors of myocardial infarction and stroke in elderly subjects. Nutr Metab Cardiovasc Dis. 2005;15:188–97.PubMedCrossRefGoogle Scholar
  67. 67.
    Poole KE, Loveridge N, Barker PJ, Halsall DJ, Rose C, Reeve J, et al. Reduced vitamin D in acute stroke. Stroke; a Journal of Cerebral Circulation. 2006;37:243–5.PubMedCrossRefGoogle Scholar
  68. 68.
    Kojima G, Bell C, Abbott RD, Launer L, Chen R, Motonaga H, et al. Low dietary vitamin D predicts 34-year incident stroke. Stroke. 2012;43:2163–7.Google Scholar
  69. 69.
    Pilz S, Marz W, Wellnitz B, Seelhorst U, Fahrleitner-Pammer A, Dimai HP, et al. Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography. J Clin Endocrinol Metab. 2008;93:3927–35.PubMedCrossRefGoogle Scholar
  70. 70.
    Arroyo M, Laguardia SP, Bhattacharya SK, Nelson MD, Johnson PL, Carbone LD, et al. Micronutrients in African-Americans with decompensated and compensated heart failure. Transl Res. 2006;148:301–8.PubMedCrossRefGoogle Scholar
  71. 71.
    Laguardia SP, Dockery BK, Bhattacharya SK, Nelson MD, Carbone LD, Weber KT. Secondary hyperparathyroidism and hypovitaminosis D in African-Americans with decompensated heart failure. Am J Med Sci. 2006;332:112–8.PubMedCrossRefGoogle Scholar
  72. 72.
    Shane E, Mancini D, Aaronson K, Silverberg SJ, Seibel MJ, Addesso V, et al. Bone mass, vitamin D deficiency, and hyperparathyroidism in congestive heart failure. Am J Med. 1997;103:197–207.PubMedCrossRefGoogle Scholar
  73. 73.
    Zittermann A, Schleithoff SS, Tenderich G, Berthold HK, Korfer R, Stehle P. Low vitamin D status: a contributing factor in the pathogenesis of congestive heart failure? J Am Coll Cardiol. 2003;41:105–12.PubMedCrossRefGoogle Scholar
  74. 74.
    Rienstra M, Cheng S, Larson MG, McCabe EL, Booth SL, Jacques PF, et al. Vitamin D status is not related to development of atrial fibrillation in the community. Am Hear J. 2011;162:538–41.CrossRefGoogle Scholar
  75. 75.
    Shapses SA, Manson JE. Vitamin D and prevention of cardiovascular disease and diabetes: why the evidence falls short. JAMA. 2011;305:2565–6.PubMedCrossRefGoogle Scholar
  76. 76.
    Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin d3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. 2003;326:469.PubMedCrossRefGoogle Scholar
  77. 77.
    Prince RL, Austin N, Devine A, Dick IM, Bruce D, Zhu K. Effects of ergocalciferol added to calcium on the risk of falls in elderly high-risk women. Arch Intern Med. 2008;168:103–8.PubMedCrossRefGoogle Scholar
  78. 78.
    Wang L, Manson JE, Song Y, Sesso HD. Systematic review: vitamin D and calcium supplementation in prevention of cardiovascular events. Ann Intern Med. 2010;152:315–23.PubMedGoogle Scholar
  79. 79.
    Hsia J, Heiss G, Ren H, Allison M, Dolan NC, Greenland P, et al. Calcium/vitamin D supplementation and cardiovascular events. Circulation. 2007;115:846–54.PubMedCrossRefGoogle Scholar
  80. 80.
    Brazier M, Grados F, Kamel S, Mathieu M, Morel A, Maamer M, et al. Clinical and laboratory safety of one year's use of acombination calcium + vitamin D tablet in ambulatory elderly women with vitamin D insufficiency: Results of a mlticenter, rndomized, double-blind, placebo-controlled study. Clin Ther. 2005;27:1885–93.PubMedCrossRefGoogle Scholar
  81. 81.
    Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003;77:204–10.PubMedGoogle Scholar
  82. 82.
    Vieth R. Vitamin D, supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999;69:842–56.PubMedGoogle Scholar
  83. 83.
    Lee JH, O'Keefe JH, Bell D, Hensrud DD, Holick MF. Vitamin D deficiency: an important, common, and easily treatable cardiovascular risk factor? J Am Coll Cardiol. 2008;52:1949–56.PubMedCrossRefGoogle Scholar
  84. 84.
    Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007;167:1730–7.PubMedCrossRefGoogle Scholar
  85. 85.
    •• Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2011:CD007470. This recent Cochrane meta-analysis of 50 randomized clinical trials involving nearly 100,000 people provides evidence that vitamin D supplements were associated with modestly lower risk of all-cause mortality. Despite limitations (e.g. popuation largely older women, formulations vary), this suggests that there may be a net benefit of vitamin D supplementation.Google Scholar
  86. 86.
    Liu S, Song Y, Ford ES, Manson JE, Buring JE, Ridker PM. Dietary calcium, vitamin d, and the prevalence of metabolic syndrome in middle-aged and older U.S. Women. Diabetes Care. 2005;28:2926–32.PubMedCrossRefGoogle Scholar
  87. 87.
    Villegas R, Gao Y-T, Dai Q, Yang G, Cai H, Li H, et al. Dietary calcium and magnesium intakes and the risk of type 2 diabetes: the shanghai women's health study. Am J Clin Nutr. 2009;89:1059–67.PubMedCrossRefGoogle Scholar
  88. 88.
    van Dam RM, Hu FB, Rosenberg L, Krishnan S, Palmer JR. Dietary calcium and magnesium, major food sources, and risk of type 2 diabetes in U.S. Black women. Diabetes Care. 2006;29:2238–43.PubMedCrossRefGoogle Scholar
  89. 89.
    Tremblay A, Gilbert J-A. Milk products, insulin resistance syndrome and type 2 diabetes. J Am Coll Nutr. 2009;28:91S–102S.PubMedGoogle Scholar
  90. 90.
    Reid IR. Effects of calcium supplementation on circulating lipids: potential pharmacoeconomic implications. Drugs Aging. 2004;21:7–17.PubMedCrossRefGoogle Scholar
  91. 91.
    •• Li K, Kaaks R, Linseisen J, Rohrmann S. 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. 2012;98:920–25. This recent observational study is important because it corroborates some of the recent clinical trial papers that suggested an increased risk of myocardial infarction with calcium supplements, while providing some reassuring evidence that moderate dietary calcium does not appear harmful and may be beneficial.Google Scholar
  92. 92.
    van Mierlo LAJ, Arends LR, Streppel MT, Zeegers MPA, Kok FJ, Grobbee DE, et al. Blood pressure response to calcium supplementation: a meta-analysis of randomized controlled trials. J Hum Hypertens. 2006;20:571–80.PubMedCrossRefGoogle Scholar
  93. 93.
    Bolland MJ, Barber PA, Doughty RN, Mason B, Horne A, Ames R, et al. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ. 2008;336:262–6.PubMedCrossRefGoogle Scholar
  94. 94.
    Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ. 2010;341:c3691.Google Scholar
  95. 95.
    •• Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR. 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. 2011;342:d2040. By carefully reanalyzing the WHI data, and observing that the adverse CVD risk associated with supplements is limited to those not previously taking supplments, these authors expand our understanding of how calcium supplemention may infuence CVD risk.Google Scholar
  96. 96.
    Lind L, Skarfors E, Berglund L, Lithell H, Ljunghall S. Serum calcium: a new, independent, prospective risk factor for myocardial infarction in middle-aged men followed for 18 years. Journal of Clinical Epidemiology. 1997;50:967–73.PubMedCrossRefGoogle Scholar
  97. 97.
    Foley RN, Collins AJ, Ishani A, Kalra PA. Calcium-phosphate levels and cardiovascular disease in community-dwelling adults: the atherosclerosis risk in communities (aric) study. Am Hear J. 2008;156:556–63.CrossRefGoogle Scholar
  98. 98.
    Jorde R, Sundsfjord J, Fitzgerald P, Bønaa KH. Serum calcium and cardiovascular risk factors and diseases: the tromsø study. Hypertension. 1999;34:484–90.PubMedCrossRefGoogle Scholar
  99. 99.
    Dhingra R, Sullivan LM, Fox CS, Wang TJ, D'Agostino Sr RB, Gaziano JM, et al. Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Arch Intern Med. 2007;167:879–85.PubMedCrossRefGoogle Scholar
  100. 100.
    IOM (Institute of Medicine). Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. 2011.Google Scholar
  101. 101.
    •• Manson JE, Bassuk SS, Lee IM, Cook NR, Albert MA, Gordon D, et al. The vitamin D and omega-3 trial (vital): Rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemporary Clinical Trials. 2012;33:159–71. Trials are needed to establish whether low vitamin D is causally related to CVD risk. Results of the VITAL Trial (design paper listed here) are eagerly awaited.Google Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Division of Epidemiology and Community HealthUniversity of MinnesotaMinneapolisUSA
  2. 2.Division of CardiologyJohns Hopkins University School of MedicineBaltimoreUSA

Personalised recommendations