Is excess calcium harmful to health?

Nutrients

Volumn 2, Issue 5, 2010, Pages 505-522

  Daly, Robin M ^a   Ebeling, Peter R ^a  

^a UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

Calcium supplementation; Cardiovascular disease; Elderly; Mortality

Indexed keywords

CALCIUM; CALCIUM CARBONATE; CHOLESTEROL; CITRATE CALCIUM; COLECALCIFEROL; PLACEBO; VITAMIN D;

BLOOD PRESSURE; BLOOD VESSEL CALCIFICATION; CALCIUM BLOOD LEVEL; CALCIUM INTAKE; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CEREBROVASCULAR DISEASE; DIET SUPPLEMENTATION; DRUG BIOAVAILABILITY; DRUG DOSE COMPARISON; DRUG FATALITY; FOOD INTAKE; HUMAN; LIPID BLOOD LEVEL; MORTALITY; NEPHROLITHIASIS; OBSERVATIONAL STUDY; PROSPECTIVE STUDY; REVIEW; RISK ASSESSMENT; RISK FACTOR; UNSPECIFIED SIDE EFFECT;

EID: 79952058074     PISSN: None     EISSN: 20726643     Source Type: Journal    
DOI: 10.3390/nu2050505     Document Type: Review

References (70)

1. Daly, R.M.; Bass, S.; Nowson, C. Long-term effects of calcium-vitamin-D3-fortified milk on bone geometry and strength in older men. Bone 2006, 39, 946-953.
2. Daly, R.M.; Brown, M.; Bass, S.; Kukuljan, S.; Nowson, C. Calcium- and vitamin D3-fortified milk reduces bone loss at clinically relevant skeletal sites in older men: a 2-year randomized controlled trial. J. Bone Miner. Res. 2006, 21, 397-405.
3. Prince, R.L.; Devine, A.; Dhaliwal, S.S.; Dick, I.M. 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. 2006, 166, 869-875.
4. Reid, I.R.; Ames, R.; Mason, B.; Reid, H.E.; Bacon, C.J.; Bolland, M.J.; Gamble, G.D.; Grey, A.; Horne, A. Randomized controlled trial of calcium supplementation in healthy, nonosteoporotic, older men. Arch. Intern. Med. 2008, 168, 2276-2282.
5. Riggs, B.L.; O'Fallon, W.M.; Muhs, J.; O'Connor, M.K.; Kumar, R.; Melton, L.J., 3rd Long-term effects of calcium supplementation on serum parathyroid hormone level, bone turnover, and bone loss in elderly women. J. Bone Miner. Res. 1998, 13, 168-174.
6. Tang, B.M.; Eslick, G.D.; Nowson, C.; Smith, C.; Bensoussan, A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet 2007, 370, 657-666.
7. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride; National Academy Press: Washington, DC, USA, 1997.
8. Hunt, C.D.; Johnson, L.K. Calcium requirements: new estimations for men and women by rosssectional statistical analyses of calcium balance data from metabolic studies. Am. J. Clin. Nutr. 2007, 86, 1054-1063.
9. Jackson, R.D.; LaCroix, A.Z.; Gass, M.; Wallace, R.B.; Robbins, J.; Lewis, C.E.; Bassford, T.; Beresford, S.A.; Black, H.R.; Blanchette, P.; Bonds, D.E.; Brunner, R.L.; Brzyski, R.G.; Caan, B.; Cauley, J.A.; Chlebowski, R.T.; Cummings, S.R.; Granek, I.; Hays, J.; Heiss, G.; Hendrix, S.L.; Howard, B.V.; Hsia, J.; Hubbell, F.A.; Johnson, K.C.; Judd, H.; Kotchen, J.M.; Kuller, L.H.; Langer, R.D.; Lasser, N.L.; Limacher, M.C.; Ludlam, S.; Manson, J.E.; Margolis, K.L.; McGowan, J.; Ockene, J.K.; O'Sullivan, M.J.; Phillips, L.; Prentice, R.L.; Sarto, G.E.; Stefanick, M.L.; Van Horn, L.; Wactawski-Wende, J.; Whitlock, E.; Anderson, G.L.; Assaf, A.R.; Barad, D. Calcium plus vitamin D supplementation and the risk of fractures. N. Engl. J. Med. 2006, 354, 669-683.
10. LaCroix, A.Z.; Kotchen, J.; Anderson, G.; Brzyski, R.; Cauley, J.A.; Cummings, S.R.; Gass, M.; Johnson, K.C.; Ko, M.; Larson, J.; Manson, J.E.; Stefanick, M.L.; Wactawski-Wende, J. Calcium plus vitamin D supplementation and mortality in postmenopausal women: the Women's Health Initiative calcium-vitamin D randomized controlled trial. J. Gerontol. A. Biol. Sci. Med. Sci. 2009, 64, 559-567.
11. Pittas, A.G.; Lau, J.; Hu, F.B.; 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, 2017-2029.
12. Lappe, J.M.; Travers-Gustafson, D.; Davies, K.M.; Recker, R.R.; Heaney, R.P. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am. J. Clin. Nutr. 2007, 85, 1586-1591.
13. Baron, J.A.; Beach, M.; Mandel, J.S.; van Stolk, R.U.; Haile, R.W.; Sandler, R.S.; Rothstein, R.; Summers, R.W.; Snover, D.C.; Beck, G.J.; Bond, J.H.; Greenberg, E.R. Calcium supplements for the prevention of colorectal adenomas. Calcium Polyp Prevention Study Group. N. Engl. J. Med. 1999, 340, 101-107.
14. Bostick, R.M.; Kushi, L.H.; Wu, Y.; Meyer, K.A.; Sellers, T.A.; Folsom, A.R. Relation of calcium, vitamin D, and dairy food intake to ischemic heart disease mortality among postmenopausal women. Am. J. Epidemiol. 1999, 149, 151-161.
15. Bell, L.; Halstenson, C.E.; Halstenson, C.J.; Macres, M.; Keane, W.F. Cholesterol-lowering effects of calcium carbonate in patients with mild to moderate hypercholesterolemia. Arch. Intern. Med. 1992, 152, 2441-2444.
16. Denke, M.A.; Fox, M.M.; Schulte, M.C. Short-term dietary calcium fortification increases fecal saturated fat content and reduces serum lipids in men. J. Nutr. 1993, 123, 1047-1053.
17. Reid, I.R.; Mason, B.; Horne, A.; Ames, R.; Clearwater, J.; Bava, U.; Orr-Walker, B.; Wu, F.; Evans, M.C.; Gamble, G.D. Effects of calcium supplementation on serum lipid concentrations in normal older women: a randomized controlled trial. Am. J. Med. 2002, 112, 343-347.
18. Griffith, L.E.; Guyatt, G.H.; Cook, R.J.; Bucher, H.C.; Cook, D.J. The influence of dietary and nondietary calcium supplementation on blood pressure: an updated metaanalysis of randomized controlled trials. Am. J. Hypertens. 1999, 12, 84-92.
19. van Mierlo, L.A.; Arends, L.R.; Streppel, M.T.; Zeegers, M.P.; Kok, F.J.; Grobbee, D.E.; Geleijnse, J.M. Blood pressure response to calcium supplementation: a meta-analysis of randomized controlled trials. J. Hum. Hypertens. 2006, 20, 571-580.
20. Bolland, M.J.; Barber, P.A.; Doughty, R.N.; Mason, B.; Horne, A.; Ames, R.; Gamble, G.D.; Grey, A.; Reid, I.R. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ 2008, 336, 262-266.
21. Pentti, K.; Tuppurainen, M.T.; Honkanen, R.; Sandini, L.; Kroger, H.; Alhava, E.; Saarikoski, S. 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 2009, 63, 73-78.
22. Reid, I.R.; Bolland, M.J.; Grey, A. The calcium controversy: balancing heart and bone effects of supplements. Int. Med. J. 2010, 40, S47.
23. German, J.B.; Gibson, R.A.; Krauss, R.M.; Nestel, P.; Lamarche, B.; van Staveren, W.A.; Steijns, J.M.; de Groot, L.C.; Lock, A.L.; Destaillats, F. A reappraisal of the impact of dairy foods and milk fat on cardiovascular disease risk. Eur. J. Nutr. 2009, 48, 191-203.
24. Gibson, R.A.; Makrides, M.; Smithers, L.G.; Voevodin, M.; Sinclair, A.J. The effect of dairy foods on CHD: a systematic review of prospective cohort studies. Br. J. Nutr. 2009, 102, 1267-1275.
25. Al-Delaimy, W.K.; Rimm, E.; Willett, W.C.; Stampfer, M.J.; Hu, F.B. A prospective study of calcium intake from diet and supplements and risk of ischemic heart disease among men. Am. J. Clin. Nutr. 2003, 77, 814-818.
26. Ascherio, A.; Rimm, E.B.; Hernan, M.A.; Giovannucci, E.L.; Kawachi, I.; Stampfer, M.J.; Willett, W.C. Intake of potassium, magnesium, calcium, and fiber and risk of stroke among US men. Circulation 1998, 98, 1198-1204.
27. Iso, H.; Stampfer, M.J.; Manson, J.E.; Rexrode, K.; Hennekens, C.H.; Colditz, G.A.; Speizer, F.E.; Willett, W.C. Prospective study of calcium, potassium, and magnesium intake and risk of stroke in women. Stroke 1999, 30, 1772-1779.
28. Nurmi-Luthje, I.; Luthje, P.; Kaukonen, J.P.; Kataja, M.; Kuurne, S.; Naboulsi, H.; Karjalainen, K. Post-fracture prescribed calcium and vitamin D supplements alone or, in females, with concomitant anti-osteoporotic drugs is associated with lower mortality in elderly hip fracture patients: a prospective analysis. Drugs Aging 2009, 26, 409-421.
29. Jones, G.; Winzenberg, T. Cardiovascular risks of calcium supplements in women. BMJ 2008, 336, 226-227.
30. Bolland, M.J.; Grey, A.B.; Reid, I.R. Re: Calcium supplementation does not increase mortality. Med. J. Aust. 2008, 189, 55; author reply 55-56.
31. Reid, I.R.; Bolland, M.J.; Grey, A. Does Calcium Supplementation Increase Cardiovascular Risk? Clin. Endocrinol. (Oxf). 2010, Feb 23. [Epub ahead of print]
32. Andrews, N.A. Calcium supplementation and vascular disease: A legitimate new worry? IBMS Bone KEy. 2008, 5, 124-129.
33. Sabbagh, Z.; Vatanparast, H. Is calcium supplementation a risk factor for cardiovascul ar diseases in older women? Nutr. Rev. 2009, 67, 105-108.
34. Lappe, J.M.; Heaney, R.P. Calcium supplementation: Results may not be generalisable. BMJ. 2008, 336, 403; author reply 404.
35. Hanzlik, R.P.; Fowler, S.C.; Fisher, D.H. Relative bioavailability of calcium from calcium formate, calcium citrate, and calcium carbonate. J. Pharmacol. Exp. Ther. 2005, 313, 1217-1222.
36. Reid, I.R.; Schooler, B.A.; Hannan, S.F.; Ibbertson, H.K. The acute biochemical effects of four proprietary calcium preparations. Aust. N. Z. J. Med. 1986, 16, 193-197.
37. Ginde, A.A.; Scragg, R.; Schwartz, R.S.; Camargo, C.A., Jr. 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, 1595-1603.
38. Kilkkinen, A.; Knekt, P.; Aro, A.; Rissanen, H.; Marniemi, J.; Heliovaara, M.; Impivaara, O.; Reunanen, A. Vitamin D status and the risk of cardiovascular disease death. Am. J. Epidemiol. 2009, 170, 1032-1039.
39. Grant, A.M.; Avenell, A.; Campbell, M.K.; McDonald, A.M.; MacLennan, G.S.; McPherson, G.C.; Anderson, F.H.; Cooper, C.; Francis, R.M.; Donaldson, C.; Gillespie, W.J.; Robinson, C.M.; Torgerson, D.J.; Wallace, W.A. Oral vitamin D3 and calcium for secondary prevention of lowtrauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Lancet 2005, 365, 1621-1628.
40. Brazier, M.; Grados, F.; Kamel, S.; Mathieu, M.; Morel, A.; Maamer, M.; Sebert, J.L.; Fardellone, P. 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. 2005, 27, 1885-1893.
41. Hsia, J.; Heiss, G.; Ren, H.; Allison, M.; Dolan, N.C.; Greenland, P.; Heckbert, S.R.; Johnson, K.C.; Manson, J.E.; Sidney, S.; Trevisan, M. Calcium/vitamin D supplementation and cardiovascular events. Circulation 2007, 115, 846-854.
42. Zhu, K.; Bruce, D.; Austin, N.; Devine, A.; Ebeling, P.R.; Prince, R.L. Randomized controlled trial of the effects of calcium with or without vitamin D on bone structure and bone-related chemistry in elderly women with vitamin D insufficiency. J. Bone Miner. Res. 2008, 23, 1343-1348.
43. Autier, P.; Gandini, S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch. Intern. Med. 2007, 167, 1730-1737.
44. Wang, L.; Manson, J.E.; Song, Y.; Sesso, H.D. Systematic review: Vitamin D and calcium supplementation in prevention of cardiovascular events. Ann. Intern. Med. 2010, 152, 315-323.
45. Govers, M.J.; Van der Meet, R. Effects of dietary calcium and phosphate on the intestinal interactions between calcium, phosphate, fatty acids, and bile acids. Gut 1993, 34, 365-370.
46. Zemel, M.B.; Shi, H.; Greer, B.; Dirienzo, D.; Zemel, P.C. Regulation of adiposity by dietary calcium. FASEB J. 2000, 14, 1132-1138.
47. Zemel, M.B. Calcium modulation of hypertension and obesity: mechanisms and implications. J. Am. Coll. Nutr. 2001, 20, 428S-435S; discussion 440S-442S.
48. Reid, I.R.; Horne, A.; Mason, B.; Ames, R.; Bava, U.; Gamble, G.D. Effects of calcium supplementation on body weight and blood pressure in normal older women: a randomized controlled trial. J. Clin. Endocrinol. Metab. 2005, 90, 3824-3829.
49. Allender, P.S.; Cutler, J.A.; Follmann, D.; Cappuccio, F.P.; Pryer, J.; Elliott, P. Dietary calcium and blood pressure: a meta-analysis of randomized clinical trials. Ann. Intern. Med. 1996, 124, 825-831.
50. Wilson, P.W.; Kauppila, L.I.; O'Donnell, C.J.; Kiel, D.P.; Hannan, M.; Polak, J.M.; Cupples, L.A. Abdominal aortic calcific deposits are an important predictor of vascular morbidity and ortality. Circulation 2001, 103, 1529-1534.
51. West, S.L.; Swan, V.J.; Jamal, S.A. Effects of calcium on cardiovascular events in patients with kidney disease and in a healthy population. Clin. J. Am. Soc. Nephrol. 2010, 5, S41-47.
52. Chertow, G.M.; Burke, S.K.; Raggi, P. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int. 2002, 62, 245-252.
53. Russo, D.; Miranda, I.; Ruocco, C.; Battaglia, Y.; Buonanno, E.; Manzi, S.; Russo, L.; Scafarto, A.; Andreucci, V.E. The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer. Kidney Int. 2007, 72, 1255-1261.
54. Bhakta, M.; Bruce, C.; Messika-Zeitoun, D.; Bielak, L.; Sheedy, P.F.; Peyser, P.; Sarano, M. Oral calcium supplements do not affect the progression of aortic valve calcification or coronary artery calcification. J. Am. Board Fam. Med. 2009, 22, 610-616.
55. Van Pelt, N.; Ruygrok, P.; Bolland, M.J.; Gamble, G.D.; Mason, B.; Ames, R.; Reid, I.R. Do calcium supplements lead to an increase in coronary calcification? Heart, Lung Circulation 2009, 18S, S241.
56. Daly, R.M.; R., E.P.; Khan, B.; Nowson, C.A. Effects of calcium-vitamin D3 fortified milk on abdominal aortic calcification in older men: Retrospective analysis of a 2-year randomized controlled trial. J. Bone Miner. Res. 2009, 24, S134.
57. Kiechl, S.; Schett, G.; Wenning, G.; Redlich, K.; Oberhollenzer, M.; Mayr, A.; Santer, P.; Smolen, J.; Poewe, W.; Willeit, J. Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease. Circulation 2004, 109, 2175-2180.
58. Nitta, K.; Akiba, T.; Uchida, K.; Otsubo, S.; Takei, T.; Yumura, W.; Kabaya, T.; Nihei, H. Serum osteoprotegerin levels and the extent of vascular calcification in haemodialysis patients. Nephrol. Dial. Transplant. 2004, 19, 1886-1889.
59. Clancy, P.; Oliver, L.; Jayalath, R.; Buttner, P.; Golledge, J. Assessment of a serum assay for quantification of abdominal aortic calcification. Arterioscler. Thromb. Vasc. Biol. 2006, 26, 2574-2576.
60. Marque, S.; Jacqmin-Gadda, H.; Dartigues, J.F.; Commenges, D. Cardiovascular mortality and calcium and magnesium in drinking water: an ecological study in elderly people. Eur. J. Epidemiol. 2003, 18, 305-309.
61. Payne, M.E.; Anderson, J.J.; Steffens, D.C. Calcium and vitamin D intakes may be positively associated with brain lesions in depressed and non depressed elders. Nutr Res. 2008, 28, 285-292.
62. Payne, M.E.; Haines, P.S.; Chambless, L.E.; Anderson, J.J.; Steffens, D.C. Food group intake and brain lesions in late-life vascular depression. Int. Psychogeriatr. 2007, 19, 295-305.
63. Curhan, G.C.; Willett, W.C.; Rimm, E.B.; Stampfer, M.J. A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones. N. Engl. J. Med. 1993, 328, 833-838.
64. Siener, R.; Glatz, S.; Nicolay, C.; Hesse, A. Prospective study on the efficacy of a selective treatment and risk factors for relapse in recurrent calcium oxalate stone patients. Eur. Urol. 2003, 44, 467-474.
65. Heaney, R.P. Calcium supplementation and incident kidney stone risk: a systematic review. J. Am. Coll. Nutr. 2008, 27, 519-527.
66. 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. J. Clin. Epidemiol. 1997, 50, 967-973.
67. Foley, R.N.; Collins, A.J.; Ishani, A.; Kalra, P.A. Calcium-phosphate levels and cardiovascular disease in community-dwelling adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am. Heart J. 2008, 156, 556-563.
68. Block, G.A.; Klassen, P.S.; Lazarus, J.M.; Ofsthun, N.; Lowrie, E.G.; Chertow, G.M. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J. Am. Soc. Nephrol. 2004, 15, 2208-2218.
69. Slinin, Y.; Blackwell, T.; Ishani, A.; Cummings, S.R.; Ensrud, K.E. Serum calcium, phosphorus and cardiovascular events in post-menopausal women. Int. J. Cardiol. 2010 Feb 26. [Epub ahead of print].
70. Heaney, R.P. Mineral balance and mineral requirement. Am. J. Clin. Nutr. 2007, 87, 1960-1961.