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calcium supplement

Indications: 1) antacid: 500-1500 mg PO PRN - hiatal hernia, pyrosis, GERD, stress ulcer prophylaxis, dyspepsia, peptic ulcer, gastritis due to H pylori 2) hypocalcemia: 0.5-1 g PO TID (up to 3 g TID, initially) - renal osteodystrophy 3) osteopenia, osteoporosis: 1-2 g PO QD divided BID/TID a) calcium supplementation in elderly does not improve bone mineral density [12] b) for women with low calcium intake only [13] c) calcium <= 1000 mg/day plus vitamin D 400 IU/day does not prevent fractures in postmenopausal women (USPSTF) [14] - vitamin D + calcium supplementation associated with a small but statistically significant absolute reduction in hip fractures or any fractures [28] - reduction not observed when analyses limited to community-dwelling elders [28] - calcium 1200 mg/day for men & women > 50 years preferably from dietary sources & vitamin D 600 IU/day, 800 IU/day recommended for elderly > 71 years [18] d) dietary calcium is preferred [18] - adequate calcium intake is achieved through diet for most populations [18] - high dietary calcium without benefit on fracture risk [29] - low dietary calcium associated with increased risk of fracture [29] - high dietary calcium + bisphosphonate +/- vitamin D is treatment of choice for osteoporosis [18] e) calcium supplements &/or dietary calcium do not significantly* increase bone mineral density or reduce risk of fractures in persons > 50 years of age [20] 4) hyperphosphatemia in renal failure: 0.5-1 g PO TID 5) treatment of electrolyte disturbances - hypermagnesemia, hyperkalemia 6) prevention of pre-eclampsia in pregnant women in populations where calcium intake is low [NGC, WHO] 7) traveler's diarrhea * clinical significance vs statistical significance; 1-2% increase in bone mineral density not clinically significant [20] Contraindications: 1) renal calculi 2) hypophosphatemia 3) ventricular fibrillation 4) insufficient data to recommend calcium plus vitamin D supplementation for primary prevention of bone fractures (USPSTF) 5) calcium supplements &/or vitamin D does not reduce fracture risk in community-dwelling older adults [26] pregnancy_category :value + pregnancy_category :value ? 1st trimester safety_in_lactation :value ? Dosage: - recommended daily allowance: 1000 mg/day - generally for use in combination with vitamin D - may be used in combination with Mg+2 - forms: calcium carbonate, calcium lactate, calcium citrate, calcium glubionate, calcium acetate, calcium chloride, calcium gluconate - combinations: calcium/magnesium/zinc/vitamin D - should be taken with food in doses < 500 mg * 1 dietary calcium serving is = 300 mg of calcium [18] Pharmacokinetics: 1) 20% absorbed & eliminated by the kidneys 2) majority is not absorbed & is eliminated in the feces Adverse effects: 1) constipation 2) dyspepsia 3) flatulence 4) hypotension 5) arrhythmias 6) lethargy 7) erythema 8) renal dysfunction, renal stones 9) nausea 10) cardiovascular mortality a) no increased risk of cardiovascular mortality [25] b) increases risk of cardiovascular mortality & all-cause mortality in women [14] - 2-fold increased risk of myocardial infarction [6,9,10,11] - dietary calcium does not confer increased risk [11,18] - calicum supplements further increase risk conferred by high dietary calcium (> 1400 mg/day) c)) increases risk of mortality from heart disease in men [15] - no increase in mortality in women [15] - no increase in risk of stroke [15] 11) excess calcium intake associated with a 62% higher cancer mortality, attributed to high-dose supplements [27] 11) increased risk for dementia in women with cerebrovascular disease [24] 12) hypercalcemia (9%) & hypercalciuria (30%) when coadministered with vitamin D in postmenopausal women [19] Drug interactions: 1) may antagonize effects of calcium channel blockers 2) may decrease absorption of tetracyclines 3) may increase toxicity of digoxin, precipitating arrhythmias Mechanism of action: - metabolic agent with diverse functions - 1200 mg/day improves bone mineral density in elderly men but does not reduce risk of fracture [8]

Interactions

drug interactions drug adverse effects of calclium supplement(s)

Related

calcium salt (Ca+2 salt)

Specific

calcium ascorbate calcium carbonate (Tums, Oscal, Oyst-Cal) calcium chloride calcium citrate (Citracal) calcium glubionate (Calcionate, Neo-Calglucon) calcium gluconate calcium iodide calcium lactate (Calphosan) calcium threonate

General

Ca+2 metabolic agent (metabolic modifier) nutritional supplement

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, 496
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  4. Greendale G, In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 25-28, 2002
  5. Prescriber's Letter 14(3): 2007 Calcium and Vitamin D Supplementation: Who Needs It? Detail-Document#: 230304 (subscription needed) http://www.prescribersletter.com
  6. Bolland MJ et al, Vascular events in healthy older women receiving calcium supplementation: Randomized controlled trial, BMJ 2008, 336:262 PMID: 18198394 - Prescriber's Letter 15(3): 2008 Calcium Supplementation and Vascular Events Detail-Document#: 240306 (subscription needed) http://www.prescribersletter.com
  7. Prescriber's Letter 15(10): 2008 CHART: Comparison of Oral Calcium Salts GUIDELINES: NAMS Position Statement on the Management of Osteoporosis in Postmenopausal Women GUIDELINES: Diagnosis and Management of Osteoporosis in Canada Detail-Document#: 241008 (subscription needed) http://www.prescribersletter.com
  8. Reid IR et al. Randomized controlled trial of calcium supplementation in healthy, nonosteoporotic, older men. Arch Intern Med 2008 Nov 10; 168:2276. PMID: 19001206
  9. Bolland MJ et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: Meta-analysis. BMJ 2010 Jul 29; 341:c3691 PMID: 20671013
  10. Bolland MJ et al 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 PMID: 21505219 http://www.bmj.com/content/342/bmj.d2040.full - Abrahamsen B and Sahota O Do calcium plus vitamin D supplements increase cardiovascular risk? BMJ 2011; 342:d2080 PMID: 21505220 http://www.bmj.com/content/342/bmj.d2080
  11. Li K, Kaaks R et al 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;98:920-925 PMID: 22626900 http://heart.bmj.com/content/98/12/920.full - Reid IR and Bolland MJ Calcium supplements: bad for the heart? Heart 2012;98:895-896 PMID: 22626897 http://heart.bmj.com/content/98/12/895.extract
  12. Anderson JJB et al Calcium intakes and femoral and lumbar bone density of elderly U.S. men and women: National Health and Nutrition Examination Survey 2005-2006 analysis. J Clin Endocrinol Metab 2012 Dec; 97:4531 PMID: 23071160
  13. Michaelsson K et al Long term calcium intake and rates of all cause and cardiovascular mortality: community based prospective longitudinal cohort study. PMID: 23403980 BMJ 2013;346:f228 http://www.bmj.com/content/346/bmj.f228
  14. Moyer VA et al Vitamin D and Calcium Supplementation to Prevent Fractures in Adults: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 26 February 2013 PMID: 23440163 http://annals.org/article.aspx?articleid=1655858 - Nestle M and Nesheim MC To Supplement or Not to Supplement: The U.S. Preventive Services Task Force Recommendations on Calcium and Vitamin D Ann Intern Med. 26 February 2013 PMID: 23440174 http://annals.org/article.aspx?articleid=1655860
  15. Xiao Q et al. Dietary and supplemental calcium intake and cardiovascular disease mortality: The National Institutes of Health-AARP Diet and Health study. JAMA Intern Med. Feb 4, 2013 PMID: 23381719 http://archinte.jamanetwork.com/article.aspx?articleid=1568523 - Larsson SC. Are calcium supplements harmful to cardiovascular disease? JAMA Intern Med. Feb 4, 2013 PMID: 23380757 http://archinte.jamanetwork.com/article.aspx?articleid=1568524
  16. Prescriber's Letter 20(4): 2013 COMMENTARY: Calcium and Cardiovascular Risk PATIENT EDUCATION HANDOUT: Calcium and Vitamin D Detail-Document#: 290409 (subscription needed) http://www.prescribersletter.com
  17. Deprecated Reference
  18. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013 - Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016 - Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  19. Gallagher JC et al Incidence of hypercalciuria and hypercalcemia during vitamin D and calcium supplementation in older women. Menopause. June 16, 2014 PMID: 24937025 http://journals.lww.com/menopausejournal/Abstract/publishahead/Incidence_of_hypercalciuria_and_hypercalcemia.98368.aspx
  20. Tai V et al Calcium intake and bone mineral density: systematic review and meta-analysis. BMJ 2015;351:h4183 PMID: 26420598 http://www.bmj.com/content/351/bmj.h4183 - Bolland MJ et al Calcium intake and risk of fracture: systematic review. BMJ 2015;351:h4580 PMID: 26420387 http://www.bmj.com/content/351/bmj.h4580 - Michaelsson K Calcium supplements do not prevent fractures. BMJ 2015;351:h4825 PMID: 26420735 http://www.bmj.com/content/351/bmj.h4825
  21. Heaney RP, Kopecky S, Maki KC et al A review of calcium supplements and cardiovascular disease risk. Adv Nutr. 2012 Nov 1;3(6):763-71. Review. PMID: 23153730 Free PMC Article
  22. Prentice RL, Pettinger MB, Jackson RD et al Health risks and benefits from calcium and vitamin D supplementation: Women's Health Initiative clinical trial and cohort study. Osteoporos Int. 2013 Feb;24(2):567-80. PMID: 23208074 Free PMC Article
  23. Reid IR, Bolland MJ, Avenell A, Grey A. Cardiovascular effects of calcium supplementation. Osteoporos Int. 2011 Jun;22(6):1649-58. PMID: 21409434
  24. Kern J, Kern S, Blennow K et al Calcium supplementation and risk of dementia in women with cerebrovascular disease. Neurology. Aug 17, 2016 PMID: 27534711 http://www.neurology.org/content/early/2016/08/17/WNL.0000000000003111
  25. Kopecky SL, Bauer DC, Gulati M et al Lack of Evidence Linking Calcium With or Without Vitamin D Supplementation to Cardiovascular Disease in Generally Healthy Adults: A Clinical Guideline From the National Osteoporosis Foundation and the American Society for Preventive Cardiology. Annals of Internal Medicine. Oct 25, 2016 PMID: 27776362 http://annals.org/aim/article/2571714/lack-evidence-linking-calcium-without-vitamin-d-supplementation-cardiovascular-disease - Chung M, Tang AM, Fu Z, Wang D, Newberry SJ Calcium Intake and Cardiovascular Disease Risk: An Updated Systematic Review and Meta-analysis. Annals of Internal Medicine. Oct 25, 2016 PMID: 27776363 http://annals.org/aim/article/2571713/calcium-intake-cardiovascular-disease-risk-updated-systematic-review-meta-analysis - Margolis KL, Manson JE Calcium Supplements and Cardiovascular Disease Risk: What Do Clinicians and Patients Need to Know? Annals of Internal Medicine. Oct 25, 2016 PMID: 27776361 http://annals.org/aim/article/2571715/calcium-supplements-cardiovascular-disease-risk-what-do-clinicians-patients-need
  26. Zhao JG, Zeng XT, Wang J et al Association Between Calcium or Vitamin D Supplementation and Fracture Incidence in Community-Dwelling Older Adults. A Systematic Review and Meta-analysis. JAMA. 2017;318(24):2466-2482 PMID: 29279934 https://jamanetwork.com/journals/jama/article-abstract/2667071
  27. Chen F, Du M, Blumberg JB et al Association Among Dietary Supplement Use, Nutrient Intake, and Mortality Among U.S. Adults: A Cohort Study. Ann Intern Med. 2019. April 9. PMID: 30959527 https://annals.org/aim/article-abstract/2730525/association-among-dietary-supplement-use-nutrient-intake-mortality-among-u
  28. Chakhtoura M, Bacha DS, Gharios C et al. Vitamin D supplementation and fractures in adults: A systematic umbrella review of meta-analyses of controlled trials. J Clin Endocrinol Metab 2022 Mar; 107:882-898 PMID: 34687206 PMCID: PMC8852203 Free PMC article https://academic.oup.com/jcem/article/107/3/882/6409080
  29. Warensjo E et al Dietary calcium intake and risk of fracture and osteoporosis: Prospective longitudinal cohort study. BMJ 2011 May 24; 342:d1473 PMID: 21610048