Calcium supplement

Calcium supplements are salts of calcium used in a number of conditions.[1] Supplementation is generally only required when there is not enough calcium in the diet.[2][3] By mouth they are used to treat and prevent low blood calcium, osteoporosis, and rickets.[1] By injection into a vein they are used for low blood calcium that is resulting in muscle spasms and for high blood potassium or magnesium toxicity.[2][4]

Calcium supplement
500 milligram calcium supplements made from calcium carbonate
Clinical data
Trade namesAlka-Mints, Calcet, Tums, others
AHFS/Drugs.comMonograph
License data
Pregnancy
category
  • and C
Routes of
administration		by mouth, intravenous
ATC code
Identifiers
CAS Number
ChemSpider
  • none
UNII

Common side effects include constipation and nausea.[1] When taken by mouth high blood calcium is uncommon.[1] Calcium supplements, unlike calcium from dietary sources, appear to increase the risk of kidney stones.[1] Adults generally require about a gram of calcium a day.[1] Calcium is particularly important for bones, muscles, and nerves.[1]

The medical use of calcium supplements began in the 19th century.[5] It is on the World Health Organization's List of Essential Medicines.[6] It is available as a generic medication.[3] In 2017, it was the 262nd most commonly prescribed medication in the United States, with more than one million prescriptions.[7][8] Versions are also sold together with vitamin D.[3] The combination, calcium/cholecalciferol was the 236th most commonly prescribed medication in the United States, with more than two million prescriptions.[7][9]

Medical use

Bone health

In healthy people, calcium supplementation is not necessary for maintaining bone mineral density, and carries risks that outweigh any benefits.[10] Calcium intake is not significantly associated with hip fracture risk in either men or women.[11] The U.S. Preventive Service Task Force recommends against a daily supplement of calcium or vitamin D.[12] Although a slight increase in bone mineral density occurred in healthy children from calcium supplementation, using additional dietary calcium is not justified, according to a 2006 review.[13]

Cardiovascular impact

In young adults with normal blood pressure, additional calcium intake caused a small reduction (- 2 mmHg) of systolic and diastolic blood pressure.[14] By contrast, a study investigating the effects of personal calcium supplementation on cardiovascular risk in the Women's Health Initiative Calcium/Vitamin D Supplementation Study (WHI CaD Study) found a modestly increased risk of cardiovascular events, particularly myocardial infarction in postmenopausal women. A broad recommendation of calcium/vitamin D supplements is therefore not warranted.[15] A 2013 literature review concluded that the benefits of calcium supplementation in some studies, such as on bone health, appear to outweigh any risk calcium supplementation may pose to the cardiovascular health.[16]

Cancer

Overall, there is no clear evidence of the effect of calcium supplements in cancer prevention: some studies suggest it might decrease the risk, but others suggest it might increase the risk. Consequently, the National Cancer Institute does not recommend the use of calcium supplements for this purpose.[17]

There is weak evidence calcium supplementation might have a preventative effect against developing colorectal adenomatous polyps, but the evidence is not sufficient to recommend such supplementation.[18]

Side effects

Excessive consumption of calcium carbonate antacids/dietary supplements (such as Tums) over a period of weeks or months can cause milk-alkali syndrome, with symptoms ranging from hypercalcemia to potentially fatal kidney failure. What constitutes "excessive" consumption is not well known and, it is presumed, varies a great deal from person to person. Persons consuming more than 10 grams/day of CaCO3 (=4 g Ca) are at risk of developing milk-alkali syndrome,[19] but the condition has been reported in at least one person consuming only 2.5 grams/day of CaCO3 (=1 g Ca), an amount usually considered moderate and safe.[20]

Although some studies have suggested that excessive intake of calcium in the diet or as supplements could be associated with increased cardiovascular mortality,[21][22] other studies found no risk,[23] leading a review to conclude that any risk could only be ascertained with specific further research.[24]

Calcium supplements may contribute to the development of kidney stones.[1]

Acute calcium poisoning is rare, and difficult to achieve without administering calcium intravenously. For example, the oral median lethal dose (LD50) for rats for calcium carbonate and calcium chloride are 6.45[25] and 1.4 g/kg,[26] respectively.

Interactions

Calcium supplements by mouth diminish the absorption of thyroxine when taken within four to six hours of each other.[27] Thus, people taking both calcium and thyroxine run the risk of inadequate thyroid hormone replacement and thence hypothyroidism if they take them simultaneously or near-simultaneously.[28]

Types

The intravenous formulations of calcium include calcium chloride and calcium gluconate.[1] The forms that are taken by mouth include calcium acetate, calcium carbonate, calcium citrate, calcium gluconate, calcium lactate and calcium phosphate.[1]

  • The absorption of calcium from most food and commonly used dietary supplements is very similar.[29] This is contrary to what many calcium supplement manufacturers claim in their promotional materials.
  • Different kinds of juices boosted with calcium are widely available.
  • Calcium carbonate is the most common and least expensive calcium supplement. It should be taken with food, and depends on low pH levels (acidic) for proper absorption in the intestine.[30] Some studies suggests that the absorption of calcium from calcium carbonate is similar to the absorption of calcium from milk.[31][32]
  • Antacids frequently contain calcium carbonate, and are a commonly used, inexpensive calcium supplement.
  • Coral calcium is a salt of calcium derived from fossilized coral reefs. Coral calcium is composed of calcium carbonate and trace minerals. Claims for health benefits unique to coral calcium have been discredited.
  • Calcium citrate can be taken without food and is the supplement of choice for individuals with achlorhydria or who are taking histamine-2 blockers or proton-pump inhibitors.[33] Calcium citrate is about 21% elemental calcium. One thousand mg will provide 210 mg of calcium. It is more expensive than calcium carbonate and more of it must be taken to get the same amount of calcium.
  • Calcium phosphate costs more than calcium carbonate, but less than calcium citrate. microcrystalline hydroxyapatite (MH) is one of several forms of calcium phosphate used as a dietary supplement. Hydroxyapatite is about 40% calcium.
  • Calcium lactate has similar absorption as calcium carbonate,[34] but is more expensive. Calcium lactate and calcium gluconate are less concentrated forms of calcium and are not practical oral supplements.[33]

Vitamin D is added to some calcium supplements. Proper vitamin D status is important because vitamin D is converted to a hormone in the body, which then induces the synthesis of intestinal proteins responsible for calcium absorption.[35]

Labeling

For U.S. dietary supplement and food labeling purposes the amount in a serving is expressed in milligrams and as a percent of Daily Value (%DV). The weight is for the calcium part of the compound - for example, calcium citrate - in the supplement. For calcium labeling purposes 100% of the Daily Value was 1000 mg, but as of May 2016 it has been revised to 1300 mg. A table of the pre-change adult Daily Values and references for the revision are provided at Reference Daily Intake. Food and supplement companies have until July 2018 to comply with the labeling change.

References
  1. "Calcium Salts". The American Society of Health-System Pharmacists. Archived from the original on 18 January 2017. Retrieved 8 January 2017.
  2. World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. p. 497. hdl:10665/44053. ISBN 9789241547659.
  3. British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. pp. 694, 703. ISBN 9780857111562.
  4. Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. pp. 215–216. ISBN 9781284057560.
  5. Tegethoff, F. Wolfgang (2012). Calcium Carbonate: From the Cretaceous Period into the 21st Century. Birkhäuser. p. 308. ISBN 9783034882453. Archived from the original on 16 January 2017.
  6. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  7. "The Top 300 of 2020". ClinCalc. Retrieved 11 April 2020.
  8. "Calcium - Drug Usage Statistics". ClinCalc. Retrieved 11 April 2020.
  9. "Calcium; Cholecalciferol - Drug Usage Statistics". ClinCalc. Retrieved 11 April 2020.
  10. Reid IR, Bristow SM, Bolland MJ (2015). "Calcium supplements: benefits and risks". J. Intern. Med. (Review). 278 (4): 354–68. doi:10.1111/joim.12394. PMID 26174589. S2CID 4679930.
  11. Bischoff-Ferrari, Heike A.; Dawson-Hughes, Bess; Baron, John A.; Burckhardt, Peter; Li, Ruifeng; Spiegelman, Donna; Specker, Bonny; Orav, John E.; Wong, John B. (1 December 2007). "Calcium intake and hip fracture risk in men and women: a meta-analysis of prospective cohort studies and randomized controlled trials". The American Journal of Clinical Nutrition. 86 (6): 1780–1790. doi:10.1093/ajcn/86.5.1780. ISSN 0002-9165. PMID 18065599.
  12. Moyer, Virginia A. (7 May 2013). "Vitamin D and calcium supplementation to prevent fractures in adults: U.S. Preventive Services Task Force recommendation statement". Annals of Internal Medicine. 158 (9): 691–696. doi:10.7326/0003-4819-158-9-201305070-00603. ISSN 1539-3704. PMID 23440163.
  13. Winzenberg, TM; Shaw, K; Fryer, J; Jones, G (2006). "Calcium supplementation for improving bone mineral density in children". The Cochrane Database of Systematic Reviews (2): CD005119. doi:10.1002/14651858.CD005119.pub2. PMID 16625624.
  14. Cormick, G; Ciapponi, A; Cafferata, ML; Belizán, JM (2015). "Calcium supplementation for prevention of primary hypertension". The Cochrane Database of Systematic Reviews (6): CD010037. doi:10.1002/14651858.CD010037.pub2. PMC 6486289. PMID 26126003.
  15. M. J. Bolland, A. Grey, A. Avenell, G. D. Gamble, I. R. Reid. (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 DOI: 10.1136/bmj.d2040 Archived 2012-05-31 at the Wayback Machine
  16. Downing L; Islam MA (July 2013). "Influence of calcium supplements on the occurrence of cardiovascular events". Am J Health Syst Pharm (Review). 70 (13): 1132–9. doi:10.2146/ajhp120421. PMID 23784160.
  17. "Calcium and Cancer Prevention: Strengths and Limits of the Evidence". National Cancer Institute. 4 May 2009. Archived from the original on 29 November 2014. Retrieved 2 November 2014.
  18. Weingarten MA; Zalmanovici A; Yaphe J (2008). "Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps". Cochrane Database Syst Rev (Review) (1): CD003548. doi:10.1002/14651858.CD003548.pub4. PMID 18254022.
  19. Beall DP; Henslee HB; Webb HR; Scofield RH (2006). "Milk-alkali syndrome: a historical review and description of the modern version of the syndrome". Am. J. Med. Sci. 331 (5): 233–42. doi:10.1097/00000441-200605000-00001. PMID 16702792. S2CID 45802184.
  20. Picolos MK & Orlander PR (2005). "Calcium carbonate toxicity: The updated milk-alkali syndrome; report of 3 cases and review of the literature". Endocrine Practice. 4 (11): 272–80. doi:10.4158/EP.11.4.272. PMID 16006300.
  21. Michaëlsson K; Melhus H; Warensjö 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. doi:10.1136/bmj.f228. PMC 3571949. PMID 23403980.
  22. 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 Internal Medicine. 173 (8): 639–646. doi:10.1001/jamainternmed.2013.3283. PMC 3756477. PMID 23381719.
  23. Paik JM, Curhan GC, Sun Q, et al. (2014). "Calcium supplement intake and risk of cardiovascular disease in women". Osteoporos Int. 25 (8): 2047–56. doi:10.1007/s00198-014-2732-3. PMC 4102630. PMID 24803331.
  24. Waldman T, Sarbaziha R, Merz CN, Shufelt C (2015). "Calcium Supplements and Cardiovascular Disease: A Review". Am J Lifestyle Med. 9 (4): 298–307. doi:10.1177/1559827613512593. PMC 4560115. PMID 26345134.
  25. Lewis, R. J. (1996). Sax's Dangerous Properties of Industrial Materials (9th ed.). New York, NY: Van Nostrand Reinhold. p. 635. ISBN 978-0-471-37858-7.
  26. ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute. 1988. p. 101.
  27. Singh, N.; Singh, P.; Hershman, J. (2000). "Effect of calcium carbonate on the absorption of levothyroxine". JAMA: The Journal of the American Medical Association. 283 (21): 2822–2825. doi:10.1001/jama.283.21.2822. PMID 10838651.
  28. Harding, Anne. "Calcium May Help With Weight Loss". Archived from the original on 3 July 2007. Retrieved 10 July 2007.
  29. Weaver, C.M. (2006). "29 Calcium". In Barbara A. Bowman; Robert M. Russell (eds.). Present Knowledge in Nutrition. I (9th ed.). ILSI Press. p. 377. ISBN 978-1-57881-198-4.
  30. Remington, Joseph (2005). Remington: The Science and Practice of Pharmacy. Lippincott Williams & Wilkins. p. 1338. ISBN 978-0-7817-4673-1.
  31. Zhao, Y; Martin, BR; Weaver, CM (2005). "Calcium bioavailability of calcium carbonate fortified soy milk is equivalent to cow's milk in young women" (PDF). J. Nutr. 135 (10): 2379–82. doi:10.1093/jn/135.10.2379. PMID 16177199. Archived (PDF) from the original on 18 September 2017.
  32. Martini, Ligia & Wood, Richard J (2002). "Relative bioavailability of calcium-rich dietary sources in the elderly" (PDF). American Journal of Clinical Nutrition. 76 (6): 1345–1350. doi:10.1093/ajcn/76.6.1345. PMID 12450902.
  33. Straub, D. A. (2007). "Calcium Supplementation in Clinical Practice: A Review of Forms, Doses, and Indications". Nutrition in Clinical Practice. 22 (3): 286–96. doi:10.1177/0115426507022003286. PMID 17507729.
  34. Martin, Berdine R.; Weaver, CM; Heaney, RP; Packard, PT; Smith, DL (2002). "Calcium Absorption from Three Salts and CaSO4-Fortified Bread in Premenopausal Women". Journal of Agricultural and Food Chemistry. 50 (13): 3874–6. doi:10.1021/jf020065g. PMID 12059174.
  35. Combs, G (2008). The Vitamins. Academic Press. p. 161. ISBN 978-0-12-183490-6.
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