Calcium

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Archived Monograph - November 2007

This monograph is intended to serve as a guide to industry for the preparation of Product Licence Applications (PLA) and labels for natural health product market authorization. It is not intended to be a comprehensive review of the medicinal ingredient. It is a referenced document to be used as a labelling standard.

Note: Text in parentheses is additional optional information which can be included on the PLA and product labels at the applicants' discretion. The solidus (/) indicates that the terms are synonyms or that the statements are synonymous. Either term or statement may be selected by the applicant.

Date: June 23, 2009

Proper name(s): Calcium (Sweetman 2007; O'Neil et al. 2006)

Common name(s): Calcium (Sweetman 2007; O'Neil et al. 2006)

Source material(s):

• Bone meal*
  (HC 2007)
• Calcium acetate
  (Sweetman 2007; IOM 2003; O'Neil et al. 2006)
• Calcium ascorbate
  (Sweetman 2007; IOM 2003; O'Neil et al. 2006)
• Calcium bisglycinate
  (Albion 2000)
• Calcium carbonate
  (Sweetman 2007; IOM 2003; O'Neil et al. 2006)
• Calcium chloride
  (Sweetman 2007; IOM 2003; O'Neil et al. 2001)
• Calcium chloride dihydrate
  (Sweetman 2007; IOM 2003; O'Neil et al. 2006)
• Calcium chloride hexahydrate
  (Sweetman 2007; O'Neil et al. 2006)
• Calcium citrate
  (Sweetman 2007; IOM 2003; O'Neil et al. 2006)
• Calcium citrate malate
  (Patrick 1999)
• Calcium citrate tetrahydrate
  (Sweetman 2007; O'Neil et al. 2006)
• Calcium fumarate
  (HC 2007)
• Calcium glubionate
  (Sweetman 2007)
• Calcium glubionate monohydrate
  (Sweetman 2007)
• Calcium gluceptate
  (Sweetman 2007)
• Calcium gluconate
  (Sweetman 2007; IOM 2003; O'Neil et al. 2006)
• Calcium gluconate monohydrate
  (Sweetman 2007; IOM 2003)
• Calcium glutarate
  (HC 2007)
• Calcium glycerophosphate
  (Sweetman 2007; IOM 2003; O'Neil et al. 2006)
• Calcium hydrolyzed animal protein (HAP) chelate
  (Albion 1996; Albion 1993)**
• Calcium hydrolyzed vegetable protein (HVP) chelate
  (Albion 1996; Albion 1993)**
• Calcium hydroxide
  (IOM 2003)
• Calcium lactate
  (Sweetman 2007; IOM 2003; O'Neil et al. 2006)
• Calcium lactate gluconate
  (Sweetman 2007)
• Calcium lactate pentahydrate
  (Sweetman 2007; IOM 2003; O'Neil et al. 2006)
• Calcium lactate trihydrate
  (Sweetman 2007; IOM 2003)
• Calcium lactobionate dihydrate
  (Sweetman 2007; IOM 2003)
• Calcium levulinate
  (Sweetman 2007; O'Neil et al. 2006)
• Calcium levulinate dihydrate
  (Sweetman 2007; O'Neil et al. 2006)
• Calcium malate
  (HC 2007)
• Calcium oxide
  (IOM 2003)
• Calcium phosphate dibasic
  (Sweetman 2007; IOM 2003)
• Calcium phosphate monobasic
  (Sweetman 2007; IOM 2003; O'Neil et al. 2006)
• Calcium phosphate tribasic
  (Sweetman 2007; IOM 2003; O'Neil et al. 2006)
• Calcium pidolate
  (Sweetman 2007)
• Calcium pyrophosphate
  (IOM 2003)
• Calcium silicate
  (Sweetman 2007; IOM 2003; O'Neil et al. 2006)
• Calcium sodium lactate
  (Sweetman 2007)
• Calcium succinate
  (O'Neil et al. 2006)
• Calcium sulfate
  (IOM 2003)
• Calcium sulfate dihydrate
  (IOM 2003)
• Coral
  (HC 2007)
• Dolomite
  (Sweetman 2007; O'Neil et al. 2006)
• Oyster shell
  (HC 2007)

* When bone meal is used as a source material for calcium, it must be sourced from a non-human animal that is not susceptible to Transmissible Spongiform Encephalopathy (TSE) diseases, including Bovine Spongiform Encephalopathy (BSE) (HC 2006).
** When calcium HAP or HVP chelate are used as a source material, the products should be indicated for an adult subpopulation only.

Route(s) of administration: Oral

Dosage form(s): Those pharmaceutical dosage forms suited to oral administration, including but not limited to chewables (eg. gummies, tablets), caplets, capsules, strips, lozenges, powders or liquids where the dose is measured in drops, teaspoons or tablespoons, are acceptable. This monograph is not intended to include foods or food-like dosage forms such as bars, chewing gums or beverages.

Use(s) or Purpose(s): Statement(s) to the effect of:

General: A factor in the maintenance of good health (IOM 2006; IOM 1997).

Specific:

• Helps in the development and maintenance of bones and teeth (Optional: "especially in childhood, adolescence and young adulthood") (IOM 2006; Shils et al. 2006; Groff and Gropper 2000; IOM 1997).
• Adequate calcium (and vitamin D) (throughout life) as part of a healthy diet, (along with physical activity) helps prevent bone loss/osteoporosis (in peri- and postmenopausal women) (in later life) (FDA 2008; NAMS 2006; Shils et al. 2006; Groff and Gropper 2000; NIH 2000; Brown and Josse 2002; Tang et al. 2007).
  
  Note: "may reduce the risk of developing osteoporosis" is an acceptable alternative to "helps prevent bone loss/osteoporosis".

Dose-specific: For products providing daily doses of calcium at or above the Adequate Intake (AI) (adjusted for the life stage groups), the following use or purpose is acceptable: Helps to prevent calcium deficiency (IOM 2006; Shils et al. 2006; Groff and Gropper 2000; IOM 1997).

See Appendix 1 for definitions and Table 2 in Appendix 2 for AI values.

Dose(s):

Table 1: Dose information for calcium presented as dose per day

Life stage group		Calcium (mg/day)
		Minimum1	Maximum2
Children	1-3 y	65	1,500
	4-8 y	65	1,500
Adolescents	9-13 y	65	1,500
	14-18 y	65	1,500
Adults3	≥ 19 y	65	1,500

¹ Based on approximately 5% of the highest AI (IOM 2006). See Appendix 1 for definitions and Table 2 in Appendix 2 for AI values.
² Maximum dose based on the Tolerable Upper Intake Level (UL) less average dietary intake (adapted from IOM 2006).
³ Includes pregnant and breastfeeding women.

Directions for use: Statement(s) to the effect of:

Take a few hours before or after taking other medications (Sweetman 2007; ASHP 2005).

Duration of use: No statement required.

Risk information:

Caution(s) and warning(s): No statement required.

Contraindication(s): No statement required.

Known adverse reaction(s): No statement required.

Non-medicinal ingredients: Must be chosen from the current NHPD Natural Health Products Ingredients Database and must meet the limitations outlined in the database.

Specifications:

• The finished product must comply with the minimum specifications outlined in the current NHPD Compendium of Monographs.
• The medicinal ingredient may comply with the specifications outlined in the applicable calcium monographs published in the USA (USP), British (BP) and European (Ph. Eur.) Pharmacopoeias.

References cited:

Albion 2000: Implications of the "other half" of a mineral compound. [online]. Albion Research Notes 2000;9(3). [Accessed 2009 June 23].Available from: http://www.news.albionminerals.com/human-nutrition/research-notes-pdf/doc_download/738-implications-of-the-qother-halfq-of-a-mineral-compound

Albion 1996: Effective calcium supplementation: not as easy as advertised!!! [online]. Albion Research Notes 1996;5(3). [Accessed 2009 June 23]. Available from: http://www.news.albionminerals.com/human-nutrition/research-notes-pdf/doc_details/725-effective-calcium-supplementation-not-as-easy-as-advertised

Albion 1993: Calcium absorption conflict. [online]. Albion Research Notes 1993;2(2). [Accessed 2009 June 23].Available from: http://www.news.albionminerals.com/human-nutrition/research-notes-pdf/doc_download/714-calcium-absorption-conflict

ASHP 2005: American Society of Health-System Pharmacists. American Hospital Formulary Service (AHFS) Drug Information. Philadelphia (PA): Lippincott Williams and Wilkins; 2005.

BP 2008: British Pharmacopoeia Commission. 2007. British Pharmacopoeia 2008, Volume 1. London (UK): The Stationary Office

Brown JP, Josse RG. 2002. 2002 Clinical Practice Guidelines for the Diagnosis and Management of Osteoporosis in Canada. Canadian Medical Association Journal 167(S10):S1-S34.

FDA 2008: United States Food and Drug Administration. Calcium and Osteoporosis, and Calcium, Vitamin D, and Osteoporosis. [online] Federal Register, Volume 73, Number 189, September 29, 2008, Final Rules. Docket Number FDA-2004-P-0205 (formerly Docket Number 2004P-0464) Rockville (MD): Department of Health and Human Services, U.S. Food and Drug Administration. [Accessed 2009 June 23].Available from: http://www.fda.gov/OHRMS/DOCKETS/98fr/E8-22730.pdf

Groff J, Gropper S. 2000. Advanced Nutrition and Human Metabolism, 3^rd edition. Belmont (CA): Wadsworth/Thomson Learning.

HC 2007: Health Canada. Drug Product Database. [online]. [Accessed 2009 May 21]. Available from: http://webprod.hc-sc.gc.ca/dpd-bdpp/index-eng.jsp

HC 2006: Health Canada. Evidence for Safety and Efficacy of Finished Natural Health Products. [online]. Ottawa (ON): Natural Health Products Directorate, Health Canada; 2006. [Accessed 2009 June 23]. Available from: http://www.hc-sc.gc.ca/dhp-mps/prodnatur/legislation/docs/efe-paie_e.html

IOM 2006: Institute of Medicine. Otten JJ, Pitzi Hellwig J, Meyers LD, editors. 2006. Institute of Medicine Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington (DC): National Academies Press.

IOM 2003: Institute of Medicine. Committee on Food Chemicals Codex, Food and Nutrition Board, Institute of Medicine. 2003. Food Chemicals Codex, 5^th edition. Washington (DC): National Academies Press.

IOM 1997: Institute of Medicine. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine. 1997. Dietary Reference Intakes for Calcium, Phosphorous, Magnesium, Vitamin D, and Fluoride. Washington (DC): National Academy Press.

NAMS (The North American Menopause Society). 2006. Position Statement - The role of calcium in peri- and postmenopausal women: 2006 position statement of The North American Menopause Society. The Journal of the North American Menopause Society 13(6):862-877.

NIH 2000: National Institute of Health. Osteoporosis Prevention, Diagnosis, and Therapy. NIH Consensus Statement Online 2000;17(1):1-36. Bethesda (MD): National Institute of Health; March 27-29, 2000. [Accessed 2009 June 23]. Available from: http://www.consensus.nih.gov/2000/2000Osteoporosis111html.htm

O'Neil MJ, Smith A, Heckelman PE, Budavari S, editors. 2006. The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 14^th edition. Whitehouse Station (NJ): Merck & Co., Inc.

O'Neil MJ, Smith A, Heckelman PE, Budavari S, editors. 2001. The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 13^th edition. Whitehouse Station (NJ): Merck & Co., Inc.

Patrick L. 1999. Comparative absorption of calcium sources and calcium citrate malate for the prevention of osteoporosis. Alternative Medicine Review 4(2):74-85.

Ph. Eur. 2008: European Pharmacopoeia Commission. 2007. European Pharmacopoeia, 6th edition, Volume 2. Strasbourg (FR): Directorate for the Quality of Medicines and HealthCare of the Council of Europe (EDQM).

Shils ME, Olson JA, Shike M, Ross AC, editors. 2006. Modern Nutrition in Health and Disease, 10^th edition. Philadelphia (PA): Lippincott Williams and Wilkins.

Sweetman SC, editor. 2007. Martindale: The Complete Drug Reference, 35^th edition. London (UK): Pharmaceutical Press.

Tang BMP, Eslick GD, Nowson C, Smith C, Bensoussan A. 2007. Use of calcium or calcium in combination with vitamin D supplementation to prevent fracture and bone loss in people aged 50 years and older: a meta-analysis. Lancet 370(9588):657-666.

USP 32: United States Pharmacopeial Convention. 2009. United States Pharmacopeia and the National Formulary (USP 32 - NF 27). Rockville (MD): The United States Pharmacopeial Convention.

References reviewed:

Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, Delmas PD, Meunier PJ. 1992. Vitamin D3 and calcium to prevent hip fractures in elderly women. The New England Journal of Medicine 327(23):1637-1642.

Prestwood KM, Pannullo AM, Kenny AM, Pilbearn CC, Raisz LG. 1996; The effect of a short course of calcium and vitamin D on bone turnover in older women. Osteoporosis International 6(4):314-319.

Ruml LA, Sakhaee K, Peterson R, Adams-Huet B, Pak CY. 1999. The effect of calcium citrate on bone density in the early and mid-postemenopausal period : a randomized placebo-controlled study. American Journal of Therapeutics 6(6):303-311.

Health Canada. 2007. Canadian Community Health Survey Cycle 2.2, Nutrition (2004). A Guide to Accessing and Interpreting the Data. [online]. Office of Nutrition Policy and Promotion. Health Products and Food Branch. [Accessed 2009 May 21] Available from: http://www.hc-sc.gc.ca/fn-an/alt_formats/hpfb-dgpsa/pdf/surveill/cchs-guide-escc_e.pdf

Appendix 1: Definitions

Adequate Intake (AI): The recommended average daily intake level based on observed or experimentally determined approximations or estimates of nutrient intake by a group (or groups) of apparently healthy people that are assumed to be adequate. An AI is used when an RDA cannot be determined (IOM 2006).

Recommended Dietary Allowances (RDA): The average daily dietary nutrient intake level sufficient to meet the nutrient requirements of nearly all (97-98%) healthy individuals in a particular life stage and gender group (IOM 2006).

Tolerable Upper Intake Level (UL): The highest average daily nutrient intake level that is likely to pose no risk of adverse health effects to almost all individuals in the general population. As intake increases above the UL, the potential risk of adverse effects may increase (IOM 2006).

Appendix 2: AI Values

The AI values for calcium are provided below. For the purpose of this monograph, these values are intended to:

• provide targets for setting appropriate supplement dosage levels;
• provide the minimum dose for the use of the dose specific use or purpose: "Helps to prevent calcium deficiency";
• facilitate the optional labelling of % AI values.

Table 2: Adequate Intake ( AI) values for calcium based on life stage group (IOM 2006)

Life stage group		Calcium (mg/day)
Children	1-3 y	500
	4-8 y	800
Adolescents	9-18 y	1,300
Adults	19-50 y	1,000
	≥ 51 y	1,200
Pregnancy	14-18 y	1,300
	19-50 y	1,000
Breastfeeding	14-18 y	1,300
	19-50 y	1,000