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Drugs and Health Products

Zinc

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

Notes

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

Date

July 17, 2013

Proper name(s)

Zinc (O'Neil et al. 2009; Sweetman 2007)

Common name(s)

Zinc (O'Neil et al. 2009; Sweetman 2007)

Source material(s)

  • Zinc acetate
    (O'Neil et al. 2009; Sweetman 2007)
  • Zinc acetate dihydrate
    (O'Neil et al. 2009; Sweetman 2007)
  • Zinc ascorbate
    (EFSA 2009b)
  • Zinc bisglycinate
    (Albion 2000)
  • Zinc chloride
    (O'Neil et al. 2009; Sweetman 2007)
  • Zinc citrate
    (O'Neil et al. 2009)
  • Zinc fumarate
    (HC 2007a)
  • Zinc gluconate
    (O'Neil et al. 2009; Sweetman 2007; IOM 2003)
  • Zinc glutarate
    (HC 2007a)
  • Zinc glycerate
    (Murray 1996)
  • Zinc hydrolyzed animal protein (HAP) chelate
    (Albion 2004; Albion 1992)
  • Zinc hydrolyzed vegetable protein (HVP) chelate
    (Albion 2004; Albion 1992)
  • Zinc malate
    (HC 2007a)
  • Zinc monomethionine
    (Murray 1996)
  • Zinc oxide
    (O'Neil et al. 2009; IOM 2003)
  • Zinc picolinate
    (EFSA 2009a)
  • Zinc phosphate
    (O'Neil et al. 2009)
  • Zinc succinate
    (HC 2007a)
  • Zinc sulfate
    (O'Neil et al. 2009; Sweetman 2007; IOM 2003)
  • Zinc sulfate heptahydrate
    (O'Neil et al. 2009; Sweetman 2007; IOM 2003)
  • Zinc sulfate monohydrate
    (O'Neil et al. 2009; Sweetman 2007; IOM 2003)

Route(s) of administration

Oral

Dosage form(s)

  • The acceptable pharmaceutical dosage forms include, but are not limited to, chewables (e.g. gummies, tablets), liquids, powders, strips or tablets.
  • 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 2001).
Specific
  • Helps in connective tissue formation (Schwartz et al. 2005; IOM 2001; Groff and Gropper 2000).
  • Helps to maintain healthy skin (Shils et al. 2006; Schwartz et al. 2005; IOM 2001; Groff and Gropper 2000).
  • Helps the body to metabolize carbohydrates (IOM 2006; Shils et al. 2006; IOM 2001; Groff and Gropper 2000).
  • Helps the body to metabolize proteins (IOM 2006; Shils et al. 2006; IOM 2001; Groff and Gropper 2000).
  • Helps the body to metabolize fats (IOM 2006; Shils et al. 2006; IOM 2001; Groff and Gropper 2000).
  • Helps to maintain immune function (Shils et al. 2006; IOM 2001; Groff and Gropper 2000).
Dose-specific
For products providing daily doses of zinc at or above the Recommended Dietary Allowance (RDA) or Adequate Intake (AI):

Helps to prevent zinc deficiency (IOM 2006; Shils et al. 2006; IOM 2001; Groff and Gropper 2000).

Dose(s)

Note

When zinc HAP chelate or zinc HVP chelate is used as a source of elemental zinc, the product should be indicated for an adult subpopulation only.

Table 1: Dose information for zinc presented as dose per day
Life stage group Zinc (mg/day)
Minimum1 Maximum2

Table 1 Footnotes

Table 1 Footnote 1

Based on approximately 5% of the highest RDA or AI (IOM 2006). See Appendix 1 for definitions and Table 3 in Appendix 2 for RDA and AI values.

Return to Table 1 footnote1 referrer

Table 1 Footnote 2

Maximum doses for children and adolescents are based on the UL which applies to total zinc intake from food and supplements (IOM 2006). Maximum dose for adults supported by the following references: HC 2007a, Milne et al. 2001, Davis et al. 2000, Yadrick et al. 1989 and Fischer et al. 1984.

Return to Table 1 footnote2 referrer

Table 1 Footnote 3

Includes pregnant and breastfeeding women (IOM 2001).

Return to Table 1 footnote3 referrer

Infants 0-12 mo 0.2 2
Children 1-3 y
4-8 y
0.4
0.4
7
12
Adolescents 9-13 y
14-18 y
0.4
0.7
23
34
Adults3 19 y 0.7 50
Directions for use

Statement(s) to the effect of

  • Take a few hours before or after taking other medications (Sweetman 2007; AHFS 2005).
  • Take with food (Sweetman 2007).

Duration(s) of use

No statement is required

Risk information

Statement(s) to the effect of

Caution(s) and warning(s)

No statement is required.

Contraindication(s)

No statement is required.

Known adverse reaction(s)

For products providing zinc at the doses specified in Table 2 below, without copper or with copper at doses less than those specified in Table 2 below, the following risk statement must be included:

Zinc supplementation can cause a copper deficiency (IOM 2006; IOM 2001).

Table 2: Zinc doses requiring the risk statement above, unless the formulation provides the minimum relevant dose of copper1
Life stage group Zinc (mg/day) Copper (g/day)

Table 2 Footnotes

Table 2 Footnote 1

When copper is added to a formulation, the maximum doses indicated in the NHPID Copper Monograph must also be considered.

Return to Table 2 footnote1 referrer

Table 2 Footnote 2

No safe copper dose has been established for this subpopulation.

Return to Table 2 footnote2 referrer

Infants 0-12 mo ≤ 2 N/A2
Children 1-3 y 5-7 280
Children 4-8 y 8-12 480
Children 9-13 y 16-23 920
Adolescents 14-18 y 25-34 1,360
Adults ≥ 19 y 31-50 2,000

Non-medicinal ingredients

Must be chosen from the current NHPID and must meet the limitations outlined in that 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 pharmacopoeial monographs listed in Table 2 below.
Table 3: Monographs published in the British Pharmacopoeia (BP), European Pharmacopoeia (Ph. Eur.) and the U.S. Pharmacopoeia (USP)
Pharmacopoeia Monographs
BP Zinc Acetate
Zinc Chloride
Zinc Oxide
Zinc Sulphate Monohydrate
Zinc Sulphate Heptahydrate
Ph. Eur. Zinc Acetate Dihydrate
Zinc Chloride
Zinc Oxide
Zinc Sulphate Monohydrate
Zinc Sulphate Heptahydrate
USP Zinc Acetate
Zinc Chloride
Zinc Gluconate
Zinc Oxide
Zinc Sulfate
Zinc Sulfate Oral Solution
Zinc Sulfate Tablets

References cited

  • Albion 2004: Next link will take you to another Web site Zinc: A mineral of complex biological activity. Albion Research Notes 2004;(1). [Accessed 2009 December 4].
  • Albion 2000: Next link will take you to another Web site Implications of the "other half" of a mineral compound. Albion Research Notes 2000;9(3). [Accessed 2009 December 4].
  • Albion 1992: Next link will take you to another Web site Zinc - the multifaceted trace mineral. Albion Research Notes 1992;1(3). [Accessed 2009 December 4].
  • ASHP 2005: American Society of Health-System Pharmacists. American Hospital Formulary Service Drug Information. Philadelphia (PA): Lippincott Williams and Wilkins.
  • BP 2008: British Pharmacopoeia Commission. 2008. British Pharmacopoeia 2009, Volume II. London (GB): The Stationary Office on behalf of the Medicines and Healthcare products Regulatory Agency (MHRA).
  • Davis CD, Milne DB, Nielsen FH. 2000. Changes in dietary zinc and copper affect zinc-status indicators of postmenopausal women, notably extracellular superoxide dismutase and amyloid precursor proteins. American Journal of Clinical Nutrition 71:781-788.
  • EFSA 2009a: European Food Safety Authority. 2009. The EFSA Journal: Scientific Opinion Chromium picolinate, zinc picolinate and zinc picolinate dehydrate added for nutritional purposes in food supplements. The EFSA Journal 1113:1-41. Adopted 2009 June 4.
  • EFSA 2009b: European Food Safety Authority. 2009.Next link will take you to another Web site Scientific Document: Calcium ascorbate, magnesium ascorbate and zinc ascorbate added for nutritional purposes in food supplements. Adopted 2009 February 24. [Accessed 2009 December 4].
  • EVM 2003: Expert Group on Vitamins and Minerals of the Food Standards Agency (FSA). 2003. Part 3: Trace Elements- Chromium and Zinc. In: Safe Upper Levels for Vitamins and Minerals; Report of the Expert Group on Vitamins and Minerals. London (GB). 1-31, 171-179, 253-262.
  • Fischer PWF, Giroux A, L'Abbe MR. 1984. Effect of zinc supplementation on copper status in adult man. American Journal of Clinical Nutrition 40:743-746.
  • Groff J, Gropper S. 2000. Advanced Nutrition and Human Metabolism, 3rd edition. Belmont (CA): Wadsworth/Thomson Learning.
  • HC 2007a: Health Canada. 2007.Next link will take you to another Web site Online Drug Product Database. Ottawa (ON): Health Canada. [Accessed 2009 December 4].
  • HC 2007b: Health Canada. 2007. NHPD Expert Advisory Committee Issue Analysis Summary: What is an acceptable maximum daily dose for oral zinc supplements? Ottawa (ON): Natural Health Products Directorate, Health Canada.
  • 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, 5th edition. Washington (DC): National Academies Press.
  • IOM 2001: Institute of Medicine. Panel on Micronutrients, Subcommittees on Upper Reference Levels of Nutrients and Interpretation and Uses of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine. 2001. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington (DC): National Academy Press.
  • Milne DB, Davis CD, Neilsen FH. 2001. Zinc alters indices of copper function and status in postmenopausal women. Nutrition 17:701-708.
  • Murray MT. 1996. Encyclopedia of Nutritional Supplements: The Essential Guide for Improving your Health Naturally. Rocklin (CA): Prima Health.
  • O'Neil MJ, Smith A, Heckelman PE, Budavari S, editors. 2009.Next link will take you to another Web site Merck Index: An Encyclopedia of Chemicals, Drugs, & Biologicals, 13th edition. Whitehouse Station (NJ): Merck & Co., Inc.; Electronic version. [Accessed 2009 December 4].
  • Ph. Eur. 2008: European Pharmacopoeia Commission. 2008. European Pharmacopoeia, 6th edition, Volume 1. Strasbourg (FR): Directorate for the Quality of Medicines and HealthCare of the Council of Europe (EDQM).
  • Sakai F, Yoshida S, Endo S, Tomita H. 2002. Double-blind, Placebo-controlled Trial of Zinc Picolinate for Taste Disorders. Informa healthcare 122:129-133.
  • SCF 2003: Scientific Committee on Food, 2003.Next link will take you to another Web site Opinion of the Scientific Committee on Food on the tolerable upper intake level of zinc (expressed on 5 March 2003). European Commission, Health and Consumer Protection Directorate-General, Directorate C - Scientific Opinions, C2 - Management of scientific committees; scientific co-operation and networks. [Accessed 2009 December 4].
  • Schwartz JR, Marsh RG, Draelos ZD. 2005. Zinc and skin health: overview of physiology and pharmacology. Dermatologic Surgery;31(7 Part 2):837-847.
  • Shils ME, Olson JA, Shike M, Ross AC, editors. 2006. Modern Nutrition in Health and Disease, 10th edition. Philadelphia (PA): Lippincott Williams and Wilkins.
  • Sweetman SC, editor. 2007. Martindale: The Complete Drug Reference, 35th edition. London (GC): Pharmaceutical Press.
  • 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.
  • Yadrick MK, Kenney MA, Winterfeldt EA.1989. Iron, copper, and zinc status: response to supplementation with zinc or zinc and iron in adult females. American Journal of Clinical Nutrition 49:145-150.

References reviewed

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  • Bailey MM, Boohaker JG, Jernigan PL, Townsend MB, Sturdivant J, Rasco JF, Vincent JB, and Hood RD. 2008. Effects of Pre- and Postnatal Exposure to Chromium Picolinate or Picolinic Acid on Neurological Development in CD-1 Mice. Biological Trace Element Research 124:70-82
  • Barrie SA, Wright JV, Pizzorno JE, Kutter E, and Barron PC. 1987. Comparative absorption of zinc picolinate, zinc citrate and zinc gluconate in humans. Agents and Actions 21: 223-228
  • Berner TO, Murphy MM, Slesinki R. 2004. Determining the safety of chromium tripicolinate. The ENVIRON Health Sciences Institute, Arlington. Food and Chemical Toxicology 42; 1029-1042
  • Beskid M, Jachimowicz J, Taraszewska A, Kukulska D. 1995. Histological and ultrastructural changes in the rat brain following systemic administration of picolinic acid. Experimental and Toxicologic Pathology 47(1):25-30.
  • Bosco MC, Rapisarda A, Massazza S, Melillo G, Young H, Varesio L. 2000. The tryptophan catabolite picolinic acid selectively induces the chemokines macrophage inflammatory protein-1α and -1β in macrophages. The Journal of Immunology 164(6):3283-3291.
  • COM 2004: Committee on Mutagenicity of Chemicals in Food, Consumer Products and the Environment.Next link will take you to another Web site Statement on the Mutagenicity of Trivalent Chromium and Chromium Picolinate. December 2004. Department of Health. United Kingdom. [Accessed 2009 December 4].
  • EFSA 2009: European Food Safety Authority. Summary of Opinion: Scientific Opinion Chromium picolinate, zinc picolinate and zinc picolinate dehydrate added for nutritional purposes in food supplements. Adopted 2009 June 4.
  • Fernandez-Pol JA. 1978. Morphological changes induced by picolinic acid in cultured mammalian cells. Experimental and Molecular Pathology 29(3):348-357.
  • Goda K, Kishimoto R, Shimizu S, Hamane Y, Ueda M. 1996. Quinolinic acid and active oxygens: possible contribution of active oxygens during cell death in the brain. Advances in Experimental Medicine and Biology. 398:247-254.
  • Goodwin FK, Sack RL. 1974. Behavioral effects of new dopamine--hydroxylase inhibitor (fusaric acid) in man. Journal of Psychiatric Research 11:211-217.
  • Guidi R, Rao M. 2004. In vitro Mammalian Chromosome Aberration Test. Bioreliance Report no AA85MC.331.BTL
  • HC 1996: Health Canada.Next link will take you to another Web site Drugs Directorate Labelling Standard: Mineral Supplements. [Accessed 2009 December 4].
  • HC 2007: Health Canada.Next link will take you to another Web site Monograph- Multi-vitamin/mineral Supplement. [Accessed 2009 December 4].
  • HC 2009: Health Canada.Next link will take you to another Web site Drug Product Database. [Accessed 2009 December 4].
  • HC 2009: Health Canada.Next link will take you to another Web site Licensed Natural Health Products Database. [Accessed 2009 December 4].
  • Kirkil G, Muz MH, Seckin D, Sahin K, Kucuk O. 2008. Antioxidant effect of zinc picolinate in patients with chronic obstructive pulmonary disease. Respiratory Medicine 102: 840-844
  • Manygoats KR, Yazzie M, Stearns DM. 2002. Ultrastructural damage in chromium picolinate-treated cells: a TEM study. Journal of Biological Inorganic Chemistry 7(7-8):791-798.
  • Mehler AH. 1956. Formation of picolinic and quinolinic acids following enzymatic oxidation of 3-hydroxyanthranilic acid. The Journal of Biological Chemistry 218(1):241-254.
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  • Speetjens JK, Parand A, Crowder MW, Vincent JB, Woski SA. 1999. Low-molecular-weight chromium-binding substance and biomimetic [Cr3O(O2CCH2CH3)6(H2O)3]+ do not cleave DNA under physiologically-relevant conditions. Polyhedron 18(20):2617-2624.
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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 Allowance (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: RDA, AI and UL Values

The AI (as indicated by an asterisk) and RDA values for zinc 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 zinc deficiency";
  • facilitate the optional labelling of % RDA and AI values.
Table 4: Recommended Dietary Allowance and Adequate Intake* values for zinc based on life stage group (IOM 2006)
Life stage group Zinc (mg/day)
Infants 0-6 mo
7-12 mo
2*
3
Children 1-3 y
4-8 y
3
5
Adolescent males 9-13 y
14-18 y
8
11
Adult males ≥ 19 y 11
Adolescent females 9-13 y
14-18 y
8
9
Adult females ≥ 19 y 8
Pregnancy 14-18 y
19-50 y
12
11
Breastfeeding 14-18 y
19-50 y
13
12

The RDA values for copper are provided below. These values are intended to provide guidance on the minimum quantity of copper required for zinc products, as zinc supplementation is known to cause copper deficiency.

Table 5: Recommended Dietary Allowance for copper based on life stage group (IOM 2006)
Life Stage Group Copper (g/day)

Table 5 Footnotes

Table 5 Footnote 1

An AI for infants exists but has not been included since copper supplementation is not appropriate in infants.

Return to Table 5 footnote1 referrer

Infants1 0-6 mo
7-12 mo
-
-
Children 1-3 y
4-8 y
340
440
Adolescent males 9-13 y
14-18 y
700
890
Adult males ≥ 19 y 900
Adolescent females 9-13 y
14-18 y
700
890
Adult females ≥ 19 y 900
Pregnancy 14-50 y 1000
Breastfeeding 14-50 y 1300
Table 6: Tolerable Upper Intake Level for zinc for adults ≥ 19 years (IOM 2006)
Life stage group Zinc (mg/day)
Adults 40