MULTI-VITAMIN/MINERAL SUPPLEMENTS MONOGRAPH

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Date

March 31, 2023

Table of Contents

MULTI-VITAMIN/MINERAL SUPPLEMENTS MONOGRAPH

Notes

1.0 Proper names, Common names and Source information

Notes

1.1 Vitamin proper names, common names and source information

Table 1. Vitamin proper names, common names and source information
Proper name(s)1 Common name(s)2 Source information3
Source ingredient(s)
Biotin Biotin
  • Biocytin
  • Biotin
Folate
  • Folate
  • Vitamin B9
  • Folic acid
  • L-5-Methyltetrahydrofolate
  • L-5-Methyltetrahydrofolate, calcium salt
  • L-5-Methyltetrahydrofolic acid, glucosamine salt
Niacin
  • Niacin
  • Vitamin B3
  • Inositol hexanicotinate
  • Niacinamide
  • Nicotinic acid
Niacinamide
  • Niacinamide
  • Nicotinamide
  • Vitamin B3
  • Niacinamide
  • Niacinamide ascorbate
Pantothenic acid
  • Pantothenic acid
  • Vitamin B5
  • Calcium D-pantothenate
  • Calcium DL-pantothenate
  • Dexpanthenol
  • DL-Panthenol
  • DL-Pantothenic acid
  • D-Pantethine
  • Panthothenic acid
Riboflavin
  • Riboflavin
  • Vitamin B2
  • Riboflavin
  • Riboflavin 5'-phosphate
  • Riboflavin 5'-phosphate sodium
Thiamine
  • Thiamine
  • Vitamin B1
  • Benfotiamine
  • Thiamine
  • Thiamine diphosphate
  • Thiamine hydrochloride
  • Thiamine mononitrate
  • Thiamine monophosphate
Vitamin A Vitamin A
  • all-trans-Retinol
  • all-trans-Retinyl acetate
  • all-trans-Retinyl palmitate
Vitamin B6 Vitamin B6
  • Pyridoxal
  • Pyridoxal 5'-phosphate
  • Pyridoxal 5'-phosphate, calcium salt
  • Pyridoxal 5'-phosphate monohydrate
  • Pyridoxal hydrochloride
  • Pyridoxamine
  • Pyridoxamine 5'-phosphate
  • Pyridoxine
  • Pyridoxine 5'-phosphate
  • Pyridoxine hydrochloride
Vitamin B12 Vitamin B12
  • Cobamamide
  • Cyanocobalamin
  • Hydroxocobalamin
  • Hydroxocobalamin acetate
  • Methylcobalamin
Vitamin C Vitamin C
  • Ascorbic acid
  • Ascorbic acid 2-O-glucoside
  • Ascorbyl methylsilanol pectinate
  • Ascorbyl palmitate
  • Calcium ascorbate
  • Calcium ascorbate, dihydrate
  • Magnesium ascorbate
  • Magnesium ascorbyl phosphate
  • Manganese (II) ascorbate
  • Niacinamide ascorbate
  • Potassium ascorbate
  • Sodium ascorbate
  • Zinc ascorbate
Vitamin D
  • Vitamin D
  • Vitamin D2
Ergocalciferol
  • Vitamin D
  • Vitamin D3
Cholecalciferol
Vitamin E Vitamin E
  • d-alpha Tocopherol
  • d-alpha Tocopheryl acetate
  • d-alpha Tocopheryl acid succinate
  • dl-alpha Tocopherol
  • dl-alpha Tocopheryl acetate
  • dl-alpha Tocopheryl acid succinate
Vitamin K1 Vitamin K1 Phytonadione
Vitamin K2 Vitamin K2
  • Menaquinone 4
  • Menaquinone 6
  • Menaquinone 7
  • Menaquinones
  • Menatetrenone

1,2 At least one of the following references was consulted per name: NIH 2015a; Sweetman 2015; USP 38 2015; FCC 9 2014; O'Neil 2013; IOM 2006.

3 At least one of the following references was consulted per source information: NIH 2015a; FAO 2012; Sweetman 2015; USP 38 2015; FCC 9 2014; O'Neil 2013; EFSA 2009a; FSANZ 2008; IOM 2006; Van Der Kuy et al. 2002; Chalmers et al. 2000; EC 2000; Zeitlin et al. 1985.

1.2 Mineral proper names, common names and source information

Table 2. Mineral proper names, common names and source information
Proper name(s)1 Common name(s)2 Source information3
Source ingredient(s) Organism group(s) Source material(s) Part(s)
Calcium4 Calcium
  • Calcium acetate
  • Calcium amino acid chelate
  • Calcium ascorbate
  • Calcium aspartate
  • Calcium bisglycinate
  • Calcium carbonate
  • Calcium chloride
  • Calcium chloride, dihydrate
  • Calcium chloride, hexahydrate
  • Calcium citrate
  • Calcium citrate malate
  • Calcium citrate, tetrahydrate
  • Calcium diglutamate
  • Calcium D-pantothenate
  • Calcium fumarate
  • Calcium glubionate
  • Calcium glubionate, monohydrate
  • Calcium gluceptate
  • Calcium gluconate
  • Calcium gluconate, monohydrate
  • Calcium glutamate
  • Calcium glutarate
  • Calcium glycerophosphate
  • Calcium hydrolyzed animal protein (HAP) chelate
  • Calcium hydrolyzed vegetable protein (HVP) chelate
  • Calcium hydroxide
  • Calcium hypophosphite
  • Calcium lactate
  • Calcium lactate gluconate
  • Calcium lactate, monohydrate
  • Calcium lactate, pentahydrate
  • Calcium lactate, trihydrate
  • Calcium lactobionate, dihydrate
  • Calcium levulinate
  • Calcium levulinate, dihydrate
  • Calcium lysinate
  • Calcium malate
  • Calcium orotate
  • Calcium oxide
  • Calcium phosphate, dibasic
  • Calcium phosphate, dibasic, dihydrate
  • Calcium phosphate, monobasic
  • Calcium phosphate, tribasic
  • Calcium pidolate
  • Calcium pyrophosphate
  • Calcium pyruvate
  • Calcium saccharate
  • Calcium saccharate, tetrahydrate
  • Calcium silicate
  • Calcium sodium lactate
  • Calcium succinate
  • Calcium sulfate
  • Calcium sulfate, dihydrate
  • Calcium sulfate, hemihydrate
  • Calcium L-threonate
  • Dicalcium malate
  • Dolomite
  • Durapatite
N/A N/A N/A
N/A Bone meal4 N/A Bone
Coral N/A Calcareous skeleton
Oyster N/A Shell
Chromium5 Chromium
  • Chromium amino acid chelate
  • Chromium (III) bisglycinate
  • Chromium (III) chloride
  • Chromium (III) chloride, hexahydrate
  • Chromium (III) citrate
  • Chromium (III) dinicocysteinate
  • Chromium (III) dinicotinate
  • Chromium (III)-enriched yeast
  • Chromium (III) fumarate
  • Chromium (III) glutarate
  • Chromium (III) hydrolyzed animal protein (HAP) chelate
  • Chromium (III) hydrolyzed vegetable protein (HVP) chelate
  • Chromium (III) lactate, trihydrate
  • Chromium (III) malate
  • Chromium (III) nicotinate
  • Chromium (III) nicotinate glycinate
  • Chromium (III) nitrate
  • Chromium (III) picolinate5
  • Chromium (III) pidolate
  • Chromium (III) potassium sulfate, dodecahydrate
  • Chromium (III) succinate
  • Chromium (III) sulfate
N/A N/A N/A
Cobalt Cobalt
  • Cobamamide
  • Cyanocobalamin
  • Hydroxocobalamin
  • Methylcobalamin
N/A N/A N/A
Copper Copper
  • Calcium copper edetate
  • Copper amino acid chelate
  • Copper (II) acetate
  • Copper (II) aspartate
  • Copper (II) bisglycinate
  • Copper (II) carbonate
  • Copper (II) chloride
  • Copper (II) chloride, dihydrate
  • Copper (II) citrate
  • Copper (II) fumarate
  • Copper (II) gluconate
  • Copper (II) glutarate
  • Copper (II) hydrolyzed animal protein (HAP) chelate
  • Copper (II) hydrolyzed vegetable protein (HVP) chelate
  • Copper (II) malate
  • Copper (II) sebacate
  • Copper (II) succinate
  • Copper (II) sulfate
  • Copper (II) sulfate, monohydrate
  • Copper (II) sulfate, pentahydrate
N/A N/A N/A
Iodine6 Iodine
  • Potassium iodate
  • Potassium iodide
  • Sodium iodide
N/A N/A N/A
N/A N/A
  • Fucus vesiculosus6
  • Fucus serratus6
  • Ascophyllum nodosum6
  • Laminaria digitata6
  • Laminaria japonica6
  • Macrocystis pyrifera6
  • Thallus
  • Whole
Iron Iron
  • Dried iron (II) sulfate
  • Ferritin
  • Ferrocholinate
  • Iron, carbonyl
  • Iron, electrolytic
  • Iron, reduced
  • Iron amino acid chelate
  • Iron hydrolyzed animal protein (HAP) chelate
  • Iron hydrolyzed vegetable protein (HVP) chelate
  • Iron (II) ascorbate
  • Iron (II) aspartate
  • Iron (II) aspartate, tetrahydrate
  • Iron (II) bisglycinate
  • Iron (II) carbonate
  • Iron (II) carbonate mass
  • Iron (II) chloride
  • Iron (II) chloride, tetrahydrate
  • Iron (II) citrate
  • Iron (II) citrate, decahydrate
  • Iron (II) citrate, monohydrate
  • Iron (II) fumarate
  • Iron (II) gluceptate
  • Iron (II) gluconate
  • Iron (II) gluconate, dihydrate
  • Iron (II) glutarate
  • Iron (II) glycine sulfate
  • Iron (II) lactate
  • Iron (II) lactate, trihydrate
  • Iron (II) malate
  • Iron (II) oxalate
  • Iron (II) oxalate, dihydrate
  • Iron (II) phosphate
  • Iron (II) pidolate
  • Iron (II) succinate
  • Iron (II) sulfate
  • Iron (II) sulfate, heptahydrate
  • Iron (II) tartrate
  • Iron (II) taurate
  • Iron (III) ammonium citrate
  • Iron (III) citrate
  • Iron (III) glycerophosphate
  • Iron (III) glycinate
  • Iron (III) phosphate
  • Iron (III) pyrophosphate
  • Polysaccharide-iron complex
N/A N/A N/A
Magnesium Magnesium
  • Dolomite
  • Magnesium acetate
  • Magnesium acetate, tetrahydrate
  • Magnesium acetyl taurate
  • Magnesium amino acid chelate
  • Magnesium ascorbate
  • Magnesium ascorbate, monohydrate
  • Magnesium aspartate
  • Magnesium aspartate, dihydrate
  • Magnesium aspartate hydrochloride, trihydrate
  • Magnesium aspartate, tetrahydrate
  • Magnesium bisglycinate
  • Magnesium carbonate
  • Magnesium chloride
  • Magnesium chloride, hexahydrate
  • Magnesium citrate
  • Magnesium citrate, tribasic
  • Magnesium citrate malate
  • Magnesium dibutyrate
  • Magnesium fumarate
  • Magnesium gluceptate
  • Magnesium gluconate
  • Magnesium gluconate, dihydrate
  • Magnesium glutarate
  • Magnesium glycerophosphate
  • Magnesium hydrolyzed animal protein (HAP) chelate
  • Magnesium hydrolyzed vegetable protein (HVP) chelate
  • Magnesium hydroxide
  • Magnesium hydroxide carbonate
  • Magnesium lactate
  • Magnesium L-threonate
  • Magnesium lysinate
  • Magnesium lysyl glycinate
  • Magnesium malate
  • Magnesium orotate
  • Magnesium orotate, dihydrate
  • Magnesium oxide
  • Magnesium phosphate, dibasic
  • Magnesium phosphate, dibasic, mixed hydrates
  • Magnesium phosphate, dibasic, trihydrate
  • Magnesium phosphate, monobasic
  • Magnesium phosphate, tribasic
  • Magnesium phosphate, tribasic, octahydrate
  • Magnesium phosphate, tribasic, pentahydrate
  • Magnesium phosphate, tribasic, tetrahydrate
  • Magnesium pidolate
  • Magnesium succinate
  • Magnesium sulfate
  • Magnesium sulfate, heptahydrate
  • Magnesium sulfate, monohydrate
  • Magnesium sulfate, trihydrate
  • Magnesium taurate
  • Magnesium trisilicate
N/A N/A N/A
Manganese Manganese
  • Manganese amino acid chelate
  • Manganese (II) ascorbate
  • Manganese (II) aspartate
  • Manganese (II) bisglycinate
  • Manganese (II) carbonate
  • Manganese (II) chloride
  • Manganese (II) chloride, tetrahydrate
  • Manganese (II) citrate
  • Manganese (II) fumarate
  • Manganese (II) gluconate
  • Manganese (II) gluconate, dihydrate
  • Manganese (II) glycerophosphate
  • Manganese (II) hydrolyzed animal protein (HAP) chelate
  • Manganese (II) hydrolyzed vegetable protein (HVP) chelate
  • Manganese (II) pidolate
  • Manganese (II) succinate
  • Manganese (II) sulfate
  • Manganese (II) sulfate, monohydrate
  • Manganese (II) sulfate, tetrahydrate
  • Manganese (IV) dioxide
N/A N/A N/A
Molybdenum Molybdenum
  • Ammonium molybdate (VI)
  • Ammonium molybdate (VI), tetrahydrate
  • Molybdenum amino acid chelate
  • Molybdenum (VI) aspartate
  • Molybdenum (VI) bisglycinate
  • Molybdenum (VI) citrate
  • Molybdenum (VI) fumarate
  • Molybdenum (VI) glutarate
  • Molybdenum (VI) hydrolyzed animal protein (HAP) chelate
  • Molybdenum (VI) hydrolyzed vegetable protein (HVP) chelate
  • Molybdenum (VI) malate
  • Molybdenum (VI) succinate
  • Potassium molybdate (VI)
  • Sodium molybdate (VI)
  • Sodium molybdate (VI), dihydrate
N/A N/A N/A
Phosphorus4 Phosphorus
  • Ammonium phosphate, dibasic
  • Ammonium phosphate, monobasic
  • Ammonium polyphosphate
  • Calcium glycerophosphate
  • Calcium phosphate, dibasic
  • Calcium phosphate, dibasic, dihydrate
  • Calcium phosphate, monobasic
  • Calcium phosphate, monobasic, monohydrate
  • Calcium phosphate, tribasic
  • Calcium polyphosphate
  • Calcium pyrophosphate
  • Durapatite
  • Magnesium phosphate, dibasic, mixed hydrates
  • Magnesium phosphate, dibasic, trihydrate
  • Magnesium phosphate, tribasic
  • Potassium phosphate, dibasic
  • Potassium phosphate, monobasic
  • Potassium phosphate, tribasic
  • Potassium polyphosphate
  • Potassium pyrophosphate
  • Sodium glycerophosphate
  • Sodium phosphate, dibasic
  • Sodium phosphate, dibasic, dihydrate
  • Sodium phosphate, dibasic, monohydrate
  • Sodium phosphate, dibasic, dodecahydrate
  • Sodium phosphate, dibasic, heptahydrate
  • Sodium phosphate, monobasic
  • Sodium phosphate, monobasic, dihydrate
  • Sodium phosphate, monobasic, monohydrate
  • Sodium phosphate, tribasic
  • Tetrasodium pyrophosphate
  • Trisodium phosphate, dodecahydrate
  • Zinc phosphate
N/A N/A N/A
N/A Bone meal4 N/A Bone
Selenium Selenium
  • Methylselenocysteine
  • Selenious acid
  • Selenium amino acid chelate
  • Selenium aspartate
  • Selenium citrate
  • Selenium dioxide, monohydrate
  • Selenium fumarate
  • Selenium glutarate
  • Selenium glycinate
  • Selenium hydrolyzed animal protein (HAP) chelate
  • Selenium hydrolyzed vegetable protein (HVP) chelate
  • Selenium malate
  • Selenium succinate
  • Selenium-enriched yeast
  • Selenocysteine
  • Selenomethionine
  • Sodium hydrogen selenite
  • Sodium selenate
  • Sodium selenite
N/A N/A N/A
Silicon7 Silicon
  • Calcium silicate
  • Choline-stabilised orthosilicic acid
  • Methylsilanetriol
  • Orthosilicic acid
  • Silicic acid
  • Silicon dioxide
  • Silicon hydrolyzed animal protein (HAP) chelate
  • Silicon hydrolyzed vegetable protein (HVP) chelate
  • Sodium metasilicate
N/A N/A N/A
N/A N/A Equisetum arvense7 Herb top
Zinc8 Zinc
  • Zinc acetate
  • Zinc acetate, dihydrate
  • Zinc amino acid chelate
  • Zinc arginate
  • Zinc ascorbate
  • Zinc aspartate
  • Zinc bisglycinate
  • Zinc carbonate
  • Zinc chloride
  • Zinc citrate
  • Zinc citrate, dihydrate
  • Zinc citrate, trihydrate
  • Zinc fumarate
  • Zinc gluconate
  • Zinc gluconate glycine
  • Zinc glutarate
  • Zinc glycerate
  • Zinc histidinate
  • Zinc hydrolyzed animal protein (HAP) chelate
  • Zinc hydrolyzed vegetable protein (HVP) chelate
  • Zinc lactate
  • Zinc lysinate
  • Zinc malate
  • Zinc methionine
  • Zinc monomethionine
  • Zinc orotate
  • Zinc oxide
  • Zinc phosphate
  • Zinc picolinate8
  • Zinc pidolate
  • Zinc propionate
  • Zinc succinate
  • Zinc sulfate
  • Zinc sulfate, heptahydrate
  • Zinc sulfate, monohydrate
N/A N/A N/A

1, 2 At least one of the following references was consulted per name: NIH 2015a; Sweetman 2015; USP 38 2015; FCC 9 2014; O'Neil 2013.

3 At least one of the following references was consulted per source information: Albion 2015; BP 2015; NIH 2015a,b; Sweetman 2015; USP 38 2015; FCC 9 2014; O'Neil 2013; Jain et al. 2012; EFSA 2010a; Summers et al. 2010; EC 2009; EFSA 2009b,c,d,e,f,g,h,i,j; EFSA 2008a,b,c,d,e,f; Nowak et al. 2008; Richards 2008; EFSA 2007; Guiry and Guiry 2007; TGA 2007; EFSA 2006; Walsdorf and Alexandrides 2005; Albion 2004a,b; ANZFA 2004; Gruenwald et al. 2004; Albion 2003a,b; Allen 2002; ANZFA 2002; Ball et al. 2002; EC 2002; Van Der Kuy et al. 2002; Anderson et al. 2001; Hendler and Rorvik 2001; Albion 2000; Chalmers et al. 2000; EC 2000; Tsuboi et al. 2000; Ishitani et al. 1999; Patrick 1999; IPCS 1998; Albion 1997a,b; Grant et al. 1997; Albion 1996a,b; Fujita et al. 1996; Murray 1996; Albion 1995; Henderson 1994; Albion 1993a,b,c,d,e; Evans and Pouchnik 1993; Albion 1992; Zeitlin et al. 1985.

4 Bone meal: When bone meal is used as a source ingredient for calcium or phosphorus, it must be sourced from a non-human animal that is not susceptible to transmissible spongiform encephalopathy diseases, including bovine spongiform encephalopathy (HC 2013).

5 Chromium picolinate: If chromium picolinate is indicated as a source ingredient of chromium, additional restrictions apply (refer to Tables 12, 13 and 14).

6 If iodine is sourced from Fucus vesiculosus, Fucus serratus, Ascophyllum nodosum, Laminaria digitata or Laminaria japonica, it should be isolated and purified. This monograph does not support algal extracts.

7 Silicon from Equisetum arvense: Data (or certification) must be submitted to the Natural and Non-Prescription Health Products Directorate (NNHPD) upon request to show that thiaminase has been inactivated. If silicon is sourced from Equisetum arvense herb top, it should be isolated and purified. This monograph does not support Equisetum arvense extracts.

8 Zinc picolinate: If zinc picolinate is indicated as a source ingredient of zinc, the product must be for Adults only and the maximum daily dose is restricted to 25 mg (refer to Table 9). In addition, additional restrictions apply (refer to Tables 12 and 14).

1.3 Other medicinal ingredient proper names, common names and source information

Table 3. Other medicinal ingredient proper names, common names and source information
Proper name(s)1 Common name(s)2 Source information3
Source ingredient(s) Source material(s) Part(s)
  • all-trans-beta-Carotene
  • beta-Carotene
  • all-trans-beta-Carotene
  • beta-Carotene
beta-Carotene N/A N/A
  • (beta-Hydroxyethyl)trimethylammonium
  • 2-Hydroxy-N,N,N-trimethylethanaminium
  • Choline
Choline
  • Choline
  • Choline alfoscerate
  • Choline bitartrate
  • Choline chloride
  • Choline citrate
  • Choline dihydrogen citrate
  • Choline orotate
N/A N/A
(3R,3'R,6'R)-beta,epsilon-Carotene-3,3'-diol4 Lutein N/A Tagetes erecta4 Herb flowering oleoresin
all-trans-Lycopene5 Lycopene Lycopene N/A N/A
N/A Solanum lycopersicum5 Fruit flesh
  • (S)-2-Amino-4-(methylthio)butanoic acid
  • L-Methionine
  • L-Methionine
  • Methionine
  • DL-Methionine
  • L-Methionine
  • N-Acetyl-L-methionine
N/A N/A
Potassium6 Potassium
  • Acesulfate potassium
  • Potassium acetate
  • Potassium ascorbate
  • Potassium aspartate
  • Potassium bicarbonate
  • Potassium carbonate
  • Potassium chloride
  • Potassium citrate
  • Potassium citrate, monohydrate
  • Potassium gluconate
  • Potassium glutarate
  • Potassium glycerophosphate
  • Potassium glycerophosphate, trihydrate
  • Potassium glycinate
  • Potassium hydroxide
  • Potassium lactate
  • Potassium malate
  • Potassium phosphate, dibasic
  • Potassium phosphate, monobasic
  • Potassium phosphate, tribasic
  • Potassium pidolate
  • Potassium sorbate
  • Potassium succinate
  • Potassium sulfate
  • Potassium tartrate
  • Potassium tartrate, hemihydrate
N/A N/A

1,2 At least one of the following references was consulted per name: NIH 2015a; Sweetman 2015; USP 38 2015; FCC 9 2014; O'Neil 2013.

3 At least one of the following references was consulted per source information: NIH 2015a; Sweetman 2015; USP 38 2015; FCC 9 2014; O'Neil 2013; EFSA 2009e; EFSA 2008d; EFSA 2007; FAO 2006.

4 If lutein is sourced from Tagetes erecta herb flowering oleoresin, it should be isolated and purified. This monograph does not support Tagetes erecta extracts.

5 If lycopene is sourced from Solanum lycopersicum fruit flesh, it should be isolated and purified. This monograph does not support Solanum lycopersicum extracts.

6 Potassium: At least 100 mg of potassium per day is required to support the uses or purposes listed in Section 4.2.3. Only general uses or purposes are permitted at daily doses below 100 mg of potassium.

1.4 Complementary medicinal ingredients proper names, common names and source information

The medicinal ingredients boron, inositol, nickel, PABA, tin and vanadium are complementary ingredients that must be combined with at least one medicinal ingredient listed in Tables 1, 2 and/or 3. No claim can be supported based on these medicinal ingredients. The product claim(s) must be supported by at least a medicinal ingredient from Tables 1, 2 and/or 3.

Table 4. Complementary medicinal ingredients proper names, common names and source information.
Proper name(s)1 Common name(s)2 Source information3
Source ingredient(s) Source material(s) Part(s)
Boron Boron
  • Borax
  • Boric acid
  • Boron aspartate
  • Boron citrate
  • Boron glycinate
  • Boron hydrolyzed animal protein (HAP) chelate
  • Boron hydrolyzed vegetable protein (HVP) chelate
  • Calcium borate
  • Calcium borogluconate
  • Calcium fructoborate
  • Magnesium borate
  • Sodium borate
N/A N/A
myo-Inositol Inositol
  • Inositol
  • Inositol, dihydrate
  • Inositol hexanicotinate
  • Inositol monophosphate
N/A N/A
Nickel Nickel
  • Nickel (II) sulfate
  • Nickel (II) sulfate, heptahydrate
  • Nickel (II) sulfate, hexahydrate
N/A N/A
  • 4-Aminobenzoic acid4
  • para-Aminobenzoic acid4
  • PABA
  • para-Aminobenzoic acid
para-Aminobenzoic acid N/A N/A
N/A Saccharomyces cerevisiae4 Whole
Tin Tin Stannous chloride N/A N/A
Vanadium Vanadium
  • Sodium metavanadate
  • Vanadium amino acid chelate
  • Vanadium aspartate
  • Vanadium citrate
  • Vanadium fumarate
  • Vanadium glutarate
  • Vanadium hydrolyzed animal protein (HAP) chelate
  • Vanadium hydrolyzed vegetable protein (HVP) chelate
  • Vanadium malate
  • Vanadium metavanadate
  • Vanadium succinate
  • Vanadyl sulfate
  • Vanadyl sulfate, dihydrate
N/A N/A

1,2 At least one of the following references was consulted per name: NIH 2015a; Sweetman 2015; USP 38 2015; FCC 9 2014; O'Neil 2013.

3 At least one of the following references was consulted per source information: NIH 2015a; Sweetman 2015; USP 38 2015; FCC 9 2014; O'Neil 2013; EFSA 2009a,e; EFSA 2008d,g; EFSA 2007; O'Neil et al 2006, EFSA 2004.

4 If PABA is sourced from Saccharomyces cerevisiae whole, it should be isolated and purified. This monograph does not support Saccharomyces cerevisiae extracts.

2.0 Route of administration

Oral

3.0 Dosage forms

This monograph excludes foods or food-like dosage forms as indicated in the Compendium of Monographs Guidance Document.

Acceptable dosage forms by age group:

Infants 0-12 months, Children 1-2 years: The acceptable dosage forms are limited to emulsion/suspension and solution/ liquid preparations (Giacoia et al. 2008; EMEA/CHMP 2006).

Children 3-5 years: The acceptable dosage forms are limited to chewables, emulsion/ suspension, powders and solution/liquid preparations (Giacoia et al. 2008; EMEA/CHMP 2006).

Children 6-11 years, Adolescents 12-17 years, and Adults 18 years and older: Acceptable dosage forms for oral use are indicated in the dosage form drop-down list of the web-based Product Licence Application form for Compendial applications.

4.0 Uses or Purposes

4.1 General use or purpose statements

Products containing any vitamin and/or mineral from Tables 1 and/or 2 and/or beta-carotene and potassium from Table 3 (not acceptable for other medicinal ingredients from Table 3 or medicinal ingredients listed in Table 4).

Products containing at least one vitamin or mineral from Tables 1 and/or 2 (all vitamins and minerals in the product must be at minimum therapeutic dose as listed in Tables 8 and 9)

Products containing at least two vitamins and/or minerals from Tables 1 and/or 2 (all vitamins and minerals in the product must be at minimum therapeutic dose as listed in Tables 8 and 9)

4.2 Specific use or purpose statements

Notes

4.2.1 Specific use or purpose statements for vitamins

Table 5. Specific uses or purposes statements for vitamins
Vitamin Specific uses or purposes1
Biotin
  • Helps to maintain/support healthy hair/nail/mucous membranes/(and) skin.
  • Helps to prevent biotin deficiency.2
  • Helps to maintain/support the body's ability to metabolize nutrients.3
Folate4
  • Helps to form red blood cells.
  • Helps to prevent folate deficiency.2
  • Helps to maintain/support the body's ability to metabolize nutrients.3
Products providing 400 μg or more of folate per day:
  • Helps to reduce the risk of neural tube defects when taken daily at least three months prior to becoming pregnant and during early pregnancy.
  • Helps to support normal early fetal development (brain and spinal cord).
Niacin/ Niacinamide5
  • Helps normal growth and development.
  • Helps in energy metabolism/(and) tissue formation.
  • Helps to prevent niacin/niacinamide/vitamin B3 deficiency.2
  • Helps to maintain/support the body's ability to metabolize nutrients.3
Pantothenic acid
  • Helps in energy metabolism/(and) in tissue formation.
  • Helps to prevent pantothenic acid deficiency.2
  • Helps to maintain/support the body's ability to metabolize nutrients.3
Riboflavin
  • Helps in energy metabolism/(and) in tissue formation.
  • Helps to maintain/support healthy mucous membranes.
  • Helps to maintain/support normal red blood cells.
  • Helps to maintain/support normal metabolism of iron.
  • Helps to prevent riboflavin deficiency.2
  • Helps to maintain/support the body's ability to metabolize nutrients.3
Thiamine
  • Helps in energy production.
  • Supports energy production.
  • Helps normal growth.
  • Helps to prevent thiamine deficiency.2
  • Helps to prevent thiamine deficiency2 which helps supports normal growth.
  • Helps to maintain/support the body's ability to metabolize nutrients.3
Vitamin A
  • Helps to maintain/support normal vision/eyesight/eye health/(and) night vision.
  • Maintains/supports normal vision/eyesight/eye health/(and) night vision.
  • Helps to maintain/support skin health/(and) mucous membranes health.
  • Maintains/supports skin health/(and) mucous membranes health.
  • Healthy skin/(and) mucous membranes support.
  • Helps to maintain/support immune function/the immune system.
  • Helps with immune function/the immune system.
  • Helps to provide eyesight/skin/mucous membranes/(and) immune function support.
  • Helps in the development and maintenance of night vision.
  • Helps in the development and maintenance of bones/(and) teeth.
  • Helps to build strong bones/(and) teeth.
  • Helps to maintain/support normal metabolism of iron.
  • Helps to prevent vitamin A deficiency.2
Vitamin B6
  • Helps in energy metabolism/(and) in tissue formation.
  • Helps to form red blood cells.
  • Helps to prevent vitamin B6 deficiency.2
  • Helps to maintain/support the body's ability to metabolize nutrients.3
Vitamin B12
  • Helps in energy metabolism.
  • Helps to form red blood cells.
  • Helps to maintain/support immune function/the immune system.
  • Helps with immune function/the immune system.
  • Helps to maintain/support healthy metabolism.
  • Helps to prevent vitamin B12 deficiency.2
  • Helps to maintain/support the body's ability to metabolize nutrients.3
Vitamin C
  • Helps in the development and maintenance of bones/cartilage/teeth/(and) gums.
  • Helps in wound healing/(and) connective tissue formation.
  • Source of/Provides (an) antioxidant(s) for the maintenance of good health.
  • Source of/Provides (an) antioxidant(s) that help(s) fight/protect (cell) against/reduce (the oxidative effect of/the oxidative damage caused by/cell damage caused by) free radicals.
  • Helps in collagen formation (to maintain/support healthy bones/cartilage/teeth/(and) gums).
  • Helps to maintain/support immune function/the immune system.
  • Helps with immune function/the immune system.
  • Helps to prevent vitamin C deficiency.2
  • Helps to maintain/support the body's ability to metabolize nutrients.3
Vitamin D
  • Helps in the development and maintenance of bones/(and) teeth.
  • Helps to build strong bones/(and) teeth.
  • Helps in the absorption (and use) of calcium and phosphorus.
  • Vitamin D intake, when combined with sufficient calcium, a healthy diet, and regular exercise, may reduce the risk of developing osteoporosis.
  • Helps to maintain/support immune function/the immune system.
  • Helps with immune function/the immune system.
  • Helps to prevent vitamin D deficiency.2
Vitamin E
  • Source of/Provides (an) antioxidant(s) for the maintenance of good health.
  • Source of/Provides an antioxidant that protects the fat in body tissues from oxidation.
  • Source of/Provides (an) antioxidant(s) that help(s) fight/protect (cell) against/reduce (the oxidative effect of/the oxidative damage caused by/cell damage caused by) free radicals.
  • Helps to prevent vitamin E deficiency.2
Vitamin K1 and K2
  • Helps in the maintenance of bones.
  • Helps to prevent vitamin K deficiency.2

1 At least two of the following references were consulted per use or purpose statement: CFIA 2015; EC 2015; IOM 2011; NIH 2011; HC 2009a,b; de Benoist 2008; IOM 2006; Shils et al. 2006; Bjørke Monsen and Ueland 2003; MacKay and Miller 2003; IOM 2001; Groff and Gropper 2000; IOM 2000; NIH 2000; IOM 1998; IOM 1997; Colombo et al. 1990.

2 For deficiency claims: This use or purpose statement is only acceptable if the vitamin is present at dosages at or above the recommended dietary allowance (RDA) or adequate intake (AI). See Appendix III for RDA and AI definitions and Appendix IV for detailed values according to life stage group. Note that most vitamin deficiencies are rare in North America.

3 These vitamins are cofactors in specific biochemical reactions (e.g. inter-conversion of amino acids). This claim is not intended to convey that taking these vitamins helps to boost metabolism, upregulate a bodily system and/or directly convert food to energy. Inferring such claims would be misleading and is not permitted. In order to avoid any misinterpretation of this claim, the terms 'carbohydrates, fats, proteins, etc.' must not be used to further specify the term 'nutrients'.

4 Folate: If a product is marketed specifically as a prenatal supplement (for pregnant women), it must have at least 400 μg of folate per day. Health Canada (HC 2009a,b) recommends that all women who could become pregnant take a daily multivitamin/mineral supplement containing 400 μg of folic acid per day. At a minimum, women who are planning to become pregnant should start taking this supplement 3 months before the pregnancy.

5 Niacin/niacinamide: A specific use or purpose statement must be made for products providing > 35 mg niacin, niacinamide or a combination of the two, per day.

4.2.2 Specific use or purpose statements for minerals

Table 6. Specific uses or purposes statements for minerals
Mineral Specific uses or purposes1
Calcium
  • Helps in the development and maintenance of bones/(and) teeth.
  • Helps in the development and maintenance of bones/(and) teeth especially in children and young adults.
  • Adequate calcium (and vitamin D) (throughout life) as part of a healthy diet, (along with physical activity) may reduce the risk of developing osteoporosis (in peri- and postmenopausal women) (in later life).
  • Adequate calcium (and vitamin D) (throughout life) as part of a healthy diet, (along with physical activity) may help prevent bone loss/osteoporosis (in peri- and postmenopausal women) (in later life).
  • As part of a healthy diet (when taken with Vitamin D) may help prevent bone loss/osteoporosis.
  • Source of/Provides (an) electrolyte(s).
  • Source of/Provides (an) electrolyte(s) for the maintenance of good health.
  • Helps to maintain/support normal muscle function.
  • Helps maintain/support bone health.
  • Helps to prevent calcium deficiency.2
Chromium
  • Provides support for healthy glucose metabolism.
  • Helps to maintain/support normal blood glucose levels.
  • Helps to prevent chromium deficiency.2
  • Helps to maintain/support the body's ability to metabolize nutrients.3
Cobalt
  • Cobalt is a structural component of vitamin B12 that helps form red blood cells.
  • Cobalt is a structural component of vitamin B12 that helps prevent vitamin B12 deficiency.2
  • Cobalt is a structural component of vitamin B12 that helps to maintain/support the body's ability to metabolize nutrients.3
Copper
  • Helps to produce and repair connective tissue.
  • Helps to form red blood cells.
  • Helps to maintain/support normal iron transport in the body.
  • Helps to prevent copper deficiency.2
Iodine
  • Helps in the function of the thyroid gland.
  • Helps to prevent iodine deficiency.2
Iron4
  • Helps to form red blood cells (and helps in their proper function).
  • Helps to prevent iron deficiency.2
  • Helps to prevent iron deficiency anaemia.2
  • Helps to prevent iron deficiency anemia and associated tiredness and fatigue.2
Products providing 16 mg or more of iron, per day:
  • Helps pregnant women meet (the) (Health Canada's) recommended intake for iron, when taken in conjunction with a healthy diet.
Magnesium5
  • Helps in the development and maintenance of bones/(and) teeth.
  • Helps in bone development.
  • Helps in energy metabolism/(and) tissue formation.
  • Helps to maintain/support normal muscle function.
  • Helps to maintain/support normal muscle function, including the heart muscle.
  • Helps to maintain/support heart muscle function.
  • Source of/Provides (an) electrolyte(s).
  • Source of/Provides (an) electrolyte(s) for the maintenance of good health.
  • Helps to maintain/support normal electrolyte balance.
  • Helps to prevent magnesium deficiency.2,6
  • Helps to maintain/support the body's ability to metabolize nutrients.3
Manganese
  • Helps in the development and maintenance of bones.
  • Helps to prevent manganese deficiency.2
  • Helps to maintain/support the body's ability to metabolize nutrients.3
Molybdenum
  • Helps to prevent molybdenum deficiency.2
  • Helps to maintain/support the body's ability to metabolize nutrients.3
Phosphorus
  • Helps in the development and maintenance of bones/(and) teeth.
  • Source of/Provides (an) electrolyte(s)
  • Source of/Provides (an) electrolyte(s) for the maintenance of good health.
  • Helps to prevent phosphorus deficiency.2
  • Helps to maintain/support the body's ability to metabolize nutrients.3
Selenium
  • Helps normal growth and development.
  • Source of/Provides (an) antioxidant(s) for the maintenance of good health.
  • Source of/Provides an antioxidant that helps protect against oxidative stress.
  • Source of/Provides (an) antioxidant(s) that help(s) fight/protect (cell) against/reduce (the oxidative effect of/the oxidative damage caused by/cell damage caused by) free radicals.
  • Helps to maintain/support normal function of the thyroid gland
  • Helps to prevent selenium deficiency.2
Zinc7
  • Helps in connective tissue formation.
  • Helps in energy metabolism/(and) tissue formation.
  • Helps to maintain/support healthy skin.
  • Helps to maintain/support immune function/the immune system.
  • Helps with immune function/the immune system.
  • Helps to maintain/support healthy bones/hair/nail/(and) skin.
  • Maintains/supports healthy bones/hair/nail/(and) skin.
  • Helps to prevent zinc deficiency.2
  • Helps to maintain/support the body's ability to metabolize nutrients.3

1 At least two of the following references were consulted per use or purpose statement: CFIA 2015; EC 2015; IOM 2011; FDA 2008; Tang et al 2007; IOM 2006; Jackson et al 2006; NAMS 2006; Shils et al. 2006; Meisel et al. 2005; Schwartz et al. 2005; Brown and Josse 2002; IOM 2001; Groff and Gropper 2000; IOM 2000; NIH 2000; IOM 1997; Klimis-Tavantis 1994.

2 For deficiency claims: This use or purpose statement is only acceptable if the mineral is present at dosages at or above the RDA or AI. See Appendix III for RDA and AI definitions and Appendix IV for detailed values according to life stage group. Note that most mineral deficiencies are rare in North America.

3 These minerals are involved as cofactors in specific biochemical reactions (e.g. inter-conversion of amino acids). This claim is not intended to convey that taking these minerals helps to boost metabolism, upregulate a bodily system and/or directly convert food to energy. Inferring such claims would be misleading and is not permitted. In order to avoid any misinterpretation of this claim, the terms 'carbohydrates, fats, proteins, etc.' must not be used to further specify 'nutrients'.

4 Iron: A specific use or purpose statement must be made for products providing > 35 mg iron per day.

5 Magnesium: A specific use or purpose statement must be made for products providing > 350 mg magnesium per day.

6 Magnesium deficiency claim: As the RDA for magnesium for children 1-3 years, children 4-8 years and adolescents 14-18 years exceeds the maximum dose, this claim is not permitted for these subpopulations.

7 Zinc: A specific use or purpose statement must be made for products providing > 40 mg zinc per day.

4.2.3 Specific use or purpose statements for other medicinal ingredients

Table 7. Specific uses or purposes statements for other medicinal ingredients
Medicinal ingredient Specific uses or purposes1
beta-Carotene
  • Provitamin A/Source of vitamin A for the maintenance of good health.
  • Source of vitamin A.
  • Provitamin A/Source of vitamin A to help maintain/support eyesight/skin/mucous membranes/(and) immune function/the immune system
  • Helps maintain/support eyesight/skin/mucous membranes/(and) immune function/the immune system.
  • Provitamin A/Source of vitamin A to help with immune function/the immune system
  • Helps with immune function/the immune system.
  • Provitamin A/Source of vitamin A to help in the development and maintenance of night vision.
  • Helps in the development and maintenance of night vision.
  • Provitamin A/Source of vitamin A to help in the development and maintenance of bones/(and) teeth.
  • Helps in the development and maintenance of bones/(and) teeth.
  • Helps to prevent vitamin A deficiency.2
Choline3
  • Helps to support liver function.
L-Methionine3
  • Helps to support liver function.
  • Source of/Provides an essential amino acid for the maintenance of good health.
  • Source of/Provides an essential amino acid involved in protein synthesis.
Lutein
  • Source of/Provides (an) antioxidant(s).
  • Source of/Provides (an) antioxidant(s) for the maintenance of good health.
  • Source of/Provides an antioxidant for the maintenance of eye health.
  • Source of/Provides (an) antioxidant(s) that help(s) fight/protect (cell) against/reduce (the oxidative effect of/the oxidative damage caused by/cell damage caused by) free radicals.
Products providing 6 mg or more of lutein per day:
  • Helps to maintain/support eyesight in conditions (associated with sunlight damage), such as cataracts and age-related macular degeneration.
  • Helps to reduce the risk of developing cataracts.
  • Helps to improve macular pigment optical density.
Lycopene
  • Source of/Provides (an) antioxidant(s).
  • Source of/Provides (an) antioxidant(s) that help(s) fight/protect (cell) against/reduce (the oxidative effect of/the oxidative damage caused by/cell damage caused by) free radicals.
Products providing 6.5 mg or more of lycopene per day:
  • Helps to support prostate health.
Potassium Products providing 100 mg or more of potassium per day:
  • Source of/Provides (an) electrolyte(s).
  • Source of/Provides (an) electrolyte(s) for the maintenance of good health.
Silicon Products providing 10 mg or more of silicon per day:
  • Helps to maintain/support healthy hair/nail/(and) skin.

1At least two of the following references were consulted per use or purpose statement: CNF 2015; EC 2015; Erdman et al. 2009; Christen et al. 2008; Fletcher et al. 2008; Johnson et al. 2008; Kristal et al. 2008; Moeller et al. 2008; Schwarz et al. 2008; Silaste et al. 2007; Wickett et al. 2007; IOM 2006; Miranda et al. 2006; Shao and Hathcock 2006; Shils et al. 2006; Zeisel 2006; Barel et al. 2005; IOM 2005a,b; Mohanty et al. 2005; Porrini et al. 2005; Alves-Rodrigues and Shao 2004; Richer et al. 2004; Blakely et al. 2003; Olmedilla et al. 2003; Giovannucci et al. 2002; IOM 2002; Kucuk et al. 2002; Dwyer et al. 2001; IOM 2001; Kucuk et al. 2001; Matos et al. 2001; Groff and Gropper 2000; Brown et al 1999; Gann et al. 1999; IOM 1998; Seyoum and Persaud 1991; Benevenga 1984.

2 beta-Carotene: Vitamin A deficiency claim: See Appendix V for guidance on the appropriate use of this claim.

3 The term "lipotropic factor" is not permitted to describe choline, methionine or inositol. This term may mislead consumers to perceive that the product is intended for the purpose of weight loss.

5.0 Doses

5.1 Subpopulations

Adults 19 and older is the only acceptable subpopulation for the source ingredients HAP or HVP as well as for the following medicinal ingredients:

5.2 Background on dose

Notes

5.3 Dose information for vitamins

Table 8. Daily doses for vitamins (Min = minimum; Max = maximum)
Life Stage Group Biotin (μg/day) Folate1 (μg/day) Niacin/niacinamide2 (mg/day)
Min Max Min Max Min Max
Infants 0-12 months - - - - - -
Children 1-3 years 1.0 500 15 300 0.6 10
4-8 years 1.0 500 15 400 0.6 15
Adolescents 9-13 years 1.0 500 15 600 0.6 20
14-18 years 1.8 500 30 800 1.0 30
Adults 19 years and older 1.8 500 30 1,000 1.0 500
Life Stage Group Pantothenic acid (mg/day) Riboflavin (mg/day) Thiamine (mg/day)
Min Max Min Max Min Max
Infants 0-12 months - - - - - -
Children 1-3 years 0.2 500 0.04 100 0.04 100
4-8 years 0.2 500 0.04 100 0.04 100
Adolescents 9-13 years 0.2 500 0.04 100 0.04 100
14-18 years 0.4 500 0.08 100 0.07 100
Adults 19 years and older 0.4 500 0.08 100 0.07 100
Life Stage Group Vitamin A3 (µg RAE/day)
Min all-trans-Retinol - Max all-trans-Retinyl acetate - Max all-trans-Retinyl palmitate - Max
Infants 0-12 months 30 600 600 600
Children 1-3 years 30 600 600 600
4-8 years 30 900 900 900
Adolescents 9-13 years 30 1,700 1,700 1,700
14-18 years 65 2,800 2,800 2,800
Adults 19 years and older 65 3,003 3,000 3,022
Life Stage Group Vitamin B6 (mg/day) Vitamin B124 (µg/day) Vitamin C (mg/day)
Min Max Min Max Min Max
Infants 0-12 months - - - - -
Children 1-3 years 0.05 30 0.09 1,000 2.2 400
4-8 years 0.05 40 0.09 1,000 2.2 650
Adolescents 9-13 years 0.05 60 0.09 1,000 2.2 1,200
14-18 years 0.10 80 0.14 1,000 6.0 1,800
Adults 19 years and older 0.10 100 0.14 1,000 6.0 2,000
Life Stage Group Vitamin D (µg/day) Vitamin E5 (mg AT/day)
Min Max Min dl-alpha-Tocopherol - Max d-alpha-Tocopherol - Max
Infants 0-12 months 0.5 25 - - -
Children 1-3 years 0.8 25 0.6 100 200
4-8 years 0.8 25 0.6 150 300
Adolescents 9-13 years 0.8 25 0.6 300 600
14-18 years 1.0 25 1.0 400 800
Adults 19 years and older 1.0 25 1.0 500 1,000
Life Stage Group Vitamin K1, vitamin K2 and total vitamin K1 + K2 (µg/day)
Min Max
Infants 0-12 months - -
Children 1-3 years 3 30
4-8 years 3 55
Adolescents 9-13 years 3 60
14-18 years 6 75
Adults 19 years and older 6 120

1 Folate: If a product is marketed specifically as a prenatal supplement (for pregnant women), it must have at least 400 μg of folate per day. Health Canada (HC 2009a,b) recommends that all women who could become pregnant take a daily multivitamin/mineral supplement containing 400 μg of folic acid per day. At a minimum, women who are planning to become pregnant should start taking this supplement 3 months before the pregnancy.

2 Niacin/niacinamide: A specific use or purpose statement must be made for products providing > 35 mg niacin, niacinamide, or a combination of the two per day.

3 Vitamin A: There is a potential risk of hypervitaminosis A resulting from the use of products which combine high doses of vitamin A and beta-carotene. See Appendix V ("Mitigating the Risk of Hypervitaminosis A") for information on how to determine acceptable daily doses of each of these medicinal ingredients when used in combination.

4 Vitamin B12 + Cobalt: As vitamin B12 is the source ingredient for cobalt, the maximum dose for vitamin B12 and cobalt combined must not exceed 1000 μg vitamin B12 per day. Refer to Appendix VI for conversion from vitamin B12 to cobalt.

5 Vitamin E: A combination of dl-alpha-tocopherol (synthetic form) and d-alpha-tocopherol (natural form) must not exceed the maximum daily dose of 1000 mg of alpha-tocopherol from all sources (IOM 2006) with a maximum of 1500 IU/day of d-alpha-tocopherol and 1100 IU/day of dl-alpha-tocopherol.

1 IU = 0.67 mg for d-alpha-tocopherol

1 IU = 0.90 mg for dl-alpha-tocopherol which is equivalent to 0.45 mg of the biologically active alpha-tocopherol equivalent.

The total amount of vitamin E should be used to determine if additional risk statements are required (refer to Table 13).

5.4 Dose information for minerals

Table 9. Daily doses for minerals (Min = minimum; Max = maximum)

Life Stage Group Calcium1 (mg/day) Chromium (µg/day) Cobalt2 (µg/day)
Min Max Min Max Min Max
Infants 0-12 months - - - - - -
Children 1-3 years 65 1,500 - - 0.004 44
4-8 years 65 1,500 - - 0.004 44
Adolescents 9-13 years 65 1,500 - - 0.004 44
14-18 years 65 1,500 - - 0.006 44
Adults 19 years and older 65 1,500 2.2 500 0.006 44
Life Stage Group Copper (µg/day) Iodine (µg/day) Iron1,3 (mg/day)
Min Max Min Max Min Max
Infants 0-12 months - - - - 0.6 40
Children 1-3 years 35 700 6 133 0.6 40
4-8 years 35 2,500 6 200 0.6 40
Adolescents 9-13 years 35 4,000 6 400 0.6 40
14-18 years 65 6,500 14 800 1.4 45
Adults 19 years and older 65 8,000 14 800 1.4 45
Life Stage Group Magnesium1,4 (mg/day) Manganese (mg/day) Molybdenum (µg/day)
Min Max Min Max Min Max
Infants 0-12 months - - - - - -
Children 1-3 years 12 65 - - - -
4-8 years 12 110 - - - -
Adolescents 9-13 years 12 350 - - - -
14-18 years 20 350 - - - -
Adults 19 years and older 20 500 0.13 9 2.5 2,000
Life Stage Group Phosphorus (mg/day) Selenium (µg/day) Silicon (mg/day)
Min Max Min Max Min Max
Infants 0-12 months - - - - - -
Children 1-3 years 62 2,000 - - - -
4-8 years 62 2,000 - - - -
Adolescents 9-13 years 62 2,000 - - - -
14-18 years 62 2,000 - - - -
Adults 19 years and older 62 2,000 3.5 200 >0 84
Life Stage Group Zinc (from non-picolinate sources)1,5,6 (mg/day) Zinc (from zinc picolinate)1,5,6 (mg/day)
Min Max Min Max
Infants 0-12 months 0.2 4 - -
Children 1-3 years 0.4 7 - -
4-8 years 0.4 12 - -
Adolescents 9-13 years 0.4 23 - -
14-18 years 0.7 34 - -
Adults 19 years and older 0.7 50 0.7 25

1 Refer to Appendix VIII for additional wording on the label to clarify that the quantity of the medicinal ingredient is the amount of elemental mineral in order to avoid misinterpretation that may lead to serious health consequences.

2Cobalt + Vitamin B12: As vitamin B12 is the source ingredient for cobalt, the maximum dose for cobalt and vitamin B12 combined must not exceed 1000 μg of vitamin B12 per day. Refer to Appendix VI for conversion from cobalt to vitamin B12.

3 Iron: A specific use or purpose statement must be made for products providing > 35 mg iron per day.

4 Magnesium: A specific use or purpose statement must be made for products providing > 350 mg magnesium per day.

5 Zinc: A specific use or purpose statement must be made for products providing > 40 mg zinc per day.

6 Zinc: As zinc supplementation can cause a copper deficiency, manufacturers of products providing high doses of zinc are encouraged to supplement with sufficient quantities of copper. Refer to Appendix VII to determine how much copper is sufficient to mitigate this risk and for information on how to determine if a risk statement is necessary.

5.5 Dose information for other medicinal ingredients

Table 10. Daily doses for other medicinal ingredients (Min = minimum; Max = maximum)
Life Stage Group beta-Carotene1 (µg/day) Choline2 (mg/day) L-Methionine2 (mg/day)
Min Max Min Max Min Max
Infants 0-12 months 180 3,600 - - - -
Children 1-3 years 180 3,600 19 1,000 40 1,000
4-8 years 180 5,400 19 1,000 40 1,000
Adolescents 9-13 years 180 10,200 19 1,000 40 1,000
14-18 years 390 16,800 27 1,000 66.5 1,000
Adults 19 years and older 390 18,000 27 1,000 66.5 1,000
Life Stage Group Lutein2 (mg/day) Lycopene2 (mg/day) Potassium3 (mg/day)
Min Max Min Max Min Max
Infants 0-12 months - - - - - -
Children 1-3 years - - - - - -
4-8 years - - - - - -
Adolescents 9-13 years - - - - - -
14-18 years - - - - - -
Adults 19 years and older >0 20 >0 30 >0 200

1 beta-Carotene: There is a potential risk of hypervitaminosis A resulting from the use of products which combine high doses of vitamin A and beta-carotene. See Appendix V for information on how to determine acceptable daily doses of each of these medicinal ingredients when used in combination.

2 At least two of the following references were consulted: Christen et al. 2008; Fletcher et al. 2008; Johnson et al. 2008; Kristal et al. 2008; Moeller et al. 2008; Silaste et al. 2007; IOM 2006; Shao and Hathcock 2006; Shils et al. 2006; Porrini et al. 2005; WHO 2005; Alves-Rodrigues and Shao 2004; Richer et al. 2004; Olmedilla et al. 2003; Giovannucci et al. 2002; IOM 2002; Kucuk et al. 2002; Brown et al. 1999; Gann et al. 1999; IOM 1998; Giovannucci et al. 1995.

3 Potassium: At least 100 mg of potassium per day is required to support the uses or purposes listed in Section 4.2.3. Only general uses or purposes are permitted at daily doses below 100 mg of potassium.

5.6 Dose information for complementary medicinal ingredients

Table 11. Daily doses for complementary medicinal ingredients (Min = minimum; Max = maximum)
Life Stage Group Boron (µg/day) Inositol (mg/day) Nickel (µg/day)
Min Max Min Max Min Max
Infants 0-12 months - - - - - -
Children 1-3 years - - >0 650 - -
4-8 years - - >0 650 - -
Adolescents 9-13 years - - >0 650 - -
14-18 years - - >0 650 - -
Adults 19 years and older >0 700 >0 650 >0 350
Life Stage Group PABA1 (mg/day) Tin (mg/day) Vanadium (µg/day)
Min Max Min Max Min Max
Infants 0-12 months - - - - - -
Children 1-3 years - - - - - -
4-8 years - - - - - -
Adolescents 9-13 years - - - - - -
14-18 years - - - - - -
Adults 19 years and older >0 1,200 >0 2 >0 182

1 The following references were consulted: Weidner et al. 2005, Bardhan et al. 2000, Tisdale et al. 1995, Clegg et al. 1994.

5.7 Directions for use

Products providing 500 mg of nicotinic acid, per day

Products providing 10 mg or more of nicotinic acid, per day

Products providing calcium, iron or zinc

In all other cases, optional statement(s), as appropriate

Products providing 400 mcg or more of folate, per day (e.g. as a prenatal supplement) (optional statement)

6.0 Durations of use

Table 12. Durations of use for specific medicinal ingredients and associated daily doses
Medicinal ingredient Daily dose Contraindication(s)
Chromium sourced from chromium picolinate All doses Consult a health care practitioner/health care provider/health care professional/doctor/physician for use beyond 6 months (Anton et al. 2008; Campbell et al. 2002; Campbell et al. 1999; Cefalu et al. 1999; Kato et al. 1998; Anderson et al. 1997; Pasman et al. 1997; Lee et al. 1994).
Zinc sourced from zinc picolinate All doses Consult a health care practitioner/health care provider/health care professional/doctor/physician for use beyond 3 months (Sakai et al. 2002)

7.0 Risk information

7.1 Cautions and warnings

Table 13. Cautions and warnings for specific medicinal ingredients and associated daily doses
Medicinal ingredient Daily dose Caution(s) and warning(s)
beta-Carotene > 6,000 μg Consult a health care practitioner/health care provider/health care professional/doctor/physician prior to use if you are a tobacco smoker (Touvier et al. 2005; Omenn et al. 1996; ATBC 1994).
Chromium sourced from chromium picolinate ≥ 200 μg Consult a health care practitioner/health care provider/health care professional/doctor/physician if you have a kidney disorder and/or diabetes (Wani et al. 2006; Cupp et al. 2003; Bunner and McGinnis 1998; Cerulli et al. 1998; McCarty et al. 1997; Wasser et al. 1997).
Iron Where the package contains more than the equivalent of 250 mg of elemental iron Keep out of reach of children. There is enough iron in this package to seriously harm a child. (Note: this must be preceded by a prominently displayed symbol that is octagonal in shape, conspicuous in colour and on a background of a contrasting colour) [As per Section 97 of the Natural Health Products Regulations, citing Sections C.01.029 and C.01.031 of the Food and Drug Regulations (JC 2011, 2008)].
Manganese > 5 mg Consult a health care practitioner/health care provider/health care professional/doctor/physician prior to use if you have a liver disorder (IOM 2006; IOM 2001; Krieger et al. 1995).
PABA All doses Consult a health care practitioner/health care provider/health care professional/doctor/physician prior to use if you are pregnant or breastfeeding or if you are taking sulfonamides (Maren 1976).
Selenium > 70 μg Consult a health care practitioner/health care provider/health care professional/doctor/physician prior to use if you have a history of non-melanoma skin cancer (Duffield-Lillico et al. 2003).
Vanadium All doses Consult a health care practitioner/health care provider/health care professional/doctor/physician prior to use if you are pregnant or breastfeeding (IOM 2006; IOM 2001).
Vitamin E ≥ 180 mg AT Consult a health care practitioner/health care provider/health care professional/doctor/physician prior to use if you have cancer (Meyer et al. 2008; Bairati et al. 2006; Bairati et al. 2005).
≥ 268 mg AT Consult a health care practitioner/health care provider/health care professional/doctor/physician prior to use if you have cardiovascular disease or diabetes (Ward et al. 2007; Winterbone et al. 2007; Lonn et al. 2005).
≥ 360 mg AT Consult a health care practitioner/health care provider/health care professional/doctor/physician prior to use if you are taking blood thinners (CPS 2012; IOM 2006; Booth et al. 2004; Corrigan and Marcus 1974).
Vitamin K1 and/or K2 All doses Consult a health care practitioner/health care provider/health care professional/doctor/physician prior to use if you are taking blood thinners (ASHP 2005; Franco et al. 2004; IOM 2001; Hansten et al. 1997).

7.2 Contraindications

Table 14. Contraindications for specific medicinal ingredients and associated daily doses
Medicinal ingredient Daily dose Contraindication(s)
Chromium sourced from chromium picolinate All doses Do not use this product if you are pregnant or breastfeeding (EFSA 2009k; IOM 2001).
Potassium ≥ 100 mg Do not use this product with other potassium-containing supplements or with potassium-containing salt-substitutes (Sweetman 2015).
Zinc sourced from zinc picolinate All doses Do not use this product if you are pregnant or breastfeeding (EFSA 2009k; IOM 2001).

7.3 Known adverse reactions

Table 15. Known adverse reactions for specific medicinal ingredients and associated daily doses
Medicinal ingredient Daily dose Known adverse reaction(s)
Iron > 35 mg Some people may experience constipation, diarrhoea and/or vomiting (IOM 2006; IOM 2001).
All doses Stop use if hypersensitivity occurs (de Barrio et al. 2008).
Magnesium > 350 mg Some people may experience diarrhoea (IOM 2006; IOM 1997).
Nicotinic acid ≥ 10 mg People sensitive to nicotinic acid may experience flushing of the skin that is generally mild and transient (IOM 2006; IOM 1998).
PABA All doses Stop use if hypersensitivity occurs (Maren 1976).
Zinc1 Infants 0-12 months ≤ 2 mg Zinc supplementation can cause a copper deficiency (IOM 2006; IOM 2001). If you are unsure whether you are taking enough copper, consult a health care practitioner prior to use.
Children 1-3 years 5-7 mg
Children 4-8 years 8-12 mg
Adolescents 9-13 years 16-23 mg
Adolescents 14-18 years 25-34 mg
Adults 19 years and older 31-50 mg

1 Zinc: Statement required if the product does not meet the minimum copper requirements outlined in Appendix VII, Table 24.

8.0 Storage conditions

Must be established in accordance with the requirements described in the Natural Health Products Regulations (NHPR).

9.0 Non-medicinal ingredients

Must be chosen from the current Natural Health Products Ingredients Database (NHPID) and must meet the limitations outlined in the database.

10.0 Specifications

11.0 References

Albion 2015: Albion Advanced Nutrition. Minerals; Science; Chelates; Clearfield (UT): Albion Advanced Nutrition, Inc. [Accessed 2018 July 24]. Available from: http://albionminerals.com/

Albion 2004a: Albion Advanced Nutrition. Magnesium: A Role in the Therapy for Asthma. Albion Research Notes 13(3). Clearfield (UT): Albion Advanced Nutrition, Inc. [Accessed 2018 July 24]. Available from: http://www.albionhumannutrition.com/index.php?option=com_docman&task=cat_view&gid=1&Itemid=6

Albion 2004b: Albion Human Nutrition. Zinc: A Mineral of Complex Biological Activity. Albion Research Notes 13(1). Clearfield (UT): Albion Laboratories, Inc. [Accessed 2018 July 24]. Available from: http://www.albionhumannutrition.com/index.php?option=com_docman&task=cat_view&gid=1&Itemid=6

Albion 2003a: Albion Advanced Nutrition. The Iron Conundrum. Albion Research Notes 12(1). Clearfield (UT): Albion Advanced Nutrition, Inc. [Accessed 2018 July 24]. Available from: http://www.albionhumannutrition.com/index.php?option=com_docman&task=cat_view&gid=1&Itemid=6

Albion 2003b: Albion Advanced Nutrition. Magnesium: Clinical and Health Benefits Still Without Limits. Albion Research Notes 12(3). Clearfield (UT): Albion Advanced Nutrition, Inc. [Accessed 2018 July 24]. Available from: http://www.albionhumannutrition.com/index.php?option=com_docman&task=cat_view&gid=1&Itemid=6

Albion 2000: Albion Human Nutrition. Implications of the "Other Half" of a Mineral Compound. Albion Research Notes 9(3). Clearfield (UT): Albion Laboratories, Inc. [Accessed 2018 July 24]. Available from: http://www.albionhumannutrition.com/index.php?option=com_docman&task=cat_view&gid=1&Itemid=6

Albion 1997a: Albion Laboratories. Is Iron Getting a Bad Rap? Albion Research Notes 6(4). Clearfield (UT): Albion Laboratories, Inc. [Accessed 2018 July 24]. Available from: http://www.albionhumannutrition.com/index.php?option=com_docman&task=cat_view&gid=1&Itemid=6

Albion 1997b: Albion Laboratories. Magnesium: Mineral Link to Energy. Albion Research Notes 6(1). Clearfield (UT): Albion Laboratories, Inc. [Accessed 2018 July 24]. Available from: http://www.albionhumannutrition.com/index.php?option=com_docman&task=cat_view&gid=1&Itemid=6

Albion 1996a: Albion Laboratories. Effective Calcium Supplementation: Not as Easy as Advertised! Albion Research Notes 5(3). Clearfield (UT): Albion Laboratories, Inc. [Accessed 2018 July 24]. Available from: http://www.albionhumannutrition.com/index.php?option=com_docman&task=cat_view&gid=1&Itemid=6

Albion 1996b: Albion Laboratories. Iron Product Safety Issue / A Non-Issue for Albion's Ferrochel! Albion Research Notes 5(1). Clearfield (UT): Albion Laboratories, Inc. [Accessed 2018 July 24]. Available from: http://www.albionhumannutrition.com/index.php?option=com_docman&task=cat_view&gid=1&Itemid=6

Albion 1995: Albion Laboratories. Chromium...Has the Public Been Misled? Albion Research Notes 4(3). Clearfield (UT): Albion Laboratories, Inc. [Accessed 2018 July 24]. Available from: http://www.albionhumannutrition.com/index.php?option=com_docman&task=cat_view&gid=1&Itemid=6

Albion 1993a: Albion Laboratories. Calcium Absorption Conflict. Albion Research Notes 2(2). Clearfield (UT): Albion Laboratories, Inc. [Accessed 2018 July 24]. Available from: http://www.albionhumannutrition.com/index.php?option=com_docman&task=cat_view&gid=1&Itemid=6

Albion 1993b: Albion Laboratories. Chromium - An Often Controversial, But Very Essential Trace Mineral. Albion Research Notes 2(5). Clearfield (UT): Albion Laboratories, Inc. [Accessed 2018 July 24]. Available from: http://www.albionhumannutrition.com/index.php?option=com_docman&task=cat_view&gid=1&Itemid=6

Albion 1993c: Albion Laboratories. A Few Words About Copper. Albion Research Notes 2(3). Clearfield (UT): Albion Laboratories, Inc. [Accessed 2018 July 24]. Available from: http://www.albionhumannutrition.com/index.php?option=com_docman&task=cat_view&gid=1&Itemid=6.

Albion 1993d: Albion Laboratories. Iron Treatment Failure. Albion Research Notes 2(6). Clearfield (UT): Albion Laboratories, Inc. [Accessed 2018 July 24]. Available from: http://www.albionhumannutrition.com/index.php?option=com_docman&task=cat_view&gid=1&Itemid=6

Albion 1993e: Albion Human Nutrition. Manganese - Beware of Marginal Deficiencies. Albion Research Notes 2(1). Clearfield (UT): Albion Laboratories, Inc. [Accessed 2018 July 24]. Available from: http://www.albionhumannutrition.com/index.php?option=com_docman&task=cat_view&gid=1&Itemid=6

Albion 1992: Albion Human Nutrition. Zinc: The Multifaceted Trace Mineral! Albion Research Notes 1(3). Clearfield (UT): Albion Laboratories, Inc. [Accessed 2018 July 24]. Available from: http://www.albionhumannutrition.com/index.php?option=com_docman&task=cat_view&gid=1&Itemid=6

Allen LH. Advantages and limitations of iron amino acid chelates as iron fortificants. Nutrition Reviews 2002;60(7 Pt 2):S18-S21.

Alves-Rodrigues A, Shao A. The science behind lutein. Toxicology Letters 2004;150(1):57-83.

Anderson RA, Cheng N, Bryden NA, Polansky MM, Cheng N, Chi J, Feug J. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes 1997; 46(11):1786-1791.

Anderson RA, Roussel AM, Zouari N, Mahjoub S, Matheau JM, Kerkeni A. Potential antioxidant effects of zinc and chromium supplementation in people with type 2 diabetes mellitus. Journal of the American College of Nutrition 2001;20(3):212-218.

Anton SD, Morrison CD, Cefalu WT, Martin CK, Coulon S, Geiselman P, Hongmei H, White CL, Williamson DA. 2008. Diabetes Technology & Therapeutics 10:405-412.

ANZFA 2004. New Zealand Food Safety Authority. Proposal P242: Food for Special Medical Purposes: Preliminary Final Assessment Report. Wellington (AU): Department of Health and Ageing, Commonwealth of Australia. [Accessed 2018 July 24]. Available from:

https://www.foodstandards.gov.au/code/proposals/documents/P242_FSMP_PFAR.pdf

ANZFA 2002. Food Standards Australia New Zealand. Proposal P93 - Review of Infant Formula: Supplementary Final Assessment Report (Inquiry - s.24) Report. Canberra (AU): Department of Health and Ageing, Commonwealth of Australia. [Accessed 2018 July 24]. Available from:

http://www.foodstandards.gov.au/code/proposals/documents/P93_completeFinalAssRep(supplement).pdf

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

ATBC (Alpha-tocopherol, beta-carotene cancer prevention) study group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The New England Journal of Medicine 1994;330(15):1029-1035.

Bairati I, Meyer F, Gélinas M, Fortin A, Nabid A, Brochet F, Mercier JP, Têtu B, Harel F, Mâsse B, et al. A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients. The Journal of National Cancer Institute 2005;97(7):481-488.

Bairati I, Meyer F, Jobin E, Gélinas M, Fortin A, Nabid A, Brochet F, Têtu B. Antioxidant vitamins supplementation and mortality: a randomized trial in head and neck cancer patients. International Journal of Cancer 2006;119(9):2221-2224.

Ball P, Woodward D, Beard T. Shoobridge A, Ferrier M. Calcium diglutamate improves taste characteristics of lower-salt soup. European Journal of Clinical Nutrition 2002;56(6):519-523.

Bardhan PK, Feger A, Kogon M, Muller J, Gillessen D, Beglinger C, Gyr N. Urinary choloyl-PABA excretion in diagnosing small intestinal bacterial overgrowth: evaluation of a new noninvasive method. Digestive Diseases and Sciences 2000;45(3):474-479.

Barel A, Calomme M, Timchenko A, De Paepe K, Demeester N, Rogiers V, Clarys P, Vanden Berghe D. Effect of oral intake of choline-stabilized orthosilicic acid on skin, nails and hair in women with photodamaged skin. Arch Dermatol Res. 2005 Oct;297(4):147-53. Epub 2005 Oct 26.

Benevenga NJ. Evidence for alternative pathways of methionine catabolism. Advances in Nutritional Research 1984;6:1-18.

Bjørke Monsen AL, Ueland PM. Homocysteine and methylmalonic acid in diagnosis and risk assessment from infancy to adolescence. American Journal of Clinical Nutrition 2003;78(1):7-21.

Blakely S, Herbert A, Collins M, Jenkins M, Mitchell G, Grundel E, O'Neill KR, Khachik F. Lutein interacts with ascorbic acid more frequently than with alpha-tocopherol to alter biomarkers of oxidative stress in female zucker obese rats. The Journal of Nutrition 2003; 133(9):2838-2844.

Booth SL, Golly I, Sacheck JM, Roubenoff R, Dallal GE, Hamada K, Blumberg JB. Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. The American Journal of Clinical Nutrition 2004;80(1):143-148.

BP 2015: British Pharmacopoeia 2015, Volume II. London (GB): The Stationary Office.

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

Brown L, Rimm EB, Seddon JM, Giovannucci EL, Chasan-Taber L, Spiegelman D, Willett WC, Hankinson SE. A prospective study of carotenoid intake and risk of cataract extraction in US men. The American Journal of Clinical Nutrition 1999;70(4):517-524.

Bunner SP, McGinnis R. Chromium-induced hypoglycemia. Psychosomatics 1998; 39(3):298-299.

Campbell WW, Joseph LJO, Anderson RA, Davey SL, Hinton J, Evans WJ. Effects of resistive training and chromium picolinate on body composition and skeletal muscle size in older women. International Journal of Sport Nutrition and Exercise Metabolism 12(2):125-135.

Campbell WW, Joseph LJO, Davey SL, Cyr-Campbell D, Anderson RA, Evans WJ. 1999. Effects of resistance training and chromium picolinate on body composition and skeletal muscle in older men. Journal of Applied Physiology 2002; 86(1):29-39.

Cefalu WT, Bell-Farrow AD, Stegner J, Wang ZQ, King T, Morgan T, Terry JG. Effect of chromium picolinate on insulin sensitivity in vivo. The Journal of Trace Elements in Experimental Medicine 1999; 12(2):71-83.

Cerulli J, Grabe DW, Gauthier I, Malone M, McGoldrick MD. Chromium picolinate toxicity. The Annals of Pharmacotherapy 1998; 32(4):428-431.

CFIA 2015: Canadian Food Inspection Agency. Guide to Food Labelling and Advertising. Ottawa (ON): Canadian Food Inspection Agency and Health Canada. [Accessed 2018 July 24]. Available from: http://www.inspection.gc.ca/food/labelling/food-labelling-for-industry/health-claims/eng/1392834838383/1392834887794?chap=8

Chalmers RA, Bain MD, Costello I. Oral cobalamin therapy. Lancet 2000;355(9198):148.

Christen WG, Liu S, Glynn RJ, Gaziano JM, Buring JE. Dietary carotenoids, vitamins C and E, and risk of cataract in women: a prospective study. Archives of Ophthalmology 2008;126(1):102-109.

Clegg DO, Reading JC, Mayes MD, Seibold JR, Harris C, Wigley FM, Ward JR, Pisko EJ, Weisman MH, Lee P. Comparison of aminobenzoate potassium and placebo in the treatment of scleroderma. The Journal of Rheumatology 1994;21(1):105-110.

CNF 2015: Canadian Nutrient File, Food and Nutrition, Health Canada. [Date modified 2012 April 26; Accessed 2018 July 24]. Available from: https://food-nutrition.canada.ca/cnf-fce/index-eng.jsp

Colombo VE, Gerber F, Bronhofer M, Floersheim GL. Treatment of brittle fingernails and onychoschizia with biotin: scanning electron microscopy. Journal of the American Academy of Dermatology 1990;23:1127-1132.

Corrigan JJ Jr, Marcus FI. Coagulopathy associated with vitamin E ingestion. The Journal of the American Medical Association 1974;230(9):1300-1301.

CPS 2012: Compendium of Pharmaceuticals and Specialties, online version (e-CPS). Ottawa (ON): Canadian Pharmacists Association; c2007. Vitamin E CPhA Monograph [Accessed 2018 July 24]. Available from: http://www.e-therapeutics.ca/

Cupp MJ, Tracy TS. Dietary Supplements: Toxicology and Clinical Pharmacology. Chapter 3 Chromium Picolinate. Totowa (NJ): Humana Press Inc. 2003.

de Barrio M, Fuentes V, Tornero P, Sanchez I, Zubeldia J, Herrero T. Anaphylaxis to oral iron salts. Desensitization protocol for tolerance induction. Journal of Investigational Allergology and Clinical Immunology 2008;18(4):305-308.

de Benoist B. Conclusions of a WHO Technical Consultation on folate and vitamin B12 deficiencies. Food and Nutrition Bulletin 2008;29(2 Suppl):S238-244.

Duffield-Lillico AJ, Slate EH, Reid ME, Turnbull BW, Wilkins PA, Combs GF Jr, Park HK, Gross EG, Graham GF, Stratton MS, Marshall JR, Clark LC; Nutritional Prevention of Cancer Study Group. Selenium supplementation and secondary prevention of non-melanoma skin cancer in a randomized trial. Journal of the National Cancer Institute 2003;95(19):1477-1481.

Dwyer JH, Navab M, Dwyer KM, Hassan K, Sun P, Shircore A, Hama-Levy S, Hough G, Wang X, Drake T, Merz CN, Fogelman AM. Oxygenated carotenoid lutein and progression of early atherosclerosis: the Los Angeles atherosclerosis study. Circulation 2001;103(24):2922-2927.

EC 2015: European Commission. EU Register of nutrition and health claims made on foods. [Accessed 2018 July 24]. Available from: http://ec.europa.eu/nuhclaims/

EC 2009: Commission of the European Communities. COMMISSION REGULATION (EC) No 1170/2009 of 30 November 2009 amending Directive 2002/46/EC of the European Parliament and of Council and Regulation (EC) No 1925/2006 of the European Parliament and of the Council as regards the lists of vitamin and minerals and their forms that can be added to foods, including food supplements. L314/36 Official Journal of the European Union 1.12.2009. [Accessed 2018 July 24]. Available from: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2009:314:0036:0042:EN:PDF

EC 2002: Commission of the European Communities. Directive 2002/46/EC of the European Parliament and of the Council of 10 June 2002 on the approximation of the laws of the Member States relating to food supplements. Official Journal of the European Communities L 183/51. [Accessed 2018 July 24]. Available from: https://www.fsai.ie/uploadedFiles/Dir%202002.46%20EC(2).pdf

EC 2000: European Commission. Opinion of the Scientific Committee on Food on the Tolerable Upper Intake level of Vitamin B12. SCF/CS/NUT/UPPLEV/42 Final. Brussels (BE): Health & Consumer Protection Directorate-General, European Commission. [Accessed 2018 July 24]. Available from: https://ec.europa.eu/food/sites/food/files/safety/docs/sci-com_scf_out80d_en.pdf

EFSA 2010a: European Food Safety Authority (EFSA) SCIENTIFIC OPINION Scientific Opinion on the use of ferric sodium EDTA as a source of iron added for nutritional purposes to foods for the general population (including food supplements) and to foods for particular nutritional uses. The EFSA Journal 2010;8(1):1414. [Accessed 2018 July 24]. Available from: http://www.efsa.europa.eu/en/efsajournal/doc/1414.pdf

EFSA 2010b: EFSA meeting summary report 3: Folic acid: an update on scientific developments. 21-22 January 2009, Uppsala, Sweden. European Food Safety Authority April 2010. [Accessed 2018 July 24]. Available from: https://efsa.onlinelibrary.wiley.com/doi/pdf/10.2903/sp.efsa.2009.EN-2

EFSA 2009a: European Food Safety Authority (EFSA) SCIENTIFIC OPINION Inositol hexanicotinate (inositol hexaniacinate) as a source of niacin (vitamin B3) added for nutritional purposes in food supplements. The EFSA Journal 2009;949:1-20 [Accessed 2018 July 24]. Available from: https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2009.949

EFSA 2009b: European Food Safety Authority (EFSA) SCIENTIFIC OPINION Calcium ascorbate, magnesium ascorbate and zinc ascorbate added for nutritional purposes in food supplements. The EFSA Journal 2009;994:1-22. [Accessed 2018 July 24]. Available from: http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/994.pdf

EFSA 2009c: European Food Safety Authority (EFSA) SCIENTIFIC OPINION Inability to assess the safety of chromium-enriched yeast added for nutritional purposes as a source of chromium in food supplements and the bioavailability of chromium from this source, based on the supporting dossiers. The EFSA Journal 2009;1083:1-8. [Accessed 2018 July 24]. Available from: http://focalpointbg.com/images/stories/efsa/contents/pdfdocs/ans_ej1083_Chromiumenrichedyeast_st_en.pdf

EFSA 2009d: European Food Safety Authority (EFSA) SCIENTIFIC OPINION Manganese ascorbate, manganese aspartate, manganese bisglycinate and manganese pidolate as sources of manganese added for nutritional purposes to food supplements. The EFSA Journal 2009;1114:1-23. [Accessed 2018 July 24]. Available from: http://focalpointbg.com/images/stories/efsa/contents/pdfdocs/ans_ej1114_Manganesesources_op_en.pdf

EFSA 2009e. European Food Safety Authority (EFSA) SCIENTIFIC OPINION Calcium acetate, calcium pyruvate, calcium succinate, magnesium pyruvate magnesium succinate and potassium malate added for nutritional purposes to food supplements. The EFSA Journal 2009;1088:1-25. [Accessed 2018 July 24]. Available from: https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2009.1088

EFSA 2009f. European Food Safety Authority (EFSA) SCIENTIFIC OPINION Chromium (III) lactate trihydrate as a source of chromium added for nutritional purposes to food supplements. The EFSA Journal 2009;1112:1-20. [Accessed 2018 July 24]. Available from: https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2009.1112

EFSA 2009g. European Food Safety Authority (EFSA) SCIENTIFIC OPINION Chromium nitrate as a source of chromium added for nutritional purposes to food supplements. The EFSA Journal 2009;1111:1-19. [Accessed 2018 July 24]. Available from: https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2009.1111

EFSA 2009h: European Food Safety Authority (EFSA) SCIENTIFIC OPINION Iron (II) taurate, magnesium taurate and magnesium acetyl taurate as sources of iron or magnesium added for nutritional purposes in food supplements. The EFSA Journal 2009;947:1- 30. [Accessed 2018 July 24]. Available from: https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2009.947

EFSA 2009i: European Food Safety Authority (EFSA) SCIENTIFIC OPINION Ferrous phosphate added for nutritional purposes to food supplements. The EFSA Journal 2009;951:1-13. [Accessed 2018 July 24]. Available from: https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2009.951

EFSA 2009j. European Food Safety Authority (EFSA) SCIENTIFIC OPINION Potassium molybdate as a source of molybdenum added for nutritional purposes to food supplements. The EFSA Journal 2009;1136:1-21. [Accessed 2018 July 24]. Available from: https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2009.1136

EFSA 2009k: 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 2009; 1113:1-41. [Accessed 2018 July 24]. Available from: http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2009.1113/epdf

EFSA 2008a: European Food Safety Authority (EFSA). SCIENTIFIC OPINION Calcium Sulphate for Use as a Source of Calcium in Food Supplements. The EFSA Journal 2008;814:1-9. [Accessed 2018 July 24]. Available from: https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2008.814

EFSA 2008b: European Food Safety Authority (EFSA) SCIENTIFIC OPINION Mixture of chromium di- and tri-nicotinate as a source of chromium added for nutritional purposes in food supplements and in foods for particular nutritional uses. The EFSA Journal 2008;887:1-24. [Accessed 2018 July 24]. Available from: http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/887.pdf

EFSA 2008c: European Food Safety Authority (EFSA) SCIENTIFIC OPINION Selenium-enriched yeast as source for selenium added for nutritional purposes in foods for particular nutritional uses and foods (including food supplements) for the general population. The EFSA Journal 2008;766:1-42. [Accessed 2018 July 24]. Available from: https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2008.766

EFSA 2008d: European Food Safety Authority (EFSA). SCIENTIFIC OPINION Magnesium aspartate, potassium aspartate, magnesium potassium aspartate, calcium aspartate, zinc aspartate, and copper aspartate as sources for magnesium, potassium, calcium, zinc, and copper added for nutritional purposes to food supplements. The EFSA Journal 2008;883:1-23. [Accessed 2018 July 24]. Available from: https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2008.883

EFSA 2008e: European Food Safety Authority (EFSA) SCIENTIFIC OPINION Magnesium L-lysinate, calcium L- lysinate, zinc L- lysinate as sources for magnesium, calcium and zinc added for nutritional purposes in food supplements. The EFSA Journal 2008;761:1-11. [Accessed 2018 July 24]. Available from: http://www.efsa.europa.eu/en/efsajournal/doc/761.pdf

EFSA 2008f: European Food Safety Authority (EFSA) SCIENTIFIC OPINION Calcium L-methionate, magnesium L-methionate and zinc mono-L-methionine sulphate added for nutritional purposes to food supplements. The EFSA Journal 2008;924:1-26. [Accessed 2018 July 24]. Available from: http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/924.pdf

EFSA 2008g: European Food Safety Authority (EFSA) SCIENTIFIC OPINION Vanadium citrate, bismaltolato oxo vanadium and bisglycinato oxo vanadium added for nutritional purposes to foods for particular nutritional uses and foods (including food supplements) intended for the general population and vanadyl sulphate, vanadium pentoxide and ammonium monovanadate added for nutritional purposes to food supplements. The EFSA Journal 2008;634:1-15. [Accessed 2018 July 24]. Available from: https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2008.634

EFSA 2007: European Food Safety Authority (EFSA) Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a request from the Commission related to Calcium, iron, magnesium, potassium and zinc L-pidolate as sources for calcium, iron, magnesium, potassium and zinc added for nutritional purposes to food supplements and to foods intended for particular nutritional uses. The EFSA Journal 2007:495-503:1-10. [Accessed 2018 July 24]. Available from: http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/495.pdf

EFSA 2006: European Food Safety Authority (EFSA). Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a request from the Commission related to Calcium, Magnesium and Zinc Malate added for nutritional purposes to food supplements as sources for Calcium, Magnesium and Zinc and to Calcium Malate added for nutritional purposes to foods for particular nutritional uses and foods intended for the general population as source for Calcium. The EFSA Journal 2006;391a,b,c,d:1-6. [Accessed 2018 July 24]. Available from: http://www.efsa.europa.eu/de/scdocs/doc/391a.pdf

EFSA 2004: European Food Safety Authority (EFSA). Statement of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a request from

the Commission related to Boric Acid and Sodium borate as nutrient sources of boron. [Accessed 2018 July 24]. Available from: http://www.efsa.europa.eu/en/scdocs/doc/1044.pdf

EMEA/CHMP 2006: European Medicines Agency: Pre-authorization Evaluation of Medicines for Human Use. Committee for Medicinal Products for Human Use. Reflection Paper: Formulations of choice for the paediatric population. Adopted September 2006. EMEA/CHMP/PEG/194810/2005. [Accessed 2018 July 24]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003782.pdf

Erdman JW Jr, Ford NA, Lindshield BL. Are the health attributes of lycopene related to its antioxidant function? Archives of Biochemistry and Biophysics 2009;483(2):229-235.

Evans GW, Pouchnik DJ. Composition and biological activity of chromium-pyridine carboxylate complexes. Journal of Inorganic Biochemistry 1993;49(3):177-187.

FAO 2012. Food and Agriculture Organization of the United Nations: Calcium L-5-Methyltetrahydrofolate. [Accessed 2018 July 24]. Available from: http://www.fao.org/fileadmin/user_upload/jecfa_additives/docs/Monograph2/Additive-090.pdf

FAO 2006. Food and Agriculture Organization of the United Nations. Joint FAO/WHO Expert Committee on Food Additives. 2006. Lutein from Tagetes erecta. In: Combined Compendium of Food Additive Specifications. Rome(IT): Food and Agriculture Organization of the United Nations. [Accessed 2018 July 24]. Available from: http://www.fao.org/ag/agn/jecfa-additives/details.html?id=894

FAO/WHO 1967: Food and Agricultural Organization of the United Nations / World Health Organization. 1967. Requirements of vitamin A, thiamine, riboflavine and niacin: report of a joint FAO/WHO Expert Group. Geneva: WHO Technical Report Series 362.

FCC 9 2014: Food Chemicals Codex. 9th edition. Rockville (MD): The United States Pharmacopeial Convention; 2014.

FDA 2008: United States Food and Drug Administration. Calcium and Osteoporosis, and Calcium, Vitamin D, and Osteoporosis. Federal Register, Volume 73, Number 189, September 29, 2008, Final Rules. Rockville (MD): Department of Health and Human Services, U.S. Food and Drug Administration. [Accessed 2018 July 24].Available from: https://www.gpo.gov/fdsys/pkg/FR-2008-09-29/pdf/E8-22730.pdf

Fletcher AE, Bentham GC, Agnew M, Young IS, Augood C, Chakravarthy U, de Jong PT, Rahu M, Seland J, Soubrane G, et al. Sunlight exposure, antioxidants, and age-related macular degeneration. Archives of Ophthalmology 2008;126(10):1396-1403.

Franco V, Polanczyk CA, Clausell N, Rohde LE. Role of dietary vitamin K intake in chronic oral anticoagulation: prospective evidence from observational and randomized protocols. The American Journal of Medicine 2004;166(10):651-656.

FSANZ 2008: Food Standards Australia-New Zealand: Final Assessment Report Application A566 L-5-methyltetrahydrofolate, calcium as a permitted vitamin form of folate. 4 June 2008. [Accessed 2018 July 24]. Available from: https://www.foodstandards.gov.au/code/applications/documents/A566%20L-Methylfolate%20FAR%20FINAL.pdf

Fujita T, Ohue T, Fujii Y, Miyauchi A, Takagi Y. Heated oyster shell-seaweed calcium (AAA Ca) on osteoporosis. Calcified Tissue International 1996;58(4):226-230.

Gann PH, Ma J, Giovannucci E, Willett W, Sacks FM, Hennekens CH, Stampfer MJ. Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis. Cancer Research 1999;59(6):1225-1230.

Giacoia GP, Taylor-Zapata P, Mattison D. Eunice Kennedy Shriver National Institute of Child Health and Human Development Pediatric Formulation Initiative: selected reports from working groups. Clinical Therapeutics 2008; 30(11):2097-2101.

Giovannucci E, Ascherio A, Rimm EB, Stampfer MJ, Colditz GA, Willett WC. Intake of carotenoids and retinol in relation to risk of prostate cancer. Journal of the National Cancer Institute 1995;87(23):1767-1776.

Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC. A prospective study of tomato products, lycopene, and prostate cancer risk. Journal of the National Cancer Institute 2002;94(5):391-398.

Grant KE, Chandler RM, Castle AL, Ivy JL. Chromium and exercise training: effect on obese women. Medicine and Science in Sports and Exercise 1997;28(8):992-998.

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

Gruenwald J, Bendler T, Jaenicke C, editors. PDR for Herbal Medicines, 3rd edition. Montvale (NJ): Thomson PDR 2004.

Guiry MD, Guiry GM. 2009. AlgaeBase [database on the Internet].Galway (IRE): World-wide electronic publication, National University of Ireland [Accessed 2018 July 24]. Available from: http://www.algaebase.org

Hansten PD, Horn JR, editors. Drug Interactions Analysis and Management. Vancouver (WA): Applied Therapeutics Inc 1997.

HC 2015: Health Canada. Prescription Drug List. [Accessed 2018 July 24]. Available from: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/pdl-ord/pdl_list_fin_ord-eng.php

HC 2013: Health Canada. Quality of Natural Health Products Guide. Ottawa (ON): Natural and Non-Prescription Health Products Directorate, Health Canada. [Accessed 2018 July 24]. Available from: http://www.hc-sc.gc.ca/dhp-mps/prodnatur/legislation/docs/eq-paq-eng.php

HC 2009a: Health Canada. Prenatal Nutrition Guidelines for Health Professionals - Folate Contributes to a Healthy Pregnancy. Ottawa (ON): Health Canada. [Accessed 2018 July 24]. Available from: http://www.hc-sc.gc.ca/fn-an/pubs/nutrition/folate-eng.php

HC 2009b: Health Canada. Prenatal Nutrition Guidelines for Health Professionals - Background on Canada's Food Guide. Ottawa (ON): Health Canada. [Accessed 2018 July 24]. Available from: http://www.hc-sc.gc.ca/fn-an/pubs/nutrition/guide-prenatal-eng.php

HC 1990: Health Canada. 1990. Nutrition Recommendations. The Report of the Scientific Review Committee. Ottawa: Minister of Supply and Services.

Henderson RW. Glucosamine, chondroitin and manganese composition for the protection and repair of connective tissue. United States patent 5,364,845. November 15, 1994.

Hendler SS, Rorvik D, editors. PDR Nutritional Supplements, 1st edition. Montvale (NJ): Thomson PDR 2001.

IOM 2011: Institute of Medicine. Ross AC, Taylor CL, Yaktine AL, Del Valle HB, editors. Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press 2011.

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

IOM 2005a: Institute of Medicine. Panel on Macronutrients, Panel on the Definition of Dietary Fiber, Subcommittee on Upper Reference Levels of Nutrients, Subcommittee on 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. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington (DC): National Academies Press 2005.

IOM 2005b: Institute of Medicine. Panel on Dietary Reference Intakes for Electrolytes and Water, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate. Washington (DC): National Academies Press 2005.

IOM 2002: Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Food and Nutrition Board, Institute of Medicine. Washington (DC): National Academy Press; 2002.

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. 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 2001.

IOM 2000: Institute of Medicine. Panel on Dietary Antioxidants and Related Compounds, 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. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium and Carotenoids. Washington (DC): National Academy Press 2000.

IOM 1998: Institute of Medicine. Panel on Folate, other B Vitamins, and Choline and Subcommittee on Upper Reference Levels of Nutrients, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline. Washington (DC): National Academy Press 1998.

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

IPCS 1998. International Program on Chemical Safety. International Agency for Research on Cancer (IARC) - Summaries & Evaluations: Iron-carbohydrate Complexes. Volume 2 (1973) p. 161. Geneva (CHE): World Health Organization on behalf of the IPCS (World Health Organization, United Nations Environment Programme, International Labour Organisation). [Accessed 2018 July 24]. Available from: http://www.inchem.org/documents/iarc/vol02/iron.html

Ishitani K, Itakura E, Goto S, Esashi T. Calcium absorption from the ingestion of coral-derived calcium by humans. Journal of Nutritional Science and Vitaminology (Tokyo) 1999;45(5):509-517.

ISMP 2021a. Institute for Safe Medication Practices Canada. "Confusing Calcium Product Labels Lead to Hospitalizations." ISMP Canada Safety Bulletin, vol. 21, no. 1, January 26, 2021, https://www.ismp-canada.org/download/safetyBulletins/2021/ISMPCSB2021-i1-Calcium.pdf

ISMP 2021b. Institute for Safe Medication Practices Canada. "Confusing Labels for Zinc Products." ISMP Canada Safety Bulletin, vol. 21, no. 11, December 14, 2021, https://www.ismp-canada.org/download/safetyBulletins/2021/ISMPCSB2021-i11-HYDROmorphone-label.pdf#page=4

ISMP 2021c. Institute for Safe Medication Practices Canada. "How Much Iron Is in Here?" SafeMedicationUse.ca Newsletter, vol. 11, no. 2, February 5, 2020, https://safemedicationuse.ca/newsletter/downloads/202002NewsletterV11N2-Iron.pdf

Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, Bassford T, Beresford SAA, Black HR, Blanchette P, et al. Calcium plus Vitamin D Supplementation and the Risk of Fractures. The New England Journal of Medicine 2006;354(7):669-683.

Jain SK, Kahlon G, Morehead L, Dhawan R, Lieblong B, Stapleton T, Caldito G, Hoeldtke R, Levine SN, Bass PF. Effect of chromium dinicocysteinate supplementation on circulating levels of insulin, TNF-α, oxidative stress and insulin resistance in type 2 diabetic subjects: randomized, double blind, placebo-controlled study. Molecular Nutrition & Food Research 2012;56(8):1333-1341.

JC 2011: Department of Justice Canada. Food and Drug Regulations. Ottawa (ON): Department of Justice Canada. [Accessed 2018 July 24]. Available from: http://laws-lois.justice.gc.ca/eng/regulations/C.R.C.%2C_c._870/

JC 2008: Department of Justice Canada. Natural Health Products Regulations. Ottawa (ON): Department of Justice Canada. [Accessed 2018 July 24]. Available from: http://laws-lois.justice.gc.ca/eng/regulations/SOR-2003-196/index.html

Johnson EJ, Chung HY, Caldarella SM, Snodderly DM. The influence of supplemental lutein and docosahexaenoic acid on serum, lipoproteins, and macular pigmentation. The American Journal of Clinical Nutrition 2008;87(5):1521-1529.

Kato I, Vogelman JH, Dilman V, Karkoszka J, Frenkel K, Durr NP, Orentreich N, Toniolo P. Effect of supplementation with chromium picolinate on antibody titers to 5-hydroxymethyl uracil. European Journal of Epidemiology 1998; 14(6):621-626.

Klimis-Tavantzis DJ, editor. Manganese in Health and Disease. Boca Raton (FL): CRC Press 1994.

Krieger D, Krieger S, Jansen O, Gass P, Theilmann L, Lichtnecker H. Manganese and chronic hepatic encephalopathy. Lancet 1995;246(8970):270-274.

Kristal AR, Arnold KB, Schenk JM, Neuhouser ML, Goodman P, Penson DF, Thompson IM. Dietary patterns, supplement use, and the risk of symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial. The American Journal Epidemiology 2008;167(8):925-934.

Kucuk O, Sarkar FH, Djuric Z, Sakr W, Pollak MN, Khachik F, Banerjee M, Bertram JS, Wood DP Jr. Effects of lycopene supplementation in patients with localized prostate cancer. Experimental Biology and Medicine 2002;227(10):881-885.

Kucuk O, Sarkar FH, Sakr W, Djuric Z, Pollak MN, Khachik F, Li YW, Banerjee M, Grignon D, Bertram JS, Crissman JD, Pontes EJ, Wood DP Jr. Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy. Cancer Epidemiology, Biomarkers & Prevention 2001;10(8):861-868.

Lee NA, Reasner CA. Beneficial effect of chromium supplementation on serum triglyceride levels in NIDDM. Diabetes Care 1994; 17(12):1449-1452.

Lonn E, Bosch J, Yusuf S, Sheridan P, Pogue J, Arnold JM, Ross C, Arnold A, Sleight P, Probstfield J, Dagenais GR; HOPE and HOPE-TOO Trial Investigators. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. The Journal of the American Medical Association 2005;293(11):1338-1347.

MacKay D, Miller AL. Nutritional support for wound healing. Alternative Medicine Review 2003;8(4):359-377.

Maren, Thomas. Relations between structure and biological activity of sulfonamides. Ann. Rev. Pharmacol. Toxicology. 1976;16:309-327.

Matos HR, Capellozzi VL, Gomes QF, Mascio PD, Medeiros MH. Lycopene inhibits DNA damage and liver necrosis in rats treated with ferric nitrolotriacetate. Archives of Biochemistry and Biophysics 2001;396(2):171-177.

McCarty MF. Over the counter chromium and renal failure [letter]. Annals of Internal Medicine 1997; 127:654-5.

Meisel P, Schwahn C, Luedemann J, John U, Kroemer HK, Kocher T. Magnesium deficiency is associated with periodontal disease. Journal of Dental Research 2005;84(10):937-941.

Meyer F, Bairati I, Fortin A, Gélinas M, Nabid A, Brochet F, Têtu B. Interaction between antioxidant vitamin supplementation and cigarette smoking during radiation therapy in relation to long-term effects on recurrence and mortality: A randomized trial among head and neck cancer patients. International Journal of Cancer 2008;122(7):1679-1683.

Miranda M, Muriach M, Roma J, Bosch-Morell F, Genovés JM, Barcia J, Araiz J, Díaz-Llospis M, Romero FJ. Oxidative stress in a model of experimental diabetic retinopathy: the utility of peroxynitrite scavengers. Archivos de la Sociedad Española de Oftalmología 2006;81(1):27-32.

Moeller SM, Voland R, Tinker L, Blodi BA, Klein ML, Gehrs KM, Johnson EJ, Snodderly DM, Wallace RB, Chappell RJ, Parekh N, Ritenbaugh C, Mares JA; CAREDS Study Group; Women's Health Initiative. Associations between age-related nuclear cataract and lutein and zeaxanthin in the diet and serum in the Carotenoids in the Age-Related Eye Disease Study, an Ancillary Study of the Women's Health Initiative. Archives of Ophthalmology 2008;126(3):354-364.

Mohanty NK, Saxena S, Singh UP, Goyal NK, Arora RP. Lycopene as a chemopreventive agent in the treatment of high-grade prostate intraepithelial neoplasia. Urologic Oncology 2005;23(6):383-385.

Murray MT. Encyclopedia of Nutritional Supplements: The Essential Guide for Improving your Health Naturally. Rocklin (CA): Prima Health 1996.

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.

NAPRA 1999: National Association of Pharmacy Regulatory Authorities. Search National Drug Schedule: Potassium salts (in oral preparations containing more than 5mmol per single dose). Recommended by NDSAC: Schedule II - December 10, 1999 [Accessed 2018 July 24]. Available from: http://napra.ca/nds/potassium-salts-0

NIH 2015a: National Institutes of Health. ChemIDplus advanced. Bethesda (MD): Specialized Information Services, U.S. National Library of Medicine, National Institutes of Health, Department of Health & Human Services. [Accessed 2018 July 24]. Available from: http://chem.sis.nlm.nih.gov/chemidplus

NIH 2015b: National Institutes of Health. Dietary Supplement Label Database. [Accessed 2018 July 24]. Available from: http://www.dsld.nlm.nih.gov/dsld/index.jsp

NIH 2011: National Institutes of Health. Dietary Supplement Fact Sheet: Vitamin B12. [Accessed 2018 July 24]. Available from: http://ods.od.nih.gov/pdf/factsheets/VitaminB12-HealthProfessional.pdf

NIH 2000: National Institute of Health. Osteoporosis Prevention, Diagnosis, and Therapy. NIH Consensus Statement 17(1):1-36 [Internet]. Bethesda (MD): National Institute of Health, Department of Health and Human Services; March 27-29, 2000. [Accessed 2018 July 24]. Available from: http://www.consensus.nih.gov/2000/2000Osteoporosis111html.htm

Nowak MG, Szulc-Musioł B, Ryszka F. Pharmacokinetics of calcium from calcium supplements in healthy volunteers. Pakistan Journal of Pharmaceutical Sciences 2008;21(2):109-112.

Olmedilla B, Granado F, Blanco I, Vaquero M. Lutein, but not alpha-tocopherol, supplementation improves visual function in patients with age-related cataracts: a 2-y double-blind, placebo-controlled pilot study. Nutrition 2003;19(1):21-24.

Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, Keogh JP, Meyskens FL, Valanis B, Williams JH, Barnhart S, Hammar S. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. New England Journal of Medicine 1996;334(18):1150-1155.

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

O'Neil MJ, Smith A, Heckelman PE, Budavari S, editors. The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 15th edition. Whitehouse Station (NJ): Merck & Co., Inc.; 2013.

Pasman WJ, Westerterp-Plantenga MS, Saris WHM. The effectiveness of long-term supplementation of carbohydrate, chromium, fibre and caffeine on weight maintenance. International Journal of Obesity and Related Metabolic Disorders 1997; 21(12):1143-1151.

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

Porrini M, Riso P, Brusamolino A, Berti C, Guarnieri S, Visioli F. Daily intake of formulated tomato drink affects caratenoid plasma and lymphocyte concentrations and improves cellular antioxidant protection. British Journal of Nutrition 2005;93(1):93-99.

Richards JD. 2008. Methods for determining the metal bioavailability of metal sources. United States Patent Application 20080090297. [Accessed 2018 July 24]. Available from: http://www.freepatentsonline.com/y2008/0090297.html

Richer S, Stiles W, Statkute L, Pulido J, Frankowski J, Rudy D, Pei K, Tsipursky M, Nyland J. Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry 2004;75(4):216-230.

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.

Schwartz JR, Marsh RG, Draelos ZD. Zinc and skin health: overview of physiology and pharmacology. Dermatologic Surgery 2005;31(7 Pt 2):837-847.

Schwarz S, Obermüller-Jevic UC, Hellmis E, Koch W, Jacobi G, Biesalski HK. Lycopene inhibits disease progression in patients with benign prostate hyperplasia. The Journal of Nutrition 2008;138(1):49-53.

Seyoum GG, Persaud TV. Can methionine and zinc prevent the embryopathic effects of alcohol? Medical Hypotheses 1991;34(2):153-156.

Shao A, Hathcock JN. Risk assessment for the carotenoids lutein and lycopene. Regulatory Toxicology and Pharmacology 2006;45(3):289-298.

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

Silaste ML, Alfthan G, Agro A, Kesäniemi YA, Hörkkö S. Tomato juice decreases LDL cholesterol levels and increases LDL resistance to oxidation. British Journal of Nutrition 2007;98(6):1251-1258.

Summers WK, Martin RL, Cunningham M, DeBoynton VL, Marsh GM. Complex antioxidant blend improves memory in community-dwelling seniors. Journal of Alzheimer's Disease 2010:19(2):429-439.

Sweetman SC, editor. 2015. Martindale: The Complete Drug Reference. London (GB): Pharmaceutical Press. [Accessed 2018 July 24]. Available from: http://www.medicinescomplete.com

Tang BMP, Eslick GD, Nowson C, Smith C, Bensoussan A. 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 2007;370(9588):657-666.

TGA 2007: Therapeutic Goods Administration. Australian Government. Department of Health. Substances that may be used in Listed medicines in Australia. [Accessed 2018 July 24]. Available from: http://www.tga.gov.au/industry/cm-listed-substances.htm

Tisdale JE, Rudis MI, Padhi ID, Svensson CK, Webb CR, Borzak S, Ware JA, Krepostman A, Zarowitz BJ. Inhibition of N-acetylation of procainamide and renal clearance of N-acetylprocainamide by para-aminobenzoic acid in humans. The Journal of Clinical Pharmacology 1995;35(9):902-910.

Touvier M, Kess E, Clavel-Chapelon F, Boutron-Rualt MC. Dual association of beta-carotene with risk of tobacco-related cancers in a cohort of French women. Journal of the National Cancer Institute 2005;97(18):1338-1344.

Tsuboi M, Shiraki M, Hamada M, Shimodaira H. Effects of phosphorus-containing calcium preparation (bone meal powder) and calcium carbonate on serum calcium and phosphorus in young and old healthy volunteers: a double-blinded crossover study. Journal of Bone and Mineral Metabolism 2000;18(6):321-327.

USP 38 2015: United States Pharmacopeia and the National Formulary (USP 38 - NF 33). Rockville (MD): The United States Pharmacopeial Convention; 2015.

Van Der Kuy PH, Merkus FW, Lohman JJ, Ter Berg JW, Hooymans PM. Hydroxocobalamin, a nitric oxide scavenger, in the prophylaxis of migraine: an open, pilot study. Cephalalgia 2002;22(7):513-519.

Walsdorf NB, Alexandrides G. Calcium glutarate supplement and phosphorous binder. United States patent 6,887,897. May 03 2005.

Wani S, Weskamp C, Marple J, Spry L. Acute tubular necrosis associated with chromium picolinate-containing dietary supplement. The Annals of Pharmacotherapy 2006; 40(3):563-566.

Ward NC, Wu JH, Clarke MW, Puddey IB, Burke V, Croft KD, Hodgson JM. The effect of vitamin E on blood pressure in individuals with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Journal of Hypertension 2007;25(1):227-234.

Wasser WG, Feldman NS, D'Agati VD. Chronic renal failure after ingestion of over-the-counter chromium picolinate. Annals of Internal Medicine 1997; 126(5):410.

Weidner W, Hauck EW, Schnitker J; Peyronie's Disease Study Group of Andrological Group of German Urologists Potassium paraaminobenzoate (POTABA) in the treatment of Peyronie's disease: a prospective, placebo-controlled, randomized study. European Urology 2005;47(4):530-535; discussion 535-536.

WHO 2005: World Health Organization. Evaluation of certain food additives: sixty-third report of the Joint FAO/WHO Expert Committee on Food Additives. (WHO technical report series; 928). Geneva (CH): World Health Organization. [Accessed 2018 July 24]. Available from: http://whqlibdoc.who.int/trs/WHO_TRS_928.pdf

Wickett RR, Kossmann E, Barel A, Demeester N, Clarys P, Vanden Berghe D and Calomme M. Effect of oral intake of choline-stabilized orthosilicic acid on hair tensile strength and morphology in women with fine hair. Archives for Dermatological Research (Archiv fur Dermatologische Forschung). 2007; 299, 499-505.

Winterbone MS, Sampson MJ, Saha S, Hughes JC, Hughes DA. Pro-oxidant effect of alpha-tocopherol in patients with type 2 diabetes after an oral glucose tolerance test-a randomised controlled trial. Cardiovascular Diabetology 2007;6:8.

Zeisel SH. Choline: Critical role during fetal development and dietary requirements in adults. Annual Review of Nutrition 2006;26:229-250.

Zeitlin HC, Sheppard K, Baum JD, Bolton FG, Hall CA. Homozygous transcobalamin II deficiency maintained on oral hydroxocobalamin. Blood 1985;66(5):1022-1027.

12.0 Appendices

Appendix I

Source ingredients with two active components

A source ingredient may provide more than one active component in this monograph. For example, calcium ascorbate provides both calcium and ascorbic acid (vitamin C). The PLA form and label must declare all active components of a source ingredient as medicinal ingredients and provide their quantity per dosage unit if the total daily dose of that active component (i.e. vitamin or mineral) exceeds the monograph's minimum dosage value.

For certain source ingredients that provide more than one active component, when one of the components is used within its acceptable dosage range it could result in the other component exceeding its acceptable dosage range.

For example, a product formulated to provide the maximum dosage value of calcium for adults (i.e. 1500 mg) from the source ingredient, calcium ascorbate, would provide 13.2 g of vitamin C. This exceeds vitamin C's adult maximum dosage value of 2000 mg; and therefore, such a product would not be supported for safety. Based on the calculation described below, the maximum dosage value of calcium from calcium ascorbate would be 228 mg as this dose provides 2000 mg of vitamin C.

The following table outlines dose restriction information for calcium ascorbate. It provides the maximum dosage values for calcium and its corresponding source ingredient. Below this table is a sample calculation which demonstrates how these values were derived.

Table 16. Dose restrictions for calcium from the source ingredient calcium ascorbate
Life Stage Group Maximum dosage value of calcium from calcium ascorbate (mg Ca/day) (mg/day calcium ascorbate)
Infants 0-12 months -
Children 1-3 years 46 (443)
4-8 years 74 (720)
Adolescents 9-13 years 137 (1,330)
14-18 years 205 (1,995)
Adults 19 years and older 228 (2,216)

Sample Calculation

Question: What is the maximum quantity of calcium (maximum dosage value for adults ≥19 y) from the source ingredient calcium ascorbate that can be used in a formulation?

Solution: In order to make this determination, the quantity of calcium from calcium ascorbate that provides the maximum dosage value for adults ≥19 y of ascorbic acid (vitamin C) must be calculated.

Source ingredient: calcium ascorbate (calcium di-ascorbate): Ca (C6H7O6)2
There are 2 molecules of ascorbate (C6H7O6) for every one of calcium (Ca)

Molecular weight = MW
Maximum dosage value (for adults, ≥19 y) = M
Number of molecules = N

Calcium = Ca

PMCa = 40,1 g/mol

MCa= ?


Ascorbic acid = Aa

PMAa = 176,1 g/mol

MAa = 2 g


[MCa]/[PMCa x n] = [MAa]/[PMAa x n]


[MCa]/[40,1 g/mol x 1] = [2 g]/[176,1 g/mol x 2]


MCa = [g x 40.1 g/mol x 1]/[176,1 g/mol x 2]


MCa = [80,2 g2/mol]/[352,2 g/mol]


MCa = 0,228 g ou 228 mg

Appendix II

Guidelines for use or purpose statements

It is mandatory for all natural health products to indicate at least one use or purpose statement.

Specific use or purpose statements:

Ingredient specific use or purpose statements can be used for any or all of the medicinal ingredients contained in a multi-ingredient product, as applicable (see Section 4.2 - Specific use or purpose statements).

A specific use or purpose statement must be made for products providing magnesium (> 350 mg per day), niacin (> 35 mg per day), iron (> 35 mg per day), or zinc (> 40 mg per day).

Inclusion of medicinal ingredient names in a specific use or purpose statement is optional; for example, the specific use or purpose statement can be applied to the whole product. However, if medicinal ingredient names are specified in a use or purpose statement, the statement must be valid for all medicinal ingredients specified.

Appendix III

Definitions and dosage value derivations

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 a RDA cannot be determined (IOM 2006).

Maximum dosage value: The highest medicinal ingredient quantity which a product can supply in a daily dose to support its safe use.

Minimum dosage value: The lowest medicinal ingredient quantity which a product can supply in a daily dose to support recommended claims.

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).

2) Derivations:

AI, RDA and UL values:

These values were established by the Food and Nutrition Board of the Institute of Medicine in collaboration with Health Canada (IOM 2006).

Maximum dosage value:

The method used to set maximum dosage values varied for each medicinal ingredient depending on numerous factors. The method used to derive maximum dosage levels for vitamins and minerals with established physiological functions was different from the method used for those with unestablished physiological functions.

  1. Maximum dosage values for vitamins and minerals with established physiological functions were developed based on the following criteria:

    1. Is there an established UL?
      • If there is an established UL, does it apply to supplements only or to food and supplements?
      • If there is an established UL, how was it derived (i.e. what was the critical adverse reaction on which it was based? was it serious or non-serious? if non-serious, could it be mitigated?)?
    2. What is the average dietary intake?
    3. What doses have previously been marketed in Canada?
    4. What do other regulatory agencies and expert groups recommend as their maximum daily dose?
    5. What doses have been used in clinical trials and have demonstrated evidence for safety and efficacy?

    The only vitamins which were excluded from the method outlined above were:

    • Vitamin D [due to its listing on the Prescription Drug List at 1,000 IU or 25 µg/day (HC 2015)];
    • Vitamin K1 and K2 [adult dose was set as per the listing on the Prescription Drug List at 120 µg/day (HC 2015) and children's doses were set at the AI level (IOM 2006)].
  2. Maximum dosage values for minerals with unestablished physiological functions (i.e. boron, nickel, silicon, tin and vanadium) were calculated from the No Observed Adverse Effect Level (NOAEL) divided by an uncertainty factor (UF). The UF chosen was based on the following: 10 for extrapolation of animal data to humans, 10 for intra-species variation, and 10 for chronic use in humans. If applicable, (i.e. NOAEL was based on animal data) the final value was multiplied by an average adult body weight of 70 kg.

With the exception of beta-carotene and potassium, the maximum dosage value for non-vitamin and non-mineral ingredients was set based on doses demonstrated to be safe in clinical trials. For beta-carotene the maximum dosage value was set as per the vitamin A UL (applying the following conversion factor: 6 µg beta-carotene = 1 µg RAE) (HC 1990; FAO/WHO 1967). For potassium, the maximum dosage value was set as per Schedule II of the National Association of Pharmacy Regulatory Authorities (NAPRA 1999).

Minimum dosage value:

For medicinal ingredients which did not have an RDA or AI, the minimum dose was set at >0. For the remaining medicinal ingredients (with the exception of potassium), the minimum was set using the following method:

For potassium, the AI was inappropriate for setting a minimum dosage value; therefore, the minimum was set at >0.

Appendix IV

Recommended dietary allowance (RDA) and adequate intake (AI)

The AI (as indicated by an asterisk) and RDA values are provided below. For the purpose of this monograph, these values are intended to:

Notes:

   For example, for vitamin A, if the subpopulation is "Adults" and if the product is not contraindicated for
   pregnant or breastfeeding women, the RDA value to be met would be 1,300 μg RAE/day.

Life Stage Group Vitamin A (μg RAE/day)
Adult males 19-30 years 900
31-50 years 900
51-70 years 900
More than 70 years 900
Adult females 19-30 years 700
31-50 years 700
51-70 years 700
More than 70 years 700
Pregnancy 14-18 years 750
19-50 years 770
Breastfeeding 14-18 years 1,200
19-50 years 1,300

Table 17. Recommended dietary allowance (RDA) and adequate intake* (AI) for vitamins (IOM 2011; IOM 2006)
Life Stage Group Biotin (μg/day) Folate (μg/day) Niacin/ niacinamide (mg/day) Panto-thenic acid (mg/day) Riboflavin (mg/day)
Infants 0-6 months - - - - -
7-12 months - - - - -
Children 1-3 years 8* 150 6 2* 0.5
4-8 years 12* 200 8 3* 0.6
Adolescent males 9-13 years 20* 300 12 4* 0.9
14-18 years 25* 400 16 5* 1.3
Adult males 19-30 years 30* 400 16 5* 1.3
31-50 years 30* 400 16 5* 1.3
51-70 years 30* 400 16 5* 1.3
More than 70 years 30* 400 16 5* 1.3
Adolescent females 9-13 years 20* 300 12 4* 0.9
14-18 years 25* 400 14 5* 1.0
Adult females 19-30 years 30* 400 14 5* 1.1
31-50 years 30* 400 14 5* 1.1
51-70 years 30* 400 14 5* 1.1
More than 70 years 30* 400 14 5* 1.1
Pregnancy 14-18 years 30* 600 18 6* 1.4
19-50 years 30* 600 18 6* 1.4
Breastfeeding 14-18 years 35* 500 17 7* 1.6
19-50 years 35* 500 17 7* 1.6
Life Stage Group Thiamine (mg/day) Vitamin A (μg RAE/day) Vitamin B6 (mg/day) Vitamin B12 (μg/day) Vitamin C (mg/day)
Infants 0-6 months - 400* - - -
7-12 months - 500* - - -
Children 1-3 years 0.5 300 0.5 0.9 15
4-8 years 0.6 400 0.6 1.2 25
Adolescent males 9-13 years 0.9 600 1.0 1.8 45
14-18 years 1.2 900 1.3 2.4 75
Adult males 19-30 years 1.2 900 1.3 2.4 90
31-50 years 1.2 900 1.3 2.4 90
51-70 years 1.2 900 1.7 2.4 90
More than 70 years 1.2 900 1.7 2.4 90
Adolescent females 9-13 years 0.9 600 1.0 1.8 45
14-18 years 1.0 700 1.2 2.4 65
Adult females 19-30 years 1.1 700 1.3 2.4 75
31-50 years 1.1 700 1.3 2.4 75
51-70 years 1.1 700 1.5 2.4 75
More than 70 years 1.1 700 1.5 2.4 75
Pregnancy 14-18 years 1.4 750 1.9 2.6 80
19-50 years 1.4 770 1.9 2.6 85
Breastfeeding 14-18 years 1.4 1,200 2.0 2.8 115
19-50 years 1.4 1,300 2.0 2.8 120
Life Stage Group Vitamin D (μg/day) Vitamin E (mg AT/day) Vitamin K1 (μg/day)
Infants 0-6 months 10* - -
7-12 months 10* - -
Children 1-3 years 15 6 30*
4-8 years 15 7 55*
Adolescent males 9-13 years 15 11 60*
14-18 years 15 15 75*
Adult males 19-30 years 15 15 120*
31-50 years 15 15 120*
51-70 years 15 15 120*
More than 70 years 20 15 120*
Adolescent females 9-13 years 15 11 60*
14-18 years 15 15 75*
Adult females 19-30 years 15 15 90*
31-50 years 15 15 90*
51-70 years 15 15 90*
More than 70 years 20 15 90*
Pregnancy 14-18 years 15 15 75*
19-50 years 15 15 90*
Breastfeeding 14-18 years 15 19 75*
19-50 years 15 19 90*

1 The AI for vitamin K is based on median dietary intakes. Vitamin K1 is the predominant form of vitamin K in the diet (IOM 2006; IOM 2001); however this AI applies to vitamin K1, vitamin K2 and total vitamin K1 + K2.

Table 18. Recommended dietary allowance (RDA) and adequate intake* (AI) for minerals (IOM 2011; IOM 2006)
Life Stage Group Boron (mg/day) Calcium (mg/day) Chromium (μg/day) Cobalt1 (μg/day) Copper (μg/day)
Infants 0-6 months - 200* - - -
7-12 months - 260* - - -
Children 1-3 years - 700 - 0.04 340
4-8 years - 1000 - 0.05 440
Adolescent males 9-13 years - 1,300 - 0.08 700
14-18 years - 1,300 - 0.10 890
Adult males 19-30 years - 1,000 35* 0.10 900
31-50 years - 1,000 35* 0.10 900
51-70 years - 1,000 30* 0.10 900
More than 70 years - 1,200 30* 0.10 900
Adolescent females 9-13 years - 1,300 - 0.08 700
14-18 years - 1,300 - 0.10 890
Adult females 19-30 years - 1,000 25* 0.10 900
31-50 years - 1,000 25* 0.10 900
51-70 years - 1,200 20* 0.10 900
More than 70 years - 1,200 20* 0.10 900
Pregnancy 14-18 years - 1,300 - 0.11 1,000
19-50 years - 1,000 30* 0.11 1,000
Breastfeeding 14-18 years - 1,300 - 0.12 1,300
19-50 years - 1,000 45* 0.12 1,300
Life Stage Group Iodine (μg/day) Iron (mg/day) Magnesium (mg/day) Manganese (mg/day) Molyb-denum (μg/day)
Infants 0-6 months - 0.27* - - -
7-12 months - 11 - - -
Children 1-3 years 90 7 80 - -
4-8 years 90 10 130 - -
Adolescent males 9-13 years 120 8 240 - -
14-18 years 150 11 410 - -
Adult males 19-30 years 150 8 400 2.3* 45
31-50 years 150 8 420 2.3* 45
51-70 years 150 8 420 2.3* 45
More than 70 years 150 8 420 2.3* 45
Adolescent females 9-13 years 120 8 240 - -
14-18 years 150 15 360 - -
Adult females 19-30 years 150 18 310 1.8* 45
31-50 years 150 18 320 1.8* 45
51-70 years 150 8 320 1.8* 45
More than 70 years 150 8 320 1.8* 45
Pregnancy 14-18 years 220 27 400 - -
19-50 years 220 27 355 2.0* 50
Breastfeeding 14-18 years 290 10 360 - -
19-50 years 290 9 315 2.6* 50
Life Stage Group Nickel (mg/day) Phosphorus (mg/day) Selenium (μg/day) Silicon (mg/day) Tin (mg/day)
Infants 0-6 months - - - - -
7-12 months - - - - -
Children 1-3 years - 460 - - -
4-8 years - 500 - - -
Adolescent males 9-13 years - 1,250 - - -
14-18 years - 1,250 - - -
Adult males 19-30 years - 700 55 - -
31-50 years - 700 55 - -
51-70 years - 700 55 - -
More than 70 years - 700 55 - -
Adolescent females 9-13 years - 1,250 - - -
14-18 years - 1,250 - - -
Adult females 19-30 years - 700 55 - -
31-50 years - 700 55 - -
51-70 years - 700 55 - -
More than 70 years - 700 55 - -
Pregnancy 14-18 years - 1,250 - - -
19-50 years - 700 60 - -
Breastfeeding 14-18 years - 1,250 - - -
19-50 years - 700 70 - -
Life Stage Group Vanadium (mg/day) Zinc (mg/day)
Infants 0-6 months - 2*
7-12 months - 3
Children 1-3 years - 3
4-8 years - 5
Adolescent males 9-13 years - 8
14-18 years - 11
Adult males 19-30 years - 11
31-50 years - 11
51-70 years - 11
More than 70 years - 11
Adolescent females 9-13 years - 8
14-18 years - 9
Adult females 19-30 years - 8
31-50 years - 8
51-70 years - 8
More than 70 years - 8
Pregnancy 14-18 years - 12
19-50 years - 11
Breastfeeding 14-18 years - 13
19-50 years - 12

1 Calculated from the vitamin B12 RDA (IOM 2006).

Appendix V

Guidance for products containing beta-carotene

Background:

Although all of the claims for beta-carotene are associated with its vitamin A activity, it is not acceptable to list beta-carotene as a source ingredient for vitamin A. This is because the rate of conversion of beta-carotene to vitamin A in the human body depends on numerous factors (e.g. vitamin A status, dietary factors such as vegetable consumption and fat intake, genetic factors, etc.). In other words, the consumption of supplemental beta-carotene does not always result in a consistent rate of conversion to vitamin A. Nevertheless, products providing beta-carotene do contribute to vitamin A requirements; therefore, all of the health claims associated with beta-carotene are linked to its vitamin A activity. Furthermore, there is a potential risk of hypervitaminosis A associated with the consumption of combinations including both beta-carotene and vitamin A.

Determining dosage requirements for the claim "Helps to prevent vitamin A deficiency":

In order to make any prevention of deficiency health claims, a nutrient must be included in a product at a dose at or above its recommended dietary allowance (RDA) or adequate intake (AI). There are three potential scenarios in which a product would qualify for the claim: "Helps to prevent vitamin A deficiency":

  1. The product could provide vitamin A on its own: See Appendix IV to determine vitamin A minimum dosage requirements;
  2. The product could provide beta-carotene on its own: See Table 19 below for minimum dosage requirements; or
  3. The product could provide both beta-carotene and vitamin A: See Appendix IV to determine vitamin A minimum dosage requirements and apply the conversion factor of 6 µg of beta-carotene = 1 µg all-trans-retinol (HC 1990; FAO/WHO 1967).
Table 19. Daily dose in microgram (μg) of beta-carotene
Life Stage Group Minimum dose of beta-carotene1 (μg/day)
Infants 0-6 months 2,400*
7-12 months 3,000*
Children 1-3 years 1,800
4-8 years 2,400
Adolescent males 9-13 years 3,600
14-18 years 5,400
Adult males 19 years and older 5,400
Adolescent females 9-13 years 3,600
14-18 years 4,200
Adult females 19 years and older 4,200
Pregnancy 14-18 years 4,500
19-50 years 4,620
Breastfeeding 14-18 years 7,200
19-50 years 7,800

1 These values are based on the RDA and AI values for vitamin A based on life stage group (IOM 2006) and were derived from the conversion factor of 6 µg of beta-carotene = 1 µg all-trans-retinol; hence, a ratio of 6:1 beta-carotene:vitamin A, on a weight to weight basis (HC 1990; FAO/WHO 1967).

Example:

As per Appendix IV, the minimum dose for the vitamin A deficiency claim for adults (excluding breastfeeding women) is 900 µg per day. This is based on the highest RDA for all adult subpopulations (i.e. 900 µg for adult males). There are three potential ways this dose can be achieved:

  1. Vitamin A alone (900 µg RAE (from vitamin A) per day);
  2. beta-Carotene alone (5400 µg beta-carotene per day); or
  3. Combinations of vitamin A plus beta-carotene (e.g. 500 µg RAE (from vitamin A) + 2400 µg beta carotene = 900 µg RAE per day).

Note: The depiction of beta-carotene in RAE is to demonstrate the efficacy of the combination of vitamin A and beta-carotene only and must not appear on the PLA form or label.

Mitigating the risk of hypervitaminosis A:

In products containing both vitamin A and beta-carotene, the risk of hypervitaminosis A is to be mitigated by ensuring that the combined doses of these two medicinal ingredients is not excessively high. Therefore, the combined dose of vitamin A plus beta-carotene must not exceed the maximum dosage value for vitamin A, measured in μg RAE (See Table 8). The conversion factor of 6 μg beta-carotene = 1 μg RAE (HC 1990; FAO/WHO 1967) can be applied for the specific purpose of ensuring safety of the combined dose. The example below illustrates how the 6:1 conversion factor can be used to determine the safety of combinations including beta-carotene and vitamin A:

Example:

The maximum dosage value of vitamin A for adults is 3000 μg RAE per day. If a product contained 2800 μg vitamin A (i.e. all-trans-retinol, vitamin A acetate, vitamin A palmitate), then it could contain no more than 1200 μg beta-carotene. See calculation below:

2800 μg vitamin A + 1200 μg beta-carotene (200 μg RAE) = 3000 μg RAE.

Note: The value of 3000 μg RAE is to demonstrate the safety of the combination of vitamin A and beta-carotene only and must not appear on the PLA form or label.

Appendix VI

Conversion factors

1.  Pantothenic acid (USP 38):
Table 20. Conversion of pantothenic acid source ingredient quantity into pantothenic acid quantity
Source ingredient (1 mg) Pantothenic acid quantity (mg)
Calcium D-pantothenate 0.92
Calcium DL-pantothenate 0.46
Dexpanthenol 1.07
DL-Panthenol 0.53
DL-Pantothenic acid 0.50

2.  Vitamin A (IOM 2006):

The quantity of vitamin A must always be provided in terms of retinol activity equivalents (RAE) (i.e. μg all-trans-retinol), irrespective of the source ingredient used.

International Units (IU) may be provided as optional additional information on the PLA form in the "additional quantity per dosage unit" field and on product labels.

Table 21. Conversion of vitamin A source ingredient quantity into vitamin A quantity in terms of retinol activity equivalents (RAE) and vitamin A activity in terms of International Units (IU)
Source ingredient (1 μg) Vitamin A quantity (μg RAE) Vitamin A activity (IU)
all-trans-Retinol 1.00 3.33
all-trans-Retinyl acetate 0.87 2.91
all-trans-Retinyl palmitate 0.55 1.82

Examples using the vitamin A conversion factors:

Converting vitamin A activity into quantity of RAE (µg)

Convert 500 IU of vitamin A activity from all-trans-retinol into μg RAE:

= 500 IU x 1 μg RAE/3.33 IU vitamin A

= 150 μg RAE

or

= 3000 IU x 0.87 μg RAE/2.91 IU vitamin A

= 897 μg RAE

3.  beta-Carotene:

The quantity of beta-carotene must always be provided in weight amount (i.e. μg).

IUs may be provided as optional additional information on the PLA form in the "additional quantity per dosage unit" field and on product labels.

1 IU beta-carotene = 0.6 μg beta-carotene (USP 38)

4.  Vitamin B12:

1.5 μg of vitamin B12 = 0.06 μg of cobalt

5.  Vitamin D:

The quantity of vitamin D must always be provided in weight amount (i.e. μg).

IUs may be provided as optional additional information on the PLA form in the "additional quantity per dosage unit" field and on product labels.

1 IU of vitamin D = 0.025 μg cholecalciferol (IOM 2006)

= 0.025 μg ergocalciferol

6.  Vitamin E (IOM 2006)

The quantity of vitamin E must always be provided in terms of alpha-tocopherol (AT) (i.e. mg 2R-alpha-tocopherol), irrespective of the source ingredient used.

IUs may be provided as optional additional information on the PLA form in the "additional quantity per dosage unit" field and on product labels.

Table 22. Conversion of vitamin E source ingredient quantity into vitamin E quantity in terms of alpha-tocopherol (mg AT) and vitamin E activity in terms of International Units (IU)
Source ingredient (1 mg) Vitamin E quantity (mg AT) Vitamin E activity (IU)
d-alpha-Tocopherol 1.00 1.49
d-alpha-Tocopheryl acetate 0.91 1.36
d-alpha-Tocopheryl succinate 0.81 1.21
dl-alpha-Tocopherol 0.50 1.10
dl-alpha-Tocopheryl acetate 0.45 1.00
dl-alpha-Tocopheryl succinate 0.40 0.89
Table 23. Conversion of vitamin E source ingredient activity (IU) into vitamin E quantity in terms of alpha-tocopherol (mg AT)
Source ingredient (1 IU) Vitamin E quantity (mg AT)
d-alpha-Tocopherol 0.67
d-alpha-Tocopheryl acetate 0.67
d-alpha-Tocopheryl succinate 0.67
dl-alpha-Tocopherol 0.45
dl-alpha-Tocopheryl acetate 0.45
dl-alpha-Tocopheryl succinate 0.45

Examples using the vitamin E conversion factors:

  1. Converting vitamin E activity into quantity of AT (mg)

    Convert 400 IU of d-alpha-tocopheryl succinate activity into mg AT:
    = 400 IU x 0.67 mg AT/IU
    = 268 mg AT

  2. Converting vitamin E source ingredient quantity into quantity of AT (mg)

    Convert 200 mg of dl-alpha-tocopheryl acetate into mg AT:
    = 200 mg x 0.45 mg AT/mg
    = 90 mg AT

Appendix VII

Zinc and copper interaction

Zinc supplements can cause a copper deficiency. In order to mitigate this risk, applicants are encouraged to supplement high dose zinc products with copper. Table 24 below outlines how much copper is sufficient to mitigate this risk based on both life stage group and zinc daily dosage. Products which do not fulfill the zinc and copper quantity guidelines below require an additional risk statement. See Section 7.0 Risk Information.

Table 24. Daily dosage of copper required to mitigate the risk of copper deficiency in products containing high doses of zinc
Life Stage Group Daily dosage range of zinc which requires added copper or a risk statement (mg/day) Daily dosage range of copper required to avoid a risk statement (µg/day)
Infants 0-12 months ≤ 2 0
Children 1-3 years 5-7 280-700
Children 4-8 years 8-12 480-2,500
Adolescents 9-13 years 16-23 920-4,000
Adolescents 14-18 years 25-34 1,360-6,500
Adults 19 years and older 31-50 2,000-8,000

Examples using Table 24:

  1. Question: Product A is targeted to adults only. The product provides a daily dose of zinc of 30 mg but does not contain copper. Is a risk statement necessary on this product?

    Answer: No. According to Table 24, for an adult subpopulation, there is no need for copper supplementation at a dose of 30 mg zinc per day. Therefore, no risk statement is required.


  2. Question:Product B is targeted to adults and adolescents ≥ 12 years. The product provides zinc and copper at daily dosages of 20 mg and 500 µg, respectively. Is a risk statement necessary on this product?
  3. Answer: Yes. According to Table 24, for an adult subpopulation, there is no need for copper supplementation at a daily dose of 20 mg zinc. However, for adolescents ≥ 12 years, products providing daily doses of zinc between 16-23 mg need at least 920 µg copper per day. As the product in this example provides 500 µg of copper per daily dose, the following risk statement is required: "Zinc supplementation can cause a copper deficiency. If you are unsure whether you are taking enough copper, consult a health care practitioner prior to use".

Appendix VIII

Guidance on labelling for specific mineral supplements: calcium, iron, magnesium and zinc

Health care professionals and consumers have reported confusion in distinguishing between the quantity of the element (i.e., the medicinal ingredient) and the quantity of the salt (i.e., the source information) of the above four mineral supplements when reading the product label, which has led to medication errors in Canada including dosing errors. In the case of these minerals, dosing errors may lead to serious health consequences (ISMP 2021a, b, c). Health care professionals may recommend or prescribe to consumers calcium, iron, magnesium or zinc by either the elemental quantity or the salt quantity. The medicinal ingredient quantity listed on the label should be clearly associated with the elemental mineral.

a) Single ingredient mineral supplements

The quantity of the element must be clearly associated with the element name, so that it is not confused with the quantity of the salt. In addition, the quantity of the element and the salt may both appear on the label. Anhydrous salts should be clearly identified in order to account for their element-to-salt ratio. Note that the label generated by the web-based PLA form has not been adjusted to represent single ingredient products as recommended above; however, the information on the marketed label should be represented as clearly as possible based on this guideline.

Examples
 Each tablet contains:
 Calcium.....500 mg (calcium carbonate 1250 mg)

 Each tablet contains:
 Calcium.....500 mg
 derived from calcium carbonate 1250 mg

 Each tablet contains:
 Iron..........60 mg (from anhydrous Iron (II) sulfate 190 mg)

In cases where a mineral supplement is derived from mixed source ingredients or complexes of the same element, the quantity of the salt(s) does not need to be identified. However, the addition of a note clarifying that the quantity of the mineral represents the amount of the element is recommended.

As per the label generated from the web-based PLA form:

Medicinal ingredient
  (Source information)
Medicinal ingredient Quantity per 1 tablet*
Calcium .....................................................................................
  (Calcium carbonate, Calcium citrate, Calcium fumarate)
500 mg

* For minerals, the medicinal ingredient quantity represents the amount of the element per tablet.

b) Multi-ingredient mineral supplements

The quantity of the element(s) must be clearly associated with the element name, so that it is not confused with the quantity of the salt(s). The quantity of the salt(s) does not need to be identified. However, the addition of a note clarifying that the quantity of the mineral represents the amount of the element would be recommended.

As per the label generated from the web-based PLA form:

Medicinal ingredient
  (Source information)
Medicinal ingredient Quantity per 1 tablet*
Calcium .....................................................................................
  (Calcium carbonate)
500 mg
Iron ..........................................................................................
  (Iron (II) sulfate)
30 mg

* For minerals, the medicinal ingredient quantity represents the amount of the element per tablet.