Report of the Scientific Committee of the Food Safety Authority of Ireland The Safety of Vitamins and Minerals in Food Supplements – Establishing Tolerable Upper Intake Levels and a Risk Assessment Approach for Products Marketed in Ireland (Revision 2) Report of the Scientific Committee of the Food Safety Authority of Ireland The Safety of Vitamins and Minerals in Food Supplements – Establishing Tolerable Upper Intake Levels and a Risk Assessment Approach for Products Marketed in Ireland Published by: Food Safety Authority of Ireland Email: [email protected] Website: www.fsai.ie Join us on LinkedIn Follow us on Twitter @FSAIinfo Say hi on Facebook Visit us on Instagram Subscribe to our Youtube channel Originally published in 2018 Revision published in 2020 Applications for reproduction should be made to the FSAI Information Unit ISBN 978-1-910348-10-9 Report of the Scientific Committee of the Food Safety Authority of Ireland The Safety of Vitamins and Minerals in Food Supplements – Establishing Tolerable Upper Intake Levels and a Risk Assessment Approach for Products Marketed in Ireland CONTENTS ABBREVIATIONS 5 FOREWORD 6 EXECUTIVE SUMMARY 7 Recommendations ......................................................8 1. SAFETY OF VITAMINS AND MINERALS IN FOOD SUPPLEMENTS 11 1.1 Purpose of this Report . 11 1.2 Micronutrients ....................................................11 1.3 Vitamins . 11 1.4 Minerals and Trace Elements . 12 1.5 Dietary Reference Values ..........................................12 1.6 Sources of Intake..................................................16 1.7 Dietary Intakes in Ireland ..........................................17 1.8 Vitamins and Minerals: Relevant Food Legislation in Ireland . 20 1.9 Issues Arising Due to the Absence of Maximum Limits for Vitamins and Minerals added to Foods and used in Food Supplements . 22 1.10 Vitamin and Mineral Tolerable Upper Limits Suitable for Ireland ........24 1.11 Risk Assessment of Micronutrients in Food Supplements ...............24 1.12 Recommendations . 25 1.13 References . 25 2. ABOUT THE WORKING GROUP AND METHODS 28 2.1 Task of the Safe Micronutrient Levels Working Group . 28 2.2 Membership of the Safe Micronutrient Levels Expert Working Group . 28 2.3 Vitamins and Minerals Considered ..................................28 2.4 Scientific Literature Considered .....................................29 2.5 General Principles for Assessing Micronutrients . 30 1 of 156 The Safety of Vitamins and Minerals in Food Supplements – Establishing Tolerable Report of the Scientific Upper Intake Levels and a Risk Assessment Committee of the Food Safety Authority of Ireland Approach for Products Marketed in Ireland 3. MICRONUTRIENT TOLERABLE UPPER LIMIT REPORTS 31 3.1 Vitamins . 31 Vitamin A . 31 β-carotene . 36 Vitamin D . 38 Vitamin E . 43 Vitamin K . 46 Thiamin (B1) . 49 Riboflavin (B2) . .51 Niacin . 53 Vitamin B6 . 56 Folic Acid . 59 Vitamin B12 . 65 Biotin . 69 Pantothenic Acid . 71 Vitamin C . 73 3.2 Minerals and Trace Elements . 76 Calcium . 76 Magnesium . 79 Phosphorus . 81 Sodium & Chloride . 84 Potassium . 87 Iron . 89 Zinc . 93 Copper . 96 Selenium . 99 Iodine . 102 Manganese . 105 Molybdenum . 108 Fluoride . 111 Chromium . 115 Boron . 118 Silicon . 121 2 of 156 APPENDIX I. FORMS OF VITAMINS AND MINERALS PERMITTED 123 Table 1a . Vitamin formulations which may be used in the manufacture of food supplements and which may be added to foods according to EU legislation . 123 Table 1b . Mineral Substances which may be used in the Manufacture of Food Supplements and which may be added to Foods according to EU Legislation . 124 APPENDIX II. TOLERABLE UPPER INTAKE LEVELS FOR IRELAND 126 Table 2 . Tolerable Upper Intake Levels for Vitamins and Minerals Recommended for Ireland Derived from EFSA . 126 Table 3 . Tolerable Upper Intake Levels for Vitamins and Minerals Recommended for Ireland Derived from the IOM . 127 APPENDIX III. FULL LIST OF TOLERABLE UPPER INTAKE LEVELS AVAILABLE FROM EFSA AND THE IOM 128 Table 4a . Tolerable Upper Intake Levels, Vitamins, EFSA . 128 Table 4b . Tolerable Upper Intake Levels, Minerals, EFSA . 129 Table 5a . Tolerable Upper Intake Levels, Vitamins, IOM . 130 Table 5b . Tolerable Upper Intake Levels, Minerals, IOM . 131 APPENDIX IV. DIETARY REFERENCE VALUES OTHER THAN ULS AVAILABLE FROM EFSA AND THE IOM 132 Table 6a . EFSA Dietary Reference Values; Recommended Dietary Allowance and Adequate Intake for Vitamins . 132 Table 6b . EFSA Dietary Reference Values; Recommended Dietary Allowance and Adequate Intake for Minerals . 133 Table 6c . EFSA Dietary Reference Values; Average Requirement for Vitamins and Minerals . .134 Table 7a . The IOM Dietary Reference Values; Recommended Dietary Allowances and Adequate Intakes for Vitamins . 135 Table 7b . The IOM Dietary Reference Values; Recommended Dietary Allowances and Adequate Intakes for Minerals . 136 Table 8a . The IOM Dietary Reference Values; Average Requirements for Vitamins . 137 Table 8b . The IOM Dietary Reference Values; Average Requirements (AR) for Minerals . 138 3 of 156 The Safety of Vitamins and Minerals in Food Supplements – Establishing Tolerable Report of the Scientific Upper Intake Levels and a Risk Assessment Committee of the Food Safety Authority of Ireland Approach for Products Marketed in Ireland APPENDIX V. NATIONAL DIETARY MICRONUTRIENT INTAKE DATA 139 Table 9a . Mean, SD and Percentile Values of Vitamin and Mineral Intakes from Food Sources only in Irish Pre-school Children for the Total Population (n500) . 139 Table 9b . Mean, SD and Percentile Values of Vitamin and Mineral Intakes from All Sources (including food supplements*) in Irish Pre-school Children for the Total Population (n500) . 140 Table 10a . Mean, SD and Percentile Values of Vitamin and Mineral Intakes from Food Sources Only in Irish Children (5-12yrs) for the Total Population by Gender . 141 Table 10b . Mean, SD and Percentile Values of Vitamin and Mineral Intakes from All Sources (including food supplements*) in Irish Children (5-12yrs) for the Total Population by Gender . 142 Table 11a . Mean, SD and Percentile Values of Vitamin and Mineral Intakes from Food Sources only in Irish Teens (13-17yrs) for the Total Population by Gender . 143 Table 11b . Mean, SD and Percentile Values of Vitamin and Mineral Intakes from All Sources (including food supplements*) in Irish Teens (13-17yrs) for the Total Population by Gender . 144 Table 12a . Mean, SD and Percentile Values of Vitamin and Mineral Intakes from Food Sources Only in Irish Adults for the Total Population by Age . 145 Table 12b . Mean, SD and Percentile Values of Vitamin and Mineral Intakes from All Sources (including food supplements*) in Irish Adults for the Total Population by Age . 146 Table 13a . Mean, SD and Percentile Values of Vitamin and Mineral Intakes from Food Sources Only in Irish Adults for the Total Population by Gender and Age . 147 Table 13b . Mean, SD and Percentile Values of Vitamin and Mineral Intakes from All Sources (including food supplements*) in Irish Adults for the Total Population by Gender and Age . 149 TERMS OF REFERENCE 151 MEMBERSHIP OF THE SAFE MICRONUTRIENT LEVELS EXPERT WORKING GROUP 152 MEMBERSHIP OF THE PUBLIC HEALTH NUTRITION SUB-COMMITTEE 153 MEMBERSHIP OF THE SCIENTIFIC COMMITTEE 154 NOTES 155 4 of 156 ABBREVIATIONS µg Micrograms LOAEL Lowest Observed Adverse Effect Level AI Adequate Intake LTI Lower Threshold Intake AMDR Acceptable Macronutrient Distribution mg Milligrams Ranges MKs Menaquinones BMDL Lower Limit on the Benchmark Dose NANS National Adult Nutrition Survey COMA Committee on Medical Aspects of Food Policy (UK) NCFS National Children’s Food Survey DFEs Dietary Folate Equivalents NOAEL No Observed Adverse Effect Level DRI Dietary Reference Intakes NPNS National Pre-School Nutrition Survey DRVs Dietary Reference Values NSIFCS North/South Ireland Food Consumption Survey EAR Estimated Average Requirement NTD Neural Tube Defect EFSA European Food Safety Authority NTFS National Teens’ Food Survey EGMV Expert Group on Vitamins and Minerals PARNUTs Foods for Particular Nutritional Uses EU European Union PN Pyridoxine FAO Food and Agricultural Organization (United Nations) POM Prescription Only Medicine FSAI Food Safety Authority of Ireland PRI Population Reference Intake g Gram RDA Recommended Dietary Allowance IARC International Agency for Research on RI Reference Intake Cancer UF Uncertainty Factor IOM Institute of Medicine UL Tolerable Upper Intake Level IU International Unit UV Ultra Violet IUNA Irish University Nutrition Alliance WHO World Health Organization JECFA Joint FAO/WHO Expert Committee on Food Additives 5 of 156 The Safety of Vitamins and Minerals in Food Supplements – Establishing Tolerable Report of the Scientific Upper Intake Levels and a Risk Assessment Committee of the Food Safety Authority of Ireland Approach for Products Marketed in Ireland FOREWORD Vitamins and minerals are required in small amounts for normal growth, development and on-going wellbeing. They are found naturally in diet; however, food supplements may be used to augment dietary intakes of vitamins and minerals and are specifically recommended at particular life stages, e.g. folic acid for women of childbearing age, and vitamin D in infancy. European Union (EU) regulation of food supplements containing vitamins and minerals was adopted in 2002 (Directive 2002/46/EC). Excess of some vitamins and minerals may have detrimental health effects; hence, EU legislation provides for, among others, the setting of maximum safe levels of