Vitamin and Mineral Safety 2 nd Edition (2004)

1. Vitamin and Mineral Safety2nd Edition (2004) John Hathcock, Ph.D. Vice President, Scientific and International Affairs Council for Responsible Nutrition Washington, DC

2. To identify the highest chronic daily supplemental intakes of vitamins and minerals that can be confidently asserted to pose no risk of adverse effects for nearly everyone in the healthy adult population. (Note: The values identified do not represent recommended intakes.) Objective

3. Quantitative evaluation by Risk Assessment procedure Scientific evidence on dose-response relationship of nutrients to adverse effects Addresses supplemental amounts of nutrients Uses accepted scientific methodology Uses Observed Safe Level (OSL), if possible, where data do not support NOAEL or LOAEL Scientific conclusions set in a practical framework International comparisons gives global utility Major Characteristics

4. Identifies Upper Level for Supplements (ULS) by UL method when a NOAEL or LOAEL can be identified Observed Safe Level (OSL), where no NOAEL or LOAEL Direct approach using supplemental data, where possible Difference approach when direct method is not possible Conservative selection of data, justifying Uncertainty Factor (UF) of 1.0, i.e., no additional correction for uncertainty CRN Method

5. Valid and internationally accepted scientific basis for decisions related to safety Help avoid harm from excessive intakes Advice to the public about safety of high intakes Establish regulatory maximums for manufactured products—established to help avoid harm from consumption of toxic excesses Objective standard for international trade, consistent with WTO (SPS) obligations WHY USE RISK ASSESSMENT?

6. RDA are not defined or identified to address safety Not valid as an indicator of safety RDA limit may preclude benefits at higher intake levels (e.g., chromium, folic acid, selenium) Cannot be applied to substances without RDA values Disproportionately restrictive, compared with high intakes from certain conventional foods (e.g., B12 in liver) Rejected by Codex (CCNFSDU) in 2003 Labeling, not limits, can address proper use WHY NOT USE RDA-BASED LIMITS?

7. All values apply to supplemental intakes only (ULS), not totals Increased values: 4 nutrients (vitamins D, E, C, and B1) Decreased values: 5 nutrients (vitamins K and B6, magnesium, iodine, iron)—note: iron is only marginally lower Newly evaluated: 3 nutrients (potassium, boron, fluoride) CHANGES in 2nd Edition

8. Vitamin A: UK sets value on bone effects; others on birth defects Vitamin D: CRN uses same data as FNB, but gains confidence from later data used by SCF Vitamin E: CRN directly uses clinical trial data Nicotinic acid: In contrast to others, CRN does not consider flushing to be “hazard” B6: International disagreement and confusion; CRN value same as by FNB but on somewhat different basis B12: CRN OSL method identifies 3,000 mcg; UK value is 2,000 mcg; others do not find “hazard” and do not set value Calcium: CRN and UK values for supplements; others for totals Chromium: CRN directly uses clinical trial data; EVM extrapolates from animal data; FNB and EC did not set values Selenium: CRN’s lower value is for supplements, not totals, and the difference is less that it appears Important Differences Among Reviews FNB, EC SCF, UK EVM, and CRN

9. Urge Food and Nutrition Board to expand the UL method to include the OSL concept Urge Codex, EC and national authorities to developed internationally accepted UL values Based on CRN modifications of UL method FUTURE: Vitamins and Minerals

10. Apply expanded UL method to safety evaluation Other nutrients (e.g., amino acids, fatty acids) Vitamin-like substances in diet (e.g., lutein, lycopene, etc.) Metabolites in physiology and/or diet (e.g., carnitine, creatine, Co Q10, etc.) Complex materials (botanical ingredients and extracts, e.g., garlic, ginkgo, ginseng, etc.) FUTURE: Non-essential nutrients

11. Risk assessment is only rational basis to identify need for and size of limits for nutrients in supplements UL method is appropriate but should be expanded to include OSL concept Safety data available on supplemental amounts of many nutrients, and thus ULS can be derived directly Strong disagreements between FNB, EC SCF (now EFSA) and UK EVM on some nutrients show need for international agreements on safety values CRN approach and outcomes provide good example of science-based safety evaluation in practical setting Conclusions