DSHEA and Bioavailability Elizabeth A. Yetley, Ph.D. Ctr. Food Safety & Applied Nutrition Food and...
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Transcript of DSHEA and Bioavailability Elizabeth A. Yetley, Ph.D. Ctr. Food Safety & Applied Nutrition Food and...
DSHEA and Bioavailability
Elizabeth A. Yetley, Ph.D.
Ctr. Food Safety & Applied Nutrition
Food and Drug Administration
Approach:
• Regulatory Applications– How has concept been applied?– General characteristics
• Specific questions for dietary supplements
• Science and research needs
Regulatory Applications
Regulatory Experience
• Drugs -- separate regulations
• Foods -- case-by-case– Safety– Labeling
Food Safety -- Bioavailability
• Safety– Food additive authorizations– GRAS status– GMPs– Infant formula quality factors
Safety Example: Food Additive
• Olestra
• Must add fat soluble vitamins
• Label information required
Safety Example -- GRAS
• GRAS -- Nutrients:
• Amounts not in excess of that required to produce intended effect
• Levels not to exceed GMPs
Safety Example -- Finished Products
• Calcium and iron supplements – Less effective than expected
• High doses of selenium -- low toxicity
• Contaminants – Mercury– Lead in calcium supplements
Safety Example-- Infant Formula
• Infant formula “Quality Factors”
• Statutory requirement
• Failure to meet --> adulteration
• Proposed definition:
Food Labeling -- Bioavailability
• Label information– Nutrition or Supplement Facts declarations– Claims– “Enriched” products
Label declarations -- History
• Based on analytical amounts
• Nutrients: – Derived from 1968 RDAs – 1968 RDA’s -- some “correction” for
bioavailability– FDA’s compliance method for some nutrients
-- microbiological assay
Label declarations -- History
• Calorie content– May use specific Atwater factors– May use specific food factors– Correct for insoluble dietary fiber– Correct for protein indigestibility
Label Declarations -- History
• Non-nutrients:– No correction for bioavailability
Claims -- History
• Truthful and not misleading
• Meets regulations
• “More” claims: >= 10% RDI
Health claims -- History
• Calcium and osteoporosis
• Folic acid and neural tube defects
• Meet USP standards: dissolution & disintegration
• Calcium: “assimilable”
“Enriched” products -- History
• Nutrient -- physiologically available
• Level --> not result in excessive intake
• Nutrient -- suitable for intended purpose
“Enriched” products -- History
• Iron and Calcium
• “Safe and suitable”, or
• “Harmless and assimilable”
• Research– Predictive validity of animal bioassays– Identification relative bioavailability of
ingredient sources
General principles -- History
• Affects both safety and effectiveness
• Case-by-case
• Physiological effects, not just absorption
• Linked to intended use
• Amounts not to exceed intended effects
• Not to deceive consumer
Current Marketed D.S. Products
Ingredients
• Vitamins and minerals
• Macronutrients
• Botanicals
• Amino Acids
• Substances intended to supplement the diet
Potential Bioavailability Issues
• Source ingredient
• Extraction and processing procedures
• Interactions -- “active” constituents
• Effects of “inert” ingredients/coatings…
• Interactions– with diet– with drugs
Next Steps -- Science & Research
Issues to be addressed
• Definition: What is it?
• Compliance (analytical) methods?
• Specific regulatory impacts– Safety requirements?– Label information?– GMPs?
Definition: Why Discuss?
• When to consider bioavailability?
• How to monitor compliance?
• Substantiation or documentation?
Definition:
• Absorption?
• Digestion?
• Metabolism?
• Excretion?
• Summary: Utilization?
Definitional Challenges?
• Case by case vs. general?
• Ingredient vs. finished product?
Definitional Challenges?
• New RDI’s based on “equivalents”– Example: Folic acid
• Applicability to other ingredients?
Definitional Challenges?
• New Upper Limits based on “synthetics”– Example: Folic acid
• Applicability to other ingredients?
Safety and Effectiveness Challenges
• How to deal with exposure levels
• Effectiveness
• Safety
• Safety factors for uncertainty
Host and Use Challenges
• Label information
• Appropriate use conditions
• Vulnerable populations
• Consumer right to know issues
Other Challenges
• Effect of processing?
• Effect of storage?
Science and Research Needs
• Bioavailability: High priority research need for CFSAN
• Definition
• Analytical methods
• Meaningfulness of measures
Key issue
• On food - drug continuum
• Where do dietary supplements fall relative to bioavailability?