Transcript DSHEA and Bioavailability

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
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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
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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
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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
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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
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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
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Vitamins and minerals
Macronutrients
Botanicals
Amino Acids
Substances intended to supplement the diet
Potential Bioavailability Issues
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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:
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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
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How to deal with exposure levels
Effectiveness
Safety
Safety factors for uncertainty
Host and Use Challenges
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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?