DSHEA%20and%20Bioavailability

1
DSHEA and Bioavailability

• Elizabeth A. Yetley, Ph.D.
• Ctr. Food Safety Applied Nutrition
• Food and Drug Administration

2
Approach

• Regulatory Applications
• How has concept been applied?
• General characteristics
• Specific questions for dietary supplements
• Science and research needs

3
Regulatory Applications
4
Regulatory Experience

• Drugs -- separate regulations
• Foods -- case-by-case
• Safety
• Labeling

5
Food Safety -- Bioavailability

• Safety
• Food additive authorizations
• GRAS status
• GMPs
• Infant formula quality factors

6
Safety Example Food Additive

• Olestra
• Must add fat soluble vitamins
• Label information required

7
Safety Example -- GRAS

• GRAS -- Nutrients
• Amounts not in excess of that required to produce
  intended effect
• Levels not to exceed GMPs

8
Safety Example -- Finished Products

• Calcium and iron supplements
• Less effective than expected
• High doses of selenium -- low toxicity
• Contaminants
• Mercury
• Lead in calcium supplements

9
Safety Example-- Infant Formula

• Infant formula Quality Factors
• Statutory requirement
• Failure to meet --gt adulteration
• Proposed definition

10
Food Labeling -- Bioavailability

• Label information
• Nutrition or Supplement Facts declarations
• Claims
• Enriched products

11
Label declarations -- History

• Based on analytical amounts
• Nutrients
• Derived from 1968 RDAs
• 1968 RDAs -- some correction for
  bioavailability
• FDAs compliance method for some nutrients --
  microbiological assay

12
Label declarations -- History

• Calorie content
• May use specific Atwater factors
• May use specific food factors
• Correct for insoluble dietary fiber
• Correct for protein indigestibility

13
Label Declarations -- History

• Non-nutrients
• No correction for bioavailability

14
Claims -- History

• Truthful and not misleading
• Meets regulations
• More claims gt 10 RDI

15
Health claims -- History

• Calcium and osteoporosis
• Folic acid and neural tube defects
• Meet USP standards dissolution disintegration
• Calcium assimilable

16
Enriched products -- History

• Nutrient -- physiologically available
• Level --gt not result in excessive intake
• Nutrient -- suitable for intended purpose

17
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

18
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

19
Current Marketed D.S. Products
20
Ingredients

• Vitamins and minerals
• Macronutrients
• Botanicals
• Amino Acids
• Substances intended to supplement the diet

21
Potential Bioavailability Issues

• Source ingredient
• Extraction and processing procedures
• Interactions -- active constituents
• Effects of inert ingredients/coatings
• Interactions
• with diet
• with drugs

22
Next Steps -- Science Research
23
Issues to be addressed

• Definition What is it?
• Compliance (analytical) methods?
• Specific regulatory impacts
• Safety requirements?
• Label information?
• GMPs?

24
Definition Why Discuss?

• When to consider bioavailability?
• How to monitor compliance?
• Substantiation or documentation?

25
Definition

• Absorption?
• Digestion?
• Metabolism?
• Excretion?
• Summary Utilization?

26
Definitional Challenges?

• Case by case vs. general?
• Ingredient vs. finished product?

27
Definitional Challenges?

• New RDIs based on equivalents
• Example Folic acid
• Applicability to other ingredients?

28
Definitional Challenges?

• New Upper Limits based on synthetics
• Example Folic acid
• Applicability to other ingredients?

29
Safety and Effectiveness Challenges

• How to deal with exposure levels
• Effectiveness
• Safety
• Safety factors for uncertainty

30
Host and Use Challenges

• Label information
• Appropriate use conditions
• Vulnerable populations
• Consumer right to know issues

31
Other Challenges

• Effect of processing?
• Effect of storage?

32
Science and Research Needs

• Bioavailability High priority research need for
  CFSAN
• Definition
• Analytical methods
• Meaningfulness of measures

33
Key issue

• On food - drug continuum
• Where do dietary supplements fall relative to
  bioavailability?