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?