The growing consumer interest in health and fitness has expanded the market for a wide range of products, from yoga mats to the multiple dietary supplements now on the market. Supplements are popular, but are they safe? Many dietary supplements are probably safe when used as recommended. However, since 1994 when Congress decided that they should be regulated as if they were foods, they are assumed to be safe unless the Food and Drug Administration can demonstrate that they pose a significant risk to the consumer. But there are many types of products that qualify as dietary supplements, and the distinctions can become muddled and vague. Manufacturers are not legally required to provide specific information about safety before marketing their products. And the sales of supplements have been steadily increasing—all together, the various types now bring in almost $16 billion per year. Given these confounding factors, what kind of information can the Food and Drug Administration use to effectively regulate dietary supplements? This book provides a framework for evaluating dietary supplement safety and protecting the health of consumers.

Contents

• THE NATIONAL ACADEMIES
• COMMITTEE ON THE FRAMEWORK FOR EVALUATING THE SAFETY OF DIETARY SUPPLEMENTS
• PROTOTYPE MONOGRAPHS
• FOOD AND NUTRITION BOARD
• BOARD ON LIFE SCIENCES
• Preface
• Executive Summary
  • THE COMMITTEE'S TASK
  • REGULATORY BACKGROUND
  • THE SAFETY FRAMEWORK FOR DIETARY SUPPLEMENTS
  • APPLICATION OF THE FRAMEWORK
  • FACTORS INFLUENCING USE OF THE FRAMEWORK
  • FINDINGS
  • RECOMMENDATIONS
  • BARRIERS TO EVALUATING THE SAFETY OF DIETARY SUPPLEMENTS
• 1. Introduction and Background
  • COMMITTEE CHARGE
  • GENERAL BACKGROUND INFORMATION ABOUT DIETARY SUPPLEMENTS
  • REFERENCES
• 2. Approaches Used by Others and Existing Safety Frameworks
  • RESOURCES ON DIETARY SUPPLEMENTS
  • CONSIDERATION OF FRAMEWORKS FOR EVALUATING THE SAFETY OF OTHER SUBSTANCES
  • SUMMARY
  • REFERENCES
• 3. The Framework
  • CONSIDERATIONS IN DESIGNING THE FRAMEWORK
  • I. THE PROCESS
  • II. APPLYING SCIENCE-BASED PRINCIPLES TO ESTABLISH RISK
  • GENERAL PRINCIPLES AND CONCEPTS WHEN CONSIDERING DATA
  • UTILIZING THE FRAMEWORK
  • SUMMARY
  • ANNEX 3-1 APPLYING THE SAFETY FRAMEWORK TO REQUIRED NUTRIENTS
  • ANNEX 3-2 MONOGRAPH PREPARATION AND PUBLIC ACCESS
  • ANNEX 3-3 THE USE OF AN EXTERNAL ADVISORY COMMITTEE
  • REFERENCES
• 4. Categories of Scientific Evidence—Human Information and Data
  • SPONTANEOUSLY REPORTED ADVERSE EVENTS
  • HISTORICAL USE
  • CLINICAL STUDIES
  • EPIDEMIOLOGICAL STUDIES
  • SUMMARY
  • REFERENCES
• 5. Categories of Scientific Evidence—Animal Data
  • POWER AND RELEVANCE OF ANIMAL DATA
  • GENERAL TYPES OF ANIMAL DATA
  • CONSIDERATIONS FOR ASSESSING ANIMAL DATA
  • WHEN DO ANIMAL DATA WARRANT CONSIDERATION AS AN INDICATOR OF SERIOUS RISK TO HUMAN HEALTH?
  • RISK ASSESSMENT STRATEGY FOR CONSIDERING ANIMAL DATA
  • SUMMARY
  • REFERENCES
• 6. Categories of Scientific Evidence—Information About Related Substances
  • CONSIDERING INFORMATION ABOUT CHEMICAL COMPONENTS AND RELATED BOTANICALS AS SIGNALS OF POTENTIAL RISK OF BOTANICAL DIETARY SUPPLEMENT INGREDIENTS
  • OTHER APPROACHES FOR CONSIDERING STRUCTURAL SIMILARITY TO KNOWN CLASSES OF TOXIC COMPOUNDS
  • CONSIDERATION OF SUBSTANCES RELATED TO ENDOGENOUS SUBSTANCES
  • CONSTITUENTS FUNCTIONALLY RELATED TO KNOWN CLASSES OF TOXIC COMPOUNDS
  • SUMMARY
  • REFERENCES
• 7. Categories of Scientific Evidence—In Vitro Data
  • CONSIDERATIONS AND RELEVANCE TO HUMANS
  • GENERAL TYPES OF IN VITRO ASSAYS
  • VALIDATED IN VITRO ASSAYS
  • SERIOUSNESS OF HARM PREDICTED BY THE ASSAY
  • SUMMARY
  • ANNEX 7-1 USE OF GENETIC TOXICOLOGY INFORMATION
  • ANNEX 7-2 IN VITRO TESTS VALIDATED FOR USE IN REGULATORY TOXICOLOGY CONTEXTS
  • ANNEX 7-3 USE OF NEW TECHNOLOGIES IN PREDICTING RISKS
  • REFERENCES
• 8. Interactions
  • TYPES OF INTERACTIONS
  • PREDICTING THE POTENTIAL OF INGREDIENTS TO CAUSE PHARMACOKINETIC INTERACTIONS
  • SUMMARY
  • REFERENCES
• 9. Vulnerable Groups and Prevalence of Use
  • USE BY VULNERABLE SUBPOPULATIONS
  • PREVALENCE OF USE IN THE POPULATION
  • REFERENCES
• 10. Scientific Principles for Integrating and Evaluating the Available Data
  • A FORMULAIC APPROACH FOR INTEGRATING DATA IS NOT PRACTICAL
  • AMOUNT OF INFORMATION NEEDED TO DRAW A CONCLUSION
  • INTEGRATING INFORMATION
  • WEIGHING EVIDENCE THAT MAY APPEAR INCONSISTENT
  • PROOF OF HARM
  • REFERENCES
• 11. Applying the Framework: Case Studies Using the Prototype Safety Monographs
  • PROTOTYPE MONOGRAPH DEVELOPMENT
  • USE OF THE FRAMEWORK IN EVALUATING PROTOTYPE INGREDIENTS
  • PRINCIPLES IDENTIFIED FROM THE PROTOTYPES
  • REFERENCES
• 12. Factors Influencing Use of the Safety Framework
  • FEATURES OF THE FRAMEWORK
  • CONSTRAINTS IN USING THE SAFETY FRAMEWORK
  • SUMMARY
• 13. Findings and Recommendations
  • ABILITY TO DETERMINE UNREASONABLE RISK
  • LEGAL AND REGULATORY BARRIERS TO EVALUATION OF THE SAFETY OF DIETARY SUPPLEMENTS
  • SPECIFIC FINDINGS AND RECOMMENDATIONS
  • REFERENCES
• Appendix A Existing Frameworks or Systems for Evaluating the Safety of Other Substances
• Appendix B Scope of Work and Comments to Initial July 2002 Framework
• Appendix C Plant Family Information
• Appendix D Chaparral: Prototype Monograph Summary
• Appendix E Glucosamine: Prototype Monograph Summary
• Appendix F Melatonin: Prototype Monograph Summary
• Appendix G Chromium Picolinate: Prototype Monograph Summary
• Appendix H Saw Palmetto: Prototype Monograph Summary
• Appendix I Shark Cartilage: Prototype Monograph Summary
• Appendix J Prototype Focused Monograph: Review of Liver-Related Risks for Chaparral
• Appendix K Prototype Focused Monograph: Review of Antiandrogenic Risks of Saw Palmetto Ingestion by Women
• Appendix L Acknowledgments
• Appendix M Biographical Sketches of Committee Members

NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.

This study was supported by Contract Number 223-00-2458 between the National Academy of Sciences and the Food and Drug Administration. Additional support came from Institute of Medicine internal funds. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the views of the organizations or agencies that provided support for the project.