Systematic Review of Dietary Supplement Efficacy and Safety Paul M. Coates, Ph.D. Office of Dietary Supplements National Institutes of Health Department of Health and Human Services AHRQ Annual Meeting September 2008

NIH Funding for Dietary Supplement Research Has Increased Significantly $ Million

ODS Mission is to Strengthen Knowledge and Understanding of Dietary Supplements  Evaluate Scientific Information  Stimulate and Support Research  Disseminate Research Results  Educate the Public to Foster an Enhanced Quality of Life and Health for U.S. Population Echinacea Echinacea purpurea

Evidence-Based Review Program

Congressional Language for FY 2001 ODS Appropriation “The Office is encouraged, in consultation with NCCAM, AHRQ, and FDA to review the current scientific evidence on the safety and efficacy of dietary supplements now on the market, which could then form a basis for further research, education of practitioners and consumers, and whether further regulatory requirements are necessary.”

Evidence-Based Review Program  Systematic review of the literature, with meta-analysis as appropriate, on DS efficacy and safety  In collaboration with the Agency for Healthcare Research and Quality (AHRQ) Evidence-Based Practice Center Network  Major reason for conducting these reviews is to assist NIH in the development of research agendas

ODS Evidence-Based Review Program  Chromium and insulin sensitivity*  Ephedra for weight management and athletic performance enhancement* (with NCCAM)  Omega-3 fatty acids for cardiovascular disease prevention* (with NHLBI) and other health indications  Health effects of soy (with NCCAM)  Antioxidant phytochemicals/B vitamins and neurodegenerative diseases*(with NCCAM)  Multivitamins/multiminerals and chronic disease prevention (with OMAR)  Coagulation, diet, and dietary supplements  Health effects of vitamin D (with multiple partners) *Congressional mandate

Health Effects of Omega-3 Fatty Acids  Asthma  Cancer  Cardiovascular Disease  Cardiovascular Disease Risk Factors  Arrhythmogenic Mechanisms  Child and Maternal Health  Cognitive Function  Eye Health  Type II Diabetes, Rheumatoid Arthritis, and Other Diseases  Mental Health  Organ Transplantation

Health Effects of Omega-3 Fatty Acids  Secondary CVD Prevention  Reduces all cause mortality and other CVD outcomes (sudden death, cardiac death, MI)  Primary CVD Prevention  Large, consistent beneficial effect found for serum triglyceride levels  Little or no effect found for other CV risk factors and markers of CVD

Omega-3 Reports  Heterogeneous data; challenging to evaluate  Methods of estimating fish or omega-3 fatty acid intake  Background diets  Methods of reporting results  Adverse events from clinical studies appear to be minor  However, reporting is spotty

Observations  “Nobody expects the Spanish Inquisition” ( Monty Python’s Flying Circus, ca.1970)  Put another way, nobody expected to be meta-analyzed

Product Concerns:  Identification  Characterization  Reproducibility Issues in Dietary Supplement Research St. John’s Wort Hypericum perforatum

Protocol Concerns:  Population(s)  Endpoints  Dose  Earlier Phase Studies  Publication Issues (cont’d) St. John’s Wort Hypericum perforatum

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