Nutritional Supplement Research: Beyond the Status Quo

1. Nutritional Supplement Research: Beyond the Status Quo

2. Overview • Background • What is the Status Quo? • Common Problems and Solutions • Quality control • Dosing

3. Background • Dietary Supplement Health and Education Act of 1994 (DSHEA) • DSHEA deregulation • No GMP’s • No quality control standards • No requirement to show safety or efficacy • The Office of Dietary Supplements (ODS) was established through DSHEA (by NIH in 1995) and collaborates with the National Center for CAM (NCCAM) • ODS and NCCAM promote and award funding for scientific research on dietary supplements Nesheim, Pub Health Nutr, 1999 www.ods.od.nih.gov

4. Background Regan et al., J Nutr, 2010 $1.9 billion $347 million NCCAM $370 million

5. IA IA Task Area I á á Mitochondria Mitochondria á á Mitochondrial Mitochondrial Year 1 enzymes enzymes 12 months > 20% change To Task II IIA IIA IIB IIB IIC IIC IID IID Task Area II Task Area II Analysis FRS Bioavailability Bioavailability Human Human Acceptable Acceptable Year 1 Year 1 Components Dosing Dosing Pharmacokinetics Pharmacokinetics Formulation Formulation 12 months 12 months Achieved Achieved Completed Completed Hedonics > 6 Hedonics > 6 To Task III To Task III Acceptable Acceptable Human Performance Testing IIIA IIIA IIIB IIIB IIIC IIIC IIID IIID IIIE IIIE Task Area III Task Area III Endurance Endurance Soldier Task Soldier Task Muscle Injury Muscle Injury Cognitive Cognitive Environmental Environmental Year 2 Year 2 Performance Performance Performance Performance â â Inflammation Inflammation Performance Performance Extremes Extremes 18 18 - - 24 months 24 months Performance Performance To Task IV To Task IV Each > 20% change: IIIA or IIIB or IIIC or IIID Each > 20% change: IIIA or IIIB or IIIC or IIID or IIIE or IIIE Transition to Ration Field Testing Final Formulation Incorporation into Task Area IV Performance Ration What is the Status Quo? Ideal? IA IA Task Area I Task Area I á á Mitochondria Mitochondria á á Mitochondrial Mitochondrial enzymes enzymes 12 > 20% change > 20% change To Task II To Task II IIA IIA IIB IIB IIC IIC IID IID Task Area II Task Area II Analysis FRS Analysis FRS Bioavailability Bioavailability Human Human Acceptable Acceptable Year 1 Year 1 Components Components Dosing Dosing Pharmacokinetics Pharmacokinetics Formulation Formulation 12 months 12 months Achieved Achieved Completed Completed Hedonics > 6 Hedonics > 6 To Task III To Task III Acceptable Acceptable Human Performance Testing Human Testing IIIA IIIA IIIB IIIB IIIC IIIC IIID IIID IIIE IIIE Task Area III Task Area III Endurance Endurance Soldier Task Soldier Task Muscle Injury Muscle Injury Cognitive Cognitive Environmental Environmental Year 2 Year 2 Performance Performance Performance Performance â â Inflammation Inflammation Performance Performance Extremes Extremes 18- 18 - 24 months 24 months Performance Performance To Task IV To Task IV Each > 20% change: IIIA or IIIB or IIIC or IIID Each > 20% change: IIIA or IIIB or IIIC or IIID or IIIE or IIIE Transition to Ration Transition to Ration Field Testing Field Testing Final Formulation Final Formulation Incorporation into Incorporation into Task Area IV Task Area IV Performance Performance Ration Ration Slide provided courtesy of Dr. Ed Zambraski, USARIEM

6. Reality? What is the ‘Status Quo?’ Source of Supplement?: Usually off-the-shelf Verification of quality?: Usually not Dose?: Usually what others have used Kinetics/bioavailability?: Usually not Study design?: Usually good! Data analysis?: Conventional and sound Data display & interpretation?: Usually marginal or poor

7. Quality Control(Problem - Dissolution) • > 50% of calcium supplements and many single and multivitamin-mineral preparations fail to meet USP disintegration and dissolution standards. • > 40% of melatonin supplements fail to meet USP disintegration standards. Carr and Shangraw, Am Pharm, 1987 (adapted from Table 3) Carr and Shangraw, Am Pharm, 1987; Shangraw, Pub Health Rep Suppl, 1990; Hahm et al., J Am Pharm Assoc, 1999

8. Quality Control(Problem - Content) Gurley et al., Am J Health Syst Pharm, 2000 Harkey et al., Am J Clin Nutr, 2001 Parasrampuria et al., JAMA 1998 Green et al., Clin J Sports Med, 2001 Andrews et al., Anal Bioanal Chem, 2007 Pharmaceutical Standard (USP)

9. Quality Control(Solution) • Good Manufacturing Practices (GMP) provide a system of processes, procedures, and documentation to assure a product has the identity, strength, composition, quality, and purity that it claims. • Three independent non-governmental programs provide GMP guidelines for dietary supplements. • Adoption is VOLUNTARY Natural Products Association (NPA GMP) NSF GMP USP Dietary Supplement Verification Program

10. Quality ControlA word about mixtures (cocktails) or “Product Testing” Effects (or lack of effects) observed using multiple ingredients violates basic scientific philosophy. There is no way to know if the ingredients (or which ingredients) are acting synergistically, antagonistically, or if they are biologically active at all. > 100 interactions possible between ingredient pairs; > than 1,000,000 interactions possible among random groupings • Product Claims: • Boost Immunity • Reverse Male-Pattern Baldness • Burn Fat • Improve Memory • Increase Energy • Enhance Labido Ingredient List: Chinese Ginseng, Siberian Ginseng, Vitamin B-12, Guarana, Yohimbine, L-Carnitine, Bee Pollen, Caffeine, Ginkgo Biloba (leaf), Coenzyme Q10, DHEA, SAMe, Fish Oil, Quercetin, Glucosamine Chondroitin, FD&C Green #2 . SuperStuff 5000 5x stronger than our 1000 formula! ≠