Nutritional Supplement Research: Beyond the Status Quo
• Background• What is the Status Quo?• Common Problems and Solutions
– Quality control– Dosing
Overview
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, 1999www.ods.od.nih.gov
Table 1. Total number of projects and funding for the NIH and USDA top 10 dietary supplement ingredients in the CARDS database, FY 1999-2007
NIH USDA
Ingredient Projects, n
Funding, USD millions Projects,
n
Funding, USD millions
Vitamins and minerals 3197 1093 1443 294
Botanicals 1583 439 592 87
Phytochemicals 1470 415 697 123
Fatty acids and lipids 1051 304 685 130
Proteins and amino acids 597 156 229 45
Antioxidants 528 142 290 82
Dietary Fiber and carbohydrates
196 79 165 24
Hormones/precursors 185 57 10 1
Other 196 63 64 9
BackgroundRegan et al., J Nutr, 2010
$1.9 billion $347 millionNCCAM
$370 million
áMitochondriaáMitochondrial
enzymes
IATask Area I
Year 1 12 months
> 20% changeTo Task II
Task Area IIIYear 2
18-24 months
IIIA IIIB IIIC IIID IIIEEndurance
PerformanceSoldier Task Performance
Muscle InjuryâInflammation
Cognitive Performance
Environmental Extremes
Performance
To Task IV Each > 20% change: IIIA or IIIB or IIIC or IIID or IIIE
Human Performance Testing
Task Area IV Field Testing Performance
Final Formulation Incorporation into Ration
Transition to Ration
Task Area IIYear 1
12 months
IIA IIB IIC IID
Bioavailability Dosing
HumanPharmacokinetics
AcceptableFormulation
AcceptableTo Task III Achieved Completed Hedonics > 6
Analysis FRS Components
áMitochondriaáMitochondrial
enzymes
IATask Area I
> 20% changeTo Task II
áMitochondriaáMitochondrial
enzymes
IAáMitochondriaáMitochondrial
enzymes
IA
Task Area I
12
> 20% changeTo Task II
Task Area IIIYear 2
18-24 months
IIIA IIIB IIIC IIID IIIEEndurance
PerformanceSoldier Task Performance
Muscle InjuryâInflammation
Cognitive Performance
Environmental Extremes
Performance
To Task IV Each > 20% change: IIIA or IIIB or IIIC or IIID or IIIE
Human Performance Testing
Task Area IIIYear 2
18-24 months
IIIA IIIB IIIC IIID IIIEEndurance
PerformanceSoldier Task Performance
Muscle InjuryâInflammation
Cognitive Performance
Environmental Extremes
Performance
To Task IV Each > 20% change: IIIA or IIIB or IIIC or IIID or IIIE
Task Area IIIYear 2
18-24 months
IIIA IIIB IIIC IIID IIIEEndurance
PerformanceSoldier Task Performance
Muscle InjuryâInflammation
Cognitive Performance
Environmental Extremes
Performance
To Task IV Each > 20% change: IIIA or IIIB or IIIC or IIID or IIIE
Human Testing
Task Area IV Field Testing Performance
Final Formulation Incorporation into Ration
Transition to Ration
Task Area IV Field Testing Performance
Final Formulation Incorporation into Ration
Transition to Ration
Task Area IIYear 1
12 months
IIA IIB IIC IID
Bioavailability Dosing
HumanPharmacokinetics
AcceptableFormulation
AcceptableTo Task III Achieved Completed Hedonics > 6
Analysis FRS Components
Task Area IIYear 1
12 months
IIA IIB IIC IID
Bioavailability Dosing
HumanPharmacokinetics
AcceptableFormulation
AcceptableTo Task III Achieved Completed Hedonics > 6
Task Area IIYear 1
12 months
IIA IIB IIC IID
Bioavailability Dosing
HumanPharmacokinetics
AcceptableFormulation
AcceptableTo Task III Achieved Completed Hedonics > 6
Analysis FRS Components
What is the Status Quo?
Slide provided courtesy of Dr. Ed Zambraski, USARIEM
Ideal?
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
Reality?
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
Quality Control(Problem - Content)
Gurley et al., Am J Health Syst Pharm, 2000Harkey et al., Am J Clin Nutr, 2001Parasrampuria et al., JAMA 1998Green et al., Clin J Sports Med, 2001Andrews et al., Anal Bioanal Chem, 2007
Pharmaceutical Standard (USP)
Ephed
ra
Ginsen
g
DHEA
Sterio
ds
Caffe
ine
0
50
100
150
200
250
300
% L
abel
Cla
im
• 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 ProductsAssociation (NPA GMP)
NSF GMP
USP Dietary Supplement Verification Program
Quality Control(Solution)
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
SuperStuff5000
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