Professor Jeffrey Blumberg, Professor in the Friedman School of Nutrition Science and Policy at Tufts University, presents "Dietary Bioactive Components: Where Do We Go From Now?" presentation at the Creator Space™ Science Symposium in Chicago.

1. BASF Creator Space Science Symposium
Sustainable Food Chain: From Field to Table
Chicago, IL – June 24, 2015
Jeffrey B. Blumberg, PhD, FASN, FACN, CNS-S
Antioxidants Research Laboratory
Jean Mayer USDA Human Nutrition Research Center on Aging
Friedman School of Nutrition Science and Policy
Tufts University
Dietary Bioactive Components:
Where Do We Go From Now?

2. What are Bioactives?
Constituents in foods or dietary supplements,
other than those needed to meet
basic human nutritional needs,
that are responsible for changes in health status
Office of Disease Prevention and Health Promotion, DHHS. Fed Reg 2004

3. Bioactives are GRAB
(Generally Recognized as Beneficial)
• present a significant portion of dietary constituents
• important to human health
• components that promote physiological function

4. Zoochemicals
• Docosahexanoic acid (DHA)
• Eicosapentaenoic acid (EPA)
• Conjugated linoleic acid
• Dairy protein hydrolysates (peptides)
α-, β-, κ-caseins, β-lactoglobulin, α-lactalbumin, etc.
CLA isomer, cis-9, trans-11
CLA isomer, trans-10, cis-12

5. Phytochemicals
• Alkaloids
• Carotenoids
• (Poly)phenols
• Nitrogen-containing compounds
• Organosulfur compounds
Caffeine
Lutein
Allicin
Avenanthramides
Flavonoid Stilbene
Phenolic Acid Lignan
(Poly)phenols

7. Potential Health Benefits of
Dietary (Poly)phenols
Del Rio et al. Antiox Redox Signal 2012

8. (Poly)phenol Databases
USDA ARS Database for the Flavonoid Content
of Selected Foods
USDA ARS Database for the Proanthocyanidin
Content of Selected Foods
USDA ARS Database for the Isoflavone Content
of Selected Foods
European Food Information Resource (EuroFIR)
Bioactive Substances in Food Plants
Information System (BASIS)
French National Institute for Agricultural Research
Phenol-Explorer

9. Dietary Intake of Polyphenols in French Adults
SU.VI.MAX
Pérez-Jiménez et al. Am J Clin Nutr 2011
Subclass Mean intake
mg/d/person
Main food contributors (%)
Flavanols 99 ± 116 tea (71), red wine (10), apples (6)
Flavonols 51 ± 28 tea (70), onions (23), spinach (13)
Flavones 33 ± 17 wheat flour (refined, 64; whole 20)
Flavanones 26 ± 29 oranges (50), OJ (44), red wine (3)
Anthocyanins 57 ± 47 red wine (41), cherries (23),
strawberries (20)
Cohort XS
• n, 4942
• age, 45-60 y

10. Anthocyanins Reduce the Risk of
Incident Hypertension and Myocardial Infarction
Nurses Health Study II
Cassidy et al. Am J Clin Nutr 2011 Circulation 2013
n 87,242 93,600
Age, y 25-42 25-42
F/U, y 14 18
Q1 – Q5, mg/d 5.7-21.9 2.5-25.1
Quintile iHT MI
1 -- --
2 6% 20%
3 7% 29%
4 9% 15%
5 13% 32%
Ptrend 0.0001 0.047

11. Blueberry Polyphenols Improve
Vascular Function in Healthy Men
Rodriguez-Mateos et al. Am J Clin Nutr 2013
RCT-XO: • n, 21
• age, 18-40 y

12. 13C-Cyanidin-3-Glucoside is
Bioavailable and Metabolized in Humans
Czank et al. Am J Clin Nutr 2013
Blood Urine
Meanconcentrationof
recoveredmetabolites,µmol/L
Meanconcentrationof
recoveredmetabolites,µmol/L

13. (Poly)phenol Mechanisms of Action
Modulation of:
• Signal transduction pathways
• Transcription factors
• DNA acylation/methylation
• Mitochondrial function
• Autophagy
• Plasma membrane proteins/phospholipids

14. Although the term dietary antioxidants
is a convenient description, these
compounds are multifunctional, and
some of the actions observed in vivo
may not represent an antioxidant
function, even though the compounds
have been classified as antioxidant
nutrients.
Are (Poly)phenols Dietary Antioxidants?
DRIs for Vitamin C, Vitamin E, Selenium, and Carotenoids. Natl Acad Press 2000

15. Developing Reference Values for Bioactives
• Provide consumers with guidance about healthy
food choices via education and food product labeling
• Provide the nutrition industry with definitions to guide
innovative agricultural and product development as
well as truthful and non-misleading communications
about products

16. Proposed Criteria for a Bioactive to be
Considered for Evaluation of DRI Framework
• Definition of the substance that is commonly used
• Method of analyzing the substance which is consistent
with the definition
• Database of the amount of bioactives in foods
• Prospective cohort studies
• Clinical trials on digestion, absorption, activation,
transport, and excretion of the substance
• Clinical trials on efficacy and dose-response
• Safety data at anticipated level of intake
• Systematic reviews and meta-analyses showing efficacy
• Plausible biological explanation for efficacy
Lupton et al. Eur J Nutr 2014

17. Meta-analyses of Cocoa Flavanols
Cardiometabolic Disorders Total and LDL Cholesterol Insulin Sensitivity
Systolic Blood Pressure Stroke Flow-Mediated Vasodilation

18. Framework for Flavonoid Reference Values
IOM framework – DRI: EAR, AI, RDA, UL
Codex framework – NRV

19. Framework for Flavonoid Reference Values
IOM framework – DRI: EAR, AI, RDA, UL
Codex framework – NRV
Adequate Intake: When sufficient evidence is not
available to set an EAR, the AI is a goal for the
intake of individuals. The AI is expected to cover
the needs of most all people.
AI
?

20. Agostoni et al. EFSA J 2012
Cocoa flavanols help maintain endothelium-dependent vasodilation,
which contributes to normal blood flow. In order to obtain the
claimed effect, 200 mg of cocoa flavanols should be consumed daily.
This amount could be provided by 2.5 g of high-flavanol cocoa
powder or 10 g of high-flavanol dark chocolate, both of which can be
consumed in the context of a balanced diet. The target population is
the general population.

21. Selected Bioactives:
• Anthocyanins
• Beta-glucan
• Docosahexaenoic acid
Model Food Matrices:
• Bakery
• Dairy
• Egg products
Primary Outcome:
• Prevent Metabolic Syndrome
http://www.pathway27.eu/topstory/bioactive-enriched-food/

22. Hierarchy of Evidence-Based Nutrition

23. Revised Hierarchy of Evidence-based Nutrition

24. The Problem of Proof
DRUGS BIOACTIVES
Control placebo low vs. high dose
Effect scope single target pan-systemic
Effect size large, specific modest, aggregated
across systems
Dose-response Monotonic threshold, homeostatic
control
Cohort specific disease not sick
Interaction excluded drugs included nutrients
Blumberg et al. Nutr Rev 2010

25. Small Portions of Agro-Food Waste are Valorized
Valorized food wastes can be
reincorporated into food products
to promote nutrient densityWaste
Value Added
Food By-Products
Agricultural application
Animal feeding
Composting, fertilizer
Energy
Compounds with added value

26. Technologies for Recovery of Added Value
Components from Food Wastes
Galanakis. Trends Food Sci Tech 2012
Established Emerging

27. Accuse not Nature!
She has done her part;
Do Thou but Thine
Milton, Paradise Lost 1667

28. Le mieux est
l'ennemi du bien
The perfect is the enemy of the good
- Voltaire (François-Marie Arouet)
1694-1778