6th International Conference on Polyphenols and HealthUniversity of Buenos Aires, Argentina

19 October 2013

The Road to Evidence-based Dietary Recommendations

for Flavonoids: How Do We Get There?

From Data to Databases to Adequate Intakes

Jeffrey Blumberg, PhD, FASN, FACN, CNSFriedman School of Nutrition Science and Policy

Jean Mayer USDA Human Nutrition Research Center on AgingTufts UniversityBoston, MA USA

Disclosures for: Jeffrey B. Blumberg

AFFILIATION FINANCIAL INTERESTS

CORPORATE ORGANIZATION

Grants/Research Support None

Scientific Advisory Board Herbalife, GlaxoSmithKline, Pharmavite

Speakers Bureau None

Stock Shareholder None

Other Financial or Material Support/Honorarium

None

Why Develop Reference Values for Flavonoids?

• Provide consumers with guidance about healthyfood choices via education and food product labeling

• Provide the nutrition industry with definitions to guideinnovative product development as well as truthful and non-misleading communications about products

Knowing is not enough; we must applyWilling is not enough; we must do.

- Johann Wolfgang von Goethe (1749-1832)

IOM FNB. DRI Coverpage 2000

From Data to Databases

Dataanalytical methods

experimental design nomenclature

quality control reporting

From Data to Databases

Data

Food Composition Analysiscultivar

environment geography

post-harvestpreparation sample size replication

From Data to Databases

Data

Food Composition Analysis

Database Classification and Organizationaccuracy

analytical methodologyaglycone vs. glycone

nomenclature incompleteness

Flavonoid 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

From Data to Databases

Data

Food Composition Analysis

Database Classification and Organization

Dietary Intakeassessment tools

bioavailabilityreliability

Dietary Intake of Polyphenols in French AdultsSU.VI.MAX

Pérez-Jiménez et al. Am J Clin Nutr 2011

From Data to Databases

Data

Food Composition Analysis

Database Classification and Organization

Dietary Intake

Validation of Exposurematrix (blood, urine)pharmacokinetics

single vs. multiple exposures

Urinary (not Dietary) Polyphenols AreAssociated with Decreased Mortality

InCHIANTI Study

Zamora-Ros et al. J Nutr 2013

Total Urinary Polyphenols Total Dietary Polyphenols

From Databases to Function

Range of Intakeusual

national vs. internationalduration in cohort

From Databases to Function

Range of Intake

Functionmaintenance of physiological function

modification of intermediary biomarkersreduction of disease risk

Cocoa Flavanols Reduce PrehypertensionSystolic Blood Pressure

Diastolic Blood Pressure

Ried et al. BMC Med 2010

RCT:• 15 trial arms• 2 wk• 18-70 y

• 168-902 mgflavanols

• 30-1008 mgpolyphenols

Anthocyanins Reduce the Riskof Incident Hypertension

Cassidy et al. Am J Clin Nutr 2011

Mu

ltiv

aria

te R

elat

ive

Ris

k

Quintiles

NHS II NHS I

HPFS Pooled

RR: 0.92 95% CI:0.86-0.98, P<0.03

Intake mg/d

• Q1= 5.7• Q5= 21.9

• n=156,957• 25-75 y• 14 y F/U

Intake of Anthocyanins and PolymersReduce the Risk of Myocardial Infarction

Nurses Health Study II

Intake, mg/d 1 2 3 4 5 P

Anthocyanins 2.5 5.0 8.4 13.5 25.1

1.0--

0.800.60-1.07

0.710.52-0.97

0.850.63-1.15

0.680.49-0.96

0.047

Polymers* 65.4 110.1 160.9 256.7 578.6

1.0--

0.890.66-1.19

0.800.59-1.08

0.640.46-0.89

0.830.62-1.11

0.051

Cassidy et al. Circulation 2013

* Polymers: proanthocyanidins, theaflavins, thearubigins • n=93,600• 25-42 y• 18 y F/U

From Databases to Function

Range of Intake

Function

Flavonoid Reference Valueframeworks for reference and risk

FAO/WHO Codex AlimentariusU.S. Institute of Medicine

From Function to Reference Values

IOM framework – DRI: EAR, AI, RDA, ULCodex framework – NRV

Adequate Intake: When sufficient evidence is notavailable to set an EAR, the AI is a goal for theintake of individuals. The AI is expected to coverthe needs of most all people.

From Function to Reference Values

IOM Tolerable Upper Intake Level (UL): The highest level of daily intake likely to pose no riskof adverse health effects to almost all individualsin the general population.

FAO/WHO Highest Observed Intake (HOI): Where notoxicity has been observed, the highest dose testedthat can be confidently concluded as safe.

Le mieux est l'ennemi du bien

The perfect is the enemy of the good

- Voltaire (François-Marie Arouet)1694-1778