Overview of Current Issues in Overview of Current Issues in

NutritionNutrition

What are the questions?What are the questions?

What are the challenges?What are the challenges?

How might risk assessment help?How might risk assessment help?

Shiriki Kumanyika, PhD, RD, MPHShiriki Kumanyika, PhD, RD, MPHCenter for Clinical Epidemiology and BiostatisticsCenter for Clinical Epidemiology and Biostatistics

Graduate Program in Public Health StudiesGraduate Program in Public Health Studies

University of Pennsylvania School of MedicineUniversity of Pennsylvania School of Medicine

OutlineOutline

•• Framing the questionsFraming the questions

–– Types of riskTypes of risk

–– Food and nutrition variablesFood and nutrition variables

–– Population considerationsPopulation considerations

–– OutcomesOutcomes

•• Quantification of riskQuantification of risk

•• ChallengesChallenges

Framing the QuestionsFraming the Questions

Who poses questions about Who poses questions about

nutritional risk (U.S. context)nutritional risk (U.S. context)

•• IOM Food and Nutrition Board and related committeesIOM Food and Nutrition Board and related committees

•• Dietary Guidelines Committees that are convened by the Dietary Guidelines Committees that are convened by the

DHHS and USDADHHS and USDA

•• DiseaseDisease--focused organizations such as the American Heart focused organizations such as the American Heart

Association, American Diabetes Association, and American Association, American Diabetes Association, and American

Cancer Society Cancer Society

•• “Life stage interest groups”, e.g., AAP or the March of Dimes.“Life stage interest groups”, e.g., AAP or the March of Dimes.

•• Food safety agenciesFood safety agencies

•• Food regulatory agenciesFood regulatory agencies

•• The food industry The food industry

•• ConsumersConsumers

Risk ConsiderationsRisk Considerations

•• AdequacyAdequacy--ToxicityToxicity

•• Food borne illness, including allergiesFood borne illness, including allergies

•• Disease prevention and management Disease prevention and management

(mid(mid--range of continuum; harm or lack range of continuum; harm or lack

of benefit)of benefit)

Population ConsiderationsPopulation Considerations

•• Life stage (growth; development; aging)Life stage (growth; development; aging)

•• Reproductive stateReproductive state

•• GeneticsGenetics

•• Environmental stressorsEnvironmental stressors

•• Behaviors (smoking)Behaviors (smoking)

•• Health statusHealth status

••Food and Nutrition BoardFood and Nutrition Board

••Dietary Guidelines Advisory CommitteeDietary Guidelines Advisory Committee

••Disease Interest GroupsDisease Interest Groups

••Life Stage Interest GroupsLife Stage Interest Groups

What should What should

people eat to be or people eat to be or

stay healthy?stay healthy?

Is this changing?Is this changing?

How does this vary How does this vary

among population among population

groups and by life groups and by life

stagesstages

What and how are What and how are

people eating? people eating?

Where are the Where are the

potential harms in potential harms in

these patterns?these patterns?

How should we How should we

react to new foods react to new foods

as they emerge?as they emerge?

What is available for people What is available for people

to eat? Is it sufficient? Safe?to eat? Is it sufficient? Safe?

What new products can be What new products can be

developed? developed?

How can products be How can products be

improved?improved?

What ingredients can be What ingredients can be

added?added?

What should be removed?What should be removed?

••U.S.D.A.U.S.D.A.

••Food IndustryFood Industry

••Food scientistsFood scientists

••NCHSNCHS

••FDAFDA

••NIHNIH

••Health ResearchersHealth Researchers

Food and Nutrition VariablesFood and Nutrition Variables

•• Macronutrients, fiber, and energy balanceMacronutrients, fiber, and energy balance

•• Vitamins in foodVitamins in food——naturally occurringnaturally occurring

•• Vitamin added to foods or taken as supplementsVitamin added to foods or taken as supplements

•• MineralsMinerals

•• Minerals added to foods or taken as supplementsMinerals added to foods or taken as supplements

•• Other naturally Other naturally ––occurring food constituentsoccurring food constituents

•• Contaminants, toxins, mutagensContaminants, toxins, mutagens

•• Other dietary supplements, e.g. botanicalsOther dietary supplements, e.g. botanicals

•• Foods and beverages, food preparation, food Foods and beverages, food preparation, food

processing, food groups, and whole dietary patternsprocessing, food groups, and whole dietary patterns

•• AlcoholAlcohol

Types of Variables: Constituents in Types of Variables: Constituents in

Fruits and VegetablesFruits and Vegetables

•• Sulfides (Sulfides (alliumallium))

•• CarotenoidsCarotenoids

•• FlavonoidsFlavonoids

•• Glucosinolates/IndolesGlucosinolates/Indoles

•• PhytoestrogensPhytoestrogens

•• IsothiocyanatesIsothiocyanates

•• PhytosterolsPhytosterols

•• Protease InhibitorsProtease Inhibitors

•• SaponinsSaponins

•• PhenolsPhenols

•• CapsaicinCapsaicin

•• ResveritrolResveritrol

•• AnthocyaninsAnthocyanins

•• TanninsTannins

•• TerpenesTerpenes

•• Dietary fiberDietary fiber

•• Vitamins/mineralsVitamins/minerals

–– C, E, Folic acid, K, C, E, Folic acid, K,

SeSe

Van Van DuynDuyn MS and MS and PivonkaPivonka E. J Am Diet Assoc 2000;100:1511E. J Am Diet Assoc 2000;100:1511--15211521

LOGIC FRAMEWORK

ILLUSTRATING

CONCEPTUAL

APPROACH TO

NUTRITION &

COMMUNITY HEALTH:

Intake Variables and Intermediate Outcomes

POPULATION FOOD INTAKE

Food Consumption Patterns

(e.g. fruits, vegetables)

Intake of Nutrients and Food

Components

Vitamins

Minerals

Fiber

Fats

Other food constituents

Dietary supplements

AlcoholEnergy balance

Life Stage

Requirements

Pregnancy

Lactation

Childhood

Adolescence

Adulthood

Older Adulthood

PhysiologicIndicators

GrowthAdipose tissue

Musculoskeletal

Gastrointestinal

Metabolic

Cardiovascular

Reproductive

Immunological

Neurological

Genetics,

Co-morbidities

Physical

ActivityPatterns

Diseases of InterestDiseases of Interest

•• Cardiovascular DiseasesCardiovascular Diseases

•• CancersCancers

•• Type 2 DiabetesType 2 Diabetes

•• ObesityObesity

•• Dental CariesDental Caries

•• OsteoporosisOsteoporosis

Example Of Diet-disease Pathways Explored For Cardiovascular Diseases

High cal dietHigh fat dietDietary fatty acidsSedentary lifestyle

Hypertension

Left ventricular hypertrophy

Heart rate

EKG abnormalities

Subclinical disease(atherosclerosis))

Impaired glucose tol

Type 2 diab. mellitus

Hyperuricemia

Elevated serum chol

Elevated LDL-C

Decreased HDL-C

Elevated TG

Plasma homocysteine

Other risk factors

CHD

Hypertensive heart disease

Other CVD

Na K

Alcohol, Cigarettes

Dietary/lifestyleReversible

intermediatesMorbid and fatal

outcomes

Overwt, ObesityAbdominal/

central obesityWeight history

Vit C, Vit E; carotenoids; flavonoids)Folic Acid, vit B6, B12

- Ca, Mg- Fruits and vegs

Ischemic Stroke

Hemorrhagic Stroke

Adapted from

Kumanyika and Adams-

Campbell, 1991

Cellular and Biochemical Mechanisms That Play a Role in the Pathogenesis of Major Chronic Diseases

Cancer Athero-

sclerosis Obesity Diabetes

Insulin resistance + + + +

Cell proliferation + + - +

Inflammation + + - +

Apotosis + + - +

Changes in signal

transduction, gene

expression

+ + + +

DNA modifications/

mutations/genetic variation

+ + + +

A plus sign indicates association; minus sign, no specific body of evidence is available to suggest that a specific mechanism or pathway correlates with the indicated disease. Adapted from; Adapted from; DeckelbaumDeckelbaum RJ, Fisher EA, Winston M, Kumanyika S, Lauer RM, PiRJ, Fisher EA, Winston M, Kumanyika S, Lauer RM, Pi--SunyerSunyer FX, St FX, St JeorJeor

S, Schaefer EJ, Weinstein IB. Summary of a scientific conferenceS, Schaefer EJ, Weinstein IB. Summary of a scientific conference on preventive nutrition: pediatrics to on preventive nutrition: pediatrics to

geriatrics. Circulation. 1999 Jul 27;100(4):450geriatrics. Circulation. 1999 Jul 27;100(4):450--6 6

Possible Matrix of Food and Nutrient Possible Matrix of Food and Nutrient

Variables, by Type of IssueVariables, by Type of Issue

XXXXXXXXXXXXXX33

XXXXXX22

XXXXXXXXXXXX11

Foods; Foods;

PatternsPatternsSuppleSupple--

mentsmentsPathogens; Pathogens;

ContaminantsContaminants

OtherOther

ConstiConsti

tuentstuentsMineralsMineralsVitaminsVitamins

MacroMacro

nutrients nutrients

1=adequacy or toxicity, both, or quality1=adequacy or toxicity, both, or quality

2=2=foodbornefoodborne illness and allergiesillness and allergies

3=disease prevention and management3=disease prevention and management

Quantification of Risk Quantification of Risk

Dietary Reference IntakesDietary Reference Intakes

Dietary GuidelinesDietary Guidelines

Dietary Reference Intakes (DRI)Dietary Reference Intakes (DRI)

•• Estimated Average Requirements (EAR)Estimated Average Requirements (EAR)

•• Adequate Intake (AI)Adequate Intake (AI)

•• Recommended Dietary Allowances (RDA)Recommended Dietary Allowances (RDA)

•• Tolerable Upper Intake Level (UL)Tolerable Upper Intake Level (UL)

•• Elements of adequacy and toxicity and disease Elements of adequacy and toxicity and disease preventionprevention

•• Age and gender groupsAge and gender groups

See See OttenOtten JJ, JJ, HellwigHellwig JP, Meyers LD, eds. Dietary Reference Intakes. The Essential GJP, Meyers LD, eds. Dietary Reference Intakes. The Essential Guide to uide to

Nutrient Requirements. Washington DC: National Academies Press,Nutrient Requirements. Washington DC: National Academies Press, 20062006

DRI ElementsDRI Elements

•• Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Energy, Carbohydrate, Fiber, Fat, Fatty Acids,

Cholesterol, Protein, and Amino Acids Cholesterol, Protein, and Amino Acids

•• Water, potassium, sodium, chloride, and sulfateWater, potassium, sodium, chloride, and sulfate

•• Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Vitamin A, Vitamin K, Arsenic, Boron, Chromium,

Copper, Iodine, Iron, Manganese, Molybdenum, Copper, Iodine, Iron, Manganese, Molybdenum,

Nickel, Silicon, Vanadium, and Zinc Nickel, Silicon, Vanadium, and Zinc

•• Vitamin C, Vitamin E, Selenium, and Vitamin C, Vitamin E, Selenium, and CarotenoidsCarotenoids

•• Thiamin, Riboflavin, Niacin, Vitamin B6, Thiamin, Riboflavin, Niacin, Vitamin B6, FolateFolate, ,

Vitamin B12, Vitamin B12, PantothenicPantothenic Acid, Biotin, and Acid, Biotin, and CholineCholine

•• Calcium, Phosphorus, Magnesium, Vitamin D, and Calcium, Phosphorus, Magnesium, Vitamin D, and

Fluoride Fluoride

2005 Dietary Guidelines Nine 2005 Dietary Guidelines Nine

Focus AreasFocus Areas

•• Adequate Adequate

Nutrients within Nutrients within

Calorie NeedsCalorie Needs

•• Weight Weight

ManagementManagement

•• Physical ActivityPhysical Activity

•• Food Groups to Food Groups to

EncourageEncourage

•• FatsFats

•• CarbohydratesCarbohydrates

•• Sodium and Sodium and

PotassiumPotassium

•• Alcoholic Alcoholic

BeveragesBeverages

•• Food SafetyFood Safety

Common Themes in Recent Dietary and Lifestyle

Recommendations

Recommendations ACS AHA ADA AdiabA NIH AAP USDA/ HHS/FDA

§ Calories to achieve

desirable weight

+ + +† + + + +

§ Total and saturated fat

and cholesterol

+ + +‡ +§ + + +

§ Variety of foods;

emphasize plant

sources

+ + + + + + +

§ Moderate sugars and

salt

+ + + + + + +

§ Adequate physical

activity

+ + + + + + +

§ Do not smoke + + + NR + + +

§ Alcohol in moderation + + + + + NR +

SOURCE: Deckelbaum et al, Circulation, July 1999

ChallengesChallenges

Issues to be addressedIssues to be addressed

•• Inconclusive or absent dataInconclusive or absent data

•• Adverse effects between adequacy and Adverse effects between adequacy and toxicity toxicity

•• Biphasic or variable effectsBiphasic or variable effects

•• Food safety risks of recommended Food safety risks of recommended foods foods

•• Evidence paradigmsEvidence paradigms–– for chronic disease outcomesfor chronic disease outcomes

–– for risk defined by foods or dietary patternsfor risk defined by foods or dietary patterns

Research Needs Identified by 2005 Research Needs Identified by 2005

Dietary Guidelines CommitteeDietary Guidelines Committee

•• Food componentsFood components

•• Vitamin D in vulnerable groupsVitamin D in vulnerable groups

•• Vitamin EVitamin E

•• Added sugarAdded sugar

•• GlycemicGlycemic loadload

•• Macronutrient ratio and body weightMacronutrient ratio and body weight

•• Contradictions, e.g., mercury in fishContradictions, e.g., mercury in fish

•• Food groups and whole dietsFood groups and whole diets

U.S. Dietary Guidelines Advisory Committee, 2005U.S. Dietary Guidelines Advisory Committee, 2005

Specific exposuresSpecific exposures

Dietary Supplements: A Framework for Evaluating Safety.

Committee on the Framework for Evaluating the Safety ofthe Dietary Supplements, National Research Council. www.iom.edu

Diet and Chronic DiseaseDiet and Chronic Disease

•• Ecological, crossEcological, cross--

sectionalsectional

•• Cohort; caseCohort; case--control control

studiesstudies

•• Clinical trials of efficacyClinical trials of efficacy

•• Randomized effectiveness Randomized effectiveness

trialstrials

•• MetaMeta--analysesanalyses

•• Animal studiesAnimal studies

•• Biochemical studiesBiochemical studies

•• Small scale clinical Small scale clinical

studiesstudies

Evolution of Evidence for Selected Nutrient andDisease Relationships

Committee on Examination of the Evolving Science for

Dietary Supplements, Institute of Medicine

INCREASED CERTAINTY

•Fluoride and dental caries•Calcium and bone status•Vitamin D and bone status

DECREASED CERTAINTY

•Beta carotene and lung CA •Vitamin C and gastric cancer•Vitamin E and cancer

SummarySummary•• Questions are framed from several different Questions are framed from several different

perspectivesperspectives

•• Types of risk X number of variables X number Types of risk X number of variables X number of endpoints X interactions among these of endpoints X interactions among these factors results in very complex questions factors results in very complex questions

•• Risk assessment approaches are being used Risk assessment approaches are being used where the questions relate to direct effects of where the questions relate to direct effects of single or relatively specific and selective single or relatively specific and selective exposures exposures

•• Applicability to circumstances of Applicability to circumstances of complex,complex,common exposures and multiple possible common exposures and multiple possible endpoints is less clearendpoints is less clear