bioactive food components in global public health...dietary fatty acids and total serum...

Bioactive food components in global public health

Professor Martin Wiseman

University of Southampton

World Cancer Research Fund International

BIOACTIVE COMPOUNDS AND CHRONIC DISEASE

• Burden of chronic disease• Nutritional aspects • Evolutionary aspects• Issues and Uncertainties• Proposed principles

CAUSE SPECIFIC MORTALITY

ENGLAND 2000

CVD40%

CVD40%

ACCIDENTS2%

OTHER20%

RESPIRATORY10%

CANCER28%

ACCIDENTS2%

RESPIRATORY11%

CANCER24%

OTHER 24%

FEMALE

Dept of Health, 2000

MALE

MAJOR CAUSES OF DEATHUSA 2002

NCHS 2005

CHD29%

Stroke7%

Cancer23%

Diabetes3%

Accidents4%

Other29%

Respiratory5%

GLOBAL DISTRIBUTION OF CAUSES OF DEATHS

0

100

200

300

400

500

600

700

800

900

High mortalitydevelopingcountries

Low mortalitydevelopingcountries

Developedcountries

Accidents

Non-communicabledisease

Communicabledisease, maternaland perinatal deaths,nutritionaldeficiencies

WHO, 2003


• Burden of chronic disease• Nutritional aspects• Evolutionary aspects• Issues and Uncertainties• Proposed principles

Nutrition and chronic disease

• Cardiovascular diseases• Cancer• Bone health• Obesity • Diabetes

CHD Mortality and Serum Cholesterol

02468

10121416

1 2 3 4 5 6 7 8 9 104.0 4.5 4.8 5.1 5.4 5.6 5.8 6.1 6.6 7.5

Serum cholesterol mmol/L

MRFIT n=356222Deaths per 1000

Decilemmol/L

Dietary Fatty Acids and Total Serum Cholesterol

-0.1

-0.05

0

0.05

0.1

0.15

14.0 16.0Average

Sats 12.0 Trans 18.1 18.0 18.2

Cha

nge

in to

tal s

erum

cho

lest

erol

(mm

ol/L

)pe

r 1%

ene

rgy

chan

ge in

kca

l fro

m fa

t

Modified from Grundy et al 1981

Dose of plant sterol or stanol (g/day)

Red

uctio

n in

LD

L ch

oles

tero

l (m

mol

/l)

00.10.20.30.40.50.60.70.80.9

1

0 0.5 1 1.5 2 2.5 3 3.5 4

Age 50-59 Age 40-49 Age 30-39

CHANGE IN LDL-CHOLESTEROL WITH PLANT STEROLS OR STANOLS

From: Law 2000

Prevalence of High Blood Pressure in Americans by Age and SexNHANES: 1999-2002

11.121.3

34.1

5.8

55.5

74.0

46.660.9

69.2

18.1

34.0

83.4

0

20

40

60

80

100

20-34 35-44 45-54 55-64 65-74 75+

Ages

Perc

ent o

f Pop

ulat

ion

Men Women

Source: CDC/NCHS and NHLBI.

2.6 4.0 5.48.4

1.1 2.0

19.122.4

14.8

27.0

6.33.5

0

5

10

15

20

25

30

A B C D E F

Estim

ated

10-

Year

Rat

e (%

)

Men Women

Estimated 10-Year Stroke Risk in 55-Year-Old Adults According to Levels of Various Risk Factors - Framingham Heart Study

AA BB CC DD EE FFSystolic BPSystolic BP 9595--105105 130130--148148 130130--148148 130130--148148 130130--148148 130130--148148DiabetesDiabetes NoNo NoNo YesYes YesYes YesYes YesYesCigarettesCigarettes NoNo NoNo NoNo YesYes YesYes YesYesPrior Prior Atrial Atrial Fib.Fib. NoNo NoNo NoNo NoNo Yes Yes YesYesPrior CVDPrior CVD NoNo NoNo NoNo NoNo NoNo YesYes

Source: Stroke 1991;22:312-318.

Estimated 10-Year CHD Risk in 55-Year-Old Adults According to Levels of Various Risk FactorsFramingham Heart Study

5

13

25

58

20

27

37

05

10152025303540

A B C D

Estim

ated

10-

Year

Rat

e (%

)

Men Women

AA BB CC DDBlood Pressure (mm Hg)Blood Pressure (mm Hg) 120/80120/80 140/90140/90 140/90140/90 140/90140/90Total Cholesterol (mg/dL)Total Cholesterol (mg/dL) 200200 240240 240240 240240HDL Cholesterol (mg/dL)HDL Cholesterol (mg/dL) 5050 5050 4040 4040DiabetesDiabetes NoNo NoNo YesYes YesYesCigarettesCigarettes NoNo NoNo NoNo YesYesmm Hg = millimeters of mercurymm Hg = millimeters of mercurymg/dL = milligrams per deciliter of bloodl mg/dL = milligrams per deciliter of blood

Source: Wilson PWF, et al. Circulation 1998;97:1837-1847.

The Dietary Approaches to Stop Hypertension (DASH) trial

Sacks et al, 2001Sacks et al, 2001

Vegetable intake and Relative Risk of CHD Mortality in Men

1.41.31.2

Rel

ativ

e R

isk

> 117g/day

62 - 117g/day

<61g/day1.1

0.91

0.80.70.60.50.4

Adjusted for age and energy, carotenoids, vitamins E and C intakesKnekt et al, 1994

VITAMINS: MAJOR VASCULAR EVENTS

Vascularevent (10269)

VITAMINS(10267)

PLACEBO Rate ratio & 95% CIVITAMINS better PLACEBO better

1063 1047Major coronary

511 518Any stroke

1058 1086Revascularisation

0% SE 3reduction(NS)

0.4 0.6 0.8 1.0 1.2 1.4

(22.5%)2306

(22.5%)2312ANY OF ABOVE

Vitamins = 600 mg E, 250 mg C and 20 mg beta-carotene Heart Protection Study 2002

Homocysteine and CHDObservational Studies

Relative Risk

Degree ofadjustment

1.3 (1.1-1.5)

0.5 1 2 4 6 8

1.6 (1.4-1.7)

+++++++++++++++++

+++++++++++++++----

-------

1.9 (1.6-2.3)

PHYTOESTROGENS AND CARDIOVASCULAR DISEASE

0

0.4

0.8

1.2

Quartile 1 Quartile 2 Quartile 3 Quartile 4

IsoflavonesLignans

Isoflavones Lignans

Hazard ratio

van der Schouw et al 2005

EPIC: Colorectal cancer risk

0,60

0,70

0,80

0,90

1,00

1,10

1 2 3 4 5quintiles of exposure

RR

FruitsFruits + VegVegetable

Statistical models adjusted by height, weight, physical activity, energy intake, smoking

B. de Mesquita, E.Riboli, P.Ferrari et al., IARC, 2002, in press

EPICRelative risk of colorectal cancer by quintile of fibre intake,

with and without adjustment for energy

0,50

0,60

0,70

0,80

0,90

1,00

1,10

1,20

1 2 3 4 5 Quintiles

Rel

ativ

e R

isk

fibre

fibreadjustedforenergy

S. Bingham et al., IARC, 2002

VITAMINS: SITE-SPECIFIC CANCER INCIDENCE

(10269) (10267)VITAMINS PLACEBO Rate ratio & 95% CI

VITAMINS better PLACEBO better

228 223Gastrointestinal

181 165Respiratory

60 68Connective tissue

247 284Genitourinary

11 8Central nervous system

58 58Haematological

3 5Other

42 43Not specified

(7.8%) (8.0%)2% SE 5reduction

800 817

(NS)

ANY CANCER (exceptnon melanoma skin)

217 228Non-melanoma skin

0.4 0.6 0.8 1.0 1.2 1.4Heart Protection Study, 2002

Chronic disease - nutritional perspective

• Human nutrition - Demand-led process; supply to meet physiological demand for function (metabolism, mechanical work)

• Demand depends on genetic background, lifetime experience, and current environment

• Human metabolism evolved through natural selection

• Natural selection operates through reproductive inheritance

Chronic disease - nutritional perspective

• Nutrient - component of metabolic pathways (or precursor) found in food/drink

• Essential nutrients - essential components of metabolism expected in the environment - biosynthetic pathways not preserved

• “Non-essential” nutrients - essential components of metabolism whose biosynthetic pathways must be preserved

Bioactive compounds- nutritional perspective

• Are they nutrients?

• Are they essential?

• Is there a physiological demand?


• Are they nutrients? NO

• Are they essential?




• Are they essential? NO





• Is there a physiological demand? NO




• Is there a physiological demand? NO

• So does their supply influence metabolism and health and if so how?

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CANCER INCIDENCE WITH AGEUK 2001



CRUK 2004

CVD DEATHS BY AGEUK 2001

BHF 2005

0

20000

40000

60000

80000

100000

120000

<35 y 35-44 y 45-54 y 55-64 y 65-74 y 75+ y

MaleFemale

Age

Deaths

Bioactive compounds -evolutionary perspective

• Post-reproductive events largely irrelevant to natural selection

• Post-reproductive effects of environmental exposures cannot be predicted on evolutionary basis

• Bioactive compounds do not meet evolutionarily determined metabolic demand

Bioactive food components• Amount and form consumed• Absorption - effects if not absorbed• Metabolism• Systemic, tissue, intracellular distribution• Effects of metabolites

– Biochemistry of etiologic pathway – Validated markers of risk?– Effects in vitro, in animal model– Effects in human in vivo

• Interactions• Biological effects vs health effects

Foods and chronic disease

• Food components vs whole diets – Interactions– Confounding

• Food, diet, behaviour– Dose– Formulation– Study design

Foods and chronic disease

• Evidence issues– Simple vs complex models and interventions– Timing of intervention– Duration of intervention

• Type of evidence – Trial vs observational– Prospective vs retrospective– Laboratory vs clinical

• Complexity of foods/diets/lifestyle– Confounding - cause/effect– Interactions


• Foods and diets associate with chronic disease risk

• Foods and diets are complex and associate with other behaviors

• Many food components have biological activity

• Some bioactive components may have health promoting potential

• Some bioactive components may have adverse effects


• Does this potential translate to reality?

• How to test this?

• What paradigm to use?

Bioactive food components

• Epidemiology - associations• Physiology - absorption, metabolism, distribution and

utilisation• Lab - potential efficacy/safety• “Omics” - human biology• Clinical - human health

– Dose/form– Population studied– Timing of intervention– Duration of intervention– Outcomes - intermediate or health

- beneficial or adverse


• Bioactive food components are incidental to nutrition

• Food components can have adverse and positive effects

• Studies need to address effectiveness in prevention and treatment - hard end points

• Better elucidation of the etiologic pathway and the effects of bioactive components is key to designing informative clinical studies

• Effects on validated determinants of risk need to be demonstrated

• Research on food components is important


• For global public health population-wide interventions are needed

• Interventions must have demonstrated high benefit to risk ratio

• Varying exposures beyond usual experience needs to demonstrate both safety and efficacy

• Unusual interventions (single component, non-nutrient, high dose) are not meeting nutritional demand and a pharmacologic paradigm is appropriate at present

• Current public health strategies should be food based

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