Evaluation of BWhat evidence is suf

Dr. Jean Mic

Council for Responsible G J lGeneva Jul

Benefit Claims:fficient and feasible ?

chel ANTOINE

Nutrition International:l 3 d 2010ly 3rd 2010

Let food be your mediccine and medicine be your food

Let food be your medic

PODALIRIUS: Healer

MACHAON : Surgeon ASCLÉMACHAON : Surgeon ASCLÉ

cine and medicine be your food

HYGEIA : Health

PANACEA : Healing

ÉPIOSÉPIOS

Let food be your mediccine and medicine be your food

Let food be your mediccine and medicine be your food

Let food be your mediccine and medicine be your food

Let food be your mediccine and medicine be your food

NUTRITION STARTEDNUTRITION STARTEDTRIALS, ERROR

We are still in a lWe are still in a l

D WITH OBSERVATIOND WITH OBSERVATIONRS, TRADITION

earning process…earning process…

OBSERVATION:

Christiaan Eijkman

Vitamin

Jacob de Bondt

KEY FOR SUCCESS

Robert R. Williams

1931

OBSERVATION: K

Burr & E 1930Evans 1930

Epidemiolog19

KEY FOR INNOVATION

gy of Eskimos970

Parenteral Nutrition

19801980

1st DEMONSTRAT

James LIND compared 6 drinks o‐ Cider,‐ H2 SO4‐ Vinegar‐ Sea waterSea water‐ Lime‐ Garlic, mustard, horser

He concluded that Acid was thebe

HMS Salisbury

TION of EFFICACY: 1747

on 6 * 2 sick subjects:

radish

e key factor,ecause of its cleaning capacity.

1st CLINICCAL TRIAL : 1794

HMS Suffolk sailing from London to India, Supported by Admiralty

Sir G. Blane  (1794) demonstrated the efficacy of lime on half the crew.

1st Randomized, not blindedControlled (nothing vs lime)Long term TrialLong term Trial.

47 years after the first report.

Validated by the Royal Academy of Medicine 50 years later !

k dCook used it since 1766 !

What is the act

• Szent-Györgyi: vitamin C

• Lemon is more than Vit. CMarti N & al: Nat Prod CommMarti N. & al: Nat Prod Comm

Hamdan D & al. Pharmazie. 2

• Lemon is still not well

tive part of lemon ?

: 1933

C. :n 2009;4:677 700 un. 2009;4:677-700.

2010; 65:141-7. : 94 compounds

characterized !

To day Observa

• Observation: - Long history of useful pg y p- Tradition is still inspirin- Reports correlationp

Intervention:• Intervention:- Cause and effect relati

Id tif th l f d- Identify the causal food

ation is not enough

practicespng modern science

onshipd / i g di td / ingredient

Scientific opinio

• ILSI Europe: FuFoSe: Br J Nconcepts of functional foods in Eu

• Growth, development and dif• Functional food science and s• Functional food science and d• Functional food science and t• Functional food science and g

function.i l f d i d b• Functional food science and b

functions.

ns in our centuries.

Nutr. 1999;81:S1-27: Scientific urope. Consensus document.

fferentiation.substrate metabolism.defense against R.O.S.the cardiovascular system.gastrointestinal physiology and

b h i d h l i l behavior and psychological

Functional Food ScienFUFOSEOutcomeFUFOSE

A working definition:Outcome

A food can be regarded gsatisfactorily demonstraone or more target funcone or more target funcadequate nutritional efferelevant to either an imprelevant to either an impand well-being and/or thdidisease.

nce

as “functional” if it is ated to affect beneficiallytions in the body, beyondtions in the body, beyondects in a way which is proved state of health proved state of health he reduction of risk of

Conclusion

• ILSI Europe: FuFoSe: Br J concepts of functional foods in Eu

• Functional foods are foods, t• They are providing benefits bey a e p ov d g be e ts b• There are examples of foods/

benefits• Markers are KEY elements to

- Exposure, Function, Intermep , ,- Indicators or Factors.

• Evidence from human studies

s from Fufose

Nutr. 1999;81:S1-27: Scientific urope. Consensus document.

herefore safe products.beyond usual nutrition.beyo d usual ut t o ./nutrients with functional

demonstrate a benefitediate end-pointp

s are THE scientific basis.

Functionaal examples:

Conclusion

• ILSI Europe: FuFoSe: Br J concepts of functional foods in Eu

• Functional foods are foods an• They are providing benefits bey a e p ov d g be e ts b• There are examples of foods/

benefits• Markers are KEY elements to

- Exposure, Function, Intermp , ,- Indicators or Factors.

• Evidence from human studies

s from Fufose

Nutr. 1999;81:S1-27: Scientific urope. Consensus document.

nd safe products.beyond usual nutrition.beyo d usual ut t o ./nutrients with functional

o demonstrate a benefitmediate end-pointp

s are THE scientific basis.

Markers for ddifferent objectives

Conclusion

• ILSI Europe: FuFoSe: Br J concepts of functional foods in Eu

• Functional foods are foods an• They are providing benefits bey a e p ov d g be e ts b• There are examples of foods/

benefits• Markers are KEY elements to

- Exposure, Function, Intermep , ,- Indicators or Factors.

• Evidence from human studie

s from Fufose

Nutr. 1999;81:S1-27: Scientific urope. Consensus document.

nd safe products.beyond usual nutrition.beyo d usual ut t o ./nutrients with functional

demonstrate a benefitediate end-pointp

es are THE scientific basis.

Functional claaims are possible !

Scientific Evid

• Eur J Nutr (2005) [Suppl 1] 44 : I/

dence: PASCLAIM

/1–I/2: Consensus on Criteria

European Jourp

Eur. J. Nutr. 2003; 42 (sup.1Ph i h Phase one: preparing the way

Eur J Nutr 2004; 43 (sup 2Eur. J. Nutr. 2004; 43 (sup.2Phase two: moving forward. N

Eur. J. Nutr. 2005; 44 (sup.1Consensus on Criteria: P.j. Aj

rnal of Nutrition

1):3 - 119 N A ly. N.g. Asp et al.

2):3 1832):3 - 183N.g. Asp et al.

1):3 - 30Aggett et al.gg

PASSCLA

T t lHuman data

Total& Weig

f Valid Markers

of EvidenFood Characteristics

AIM Summary Scheme

itityght Substantiated

claimnce

claim

CommVaVa

• Characterised Food• Specified claim or be• Validated marker(s) • Validated marker(s) • Human intervention

R l t t di P dRelevant studies: Prod

• Convincing evidencegSignificant changesRepetition (Literature,

mon Sense Criteriaalid everywherealid everywhere

enefit data

t S bj tuct, Subjects

e:

, or trials)

Some probiotics provthat help dithat help di

• Tradition told us: Yogurtone can enjoyone can enjoy.

ll• Science tells us : Yogurt malabsorbers to digest la

vide enzymatic activities gestion of foodgestion of food

t is a dairy food every

helps lactose ctose.

Lactose digesg

Lactase Lactose

+

G

+G-Gl G-Gl G-Gl

stion assessment

Activity

G + Gl

Breath-t

Lactose Lactase

G-Gl G-Gl G-Gl

80 % of adults can80 % of adults canin milk but the no

(D i h

est methodologygy

H²e Activity

G-Gl

nnot digest lactosennot digest lactose orthern European h bit )

Breath test t

Lactose in milk

60

70

40

50

20

30

0

10

-10

00 1 2 3 4

TIME (H(

to assess Lactose digestion

is not absorbed

MILK

n= 50

5 6 7 8

H))

Yoghurt imp

YOGHURT IMPROVED L

60

70

50

60

30

40

10

20

-10

00 1 2 3 4

10

TIME (H)

proves lactose absorption

LACTOSE ABSORPTION

MILKMILK

YOGHURT

n= 50

5 6 7 8

)

Not al Lactose D

75

100

n %

50

tibili

ty i

0

25

Dig

est

GHURTga

ricus

mophil

usdo

ph

YOGHL.

Bulga

S. The

rmo

L. ac

idop

BiS. B

ll species are egaligestibility

philu

scte

rium

soph

ilic Milk

pBifid

obac

t

Meso

B

Yoghurt cultur

Killing yogurtKilling yogurt suppressed lactos

y

100

tibili

tyct

ose

50

75

dige

stbe

d la

c

25

% o

f dab

sorb

0YOGHURT

%res must be ALIVE

cultures (heat)cultures (heat) se digestion benefit

Heat-treatment Milk

23 published human trial clactose digestibilitylactose digestibility

YOGURTS & LACT

100

120

milk

80

100

est w

ith m

40

60

brea

th te

0

20

0 5 10 15

% o

f b

0 5 10 15

studies

confirmed improvement of by different yogurtsby different yogurts

TOSE DIGESTION

MILK CONTROLYOGURT

20 2520 25

Effect still chall

J Nutr. 2010 Mar;140(3):677S

lenged by scientists

S-89S.

We Know the Response to

Variation in thethe

RESPONSEo foods and m

g/dl

o foods and omponents

iscommon-

placep

Kris-Etherton, et a

o Foods/Components Vary

al. (1993) Metabolism 42:121-9

Improve slow g

Transit time: Time during which a mark

E

LiverSto

rofeacal TT=whole gut TTolored marker in stools éance et al, 2001éance et al, 2003

Large intestine

Smintes

,shida et al, 2008

astrointestinal transit

er pass through the digestive tract .

Segmental transit

Esophagus

Small bowel TTBreath test

omach

Breath testAgrawal et al., 2009

mall stine

Colonic TTRadio-opaque marker (abdominal x-rayAgrawal et al., 2009Bouvier et al, 2001Marteau et al, 2002

7

Design o

Day -7

n=50

Day 7

With TT < 40h

n=50n=50With TT > 40h(MTT + STT)

Oro-fecal TT

n = 100 free living elderly (o2 or 3 serving per day of ActTransit time (O-f TT) was me

of gut transit study

Day 0 Day 15y y

2 / day

3 / day

2 / day

3 / day3 / dayOro-fecal TT Oro-fecal T

over 65 years old) eatingtivia for 15 days.easured by coloured markers.

Improves sl

Méance S. et al., Micr. Ecol.

BVolunteers :Free livingFree living

elderly

Products : 10 15 20 25 30 35Products :Activia (125ml)

per day

Transit Time: Coloured

markersTran

low transit time

Health dis. 2001; 13: 217-222

Before consumpttion

6

ulat

ion

24

popu

40 45 50 55 60 65 70 75 80

nsit time (h)

Improves slo

Méance S. et al., Micr. Ecol.

BVolunteers :Free livingFree living

elderly

Products : 10 15 20 25 30 35Af

Products :Activia (125ml)

per day

10 15 20 25 30 35

Transit Time: Coloured

markersTran

ow transit time

Health dis. 2001; 13: 217-222

Before consumpttion

6

ulat

ion

24

popu

40 45 50 55 60 65 70 75 80

ion

fter 15 days of intake 10 0

popu

lati

2 55,07,510,0

2,5

40 45 50 55 60 65 70 75 80

nsit time (h)

ScientificDose-effect of Activia on transit

(summary of 2 studies)

R2= 0 9929

35on (h

)

h) 8

9

R2 = 0,9835

R = 0,9929

202530

e re

duct

i

sit t

ime

(h

6

7

8

05

1015

rans

it tim

e

Tran

s3

4

5

MTT Logarithmic model

00 1 2 3

Servings/day

Tr 3

MTT

STT

Logarithmic model(MTT)Logarithmic model(STT)

c demonstration

The effect is long lasting

80

90

60

70

80

30

40

50

Time (week)

30BM start BM end 2* 4* 6*

1BM (n=40)( )

2BM (n=38)

* p<0.05 paired t test for baseline versus follow-upat 2 4 and 6 eeksat 2, 4 and 6 weeks

Similar Benetransit time in w

Effect of Activia on G

transit time in w

Effect of Activia on G

80

60

hour

s)

40

ttim

e (h

20

Tran

sit

0Italy 2 weeks China 1 we

efits of Activia on slow women in Italy and China

Gut Transit Time

women in Italy and China

Gut Transit Time

beforeafter

eek China 2 week

NORMALISATION OF SNORMALISATION OF S

IS IT A DEMONST

Consumers’ anConsumers an

EXPERTS’ ANSWE

SLOW TRANSIT TIME:SLOW TRANSIT TIME:

TRATED BENEFIT ?

nswer: YES !nswer: YES !

ER: no evidence !

Karl Popp

A the"sciescieonly

ScientiScientiquestio

They agapsTh tgaps.They are not o

assessors,

nor gap manag

per principle:

eory is entific"entific if it is refutablests are looking forsts are looking for

ons.

are good at identifying

ft doften good gap

ers

Old chal

pen the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again.

lenge were:

Up-coming challenges are:

DIETARY BENEFITS M

Food is a key partne

IImprovement

We can benchmarWith risk idrisk quantiCliquez et modi

Cliquez pour modifier

risk quantirisk manq p

MUST BE AFFORDABLE

er to improve health.

d dts are needed

rk risk managementdentification, fication and fiez le titre

r le sous-titre

fication and nagement

DIETARY BENEFITS M

•There is a need fo• of benefit i• of benefit i

•benefit qu•and benefit

Specially when scieaccessible to all on tCliquez et modi

Cliquez pour modifier

accessible to all on t

q p

MUST BE AFFORDABLE

or a fair assessmentdentification dentification,

uantification management

entific evidence are the web to everyonefiez le titrer le sous-titre

the web to everyone.

Convincing & affo

DONE BYCRO (CONTRACT RESARCH ORGANIZATION)

Statistical analysisOne clinical

ORGANIZATION)Sr

Control of the datastudy costs

d TEN Validscieevid

Biological analysis

R it t

around TEN millions

S

Recruitment of volunteers and study implemen‐tation

millions meals of theCliquez et modi

Cliquez pour modifierEXPERIMENTAL PHASE DONE IN HOSPITALS OR CLINICAL SITES

Production of batches 

(products)

Stmeals of the

averageq paverage population

ordable evidence

Protocoland designof the study

Study report

Choice of products

INNOVATIONDESIGNS

dated ntific dence

Choice of partners

Study document writing

partners

Submission of

fiez le titrer le sous-titreETHICAL COMMITTEE

S B SS O

writingSubmission of the project to the health authorities

SUBMISSION

Slide 50

m2 Key-message: Clinical studies in nutrition are specific, and especially the accentuated steps (boxes 1, 2, 5, 7, 9).

Even if clinical studies have the same pattern in pharma and food, the effects to demonstrate are smaller in food and thus more difficult to detect.maricye, 5/19/2010