SATURDAY MARCH 15TH 2014

Eline M. van der Beek

Research Director, Singapore

PPP INSIGHTS FROM PRECLINICAL AND

EPIDEMIOLOGICAL STUDIES:

tools to shape nutritional intervention trials

For non-commercial use only

THE FIRST 1,000 DAYS OF LIFE

ARE CRUCIAL

-9 to 0 m 0 to 6 m > 12 m 6 to 12 m

INNOVATION EXAMPLE 1:

SAFETY & EFFICACY of scGOS-lcFOS

Clinical studies

(Proof of Concept)

Clinical studies

(Proof of Efficacy)

Excellence in clinical studies to provide the credible evidence

ICH – GCP (Int’l Conference on Harmonisation / WHO Good Clinical Practice)

ISO 9001-2000 certified since 2007. Recertified in March 2013

OUR TRANSLATIONAL R&D APPROACH:

Clinical trials in humans

In vivo animal models

In vitro animal cells

In vitro human cells

In vitro mechanistic

Clinical trial design:

To test a possible effect on growth & body composition development in young children

Age (months)

0 3 12 24 36 48 60 72 84 96

BM

I (kg

/m2 )

13

14

15

16

17

18

19

20

21

normal weight at 8 yrs of ageoverweight at 8 yrs of age

1.4% obese 9.1% overweight

Peak BMI

Adiposity rebound

Dutch Birth Cohort 1996-1997 N = 3963

Scholtens et al, Ped Res, 2007; Willers, PLoSOne, 2012

Infant BMI predictive for childhood

overweight

FOCUS ON 2: EARLY GROWTH AND ADIPOSITY

Toolbox development

1. Validation of pre-peritoneal fat mass as proxy for visceral fat

2. Ultrasound methodology is a valid methodology for visceral fat measurements in epidemiological and clinical studies

Mook-Kanamori et al (2009) Ultrasound Med Biol 35: 1938-1946

Method implemented in VENUS trial

FOCUS ON 2: EARLY GROWTH AND ADIPOSITY

Rapid growth rate is associated with increased abdominal fat mass

Durmuş et al (2010) Clin Endocrin 72: 633-640

FOCUS ON 2: EARLY GROWTH AND ADIPOSITY

Growth patterns associated with visceral fat mass development

Durmuş et al (2010) Clin Endocrin 72: 633-640

Infants at higher risk Preterm, SGA, failure to thrive

1st tertile

2nd tertile

3rd tertile

-25

-20

-15

-10

-5

0

5

10

15

20

catch downnon-changers

catch-up

Diff

eren

ce in

prep

erito

neal

are

a(%

)

Association between infant growth patterns and visceral fat mass at 2 year

KEY OUTCOMES FOCUS ON 2

Validation of US measurements: non-invasive, low costs, detailed insights

Pre-peritoneal fat mass as proxy for visceral fat mass

Distribution of fat mass changes in first 2 years

Early postnatal (but not fetal) growth is associated with visceral fat mass at 2 years of age

Slow fetal growth and rapid postnatal growth increases adiposity at 2 years of age

Toolbox:

US measurements to assess visceral fat in clinical trial (VENUS)

KEY OUTCOMES FOCUS ON 5

Beneficial effects of breastfeeding duration and exclusivity on later adiposity and metabolic disease risk are strongly ameliorated by life style factors

Fetal growth deceleration and postnatal growth acceleration is associated with increased adiposity at 6 yrs

Postnatal, but not fetal, growth is linked to adiposity at 6 yrs.

Gishti et al, AJCN accepted; Gishti et al, JCEM accepted

Food industry is the bridge between

science, regulation and consumer

Regulation

Food

Industry

Consumer

Science

Production capacity Distribution Marketing Education

Industry

R&D

15 May 2011

13 Early Life Nutrition Forum

DANONE RESEARCH

% of women of child-bearing age

NNHS (2002)

1 NNS (2000); 2 NSW Pop. HS

(2005)

4th HES (2010)

Mans (2003)

WHO (1998)

Riskesdas (2007)

Underweight

BMI <18.5 8%

BMI <18.5 26.3% 1

BMI <18.5 17.2% (15-29yo)

3.4% (30-44yo)

BMI <18.5 13.5% (20-29yo)

5.8% (30-39yo)

-

Mid upper arm circumference

<1SD 13.6% (15-45 yo)

Overweight and Obesity

BMI ≥ 24 30.2%

BMI ≥ 25 16.3% (≥ 16yo) 2

BMI ≥ 25 20.6%

(15-29yo)

44.2% (30-44yo)

BMI ≥ 25 28.8%

(20-29yo)

38.6% (30-39yo)

BMI ≥ 25 27%

(≥ 18yo)

Central obesity, M>90cm, F>80cm:

17.9% (25-34yo, M&F)

24.4% (35-44yo, M&F)

Pre-pregnancy Nutritional Status

Many women in the region enter pregnancy with suboptimal weight.

Female overall: 29%

14

folic acid↓ iron↓ iodine↓

iron↓ folic acid↓

vit A↓ vit D↓ iodine↓

iron↓ folic acid↓ vit A↓ iodine↓

vit D↓

iodine↓ calcium↓ iron↓

vit D↓ iron↓

folic acid↓

iodine↓ calcium↓

Nutritional issues in Europe (NP data)

Key issues (intake vs RDA*): • Iron (42-95% of RDA) • Folic acid (42-87% of RDA) • Iodine (65->100% of RDA) • Vit D (23-64% of RDA)

Literature search + expert interviews low mid high evidence

* RDA: recommended daily allowance

15

iron↓ calcium↓ vit D↓

iron↓ vit D↓

folic acid↓

Literature search + expert interviews low mid high evidence

iron↓

sodium↑

vit A↓ vit B1/B2↓ calcium↓

iron↓

calcium↓ iron↓ magn.↓

Nutritional issues in Asia (NP data)

vit D↓

iodine↓

iron↓ vit B1↓

calcium↓

vit A↓ vit B2↓

iodine↓ vit A↓

folic acid↓

iron↓

calcium↓

Additional issues in Asia (intake vs RDA*): • Calcium (32-40% of RDA) • Vit A (32-63% of RDA) • Vit B1 (60-86% of RDA) • Vit B2 (41-93% of RDA) * RDA: recommended daily allowance

HEALTH / CONSUMER NEEDS of Maternal Milk

* Literature review

* Nutritional & health status

* Public health issues

Phase 1

* Local experts

interviews

* Identify gaps

of knowledge

Phase 2

* Additional studies to fill

the knowledge gaps e.g.

food intake & nutritional

status studies

Phase 3

Many micro-nutrients intake during pregnancy was unknown.

Seafast study to evaluate nutritional gaps and the

barriers of milk consumption during pregnancy

Pre-pregnancy: Folate or vit D insufficiency, low Ca intake.

Poor nutritional status during Pregnancy: Low weight gain, iron deficiency anemia, low vit A intake.

Low SES is one of the factors.

Food taboos is common.

INDONESIA (SariHusada)

Nutriplanet Indonesia

HEALTH / CONSUMER NEEDS of Maternal Milk

INDONESIA (SariHusada)

Phase 4

* SET UP business & nutritional

objectives & APPLY study results in terms

of products Reno/Inno, communication

support, partnership for endorsement

Innovation to fill the nutritional gaps: Innovation to address the milk consumption barrier: Fresh fruity taste (to overpower

the nauseating effect) One glass a day with essential

nutrients (practical) Affordable price Rp 3000/day (<10% of monthly expenditure)

Other brands: 19-27%

Phase 5

MEASURE

business

impact

CO/CANN: 45-48 %

Additional CANN: 81.5 bio IDR (6,7 M€)

Volumes: 1200 Tons (budgeted 1312)

Maternal Nutritional Products

in 3 ASPAC countries

Context: Barriers of consuming milk (nauseating) in CDE SE-class.

•Affordable maternal product to fill nutrient gaps during pregnancy.

• Fresh fruity taste, 1 glass a day

Indonesia

Australia

Context: Supplement to fill a gap in 5 key nutrients in pregnancy and during breastfeeding based on Nutritional Survey Data & recommendations by the Australian Government.

Context: Milk is perceived as nutritious & important during pregnancy but is not part of dietary habit. Maternal milk supplement in the country tailored for the specific periods of pregnancy & lactation Concentrated format for convenience: one serving a day

Thailand

OUR TRANSLATIONAL

R&D APPROACH:

To know specific concerns regarding age-specific nutritional intake

To translate the science into concepts that may help to address nutritional gaps and improve health

To investigate the effects of these concepts in clinical setting

To understand the mechanisms behind the observed effects

Clinical trials in humans

In vivo animal models

In vitro animal cells

In vitro human cells

In vitro mechanistic

THANK YOU